Objective: To explore the clinical efficacy of using the anterolateral thigh flap (ALTF) combined with "Y"-shaped great saphenous vein graft in repairing large soft tissue defects in the proximal-middle segment of the lower leg. Methods: This study was a retrospective case series study. From January 2019 to December 2023, 8 patients with large soft tissue defects in the proximal-middle segment of the lower leg meeting the inclusion criteria were admitted to the Department of Hand & Foot and Reconstructive Microsurgery of Shandong Provincial Hospital Affiliated to Shandong First Medical University, including 7 males and 1 female, aged 15 to 63 years. After the wounds were cleaned and the infection was controlled, the areas of soft tissue defects in the lower leg ranged from 18 cm×7 cm to 30 cm×14 cm. The ALTF combined with "Y"-shaped great saphenous vein graft was conducted to repair the soft tissue defects in the lower leg. The flap harvest areas were 19 cm×8 cm to 31 cm×15 cm. Intraoperatively, the bifurcated ends of the "Y"-shaped great saphenous vein were end-to-end anastomosed with the descending genicular artery and the medial femoral muscle branch (MFMB), respectively, and the main trunk end was end-to-end anastomosed with the descending branch of lateral femoral circumflex artery (LFCA-DB), constructing a "dual-in, single-out" venous bridging mode. The dominant concomitant vein of LFCA-DB was end-to-end anastomosed with the recipient great saphenous vein. If there was no suitable vein in the recipient area of the lower leg for anastomosis with the dominant concomitant vein of LFCA-DB, a segment of the great saphenous vein from the contralateral lower leg was harvested and bridged to the dominant concomitant vein of LFCA-DB, and then end-to-end anastomosed with the above-knee great saphenous vein. The flap donor site wounds were directly sutured in 3 cases, and repaired with full-thickness skin grafts from the ipsilateral inguinal region in 5 cases. The length of the flap pedicle vessels and the length of the defect between the flap pedicle vessels and the planned anastomotic descending genicular artery and MFMB were recorded. Postoperatively, the flap survival and the wound healing in the donor sites were observed. During follow-up, the appearance, texture, and sensory recovery of the flaps, the recovery of flap donor sites, and the limb swelling in the vein donor sites were observed. At the last follow-up, the 5-point Likert scale was used to investigate the satisfaction of patients with the treatment effects in the flap recipient and donor sites. Results: The lengths of the flap pedicle vessels of patients were 12 to 17 cm, with an average of 14.1 cm. The lengths of the defects between the flap pedicle vessels and the planned anastomotic descending genicular artery and MFMB were 9 to 16 cm, with an average of 12.3 cm. Postoperatively, all flaps survived completely, without vascular crisis; all flap donor site wounds healed well. During follow-up of 12 to 40 months, the flaps of 6 patients showed no bulkiness; two flaps developed local bulkiness due to compression during the subsequent tibial bone transport treatment, of which one case improved after surgical debulking, and one case received no modification treatment. The flaps were soft in texture, with moderate tension and no ulcer, and all regained protective sensation. The flap donor sites all recovered well. The direct suture areas left slight linear scars, the skin grafted areas left slight scars, and the limbs in the vein donor sites showed no swelling. At the last follow-up, the satisfaction scores of patients with the treatment effects in the recipient and donor sites were all 4 and 5. Conclusions: The application of ALTF combined with "Y"-shaped great saphenous vein graft anastomosed to the descending genicular artery and MFMB to repair large soft tissue defects in the proximal-middle segment of the lower leg can effectively achieve the caliber physiological matching of the donor and recipient vessels, ensure the blood supply of the large-area flaps through dual blood supply, and avoid the periwound inflammation to reduce the risk of vascular crisis. The patients are satisfied with the treatment effect of the donor and recipient sites. 目的： 探讨应用股前外侧皮瓣（ALTF）联合“Y”形大隐静脉移植修复小腿近中段大面积软组织缺损的临床效果。 方法： 该研究为回顾性病例系列研究。2019年1月—2023年12月，山东第一医科大学附属省立医院手足与显微重建外科收治8例符合入选标准的小腿近中段大面积软组织缺损患者，其中男7例、女1例，年龄15~63岁。待创面清洁、感染控制后，小腿软组织缺损面积为18 cm×7 cm~30 cm×14 cm。采用ALTF联合“Y”形大隐静脉移植修复小腿软组织缺损，皮瓣切取面积为19 cm×8 cm~31 cm×15 cm。术中将“Y”形大隐静脉分叉端分别与膝降动脉、股内侧肌支（MFMB）行端端吻合，主干端与旋股外侧动脉降支（LFCA-DB）行端端吻合，构建“双入单出”的静脉桥接方式。将LFCA-DB优势伴行静脉与受区大隐静脉端端吻合；若小腿受区无合适静脉可与LFCA-DB优势伴行静脉吻合，则另截取对侧小腿大隐静脉段并将其桥接至LFCA-DB优势伴行静脉后与膝上大隐静脉行端端吻合。皮瓣供区创面直接缝合者3例，取同侧腹股沟区全厚皮片修复者5例。记录皮瓣蒂部血管长度、皮瓣蒂部血管与拟吻合膝降动脉和MFMB之间的缺损长度。术后观察皮瓣成活情况、皮瓣供区创面愈合情况。随访时，观察皮瓣外观、质地、感觉恢复情况，皮瓣供区恢复情况及静脉供区所在肢体肿胀情况。末次随访时，参照利克特5级量表调查患者对皮瓣供受区治疗效果的满意度。 结果： 该组患者皮瓣蒂部血管长度为12~17 cm，平均14.1 cm；皮瓣蒂部血管与拟吻合膝降动脉和MFMB之间的缺损长度为9~16 cm，平均12.3 cm。术后皮瓣均完全成活，未发生血管危象；皮瓣供区创面均愈合良好。随访12~40个月显示，6例患者皮瓣无臃肿；2例患者因后期胫骨骨搬运治疗导致皮瓣局部受压臃肿，其中1例患者经修整手术后改善，1例患者未行修整治疗。皮瓣质地柔软，张力适中，无溃疡，均恢复保护性感觉。皮瓣供区均恢复良好，其中直接拉拢缝合区遗留轻微线性瘢痕，植皮区遗留轻微瘢痕；静脉供区所在肢体无肿胀。末次随访时，患者对供受区治疗效果满意度评分均为4、5分。 结论： 利用ALTF联合“Y”形大隐静脉移植吻合膝降动脉和MFMB修复小腿近中段大面积软组织缺损，能有效实现供受区血管口径的生理性匹配，通过双重供血保障大面积皮瓣血运，规避创周炎症以降低血管危象风险，患者对供受区治疗效果满意。.
Objective: To analyze the incidence, mortality, and changing trends of malignant tumors among the elderly in tumor registration areas of Yunnan Province from 2012 to 2020. Methods: Tumor registry data from qualified registration sites in Yunnan Province from 2012 to 2020 were obtained from the Yunnan Tumor Follow-up Registration System. The annual and overall (2012-2020) incidence and mortality rates of all and major malignant tumors were calculated. The age-standardized rates were calculated using the 2000 Chinese standard population and Segi's world standard population. Joinpoint 4.9 software was used to calculate the average annual percentage change (AAPC) in the incidence and mortality rates of all and major malignant tumors from 2012 to 2020. Results: From 2012 to 2020, the incidence of malignant tumors among the elderly in tumor registry areas of Yunnan Province was 720.10/100 000, with a Chinese age-standardized rate of 708.83/100 000 and a world age-standardized rate of 691.71/100 000.Among them, the incidence rate was 901.52/100 000 for males and 550.45/100 000 for females. During the same period, the mortality rate of malignant tumors among the elderly in tumor registry areas of Yunnan Province was 538.76/100 000, with a Chinese age-standardized rate of 516.24/100 000 and a world age-standardized rate of 498.32/100 000. Among them, the mortality rate was 706.15/100 000 for males and 382.24/100 000 for females. Age-specific analysis of incidence and mortality showed that the 60～age group had the lowest incidence rate (556.23/100 000), while the 75～age group had the highest incidence rate (927.82/100 000). The 60～age group also had the lowest mortality rate (335.81/100 000), whereas the 80～age group had the highest mortality rate (855.31/100 000). From 2012 to 2020, the top five malignant tumors in terms of incidence were lung cancer, colorectal cancer, liver cancer, prostate cancer, and stomach cancer, while the top five in terms of mortality were lung cancer, liver cancer, colorectal cancer, stomach cancer, and prostate cancer. From 2012 to 2020, the incidence rate of all malignant tumors among the elderly in Yunnan Province showed no significant upward or downward trend (AAPC=-0.04%, 95% CI: -1.23% to 1.17%). Among major malignant tumors, the incidence rates of liver cancer and esophageal cancer showed an increasing trend, with an AAPC of 2.07% and 7.57%, respectively; while the incidence rates of bladder cancer and pancreatic cancer showed a decreasing trend, with an AAPC of -3.36% and -2.86%, respectively. The mortality rate of all malignant tumors also showed no significant upward or downward trend (AAPC=0.09%, 95% CI: -1.17% to 1.37%). Among major malignant tumors, the mortality rates of liver cancer and esophageal cancer showed an increasing trend, with AAPCs of 2.73% and 8.92%, respectively, while the mortality rate of breast cancer showed a decreasing trend (AAPC=-7.34%). Conclusions: From 2012 to 2020, the incidence and mortality of malignant tumors among the elderly in Yunnan Province remained relatively high, with no obvious downward trend. Lung cancer has long been the leading cause of both incidence and mortality in this population, while the trends of liver cancer and esophageal cancer remain concerning and warrant attention. 目的： 分析2012—2020年云南省肿瘤登记地区老年人恶性肿瘤发病和死亡水平及变化趋势。 方法： 从云南省肿瘤随访登记系统获取2012—2020年各年份云南省符合要求的登记点的肿瘤登记数据，计算各年度及2012—2020年合计全部恶性肿瘤和主要恶性肿瘤的发病率和死亡率，以2000年中国人口进行标化计算中标率，以Segi′s世界人口进行标化计算世标率。采用Joinpoint 4.9软件计算2012—2020年全部恶性肿瘤和主要恶性肿瘤发病率和死亡率平均年度变化百分比（AAPC）。 结果： 2012—2020年云南省肿瘤登记地区老年人恶性肿瘤发病率为720.10/10万，中标率为708.83/10万，世标率为691.71/10万。其中男性发病率为901.52/10万，女性发病率为550.45/10万。同时期，云南省肿瘤登记地区老年人恶性肿瘤死亡率为538.76/10万，中标率为516.24/10万，世标率为498.32/10万。其中男性死亡率为706.15/10万，女性死亡率为382.24/10万。年龄别发病和死亡分析显示，60～岁组发病率最低（556.23/10万），75～岁组发病率最高（927.82/10万）；60～岁组死亡率最低（335.81/10万），80～岁组死亡率最高（855.31/10万）。2012—2020年发病前5位的恶性肿瘤依次为肺癌、结直肠癌、肝癌、前列腺癌和胃癌，死亡前5位的恶性肿瘤依次为肺癌、肝癌、结直肠癌、胃癌和前列腺癌。2012—2020年云南省老年人全部恶性肿瘤发病率无明显上升或下降趋势（AAPC=-0.04，95% CI：-1.23%～1.17%）。主要恶性肿瘤中，肝癌和食管癌的发病率呈上升趋势，AAPC分别为2.07%和7.57%；膀胱癌和胰腺癌的发病率呈下降趋势，AAPC分别为-3.36%和-2.86%。全部恶性肿瘤死亡率亦无明显上升和下降趋势（AAPC=0.09，95% CI：-1.17～1.37）。主要恶性肿瘤中，肝癌和食管癌的死亡率呈上升趋势，AAPC分别为2.73%和8.92%；乳腺癌的死亡率呈下降趋势，AAPC为-7.34%。 结论： 2012—2020年云南省老年人恶性肿瘤发病和死亡水平一直偏高，无明显下降趋势。肺癌多年来一直是云南省老年人恶性肿瘤发病和死亡的主要原因，肝癌、食管癌的发病和死亡形势不容乐观，应引起重视。.
Objective: To investigate the effects of miR-1910-3p on proliferation, invasion, epithelial-mesenchymal transition (EMT) and in vivo tumor growth of lung adenocarcinoma (LUAD) cells. Methods: Bioinformatics analysis was performed using The Cancer Genome Atlas (TCGA) database and the Starbase database to compare the expression of miR-1910-3p between LUAD tissues and adjacent normal tissues. In vitro experiments were conducted using human LUAD cell lines (H1299, A549) and normal lung epithelial cells (BEAS-2B). The expression level of miR-1910-3p was verified by real-time quantitative polymerase chain reaction (RT-qPCR). H1299 and A549 cells were transfected with liposomes to establish miR-1910-3p overexpression (mimic group), knockdown (inhibitor group) and negative control (NC group) cell models. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8) assay and plate colony formation assay. Cell invasion was evaluated by Transwell invasion assay. The protein expression changes of EMT markers (E-cadherin, N-cadherin, Vimentin, Snail) were quantitatively analyzed by Western blot. For in vivo experiments, a subcutaneous xenograft model was established in nude mice, and tumor growth was monitored on days 7, 14, 21 and 28. At the end of the experiment, the nude mice were euthanized and the tumors were harvested for analysis. Results: Bioinformatics analysis showed that the expression level of miR-1910-3p was significantly higher in LUAD tissues than in adjacent normal tissues (P＜0.01). RT-qPCR results confirmed that compared with BEAS-2B cells, the relative expression levels of miR-1910-3p were significantly upregulated in A549 and H1299 LUAD cell lines (both P＜0.05). CCK-8 assay results showed that compared with the mimic NC group, overexpression of miR-1910-3p significantly enhanced the proliferative activity of A549 cells [mimic NC group (111.00±7.69)% vs. miR-1910-3p mimic group (119.70±7.54)%, P＜0.01] and H1299 cells [mimic NC group (113.40±15.21)% vs. miR-1910-3p mimic group (118.3±18.82)%, P＜0.01]; conversely, compared with the inhibitor NC group, knockdown of miR-1910-3p significantly inhibited the proliferative activity of A549 cells [inhibitor NC group (115.90±11.39)% vs. miR-1910-3p inhibitor group (111.90±8.83)%, P＜0.05] and H1299 cells [inhibitor NC group (113.20±15.34)% vs. miR-1910-3p inhibitor group (109.60±12.53)%, P＜0.05]. Plate colony formation assay showed that compared with the mimic NC group, overexpression of miR-1910-3p significantly enhanced the colony formation ability of A549 cells [mimic NC group (18.96±1.92)% vs. miR-1910-3p mimic group (37.33±3.66)%, P＜0.01] and H1299 cells [mimic NC group (22.86±2.78)% vs. miR-1910-3p mimic (42.33±2.58)%, P＜0.01]; conversely, compared with the inhibitor NC group, knockdown of miR-1910-3p significantly inhibited the colony forming ability of A549 cells [inhibitor NC group (19.46±3.33)% vs. miR-1910-3p inhibitor group (10.79±2.86)%, P＜0.01] and H1299 cells [inhibitor NC group (22.63±1.27)% vs. miR-1910-3p inhibitor group (12.96±1.45)%, P＜0.01]. Western blot analysis showed that compared with the mimic NC group, overexpression of miR-1910-3p significantly upregulated the expression of N-cadherin, Vimentin and the transcription factor Snail, while downregulating the expression level of E-cadherin (all P＜0.05). Transwell invasion assay showed that compared with the mimic NC group, overexpression of miR-1910-3p significantly enhanced the invasion ability of A549 cells [mimic NC group (333.00±35.68) vs. miR-1910-3p mimic group (521.67±46.92), P＜0.01] and H1299 cells [mimic NC group (341.67 ±32.87) vs. miR-1910-3p mimic group (537.66±33.13), P＜0.01]; conversely, compared with the inhibitor NC group, knockdown of miR-1910-3p significantly inhibited the invasive ability of A549 cells [inhibitor NC group (363.67±49.24) vs. miR-1910-3p inhibitor group (211.33±27.79), P＜0.01] and H1299 cells [inhibitor NC group (351.67±24.11) vs. miR-1910-3p inhibitor group (154.33±9.29), P＜0.01]. Subcutaneous xenograft experiment in nude mice showed that compared with the mimic NC group, overexpression of miR-1910-3p significantly promoted tumor growth in vivo, manifested as an increased tumor weight and volume (both P＜0.01). In the mimic NC group, tumor weights on days 7, 14, 21 and 28 were (0.08±0.01) g, (0.18±0.03) g, (0.41±0.06) g and (0.73±0.06) g, respectively; in the the miR-1910-3p mimic group, tumor weights on days 7, 14, 21 and 28 were (0.07±0.01) g, (0.35±0.06) g, (0.72±0.08) g, and (0.96±0.09) g, respectively. In the mimic NC group, tumor volumes on days 7, 14, 21 and 28 were (132.00±1.00) mm3, (254.67±7.10) mm3, (530.67± 42.71) mm3 and (853.33±74.10) mm3; in the miR-1910-3p mimic group, tumor volumes on days 7, 14, 21 and 28 were (132.00±2.00) mm3, (425.33±29.94) mm3, (829.00±62.00) mm3, and (1 123.33±95.38) mm3, respectively. Conclusion: miR-1910-3p acts an oncogene in LUAD, promoting tumor cell proliferation, invasion and in vivo tumorigenesis by activating EMT process. 目的： 探讨miR-1910-3p对肺腺癌细胞增殖、侵袭、上皮-间质转化（EMT）和体内肿瘤生长的影响。 方法： 通过癌症基因组图谱数据库和Starbase数据库进行生物信息学分析，分析miR-1910-3p在肺腺癌组织与癌旁正常组织中的表达差异。体外实验采用人肺腺癌细胞系（H1299、A549）及正常肺上皮细胞（BEAS-2B），应用实时荧光定量聚合酶链反应（RT-qPCR）验证miR-1910-3p表达水平。H1299和A549细胞分别通过脂质体转染法构建miR-1910-3p过表达（mimic组）、沉默（inhibitor组）及阴性对照（NC组）细胞模型。采用细胞计数试剂盒8（CCK-8）、平板克隆形成实验评估细胞增殖能力，Transwell侵袭实验检测细胞侵袭能力，Western blot技术定量分析EMT标志物（E-cadherin、N-cadherin、Vimentin、Snail）的蛋白表达变化。体内实验建立裸鼠皮下移植瘤模型，分别于第7天、第14天、第21天及第28天监测肿瘤生长情况，实验终点处死裸鼠并取瘤分析。 结果： 生物信息学分析显示，与癌旁正常组织比较，miR-1910-3p在肺腺癌组织中表达水平升高（P<0.01）。RT-qPCR验证结果显示，与BEAS-2B细胞比较，miR-1910-3p在肺腺癌细胞系A549细胞和H1299细胞中的相对表达水平均上调（均P<0.05）。CCK-8检测结果显示，与mimic NC组比较，过表达miR-1910-3p能够促进A549细胞［mimic NC组（111.00±7.69）%，miR-1910-3p mimic组（119.70±7.54）%，P<0.01］和H1299细胞［mimic NC组（113.40±15.21）%，miR-1910-3p mimic组（118.3±18.82）%，P<0.01］的增殖能力；反之，与inhibitor NC组比较，敲低miR-1910-3p能够抑制A549细胞［inhibitor NC组（115.90±11.39）%，miR-1910-3p inhibitor组（111.90±8.83）%，P<0.05］和H1299细胞［inhibitor NC组（113.20±15.34）%，miR-1910-3p inhibitor组（109.60±12.53）%，P<0.05］的增殖能力。平板克隆实验表明，与mimic NC组比较，过表达miR-1910-3p能够促进A549细胞［mimic NC组（18.96±1.92）%，miR-1910-3p mimic组（37.33±3.66）%，P<0.01］和H1299细胞［mimic NC组（22.86±2.78）%，miR-1910-3p mimic组（42.33±2.58）%，P<0.01］的克隆形成能力；反之，与inhibitor NC组比较，敲低miR-1910-3p能够抑制A549细胞［inhibitor NC组（19.46±3.33）%，miR-1910-3p inhibitor组（10.79±2.86）%，P<0.01］和H1299细胞［inhibitor NC组（22.63±1.27）%，miR-1910-3p inhibitor组（12.96±1.45）%，P<0.05］的克隆形成能力。Western blot分析结果显示，与mimic NC组比较，过表达miR-1910-3p能够同时上调N-cadherin、Vimentin及Snail转录因子的表达，下调E-cadherin的表达水平（均P<0.05）。Transwewll检测结果显示，与mimic NC组比较，过表达miR-1910-3p能够促进A549细胞［mimic NC组（333.00±35.68）个，miR-1910-3p mimic组（521.67±46.92）个，P<0.01］和H1299细胞［mimic NC组（341.67±32.87）个，miR-1910-3p mimic组（537.66±33.13）个，P<0.01］的侵袭能力；反之，与inhibitor NC组比较，敲低miR-1910-3p能够抑制A549细胞［inhibitor NC组（363.67±49.24）个，miR-1910-3p inhibitor组（211.33±27.79）个，P<0.01］和H1299细胞［inhibitor NC组（351.67±24.11）个，miR-1910-3p inhibitor组（154.33±9.29）个，P<0.01］的侵袭能力。裸鼠皮下成瘤实验显示，与mimic NC组比较，过表达miR-1910-3p能够促进裸鼠体内肿瘤生长，肿瘤重量和体积增加（均P<0.01）。mimic NC组裸鼠第7天、第14天、第21天及第28天肿瘤重量分别为（0.08±0.01）g、（0.18±0.03）g、（0.41±0.06）g和（0.73±0.06）g；miR-1910-3p mimic组分别为（0.07±0.01）g、（0.35±0.06）g、（0.72±0.08）g和（0.96±0.09）g。mimic NC组裸鼠第7天、第14天、第21天及第28天肿瘤体积分别为（132.00±1.00）mm3、（254.67±7.10）mm3、（530.67±42.71）mm3和（853.33±74.10）mm3；miR-1910-3p mimic组分别为（132.00±2.00）mm3、（425.33±29.94）mm3、（829.00±62.00）mm3和（1 123.33±95.38）mm3。 结论： miR-1910-3p在肺腺癌中发挥促癌基因作用，其通过激活EMT进程促进肿瘤细胞增殖、侵袭及体内成瘤。.
Objective: To investigate the impact of different low density lipoprotein-cholesterol (LDL-C) levels on the risk of gastrointestinal cancer. Methods: A prospective cohort study was used to observe 126 050 in service and retired employees of Kailuan Group who participated in the physical examination for the first time in 2006 or 2008. A total of 122 734 people were finally included in the statistical analysis. The subjects were divided into five groups according to the baseline quintile of low-density lipoprotein cholesterol, namely Q1 group, Q2 group, Q3 group, Q4 group and Q5 group. The impact of different LDL-C groups on the incidence of gastrointestinal tumors was analyzed by Cox proportional hazard model. Results: During follow-up of (12.83±2.43) years, 1 460 cases of gastrointestinal tumors occurred, including 225 cases of esophageal cancer, 431 cases of gastric cancer and 804 cases of colorectal cancer. Cox proportional hazard model analysis found that after adjusting for age, sex, body mass index, high-sensitivity C-reactive protein, education, smoking, alcohol consumption, diabetes, hypertension, physical exercise, excessive salt intake, family history of cancer and taking lipid-lowering drugs, compared with Q5 group, the hazard ratio (HR) values of gastrointestinal tumors in Q1, Q2, Q3 and Q4 groups were 1.28 (95% CI: 1.08, 1.50), 1.07 (95% CI: 0.90, 1.26), 1.31 (95% CI: 1.11, 1.54) and 1.12 (95% CI: 0.94, 1.33), respectively. The HR values of esophageal cancer were 1.21 (95% CI: 0.80, 1.82), 0.82 (95% CI: 0.52, 1.30), 1.47 (95% CI: 1.00, 2.17) and 0.84 (95% CI: 0.54, 1.31), respectively. The HR values of gastric cancer were 1.05 (95% CI: 0.78, 1.41), 0.84 (95% CI: 0.61, 1.16), 1.21 (95% CI: 0.91, 1.63) and 1.04 (95% CI: 0.77, 1.41), respectively. The HR values of colorectal cancer were 1.44 (95% CI: 1.15, 1.80), 1.28 (95% CI: 1.02, 1.62), 1.31 (95% CI: 1.04, 1.65) and 1.26 (95% CI: 1.00, 1.59), respectively. Conclusions: The decrease of baseline LDL-C level may be a risk factor for gastrointestinal malignant tumors, but low LDL-C increases the risk of malignant tumors in a location dependent manner. Although low LDL-C level increases the risk of colorectal cancer, it has no significant correlation with esophageal cancer and gastric cancer. 目的： 探讨不同低密度脂蛋白胆固醇（LDL-C）水平对胃肠道肿瘤发病的影响。 方法： 采用前瞻性队列研究方法，以首次参加2006年度或2008年度健康体检的126 050名开滦集团在职及离退休职工作为观察对象，最终共有122 734人纳入统计分析，根据基线LDL-C五分位数将观察对象分为5组，即Q1组、Q2组、Q3组、Q4组和Q5组。采用Cox比例风险模型分析不同LDL-C分组对胃肠道肿瘤发病的影响。 结果： 随访（12.83±2.43）年，发生胃肠道肿瘤1 460例，其中食管癌225例，胃癌431例，结直肠癌804例。Cox比例风险模型分析显示，校正年龄、性别、体质指数、超敏C-反应蛋白、受教育程度、吸烟、饮酒、糖尿病、高血压、体育锻炼、过量盐摄入、恶性肿瘤家族史和服用降脂药，与Q5组比较，Q1、Q2、Q3、Q4组发生胃肠道肿瘤的风险比（HR）值分别为1.28（95% CI：1.08～1.50）、1.07（95% CI：0.90～1.26）、1.31（95% CI：1.11～1.54）、1.12（95% CI：0.94～1.33）；发生食管癌的HR值分别为1.21（95% CI：0.80～1.82）、0.82（95% CI：0.52～1.30）、1.47（95% CI：1.00～2.17）、0.84（95% CI：0.54～1.31）；发生胃癌的HR值分别为1.05（95% CI：0.78~1.41）、0.84（95% CI：0.61~1.16）、1.21（95% CI：0.91～1.63）、1.04（95% CI：0.77～1.41）；发生结直肠癌的HR值分别为1.44（95% CI：1.15～1.80）、1.28（95% CI：1.02～1.62）、1.31（95% CI：1.04～1.65）、1.26（95% CI：1.00～1.59）。 结论： 基线LDL-C水平降低可能是胃肠道发生恶性肿瘤的危险因素，但低LDL-C增加恶性肿瘤的风险呈部位依赖性，低LDL-C水平虽增加了结直肠癌的发病风险，但与食管癌和胃癌无显著相关性。.
Objective: To investigate the clinical efficacy, toxicity and prognosis of SOX regimen (Oxaliplatin plus S-1) combined with Pabolizumab in the treatment of patients with metastatic gastric cancer. Methods: The clinical data of 107 patients with advanced metastatic gastric cancer admitted to Wuxi Branch of Ruijin Hospital Shanghai Jiao Tong University School of Medicine from May 2020 to May 2024 were retrospectively collected. According to the treatment methods, the patients in the chemotherapy group (n=56) only received SOX chemotherapy, and the patients in the combined group (n=51) were given SOX chemotherapy combined with Pembrolizumab. The differences of objective response rate (ORR), median progression-free survival (PFS), median overall survival (OS), grade Ⅲ-Ⅳ toxicity and quality of life improvement rate between the two groups were analyzed and compared. Results: According to the efficacy evaluation criteria of RECIST1.1, among all subjects, there were 1 case of complete response (CR) and 21 cases of partial response (PR) in chemotherapy group, 2 cases of CR and 31 cases of PR in combination group. The objective response rate (CR+PR%) in combination group was significantly higher than that in chemotherapy group (64.7% vs 39.3%, P=0.015). Stratified analysis showed that in patients with PD-L1 combined positive score (CPS) ≥1, the ORR of the combination group further increased to 75.9% (22/29), with a more significant advantage than the ORR of 38.9% (14/36) in the chemotherapy group (P=0.004). Survival analysis showed that among all enrolled patients, median PFS and median OS in combination group were 9.3 months and 17.4 months respectively, which were significantly longer than 8.4 and 13.1 months in chemotherapy group (PFS: P=0.020; OS: P=0.011). In addition, among patients with PD-L1 CPS ≥1, the median PFS and OS of the combination group showed a more significant advantage in prolonging compared to the chemotherapy group (median PFS: 10.7 months vs 8.2 months, P=0.003; median OS: 19.0 months vs 12.8 months, P=0.005). Among all enrolled patients, 14 cases showed improvement in quality of life in the chemotherapy group and 23 cases in the combination group, and the improvement rate of quality of life in combination group was significantly higher than that in chemotherapy group (45.1% vs 25.0%, P=0.029). There was no statistical difference in the incidence [67.9% (38/56) in chemotherapy group vs 78.4% (40/51) in combination group] of grade Ⅲ-Ⅳ toxicity between the two groups (P=0.219). Conclusion: In patients with PD-L1 CPS ≥1 or all enrolled patients, compared with chemotherapy alone, SOX regimen combined with pembrolizumab in the treatment of metastatic gastric cancer can significantly improve ORR, prolong PFS and OS, improve prognosis and quality of life, while the toxicity has not increased significantly. 目的： 探讨SOX方案（奥沙利铂+替吉奥）联合帕博利珠单抗治疗转移性胃癌患者的临床疗效、不良反应及预后。 方法： 回顾性收集上海交通大学医学院附属瑞金医院无锡分院2020年5月至2024年5月收治的107例晚期转移性胃癌患者的临床资料，根据治疗方法分为化疗组（n=56）和联合组（n=51），化疗组患者仅接受SOX方案化疗，联合组患者给予SOX方案联合帕博利珠单抗治疗。比较客观缓解率（ORR）、中位无进展生存时间（PFS）、中位总生存时间（OS）、Ⅲ～Ⅳ级不良反应、生活质量改善率等观察指标在两组间的差异。 结果： 根据实体瘤的疗效评价标准1.1版评估疗效，在全部受试者中，化疗组有1例完全缓解（CR）、21例部分缓解（PR），联合组有2例CR、31例PR，联合组ORR（CR+PR）显著高于化疗组（64.7%和39.3%，P=0.015）。分层分析显示，在程序性死亡受体配体1（PD-L1）联合阳性评分（CPS）≥1分的患者中，联合组ORR进一步提升至75.9%（22/29），较化疗组ORR 38.9%（14/36）升高优势更为明显（P=0.004）。生存分析显示，在全部入组患者中，化疗组中位PFS、中位OS分别为8.4和13.1个月，而联合组中位PFS、中位OS分别为9.3和17.4个月，均较化疗组明显延长（PFS P=0.020，OS P=0.011）；此外，在PD-L1 CPS≥1分的患者中，联合组的中位PFS及OS对比化疗组的延长优势均更加显著（中位PFS：10.7和8.2个月，P=0.003；中位OS：19.0和12.8个月，P=0.005）。所有入组患者中化疗组生活质量改善者14例，联合组为23例，联合组生活质量改善率较化疗组显著升高［45.1%（23/51）和25.0%（14/56），P=0.029］。化疗组和联合组间Ⅲ～Ⅳ级不良反应发生率［化疗组67.9%（38/56），联合组78.4%（40/51）］差异无统计学意义（P=0.219）。 结论： 在PD-L1 CPS≥1分的患者或所有入组胃癌患者中，与单纯化疗相比，SOX方案联合帕博利珠单抗治疗转移性胃癌可显著提升ORR，并延长PFS、OS，改善预后，提高生活质量，而不良反应未见明显增加。.
Objective: To investigate the efficacy and safety of 36 000 IU recombinant human erythropoietin (rhEPO) in the treatment of cancer-related anemia (CRA) and to evaluate whether 36 000 IU rhEPO can serve as a rational "reduced-dose alternative" to the 40 000 IU rhEPO regimen. Methods: The multicenter, open-label, non-inferiority, randomized controlled trial was conducted from March 2023 to July 2024 across 12 hospitals in China, including Liaoning Cancer Hospital. A total of 119 patients with CRA were enrolled and randomly assigned to receive the 36 000 IU rhEPO (n=61) or 40 000 IU rhEPO (n=58). The primary efficacy endpoint was the change in hemoglobin (Hb) levels from baseline at weeks 9-13. Secondary efficacy endpoints included hematologic and other biochemical parameters, transfusion requirements, quality of life (QOL), which was assessed by QOL scores and Karnofsky performance status (KPS) scores, and overall survival. Safety was evaluated by the incidence of treatment-emergent adverse events (TEAEs). Results: The least-squares mean changes in Hb from baseline to weeks 9-13 were (12.9±2.3) g/L in the 36 000 IU group and (13.4±2.4) g/L in the 40 000 IU group. Analysis of covariance showed no statistically significant difference between groups (F=-0.21, P=0.836), with a between-group difference of (-0.5±2.5) g/L (95% CI: -5.4 g/L, 4.4 g/L). The lower limit of the 95% CI (-5.4 g/L) exceeded the predefined non-inferiority margin of -10 g/L, indicating non-inferiority of the 36 000 IU dose compared to the 40 000 IU. At week 13, the proportions of patients with Hb increase ≥10 g/L were 82.0% (50/61) in the 36 000 IU group and 86.2% (50/58) in the 40 000 IU group, with no significant difference between groups (Qmh=0.40, P=0.527). The average weekly transfusion rate was 2.0% in both groups. No significantly significant differences were observed between the two groups in terms of changes in hematocrit, reticulocyte percentage, folate, vitamin B12, albumin, iron metabolism markers, QOL scores, KPS scores, or overall survival (all P＞0.05). Regarding safety, the incidence of TEAE was 80.3% (49/61) in the 36 000 IU group and 84.5% (49/58) in the 40 000 IU group, with nausea, fever, and fatigue being the most common symptoms (incidence＞5%). No drug-related serious adverse events were reported, and there were no significant differences between the groups (P＞0.05). Conclusions: The 36 000 IU dose of rhEPO is non-inferior to the 40 000 IU dose in terms of efficacy and has a favorable safety profile for the treatment of CRA. These findings support the use of 36 000 IU rhEPO as a reasonable clinical option for managing CRA. 目的： 探索36 000 IU重组人促红细胞生成素（rhEPO）治疗肿瘤相关性贫血（CRA）的有效性和安全性，评估36 000 IU rhEPO能否成为40 000 IU rhEPO的合理“减量替代”。 方法： 采用多中心、开放标签、非劣效、随机对照试验设计，于2023年3月至2024年7月在辽宁省肿瘤医院等中国12家医院开展。共纳入119例CRA受试者，根据rhEPO给药剂量规格随机分为36 000 IU组（n=61）和40 000 IU组（n=58）。主要疗效指标为第9～13周血红蛋白（Hb）水平较基线的变化值，次要疗效指标包括血细胞比容等血液生化指标、输血需求、生活质量［生活质量（QOL）评分和卡氏功能状态（KPS）评分］及总生存时间。安全性指标为治疗期不良事件（TEAE）发生率。 结果： 36 000 IU组和40 000 IU组受试者在第9～13周Hb较基线变化值的最小二乘均值分别为（12.9±2.3）g/L与（13.4±2.4）g/L，协方差分析显示组间差异无统计学意义（F=-0.21，P=0.836），组间差值为（-0.5±2.5）g/L（95% CI：-5.4～4.4 g/L），95% CI下限（-5.4 g/L）高于预设的非劣效界值（-10 g/L），表明36 000 IU组相对于40 000 IU组具有非劣效性。在第13周时，36 000 IU组和40 000 IU组Hb升高≥10 g/L的受试者比例分别为82.0%（50/61）和86.2%（50/58），差异无统计学意义（Qmh=0.40，P=0.527），且两组平均周输血率均为2.0%。两组受试者治疗前后的血细胞比容、网织红细胞百分比、叶酸、维生素B12、白蛋白、铁代谢指标、QOL评分、KPS评分以及总生存时间差异均无统计学意义（均P＞0.05）。在安全性方面，36 000 IU组和40 000 IU组TEAE发生率分别为80.3%（49/61）与84.5%（49/58），以恶心、发热和乏力症状为主（发生比例高于5%），均未报告任何药物相关严重不良事件，组间差异无统计学意义（均P＞0.05）。 结论： 36 000 IU rhEPO在治疗CRA方面对比40 000 IU rhEPO具有非劣效性，且安全性良好，36 000 IU剂量可作为临床治疗CRA的合理选择。.
Comprehensive genomic profiling (CGP) based on next-generation sequencing (NGS) has emerged as a mainstream approach for clinical diagnosis and treatment with the development of precision oncology. However, as the first stage of NGS testing, probe design has not yet been standardized by a reliable assessment framework. In response to this unmet need, the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, in collaboration with the Tumor Pathology Committee of China Anti-Cancer Association, the National Institutes for Food and Drug Control, and other authoritative institutions, convened clinical experts, pathologists, and representatives from third-party medical laboratories for in-depth discussions on standardization strategies. The expert panel formulated six core technical consensus statements, including the selection of target genes and regions, gene combination strategies, probe performance evaluation, and probe updates, based on a thorough analysis of both international studies and domestic clinical experience. For the design of the probe pool, this consensus methodically suggests a full-process technical specification. It fills a technical gap in tumor NGS probe design by standardizing probe design, establishing a multi-level performance validation system, and dynamically managing probe modifications. Furthermore, it supports the shift of genomic testing from "clinically available" to "clinically reliable" by offering a scientific basis for the National Medical Products Administration's (NMPA) regulatory review of laboratory-developed tests (LDTs) for oncology. 随着肿瘤精准医学发展，基于二代测序（NGS）的肿瘤全景变异（CGP）检测成为临床诊疗的主流检测手段。然而，作为NGS检测的起始环节，探针设计尚未建立技术标准或评估体系。中国医学科学院北京协和医学院肿瘤医院联合中国抗癌协会病理专委会、中国食品药品检定研究院等权威机构组织临床专家、病理专家及第三方医学检验机构深入研讨，参考国内外文献，结合中国临床实践，针对CGP检测产品的目标基因及目标区域选择、基因组合方式、探针性能评估、探针变更等多个关键环节达成6条纲领性的技术共识，系统提出探针池设计全流程技术规范。共识通过探针设计标准化、多层级性能验证体系的构建及探针动态变更管理，填补了肿瘤NGS探针设计技术标准空白，为国家药品监督管理局对肿瘤NGS实验室自建方法的合规性审查提供科学依据，推动肿瘤基因检测从“临床可用”向“临床可信”转变。.
Objective: To construct a non-invasive detection platform based on surface enhanced Raman spectroscopy (SERS) combined with machine learning, achieving high-precision recognition of precancerous lesions of gastric cancer. Method: Serum samples were collected from 213 subjects at Jiangdu People's Hospital Affiliated to Yangzhou University from July 6, 2023 to January 1, 2025, including 51 healthy controls and 162 gastric lesion patients (48 cases of high-grade intraepithelial neoplasia [HGIN], 60 cases of early gastric cancer, and 54 cases of advanced gastric cancer). Au Octahedral Nanoparticles (Au OCNPs) substrates was synthesized by seed mediated method, and its morphology was characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Serum samples were dropped onto the Au OCNPs array, and SERS spectra were acquired using a confocal micro-Raman spectrometer (excitation wavelength 785 nm, laser power 5 mW, exposure time 10 s). All original spectral data were preprocessed using Origin 2019 software, including spectral band selection, Savitzky-Golay smoothing, airPLS baseline correction, and Min-Max normalization. A principal component analysis-diagonal quadratic discriminant analysis (PCA-DQDA) model was constructed in MATLAB R2023a to evaluate the classification performance for healthy subjects and gastric lesion patients at different stages, and the model's accuracy and area under the curve (AUC) were validated by five-fold cross-validation. Results: The Au OCNPs arrays showed uniform morphology, sharp edges, a lattice spacing of 0.226 nm, and a characteristic absorption peak at 534 nm, with significant SERS enhancement and good reproducibility. The characteristic peak differences in SERS spectra between healthy subjects and gastric lesion patients were mainly concentrated at 625, 728, 1 006, 1 326, 1 446, and 1 584 cm-1, indicating significant differences in the vibrational modes of biomolecules such as proteins and nucleic acids in serum during the progression of gastric precancerous lesions. For the binary classification of healthy subjects and all gastric lesion patients, the PCA-DQDA model achieved an overall accuracy of 97.2% (207/213). For the multi-class classification of healthy subjects and gastric lesion patients at different stages, the model achieved an overall accuracy of 93.4% (199/213), and an AUC of 0.872. Misclassifications occurred between adjacent subgroups with similar biological characteristics: among 51 healthy subjects, 4 were misclassified as HGIN, with a classification accuracy of 92.2% (47/51); among 48 HGIN samples, 1 was misclassified as healthy and 2 as early gastric cancer, with a classification accuracy of 93.6% (45/48). Conclusion: The serum SERS detection platform based on Au OCNPs arrays and the PCA-DQDA model exhibits advantages of non-invasiveness, high sensitivity, and molecular specificity in identifying gastric precancerous lesions, providing a new strategy for their recognition. 目的： 构建一种基于表面增强拉曼光谱（SERS）与机器学习相结合的无创检测平台，实现对胃癌前病变的高精度识别。 方法： 收集2023年7月6日至2025年1月1日扬州大学附属江都人民医院213例受试者血清样本，包括健康对照51例和胃病变患者162例［含高级别上皮内瘤变（HGIN）48例，早期胃癌60例，进展期胃癌54例］。通过种子介导法合成金八面体纳米颗粒（Au OCNPs）阵列基底，并利用扫描电镜和透射电镜表征其形貌。将血清样本滴加至Au OCNPs阵列，采用共聚焦显微拉曼光谱仪（激发波长785 nm，激光功率5 mW，曝光时间10 s）采集SERS光谱。通过Origin 2019软件对所有原始光谱数据预处理（频段截取、Savitzky-Golay平滑、airPLS基线校正、Min-Max归一化）。在MATLAB R2023a软件中构建主成分分析-对角二次判别分析（PCA-DQDA）模型检测对健康受试者及各阶段胃病变患者的分类性能，五折交叉验证模型的准确率和曲线下面积（AUC）。 结果： Au OCNPs阵列形貌均一，棱角锐利，晶格间距0.226 nm，在534 nm处显示特征吸收峰，具有显著的SERS增强效应和良好重现性。健康受试者及各阶段胃病变患者光谱的特征峰差异主要集中在625、728、1 006、1 326、1 446和1 584 cm-1，表明胃癌前病变及进展过程中，血清内蛋白质、核酸等生物分子的振动模式出现显著差异，并体现在SERS光谱数据中。PCA-DQDA模型区分健康受试者与总体胃病变患者的二分类预测结果显示，总体分类准确率为97.2%（207/213）；PCA-DQDA模型区分健康受试者与各阶段胃病变患者的多分类预测结果显示，总体分类准确率为93.4%（199/213），AUC为0.872。误判均发生在生物学特征相近的相邻亚组之间，其中，51个健康受试者中，有4个误判为HGIN，分类准确率为92.2%（47/51）。48例HGIN样本中，有1个错分为健康受试者，2个错分为早期胃癌，分类准确率为93.6%（45/48）。 结论： 基于Au OCNPs阵列与PCA-DQDA模型的血清SERS检测平台，在识别胃癌前病变方面具有非侵入性、高灵敏度和分子特异性检测优势，为胃癌前病变识别提供了新策略。.
The incidence of prostate cancer in China is increasing year by year. Data from 2022 indicate that its incidence ranks sixth among male malignant tumors, with a high proportion of advanced-stage patients and high mortality rate among new cases each year, leading to a continuously increasing disease burden. Androgen deprivation therapy (ADT) has been the cornerstone of treatment for advanced prostate cancer since its establishment in 1941. Whether as monotherapy or in combination with novel endocrine therapeutic agents, ADT-based regimens should be maintained throughout the entire treatment course of advanced prostate cancer. Testosterone is a critical biomarker for monitoring the efficacy of ADT, and testosterone management is of great significance in achieving refined ADT goals and improving patient prognosis. This consensus recommends a testosterone level of ＜50 ng/dL as the castration standard. On this basis, deep testosterone suppression, defined as reducing testosterone levels to below 20 ng/dL, may serve as a reference indicator for improving patient prognosis. Regarding testosterone measurement, radioimmunoassay (RIA), chemiluminescence immunoassay (CLIA), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) are all available methods. Considering the balance between cost and efficiency, this consensus recommends that a stepwise testing approach for testosterone monitoring be adopted if conditions permit, to improve sensitivity, accuracy, and stability. Testosterone monitoring should be performed throughout the entire process of prostate cancer diagnostic and treatment. Baseline level should be measured before ADT initiation; monitoring should be performed monthly for the first 6 months of treatment; after disease stabilization, every 3 months for the first 3 years, and every 6 months thereafter. Patients in critical phases such as neoadjuvant therapy, initiation of adjuvant therapy, biochemical recurrence, and metastatic castration-sensitive prostate cancer require particular attention to testosterone surveillance. In the whole-process management of prostate cancer diagnosis and treatment, attention should be paid to testosterone monitoring alongside prostate-specific antigen (PSA) surveillance. PSA cannot directly replace testosterone levels in evaluating ADT efficacy, as there is no linear correlation between the two parameters. Maintaining an appropriate frequency of testosterone testing and using the results of both tests to guide personalized therapeutic decisions can facilitate timely detection of testosterone escape and confirmation of castration-resistant status, provide evidence for treatment switching, and ultimately improve patient survival benefits and quality of life. 中国前列腺癌发病率逐年上升，2022年数据显示其发病率已位列男性恶性肿瘤第6位，且每年新发病例中晚期患者占比高、病死率高，疾病负担持续加重。雄激素剥夺治疗（ADT）自1941年确立以来始终是晚期前列腺癌治疗的基石，无论是基础的单药或联合新型内分泌治疗药物方案均应贯穿晚期前列腺癌治疗全周期。睾酮是ADT治疗疗效监测的关键指标，睾酮管理对实现ADT精细化管理目标、改善患者预后具有重要意义。共识推荐睾酮水平＜50 ng/dl为去势标准，在此基础上，深度降酮即将睾酮水平抑制到＜20 ng/dl的更低水平可作为改善患者预后的参考指标。在睾酮水平检测方面，放射性免疫分析法、化学发光免疫分析法及液相色谱-质谱联用法均为可及的检测手段。考虑到成本与效能的平衡，建议有条件可采用分步检测法监测睾酮，以提高敏感性、精确性及稳定性。睾酮监测应贯穿前列腺癌诊疗全程，ADT治疗开始前需检测基线水平，治疗开始后前6个月应每月监测，病情稳定后3年内每3个月检测1次，3年后每6个月检测1次；处于新辅助治疗、辅助治疗起始、生化复发及转移性去势敏感性前列腺癌等关键阶段的患者，更需重视睾酮监测。前列腺癌诊疗全程管理中，关注前列腺特异性抗原（PSA）的同时应重视睾酮监测。PSA无法直接替代睾酮水平评估ADT疗效，两者无线性相关性。维持合理的睾酮检测频率，结合两者检测结果指导个性化治疗决策，可及时发现睾酮逃逸、确认去势抵抗状态等，为治疗切换提供依据，最终提高患者生存获益和生活质量。.
Objective: To explore the predictive value of 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) for the major pathologic response (MPR) in non-small cell lung cancer (NSCLC) patients receiving neoadjuvant immunotherapy. Methods: A total of 36 patients who received neoadjuvant immunotherapy monotherapy and 54 patients who received neoadjuvant immunotherapy combined with other treatments at the Cancer Hospital, Chinese Academy of Medical Sciences from April 2018 to February 2022 were enrolled in this study. Radiologists measured the standardized uptake value lean body mass (SUL), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor before and after neoadjuvant immunotherapy, and evaluated the treatment response in accordance with the PET Response Criteria in Solid Tumors (PERCIST). Pathologists assessed the pathologic response of the primary tumor. The expression level of programmed cell death-ligand 1 (PD-L1) was detected by immunohistochemistry, and the tumor mutational burden (TMB) level was detected by next-generation sequencing. Receiver operating characteristic (ROC) curves were used to evaluate the performance of PET-CT metabolic parameters (baseline, post-neoadjuvant immunotherapy, and percentage change), PERCIST, PD-L1 expression, and TMB in predicting MPR. Results: Among the 90 patients, 40 (44.4%) achieved MPR after neoadjuvant immunotherapy. Compared with the baseline, the SULmax, SULpeak, SULmean, MTV and TLG in the MPR group decreased after neoadjuvant immunotherapy (all P＜0.001), while no significant changes in SULmax, SULpeak, SULmean, MTV, and TLG were observed in the non-MPR group (all P＞0.05). ROC curve analysis showed that baseline PET-CT metabolic parameters had no predictive value for MPR in NSCLC after neoadjuvant immunotherapy, with the AUCs ranging from 0.504 to 0.619 (all P＞0.05). The AUCs of post-neoadjuvant PET-CT metabolic parameters for predicting MPR ranged from 0.757 to 0.927 (all P＜0.001). The AUCs of the percentage changes in PET-CT metabolic parameters before and after neoadjuvant immunotherapy for predicting MPR ranged from 0.848 to 0.976 (all P＜0.001). Among these metabolic parameters, the ΔSULmax% exhibited the highest predictive performance, with an AUC of 0.976 (P＜0.001). When the optimal cutoff value of ΔSULmax% was set at -33%, the sensitivity, specificity, and accuracy were 0.960, 0.975, and 0.967, respectively. The AUC of PERCIST for predicting MPR in NSCLC after neoadjuvant immunotherapy was 0.931 (95% CI: 0.881-0.981). The AUCs of PD-L1 expression and TMB for predicting MPR in NSCLC after neoadjuvant immunotherapy were 0.686 (95% CI: 0.562-0.810) and 0.693 (95% CI: 0.566-0.820), respectively. The AUCs of PET-CT metabolic parameters (post-neoadjuvant immunotherapy, percentage changes and PERCIST) for predicting MPR were superior than those of PD-L1 expression (all P＜0.05) and TMB (all P＜0.05). Conclusions: PET-CT metabolic parameters post neoadjuvant immunotherapy and the percentage changes of metabolic parameters before and after neoadjuvant immunotherapy along with PERCIST can predict MPR in NSCLC receiving neoadjuvant immunotherapy. Among these parameters, the ΔSULmax% exhibited the highest predictive performance. 目的： 探究18F-氟脱氧葡萄糖（FDG）正电子发射计算机体层摄影（PET-CT）对非小细胞肺癌（NSCLC）新辅助免疫治疗后主要病理缓解（MPR）的预测价值。 方法： 纳入2018年4月至2022年2月在中国医学科学院肿瘤医院行新辅助免疫单药治疗的患者36例，行新辅助免疫联合其他治疗的患者54例。由PET-CT医师测量新辅助免疫治疗前后肿瘤原发灶瘦体质量校正的标准摄取值（SUL）、肿瘤代谢体积（MTV）和肿瘤总糖酵解值（TLG），依据实体瘤疗效PET评价标准（PERCIST）评估治疗反应。由病理科医师评估肿瘤原发灶的病理反应。采用免疫组织化学法检测程序性细胞死亡配体1（PD-L1）的表达水平，采用二代测序技术检测肿瘤突变负荷（TMB）水平。采用受试者操作特征曲线评估PET-CT代谢参数（基线、新辅助免疫治疗后和变化百分数）、依据PERCIST、PD-L1表达水平和TMB对MPR的预测效能。 结果： 90例患者中，40例（44.4%）新辅助免疫治疗后达到MPR。与基线比较，新辅助免疫治疗后MPR组SULmax、SULpeak、SULmean、MTV和TLG均降低（均P＜0.001），而非MPR组SULmax、SULpeak、SULmean、MTV和TLG变化无统计学意义（均P＞0.05）。ROC曲线分析显示，基线PET-CT代谢参数对NSCLC新辅助免疫治疗后MPR无预测价值，曲线下面积（AUC）为0.504～0.619（均P＞0.05）。新辅助免疫治疗后PET-CT代谢参数预测NSCLC新辅助免疫治疗后MPR的AUC为0.757～0.927（均P＜0.001）。新辅助免疫治疗前后PET-CT代谢参数变化百分数预测NSCLC新辅助免疫治疗后MPR的AUC为0.848～0.976（均P＜0.001），其中ΔSULmax%的预测效能最高，AUC为0.976（P＜0.001），最佳界值为ΔSULmax%=-33%时，灵敏度为0.960，特异度为0.975，准确度为0.967。依据PERCIST评估NSCLC新辅助免疫治疗后MPR的AUC为0.931（95% CI：0.881～0.981）。PD-L1表达和TMB对NSCLC新辅助免疫治疗后MPR的AUC分别为0.686（95% CI：0.562～0.810）和0.693（95% CI：0.566～0.820）。通过PET-CT（新辅助免疫治疗后PET-CT代谢参数、新辅助免疫治疗前后PET-CT代谢参数变化百分数、依据PERCIST）预测NSCLC新辅助免疫治疗后MPR的AUC均明显优于PD-L1表达的AUC（均P＜0.05）和TMB的AUC（均P＜0.05）。 结论： 新辅助免疫治疗后的PET-CT代谢参数、治疗前后代谢参数变化百分数、依据PERCIST均能预测NSCLC新辅助免疫治疗后MPR，其中ΔSULmax%的预测效能最高。.
Objective: To investigate the diagnostic value of multimodal blood flow imaging in differentiating benign and malignant small renal masses (SRMs). Methods: A total of 170 patients with renal tumors (172 lesions) who underwent surgical treatment at Tianjin Medical University Cancer Institute and Hospital from January 2020 to December 2023 were enrolled.The maximum diameter of the tumors was ≤4 cm. All patients received Color Doppler flow imaging (CDFI), Power Doppler imaging (PDI), Microflow imaging (MFI), and Contrast-enhanced ultrasound (CEUS) examinations before surgery. Two sonologists were responsible for grading the blood flow and evaluating the vascular morphology to make a diagnosis of whether the tumors were benign or malignant. Taking the postoperative pathological diagnosis as the gold standard, the receiver operating characteristic (ROC) curve analysis was used to compare the diagnostic efficacy of the four ultrasound examination methods. Results: Among the 172 lesions, 141 were malignant and 31 were benign. In the MFI imaging mode, the Kappa value for the evaluation of SRMs blood flow grading by two independent sonologists was 0.819, and the Kappa value for vascular morphology was 0.806.The detection rate of MFI for lesions with blood flow grading of 2-3 and vascular morphology of types Ⅳ-Ⅴ was 77.9% (134/172), which was higher than that of CDFI [36.6% (63/172)] and PDI [43.0% (74/172)]. Blood flow grading of 2-3 and vascular morphology of types Ⅳ-Ⅴ in the MFI mode could serve as independent predictors for malignant SRMs (P＜0.001). In the CEUS mode, malignant SRMs mainly manifested as fast wash-in (75.9%), fast wash-out (70.9%), and high enhancement (85.1%). In contrast, benign SRMs mainly showed slow wash-in (51.6%), slow wash-out (45.2%), and low enhancement (45.2%). Ring enhancement was observed in 37.6% of malignant SRMs, while no ring enhancement was detected in any of the benign SRMs. All these differences were statistically significant (P＜0.001).The accuracy of CDFI, PDI, MFI, and CEUS in diagnosing malignant SRMs was 0.500, 0.552, 0.855, and 0.901, respectively; the sensitivity was 0.418, 0.489, 0.887, and 0.986, respectively; the specificity was 0.871, 0.839, 0.710, and 0.516, respectively; and the area under the curve (AUC) was 0.645, 0.664, 0.798, and 0.751, respectively. Overall, MFI and CEUS demonstrated more superior diagnostic efficacy for SRMs. Conclusions: MFI exhibits high sensitivity in detecting the microvascular flow signals of SRMs. It shows comparable diagnostic performance to CEUS in differentiating the benign and malignant SRMs. It is a non-invasive, safe, cost-effective, and highly repeatable examination method. 目的： 探讨多模态血流成像对肾脏小肿瘤（SRMs）的良恶性诊断价值。 方法： 2020年1月至2023年12月在天津医科大学肿瘤医院行手术治疗的肾肿瘤患者170例（病灶172个），肿瘤最大径≤4 cm，术前均行彩色多普勒血流成像（CDFI）、能量多普勒血流成像（PDI）、微视血流成像（MFI）和超声造影（CEUS）检查。由2位超声医师进行血流分级和血管形态评估并进行良恶性诊断。以术后病理诊断为金标准，采用受试者操作特征曲线（R0C）分析比较4种超声检查方法的诊断效能。 结果： 172个病灶中，恶性141个，良性31个。MFI成像模式下，2位独立超声医师评估SRMs血流分级的Kappa值为0.819，血管形态的Kappa值为0.806。MFI对血流分级为2～3级和血管形态为Ⅳ～Ⅴ型病灶的显示率为77.9%（134/172），高于CDFI［36.6%（63/172）］和PDI［43.0%（74/172）］，MFI模式下血流分级为2～3级和血管形态为Ⅳ～Ⅴ型可作为恶性SRMs的独立预测因子（P＜0.001）。CEUS模式下，恶性SRMs主要表现为快进（75.9%）、快退（70.9%）和高增强（85.1%），而良性SRMs主要表现为慢进（51.6%）、慢退（45.2%）和低增强（45.2%），37.6%的恶性SRMs可见环状增强，良性SRMs均未见环状增强，差异均有统计学意义（P＜0.001）。CDFI、PDI、MFI和CEUS诊断恶性SRMs的准确性分别为0.500、0.552、0.855和0.901，灵敏度分别为0.418、0.489、0.887和0.986，特异度分别为0.871、0.839、0.710和0.516，曲线下面积分别为0.645、0.664、0.798和0.751。综合来看，MFI和CEUS对SRMs的诊断效能更为优越。 结论： MFI在检测SRMs的微血流信号时表现出较高的灵敏度，在区分SRMs良恶性方面表现出与CEUS相当的诊断性能，是一种无创、安全、经济、可重复性较好的检查方法。.
Objective: To construct a prediction model integrating molecular markers, imaging features, and clinicopathological characteristics for brain metastasis (BM) of breast cancer and provide a quantitative tool for clinical precise stratification of breast cancer. Methods: A total of 346 breast cancer patients admitted to the Affiliated Tumor Hospital of Xinjiang Medical University from January 2018 to December 2023 were enrolled, including 214 cases in the BM group and 132 cases in the control group. The patients were divided into a training set (242 cases) and an internal validation set (104 cases) at a ratio of 7∶3. A total of 1,483 female breast cancer patients from the Surveillance, Epidemiology, and End Results Program (SEER) database (2017-2021) were used as the external validation set, including 530 cases in the BM group and 953 cases in the control group. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to screen key features, and a nomogram prediction model for breast cancer BM was constructed based on the results of multivariate logistic regression analysis of factors influencing breast cancer BM. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the model performance, and internal and external validations of the model were conducted. Results: LASSO regression based on the training set screened out 11 key features, namely, primary side, primary quadrant, number of lesions, histological grade, differentiation degree, Ki-67 index, N stage, clinical stage, lymphovascular invasion, aspect ratio, and lesion margin morphology. Multivariate logistic regression analysis showed that the number of lesions (multiple lesions: OR=7.49, 95% CI: 3.59-15.64), histological grade (grade 2: OR=9.02, 95% CI: 4.87-16.70; grade 3: OR=12.57, 95% CI: 6.60-23.94), differentiation degree (moderate differentiation: OR=0.18, 95% CI: 0.06-0.53; well differentiation: OR=0.02, 95% CI: 0.01-0.06), Ki-67 index (15%-29%: OR=0.28, 95% CI: 0.11-0.74; ≥30%: OR=4.01, 95% CI: 2.45-6.58), clinical stage (stageⅢ: OR=3.53, 95% CI: 1.76-7.07; stage Ⅳ: OR=35.43, 95% CI: 13.97-89.91), and lymphovascular invasion (presence of lymphovascular invasion: OR=12.42, 95% CI: 6.84-22.53) were independent influencing factors for breast cancer BM. The nomogram prediction model for breast cancer BM constructed based on the results of multivariate logistic regression analysis had areas under the curve (AUCs) for predicting breast cancer BM of 0.869 (95% CI: 0.826-0.912), 0.857 (95% CI: 0.817-0.897), and 0.868 (95% CI: 0.849-0.887) in the training set, internal validation set, and external validation set, respectively. All calibration curves were close to the reference line, and when the threshold probability was >0.2, the net benefit was significantly higher than that of the "treat all" or "treat none" strategy. Conclusions: A nomogram prediction model for breast cancer BM integrating multi-dimensional information (molecular subtypes, imaging features, and clinicopathological characteristics) was successfully constructed. This model has good ability to distinguish breast cancer patients with BM from thosewithout, with favorable calibration and clinical applicability, and provides a quantitative tool for clinical assessment of the risk of breast cancer BM. 目的： 构建整合分子标志、影像学特征及临床病理特征的乳腺癌脑转移预测模型，为乳腺癌的临床精准分层提供量化工具。 方法： 纳入2018年1月至2023年12月新疆医科大学附属肿瘤医院收治的346例乳腺癌患者，其中脑转移组214例，对照组132例。按照7︰3的比例分为训练集（242例）和内部验证集（104例）。将监测、流行病学和结果（SEER）数据库中2017—2021年的1 483例女性乳腺癌患者作为外部验证集，其中脑转移组530例，对照组953例。采用最小绝对收缩与选择算子（LASSO）回归筛选关键特征，并基于乳腺癌脑转移影响因素的多因素logistic回归分析结果构建乳腺癌脑转移列线图预测模型。采用受试者操作特征曲线、校准曲线及决策曲线分析评估模型性能，并对模型进行内部和外部验证。 结果： 基于训练集的LASSO回归筛选出11个关键特征，分别为原发侧别、原发象限、病灶数量、组织学分级、分化程度、Ki-67指数、N分期、临床分期、脉管瘤栓、纵横比、病灶结构形态。多因素logistic回归分析显示，病灶数量（多病灶：OR=7.49，95% CI：3.59～15.64）、组织学分级（2级：OR=9.02，95% CI：4.87～16.70；3级：OR=12.57，95% CI：6.60～23.94）、分化程度（中分化：OR=0.18，95% CI：0.06～0.53；高分化：OR=0.02，95% CI：0.01～0.06）、Ki-67指数（15%～29%：OR=0.28，95% CI：0.11～0.74；≥30%：OR=4.01，95% CI：2.45～6.58）、临床分期（Ⅲ期：OR=3.53，95% CI：1.76～7.07；Ⅳ期：OR=35.43，95% CI：13.97～89.91）和脉管瘤栓（有脉管瘤栓：OR=12.42，95% CI：6.84～22.53）是乳腺癌脑转移的独立影响因素。基于多因素logistic回归分析结果构建的乳腺癌脑转移列线图预测模型，在训练集、内部验证集和外部验证集预测乳腺癌脑转移的曲线下面积分别为0.869（95% CI：0.826～0.912）、0.857（95% CI：0.817～0.897）和0.868（95% CI：0.849～0.887），校准曲线均贴近参考线，当阈值概率＞0.2时的净获益均显著高于“全干预”或“全不干预”策略。 结论： 成功构建了整合分子亚型、影像学特征及临床病理特征等多维度信息的乳腺癌脑转移列线图预测模型，该模型对乳腺癌脑转移与非脑转移患者的区分能力良好，具有较好的校准度和临床适用性，为临床评估乳腺癌脑转移的风险提供了量化工具。.
Objective: To investigate the preoperative diagnostic value of ultrasound-guided fine-needle aspiration biopsy wash-out fluid (FNA-CT) in medullary thyroid carcinoma (MTC) with mildly elevated serum calcitonin levels. Methods: 267 patients with MTC diagnosed in Tianjin Cancer Hospital between Jan 2015 and Jan 2024 were enrolled in the study. Based on serum calcitonin, patients were divided into two groups:＞100 ng/L and 10-100 ng/L. Sonographic features, clinicopathological characteristics and prognostic outcomes were evaluated between the two groups. The diagnostic efficacy of serum calcitonin and FNA-CT in MTC and non-medullary thyroid carcinoma with slightly high serum calcitonin were evaluated. The best cutoff values of serum calcitonin and FNA-CT were calculated by subject operating characteristic curve (ROC). The diagnostic efficacy was analyzed for MTC with mildly elevated serum calcitonin according the best cut off points. Results: Compared to the >100 ng/L group, MTC patients with serum calcitonin 10-100 ng/L exhibited distinct ultrasonographic features: taller-than-wide shape, non-adjacent to thyroid capsule, less vascularity, and CACA-TIRADS 4 (all P＜0.05). Clinicopathologically, the serum calcitonin 10-100 ng/L group demonstrated single focus rather than multifocality, smaller tumor size, higher prevalence of microcarcinoma, a lower degree of local invasion, earlier tumor stages (T stage, N stage, TNM stage), smaller extent of thyroidectomy and lymphadenectomy and lower diagnostic accuracy of FNA (all P＜0.05). The group also showed higher biochemical cure rate (90.0% and 54.2%)and lower rates of biochemical recurrence (5.5% and 23.1%) and tumor recurrence (3.6% and 22.6%, P＜0.001). Among MTC with serum calcitonin 10-100 ng/L, the median of serum calcitonin levels were 40.0 ng/L (19.5, 65.8 ng/L) for MTC vs. 16.6 ng/L (13.2, 20.8 ng/L, P＜0.001) for non-medullary thyroid carcinoma. The median of FNA-CT were 2 000.0 ng/L (1 334.0, 2 000.0 ng/L) vs. 0.8 ng/L (0.5, 2.0 ng/L, P＜0.001). The best cutoff points were 22.9 ng/L for serum calcitonin and 58.7 ng/L for FNA-CT. The sensitivity, specificity, negative predictive value, positive predictive value and the area under curve (AUC) were 67.3%, 82.9%, 65.4%, 61.2% and 0.829 (95% CI: 0.731-0.903) at the best cutoff point of 22.9 ng/L for serum calcitonin. The sensitivity, specificity, negative predictive value, positive predictive value and AUC were 98.2%, 97.6%, 97.61%, 98.1% and 0.998 (95% CI: 0.989-0.998) at the best cutoff point of 58.7 ng/L for FNA-CT. Conclusions: MTC with slightly elevated serum calcitonin commonly correlates with an early-stage disease. FNA-CT has demonstrated near-perfect diagnostic performance and improved the early detection in this population. 目的： 探讨超声引导下细针穿刺洗脱液降钙素（FNA-CT）检测对血清降钙素轻度升高甲状腺髓样癌（MTC）的术前诊断价值。 方法： 回顾性纳入2015年1月至2024年1月于天津医科大学肿瘤医院手术治疗的MTC患者共267例，根据术前血清降钙素水平将患者分为＞100 ng/L组和10～100 ng/L组，分析两组患者的超声和临床病理学特征以及预后。选取同期血清降钙素为10～100 ng/L的甲状腺非髓样癌患者为对照组，受试者操作特征（ROC）曲线计算血清降钙素和FNA-CT诊断MTC的最佳临界值，分析二者对血清降钙素轻度升高MTC的诊断效能。 结果： 与＞100 ng/L组比较，10～100 ng/L组MTC超声特征主要表现为纵横比≥1、未靠近甲状腺被膜、血流信号不丰富和中国抗癌协会甲状腺影像报告与数据系统分类集中在4类（均P＜0.05）；临床病理学特征主要表现为单发病灶、原发灶较小、以微小癌居多、局部侵犯程度小、具有较早的肿瘤分期（T分期、N分期、TNM分期）、接受范围较小甲状腺和颈部淋巴结清扫术式即（单侧甲状腺叶切除而非全甲状腺切除、中央区淋巴结清扫而非侧颈部淋巴结清扫术式）、细针穿刺细胞学病理诊断率较低（均P＜0.05）。预后分析显示，与＞100 ng/L组比较，10～100 ng/L组MTC患者具有较高的生化治愈率（分别为90.9%和54.2%）和较低的生化复发率（分别为5.5%和23.1%）及肿瘤复发率（分别为3.6%和22.6%；P＜0.001）。血清降钙素轻度升高10~100 ng/L患者中，MTC患者与甲状腺非髓样癌血清降钙素中位数分别为40.0 ng/L（19.5，65.8 ng/L）和16.6 ng/L（13.2，20.8 ng/L；P＜0.001），FNA-CT中位数分别为2 000.0 ng/L（1 334.0，2 000.0 ng/L）和0.8 ng/L（0.5，2.0 ng/L；P＜0.001）。血清降钙素诊断MTC的最佳临界值为22.9 ng/L，灵敏度、特异度、阴性预测值、阳性预测值分别为67.3%、82.9%、65.4%、61.2%，ROC曲线下面积（AUC）为0.829（95% CI：0.731～0.903）；FNA-CT诊断MTC的最佳临界值为58.7 ng/L，灵敏度、特异度、阴性预测值、阳性预测值分别为98.2%、97.6%、97.6%、98.1%，AUC为0.998（95% CI：0.989～0.998）。 结论： MTC中血清降钙素轻度升高多见于早期患者，FNA-CT的高诊断效能有助于MTC患者的早期诊断。.
Objective: To investigate the mechanism through which timosaponin AⅢ (TAⅢ)-based liposomes loaded with auranofin (AUF) (T-AUF-LPs) induce ferroptosis in anaplastic thyroid carcinoma cells. Methods: T-AUF-LPs were prepared using the thin-film hydration method, and their physicochemical properties and stability were characterized. Additionally, conventional liposomes (C-AUF-Lips) were prepared using cholesterol as the membrane material. Cellular uptake efficiency was evaluated in CAL-62 cells using coumarin-6-labeled liposomes. Cell viability was assessed via CCK-8 assay. The role of ferroptosis was confirmed using the inhibitor Ferrostatin-1 (Fer-1) and flow cytometric analysis of cell death. The expression of ferroptosis-related markers (ACSL4, NCOA4, GPX4) were detected using RT-qPCR and Western blot. Levels of intracellular iron, glutathione (GSH), and lipid peroxidation were measured. A nude mouse tumor xenograft model was established to evaluate the in vivo antitumor efficacy of T-AUF-LPs, and hematoxylin-eosin (HE) staining was performed to assess potential systemic toxicity. Results: T-AUF-LPs appeared as uniformly distributed spherical particles with an average size of (119.40±3.11) nm, which was significantly smaller than that of the conventional liposomes C-AUF-LPs (P＜0.001). The zeta potential of T-AUF-LPs was (-12.07±0.65) mV, lower than that of C-AUF-LPs (P=0.002). Furthermore, CAL-62 cells exhibited significantly enhanced cellular uptake of T-AUF-LPs compared to C-AUF-LPs. Cell experiments demonstrated that among the established groups, i.e., Control, TAⅢ, AUF, AUF+TAⅢ, C-AUF-LPs, and T-AUF-LPs, the T-AUF-LPs group exhibited the lowest half-maximal inhibitory concentration (IC50=0.66 μmol/L) and the highest CAL-62 cell mortality (14.7±1.3)%. Furthermore, this group showed significantly elevated lipid peroxidation (2.07±0.28), increased iron content (4.64±0.17), and markedly reduced glutathione (GSH) levels (0.11±0.05). At the molecular level, mRNA expression of ACSL4 and NCOA4 was up-regulated (13.10±0.94 and 7.52±0.49, respectively), while GPX4 mRNA was down-regulated (0.16±0.21). Consistently, ACSL4 and NCOA4 protein expression was increased (1.30±0.06 and 1.13±0.31, respectively), whereas GPX4 protein expression was decreased (0.31±0.18).Notably, pretreatment with the ferroptosis inhibitor Fer-1 significantly reversed T-AUF-LPs-induced cell death, reducing mortality to (8.8±0.8)%. Animal studies demonstrated that among all groups, tumor growth was most significantly suppressed in the T-AUF-LPs group, which exhibited the smallest tumor volume on day 15 post-inoculation. No significant body weight loss was observed in nude mice, and histopathological assessment of the heart, liver, lungs, and kidneys revealed no apparent toxic damage. In tumor tissues of the T-AUF-LPs group, mRNA expression of ACSL4 and NCOA4 was significantly up-regulated (1.59±0.29 and 8.65±3.48, respectively), while GPX4 mRNA expression was markedly down-regulated (0.11±0.01). Consistently, ACSL4 and NCOA4 protein levels were increased (1.26±0.31 and 1.14±0.39, respectively), whereas GPX4 protein expression was significantly reduced (0.56±0.12). Conclusion: T-AUF-LPs inhibited the growth of anaplastic thyroid carcinoma cells by activating the ferroptosis pathway. 目的： 探讨负载金诺芬（AUF）的知母皂苷AⅢ（TAⅢ）脂质体（T-AUF-LPs）诱导未分化甲状腺癌细胞发生铁死亡的作用机制。 方法： 采用薄膜水化法制备脂质体T-AUF-LPs，并对其理化性质和稳定性进行表征。同时，以胆固醇为膜材制备普通脂质体C-AUF-LPs。使用香豆素6标记脂质体评估未分化甲状腺癌CAL-62细胞对其的摄取效率。采用细胞计数试剂盒8检测细胞增殖活力，流式细胞术用于检测细胞死亡情况。联合使用铁死亡抑制剂Ferrostatin-1（Fer-1），以明确铁死亡在T-AUF-LPs抑制CAL-62细胞效应中的作用。采用反转录定量聚合酶链反应（RT-qPCR）和蛋白免疫印迹法分别检测铁死亡相关基因酰基辅酶A合成酶长链家族成员4（ACSL4）、核受体辅激活蛋白4（NCOA4）和谷胱甘肽过氧化物酶4（GPX4）的mRNA和蛋白表达水平，采用相应试剂盒检测细胞内脂质过氧化水平及铁、谷胱甘肽（GSH）含量。建立裸鼠移植瘤模型评估T-AUF-LPs的体内抗肿瘤效果，并取裸鼠的心、肝、肺、肾进行病理学观察评估其毒性。 结果： T-AUF-LPs呈分布均匀的球形，粒径为（119.40±3.11）nm，小于普通脂质体C-AUF-LPs（P＜0.001），Zeta电位为（-12.07±0.65）mV，低于C-AUF-LPs（P=0.002），CAL-62细胞对T-AUF-LPs的摄取能力显著强于C-AUF-LPs。细胞实验显示，在所设置的对照组、TAⅢ组、AUF组、AUF+TAⅢ组、C-AUF-LPs组和T-AUF-LPs组中，T-AUF-LPs组CAL-62细胞的半数抑制浓度最低（0.66 μmol/L），细胞死亡率最高［（14.7±1.3）%］，脂质过氧化水平显著升高（2.07±0.28），铁含量明显增加（4.64±0.17），GSH水平显著下降（0.11±0.05），ACSL4和NCOA4 mRNA水平上调（分别为13.10±0.94和7.52±0.49），GPX4 mRNA水平下调（0.16±0.21），ACSL4和NCOA4蛋白高表达（分别为1.30±0.06和1.13±0.31），GPX4蛋白低表达（0.31±0.18）。以铁死亡抑制剂Fer-1预处理后，T-AUF-LPs组细胞的死亡被显著逆转，细胞死亡率降至（8.8±0.8）%。动物实验显示，各组中T-AUF-LPs组的肿瘤受到最明显抑制，接种第15天时肿瘤体积最小，裸鼠体重均未见明显减轻，心、肝、肺、肾病理学评估未见明显毒性损伤。T-AUF-LPs组肿瘤组织中ACSL4和NCOA4 mRNA表达显著上调（分别为1.59±0.29和8.65±3.48），GPX4 mRNA表达显著下调（0.11±0.01），ACSL4和NCOA4蛋白表达明显增加（分别为1.26±0.31和1.14±0.39），GPX4蛋白表达明显减低（0.56±0.12）。 结论： T-AUF-LPs可通过激活铁死亡通路抑制未分化甲状腺癌细胞生长。.
Objective: To systematically summarize the research progress of clinical trials on breast cancer drugs in China from 2011 to 2022, as well as provide an overview of the marketed drugs. The goal is to offer data and decision-making evidence for relevant departments. Methods: Based on the registration database of the China National Medical Products Administration's Clinical Trial Registration and Information Disclosure Platform, as well as data from the domestic and imported drug query systems, an analysis was conducted on clinical trials of breast cancer drugs, including information on investigational drugs and marketed drugs from January 1, 2011, to December 31, 2022. The study compared differences between Chinese and foreign enterprises in terms of trial scope, trial phases, number of treatment lines, drug types, and mechanisms of action. Results: From 2011 to 2022, a total of 401 clinical trials for breast cancer were registered in China, accounting for 8.0% of the country's overall anti-tumor clinical trials (401/5 011), with 304 trials (75.8%) initiated by domestic enterprises. Over the past decade, clinical trials for breast cancer showed fluctuating growth, reaching a peak of 84 trials in 2020. These trials involved 254 drugs, with 156 (61.4%) being original drugs and 174 (68.5%) being targeted therapies. The most focused targets included human epidermal growth factor receptor 2 (HER-2), cyclin-dependent kinases 4/6 (CDK4/6), and estrogen receptors (ER). There are 50 drugs targeting HER-2 (28.7%), 35 targeting CDK4/6 (20.1%), and 31 targeting ER (17.8%). During the period from 2011 to 2022, a total of 15 drugs for treating breast cancer were approved and launched in China, covering 19 indications. Among these, 7 indications are for adjuvant or neoadjuvant therapy of early-stage breast cancer, and 12 indications are for advanced breast cancer. Conclusions: Substantial achievements have been made in the development of new breast cancer drugs in China from 2011 to 2022. However, there remains a significant gap in the innovation capabilities of domestic pharmaceutical companies compared to international counterparts in the field of breast cancer. Future efforts should be directed towards strengthening research and development in breast cancer, exploring new target points, and investigating combination therapy mechanisms. 目的： 系统分析2011—2022年中国乳腺癌药物临床试验的研究进展及上市药物概况，为相关部门提供数据及决策证据。 方法： 基于中国国家药品监督管理局药物临床试验登记与信息公示平台及国产药品及进口药品数据查询系统，分析2011年1月1日至2022年12月31日乳腺癌药物临床试验、试验用药品及上市药物信息，比较中国企业和国外企业在试验范围、试验分期、治疗线数及药物类型、作用机制等方面的差异。 结果： 2011—2022年，中国共注册登记401项乳腺癌药物临床试验，占中国抗肿瘤药物临床试验的8.0%（401/5 011），其中国内企业发起304项（75.8%）。近10年乳腺癌临床试验数量呈波动式增长，2020年达峰（84项）。上述试验共涉及254种药物，156种（61.4%）为原研药，174种（68.5%）为靶向药，其中，人表皮生长因子受体2（HER-2）、细胞周期蛋白依赖性激酶4/6（CDK4/6）、雌激素受体（ER）是乳腺癌临床试验更受关注的3个靶点，靶向HER-2的药物有50种（28.7%），靶向CDK4/6的35种（20.1%），靶向ER的31种（17.8%）。2011—2022年间共有15种治疗乳腺癌的药物在中国获批上市，涉及19种适应证，其中7个适应证针对早期乳腺癌的辅助或新辅助治疗，12个适应证为晚期乳腺癌。 结论： 中国乳腺癌新药研发在2011—2022年取得了巨大成果，但是国内药企在乳腺癌方面的新药创新能力较国际仍有较大差距，靶点分布有同质化趋向，建议国内企业挖掘中国乳腺癌人群特点，加大创新乳腺癌药物研发投入。.
Lung cancer is the malignant tumor with the highest incidence and mortality rates in China. Driver gene-negative non-small cell lung cancer (NSCLC), as a common subtype of lung cancer, imposes a substantial disease burden. With the continuous enrichment of treatment options, these patients have many treatment choices, but the translation of efficacy data from clinical research to real-world clinical practice still faces many challenges. Furthermore, as a highly heterogeneous disease, lung cancer is full of complexity in clinical diagnosis and prognosis assessment, and there are numerous controversies in diagnostic and therapeutic strategies. Multi-disciplinary team (MDT) management can fully consider individual differences and tumor heterogeneity, bringing comprehensive clinical benefits to patients with driver gene-negative NSCLC from diagnosis to treatment, but there are still many unclear aspects regarding its application scenarios. Therefore, the Oncology Multidisciplinary Medical Committee of the Chinese Medical Doctor Association, the Lung Cancer Group of the Oncology Branch of the Chinese Medical Doctor Association, the Expert Committee on Quality Control of Lung Cancer of the National Cancer Quality Control Center, and the Non-Small Cell Lung Cancer Committee of the Chinese Society of Clinical Oncology jointly initiated and organized a multidisciplinary panel of experts to conduct an in-depth discussion on the application scenarios of MDT in the clinical practice of driver gene-negative NSCLC. Based on the discussions and voting results of the expert panel, a final expert consensus on the implementation of MDT in different clinical scenarios was developed, aiming to provide Chinese clinicians with practical guidance for MDT practice. 肺癌是中国发病率和死亡率最高的恶性肿瘤，驱动基因阴性非小细胞肺癌（NSCLC）作为肺癌中的常见亚型，疾病负担沉重。随着治疗手段的不断丰富，该类患者拥有诸多治疗选择，但临床研究中的疗效数据向真实世界临床实践转化仍面临诸多挑战。此外，肺癌作为一种高度异质性疾病，在临床诊断和预后评估中充满复杂性，诊疗策略存在诸多争议。多学科诊疗（MDT）可充分考虑个体差异和肿瘤异质性，从诊断到治疗为驱动基因阴性NSCLC患者带来全方位的临床获益，但其应用场景仍存在诸多不明确之处。因此，中国医师协会肿瘤多学科诊疗专业委员、中国医师协会肿瘤医师分会肺癌学组、国家肿瘤质控中心肺癌质控专家委员会、中国临床肿瘤学会非小细胞肺癌专家委员会共同发起并组织多学科专家，就驱动基因阴性NSCLC临床实践中MDT的应用场景展开深入探讨。基于专家组的讨论及投票结果，最终形成了针对不同临床情境下MDT实施的专家共识，旨在为中国临床医师提供切实可行的MDT实践指导。.
Antibody-drug conjugates (ADCs) are covalently conjugated molecules composed of a monoclonal antibody, a payload, and a linker. They represent an innovative therapeutic approach that combines the precise targeting capability of target therapies with the cytotoxic effects of chemotherapeutic agents. Given the unique molecular structure of ADCs, drug-related adverse reactions have drawn a considerable attention. Based on the safety data of ADCs currently available in the field of lung cancer, the common adverse drug reactions primarily involve the digestive system, hematologic system, hepatobiliary system, pulmonary system, skin, eyes, sensory nervous system, and musculoskeletal system. Unlike other cancer types, lung cancer is characterized by complex disease subtypes and molecular pathological mechanisms, as well as diverse treatment modalities. Moreover, patients with advanced lung cancer often have comorbidities such as chronic obstructive pulmonary disease and pulmonary inflammation, making the comprehensive management of ADC-related adverse reactions even more challenging. To address this, the Precision Treatment Branch of Thoracic Oncology, Chinese Geriatric Health Association, has taken the lead in organizing a multidisciplinary panel of domestic experts in gastroenterology, dermatology, respiratory medicine, ophthalmology and oncology, to discuss and jointly formulate the "Consensus of Chinese experts on the multidisciplinary management of adverse reactions to antibody-drug conjugates in the treatment of Lung Cancer (2025 edition)". A total of 21 recommendations are proposed in this consensus, covering pre-ADC safety assessments, comprehensive monitoring and management of relevant adverse reactions during ADC treatment, patient education, and medication guidance for special populations. The consensus aims is to provide clinicians with practical guidelines for the application of ADC, thereby maximizing therapeutic benefits for patients with lung cancer. 抗体药物偶联物（ADC）由单克隆抗体、有效载荷和连接子3部分共价偶联组成，是将靶向药物的精准定位与化疗药物的细胞毒性杀伤作用相结合的创新疗法。鉴于ADC独特的分子结构，其药物相关的不良反应一直备受关注。根据已披露的肺癌领域ADC安全性数据，目前常见的药物不良反应主要涉及消化系统、血液系统、肝胆系统、肺部、皮肤、眼部、外周感觉神经系统及肌肉骨骼系统等。与其他癌种不同的是，肺癌不仅疾病亚型及分子病理学机制复杂，治疗模式多样，而且晚期肺癌患者常合并慢性阻塞性肺疾病、肺部炎症等多种共患病，致使ADC相关不良反应的全程化管理更具挑战。为此，由中国老年保健协会胸部肿瘤精准治疗分会专业委员会牵头，组织国内消化科、皮肤科、呼吸科、眼科及肿瘤科等多学科专家讨论并联合制定了《抗体药物偶联物治疗肺癌不良反应多学科管理专家共识（2025版）》，共提出21条推荐意见，贯穿ADC使用前安全评估、ADC治疗期间发生相关不良反应的全面监测管理、ADC治疗的患者教育以及特殊人群的用药指导，旨在为临床医师提供切实可行的ADC应用参考准则，确保肺癌患者治疗获益最大化。.
Objective: To investigate the surgical approach for the resection of complex tumors located on the lateral side of the pelvic floor. Methods: A retrospective analysis was conducted on 24 patients with complex tumors on the lateral side of the pelvic floor who were treated at The First Affiliated Hospital of Zhengzhou University from April 2023 to April 2025. Among the 24 patients, there were 16 cases of aggressive pelvic myxoma of the pelvic floor (including 10 recurrent cases), 6 cases of soft tissue sarcoma (4 recurrent cases), and 2 cases of nerve sheath tumor. The perineal lateral arc-shaped incision was used as the primary approach in all surgeries, with some patients receiving an auxiliary abdominal incision. The operation time, intraoperative blood loss, R0 resection rate of the tumor, wound healing, and the impact of the incision on postoperative defecation, urination and lower limb function were analyzed. Results: The median operation time of the perineal lateral arc-shaped incision approach was 60 minutes (range: 35-180 min), and the median intraoperative blood loss was 130 ml (range: 20-600 ml) and the R0 resection rate was 100.0% (26/26). Primary healing of the perineal lateral incision was achieved in 21 cases, and secondary healing in 3 cases. No postoperative defecation or urination dysfunction was observed, and all patients had normal lower limb function postoperatively. Conclusion: The perineal lateral arc-shaped incision can effectively improve the resection rate of complex tumors on the lateral side of the pelvic floor, reduces surgical risks, and is not associated with significant postoperative complications. 目的： 探讨盆底侧方型复杂肿瘤切除的手术入路方法。 方法： 回顾性分析2023年4月至2025年4月在郑州大学第一附属医院诊治的24例盆底侧方型复杂肿瘤患者的临床资料，24例患者中，盆底血管侵袭性黏液瘤16例（其中复发型10例），软组织肉瘤6例（复发型4例），神经鞘瘤2例。所有手术均采用会阴侧弧形切口为主，部分患者给予辅助腹部切口。分析该手术方法的手术时间、术中出血量、肿瘤R0切除率、切口的愈合情况以及切口对患者术后排尿、排便及下肢功能的影响。 结果： 会阴侧弧形切口手术入路中位手术时间为60（35～180）min，术中中位出血量130（20～600）ml，肿瘤R0切除率为100.0%（26/26）。会阴侧方型切口Ⅰ期愈合21例，Ⅱ期愈合3例。术后患者无排尿、排便功能障碍，下肢功能均无异常。 结论： 会阴侧弧形切口能有效提高盆底侧方型复杂肿瘤切除率，降低手术风险，无明显手术后并发症。.
Objective: The National Central Cancer Registry estimates the cancer diseases burden in China in 2024. Methods: We incorporated the surveillance data from 919 cancer registries of year 2019 and the longitudinal surveillance data from 106 registries during 2010 to 2019. We estimated the age-standardized incidence (ASIR) and mortality rates (ASMR) of overall and 23 major cancers in China in 2024 using the age-period-cohort model, stratified by sex and area. The age-standardized incidence (ASIRC) and mortality (ASMRC) rates by Chinese population were calculated based on the age structure of the population from the national census in 2000. The age-standardized incidence (ASIRW) and mortality (ASMRW) rates by World population were calculated using Segi's world standard age structure. Results: In 2024, there were approximately 5 150 600 new cancer cases in China (2 672 000 for males and 2 478 600 for females), with an ASIRW of 207.70 per 100 000 (215.71 per 100 000 in urban areas and 193.74 per 100 000 in rural areas). The estimated number of cancer deaths in China was 2 582 200 (1 640 500 for males and 941 700 for females), with an ASMRW of 90.90 per 100 000 (87.34 per 100 000 in urban areas and 96.27 per 100 000 in rural areas). When comparing between different sexes, the cancer ASIRs for both males and females were relatively close. The ASMRs for males were 1.9 times that of females. When comparing among different areas, the crude cancer incidence rate in rural areas was higher than that in urban areas, while the ASIRs were lower than that in urban areas. Both the crude mortality rate and the ASMRs in rural areas were higher than those in urban areas. Among different cancer types, lung cancer ranked first in terms of both incidence and mortality, with 1 175 900 new cases and 743 300 deaths, accounting for 22.8% and 28.8% of all cancer cases and deaths, respectively. In both males and females, the ASIRs and ASMRs of liver, stomach and esophageal cancer in rural areas were higher than those in urban areas, while the ASIRs and ASMRs of colorectal cancer in urban areas were higher than those in rural areas. The ASIRs and ASMRs of cervical cancer in rural areas were higher than those in urban areas. The disease burden of prostate cancer and breast cancer in urban areas was higher than that in rural areas. The incidence and mortality rates of lung cancer ranked first in most provinces of China. The incidence rate of nasopharyngeal cancer was relatively high in Guangxi, Guangdong, Hainan and Jiangxi. Renal cancer was more prevalent in northern regions, and prostate cancer was more common in economically developed areas. The incidence rate of thyroid cancer ranked second in Zhejiang, Fujian and Xinjiang. The incidence rates of esophageal cancer and cervical cancer were significantly lower in Beijing, Tianjin, Shanghai and Guangdong. Conclusions: The overall burden of cancer in China remains significant. Different regions should formulate targeted prevention and control strategies based on the characteristics of regional cancer disease burdens. 目的： 根据全国肿瘤登记中心收集的恶性肿瘤登记数据，估计2024年中国恶性肿瘤流行情况。 方法： 纳入919个肿瘤登记处的2019年肿瘤监测数据和106个登记处的2010—2019年纵向监测数据，采用年龄-时期-队列模型，按性别、城乡分层，估计2024年总体恶性肿瘤及23类主要恶性肿瘤的年龄标化发病率和死亡率。中国人口标化率（中标率）采用2000年中国普查的人口年龄构成计算，世界人口标化率（世标率）采用Segi's世界标准人口年龄构成计算。结合2024年人口数据，估计2024年中国恶性肿瘤发病和死亡例数。 结果： 2024年中国恶性肿瘤新发病例估计为515.06万（男性267.20万，女性247.86万），世标发病率为207.70/10万（城市地区215.71/10万，农村地区193.74/10万）；死亡病例258.22万（男性164.05万，女性94.17万），世标死亡率为90.90/10万（城市地区87.34/10万，农村地区96.27/10万）。不同性别比较，男女恶性肿瘤标化发病率较为接近，标化死亡率男性是女性的1.9倍。不同地区比较，农村恶性肿瘤粗发病率高于城市，标化发病率低于城市，而粗死亡率和标化死亡率均高于城市。不同癌种中，肺癌居恶性肿瘤发病和死亡首位，新发病例117.59万，死亡74.33万，分别占全部恶性肿瘤的22.8%和28.8%。无论在男性还是女性人群中，农村地区肝癌、胃癌、食管癌的标化发病率和标化死亡率均高于城市地区，城市地区结直肠癌标化发病率和标化死亡率均高于农村地区。子宫颈癌标化发病率和标化死亡率农村高于城市，前列腺癌和乳腺癌疾病负担城市高于农村。在中国不同省（自治区、直辖市）中，肺癌在大部分地区居恶性肿瘤发病和死亡首位，鼻咽癌在广西壮族自治区、广东省、海南省、江西省等地区发病顺位较高，肾癌在北方地区相对高发，前列腺癌在经济较发达的地区相对高发，甲状腺癌在浙江省、福建省和新疆维吾尔自治区发病仅次于肺癌，食管癌和子宫颈癌在北京市、天津市、上海市和广东省的发病顺位明显靠后。 结论： 中国恶性肿瘤负担总体仍然沉重，不同地区应根据区域肿瘤疾病负担特征，制定精准化防控策略。.
Objective: To explore the independent risk factors of brain metastasis after systematic treatment in newly diagnosed non-stage Ⅳ breast cancer patients with HER-2-low expression, and to determine the recurrence risk stratification of brain metastasis, so as to guide the follow-up pattern of patients with different risk stratification. Methods: A retrospective analysis was performed on non-stage Ⅳ breast cancer patients admitted to Shandong First Medical University Affiliated Tumor Hospital from January 2012 to January 2020 with complete follow-up data. According to the immunohistochemical test results, only HER-2-low breast cancer patients confirmed by postoperative pathology were enrolled. The independent risk factors and the rate of brain metastasis were analyzed, and brain metastasis risk stratification was performed based on the number of independent risk factors. Results: 247 patients were enrolled, with a median follow-up of 51 months, 138 patients developed brain metastasis during follow-up, and the median development time was 55.5 months. Univariate analysis showed that age, menopause status, ER, tissue grade, T stage, N stage, CEA, CA125 and CA153 were associated with brain metastasis (P＜0.05). Multivariate logistic regression analysis showed that negative ER (OR=2.486, 95% CI: 1.117-5.533), tissue gradeⅡ (OR=12.175, 95% CI: 2.991-49.567), tissue grade Ⅲ (OR=14.03, 95% CI: 3.383-58.184), T2 stage (OR=2.272, 95% CI: 1.122-4.602), T3 stage (OR=9.05, 95% CI: 1.804-45.398), T4 stage (OR=6.691, 95% CI: 1.814-24.676), number of axillary lymph node metastasis≥10, N3 (OR=2.748, 95% CI: 1.041-7.260), CA125 higher than the reference value (OR=3.933, 95% CI: 1.601-9.66) and CA153 higher than the reference value (OR=2.578, 95% CI: 1.161-5.724) were independent risk factors for brain metastasis (P＜0.05). The risk of brain metastasis was assessed according to the number of independent risk factors in patients: Those with 0 risk factor were classified as low-risk group, 1-2 risk factors as medium-risk group, 3-4 risk factors as high-risk group, and 5-6 risk factors as extremely high-risk group. The incidence of brain metastases in each group were 0 (0/3), 33.33% (39/117), 74.55% (82/110) and 100.00% (17/17), respectively. Conclusion: The risk stratification of brain metastasis based on clinicopathological characteristics and levels of related tumor markers are helpful to predict the risk of brain metastasis in non-stage Ⅳ breast cancer patients with HER-2 low expression after systematic treatment, so as to accurately identify patients with high recurrence risk and formulate targeted follow-up strategies for them. 目的： 探讨初诊非Ⅳ期人表皮生长因子受体2（HER-2）低表达乳腺癌患者接受系统治疗后脑转移的独立风险因素，明确脑转移的复发风险分层，以指导不同风险分层患者的随诊。 方法： 回顾性分析2012年1月至2020年1月山东第一医科大学附属肿瘤医院收治的随访资料完整的非Ⅳ期乳腺癌患者，根据免疫组织化学检测结果，入组术后病理证实为HER-2低表达的乳腺癌患者，分析脑转移率，采用Logistic回归模型分析脑转移的独立风险因素，基于独立风险因素数目进行脑转移风险分层。 结果： 共入组247例患者，中位随访51个月，138例患者随访中出现脑转移，脑转移发生中位时间为55.5个月。单因素分析显示，脑转移与患者年龄、绝经状态、雌激素受体（ER）、组织分级、T分期、N分期、癌胚抗原、糖类抗原125（CA125）、CA153有关（P＜0.05）。多因素分析显示，ER阴性（OR=2.486，95% CI：1.117～5.533）、组织分级Ⅱ级（OR=12.175，95% CI：2.991～49.567）、组织分级Ⅲ级（OR=14.03，95% CI：3.383～58.184）、T2期（OR=2.272，95% CI：1.122～4.602）、T3期（OR=9.05，95% CI：1.804～45.398）、T4期（OR=6.691，95% CI：1.814～24.676）、腋窝淋巴结转移数目≥10枚即N3期（OR=2.748，95% CI：1.041～7.260）、CA125高于参考值（OR=3.933，95% CI：1.601～9.660）以及CA153高于参考值（OR=2.578，95% CI：1.161～5.724）是脑转移的独立风险因素（均P＜0.05）。按照患者存在独立风险因素个数进行脑转移风险评估，将具有0个风险因素者归为低危组，1～2个风险因素者归为中危组，3～4个风险因素者归为高危组，5～6个风险因素者归为极高危组，各组的脑转移发生率分别为0（0/3）、33.33%（39/117）、74.55%（82/110）和100.00%（17/17）。 结论： 根据临床病理特征及相关肿瘤标志物水平构建脑转移的风险分层，有助于预测HER-2低表达非Ⅳ期乳腺癌患者系统治疗后脑转移风险，以便准确识别高复发风险患者，对其制定有针对性的随访策略。.