Bladder cancer, particularly in older adults, poses significant therapeutic challenges due to its high recurrence rates, metastatic potential, and the toxicity associated with standard treatments. This case report describes a 75-year-old male with advanced muscle-invasive urothelial carcinoma of the bladder, exhibiting metastases to the prostate and lymph nodes. Following intolerance to conventional palliative chemotherapy, the patient underwent a structured integrative oncology protocol (systemic cancer therapies combined with adjuvant complementary therapies) that combined metabolic therapies, oncothermia, high-dose intravenous vitamin C, targeted nutraceutical supplementation, acupuncture, laser therapy, diet therapy, and yoga-based interventions. After initial metabolic optimization, an oral chemotherapy regimen comprising Afatinib, Axitinib, Relugolix, and Abiraterone was initiated. The patient demonstrated excellent tolerance to treatment, significant symptomatic relief, normalization of cancer-related biomarkers, and marked metabolic response with stable residual metabolic activity on PET-CT within six months. Quality of life measures improved substantially, and prognostic indices, including the Chuang Survival Score, reflected enhanced survival potential. This report underscores the potential of systemic cancer therapies along with integrative oncology to improve clinical outcomes, mitigate treatment-related toxicity, and enhance quality of life in advanced bladder cancer. While the findings are encouraging, they warrant validation through larger, controlled studies to better define the role of integrative approaches within the contemporary oncology framework.
Objective:To investigate the clinical features of inflammatory lesions originated from the infratemporal fossa with clinical suspicion of malignancy, and provide clinical reference for treatment and outcomes for this rare disease. Methods:Clinical information of 10 cases diagnosed with infratemporal fossa masses from July 2013 to July 2022 in Department of Otolaryngology Head and Neck Surgery, Xijing Hospital, Air Force Military Medical University were retrospectively analyzed. Preoperative imaging studies in these patients suggested the possibility of malignancy. They underwent transnasal endoscopic surgery procedures. Postoperative pathological examination confirmed inflammatory lesions. Among 10 patients, there were seven males and three females ranged from 22 to 73 years old（54.4±16.3）. Intravenous antibiotics were postoperatively administered for 3-5 days and oral antibiotics for 4-8 weeks were given with regular follow-up. Results:The follow-up duration ranged from 7 to 34 months. Among the 10 patients, 6 had complete or near-complete resolution of clinical symptoms, with imaging studies showing near-total resolution of the lesions; 2 patients showed significant symptom improvement with marked reduction in lesion extent on imaging; and 2 patients demonstrated minimal symptomatic improvement. Conclusion:Inflammatory lesions originating in the infratemporal fossa may share several imaging features with malignant tumors, including indistinct borders, infiltrative growth, bone destruction, and significant enhancement. Consequently, they are commonly misdiagnosed, and the final diagnosis is often confirmed by pathology. Moreover, the etiology and prognostic factors remain unclear. Therefore, clinicians should maintain a high degree of vigilance for this entity and provide prompt treatment. 目的：探讨原发于颞下窝并以肿瘤为表象的炎症性病变的临床特征，为临床诊断及治疗提供参考。 方法：回顾性分析2013年7月至2022年7月于空军军医大学第一附属医院耳鼻咽喉头颈外科收治的10例初诊颞下窝肿物患者的临床资料。其中男7例，女3例；年龄22～73岁，平均（54.4±16.3）岁。所有患者术前影像学检查均提示恶性肿瘤可能，均行经鼻内镜手术，术后病理均证实为颞下窝炎症性病变（右侧7例，左侧3例）。术后予抗炎、消肿等对症治疗3～5 d出院，出院后经验性口服抗生素4～8周，并嘱其定期复查。 结果：随访时间7～34个月，10例患者中，6例临床症状消失或基本消失，影像学检查提示病变基本消失；2例症状明显改善，影像学检查提示病变范围明显缩小；2例症状改善不明显。 结论：原发性颞下窝炎症性病变复杂且易于误诊。此类疾病具有与恶性肿瘤相似的影像学特点，如边界不清、呈浸润性生长、伴有骨质破坏、病灶强化明显等，但也具有其特有的影像学表现。最终诊断仍依赖于病理检查，目前病因及影响预后的因素尚不明确，临床医师在工作中应注意此类疾病的及时鉴别诊断。.
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。.
Nickel-oxygen species are proposed as key intermediates in various biological nickel-containing catalytic and enzymatic processes. We report the successful synthesis and crystallographic characterization of the first terminal nickel-oxygen complex featuring a tridentate N-aryl-N'-methylpyridyl β-diketiminate ligand. This species can be formally classified as either a nickel-oxo (NiIII=O) or nickel-oxyl (NiII-O•) species, exhibiting dual bonding characteristics. The experimental observations and DFT calculations suggest the bonding is best described as a resonance hybrid of NiIII=O and NiII-O• states, with the NiII-O• form likely predominant.
Patients with advanced chronic kidney disease (CKD), defined as having an estimated glomerular filtration rate (eGFR) < 45 ml/min/1.73 m², are vulnerable to infections leading to hospitalization. Predicting such events using routine clinical data may facilitate early intervention. This study aimed to develop a machine-learning models to predict infection-related hospitalization within 30 days of a nephrology visit. We conducted a single center retrospective cohort study of patients in the pre-ESRD pay-for-performance program at Taichung Veterans General Hospital (2010-2022). The primary outcome was infection-related hospitalization within 30 days of the index visit; qualifying admissions required intravenous antibiotic use. We excluded visits from patients < 18 years and those with < 2 nephrology visits in the prior year. Predictor variables included longitudinal laboratory parameters (means and variances within the prior 3 months), comorbidities, and recent medication use. Five machine learning models (XGBoost, random forest, logistic regression, support vector machine, and k-nearest neighbor) were trained and evaluated, with feature importance assessed using Shapley Additive explanations (SHAP). The analysis included 11,502 index visits from 11,018 patients, with 2,195 infection-related hospitalizations. Among tested models, the XGBoost algorithm achieved the highest predictive performance (AUROC 85.5%, sensitivity 71.3%, specificity 84.8%). The top ten predictors, as ranked by SHAP importance, were recent use of diuretics, serum albumin, Charlson comorbidity index (CCI) excluding renal disease, mean eGFR, corticosteroid use, albumin variance, age, eGFR variance, mean potassium, and mean uric acid. SHAP dependence plots were used to illustrate nonlinear relationships and approximate thresholds associated with increased risk of infection. Machine learning models using routinely available outpatient data can effectively predict short-term infection-related hospitalization in advanced CKD patients. This approach has the potential to inform individualized surveillance and early intervention strategies in nephrology care. Not applicable.
Tirzepatide (TZP) and thiazolidinediones (TZDs) have both shown promise in treating metabolic dysfunction-associated steatotic liver disease (MASLD), yet direct comparative evidence remains scarce. This real-world study aimed to compare the clinical effectiveness of TZP and TZDs in adults diagnosed with MASLD. We conducted a retrospective, multi-institutional cohort study using data from the TriNetX global health research network. Adults with MASLD who were newly initiated on TZP or TZD were included. The primary outcome was a composite measure encompassing all-cause mortality, major adverse liver outcome (MALO), major adverse cardiovascular event (MACE), and major adverse kidney event (MAKE). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. After 1:1 propensity score matching, each treatment arm included 9,262 patients. TZP use was significantly associated with a reduced risk of the composite primary outcome compared to TZD (HR, 0.66; 95% CI, 0.58-0.42). Additionally, TZP was linked to lower risks of all-cause mortality (HR, 0.48; 95% CI, 0.32-0.71), MALO (HR, 0.50; 95% CI, 0.36-0.69), MACE (HR, 0.65; 95% CI, 0.51-0.82), and MAKE (HR, 0.50; 95% CI, 0.36-0.69). These associations were consistent across subgroups stratified by age, sex, body mass index, and underlying comorbidities. In this large real-world cohort study, TZP was associated with lower risks of all-cause mortality, MALO, MACE, and MAKE compared to TZDs in adults with MASLD. While these findings suggest a potential clinical advantage, the observational design precludes causal inference. Prospective randomized trials are needed to confirm these associations and establish evidence-based treatment recommendations.
Human serum albumin (HSA) is the most abundant circulating protein and a central mediator of extracellular redox homeostasis. Its antioxidant function has been attributed primarily to the free thiol at cysteine residue 34 (Cys34), whose progressive oxidation-yielding nonmercaptoalbumin isoforms HNA1 and HNA2-serves as a sensitive biomarker of systemic oxidative stress. Advances in electrospray ionisation time-of-flight mass spectrometry have enabled precise quantification of Cys34 modifications, establishing cysteinylated albumin as a clinically applicable marker in chronic kidney disease, chronic liver disease, diabetes, and ageing-related functional decline. Beyond its role as a biomarker, oxidized albumin is now recognized as an active pathogenic mediator in preclinical models, with emerging evidence implicating ferroptosis as a potential mechanism of renal tubular cell injury, and contributing to cardiovascular risk and sarcopenia. A previously unrecognized dimension of albumin redox biology has also emerged: the presence of endogenous oxidized polysulfide bonds (Ox-PSS; RSSn-R', n > 1) across multiple intramolecular cysteine bridges. Quantified using the newly developed Elimination Method for Sulfide from Polysulfide, albumin polysulfides are dynamically regulated by oxidative stress and are significantly depleted in chronic kidney disease and early hepatitis, even when conventional Cys34-based markers remain unchanged. Polysulfide depletion impairs both Site II drug-binding capacity and reactive oxygen species scavenging activity, with direct implications for pharmacokinetics and therapeutic efficacy. These findings collectively reframe HSA as a dynamic polysulfide reservoir and extracellular redox regulator, highlighting albumin polysulfide modulation as a compelling emerging therapeutic strategy.
Objective: To investigate the effects of glutathione on acute cutaneous photodamage in mice and its mechanism. Methods: This study was a group-designed experimental study. Fifteen 8-week-old male C57BL/6 mice were shaved on the dorsal skin and divided into blank control group, model group, low-dose intervention group, medium-dose intervention group, and high-dose intervention group using a random number table, with 3 mice in each group. Mice in model group received daily combined irradiation of ultraviolet B and ultraviolet A on the dorsal skin to cause acute photodamage, followed by intraperitoneal injection of phosphate-buffered saline (PBS). Mice in blank control group were subjected to sham injury without ultraviolet irradiation and received daily intraperitoneal injection of PBS only. Mice in low-dose intervention group, medium-dose intervention group, and high-dose intervention group received daily ultraviolet irradiation as the model group, followed by intraperitoneal injection of 50, 100, and 200 mg/kg of glutathione, respectively. Two hours after the last injection on day 7 post injury (hereinafter referred to as day 7 post injury), the color and morphology of the dorsal skin of mice in each group were observed grossly. Then, dorsal skin tissue was excised for the following assays. Hematoxylin-eosin staining was used to examine the structure of the stratum corneum, epidermis, and dermis, the morphology of appendages (hair follicles, sweat glands, and sebaceous glands), the presence of hemorrhage, inflammatory cell infiltration, and the thickness of epidermis were also measured. Masson staining was used to detect collagen fiber deposition in the skin tissue. Western blotting was used to detect the protein expressions of inflammation-related proteins (interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and matrix metalloproteinase 1 (MMP-1)) in the skin tissue. Results: On day 7 post injury, compared with that in blank control group, the skin of mice in model group showed extensive scaling, redness, swelling, and crusting. Compared with that in model group, the severity of photodamage of the skin of mice in low-dose intervention group, medium-dose intervention group, and high-dose intervention group was alleviated successively. On day 7 post injury, compared with that in blank control group, the skin tissue structure of mice in model group was disorganized, characterized by thickened and detached stratum corneum, increased number and disordered arrangement of epidermal cell layers, dermal edema, abnormal morphology of appendages (hair follicles, sweat glands, sebaceous glands), scattered hemorrhagic foci, and extensive inflammatory cell infiltration. Compared with that in model group, the degree of tissue disorganization in the skin of mice in low-dose intervention group, medium-dose intervention group, and high-dose intervention group was alleviated successively. On day 7 post injury, the epidermal thickness of the skin of mice in model group was (116.4±6.4) μm, which was significantly greater than (20.9±1.6) μm in blank control group (P<0.05). Compared with that in model group, the epidermal thickness of the skin of mice in medium-dose intervention group and high-dose intervention group ((77.7±5.6) μm and (56.9±0.8) μm, respectively) was significantly decreased (with P values both <0.05). On day 7 post injury, compared with that in blank control group, the skin tissue of mice in model group showed a significant increase in collagen fiber content and disorganized fiber arrangement, indicating a certain degree of collagen fiber proliferation. Compared with that in model group, the arrangement of collagen fibers in the skin tissue of mice in low-dose intervention group, medium-dose intervention group, and high-dose intervention group became progressively more regular, and the overall tissue structure gradually recovered to normal. On day 7 post injury, compared with those in blank control group, the protein expression levels of IL-1β, IL-6, TNF-α, and MMP-1 in the skin tissue of mice in model group were significantly increased (with P values all <0.05). Compared with those in model group, the protein expression levels of IL-1β and IL-6 in the skin tissue of mice in low-dose intervention group were significantly decreased (with P values both <0.05), while the protein expression levels of IL-1β, IL-6, TNF-α, and MMP-1 in the skin tissue of mice in medium-dose intervention group and high-dose intervention group were significantly decreased (with P values all <0.05). Conclusions: Glutathione can significantly alleviate acute cutaneous photodamage induced by combined irradiation of ultraviolet B and ultraviolet A in mice, with a clear dose-dependent protective effect, and its mechanism may be related to inhibiting the expression of inflammatory factors, reducing MMP-1-mediated collagen degradation, and improving dermal collagen structure. 目的： 探讨谷胱甘肽对小鼠皮肤急性光损伤的作用及其机制。 方法： 该研究为成组设计实验研究。取15只8周龄雄性C57BL/6小鼠，剃去背部毛发后按随机数字表法分为空白对照组、模型组、低剂量干预组、中剂量干预组、高剂量干预组，每组3只。模型组小鼠背部皮肤每日接受中波紫外线联合长波紫外线照射造成急性光损伤，然后经腹腔注射磷酸盐缓冲液（PBS）；空白对照组小鼠不照射紫外线做假伤处理，仅每日经腹腔注射PBS；低剂量干预组、中剂量干预组、高剂量干预组小鼠每日同模型组接受紫外线照射后分别经腹腔注射50、100、200 mg/kg的谷胱甘肽。伤后第7天末次注射后2 h时（下称伤后7 d），大体观察各组小鼠背部皮肤色泽、形态，然后切取小鼠背部皮肤组织进行下述检测。采用苏木精-伊红染色检测皮肤组织的角质层、表皮层和真皮层结构，毛囊、汗腺、皮脂腺等附属器官的形态，有无出血现象及炎症细胞浸润等情况，并统计表皮厚度；采用Masson染色检测皮肤组织中胶原纤维沉积情况；采用蛋白质印迹法检测皮肤组织中的炎症相关蛋白白细胞介素-1β（IL-1β）、IL-6、肿瘤坏死因子-α（TNF-α）、基质金属蛋白酶1（MMP-1）的蛋白表达情况。 结果： 伤后7 d，与空白对照组相比，模型组小鼠皮肤出现大范围皮屑、红肿、痂壳；与模型组相比，低剂量干预组、中剂量干预组、高剂量干预组小鼠皮肤的光损伤程度依次减轻。伤后7 d，与空白对照组相比，模型组小鼠皮肤组织结构紊乱，角质层增厚、剥脱，表皮层细胞层数增多、排列紊乱，真皮层水肿，毛囊、汗腺、皮脂腺等附属器官形态异常，可见散在出血灶及大量炎症细胞浸润。与模型组相比，低剂量干预组、中剂量干预组、高剂量干预组小鼠皮肤组织结构紊乱程度依次减轻。伤后7 d，模型组小鼠皮肤的表皮厚度为（116.4±6.4）μm，明显厚于空白对照组的（20.9±1.6）μm，P<0.05；与模型组相比，中剂量干预组、高剂量干预组小鼠皮肤的表皮厚度［分别为（77.7±5.6）、（56.9±0.8）μm］明显变薄（P值均<0.05）。伤后7 d，与空白对照组相比，模型组小鼠皮肤组织中胶原纤维含量显著增加，且纤维排列紊乱，呈现出一定程度的胶原纤维增生现象；与模型组相比，低剂量干预组、中剂量干预组、高剂量干预组小鼠皮肤组织中胶原纤维的排列依次趋于规则，整体组织结构逐渐恢复至接近正常皮肤。伤后7 d，与空白对照组相比，模型组小鼠皮肤组织中IL-1β、IL-6、TNF-α和MMP-1的蛋白表达水平显著升高（P值均<0.05）；与模型组相比，低剂量干预组小鼠皮肤组织中IL-1β、IL-6的蛋白表达水平明显降低（P值均<0.05），中剂量干预组、高剂量干预组小鼠皮肤组织中IL-1β、IL-6、TNF-α和MMP-1的蛋白表达水平显著降低（P值均<0.05）。 结论： 谷胱甘肽可显著减轻中波紫外线与长波紫外线联合诱导的小鼠皮肤急性光损伤，且具有明显的剂量依赖性保护作用，其机制可能与抑制炎症因子表达、减少MMP-1介导的胶原降解及改善真皮胶原结构有关。.
Chronic obstructive pulmonary disease (COPD) is a prevalent, debilitating condition linked to significant morbidity and mortality. While glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated clinical benefits for COPD, the effect of tirzepatide on COPD outcomes remains to be fully elucidated. This study utilized the TriNetX Global Collaborative Network to analyze data from adults with COPD who were prescribed tirzepatide between 1 January 2022, and 28 February 2025. Patients were divided into two groups: those prescribed tirzepatide and those receiving standard care (control group). Propensity score matching (PSM) was applied to balance covariates. The primary outcome was the risk of COPD exacerbations. After PSM, the study included 12,110 patients (6,055 in each group). The tirzepatide group was associated with a lower risk of COPD exacerbations (HR, 0.77; 95% CI, 0.63-0.93) compared to the control group. Additionally, tirzepatide use was associated with a lower risk of mortality (HR, 0.52; 95% CI, 0.37-0.73), pneumonia (HR, 0.71; 95% CI, 0.59-0.86), and acute respiratory failure (HR, 0.59; 95% CI, 0.48-0.73). Tirzepatide use was associated with a potentially reduced risk of COPD exacerbations, lower mortality, and a decreased incidence of pneumonia and acute respiratory failure. These findings should be interpreted with caution, given the inherent limitations of observational study designs, including the possibility of residual confounding and selection bias. The observed associations do not establish causality, and the clinical generalizability of these results remains uncertain. Prospective randomized controlled trials are warranted to confirm these preliminary findings.
Background Differentiating progressive supranuclear palsy (PSP) from Parkinson disease and other parkinsonisms is challenging. MRI measures have been investigated, but most studies included small samples, limiting result reliability. Purpose To compare the performance of planimetric and linear MRI measurements in differentiating PSP from other parkinsonisms and identify an optimized linear marker. Materials and Methods Participants with PSP and non-PSP parkinsonisms and controls were included in this secondary analysis of multiple international prospective studies (enrollment: 2006-2024). The previously established midbrain line, midbrain area, pons to midbrain area ratio, and MR parkinsonism index were compared with a new simple linear marker based on two midbrain measures performed on midsagittal T1-weighted sections (dual-line midbrain PSP index [DMPI]). Logistic regression including DMPI, age, and sex was used to differentiate participants with PSP (PSP-Richardson syndrome, PSP variants) from those with non-PSP parkinsonisms and controls in two large independent cohorts and in a small cohort of participants with pathologically proven diagnoses. Results A total of 2111 participants (mean age, 67.8 years ± 8.4 [SD]; 54% male) were included (Italian: 136 PSP, 238 non-PSP, 85 controls; international: 520 PSP, 564 non-PSP, 525 controls). All markers were compared in a subcohort (PSP [n = 161]; non-PSP parkinsonisms [n = 203]) representative of the overall cohort. All measures showed area under the receiver operating characteristic curve (AUC) values over 0.90 for differentiating PSP from non-PSP parkinsonisms, with the DMPI and midbrain area performing best (AUCs, 0.97 [95% CI: 0.95, 0.98] and 0.95 [95% CI: 0.93, 0.97], respectively) and the DMPI showing the smallest percentage of uncertain cases (gray zone, 29 of 364 participants [7.97%]). In the entire Italian and international cohorts, the DMPI distinguished participants with PSP from those with non-PSP, with AUCs of 0.97 (95% CI: 0.97, 0.98) and 0.96 (95% CI: 0.95, 0.97), respectively. Excellent DMPI performance was also observed in participants with early-stage disease (AUC, 0.97 [95% CI: 0.95, 0.99]) and those with pathologically confirmed diagnoses (n = 43) (AUC, 0.94 [95% CI: 0.86, 1.00]). Conclusion The DMPI and midbrain area performed well for differentiating PSP from other neurodegenerative parkinsonisms. Clinical trial registration nos. NCT03068468, NCT01110720, NCT01049399, NCT01804452 © The Author(s) 2026. Published by the Radiological Society of North America under a CC BY 4.0 license. Supplemental material is available for this article.
Objective: To investigate the influence and mechanism of exosomes derived from rat bone marrow mesenchymal stem cells (BMSCs) on rat fibroblasts (Fbs) under high glucose conditions, with the aim of exploring a potential novel strategy for the treatment of diabetic wounds. Methods: This study was designed as grouped experimental study. The exosomes derived from BMSCs (BMSC-Exos) were extracted from the rat primary BMSCs and were identified successfully. The BMSC-Exos were divided into control group and high-glucose group. The BMSC-Exos in control group were cultured routinely, while the BMSC-Exos in high-glucose group were cultured in DMEM medium containing glucose at a final molarity of 30 mmol/L (hereinafter referred to as high-glucose medium). The eukaryotic mRNA sequencing was performed on BMSC-Exos in both groups, combined with multi-database prediction and enrichment analysis, differentially expressed genes that strongly interacted with the classical pyroptosis signaling pathway were screened and identified. The rat BMSCs of passages 1 to 3 were divided into microRNA-140-3p (miR-140-3p) mimic control group, miR-140-3p mimic group, miR-140-3p inhibitor control group, and miR-140-3p inhibitor group according to the random number table method, then the corresponding miR-140-3p mimic control, miR-140-3p mimic, miR-140-3p inhibitor control, and miR-140-3p inhibitor were transfected into cells, respectively, after 24 hours of culture. The BMSC-Exos were extracted at 24 hours post-transfection, and the expression of miR-140-3p in BMSC-Exos was detected by real-time fluorescence quantitative polymerase chain reaction. The rat Fbs in the logarithmic growth phase were divided into miR-140-3p mimic control group, miR-140-3p mimic group, miR-140-3p inhibitor control group, and miR-140-3p inhibitor group. After 24 hours of culture in high-glucose medium, the Fbs were added with the exosomes secreted by BMSCs after being transfected with miR-140-3p mimic control, miR-140-3p mimic, miR-140-3p inhibitor control, and miR-140-3p inhibitor, respectively (the same grouping and treatment below). At 24 hours post-transfection, the cell absorbance value was detected using cell counting kit-8, representing cell proliferation activity. The rat Fbs in the logarithmic growth phase were grouped and treated, then the cell migration rate at 24 hours after scratching was detected by scratch test. At 24 hours post-transfection, the protein expression levels of pyroptosis-related protein, including interleukin-1β (IL-1β), IL-18, NOD-like receptor pyrin domain-containing protein 3 (NLRP3), cysteine aspartic acid specific protease-1 (caspase-1), and gasdermin D in cells were detected by Western blotting. The sample size was 3. Results: Compared with that in control group, the expressions of miR-140-3p and miR-542-5p were significantly upregulated in BMSC-Exos of high-glucose group. MiR-140-3p was identified as the differentially expressed gene that strongly interacted with the classical pyroptosis signaling pathway. At 24 hours post-transfection, the expression of miR-140-3p in BMSC-Exos of miR-140-3p mimic group was significantly higher than that in miR-140-3p mimic control group (P<0.05), and the expression of miR-140-3p in BMSC-Exos of miR-140-3p inhibitor group was significantly lower than that in miR-140-3p inhibitor control group (P<0.05). At 24 hours post-transfection, the absorbance value of Fbs in miR-140-3p mimic group was 0.940±0.031, which was significantly higher than 0.781±0.020 in miR-140-3p mimic control group (P<0.05); the absorbance value of Fbs in miR-140-3p inhibitor group was 0.510±0.041, which was significantly lower than 0.822±0.061 in miR-140-3p inhibitor control group (P<0.05). The Fb migration rate at 24 hours after scratching in miR-140-3p mimic group was significantly higher than that in miR-140-3p mimic control group (P<0.05), and the Fb migration rate at 24 hours after scratching in miR-140-3p inhibitor group was significantly lower than that in miR-140-3p inhibitor control group (P<0.05). At 24 hours post-transfection, the protein expressions of NLRP3, IL-18, IL-1β, caspase-1, and gasdermin D in Fbs of miR-140-3p mimic group were significantly lower than those in miR-140-3p mimic control group (P<0.05); the protein expressions of NLRP3, IL-18, IL-1β, caspase-1, and gasdermin D in Fbs of miR-140-3p inhibitor group were significantly higher than those in miR-140-3p inhibitor control group (P<0.05). Conclusions: The rat BMSC-Exos can deliver miR-140-3p to promote the proliferation and migration of rat Fbs under high-glucose conditions, inhibit the expression of pyroptosis-related protein, and alleviate cell pyroptosis. This study provides a promising therapeutic target for diabetic wound repair. 目的： 探讨大鼠骨髓间充质干细胞（BMSC）来源外泌体（BMSC-Exo）对高糖环境下大鼠成纤维细胞（Fb）的影响及其机制，为糖尿病创面的治疗探索潜在的新途径。 方法： 该研究为成组设计实验研究。取大鼠原代BMSC提取BMSC-Exo，并成功鉴定。取BMSC-Exo，分为对照组和高糖组，其中对对照组BMSC-Exo行常规培养，对高糖组BMSC-Exo采用含终物质的量浓度30 mmol/L葡萄糖的DMEM培养基（以下简称高糖培养基）培养。对2组BMSC-Exo行真核mRNA测序，结合多数据库预测与富集分析，鉴定出与经典焦亡信号通路高度互相作用的差异表达基因。取第1~3代大鼠BMSC，采用随机数字表法分为微小RNA-140-3p（miR-140-3p）模拟物对照组、miR-140-3p模拟物组、miR-140-3p抑制剂对照组、miR-140-3p抑制剂组，培养24 h后分别转染miR-140-3p模拟物对照剂、miR-140-3p模拟物、miR-140-3p抑制剂对照剂、miR-140-3p抑制剂，转染24 h后提取BMSC-Exo，用实时荧光定量PCR法检测BMSC-Exo中miR-140-3p的表达。取对数生长期大鼠Fb，分为miR-140-3p模拟物对照组、miR-140-3p模拟物组、miR-140-3p抑制剂对照组、miR-140-3p抑制剂组，采用高糖培养基培养24 h后分别加入转染miR-140-3p模拟物对照剂、miR-140-3p模拟物、miR-140-3p抑制剂对照剂、miR-140-3p抑制剂后的BMSC分泌的外泌体（分组及处理后同），于转染24 h后，采用细胞计数试剂盒-8测量细胞吸光度值，代表细胞增殖活力。取对数生长期大鼠Fb，分组及处理后行划痕试验检测划痕后24 h的细胞迁移率；于转染24 h后，采用蛋白质印迹法检测细胞中焦亡相关蛋白白细胞介素-1β（IL-1β）、IL-18、含pyrin结构域的NOD样受体蛋白3（NLRP3）、胱天蛋白酶-1（caspase-1）和消皮素D的蛋白表达。样本数均为3。 结果： 与对照组相比，高糖组BMSC-Exo中miR-140-3p、miR-542-5p的表达显著上调。结合多数据库预测与富集分析，鉴定出与经典焦亡信号通路高度互相作用的差异表达基因为miR-140-3p。转染24 h后，miR-140-3p模拟物组BMSC-Exo中miR-140-3p的表达明显高于miR-140-3p模拟物对照组（P<0.05），miR-140-3p抑制剂组BMSC-Exo中miR-140-3p表达明显低于miR-140-3p抑制剂对照组（P<0.05）。转染24 h后，miR-140-3p模拟物组Fb吸光度值为0.940±0.031，明显高于miR-140-3p模拟物对照组的0.781±0.020（P<0.05）；miR-140-3p抑制剂组Fb吸光度值为0.510±0.041，明显低于miR-140-3p抑制剂对照组的0.822±0.061（P<0.05）。miR-140-3p模拟物组Fb划痕后24 h迁移率明显高于miR-140-3p模拟物对照组（P<0.05），miR-140-3p抑制剂组Fb划痕后24 h迁移率明显低于miR-140-3p抑制剂对照组（P<0.05）。转染24 h后，miR-140-3p模拟物组Fb中NLRP3、IL-18、IL-1β、caspase-1、消皮素D的蛋白表达均明显低于miR-140-3p模拟物对照组（P<0.05），miR-140-3p抑制剂组Fb中NLRP3、IL-18、IL-1β、caspase-1、消皮素D的蛋白表达均明显高于miR-140-3p抑制剂对照组（P<0.05）。 结论： 大鼠BMSC-Exo通过递送miR-140-3p，促进高糖环境下大鼠Fb的增殖、迁移并抑制其焦亡相关蛋白的表达，减少细胞焦亡，为糖尿病创面修复提供了潜在治疗靶点。.
Canine parvovirus type 2 (CPV-2) remains one of the most significant viral pathogens causing infectious disease in domestic dogs worldwide, particularly causing severe hemorrhagic gastroenteritis in puppies. In recent years, canine circovirus (CanineCV) has emerged as an additional enteric virus of concern, although its role in co-infection with CPV-2 remains poorly characterized in Southeast Asia. This study determines the prevalence, co-infection rate, and molecular characteristics of CPV-2 and CanineCV co-infections in domestic dogs across three major regions of Vietnam. A total of 254 rectal swab samples were collected from 2023 to 2024 from dogs exhibiting clinical signs consistent with CPV-2 infection. All samples were tested for CPV-2 and CanineCV by real-time PCR, and CPV-2-positive samples were genotyped using a SimpleProbe® assay. CPV-2-only infection resulted in a prevalence of 77.17%, while CPV-2-CanineCV co-infection had a prevalence of 22.83%. Vaccinated canines have 11.36% co-infection, while those with unknown vaccination history has 28.79% and unvaccinated has 19.23%. Genotyping results demonstrated that CPV-2c was the dominant variant, accounting for 93.31% overall and 93.1% in co-infections at a 22.78% co-infection rate, whereas CPV-2a was infrequent, at 6.69% overall and 6.9% in co-infections at a 23.53% co-infection rate, and CPV-2b was not detected. The highest co-infection rate was recorded in the Central region of Vietnam at 50%, compared with 9.38% in the North and 4.55% in the South. Seasonal analysis showed a high co-infection rate during the fall with no significant difference. Age distribution revealed that younger puppies were most affected and vulnerable to co-infection, with 37.50% in < 2 months, 24.24% in 2-3 months, 23.20% in 3-6 months, and 18.18% in 6-12 months. These findings suggest that CanineCV co-circulates extensively with CPV-2, particularly in younger dogs. The results also highlight the continued dominance of CPV-2c in Vietnam and underscore the importance of including CanineCV in diagnostic, vaccines, and epidemiological surveillance of canine enteric diseases.
The foot and ankle have a special anatomical structure and bear crucial functions of body such as weight bearing, walking, running, and jumping. High-energy injuries to these areas are complex, posing challenges to clinical tissue reconstruction. Complex foot-ankle tissue defects mostly present as multicompartmental defects involving skin and soft tissue, tendons, bones, and joints, as well as large-area skin and soft tissue defects. We divided the foot and ankle into nine regions based on the anatomical characteristics and physiological functions of different sites. Ten clinical types were then classified according to the involved regions of tissue defects and the presence of combined deep tissue defects. For each clinical type, appropriate flap donor sites and suitable special form of perforator flap procedures can be selected based on the requirements of microsurgical reconstruction to achieve personalized and precise reconstruction, so as to achieve the optimal restoration of the appearance and function of the foot and ankle with minimal donor-site damage. 足踝部解剖结构特殊，承担负重、行走、跑跳等重要的人体功能，高能损伤后伤情复杂，临床组织重建困难。足踝部复杂组织缺损多表现为累及皮肤软组织、肌腱、骨、关节等多元组织的缺损和巨大面积的皮肤软组织缺损。笔者根据足踝部各区域解剖特点与生理功能，将该部位划分为9个区域，然后根据组织缺损累及区域和是否合并深部组织缺损，将该部位缺损划分为10种临床类型。对于每一种临床类型，都可依据其显微重建要求选择合适的皮瓣供区和适宜的特殊形式穿支皮瓣术式，以实现个性化精准重建，达到以最小的供区损害获得最佳的足踝部外形与功能的恢复。.
Diabetic foot ulcer (DFU) is a common and serious chronic complication in patients with diabetes, characterized by high recurrence rates, risks of disability and mortality, which imposes a heavy burden on individual health and the social healthcare system. Mitochondrial dynamics refer to the dynamic balance between mitochondrial fission and fusion that maintains cellular energy metabolism and homeostasis. However, in the pathological environment of diabetes, hyperglycemia and oxidative stress disrupt this balance, leading to mitochondrial dysfunction and further exacerbating the inflammatory response and tissue damage in DFU. In recent years, intervention strategies targeting mitochondrial dynamics have been considered a potential therapeutic approach to alleviate DFU symptoms and promote wound healing. Based on the latest domestic and international research, this article reviews the progress of research on mitochondrial dynamics in DFU, with a focus on exploring its core mechanisms and regulatory factors in the pathological process of DFU, and summarizes the current main intervention strategies. Through systematic analysis, this article aims to deepen the understanding of the mechanisms underlying mitochondrial dynamics in DFU and to provide new ideas for targeted therapy in clinical practice. 糖尿病足溃疡（DFU）是糖尿病患者常见且严重的慢性并发症，具有高复发率、致残和致死风险，给个人健康与社会医疗系统带来沉重负担。线粒体动力学指线粒体通过分裂与融合的动态平衡维持细胞的能量代谢和稳态，而在糖尿病病理环境中，高血糖和氧化应激会破坏这一平衡，导致线粒体功能紊乱，进一步加剧DFU的炎症反应和组织损伤。近年来，靶向线粒体动力学的干预策略被认为是改善DFU症状、促进创面愈合的潜在治疗手段。该文基于国内外最新研究，综述DFU中线粒体动力学的研究进展，重点探讨其在DFU病理过程中的核心作用机制及调控因素，并总结当前主要的干预策略。通过系统分析，该文旨在加深对DFU相关线粒体动力学机制的理解，为临床提供新的靶向治疗思路。.
The definition of Parkinson's disease (PD) is undergoing a profound transformation from a "clinical syndrome" to a "biological entity", with development of two objective biological classification systems, the NSD-ISS (Neuronal Alpha-Synuclein Disease Integrated Staging System) and the SynNeurGe framework. Multimodal diagnostic tools further improve the detection of PD. This review synthesizes advances in three key domains of PD detection. First, fluid and tissue biomarkers, particularly using α-synuclein (αSyn) seed amplification assays, allow detection of synucleinopathy in cerebrospinal fluid, blood, saliva, and skin. This supports pathological diagnosis and differential classification. Extracellular vesicles provide cell-type-specific cargo profiles, while neurofilament light chain indicates neuroaxonal injury. Second, neuroimaging captures in vivo pathology. MRI identifies nigral degeneration (nigrosome-1 loss, iron accumulation, neuromelanin depletion), MRS reveals metabolic and neurotransmitter imbalances, and αSyn positron emission tomography tracers enable direct visualization of aggregation. Third, digital biomarkers derived from wearable devices, videos, and audios quantify real-world motor and non-motor symptoms, enabling continuous, ecological monitoring. Integration of these complementary biomarker streams is essential for biological definition and stratification of PD patients, and development of targeted therapies. Standardization of assays, multicenter validations, and clear guidance on who should be tested, when testing is appropriate, and how results should inform diagnosis, stratification, or monitoring are required for the translation of these methods into clinical practice in PD.
Helicobacter pylori infection is the leading cause of gastric cancer, yet the economic value of population-based screening and eradication remains uncertain. To project the lifetime health benefits and costs of invitation to 1-time H pylori stool antigen testing added to biennial fecal immunochemical test (FIT) screening compared with FIT alone. Lifetime cost-effectiveness analysis conducted using a Markov decision-analytic model to simulate a cohort informed by a pragmatic randomized clinical trial in Changhua County, Taiwan. The model adopted a 30-year time horizon and projected long-term outcomes, including gastric and colorectal cancer mortality, quality-adjusted life-years (QALYs; incorporating both life expectancy and health-related quality of life), and health care expenditures. Costs were evaluated from a societal perspective. One-way and probabilistic sensitivity analyses were performed. Future costs and QALYs were discounted at an annual rate of 3%. Helicobacter pylori stool antigen testing plus FIT or FIT alone. Incremental cost-effectiveness ratio of invitation for H pylori stool antigen testing plus FIT vs FIT alone, measured as the additional cost required to gain 1 QALY per person. Secondary outcomes included net monetary benefit and benefit-cost ratio. Compared with FIT alone, invitation to co-testing was more effective and less expensive (dominant), with a base-case cost-saving incremental cost-effectiveness ratio of $2094 per QALY gained (95% CI, $12 359 saved to $7291 additional cost). This resulted in a positive net monetary benefit, indicating that health benefits exceeded costs, and a benefit-cost ratio of 5.08, indicating an approximately 5-fold return on investment in the Taiwanese population. At a willingness-to-pay threshold of 1 × the Taiwan gross domestic product per QALY ($33 365), invitation to co-testing remained cost-saving in 65.7% of simulations. From a US cost perspective, invitation to co-testing was not cost-saving but remained cost-effective at the trial base-case H pylori prevalence. Sensitivity analyses identified H pylori prevalence as the dominant driver; co-testing exceeded a $100 000-per-QALY threshold when prevalence fell below 21.9%. In a pragmatic real-world setting with incomplete adherence, invitation to combined H pylori stool antigen testing and FIT was more cost-effective than FIT alone, improving lifetime outcomes and yielding cost savings in Taiwan while remaining cost-effective in higher-cost settings under moderate H pylori prevalence. ClinicalTrials.gov Identifier: NCT01741363.
Airway lavage therapy is an important method for clearing airway secretions and sloughed tissue in burn patients. It primarily includes fiberoptic bronchoscopy-guided lavage and direct airway lavage. To further improve the standardization, safety, and effectiveness of airway lavage therapy in burn patients, the consensus writing group, based on evidence from evidence-based medicine and guided by the Delphi method, conducted literature searches, quality evaluations, evidence synthesis, and expert consultations. They formulated the Expert consensus on airway lavage therapy for adult burn patients (2026 edition), which provides a reference for clinical practice, covering topics such as indications, contraindications, pre-operational preparation, timing and protocols of operation, monitoring, and complication management of airway lavage therapy for adult burn patients. 气道灌洗疗法是烧伤患者清除气道分泌物和脱落组织的重要方法之一，包括纤维支气管镜灌洗与气道直接灌洗。为进一步推进临床医务人员规范、安全、有效地实施烧伤患者气道灌洗疗法，共识编写组以循证医学证据为基础，德尔菲法为指导，围绕成人烧伤患者气道灌洗疗法的适应证与禁忌证、操作前准备、操作时机与方案、监测及并发症管理等进行文献检索、质量评价、证据综合、专家函询，制订了《成人烧伤患者气道灌洗疗法专家共识（2026版）》，为临床实践提供参考。.
Objective:To investigate the characteristics of consonant distortion in children aged 4-15 years with functional articulation disorders（FAD）, in order to provide scientific basis for clinical intervention. Methods:A retrospective analysis was conducted on 2 905 children with articulation disorders who were treated at Yunnan Children's Hospital between 2022 and 2024. Consonant errors were analyzed across three dimensions: place of articulation, vowel environment, and manner of articulation. Results:Among the 2 905 children, 234 cases（8.06%） exhibited consonant distortion with 724 errors in total. By place of articulation, distortion frequencies ranked as follows: Alveolar consonants（217/29.97%）>Retroflex consonants（215/29.70%）>Dental consonants（134/18.51%）>Velar consonants（83/11.46%）>Palatal consonants（75/10.36%）. No distortions of labiodental or bilabial consonants were identified under this sample set and evaluation criteria. The error frequency distribution across the five places of articulation showed a statistically significant difference（χ²=130.86, P<0.001）. By vowel environment, the highest occurrence of distortion happened when consonants were combined with /i/ as the following vowel（299/41.30%）, secondly by /a/, /o/, and /e/（240/33.15%）, and lastly with /u/（185/25.55%）. Differences in error frequency were statistically significant（χ²=26.94, P<0.001）. By manner of articulation, errors occurred in the following order: affricates（285/39.36%）>stops（180/24.86%）>fricatives（162/22.38%）>laterals（60/8.29%）>nasals（37/5.11%）. The error frequency distribution across these five manners of articulation also showed a statistically significant difference（χ²=276.26, P<0.001）. Conclusion:Consonant distortion in children with FAD demonstrates distinct specificity in place of articulation, vowel structure, and manner of articulation. Clinicians should particularly pay attention to anomalies involving tonguetip related consonants, affricates, and consonants followed by specific vowels（such as /i/）, so as to avoid diagnostic errors. 目的：探究4～15岁功能性构音障碍（functional articulation disorders，FAD）儿童辅音歪曲的特点，旨在为临床干预提供科学依据。 方法：采用回顾性分析方法，对2022年1月至2024年1月在昆明医科大学附属儿童医院就诊的2 905例构音障碍儿童的辅音错误特点进行统计分析，从辅音发声部位、后续韵母和发声方法3个维度分析辅音歪曲的特征。 结果：在2 905例构音障碍儿童中，有234例（8.06%）出现辅音歪曲，总共错误724频次，按发声部位划分，辅音歪曲频率由高到低依次为舌尖中音（217/29.97%）>舌尖后音（215/29.70%）>舌尖前音（134/18.51%）>舌根音（83/11.46%）>舌面音（75/10.36%），在此样本和评判标准下未发现唇齿音和双唇音歪曲现象。5个发声部位的错误频率分布差异有统计学意义（χ²=130.86，P<0.001）。按后接不同韵母划分，发生率最高的错误方式为辅音与/i/为韵头的韵母结合时歪曲（299/41.30%），其次为后接/a/、/o/、/e/为韵头的韵母发生歪曲（240/33.15%），最后为与/u/为韵头的韵母结合时歪曲（185/25.55%），不同错误频率比较差异有统计学意义（χ²=26.94，P<0.001）。按发声方式划分，塞擦音（285/39.36%）>塞音（180/24.86%）>擦音（162/22.38%）>边音（60/8.29%）>鼻音（37/5.11%）。5种发声方式的错误频率分布差异有统计学意义（χ²=276.26，P<0.001）。 结论：FAD儿童的辅音歪曲具有明显的发声部位、韵母结构和发声方式的特异性。临床工作中应重点关注舌尖相关辅音、塞擦音及与特定韵母（如/i/韵头）的组合异常，以免漏诊误诊。.
To provide updated agent-level comparative estimates of GLP-1-based therapies for cardiovascular outcomes in adults with Type 2 diabetes mellitus (T2DM) using a hazard ratio (HR)-based systematic review and network meta-analysis (NMA). PubMed, Cochrane Library and Scopus were searched through December 2025 for randomized controlled trials evaluating GLP-1-based therapies in adults with T2DM and reporting time-to-event cardiovascular outcomes. Pairwise meta-analyses and a frequentist random-effects NMA were performed for all-cause mortality, cardiovascular mortality, major adverse cardiovascular events (MACE), non-fatal myocardial infarction (MI) and non-fatal stroke. Fifteen trials involving 97,173 participants were included. In pairwise placebo-controlled analyses, GLP-1-based therapies significantly reduced all-cause mortality, cardiovascular mortality and MACE. In the NMA, mortality estimates for several agents favoured benefit, although most comparisons were not statistically significant. For MACE, efpeglenatide, albiglutide and injectable semaglutide showed the most favourable comparative profiles. Albiglutide reduced non-fatal MI versus placebo, whereas non-fatal stroke estimates were imprecise. GLP-1-based therapies were associated with an overall favourable cardiovascular profile in T2DM. Pairwise analyses supported class-level benefit, whereas between-agent differences were more evident for MACE than for mortality outcomes in the NMA.
Objective:To investigate the expression of thioredoxin interacting protein（TXNIP）/nod like receptor thermoprotein domain related protein 3（NLRP3） signaling pathway in nasal polyps of patients with chronic sinusitis with nasal polyps（CRSwNP）, and to analyze its predictive value for postoperative recurrence. Methods:A prospective study was conducted on 130 patients with CRSwNP who underwent endoscopic sinus surgery at Wenzhou People's Hospital from January 2019 to January 2024. These patients were divided into a recurrence group and a non-recurrence group based on the recurrence status within one year after surgery. The clinical data and the expression of TXNIP, NLRP3 mRNA, and protein in nasal polyp tissues were compared between the two groups. The impact of TXNIP and NLRP3 expression on postoperative recurrence was analyzed. The interaction between TXNIP and NLRP3 expression in postoperative recurrence was also analyzed. The predictive value of TXNIP and NLRP3 expression for postoperative recurrence was evaluated. Results:The recurrence group had a higher proportion of eosinophilic（EOS） nasal polyps, postoperative infection, allergic rhinitis, preoperative Lund-Mackay score, and sinus CT score, as well as higher levels of serum interleukin-5（IL-5） and interleukin-21（IL-21） than those in the non-recurrence group（P<0.05）. The expression levels of TXNIP and NLRP3 mRNA and protein in nasal polyps from the recurrence group were also higher than those from the non-recurrence group（P<0.05）. After adjusting for EOS nasal polyps, postoperative infection, preoperative Lund-Mackay score, and serum IL-5 and IL-21 levels, the expression of TXNIP and NLRP3 proteins in nasal polyps remained independent risk factors for postoperative recurrence（P<0.05）. High levels of TXNIP and High levels of NLRP3 showed a positive interaction in the risk of postoperative recurrence（P<0.05）. A conventional prediction model was constructed based on EOS nasal polyps, postoperative infection, preoperative Lund-Mackay score, and serum IL-5 and IL-21 levels. A novel prediction model was constructed based on these factors as well as the expression of TXNIP and NLRP3 proteins in nasal polyps. The AUC value of the novel prediction model for predicting postoperative recurrence was significantly higher than that of the conventional model（P<0.05）. Conclusion:The expression levels of TXNIP and NLRP3 in nasal polyps of patients with postoperative recurrence of CRSwNP are increased. High levels of TXNIP and high levels of NLRP3 have a positive interaction in the risk of postoperative recurrence. Detection of their levels has a certain predictive value for postoperative recurrence, and TXNIP and NLRP3 have a significant gain value in the construction of the prediction model of postoperative recurrence in patients with CRSwNP. 目的：探讨慢性鼻窦炎伴鼻息肉（CRSwNP）患者鼻息肉组织中硫氧还蛋白相互作用蛋白（TXNIP）/NOD样受体热蛋白结构域相关蛋白3（NLRP3）信号通路表达，并分析其对术后复发的预测价值。 方法：前瞻性选取2019年1月至2024年1月于温州市人民医院接受鼻内镜手术治疗的130例CRSwNP患者为研究对象，依据术后1年内复发情况分为复发组与未复发组。比较2组临床资料及鼻息肉组织中TXNIP、NLRP3 mRNA及蛋白表达。分析TXNIP、NLRP3表达对术后复发的影响。分析TXNIP、NLRP3表达在术后复发中的交互作用。评价TXNIP、NLRP3表达对术后复发的预测价值。 结果：复发组伴有嗜酸性粒细胞（EOS）型鼻息肉占比、术后感染占比、变应性鼻炎占比及术前Lund-Mackay评分、鼻窦CT评分高于未复发组，血清白细胞介素-5（IL-5）、白细胞介素-21（IL-21）水平高于未复发组（P<0.05）；复发组鼻息肉组织中TXNIP、NLRP3 mRNA及蛋白表达水平高于未复发组（P<0.05）；校正了EOS型鼻息肉、术后感染、术前Lund-Mackay评分及血清IL-5、IL-21水平后，鼻息肉组织中TXNIP蛋白、NLRP3蛋白表达仍为术后复发的独立危险因素（P<0.05）；TXNIP高水平、NLRP3高水平在术后复发风险中呈正向交互作用（P<0.05）；以EOS型鼻息肉、术后感染、术前Lund-Mackay评分及血清IL-5、IL-21水平构建常规预测模型，以EOS型鼻息肉、术后感染、术前Lund-Mackay评分、血清IL-5、IL-21水平及鼻息肉组织中TXNIP蛋白、NLRP3蛋白表达构建新型预测模型，新型预测模型预测术后复发的曲线下面积（AUC）明显高于常规预测模型（P<0.05）。 结论：CRSwNP术后复发患者鼻息肉组织中TXNIP、NLRP3表达水平升高，TXNIP高水平、NLRP3高水平在术后复发风险中呈正向交互作用，检测其水平对术后复发具有一定预测价值，且TXNIP、NLRP3在构建CRSwNP患者术后复发预测模型中具有显著的增益价值。.