The rapid evolution of deep learning is revolutionizing critical care medicine by enabling highly accurate early warning systems. These systems are capable of predicting diverse clinical deteriorations, including acute kidney injury, myocardial infarction, and circulatory failure. While demonstrating strong predictive capabilities, conventional deep learning models face two fundamental limitations in clinical implementation: their opaque decision-making processes and limited generalizability across diverse patient populations and care environments. To address these challenges, we present a causally-informed deep learning framework that integrates causal discovery to jointly identify the causal drivers of clinical outcomes alongside prediction. This approach yields two unique advantages: demonstrating the explicit interpretation of the prediction while exhibiting decent performance when applied to unfamiliar environments. Benefiting from these features, our approach achieves superior accuracy across six different critical deteriorations and also demonstrates improved generalizability across diverse patient groups compared to various baseline algorithms. Besides, we provide explicit causal pathways to serve as references for assistant clinical diagnosis and potential interventions. By incorporating causal reasoning into clinical prediction, our approach can enhance clinical decision support through both reliable forecasting and transparent physiological interpretation, paving the way for more trustworthy AI implementation in critical care.
In response to the increasingly serious traffic safety issues and regulatory challenges of electric bicycles (e-bikes), this study proposes an advanced multi-task detection model called P-YOLOv10. The model aims to achieve end-to-end unified recognition of riding safety factors and fine-grained regional attributes of license plates. To address inaccurate small-object detection and difficulty in distinguishing fine-grained features in complex real-world scenes, P-YOLOv10 introduces systematic optimizations based on the latest YOLOv10 architecture. First, it integrates the Selective Channel-Spatial Attention (SCSA) module to enhance the network's ability to capture key local features. Second, it adopts the minimum point distance intersection over union (MPDIoU) loss function to improve bounding box regression accuracy, especially for small objects such as license plates. Finally, it uses the Gaussian error linear unit (GELU) activation function to improve nonlinear representation and training stability. This study trains and evaluates the model on a self-built dataset with 2,237 images. The dataset covers diverse scenes in Guangzhou and Foshan and includes new fine-grained regional annotations. The experimental results show that P-YOLOv10 achieves excellent performance. Its overall mean average precision (mAP) reaches 96.5%, which is 1% higher than the baseline YOLOv10. It also achieves high accuracy on the newly added license plate region recognition task. The results of this study confirm the effectiveness of the integrated optimization strategy. They provide a more accurate and more comprehensive technical solution for intelligent traffic regulation systems.
Halofantrine (halo) is an antimalarial drug that has recently been proven to have the potential to treat Glioblastoma (GBM). The aim of the study is to explore the inhibitory effect of halos on GBM and its mechanism. The expression of ATP6V0D2 in GBM was analyzed using the Cancer Genome Atlas (TCGA), the comprehensive database of gene expression, and clinical patient samples. In vitro, we evaluated the inhibitory effect of halo on U251 cells; qPCR, Western blot, and immunofluorescence were used to detect the changes in ATP6V0D2 and autophagy-related genes and proteins. Transmission electron microscopy was used to detect the formation of autophagosomes. A stable ATP6V0D2 knockdown and overexpression model was constructed in U251 cells to verify the criticality of ATP6V0D2. The in vivo anti-tumor effect and mechanism of halo were evaluated using a U251 cell axillary tumor-bearing mouse model (independent experiment repeat number (n = 5) and tail vein administration injection. The expression level of ATP6V0D2 is relatively low in GBM patients. Halo upregulates ATP6V0D2 and induces cytotoxic autophagy (TA) in U251. Knockdown of ATP6V0D2 can inhibit halo-mediated TA and cytotoxicity, while overexpression can enhance these effects. Halo also demonstrated significant anti-GBM activity in vivo, and its mechanism was consistent with the results of in vitro studies. This study has preliminarily demonstrated that the anti-malarial drug halo can promote autophagy in GBM cells by upregulating the ATP6V0D2 gene, thereby exerting an anti-GBM effect. So far, no experimental studies have been conducted on the permeability of the blood-brain barrier within the halo body. Furthermore, the potential cardiac toxicity of halo is a point that deserves particular attention. Halo triggers cytotoxic autophagy in U251 cells by upregulating ATP6V0D2, establishing the key tumor suppressor factor status of ATP6V0D2 in GBM.
The development of catalytic systems for the enantioselective epoxidation of sterically hindered trisubstituted alkenes using molecular oxygen (O₂) as the terminal oxidant remains a formidable challenge. Here, we report a biomimetic bifunctional photocatalyst that integrates a chiral manganese center and a covalently tethered anthraquinone photosensitizer within a single molecular scaffold. This unified design emulates the enzymatic principle of spatially coupled oxygen activation and chiral induction. Under visible light and ambient O₂, the catalyst enables the asymmetric epoxidation of challenging trisubstituted alkenes, including cyclic sulfones and linear α,β-unsaturated carbonyls, in up to 99% enantiomeric excess (ee), and also facilitates the efficient conversion of sulfilimines to (chiral) sulfoximines. Mechanistic studies reveal a cascade involving singlet-oxygen-mediated oxidation, oxidative decarboxylation, and acid-assisted O-O bond heterolysis to generate a high-valent Mn⁴⁺=O species as the key active intermediate. By unifying light harvesting, O₂ activation, and asymmetric catalysis in a precious-metal-free platform, this work establishes a versatile, sustainable strategy for the selective oxidation of traditionally recalcitrant substrates.
Epidermal growth factor receptor (EGFR) mutation is the most common driver mutation in non-small cell lung cancer (NSCLC) among Asian populations. For patients with resectable EGFR-mutant NSCLC, the high risk of postoperative recurrence remains a major clinical challenge. The neoadjuvant treatment paradigm has shifted from conventional chemotherapy to precision therapies centered on EGFR-tyrosine kinase inhibitors (TKIs), aiming to downstage tumor and eradicate micrometastases before surgery, thereby improving surgical outcomes and long-term survival. This article systematically reviews the evolution and recent advances in neoadjuvant therapy for EGFR-mutant NSCLC. As of December 2025, osimertinib-based regimens, whether used as monotherapy or in combination with chemotherapy, have emerged as potential options in this field and are supported by high-level evidence-based medicine. The article also discusses the limitations of immunotherapy in the EGFR-mutant NSCLC population and the future development trends of combination strategies, emphasizing that biomarker-guided individualized therapy represents the corner direction moving forward. 表皮生长因子受体（EGFR）突变是亚裔非小细胞肺癌（NSCLC）中最常见的驱动基因突变。对于可切除的EGFR突变NSCLC患者，术后高复发风险是目前的主要挑战。新辅助治疗模式已从传统化疗转向以EGFR-酪氨酸激酶抑制剂为核心的精准治疗，旨在术前缩小肿瘤、清除微转移灶，从而改善手术结局和长期生存。文章系统回顾了EGFR突变NSCLC新辅助治疗的演变历程和最新进展。截至2025年12月，以奥希替尼为基础的方案，无论是单药还是联合化疗方案，已成为该领域的潜在选择之一，并获得高级别循证医学证据支持。文章亦探讨了免疫治疗在EGFR突变NSCLC人群中的局限性以及联合治疗策略的未来发展趋势，并强调基于生物标志物的个体化治疗是未来的核心方向。.
The classic donor-acceptor (D-A) conjugated polymers are highly developed in organic electronics for their potential in organic light-emitting diodes, organic field-effect transistors, and organic photovoltaics. Since 2017, we reported aggregation-induced radical (AIR) and ground-state charge transfer (GSCT), which render these materials sensitive to oxygen doping and low stability in devices. In this work, we propose a strategy to design oxygen-rich conjugated radical (ORCR) by intentionally incorporating oxygen-centered radicals into the D-A backbones. A series of D-A polymers were synthesized via atom-economical direct arylation polymerization, followed by quantitative post-synthetic dealkylation to yield the corresponding oxygen-radical polymers. The introduction of oxygen radicals showed highly lowered bandgap and highly quenched fluorescence, signaling an enhanced non-radiative relaxation pathway. Electron paramagnetic resonance confirmed their high spin concentration with high air stability. Notably, BDTO2-BBT exhibited an extraordinary photothermal conversion temperature of 170°C under 808 nm laser irradiation for 60 s, maintaining performance over multiple cycles. This study reported robust open-shell ORCR materials but also provides a simple design paradigm for stable high-spin organic radical semiconductors.
With the increasing frequency of electrocoagulation hemostasis used in endoscopic submucosal dissection (ESD), the incidence of postoperative bleeding is gradually decreasing, while the incidence of post-ESD electrocoagulation syndrome (PECS) is gradually increasing. Water cooling can reduce thermal injury to the intestinal wall after electrocoagulation. Therefore, this study intends to conduct a prospective, multi-center randomized controlled trial to explore the effectiveness of water cooling after electrocoagulation in reducing the occurrence of PECS. From November 2022 to October 2023, 420 patients were prospectively included. The patients were 1:1 randomly divided into two groups, named the standard ESD (S-ESD) group and the water-cooled ESD (W-ESD) group. The main outcome measure was the incidence of PECS. Secondary outcomes were ESD operative time, complete resection rates, and adverse effects. The incidence of PECS in the W-ESD group was significantly lower than that in the S-ESD group (7.6% vs. 17.1%, P = 0.003). The median operation time was also shorter in the W-ESD group than in the S-ESD group (37.0 minutes, IQR: 30.0-47.0 minutes vs 42.5 minutes, IQR: 33.0-60.0 minutes, P < 0.001). There was no significant difference in specimen size between the two groups (3.8cm2, IQR: 3.1-6.3cm2 vs 4.6cm2, IQR: 3.1-7.1cm2, P = 0.286), and the complete resection rate was 100%. No perforation occurred in any patient. Water-cooled ESD technology can significantly reduce the occurrence of PECS.
Recent advances in human mobility research have revealed consistent pairwise characteristics in movement behaviour, yet existing mobility models often overlook the spatial and topological structure of mobility networks. By analysing millions of devices' anonymized cell phone trajectories, we show that human mobility networks exhibit a pronounced polycentric and modular structure, in which movements within spatial modules differ fundamentally from movements between modules. This finding challenges the common assumption of uniform mobility dynamics across spatial scales. Inspired by switching behaviours in animal movement patterns, we introduce a 'switch mechanism' to distinguish intra-module and inter-module exploration modes. Incorporating this mechanism into a generative mobility model allows us to simultaneously reproduce individual-level mobility statistics and emergent network-level structures, including high modularity, long topological distances and frequent long-range travel. Our results provide a unified mechanistic explanation for the emergence of polycentric human mobility patterns and highlight the importance of scale-dependent movement dynamics, with implications for urban planning, transportation modelling and epidemic forecasting.
Transplantation surgery induces severe immune stress in pearl oysters Pinctada fucata martensii, yet effective immunomodulatory strategies remain limited. This study establishes a proteomics-guided strategy for immunomodulation by identifying cyclophilin as a candidate mediator through iTRAQ-based quantitative analysis and validating cyclosporin A (CsA) through serum immune indicator and transcriptome analysis. Serum iTRAQ analysis identified 1,069 differentially expressed proteins following transplantation, among which cyclophilin exhibited significant up-regulation and was selected as a candidate target for therapeutic intervention. Dose-response assays determined 3.9 × 10-3 mol/L as the optimal concentration, which significantly suppressed TNF-α levels under LPS stimulation (P < 0.05). At this concentration, CsA pre-treatment markedly decreased circulating IL-17 concentrations, while it enhanced SOD and CAT enzymatic activities (P < 0.05). Transcriptome analysis revealed that CsA treatment was associated with upregulation of HIF-1 and Notch signaling pathway-related genes, concomitant with alleviation of LPS-induced downregulation in DNA replication and cell cycle pathways. Furthermore, CsA significantly inhibited hemocyte apoptosis compared to the control group (P < 0.05). These findings demonstrate that iTRAQ-based proteomic screening enables rational target identification for immunomodulation, and CsA exerts protective effects associated with altered expression of HIF-1/Notch pathway-related genes and apoptosis inhibition. These findings provide a molecular basis for developing immunomodulatory strategies in pearl oyster aquaculture.
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。.
Cerebral palsy (CP) is traditionally characterized as a disorder of motor impairment; however, growing evidence suggests it reflects broader dysregulation across multiple physiological systems. We present a longitudinal case study examining whether pairing transcutaneous spinal neuromodulation (TSN) with a proprioceptive-derived intervention (PDI) can engage systems-level functional adaptation in an adolescent with CP spastic diplegia, whose progress had plateaued after years of conventional therapy. Across two years of the intervention, structured clinical observations revealed progressive and reversible improvements spanning posture, locomotion, fine motor control, speech, vision, hearing, sleep, endurance, executive function, and psychosocial engagement. Motor coordination often changed rapidly with stimulation, autonomic functions evolved over intermediate timescales, and longer-lasting changes consistent with support of physiological capacity and recovery emerged more gradually. The task specificity, state dependence, and reversibility of these effects are consistent with activity-dependent processes guided by enhanced proprioceptive signaling during TSN + PDI. Importantly, these adaptations did not emerge uniformly across domains. These findings support a reconceptualization of CP not solely as an isolated motor disorder, but as a condition of maladaptive multisystem regulation that may be amenable to noninvasive, proprioceptively derived neuromodulatory rehabilitation strategies. While limited to a single case, this work highlights underappreciated neuroadaptive potential in CP and motivates future controlled studies targeting systems-level recovery.
Hilar cholangiocarcinoma (HCCA) is a malignant tumor at the hepatic hilum with poor prognosis and survival despite surgical resection. While existing staging systems, including AJCC, Gazzaniga T, MSKCC and Blumgart, provide prognostic frameworks, their predictive accuracy remains suboptimal. This study aimed to develop and validate a novel machine learning-based postoperative staging system to predict overall survival (OS) and enhance prognostic stratification for HCCA patients undergoing surgery. We retrospectively analyzed 426 HCCA patients who underwent surgical resection at Eastern Hepatobiliary Surgery Hospital (EHBH) between February 2011 and May 2022. Seventy clinical variables, encompassing demographic characteristics, laboratory parameters, and imaging data, were evaluated. Eight machine learning algorithms were employed for feature selection and model development. A multivariable Cox regression analysis was subsequently performed to establish a staging system. External validation was performed using an independent cohort of 88 HCCA patients for further evaluation. The final model incorporated key prognostic factors including tumor stage, vascular invasion, and tumor biomarkers (CA199,CA125,CEA). The CatBoost algorithm demonstrated superior performance on the validation set (AUC = 0.88). The developed EHBH-HCCA staging system based on CatBoost stratified patients into four risk levels, significantly differentiating 3-year survival outcomes (P < 0.001). Median survival times were: Level I (> 36 months), Level II (25.0 months), Level III (18.0 months), and Level IV (< 12 months). The system showed superior discrimination (Harrell's C-index: 0.717, 95% CI: 0.662-0.793) and predictive accuracy (Brier score: 0.144) compared with conventional staging systems. In the external validation cohort, the CatBoost model demonstrated good discriminative performance for 3-year survival prediction, with an AUC of 0.84. For survival time prediction, the TabNet model achieved an RMSE of 4.71 months, MAE of 3.49 months, and R² of 0.53. The EHBH-HCCA staging system provides enhanced prognostic stratification for HCCA patients following surgical resection. This novel approach offers potential for improved clinical decision-making and personalized treatment regimen.
Objective: To investigate the expression of miR-527 in bladder urothelial cell carcinoma tissues (UCC) and cell lines, and to explore the mechanism by which miR-527 inhibits bladder cancer cell migration and promotes apoptosis through targeting Bcl-2. Methods: The expression of miR-527 in bladder UCC was analyzed using The Cancer Genome Atlas database. The expression of miR-527 in bladder UCC cell lines was verified by real-time quantitative reverse transcription polymerase chain reaction. The relationship between miR-527 and its target gene Bcl-2 was validated using a dual-luciferase reporter assay. miR-527 inhibitor and miR-527 mimic were constructed for cell transfection. Cell migration and apoptosis were assessed using wound healing assay and flow cytometry. Protein expression was detected by Western blot. In vivo tumorigenesis and the expressions of Bcl-2 and Ki-67 were evaluated using a nude mouse cell-derived xenograft model and immunohistochemistry. Results: Analysis of The Cancer Genome Atlas database revealed that miR-527 expression was significantly higher in bladder cancer tissues than in normal bladder tissues, whereas Bcl-2 protein expression was significantly lower. Dual-luciferase reporter assay confirmed that miR-527 directly targeted Bcl-2. Inhibition of miR-527 significantly upregulated Bcl-2 mRNA and protein levels (both P＜0.01), enhanced cell migration, and reduced apoptosis [migration rate: (100.00±0.00)% in the miR-527 inhibitor group vs. (47.74 ± 2.18)% in the T24 control group; apoptosis rate: (2.68±1.28)% vs. (11.82±5.19)%; both P＜0.05]. Overexpression of miR-527 produced opposite effects [migration rate: (45.22±3.66)% in the miR-527 overexpression group vs. (100.00±0.00)% in the UMUC-3 control group; apoptosis rate: (11.74±0.64)% vs. (3.81±0.75)%; both P＜0.05]. In animal experiments, overexpression of miR-527 significantly inhibited tumor growth and reduced the expressions of Bcl-2 and Ki-67 in tumor tissues, whereas inhibition of miR-527 promoted tumor growth, increased tumor cellular atypia, and enhanced the expressions of Bcl-2 and Ki-67. Conclusions: miR-527, as a tumor-associated gene, is highly expressed in bladder cancer tissues. Overexpression of miR-527 inhibits the growth and migration of bladder cancer cells and induces apoptosis by negatively regulating the Bcl-2. 目的： 探讨miR-527在膀胱尿路上皮癌组织和细胞系中的表达及其通过靶向Bcl-2抑制膀胱癌细胞迁移并促进癌细胞凋亡的机制。 方法： 利用癌症基因组图谱数据库分析miR-527在膀胱尿路上皮癌组织中的表达，通过实时荧光定量逆转录聚合酶链反应验证膀胱尿路上皮癌细胞系中miR-527的表达，双荧光素酶报告基因验证miR-527与靶基因Bcl-2的关系，构建miR-527 inhibitor和miR-527 mimic进行细胞转染，细胞划痕实验及流式细胞术检测细胞迁移和凋亡情况，Western blot检测相关蛋白表达，裸鼠细胞源性异种移植和免疫组化验证体内成瘤和Bcl-2、Ki-67表达情况。 结果： 通过癌症基因组图谱数据库分析，膀胱癌组织中miR-527表达显著高于正常膀胱组织，Bcl-2蛋白表达显著降低。双荧光素酶报告基因实验证实miR-527可直接靶向Bcl-2。抑制miR-527表达后，Bcl-2 mRNA及蛋白表达水平显著升高（均P＜0.01），细胞迁移能力增强，凋亡细胞减少［T24细胞miR-527抑制组、T24细胞对照组细胞迁移率：（100.00±0.00）%、（47.74±2.18）%，细胞凋亡率：（2.68±1.28）%、（11.82±5.19）%，均P＜0.05］，但过表达miR-527则相反［UMUC-3细胞miR-527过表达组和UMUC-3 细胞对照组细胞迁移率：（45.22±3.66）%、（100.00±0.00）%，细胞凋亡率：（11.74±0.64）%、（3.81±0.75）%，均P＜0.05］。在动物实验中，过表达miR-527显著抑制肿瘤生长，肿瘤组织中Bcl-2及Ki-67表达减弱；抑制miR-527则促进肿瘤生长，肿瘤细胞异型性增加，Bcl-2及Ki-67表达增强。 结论： miR-527作为一种肿瘤相关基因，在膀胱癌组织中高表达，同时过表达miR-527可通过靶向负调控Bcl-2基因抑制膀胱癌肿瘤细胞生长和迁移，并诱导肿瘤细胞凋亡。.
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。.
Predicting the subcellular localization of multi-site bacterial proteins remains challenging because label correlations, limited sample size, and low sequence similarity reduce the effectiveness of conventional multi-label classifiers. In this study, we propose a multi-label cascade flexible neural forest (MLCFN Forest) that combines label-powerset-style coding-classification-decoding with a cascade ensemble of flexible neural tree (FNT) groups. The framework preserves label dependencies, decomposes the induced multi-class task into coordinated binary FNT outputs, and progressively reallocates model capacity to low-confidence samples through confidence-guided sample propagation and feature enhancement across layers. We explicitly note that the cascade FNT backbone builds on our previous CFNForest studies for cancer subtype classification, whereas the present work adapts that backbone to multi-label bacterial protein localization by introducing label-set encoding/decoding, multiclass FNT grouping, and a multi-site protein subcellular localization evaluation workflow. Using Gram-negative and Gram-positive benchmark datasets together with AECA-PSSM and PSSM-DWT features, MLCFN Forest consistently outperformed ML-RBF, ML-KNN, ML-LOC, INSDIF, and MLASSO under jackknife evaluation. For example, it achieved OLA/OAA values of 78.3%/76.4% on the Gram-negative AECA-PSSM dataset, 80.7%/78.5% on the Gram-negative PSSM-DWT dataset, and 80.2%/77.6% on the Gram-positive AECA-PSSM dataset. PCA-based low-dimensional experiments further suggested that the model retained good predictive ability after substantial dimensionality reduction. The present study is limited to classical benchmark datasets and does not yet include an independent external test set, strict nested model selection, or direct benchmarking against protein language model predictors; these points are therefore discussed as limitations and future directions.
Polymer-based dielectrics are widely employed in electrostatic energy storage capacitors serving as pulse power supply owing to their lightweight nature and rapid charge-discharge capability. However, their intrinsically low dielectric constant severely limits energy storage density. Although high-dielectric-constant nanofillers are commonly incorporated to enhance permittivity, organic-inorganic interfacial incompatibility often induces particle agglomeration and structural defects. In this work, we propose a confined co-doping strategy for structured polymer dielectrics, wherein BaTiO3 and Al2O3 nanoparticles are co-doed within the ferroelectric core P(VDF-HFP) of coaxial fibers and undergo self-assembly. This approach simultaneously enhances both energy density and charge-discharge efficiency. As a result, the 1 wt% BaTiO3/1 wt% Al2O3 core co-doping composite dielectric achieves a discharged energy density of 19.2 J/cm3 and a charge-discharge efficiency of 81.0%, and maintains stable performance over 1 × 105 cycles under an electric field of 400 kV/mm. This confined co-doping strategy thus provides an effective and scalable route for developing polymer-based dielectrics with high energy density and high reliability.
Percutaneous endoscopic lumbar discectomy (PELD) is a preferred minimally invasive surgery for lumbar disc herniation (LDH); however, postoperative recurrence, nerve root damage, and hyperesthesia continue to present key clinical challenges. Chitosan represents a novel preventive approach against postoperative complications. This study aimed to assess the clinical efficacy of ultrasound-guided percutaneous endoscopic interlaminar discectomy (PEID) plus medical chitosan in treating lumbar 4-5 disc herniation (L4-5 LDH). Totally, 200 L4-5 LDH patients were prospectively recruited and randomly divided into the control group (ultrasound-guided PEID) and observation group (ultrasound-guided PEID plus medical chitosan). Low back and leg pain and lumbar dysfunction were assessed preoperatively and postoperatively using Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and Japanese Orthopaedic Association (JOA). Efficacy and postoperative complications were evaluated according to the modified MacNab criteria. Logistic regression analyses identified the risk factors. Mann-Whitney U test was used for inter-group comparisons, and the Kruskal-Wallis test for timepoint comparisons. The two groups showed significant differences in pre-treatment Pfirrmann classification and operation time. As time progressed, patients exhibited reduced VAS and ODI scores and increased JOA scores postoperatively. Significant differences were observed in VAS, JOA, and ODI scores in the observation group at 2 weeks postoperatively. The observation group demonstrated superior treatment efficacy and a lower complication incidence than the control group. Age, disease course, and postoperative bleeding were independent risk factors affecting clinical efficacy of ultrasound-guided PEID plus chitosan. Ultrasound-guided PEID plus medical chitosan reduces postoperative pain and perioperative complications, demonstrating superior clinical efficacy.
Secondary organic aerosol (SOA) formation is strongly influenced by relative humidity (RH), yet the underlying processes remain insufficiently understood under realistic atmospheric conditions. This study investigates RH-dependent SOA formation from ambient urban air using a field-deployable oxidation flow reactor (OFR), focusing on the multigenerational oxidation of volatile organic compound (VOC) precursors and their gas-to-particle transformation. Elevated RH markedly enhanced SOA production, yielding nearly 5-fold higher OA mass growth compared to low-RH oxidation under comparable photochemical ages. Evolution patterns of oxygenated VOCs (OVOCs) reveal that high RH accelerates the oxidative transformation of less-oxidized, higher-volatility intermediates into more-oxidized, lower-volatility products. These generational products facilitate SOA formation via condensation onto pre-existing particles and through formation and growth of new particles. This is corroborated by the more pronounced increase in particle number concentrations at 20-200 nm during high-RH oxidation, alongside substantial OA mass growth in both newly formed particles (100-200 nm) and pre-existing particles (∼500 nm). Potential water photolysis and thus OH production within the particle phase under high RH may also contribute to the oxidation processes. Overall, this work highlights the multifaceted role of RH in urban SOA formation, reflecting its concurrent influences on OVOC transformation, particle formation and growth, and gas-particle partitioning of oxidized products. These insights refine our understanding of SOA formation mechanisms under realistic atmospheric conditions.
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This study aimed to investigate pollen types on the fruit quality of 'Hongyang' kiwifruit, providing a scientific basis for rational pollinizer tree allocation. Using 'Hongyang' as the test material and commercial pollen as the control, pollen from 12 male plants of 2 species ( Actinidia chinesis var. Deliciosa and A. chinensis ) was used to pollinate in orchards. PCA was applied for comprehensive evaluation of the pollinated fruit. The results were as follows: (1) Male A. chinesis var. deliciosa plants had a later flowering period but more pollen than male A. chinensis plants did, and there were notable intraspecific differences in floral traits. Among the six tested male plants of A. chinensis ('a-1', 'a-2', 'a-3', 'a-5', 'a-6', 'a-7'), their flowering periods basically overlap with those of 'Hongyang', while the other materials were 5-23 days later than 'Hongyang'.(2) 'Hongyang' had a significant pollen xenia on the fruit set, quality, and seed characteristics, particularly showing large differences in single fruit weight, sugar-acid ratio, vitamin C content, flesh color, and seed number. Different pollen pollination treatments had different impacts on 'Hongyang' fruit quality. (3) According to principal component scores, floral organ characteristics, and flowering period evaluations, male A. chinensis plants 'a-6', 'a-2', and 'a-7' are suitable and compatible pollinizers for 'Hongyang', whereas the male A. chinensis var. deliciosa male plants 'a-10' and 'a-12' are recommended for poststorage artificial pollination. In conclusion, there are significant differences in floral traits among inter- and intraspecific male kiwifruit plants. Pollen donor choice notably affects the key quality indicators of 'Hongyang'.