[摘 要] 目的：探究半乳糖凝集素-9（Gal-9）对胰腺癌细胞的侵袭与迁移功能的促进作用及其机制。方法：基于公开单细胞转录组数据分析胰腺癌中免疫检查点分子的表达谱，结合Western blotting和ELISA验证Gal-9在胰腺癌细胞及临床相关模型中的表达与分泌特征。建立C57BL/6小鼠胰腺原位移植瘤模型，通过免疫组化、免疫荧光染色和流式细胞术分析Gal-9对肿瘤细胞增殖及其对瘤内CD8+ T细胞浸润与功能状态的影响。Gal-9重组蛋白及肿瘤细胞条件培养基（CM）处理肿瘤相关成纤维细胞（CAF），Western blotting、RT-qPCR和免疫荧光检测CAF中Ⅰ型胶原表达变化。免疫共沉淀、免疫荧光染色和Western blotting分析Gal-9与CD44的相互作用及JAK2/STAT3通路相关蛋白的表达。构建过表达Gal-9胰腺癌细胞与CAF共移植的裸鼠皮下荷瘤模型，结合天狼星红和马松染色评估小鼠肿瘤组织中胶原沉积情况。脱细胞外基质法提取CAF中沉积的细胞外基质（ECM）蛋白；通过细胞划痕、Transwell迁移及侵袭实验，检测CAF来源Ⅰ型胶原对胰腺癌细胞侵袭、迁移功能的影响，并通过siRNA干扰Gal-9表达进行功能反向验证。结果：与经典免疫检查点分子PD-L1和CTLA-4相比，Gal-9在胰腺癌中显著高表达（P < 0.000 1）。体内实验表明，Gal-9促进肿瘤生长（P < 0.001），上调Ki-67表达，同时减少肿瘤内CD8⁺ T细胞浸润并诱导肿瘤组织中TIM-3⁺细胞比例升高，Granzyme B、IFN-γ及TNF-α表达下降（P < 0.05）。体外实验显示，外源性Gal-9及肿瘤细胞来源的CM均可上调CAF中Ⅰ型胶原表达（P < 0.001）。机制研究表明，在CAF中抗Gal-9抗体免疫沉淀复合物中检测到CD44，且JAK2/STAT3蛋白表达水平增加。CAF来源的Ⅰ型胶原处理胰腺癌细胞后，肿瘤细胞的迁移和侵袭数量增加。相反，肿瘤细胞中敲低Gal-9表达后，CAF来源Ⅰ型胶原水平下降，同时肿瘤细胞侵袭和迁移数量下降。结论：胰腺癌来源的Gal-9具有双重作用：一方面，通过促进肿瘤细胞增殖和诱导CD8+ T细胞耗竭促进肿瘤进展；另一方面，通过结合CAF上的CD44受体，激活JAK2/STAT3信号通路，刺激CAF合成并分泌Ⅰ型胶原，进而增强胰腺癌细胞的侵袭迁移能力。

Work serves as a critical means of obtaining resources, facilitating personal growth, realizing self-worth, and engaging in social interactions. However, work-related diseases pose significant threats to workers’ health and productivity, and impose considerable economic burdens. This article categorized work-related diseases into six major types, including musculoskeletal disorders, mental and behavioral disorders, cardiovascular and metabolic diseases, digestive system diseases, reproductive system diseases, and non-specific respiratory diseases, and summarized their risk factors, assessment methods, policy regulation, and prevention and control measures. Current research in this field predominantly relies on cross-sectional studies, which present limitations in causal inference and potential risks of bias. Future studies should expand sample sizes, optimize research designs, and establish multidimensional evaluation systems to comprehensively assess the health and economic impacts of work-related diseases. It is recommended to enhance the translation of research findings into practice, thereby providing a scientific basis for the occupational health protection system and promoting the well-being and sustainable development of the working population.

ObjectiveTo investigate the changes in the expression levels of Yes-associated protein 1 （YAP1） and human collagen type Ⅵ alpha 1 （COL6A1） in pancreatic cancer under hyperglycemic conditions and their association with prognosis. MethodsGEPIA database and R software were used to analyze the expression levels of YAP1 and COL6A1 and their correlation in pancreatic cancer， as well as their impact on the prognosis of patients with pancreatic cancer. The cBioPortal database was used to identify the co-expressed genes of YAP1 and COL6A1 in pancreatic cancer， and the gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses were performed. Quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression levels of YAP1 and COL6A1 in human pancreatic cancer PANC-1 cells cultured under hyperglycemic or normoglycemic conditions. A nude mouse model of pancreatic cancer with type 2 diabetes was established， and immunohistochemistry was used to measure the expression of YAP1 and COL6A1 in subcutaneous tumor tissue. Clinical specimens and data of 96 patients with pancreatic cancer were collected from January 2016 to January 2020 in the First Affiliated Hospital of Guangxi Medical University， Guangxi Medical University Cancer Hospital and Wuming Hospital Affiliated to Guangxi Medical University. Among them， 48 patients with pancreatic cancer and diabetes were enrolled as study group， and 48 patients with pancreatic cancer alone were enrolled as control group； immunohistochemistry was used to measure the expression levels of YAP1 and COL6A1 in tissue samples from both groups， and their association with clinical indicators and survival outcomes was analyzed. The t-test was used for comparison of continuous data between groups， and the chi-square test or the Mann-Whitney U test was used for comparison of categorical data between groups； the Pearson correlation analysis was used for normally distributed continuous variables， while the Spearman correlation analysis was used for discontinuous variables or non-normally distributed variables. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison of survival rates. The Cox proportional hazards model was used to perform univariate and multivariate analyses. ResultsBoth YAP1 and COL6A1 were highly expressed in pancreatic cancer， with a strong correlation between them （r=0.85， P<0.001）， and they were associated with the poor prognosis of patients （hazard ratio ［HR］=1.8 and 1.5， both P<0.05）. YAP1 and COL6A1 were significantly correlated with 219 and 122 genes， respectively （r=0.83 and 0.86， both P<0.05）， and the GO and KEGG enrichment analyses showed that these genes affected the development and progression of pancreatic cancer through extracellular matrix-receptor interaction， the Hippo signaling pathway， and the phosphatidylinositol 3-kinase/protein kinase B signaling pathway. Quantitative real-time PCR and Western blot showed that there were significant increases in the mRNA and protein expression levels of YAP1 and COL6A1 in human pancreatic cancer PANC-1 cells under hyperglycemic conditions （mRNA expression： t=4.726 and 6.197， both P<0.05； protein expression： t=6.826 and 5.254， both P<0.05）. Immunohistochemistry showed that there were significant increases in the expression levels of YAP1 and COL6A1 in subcutaneous tumor tissue of nude mice， with a positive correlation between them （r=0.985， P<0.001）. For the clinical specimens of pancreatic cancer tissue， immunohistochemistry showed that there were significant increases in the positive expression levels of YAP1 and COL6A1 proteins in the study group， with a positive correlation between them （r=0.882， P<0.001）. The multivariate analysis of clinical data showed that lymph node metastasis （HR=0.083， 95% confidence interval ［CI］： 0.030 — 0.231， P<0.05）， distant organ metastasis （HR=0.166， 95%CI： 0.065 — 0.420， P<0.05）， YAP1 expression level （HR=2.027， 95%CI： 1.065 — 3.857， P<0.05）， and COL6A1 expression level （HR=2.044， 95%CI： 1.019 — 4.099， P<0.05） were independent influencing factors for the prognosis of patients with pancreatic cancer. The survival analysis showed that the high YAP1 expression group had a significantly lower 2-year survival rate than the low YAP1 expression group （6.82% vs 25.00%， χ²=16.382， P<0.001）， and the high COL6A1 expression group had a significantly lower 2-year survival rate than the low COL6A1 expression group （14.58% vs 18.75%， χ²=4.579， P=0.032）. ConclusionThe hyperglycemic environment promotes the high expression of YAP1 and COL6A1 in pancreatic cancer， which is associated with poor prognosis in patients.

Pathologic myopia(PM)is characterized by progressive axial elongation, posterior staphyloma, and fundus degenerative changes, representing a leading cause of blindness in Asian countries.Posterior scleral reinforcement(PSR)is currently the only surgical intervention to slow axial elongation. Its mechanisms involve mechanical reinforcement, improved blood circulation, and biological stimulation of scleral remodeling. This article reviews recent advances in PSR: surgical techniques have evolved from complex, classic procedures to standardized single-strip methods, incorporating 3D MRI to quantify posterior staphyloma morphology for personalized graft design and facilitating minimally invasive, precision surgery. Among implant materials, biomaterials such as allogeneic dura mater are being continuously optimized, while biomimetic piezoelectric smart materials actively promote scleral collagen synthesis through electrical signals, achieving a paradigm shift from “passive support”to “active reinforcement”. Clinical outcomes indicate advantages in regulating axial length, enhancing visual function and blood circulation, and facilitating early intervention in children. Combined procedures with ICL implantation, cataract surgery or vitrectomy provide comprehensive treatment regimens for individual patients with varied conditions. This article also analyzes long-term issues and core controversies including ectopic posterior staphyloma and reoperation, and prospects future research directions such as artificial intelligence assistance, translation of smart materials and full-cycle prevention and treatment systems, so as to provide references for clinical practice and scientific research.

Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.
Reperfusion Injury/drug therapy* ; Reactive Oxygen Species/metabolism* ; Reactive Nitrogen Species/metabolism* ; Humans ; Liver/drug effects* ; Animals ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*

Clinical chemotherapy for prostate cancer is still compromised by high treatment thresholds and severe off-target toxicity of drugs. Given the limited progress in improving therapeutic outcomes and reducing toxicity with the existing toolbox, efforts to broaden the chemotherapeutic window are highly desired. Here, we discover that gossypol (GSP, a natural compound) dramatically enhances the chemosensitivity of cabazitaxel (CTX), even at previously ineffective concentrations. Based on this interesting finding, we exploit a carrier-free chemotherapeutic nano-booster for prostate cancer treatment, which is molecularly co-assembled by GSP and cabazitaxel (CTX). GSP not only readily forms nanoassembly with CTX, but also functions as a chemotherapeutic enhancer that unlocks an ultra-low-dose chemotherapeutic window. Not only that, precise dual-drug nanoassembly confers CTX a significantly larger maximum tolerable dose. As expected, the nano-booster exerts striking therapeutic benefits in mouse prostate tumor xenograft models. This study advances chemotherapeutic window expansion and self-sensitized chemotherapy toward clinical applicability.

The diagnosis of hematological disorders is currently established from the combined results of different tests, including those assessing morphology (M), immunophenotype (I), cytogenetics (C), and molecular biology (M) (collectively known as the MICM classification). In this workflow, most of the results are interpreted manually (i.e., by a human, without automation), which is expertise-dependent, labor-intensive, time-consuming, and with inherent interobserver variability. Also, with advances in instruments and technologies, the data is gaining higher dimensionality and throughput, making additional challenges for manual analysis. Recently, artificial intelligence (AI) has emerged as a promising tool in clinical hematology to ensure timely diagnosis, precise risk stratification, and treatment success. In this review, we summarize the current advances, limitations, and challenges of AI models and raise potential strategies for improving their performance in each sector of the MICM pipeline. Finally, we share perspectives, highlight future directions, and call for extensive interdisciplinary cooperation to perfect AI with wise human-level strategies and promote its integration into the clinical workflow.

OBJECTIVES: To study the effects of early respiratory training combined with swallowing function training on physical development and neurodevelopment at a corrected gestational age of 6 months in infants with bronchopulmonary dysplasia (BPD). METHODS: A total of 69 BPD infants who could not be fed completely orally were prospectively selected from the Department of Neonatology of Hunan Children's Hospital between January 2018 and January 2021. Based on a random number table, the infants were divided into a conventional group (35 cases) and a training group (34 cases) (with 8 cases lost to follow-up; the final follow-up included 31 cases in the training group and 30 cases in the conventional group). Both groups received routine clinical treatment and care, while the training group additionally received respiratory and swallowing function training until the infants could independently feed orally. The weight, length, Gesell Developmental Schedule (GDS) results, readmission rate, and multiple readmission rate (two or more admissions) were compared between the two groups at a corrected age of 6 months. RESULTS: At corrected gestational age of 6 months, the training group had higher weight, length, and GDS scores in personal-social, language, gross motor, fine motor, and adaptive development compared to the conventional group (P<0.05). The readmission rate and multiple readmission rate were lower in the training group compared to the conventional group (P<0.05). CONCLUSIONS Early respiratory training combined with swallowing function training for BPD infants in a neonatal intensive care unit setting helps improve physical and neurological development and reduces the readmission rate.
Humans ; Bronchopulmonary Dysplasia/physiopathology* ; Prospective Studies ; Male ; Female ; Infant ; Deglutition/physiology* ; Gestational Age ; Infant, Newborn ; Breathing Exercises ; Child Development

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

Nitrogen oxides(NOx=NO+NO2)are important precursors of ozone(O3),and NOx and its oxides together constitute reactive nitrogen oxides(NOy)in the atmosphere.A comprehensive understanding of the total NOy level in the atmosphere is of great significance for a deeper understanding of the atmospheric nitrogen cycle and oxidation,as well as for formulating strategies for air pollution prevention and control.In this work,a thermal decomposition-broadband cavity enhanced absorption spectroscopy(TD-BBCEAS)technique for online measurement of total NOy in the atmosphere was developed.With this method,the NOy was efficiently converted into NO2,and the total NOy concentration in the atmosphere was indirectly obtained by measuring NO2.Focusing on the key factors affecting the measurement of total NOy,the influence of NO titration efficiency and other NOy component TD efficiency on measurement accuracy was emphasized.By changing the oxygen(O2)flow rate through the mercury lamp to alter the O3 concentration for titrating NO,the conversion efficiency of NO was evaluated.At O2 flow rate of 6 mL/min,the conversion efficiency of NO was greater than 99%.TD efficiency testing and analysis on NO2,peroxyacetyl nitrate(PAN),nitric acid(HNO3),and nitrous acid(HONO),which account for a large proportion of atmospheric NOy components,was carried out using 680℃as the optimal TD temperature for efficient conversion of NOy.With NO and HONO sample gases as typical verification gases,the conversion efficiency of NOy and the accuracy of NOy measurement by TD-BBCEAS system were verified by switching the on and off modes of mercury lamp and TD device.At integration time of 60 s,the detection limit of the system for NOy was 2.83×1010 molecules/cm3(60 s,2σ).A comparative measurement of actual atmospheric NOy was conducted between the TD-BBCEAS system and the NOy analyzer.The observation results showed a correlation coefficient(R2)of 0.98 and a slope of 0.93,further verifying the feasibility and accuracy of applying the TD-BBCEAS system to measurement of total NOy.