[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。

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.

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.

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.

ObjectiveTo investigate the relationship between mitochondrial DNA copy number (mtDNAcn) and cognitive dysfunction, and its mediating role between type 2 diabetes mellitus (T2DM) and cognitive dysfunction. MethodsA case-control study was conducted from May 2019 to April 2021 at the Shanghai Yangpu District Central Hospital, China. A total of 193 subjects were recruited and divided into two groups based on the Montreal Cognitive Assessment (MoCA): normal control (NC) group (n=95) and cognitive impairment group (n=98). The prevalence of T2DM was determined on the basis of medical history, while mtDNAcn in peripheral blood samples was quantified using realtime fluorescent quantitative polymerase chain reaction. ResultsUnivariate analyses revealed that the mean mtDNAcn in the cognitive impairment group was 0.76±0.37, significantly lower than that in the NC group (1.06±0.45) (P<0.05). Logistic regression analyses showed that higher mtDNAcn was associated with a reduced risk of cognitive impairment (OR=0.315, 95%CI: 0.125‒0.795). Additionaly, a statistically significant positive correlation was observed between mtDNAcn and the total MoCA score (r=0.381, P<0.01). Morever, T2DM history (OR=2.741, 95%CI: 1.002‒7.497) and elevated glycosylated hemoglobin (HbA1c) levels (OR=1.796, 95%CI: 1.190‒2.711) were identified as risk factors for cognitive impairment. Mediation analyses indicated that mtDNAcn served as a mediator between T2DM/HbA1c and the risk of cognitive impairment, with proportions of mediating effect of 9.04% and 9.18%, respectively. ConclusionPatients with mild and moderate cognitive impairment have significantly lower mtDNAcn than those with normal cognitive function. Reduced mtDNAcn is an influencing factor for cognitive dysfunction and may play a mediating role in the association between T2DM and mild to moderate cognitive impairment.

(±)-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*

In recent years, with the continuous advancement of related research, the clinical value of clot waveform analysis (CWA) in the diagnosis and management of thrombotic diseases has become increasingly prominent. As a dynamic coagulation monitoring technology based on optical principles, CWA overcomes the limitations of traditional coagulation tests (e.g., APTT, PT), which rely on single time-point parameters, in identifying hypercoagulable states, predicting thrombotic risk, and monitoring anticoagulant efficacy. By analyzing the kinetic profiles of the coagulation cascade, CWA provides multidimensional insights. This article elucidates the theoretical basis and principles of CWA, systematically reviews its applications in arterial/venous thrombosis, other hypercoagulability-related disorders, and anticoagulation therapy monitoring, and synthesizes recent advances of CWA for thrombotic diseases. Specifically, multiple studies demonstrate that CWA-APTT parameters (e.g., peak height Min1, Min2, Delta) can sensitively detect hypercoagulability. Combining CWA with the Padua score significantly enhances the predictive power for venous thromboembolism (VTE) risk assessment. CWA shows clinical utility in evaluating hypercoagulability in patients with acute myocardial infarction (AMI) and acute cerebral infarction (ACI), where parameters such as Min1, Min2, and Max2 exhibit greater sensitivity than conventional APTT. These metrics may predict AMI complications and guide clinical management. Additionally, CWA demonstrates value in diverse scenarios including pregnancy, inflammation-associated hypercoagulability (e.g., COVID-19, Kawasaki disease), and rare thrombotic conditions (e.g., chronic spontaneous urticaria). Beyond diagnostic and risk-stratification advantages, CWA serves as a novel tool for personalized anticoagulation monitoring. Its derivative technology, clot-fibrinolysis waveform analysis (CFWA), extends applications to fibrinolysis assessment—aiding in identifying coagulation status in deep vein thrombosis (DVT) patients, tracking coagulation/fibrinolysis dynamics in COVID-19, and evaluating efficacy of anticoagulant/antifibrinolytic therapies. Nevertheless, despite its unique strengths, challenges such as device dependency, insufficient standardization, and heterogeneity in parameter interpretation hinder widespread clinical adoption, necessitating further investigation. Future directions include establishing multidimensional thrombotic risk assessment systems integrating CWA and developing AI-powered automated CWA analysis platforms to enhance clinical accessibility.

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.

To investigate the effectiveness of a self-developed intelligent medical record writing assistant in enhancing the efficiency of discharge record writing and improving the quality of discharge records, and to assess physicians' satisfaction with the assistant.

Background::Intrauterine growth restriction (IUGR) is associated with adverse metabolic outcomes during adulthood. Histone modifications and changes in DNA methylation-affected genes are important for fetal development. This study aimed to investigate the epigenetic mechanisms in IUGR.Methods::IUGR models were established in Sprague–Dawley rats using a maternal nutritional restriction approach during pregnancy. The abundance of insulin-like growth factor 2 (IGF2), phosphoinositide 3-kinase (PI3K), AKT serine/threonine kinase 2 (AKT2), and peroxisome proliferators-activated receptor gamma coactivator 1 alpha (PGC-1α) was examined by real-time polymerase chain reaction (RT-PCR) and Western blotting analysis. Chromatin immunoprecipitation RT-PCR was employed to analyze histone modification in CCCTC-binding factor (CTCF) 1–4 binding sites of the Igf2/H19 imprinting control region (ICR). The methylation states of CTCF1–4 binding sites were studied by pyrosequencing. Results::The IUGR models were constructed successfully. Igf2 mRNA abundance in the placenta, fetal liver, and newborn liver was decreased in the IUGR group ( P <0.01). Meanwhile, as compared with the control group, the expression levels of AKT2, PI3K, and PGC-1α were lower in newborn and 8-week-old livers in the IUGR group ( P <0.05). In addition, knocking down Igf2 reduced the protein expression levels of AKT2-phosphorylation and PGC-1α ( P <0.05). In CTCF binding sites 1-4 of the Igf2/ H19 ICR, acetylated histones H3 (AcH3) enrichment was significantly lower in CTCF1-3 in newborn and 8-week-old IUGR rats. Histone H3 tri-methylated lysine 4 (H3K4me3) enrichment was significantly lower in the CTCF1–4 of newborn and 8-week-old IUGR groups ( P <0.01). H3K9me2 enrichment was significantly higher in the IUGR group ( P <0.01). The CpG dinucleotide methylation levels of CTCF1 and CTCF3, but not those of CTCF2 and CTCF4 binding sites in IUGR rat fetal, 4-week old, and 8-week-old livers decreased significantly ( P <0.05). Conclusion::The methylation status and histone modification in the Igf2/H19 ICR are related to growth and lipid metabolism via the PGC-1α/PI3K/AKT2 pathway in IUGR rats.