ObjectiveTo investigate the association between immunoglobulin G （IgG）/immunoglobulin M （IgM） ratio and prognosis in patients with initially unresectable hepatocellular carcinoma （iuHCC） receiving TTP triple therapy with transcatheter arterial chemoembolization （TACE）， tyrosine kinase inhibitor （TKI）， and programmed cell death protein-1 （PD-1） inhibitors. MethodsA retrospective analysis was performed for the clinical data of 151 iuHCC patients who received TTP triple therapy in Department of Hepatobiliary Surgery， Guangxi Medical University Cancer Hospital， from November 2019 to December 2022， and according to IgG/IgM ratio， they were divided into high IgG/IgM group （IgG/IgM ratio >13.23） and low IgG/IgM group （IgG/IgM ratio ≤13.23）. The t-test was used for comparison of continuous data between groups， and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method and the log-rank test were used for survival analysis， and the Cox proportional hazards model was used to investigate the potential influencing factors for overall survival （OS）. ResultsThe 151 patients had a median OS of 26.7 months （95% confidence interval ［CI］： 19.8-not reached） and a median progression-free survival of 12.5 months （95%CI： 10.4 — 15.8）. The objective response rate was 83.4% and the disease control rate was 94.0%. There were no significant differences in baseline data between the high IgG/IgM group and the low IgG/IgM group （all P>0.05）. There was a significant difference in median OS between the high IgG/IgM group and the low IgG/IgM group （20.6 months vs not reached， P=0.016）. In both the high IgG/IgM group and the low IgG/IgM group， salvage hepatectomy was significantly associated with the improvement in OS （χ²=8.297 and 10.307， both P<0.05）. The multivariate analysis showed that high IgG/IgM ratio （hazard ratio ［HR］=1.799， 95%CI： 1.077 — 3.006， P=0.025）， baseline alpha-fetoprotein >400 ng/mL （HR=1.762， 95%CI： 1.017 — 3.050， P=0.043）， and BCLC stage （HR=2.265， 95%CI： 1.212 — 4.232， P=0.010） were independent influencing factors for OS. ConclusionHigh IgG/IgM ratio is associated with a poorer prognosis in iuHCC patients receiving TTP triple therapy， and salvage hepatectomy has a potential value in improving the prognosis of patients with a high IgG/IGM ratio.

ObjectiveTo explore the relationship between negative life events and depression severity in adolescent patients with depressive disorder， as well as the chain mediating role of insomnia symptoms and quality of life. Methods374 outpatient patients and hospitalized patients with adolescent depressive disorders were enrolled. The Adolescent Life Event Scale （ASLEC）， the Insomnia Severity Index （ISI）， the World Health Organization Quality of Life Questionnaire Short Form （WHOQOL-BREF）， and the Center for Epidemiology Depression Scale （CES-D） were used to evaluate the negative life event situation， insomnia symptoms， quality of life level and depression severity of the subjects， respectively. In addition， the PROCESS 4.0 macroprogram was used to analyze the chain mediating effect of insomnia symptoms and quality of life between negative life events and depression severity in patients with adolescent depressive disorder. ResultsThe results of correlation analysis showed that there was a significant correlation between negative life events and insomnia symptoms， quality of life， and depression severity （all P<0.05）. In addition， the results of chain mediation showed that negative life events had a significant direct effect on depression severity， with an effect size of 0.12 （P<0.001）. Insomnia symptoms and quality of life played a mediating role in the relationship between negative life events and depression severity in patients with adolescent depressive disorders， with indirect effect sizes of 0.062 （95%CI： 0.040-0.087） and 0.091 （95%CI： 0.059-0.123）， respectively. It could also play a chain mediation role， and the effect size was 0.039 （95%CI： 0.024-0.057）. ConclusionNegative life events experienced by patients with adolescent depressive disorder not only directly affect the severity of depressive symptoms， but may also indirectly exacerbate depression through insomnia symptoms and quality of life.

It is very limited that the benefit of perioperative chemotherapy in early non-small cell lung cancer (NSCLC), and the 5-year survival rate is only 5% higher than surgery. Antibodies that block programmed cell death protein 1/programmed death-ligand 1 significantly improve the survival of advanced NSCLC. The value of immunotherapy in early NSCLC is also being explored. This paper firstly summarized and analyzed the progress of immunotherapy in the perioperative period of NSCLC. Secondly, the safety and feasibility of surgical resection after neoadjuvant immunotherapy were discussed. Finally, the clinical value of different therapeutic efficacy prediction indicators was summarized, in order to clarify the current status of immunotherapy in the perioperative period, so as to improve the clinical benefits of early NSCLC patients.

Objective: The cross sectional study aimed to identify predominant co-occurrence patterns among six common mental health issues in college students, so as to provide empirical basis for designing targeted interventions. Methods: From October 2024, a total of 9 837 students from 4 universities in Xiangtan City, Hunan Province, participated in the current study by multistage random cluster sampling method. Participants completed self report measures, including the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7 item Scale (GAD-7), Young s Internet Addiction Diagnostic Questionnaire, the Adolescent Insomnia Symptom Self rating Scale, the Ottawa Self injury Inventory, and the Brief Community Assessment of Psychic Experiences Questionnaire. Demographic and co-occurrence characteristics were first compared using Chi square or trend Chi-square tests, followed by application of the Apriori algorithm to mine association rules for primary co-occurrence patterns. Results: The detection rate of co-occuring the common mental health issues was 46.44%. The detection rate was significantly higher in female than in male students (50.42%, 43.61%; χ 2=44.46) and in students from rural versus urban areas (47.22%, 44.60%; χ 2=5.67) (both P <0.05). Significant differences were observed among freshmen, sophomores, juniors, and seniors (46.63%, 48.35%, 45.05% , 43.66%, respectively; χ 2=9.22, P <0.05), although no statistically significant trend was detected ( χ 2 trend =3.75, P = 0.05 ). Association rule mining identified “anxiety + depression” “anxiety + psychotic experiences + depression” and “anxiety + sleep disorder + depression” as the combinations with the highest support. In addition, “anxiety+depression+Internet addiction+psychotic experiences =>sleep disorder (>= refered to the occurrence of the latter item under the condition that the former item occurs)” and “anxiety + depression+Internet addiction=>sleep disorder” were combinations with relatively high confidence. Conclusions Co-occurrence of these mental health issues among college students is high and exhibits diverse patterns. Strategies to address this burden should prioritize integrated interventions that target these specific combinations of factors.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disease worldwide, affecting approximately 32%-38% of the adult population and posing a growing public health burden. MASLD represents a continuous disease spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), progressive hepatic fibrosis, cirrhosis, and ultimately hepatocellular carcinoma (HCC). The pathological core of MASLD lies in disruption of hepatic lipid metabolic homeostasis, characterized by an imbalance among de novo lipogenesis, fatty acid β-oxidation, and very-low-density lipoprotein (VLDL)-mediated lipid export. This metabolic disequilibrium subsequently drives inflammatory injury and fibrotic progression. Among the multiple regulatory pathways involved, thyroid hormone (TH) signaling has emerged as a central regulator of hepatic metabolic homeostasis. The liver is a major peripheral target organ of TH action, where TH predominantly exerts its metabolic effects through thyroid hormone receptor β (TRβ). Large-scale epidemiological studies and meta-analyses have demonstrated that hypothyroidism is significantly associated with increased MASLD prevalence, more severe histological injury, and advanced hepatic fibrosis, suggesting that dysregulation of TH signaling may participate throughout the entire MASLD disease spectrum. At the molecular level, TH regulates hepatic lipid metabolism by coordinating suppression of lipogenesis, enhancement of mitochondrial fatty acid oxidation, and promotion of VLDL assembly and secretion through integrated genomic actions of the T3-TRβ axis and non-genomic signaling pathways. Across different stages of MASLD, TH signaling exerts stage-dependent protective effects. In the steatosis stage, TH improves metabolic flexibility by modulating insulin sensitivity, glucose metabolism, and lipid droplet clearance, thereby alleviating early lipotoxic stress. During progression to MASH, TH attenuates inflammatory amplification by improving mitochondrial homeostasis, suppressing activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, and modulating the gut-liver axis microenvironment. In advanced stages, TH signaling influences hepatic stellate cell activation and extracellular matrix deposition, partly through interaction with the transforming growth factor-β (TGF-β)/SMAD pathway, while alterations in intrahepatic TH availability, mediated by dynamic changes in iodothyronine deiodinase 1 (DIO1), contribute to fibrosis progression and hepatocellular dedifferentiation. In hepatocellular carcinoma, coordinated downregulation of TRβ and DIO1 establishes a tumor-associated hypothyroid state that promotes metabolic reprogramming and tumor progression. The clinical relevance of TH signaling in MASLD has been underscored by the recent approval of Resmetirom, a liver-targeted TRβ‑selective agonist, for the treatment of non-cirrhotic MASH with moderate-to-severe fibrosis (F2-F3). This approval represents a landmark transition from mechanistic understanding to metabolism-centered precision therapy in MASLD. Clinical trials have demonstrated that Resmetirom not only improves key histological endpoints, including MASH resolution and fibrosis regression, but also favorably modulates atherogenic lipid profiles, highlighting the therapeutic potential of selectively targeting hepatic TH pathways. This review systematically summarizes the multidimensional regulatory roles of TH across the MASLD disease spectrum and discusses emerging diagnostic and therapeutic implications of TH-based interventions, aiming to inform future mechanistic research and optimize clinical management strategies.

ObjectiveTo investigate the association of the traditional Chinese medicine （TCM） syndrome types of primary liver cancer （PLC） with clinical features and multimodal quantitative radiological features on computed tomography （CT） and magnetic resonance imaging （MRI）， and to provide a reference for the objectification of TCM syndrome differentiation and precise diagnosis and treatment. MethodsA retrospective analysis was performed for the clinical data of 312 patients who were diagnosed with PLC in The First Affiliated Hospital of Hunan University of Chinese Medicine from March 2020 to June 2025， and according to the TCM syndrome type， they were divided into stagnation of liver Qi group with 40 patients， stagnation of liver Qi and spleen deficiency group with 109 patients， Qi stagnation and blood stasis group with 62 patients， dampness-heat toxin amassment group with 81 patients， and liver-kidney Yin deficiency group with 20 patients. Clinical features and multimodal quantitative radiological features were compared between the patients with different TCM syndrome types. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups， and the Dunn’s multiple test was used for further comparison between two groups； the chi-square test was used for comparison of categorical data between groups， and the Bonferroni method was used for further comparison between two groups. ResultsThere were significant differences between the patients with different TCM syndrome types in China liver cancer staging （CNLC）， Child-Pugh class， alanine aminotransferase， aspartate aminotransferase， albumin， direct bilirubin， total bilirubin， prothrombin time， neutrophil， and albumin-bilirubin score （all P<0.05）. In the stagnation of liver Qi group， the patients with Child-Pugh class A accounted for 75.00%； among the patients with CNLC stage I PLC， the patients with stagnation of liver Qi accounted for 60.00%， and those with Qi stagnation and blood stasis syndrome accounted for 59.68%， while among the patients with CNLC stage IV PLC， the distribution proportion of dampness-heat toxin amassment （27.16%） and liver-kidney Yin deficiency （30.00%） was significantly higher than that of stagnation of liver Qi （2.50%） （all P<0.05）. Radiological examination showed that there were significant differences between the patients with different TCM syndrome types in the number of tumors， ascites， venous tumor thrombus， maximum tumor diameter， intrahepatic metastasis， and lymph node metastasis in the hepatic hilar and retroperitoneal regions （all P<0.05）. Compared with the patients with stagnation of liver Qi， the patients with liver depression and spleen deficiency or liver-kidney Yin deficiency were more likely to develop intrahepatic metastasis； the patients with liver depression and spleen deficiency， dampness-heat toxin amassment， or liver-kidney Yin deficiency were more likely to develop lymph node metastasis in the hepatic hilar and retroperitoneal regions； the patients with liver-kidney Yin deficiency were more likely to experience multiple tumors； the patients with liver depression and spleen deficiency or dampness-heat toxin amassment were more likely to develop ascites （all P<0.05）. Compared with the patients with Qi stagnation and blood stasis syndrome， the patients with liver depression and spleen deficiency had a significantly longer maximum tumor diameter and a significantly higher proportion of patients with venous tumor thrombus （both P<0.05）. Furthermore， among the 184 patients with MRI diffusion-weighted imaging sequences， the patients with dampness-heat toxin amassment or Qi stagnation and blood stasis syndrome had significantly higher ADC values and relative ADC values than those with stagnation of liver Qi （all P<0.05）. ConclusionThere are significant differences in CT/MRI radiological features and clinical features between PLC patients with different TCM syndrome types， among whom the patients with liver depression and spleen deficiency， dampness-heat toxin amassment， and liver-kidney Yin deficiency tend to exhibit progressive radiological features， and those with dampness-heat toxin amassment or Qi stagnation and blood stasis syndrome tend to have higher ADC values. These findings provide an objective basis for TCM syndrome differentiation in PLC.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

Objective:To investigate the effect of ligation methods of inferior mesenteric artery (IMA) on preserving left colic artery (LCA) in laparoscopic radical resection of rectal cancer.Methods:The prospective randomized controlled study was conducted. The clinical data of 864 patients who underwent laparoscopic radical resection of rectal cancer at Renji Hospital of Shanghai Jiaotong University School of Medicine from January 2020 to December 2024 were selected. Patients were randomly divided into the low ligation group and high ligation group using a random number table. Patients of the low ligation group underwent laparoscopic radical resection of rectal cancer with preserving LCA by low ligation of IMA and apical lymph node dissection, and patients of the high ligation group underwent laparoscopic radical resection of rectal cancer with traditional high ligation of IMA. Observation indicators: (1) grouping of the enrolled patients; (2) intraoperative conditions; (3) postoperative pathological examination; (4) postoperative recovery. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was conducted using the non-parametric test. Results:(1) Grouping of the enrolled patients. A total of 864 patients with rectal cancer who underwent laparoscopic radical resection of rectal cancer were screened for eligibility, including 410 males and 454 females, aged (63±11)years. All 864 patients were randomly divided into the low ligation group and high ligation group, with 432 patients in each group. There was no significant difference in gender, age, body mass index, carcinoembryonic antigen, distance from tumor to anal margin, diabetes, hypertension, neoadjuvant radiochemotherapy, IMA subtypes and IMA length between the two groups ( P>0.05), ensuring comparability. (2) Intraoperative conditions. All patients of the two groups successfully completed surgery, with no errors in blood vessel ligation during operation or conversion to open surgery. There was a significant difference in time of IMA dissection between the low ligation group and high ligation group [(31±11)minutes vs. (28±9)minutes, t=4.39, P<0.05], and there was no significant difference in total operation time, volume of intra-operative blood loss or prophylactic stoma rate between the two groups ( P>0.05). (3) Postopera-tive pathological examination. There was a significant difference in the number of lymph node dissected between the low ligation group and high ligation group (1.8±1.4 vs. 1.5±1.4, t=2.51, P<0.05), and there was no significant difference in tumor diameter, the total number of lymph node dissected, total lymph node positive status, No.253 lymph node positive status, TNM staging between the two groups ( P>0.05). (4) Postoperative recovery. The time to postoperative first flatus and the number of anastomotic leakage of patients in the low ligation group were (74±22)hours and 16 cases, versus (78±20)hours and 31 cases in the high ligation group, respectively, showing significant differences in the above indicators between the two groups ( t=2.52, χ2=5.06, P<0.05). There was no significant difference in the time to postoperative initial liquid food intake, duration of post-operative hospital stay, duration of abdominal drainage tube indwelling, duration of anal tube indwelling, postoperative wound infection, pulmonary infection, intestinal obstruction, or urinary dysfunction between the two groups ( P>0.05). None of patients in the two groups had readmission or death during the postoperative 30 days. Conclusion:Low ligation of IMA in laparoscopic radical resection of rectal cancer can guide precise LCA preservation, which is beneficial for accelerating the recovery of intestinal function and reducing the incidence of anastomotic leakage.

The integration of science and education is not only an important strategy for promoting social progress and technological development,but also a modern form of higher education aiming at cultivating innovative talents.Conducting scientific research training for undergraduate medical students is one of the important ways to cultivate their innovative abilities and comprehensive qualities.Our team proposed a"teaching,science,and ideology trinity"teaching model to comprehensively cultivate students' scientific research comprehensive abilities under the value orientation of ideological and political education by or-ganically integrating molecular biology experimental teaching with the scientific research training of under-graduate medical students.In this teaching activity,taking the experiment of gene polymorphism as an example,our team selected students with research potential from the whole grade and divided them into 4 project groups that were instructed by 4 teachers.The students were trained in the whole process of scien-tific research,including topic selection,project writing,experimental designing,application for research ethics,and project summary.Our team has always adhered to student-contentedness of educational con-cepts to stimulate students' intrinsic motivation throughout the teaching process.Students are the design-ers and implementers of the project,and teachers are only guides and promoters of learning.After this training,students not only became familiar with the writing and implementation of scientific research pro-jects,but also improved their literature reading,experimental designing,experimental skills,and prob-lem-solving abilities.More importantly,this teaching activity also cultivated students' awareness of re-search ethics and academic moral standards.

Objective To establish a flow cytometric assay for detecting heat shock protein A2(HSPA2)in sperm and explore the role of HSPA2 expression levels in predicting low fertilization rates in in vitro fertilization(IVF).Methods The principle of in-direct immunofluorescence(IIF)was used to fluorescently stain sperm HSPA2.After the sperm sample was permeabilized and sealed,rabbit anti-human HSPA2 antibody(primary antibody)and fluorescein isothiocyanate(FITC)labeled goat anti-rabbit IgG antibody(secondary antibody)were sequentially added as detection tubes.At the same time,a sample without primary anti-body was set up as a control tube,and the positive rates of the two tubes were measured by flow cytometer.The ratio of the posi-tive rate of the detection tube to the control tube(positive rate ratio)was calculated.The optimal number of sperm for detection and the optimal working dilutions of primary and secondary antibodies were explored using the chessboard method.Under the optimal conditions,the repeatability,linear range and reference range of the method were evaluated separately,in order to estab-lish a preliminary method for detecting sperm HSPA2 expression levels using flow cytometry.After the establishment of the method,preliminary testing was conducted on a total of 85 sperm samples from couples who underwent IVF at the Reproductive Medicine Center of Jiangmen Central Hospital in 2023.The ratio of HSPA2 positivity rates between the group with IVF success-ful(n=63)and the group with low fertilization rate(n=22)was compared,and the receiver operating characteristic(ROC)curve was used to analyze the threshold.Results The positive rate of HSPA2 in the control tube was relatively low,showing a low background signal,while the fluorescence signal of the detection tube was significantly enhanced,indicating that this method can effectively detect HSPA2.The optimal number of sperm samples for detection determined by the chessboard method was 2×106,and the optimal working dilutions for primary and secondary antibodies were 1∶300 and 1∶400,respectively.Evaluation of repeatability and linear range showed good methodological performance.Comparative analysis between the group with IVF success-ful and the group with low fertilization rate showed that the ratio of sperm HSPA2 positivity rate in the group with low fertilization rate(6.19±4.07)was lower than successful fertilization group(10.69±8.26),the difference was statistically significant(t=2.446,P<0.05).The ROC curve and Youden index showed that the best predictive power was achieved when the cutoffvalue for the ratio of positivity rate was 5.5067,with a sensitivity and a specificity of 71.4%,55.5%,respectively.Conclusion A flow cytometric method for detecting HSPA2 in sperm is successfully established.The expression level of sperm HSPA2 detected by this method suggests its predictive value for low fertilization rate in IVF,providing a basis for future clinical scientific selection of fertilization methods.