BACKGROUND:Knee osteoarthritis(KOA)is a common chronic inflammatory disease that causes damage to joint cartilage and surrounding tissues.Immune cells play an important role in the immune-inflammatory response in knee osteoarthritis,but the specific mechanisms involved are still not fully understood. OBJECTIVE:To evaluate the potential causal relationship between 731 immune cell phenotypes and the risk of knee osteoarthritis using Mendelian randomization. METHODS:Summary statistics of genome-wide association studies(GWAS)for 731 immune cell phenotypes(from GCST0001391 to GCST0002121)obtained from the GWAS catalog and GWAS data for knee osteoarthritis from the IEUGWAS database(ebi-a-GCST007090)were used.Inverse variance-weighted method,MR-Egger regression,weighted median method,weighted mode method,and simple mode method were employed to investigate the causal relationship between immune cells and knee osteoarthritis.Sensitivity analyses were conducted to assess the reliability of the Mendelian randomization results.Reverse Mendelian randomization analysis was also performed using the same methods. RESULTS AND CONCLUSION:The forward MR analysis indicated significant causal relationships(FDR<0.20)between knee osteoarthritis and four immune cell phenotypes,namely CD27 on CD24+CD27+in B cells(OR=1.026,P=0.000 26,Pfdr=0.18),CD33 on CD33dim HLA DR-in myeloid cells(OR=1.014,P=0.000 50,Pfdr=0.18),and CD45RA+CD28-CD8br%CD8br in Treg cells(OR=1.001,P=0.000 78,Pfdr=0.18),and PDL-1 on monocytes in mononuclear cells(OR=0.952,P=0.000 98,Pfdr=0.18).These immune cell phenotypes showed direct positive or negative causal associations with the risk of knee osteoarthritis.Reverse Mendelian randomization analysis revealed no significant causal relationships(FDR<0.20)between knee osteoarthritis as exposure and any of the 731 immune cell phenotypes.The results of sensitivity analysis show that the P-values of the Cochran's Q test and the MR-Egger regression method for bidirectional Mendelian randomization were both greater than 0.05,indicating that there is no significant heterogeneity and pleiotropy in the causal effect analysis between immune cell phenotypes and knee osteoarthritis.To conclude,there may be four potential causal relationships between immune cell phenotypes,such as CD27 on CD24+CD27+cells,CD33 on CD33dim HLA DR-cells,CD45RA+CD28-CD8br%CD8br cells,and PDL-1 on monocytes,and knee osteoarthritis.These findings provide valuable clues for studying the biological mechanisms of knee osteoarthritis and exploring early prevention and treatment strategies.They also offer new directions for the development of intervention drugs.

Hepatocellular carcinoma(HCC)is a malignant tumor that poses a serious threat to human health.The burden of HCC in China is substantial,and most patients are diagnosed at intermediate or advanced stages,with a 5-year survival rate of only 14.4%.Conversion therapy aims to transform initially unresectable HCC into resectable disease to improve patient prognosis,but it faces numerous challenges in clinical practice.First,Chinese HCC patients differ significantly from those in North America,Japan,and other regions in terms of tumor characteristics and etiology,necessitating exploration of localized conversion therapy strategies suitable for Chinese patients.Second,the target population for conversion therapy remains unclear,with controversies over the distinction and patient selection between neoadjuvant and conversion therapies,and a lack of high-level evidence to guide practice.Third,the selection of conversion therapy regimens is challenging,as there are many drug options but no unified standards,and the choice and timing of combined local therapies are difficult to determine,requiring further clinical validation.Moreover,post-conversion treatment strategies are contentious;it remains unclear whether patients achieving radiological or clinical complete response should undergo surgery,preoperative prediction of complete pathological response is difficult,and postoperative sequential strategies and regimen selection are not well defined.Future efforts should focus on identifying biomarkers,conducting multicenter,large-sample,prospective clinical trials,and standardizing treatment protocols and processes to improve the prognosis and quality of life of HCC patients.

Hepatocellular carcinoma(HCC)is a malignant tumor that poses a serious threat to human health.The burden of HCC in China is substantial,and most patients are diagnosed at intermediate or advanced stages,with a 5-year survival rate of only 14.4%.Conversion therapy aims to transform initially unresectable HCC into resectable disease to improve patient prognosis,but it faces numerous challenges in clinical practice.First,Chinese HCC patients differ significantly from those in North America,Japan,and other regions in terms of tumor characteristics and etiology,necessitating exploration of localized conversion therapy strategies suitable for Chinese patients.Second,the target population for conversion therapy remains unclear,with controversies over the distinction and patient selection between neoadjuvant and conversion therapies,and a lack of high-level evidence to guide practice.Third,the selection of conversion therapy regimens is challenging,as there are many drug options but no unified standards,and the choice and timing of combined local therapies are difficult to determine,requiring further clinical validation.Moreover,post-conversion treatment strategies are contentious;it remains unclear whether patients achieving radiological or clinical complete response should undergo surgery,preoperative prediction of complete pathological response is difficult,and postoperative sequential strategies and regimen selection are not well defined.Future efforts should focus on identifying biomarkers,conducting multicenter,large-sample,prospective clinical trials,and standardizing treatment protocols and processes to improve the prognosis and quality of life of HCC patients.

The high incidence and mortality rates of gastric cancer pose a significant burden on human health and public health systems. Peritoneal metastasis is one of the main routes of metastasis in gastric cancer, and patients with this condition have poor prognosis. With advancements in medicine and sociology, the concept of integrated medicine emerged in the late 1980s. It emphasizes treating patients as holistic entities, integrating various medical fields multidimensionally, and combining medicine with other fields. This article organizes the management of gastric cancer peritoneal metastasis around the core concept of "Prevention, Screening, Diagnosis, Treatment, and Rehabilitation": Prevention relies on standardized tumor-free surgical techniques and intraoperative interventions. Screening involves early detection of peritoneal metastasis through integrated technologies. Diagnosis combines multiple methods, including laparoscopic exploration with cytological and histopathological examination, imaging studies, peritoneal fluid cytology, and artificial intelligence. Treatment encompasses comprehensive strategies such as intraperitoneal and systemic chemotherapy, cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy, pressurized intraperitoneal aerosolized chemotherapy, dendritic cell vaccines combined with nivolumab, and supportive care for managing ascites, malignant bowel obstruction, and nutritional support. This integrated medical perspective offers new insights into the management of gastric cancer peritoneal metastasis.

The high incidence and mortality rates of gastric cancer pose a significant burden on human health and public health systems. Peritoneal metastasis is one of the main routes of metastasis in gastric cancer, and patients with this condition have poor prognosis. With advancements in medicine and sociology, the concept of integrated medicine emerged in the late 1980s. It emphasizes treating patients as holistic entities, integrating various medical fields multidimensionally, and combining medicine with other fields. This article organizes the management of gastric cancer peritoneal metastasis around the core concept of "Prevention, Screening, Diagnosis, Treatment, and Rehabilitation": Prevention relies on standardized tumor-free surgical techniques and intraoperative interventions. Screening involves early detection of peritoneal metastasis through integrated technologies. Diagnosis combines multiple methods, including laparoscopic exploration with cytological and histopathological examination, imaging studies, peritoneal fluid cytology, and artificial intelligence. Treatment encompasses comprehensive strategies such as intraperitoneal and systemic chemotherapy, cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy, pressurized intraperitoneal aerosolized chemotherapy, dendritic cell vaccines combined with nivolumab, and supportive care for managing ascites, malignant bowel obstruction, and nutritional support. This integrated medical perspective offers new insights into the management of gastric cancer peritoneal metastasis.

Objective: To investigate the detection of depressive symptoms and its influencing factors among middle school students in Huzhou City, so as to provide insights for improving the mental health levels among middle school students. Methods: From September to November 2024, a total of 4 729 middle school students from five counties (districts) in Huzhou City were selected through the stratified cluster random sampling method. Demographic information, lifestyle, and school bullying were collected through questionnaire surveys. Depressive symptoms were assessed using the Center for Epidemiological Studies Depression Scale (CES-D). Factors affecting depressive symptoms among middle school students were analyzed using a multivariable logistic regression model. Results: A total of 4 729 middle school students were surveyed, including 2 200 boys (46.52%) and 2 529 girls (53.48%). Depressive symptoms were detected in 1 026 students, with a detection rate of 21.70%. Multivariable logistic regression analysis showed that girl (OR=1.960, 95%CI: 1.659-2.317), high school (ordinary high school, OR=1.789, 95%CI: 1.465-2.186; vocational high school, OR=1.581, 95%CI: 1.105-2.263), consumption of sugar-sweetened beverages >0 time/day (<1 time/day, OR=1.363, 95%CI: 1.009-1.841; ≥1 time/day, OR=1.568, 95%CI: 1.098-2.239), fried food intake ≥1 time/day (OR=1.890, 95%CI: 1.291-2.769), skipping breakfast daily (OR=2.178, 95%CI: 1.825-2.599), TV viewing time ≥2 hours/day (OR=1.457, 95%CI: 1.154-1.838), insufficient sleep duration (OR=1.761, 95%CI: 1.422-2.181), smoking (OR=2.798, 95%CI: 1.834-4.269), alcohol consumption (OR=2.282, 95%CI: 1.861-2.798), experiencing school bullying (OR=5.440, 95%CI: 3.148-9.402) and parental physical/verbal abuse (OR=3.954, 95%CI: 3.189-4.902) were associated with a higher risk of depressive symptoms among middle school students. Conversely, the middle school students who engaged in moderate-to-vigorous physical activity ≥3 times/week (OR=0.784, 95%CI: 0.668-0.921) and attended physical education classes ≥3 sessions/week (OR=0.736, 95%CI: 0.613-0.884) were associated with a lower risk of depressive symptoms. Conclusion The prevalence of depressive symptoms among middle school students in Huzhou City was lower than national average, and was influenced by dietary habits, physical exercise, sleep duration, smoking, alcohol consumption, and experiencing school bullying.

Objective:To analyze the condition of subclinical atherosclerosis (SCA) in patients with psoriatic arthritis (PsA) and to provide a reference for better management of the associated cardiovascular risk in patients with PsA.Methods:Based on the cohort of PsA patients (PKUPsA) in the Department of Rheumatism and Immunology, Peking University First Hospital, 240 PsA patients without previous clinical atherosclerotic disease between July 2018 and June 2024 were included. The demographic data traditional cardiovascular disease risk factors, PsA related indicators and medications were collected when all patients were entered into the cohort. Increased intima-media thickness and/or arterial plaque formation in bilateral carotid arteries examined by ultrasonography are defined as the presence of SCA. Based on this, patients were divided into SCA and no SCA groups, and the two groups were compared and analyzed. Statistics were performed using the Mann-Whitney U test, independent sample t test, χ2 test and Logistic regression analysis. Results:Eighty-five of 240 patients (35.4%) had SCA, including 55 (22.9%) with cIMT thickening and 51 (21.2%) with carotid plaque. Compared with the PsA patients without SCA, patients with SCA were older [55.0 (42.0, 62.5) vs. 42.0(35.0, 53.0) year of age, Z=-4.90, P<0.001], had longer disease course of arthritis [4.6 (1.0, 10.1) vs. 3.0(1.0, 6.1) years, Z=-1.98, P=0.048], more patients with combined hypertension [34.1%(29/85) vs. 15.5%(24/155), χ2=11.08, P<0.001], hyperlipidemia [47.1%(40/85) vs. 27.1%(42/155), χ2=1.22, P=0.002] and the taking of statins [14.1%(12/85) vs. 5.8%(9/155), χ2=4.75 , P=0.029], hypoglycemic agents [10.6%(9/85) vs. 3.9%(6/155), χ2=4.23, P=0.040] and antihypertensive drugs [17.6%(15/85) vs 6.5%(10/155), χ2=7.37, P=0.007]. They also had a higher blood glucose level[5.37 (5.17, 6.09)mmol/L vs. 5.26(4.97, 5.67)mmol/L, Z=-2.82 , P=0.005], low-density lipoprotein [(3.05± 0.76)mmol/L vs. (2.78±0.75)mmol/L, t=2.60, P=0.010] and blood uric acid level[351 (312, 412)μmol/L vs. 333(279, 408)μmol/L, Z=-2.10, P=0.036]. Multivariate analysis showed that older [ OR (95% CI) =1.059 (1.033, 1.086), P<0.001], increased low density lipoprotein [ OR (95% CI) =1.519 (1.018, 2.267), P=0.041] and increased blood uric acid levels [ OR (95% CI)=1.004 (1.001, 1.007), P=0.017] were an independent risk of SCA in PsA patients. Conclusion:More than 1/3 of PsA patients with SCA without past history of clinical atherosclerosis with SCA, advanced age, increased blood low density lipoprotein level, and elevated uric acid level are independent risk factors for PsA with SCA, so attention should be paid to the assessment and management of cardiovascular-related risk. Early intervention can help to improve patient prognosis.

Objective:To analyze the condition of subclinical atherosclerosis (SCA) in patients with psoriatic arthritis (PsA) and to provide a reference for better management of the associated cardiovascular risk in patients with PsA.Methods:Based on the cohort of PsA patients (PKUPsA) in the Department of Rheumatism and Immunology, Peking University First Hospital, 240 PsA patients without previous clinical atherosclerotic disease between July 2018 and June 2024 were included. The demographic data traditional cardiovascular disease risk factors, PsA related indicators and medications were collected when all patients were entered into the cohort. Increased intima-media thickness and/or arterial plaque formation in bilateral carotid arteries examined by ultrasonography are defined as the presence of SCA. Based on this, patients were divided into SCA and no SCA groups, and the two groups were compared and analyzed. Statistics were performed using the Mann-Whitney U test, independent sample t test, χ2 test and Logistic regression analysis. Results:Eighty-five of 240 patients (35.4%) had SCA, including 55 (22.9%) with cIMT thickening and 51 (21.2%) with carotid plaque. Compared with the PsA patients without SCA, patients with SCA were older [55.0 (42.0, 62.5) vs. 42.0(35.0, 53.0) year of age, Z=-4.90, P<0.001], had longer disease course of arthritis [4.6 (1.0, 10.1) vs. 3.0(1.0, 6.1) years, Z=-1.98, P=0.048], more patients with combined hypertension [34.1%(29/85) vs. 15.5%(24/155), χ2=11.08, P<0.001], hyperlipidemia [47.1%(40/85) vs. 27.1%(42/155), χ2=1.22, P=0.002] and the taking of statins [14.1%(12/85) vs. 5.8%(9/155), χ2=4.75 , P=0.029], hypoglycemic agents [10.6%(9/85) vs. 3.9%(6/155), χ2=4.23, P=0.040] and antihypertensive drugs [17.6%(15/85) vs 6.5%(10/155), χ2=7.37, P=0.007]. They also had a higher blood glucose level[5.37 (5.17, 6.09)mmol/L vs. 5.26(4.97, 5.67)mmol/L, Z=-2.82 , P=0.005], low-density lipoprotein [(3.05± 0.76)mmol/L vs. (2.78±0.75)mmol/L, t=2.60, P=0.010] and blood uric acid level[351 (312, 412)μmol/L vs. 333(279, 408)μmol/L, Z=-2.10, P=0.036]. Multivariate analysis showed that older [ OR (95% CI) =1.059 (1.033, 1.086), P<0.001], increased low density lipoprotein [ OR (95% CI) =1.519 (1.018, 2.267), P=0.041] and increased blood uric acid levels [ OR (95% CI)=1.004 (1.001, 1.007), P=0.017] were an independent risk of SCA in PsA patients. Conclusion:More than 1/3 of PsA patients with SCA without past history of clinical atherosclerosis with SCA, advanced age, increased blood low density lipoprotein level, and elevated uric acid level are independent risk factors for PsA with SCA, so attention should be paid to the assessment and management of cardiovascular-related risk. Early intervention can help to improve patient prognosis.

BACKGROUND:Rapid developments in the field of bioinformatics have provided new methods for the diagnosis of osteoarthritis.Artificial neural networks have powerful data computing and classification capabilities,which have shown better performance in disease diagnosis. OBJECTIVE:To establish a new diagnostic predictive model of osteoarthritis based on artificial neural network and to verify the diagnostic value of the model in osteoarthritis with an external dataset. METHODS:The eligible osteoarthritis-related data sets were downloaded through GEO database search and divided into Train group and Test group.The gene expression matrix of the Train group was analyzed to screen the differentially expressed genes.GO and KEGG enrichment analyses were performed on the differentially expressed genes.Through Lasso regression model,support vector machine model and random forest tree model,the key genes of osteoarthritis were further identified from the differentially expressed genes.The R software"Neuralnet"package was then used to construct the osteoarthritis diagnosis model based on artificial neural network,and the model performance was evaluated by the five-fold cross-validation.Two independent data sets in the Test group were used to verify their diagnostic results. RESULTS AND CONCLUSION:A total of 90 differentially expressed genes related to osteoarthritis were obtained by differential analysis,of which 33 were down-regulated and 57 were up-regulated.GO enrichment analysis showed that the differentially expressed genes were mainly involved in the following biological processes,including leukocyte-mediated immunity,leukocyte migration in bone marrow and chemokine production.KEGG enrichment analysis showed that these genes were mainly enriched in rheumatoid arthritis,interleukin-17 signaling pathway and osteoclast differentiation pathway.Five key genes for the diagnosis of osteoarthritis,HMGB2,GADD45A,SLC19A2,TPPP3 and FOLR2,were identified by three machine learning methods.The artificial neural network model of five key genes in the Train group showed that the accuracy was 96.36%and the area under the curve was 0.997.The five-fold cross validation of the neural network model showed that the average area under the curve was greater than 0.9 and the model was of robustness.Two independent data sets in the Test group showed its area under the curve was 0.814 and 0.788 respectively.Therefore,the establishment of an artificial neural network model for the diagnosis of osteoarthritis has a certain diagnostic value.

BACKGROUND:Rheumatoid arthritis is a chronic systemic autoimmune disease.It is important to study the immunological changes involved in it for diagnosis and treatment. OBJECTIVE:To identify immune-related biomarkers associated with rheumatoid arthritis utilizing bioinformatics techniques and examine alterations in immune cell infiltration as well as the relationship between immune cells and biomarkers. METHODS:Differential expression analysis was used to identify the immune-related genes that were up-regulated in rheumatoid arthritis based on the GEO and Immport databases.Kyoto encyclopedia of genes and genomes(KEGG)and gene ontology(GO)enrichment analyses were used to investigate the possible function of these elevated genes.The immunological characteristic genes associated with rheumatoid arthritis were screened using least absolute shrinkage and selection operator(Lasso)and support vector machine recursive feature elimination(SVM-RFE).Independent datasets were used for difference validation,and the diagnostic performance was evaluated by plotting receiver operating characteristic curves for feature genes.Immune cell infiltration was used to analyze the differential profile of immune cells in rheumatoid arthritis and the correlation between the characterized genes and immune cells.In order to ascertain the causal relationship between monocytes and rheumatoid arthritis in immune cells,Mendelian randomization analysis was ultimately employed. RESULTS AND CONCLUSION:There were 39 upregulated differentially expressed genes in rheumatoid arthritis.The genes were primarily enriched in chemotaxis,cytokine activity,and immune receptor activity,according to GO enrichment analysis,while kEGG enrichment analysis revealed that the genes were considerably enriched in the tumor necrosis factor signaling pathway and peripheral leukocyte migration.Lasso and SVM-RFE identified five feature genes:CXCL13,SDC1,IGLC1,PLXNC1,and SLC29A3.Independent dataset validation of the feature genes found them to be similarly highly expressed in rheumatoid arthritis samples,with area under the curve values greater than 0.8 for all five feature genes in both datasets.Immune cell infiltration indicated that most immune cells,including natural killer cells and monocytes,exhibited increased levels of infiltration in rheumatoid arthritis samples.The correlation analysis revealed a significant positive correlation between memory B cells and immature B cells and these five feature genes.Correlation analysis showed that the five feature genes were positively correlated with memory B cells and immature B cells.The inverse variance weighting method revealed that monocytes were associated with the risk of developing rheumatoid arthritis.