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.

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.

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.

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.

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.

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.

Objectives:To investigate the effect of the expression of low-density lipoprotein receptor associated protein (LDLR) on the vascular abnormalities in hepatocellular carcinoma (HCC) and its mechanisms.Methods:Based on the information of Oncomine Cancer GeneChip database, we analyzed the correlation between the expression level of LDLR and the expression level of carcinoembryonic antigen (CEA) and CD31 in hepatocellular carcinoma tissues. Lentiviral transfection of short hairpin RNA target genes was used to construct LDLR-knockdown MHCC-97H and HLE hepatocellular carcinoma cells. The differential genes and their expression level changes in LDLR-knockdown hepatocellular carcinoma cells were detected by transcriptome sequencing, real-time fluorescence quantitative polymerase chain reaction, and protein immunoblotting. The gene-related signaling pathways that involve LDLR were clarified by enrichment analysis. The effect of LDLR on CEA was assessed by the detection of CEA content in conditioned medium of hepatocellular carcinoma cells. Angiogenesis assay was used to detect the effect of LDLR on the angiogenic capacity of human umbilical vein endothelial cells, as well as the role of CEA in the regulation of angiogenesis by LDLR. Immunohistochemical staining was used to detect the expression levels of LDLR in 176 hepatocellular carcinoma tissues, and CEA and CD31 in 146 hepatocellular carcinoma tissues, and analyze the correlations between the expression levels of LDLR, CEA, and CD31 in the tissues, serum CEA, and alanine transaminase (ALT).Results:Oncomine database analysis showed that the expressions of LDLR and CEA in the tissues of hepatocellular carcinoma patients with portal vein metastasis were negatively correlated ( r=-0.64, P=0.001), whereas the expressions of CEA and CD31 in these tissues were positively correlated ( r=0.46, P=0.010). The transcriptome sequencing results showed that there were a total of 1 032 differentially expressed genes in the LDLR-knockdown group and the control group of MHCC-97H cells, of which 517 genes were up-regulated and 515 genes were down-regulated. The transcript expression level of CEACAM5 was significantly up-regulated in the cells of the LDLR-knockdown group. The Gene Ontology (GO) function enrichment analysis showed that the differential genes were most obviously enriched in the angiogenesis function. The Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis showed that the relevant pathways involved mainly included the cellular adhesion patch, the extracellular matrix receptor interactions, and the interactions with the extracellular matrix receptors. The CEA content in the conditioned medium of the LDLR-knockdown group was 43.75±8.43, which was higher than that of the control group (1.15±0.14, P＜0.001). The results of angiogenesis experiments showed that at 5 h, the number of main junctions, the number of main segments, and the total area of the lattice formed by HUVEC cells cultured with the conditioned medium of MHCC-97H cells in the LDLR-knockdown group were 295.3±26.4, 552.5±63.8, and 2 239 781.0±13 8211.9 square pixels, which were higher than those of the control group (113.3±23.5, 194.8±36.5, and 660 621.0±280 328.3 square pixels, respectively, all P＜0.01).The number of vascular major junctions, the number of major segments, and the total area of the lattice formed by HUVEC cells cultured in conditioned medium with HLE cells in the LDLR-knockdown group were 245.3±42.4, 257.5±20.4, and 2 535 754.5±249 094.2 square pixels, respectively, which were all higher than those of the control group (113.3±23.5, 114.3±12.2, and 1 565 456.5±219 259.7 square pixels, respectively, all P＜0.01). In the conditioned medium for the control group of MHCC-97H cells,the number of main junctions, the number of main segments, and the total area of the lattice formed by the addition of CEA to cultured HUVEC cells were 178.9±12.0, 286.9±12.3, and 1 966 990.0±126 249.5 spixels, which were higher than those in the control group (119.7±22.1, 202.7±33.7, and 1 421 191.0±189 837.8 square pixels, respectively). The expression of LDLR in hepatocellular carcinoma tissues was not correlated with the expression of CEA, but was negatively correlated with the expression of CD31 ( r=-0.167, P=0.044), the level of serum CEA ( r=-0.061, P=0.032), and the level of serum ALT (r=-0.147, P=0.05). The expression of CEA in hepatocellular carcinoma tissues was positively correlated with the expression of CD31 ( r=0.192, P=0.020). The level of serum CEA was positively correlated with the level of serum ALT ( r=0.164, P=0.029). Conclusion:Knocking down LDLR can promote vascular abnormalities in HCC by releasing CEA.

Objectives:To investigate the effect of the expression of low-density lipoprotein receptor associated protein (LDLR) on the vascular abnormalities in hepatocellular carcinoma (HCC) and its mechanisms.Methods:Based on the information of Oncomine Cancer GeneChip database, we analyzed the correlation between the expression level of LDLR and the expression level of carcinoembryonic antigen (CEA) and CD31 in hepatocellular carcinoma tissues. Lentiviral transfection of short hairpin RNA target genes was used to construct LDLR-knockdown MHCC-97H and HLE hepatocellular carcinoma cells. The differential genes and their expression level changes in LDLR-knockdown hepatocellular carcinoma cells were detected by transcriptome sequencing, real-time fluorescence quantitative polymerase chain reaction, and protein immunoblotting. The gene-related signaling pathways that involve LDLR were clarified by enrichment analysis. The effect of LDLR on CEA was assessed by the detection of CEA content in conditioned medium of hepatocellular carcinoma cells. Angiogenesis assay was used to detect the effect of LDLR on the angiogenic capacity of human umbilical vein endothelial cells, as well as the role of CEA in the regulation of angiogenesis by LDLR. Immunohistochemical staining was used to detect the expression levels of LDLR in 176 hepatocellular carcinoma tissues, and CEA and CD31 in 146 hepatocellular carcinoma tissues, and analyze the correlations between the expression levels of LDLR, CEA, and CD31 in the tissues, serum CEA, and alanine transaminase (ALT).Results:Oncomine database analysis showed that the expressions of LDLR and CEA in the tissues of hepatocellular carcinoma patients with portal vein metastasis were negatively correlated ( r=-0.64, P=0.001), whereas the expressions of CEA and CD31 in these tissues were positively correlated ( r=0.46, P=0.010). The transcriptome sequencing results showed that there were a total of 1 032 differentially expressed genes in the LDLR-knockdown group and the control group of MHCC-97H cells, of which 517 genes were up-regulated and 515 genes were down-regulated. The transcript expression level of CEACAM5 was significantly up-regulated in the cells of the LDLR-knockdown group. The Gene Ontology (GO) function enrichment analysis showed that the differential genes were most obviously enriched in the angiogenesis function. The Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis showed that the relevant pathways involved mainly included the cellular adhesion patch, the extracellular matrix receptor interactions, and the interactions with the extracellular matrix receptors. The CEA content in the conditioned medium of the LDLR-knockdown group was 43.75±8.43, which was higher than that of the control group (1.15±0.14, P＜0.001). The results of angiogenesis experiments showed that at 5 h, the number of main junctions, the number of main segments, and the total area of the lattice formed by HUVEC cells cultured with the conditioned medium of MHCC-97H cells in the LDLR-knockdown group were 295.3±26.4, 552.5±63.8, and 2 239 781.0±13 8211.9 square pixels, which were higher than those of the control group (113.3±23.5, 194.8±36.5, and 660 621.0±280 328.3 square pixels, respectively, all P＜0.01).The number of vascular major junctions, the number of major segments, and the total area of the lattice formed by HUVEC cells cultured in conditioned medium with HLE cells in the LDLR-knockdown group were 245.3±42.4, 257.5±20.4, and 2 535 754.5±249 094.2 square pixels, respectively, which were all higher than those of the control group (113.3±23.5, 114.3±12.2, and 1 565 456.5±219 259.7 square pixels, respectively, all P＜0.01). In the conditioned medium for the control group of MHCC-97H cells,the number of main junctions, the number of main segments, and the total area of the lattice formed by the addition of CEA to cultured HUVEC cells were 178.9±12.0, 286.9±12.3, and 1 966 990.0±126 249.5 spixels, which were higher than those in the control group (119.7±22.1, 202.7±33.7, and 1 421 191.0±189 837.8 square pixels, respectively). The expression of LDLR in hepatocellular carcinoma tissues was not correlated with the expression of CEA, but was negatively correlated with the expression of CD31 ( r=-0.167, P=0.044), the level of serum CEA ( r=-0.061, P=0.032), and the level of serum ALT (r=-0.147, P=0.05). The expression of CEA in hepatocellular carcinoma tissues was positively correlated with the expression of CD31 ( r=0.192, P=0.020). The level of serum CEA was positively correlated with the level of serum ALT ( r=0.164, P=0.029). Conclusion:Knocking down LDLR can promote vascular abnormalities in HCC by releasing CEA.