ObjectiveTo investigate whether Huanglian Jiedutang （HLJD） and its major active constituents （geniposide， baicalin， and berberine） can inhibit the inflammatory response of BV2 cells under lipopolysaccharide （LPS） stimulation via the high-mobility group protein B1 （HMGB1）/Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway， and to explore differences in therapeutic efficacy among the three monomers， their combined formula， and HLJD under equal content ratios. MethodsBV2 microglial cells were used as the primary experimental model. Cell viability was assessed using the cell counting kit-8 （CCK-8） method to examine the effects of different concentrations of dimethyl sulfoxide （DMSO， 0.8%， 0.4%， 0.2%， 0.1%， and 0.05%） on cell viability. IncuCyte was employed to monitor the growth of cells under different concentrations of HLJD （200， 100， 50， 25， 12.5， 6.25 mg·L^-1）. Nitric oxide （NO） assay was used to screen the optimal HLJD concentration. High-performance liquid chromatography （HPLC） determined the content of geniposide， baicalin， and berberine in HLJD， and experimental groups were subsequently established according to the relative proportions of these constituents. CCK-8 assay evaluated cell viability under different treatments. Enzyme-linked immunosorbent assay （ELISA） measured levels of inflammatory factors （TNF-α， IL-1β， IL-6， IL-10） in the supernatant. Flow cytometry assessed the effects of treatments on M1-type polarization of BV2 cells. Western blot determined the expression levels of HMGB1， TLR4， and NF-κB-related proteins. ResultsCompared with the blank group， DMSO at concentrations ≤0.2% did not affect cell viability within 48 h. BV2 cell growth plateaued at 24 h after treatment with 200 mg·L^-1 HLJD. Under stimulation with 2 mg·L^-1 LPS， this concentration of HLJD effectively reduced NO release， and 6 h pre-treatment had a stronger inhibitory effect on NO than direct administration. HPLC results showed that 1 mg of HLJD freeze-dried powder contained approximately 24 μg of geniposide， 15 μg of baicalin， and 30 μg of berberine. Based on these ratios， experimental groups were blank， LPS （2 mg·L^-1）， HLJD （200 mg·L^-1）， monomer combination， geniposide （4.8 mg·L^-1）， baicalin （3 mg·L^-1）， and berberine （6 mg·L^-1）. The monomer combination group consisted of all three active constituents dissolved together. LPS and HLJD or its active constituents did not affect cell viability compared with the blank group. LPS significantly increased TNF-α， IL-1β， IL-6， and IL-10 in the supernatant （P<0.01）. HLJD and its active constituents significantly reduced pro-inflammatory factors TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01） while upregulating anti-inflammatory IL-10 （P<0.01）， with the monomer combination showing the strongest effect （P<0.05， P<0.01）. Compared with the blank group， LPS significantly increased the proportion of CD80⁺CD86⁺ （M1-type） BV2 cells （P<0.01）. HLJD and its constituents partially inhibited M1 polarization （P<0.05， P<0.01）， with the monomer combination exhibiting the most pronounced effect （P<0.05， P<0.01）. Compared with the blank group， LPS upregulated HMGB1， TLR4， and NF-κB-related proteins （P<0.01）， whereas HLJD and its active constituents significantly reduced their expression （P<0.05， P<0.01）， with the monomer combination having the strongest regulatory effect （P<0.05， P<0.01）. ConclusionHLJD and its major active constituents （geniposide， baicalin， berberine） can inhibit LPS-induced inflammatory responses in BV2 cells. The combination of the three active constituents demonstrates the most potent anti-inflammatory effect， significantly attenuating M1-type polarization of BV2 cells via the HMGB1/TLR4/NF-κB signaling pathway.

Objective To investigate the prognostic value of albumin-corrected anion gap (ACAG) in patients with advanced lung cancer receiving immune checkpoint inhibitors (ICIs). Methods A total of 637 patients with advanced lung cancer who received ICI treatment were enrolled. Baseline clinical data and laboratory parameters were collected, and ACAG was calculated. The optimal prognostic Cut-off value for ACAG (11.58 mmol/L) was determined using X-Tile software, and patients were divided into low (≤11.58 mmol/L) and high (>11.58 mmol/L) ACAG groups. Propensity score matching was performed to control for confounding factors. Survival curves were plotted using the Kaplan-Meier method. A Cox proportional hazards regression model was employed to analyze prognostic factors, and subgroup analyses were conducted. Results Among 637 patients, 440 patients remained in the matched cohort. Multivariate Cox analysis showed that after adjusting for clinical and laboratory parameters, ACAG >11.58 mmol/L was an independent risk factor for OS (HR=1.74, 95%CI: 1.02–2.98, P=0.044) but was not an independent predictor for PFS. After adjusting for different sets of covariates, stratified analysis further confirmed that ACAG >11.58 mmol/L was consistently associated with a significantly shortened OS. Survival curves demonstrated that the median OS in the high ACAG group (47.0 months) was significantly lower than that in the low ACAG group. Subgroup analysis indicated that the predictive value of ACAG for OS was more pronounced in males, patients aged <65 years, and patients with squamous cell carcinoma than in other patients. Conclusion In patients with advanced lung cancer treated with ICIs, a high baseline ACAG level (>11.58 mmol/L) is an independent risk factor for shortened OS but is not significantly associated with PFS. ACAG may serve as a simple and effective biological marker for assessing overall survival prognosis in patients with advanced lung cancer undergoing immunotherapy.

Objective: To analyze the health literacy possession rate and its trend among residents in Lishui City, Zhejiang Province from 2016 to 2024, so as to provide the evidence for improving health promotion strategies and intervention measures. Methods: Multi-stage stratified random sampling combined with probability proportionate to size sampling method was adopted to select permanent residents aged 15-69 years in Lishui City as survey subjects. Demographic information and health literacy possession status were collected through questionnaire survey. The health literacy possession rate was calculated. The data from 2016 to 2019 and from 2020 to 2024 were standardized using the population data of Lishui City from the Sixth National Population Census in 2010 and the Seventh National Population Census in 2020, respectively. The trend of health literacy possession rate from 2016 to 2024 was analyzed. Results: A total of 42 691 people were surveyed, including 20 509 males (48.04%) and 22 182 females (51.96%), with an average age of (51.63±12.13) years. From 2016 to 2024, the health literacy possession rates were 20.40%, 25.83%, 26.96%, 28.82%, 32.30%, 34.02%, 37.53%, 39.21% and 43.17%, respectively, showing an upward trend (P<0.05). Among the three aspects, the possession rates of basic knowledge and concepts, healthy lifestyle and behaviors, and basic skills all showed upward trends (all P<0.05), with basic knowledge and concepts showing the largest increase and basic skills showing the smallest increase. Among the six health issues, the possession rates of scientific health view, chronic disease prevention and control, safety and first aid, basic medical care, and health information showed upward trends, while the infectious disease prevention and control literacy possession rate showed a downward trend (all P<0.05). The possession rates in the 65-69 age group, illiterate/semi-literate residents, and farmers showed upward trends (all P<0.05), but with small increases and remaining at low levels. Conclusions From 2016 to 2024, the health literacy possession rate of residents in Lishui City showed an overall upward trend, but the increase in basic skills literacy possession rate was relatively slow, and the infectious disease prevention and control literacy possession rate showed a downward trend. It is necessary to strengthen health education for weak links and knowledge among elderly people, residents with low educational level, and farmers to improve health literacy level.

Purpose To explore the predictive value of hepatosplenic hemodynamic indexes obtained by dual-energy CT combined with clinical features in non-invasive assessment of high-risk esophageal varices(EV)in cirrhosis.Materials and Methods We retrospectively collected 93 patients with cirrhosis from March 2022 to May 2023 in Zengcheng Branch of Nanfang Hospital.All patients underwent epigastric enhanced energy spectrum scan and gastroscopy.EV severity as assessed by gastroscopy(none,EV0;mild,EV1;medium,EV2;severe,EV3)were divided into low-risk EV group(EV0 and EV1)and high-risk EV group(EV2 and EV3).Age,gender,Child-Pugh grade,ascites and platelet of the two groups were collected,and dual-energy CT parameters including liver and spleen volume,mean iodine content in liver and spleen and liver and spleen iodine volume were measured.The difference of parameters between the low-risk EV and the high-risk EV group were analyzed,and the model was constructed by Logistic regression analysis.Receiver operating characteristic curve was used to evaluate the diagnostic performance of the model for high-risk EV.Results There were significant differences in age,Child-Pugh grade,ascites,platelet,liver and spleen volume,liver and spleen iodine volume between low-risk EV and high-risk EV groups(Z/χ2=-5.921-16.343,all P<0.05).Ascites,platelet,liver and spleen volume,liver and spleen iodine volume were included in multivariate regression analysis to construct regression models,and the results showed that spleen iodine volume(OR=1.002,P<0.001),ascites(OR=5.319,P=0.009),platelet(OR=0.99,P=0.062)were independent risk factors for predicting the high risk of EV.Hosmer-Lemeshow test showed that the regression model fit the observed values well(P=0.303),with accuracy of 83.9%,sensitivity of 78.6%,specificity of 88.2%,positive prediction rate of 84.6%and negative prediction rate of 83.3%.The area under the curve of this regression model was 0.894.Conclusion Spleen iodine content based on dual-energy CT,platelet and ascites can noninvasively predict high-risk EV.

Purpose To explore the predictive value of hepatosplenic hemodynamic indexes obtained by dual-energy CT combined with clinical features in non-invasive assessment of high-risk esophageal varices(EV)in cirrhosis.Materials and Methods We retrospectively collected 93 patients with cirrhosis from March 2022 to May 2023 in Zengcheng Branch of Nanfang Hospital.All patients underwent epigastric enhanced energy spectrum scan and gastroscopy.EV severity as assessed by gastroscopy(none,EV0;mild,EV1;medium,EV2;severe,EV3)were divided into low-risk EV group(EV0 and EV1)and high-risk EV group(EV2 and EV3).Age,gender,Child-Pugh grade,ascites and platelet of the two groups were collected,and dual-energy CT parameters including liver and spleen volume,mean iodine content in liver and spleen and liver and spleen iodine volume were measured.The difference of parameters between the low-risk EV and the high-risk EV group were analyzed,and the model was constructed by Logistic regression analysis.Receiver operating characteristic curve was used to evaluate the diagnostic performance of the model for high-risk EV.Results There were significant differences in age,Child-Pugh grade,ascites,platelet,liver and spleen volume,liver and spleen iodine volume between low-risk EV and high-risk EV groups(Z/χ2=-5.921-16.343,all P<0.05).Ascites,platelet,liver and spleen volume,liver and spleen iodine volume were included in multivariate regression analysis to construct regression models,and the results showed that spleen iodine volume(OR=1.002,P<0.001),ascites(OR=5.319,P=0.009),platelet(OR=0.99,P=0.062)were independent risk factors for predicting the high risk of EV.Hosmer-Lemeshow test showed that the regression model fit the observed values well(P=0.303),with accuracy of 83.9%,sensitivity of 78.6%,specificity of 88.2%,positive prediction rate of 84.6%and negative prediction rate of 83.3%.The area under the curve of this regression model was 0.894.Conclusion Spleen iodine content based on dual-energy CT,platelet and ascites can noninvasively predict high-risk EV.

Objective To explore the prognostic impact and clinical application value of therapeutic plasma exchange(TPE)intervention timing and liver injury periodization in patients with exertional heat stroke(EHS).Methods Data of 127 EHS patients from the First Medical Center of the General Hospital of the People′s Liberation Army from January 2011 to December 2023 were collected,then divided into the death group and the survival group based on therapeutic outcomes and into 5 stages according to the dynamic changes of ALT,AST,TBIL and DBIL.According to propensity score matching analysis,11 patients in the survival group and 12 patients in the death group were included in the statistical analysis,and 20 of them were treated with TPE.The changes in indicators and clinical outcomes before and after TPE were observed,in order to evaluate the impact of intervention timing on prognosis.Results Among the 23 patients,14 had no liver injury or could progress to the repair phase,resulting in 3 deaths(with the mortality rate of 21.43%),while 9 patients failed to pro-gress to the repair phase,resulting in 9 deaths(with the mortality rate of 100%),with significant differences(P＜0.05).The mortality rate of the first TPE intervention before the third stage of liver injury was 23.08%(3/13),while that of interven-tion after reaching or exceeding the third stage was 85.71%(6/7),and the difference was statistically significant(P＜0.05).Conclusion TPE should be executed actively in EHS patients combined with liver injury before the third phase to lock its pathological and physiological processes,thereby improving prognosis and reducing mortality.

【Objective】 To investigate the association of depressive symptoms with the predicted risk of coronary heart disease in middle-aged and elderly Chinese based on a large community study. 【Methods】 A total of 2532 cases in the group without depression and 2758 cases in the group with depression were included. We compared the two groups in general demographics, information related to coronary heart disease risk, and physical function and ability to perform daily living. We also analyzed the factors associated with coronary heart disease risk by linear regression. 【Results】 ① Demographic information: The group with depression had a higher mean age, a higher proportion of women, more people with poor marital status, and a higher number of comorbid chronic diseases compared with the group without depression (all P<0.05). ② Risk indicators related to coronary heart disease: The group with depression had more people with diabetes and a significantly higher systolic blood pressure compared with the group without depression (P<0.05). The two groups did not significantly differ in the proportion of smokers, diastolic blood pressure, LDL-C, or HDL-C (all P>0.05). The risk of coronary heart disease was significantly higher in the group with depression than in the group without depression (P<0.05). ③ Physical function and ability of daily living: The physical function score, physical self-care score, and instrumental daily living ability were significantly higher in the group with depression than in the group without depression (all P<0.001). ④ Linear regression showed that except for gender, age, marital status, comorbid diabetes, smoking, systolic and diastolic blood pressure, HDL-C and LDL-C were associated with risk of coronary heart disease (P<0.05); CESD was the only factor associated with the risk of coronary heart disease [B=0.019, 95% CI: (0.015, 0.032), P=0.032]. 【Conclusion】 The risk of coronary heart disease is higher in middle-aged and elderly people with depressive symptoms than in those without depressive symptoms. Having depressive symptoms is one of the risk factors for coronary heart disease in middle-aged and elderly people.

Objective:To examine the expression of transmembrane emp24 domain-containing protein 4(TMED4) in liver tissue of patients with hepatocellular carcinoma, and to investigate the effects of TMED4 gene on the proliferation and migration of hepatocellular carcinoma cells and related molecular mechanisms. Methods:The expression of TMED4 at protein level in liver cancer tissue and paracancerous tissue of patients with hepatocellular carcinoma were detected by Western blotting and immunohistochemical stainning, and the correlation between its expression and clinicopathological features was analyzed. The effects of TMED4 overexpression or knockdown on proliferation, migration and healing ability of hepatocellular carcinoma cells in vitro and in vivo were determined by cell proliferation test, Transwell test, wound healing test and subcutaneous tumor formation in nude mice. The molecular mechanism of TMED4 in regulating the biological behavior of hepatocellular carcinoma cells was preliminarily explored by pathway analysis. Independent sample t test, Mann-Whitney U test and chi-square test were used for statistical analysis. Results:The results of Western blotting showed that the expression of TMED4 at protein level in hepatocellular carcinoma tissue was lower than that in paracancerous tissue(0.52±0.29 vs. 0.83±0.22), and the difference was statistically significant( t=2.54, P=0.022). The results of immunohistochemical examination indicated that the expression of TMED4 at protein level in liver cancer tissue was lower than that in paracancerous tissue(5.46±3.37 vs. 7.58±3.08), and the difference was statistically significant( t=3.49, P<0.001). The expression of TMED4 at protein level was significantly correlated with vascular invasion and Barcelona clinic liver cancer stage( χ2=6.83 and 4.20, P=0.009 and 0.040). The results of cell proliferation assay showed that the absorbance value of SMMC-7721 cells in TMED4 overexpression group was lower than that in control group(1.38±0.05 vs. 2.37±0.08), while the optical density value of HepG2 in TMED4 knockdown group was higher than that in control group(0.76±0.04 vs. 0.54±0.01), and the differences were statistically significant( t=18.23 and 8.85, both P<0.001). The results of Transwell test showed that the number of migrated SMMC-7721 cells in TMED4 overexpression group was less than that in control group(286.30±13.01 vs. 439.70±12.34), while the number of migrated HepG2 cells in TMED4 knockdown group was higher than that in control group(249.00±6.00 vs. 160.00±6.56), and the differences were statistically significant( t=14.81 and 17.34, both P<0.001). The wound healing test showed that the healing rate of SMMC-7721 cells in TMED4 overexpression group was lower than that in control group((0.21±0.01)% vs.(0.45±0.01)%), the healing rate of HepG2 cells in TMED4 knockdown group was higher than that in control group((0.46±0.01)% vs.(0.20±0.01)%), and the differences were statistically significant( t=200.10 and 30.46, both P<0.001). The results of subcutaneous tumor formation assay in nude mice showed that the growth rate of cells in TMED4 overexpression group was slower than that in control group. After cell inoculation for 6 weeks, the subcutaneous tumor volume of mice in TMED4 overexpression group was smaller than that in control group(27.36 mm 3(138.70 mm 3) vs. 1 741.62 mm 3(1 783.39 mm 3)), the tumor weight was lower than that in control group(0.06 g(0.14 g) vs. 1.46 g(1.09 g)), and the differences were statistically significant(both Z=-2.31, both P<0.001). The results of Western blotting showed that the expression of Snail at protein level in SMMC-7721 cells of the TMED4 overexpression group was lower than that of the control group(0.32±0.01 vs. 0.90±0.03), the protein level of Snail in HepG2 cells of TMED4 knockdown group was higher than that of control group(1.03±0.01 vs. 0.97±0.01), and the differences were statistically significant( t=28.49 and 12.31, both P<0.001). The results of real time fluorescent quantitative polymerase chain reaction showed that the expression of Snail at mRNA level in SMMC-7721 cells of TMED4 overexpression group was lower than that of control group(0.13±0.05 vs. 1.00±0.15), the expression of Snail at mRNA level in HepG2 cells of TMED4 knockdown group was higher than that of control group(1.25±0.32 vs. 0.21±0.14), and the differences were statistically significant( t=9.62 and 5.10, P<0.001 and P=0.007). Conclusion:TMED4 may affect the proliferation and migration of hepatocarcinoma cells by regulating the expression of Snail, and which is expected to become a potentially therapeutic target for hepatocellular carcinoma.

ObjectiveTo investigate the clinical significance of highly sensitive nucleic acid detection in precise antiviral therapy for patients with liver cirrhosis and its association with aminotransferase level. MethodsA total of 377 patients with hepatitis B cirrhosis who were hospitalized or attended the outpatient service from May 2013 to April 2019 were enrolled and tested by both domestic HBV DNA detection and highly sensitive Cobas HBV DNA detection. All patients underwent biochemical examination, four blood coagulation tests, routine blood test, and upper abdominal computed tomography or ultrasound. Sensitivity of different HBV DNA detection reagents was compared in liver cirrhosis patients with a low viral load, and the correlation between alanine aminotransferase (ALT) level and viral load was analyzed. The paired t-test was used for comparison of continuous data before and after treatment. The receiver operating characteristic (ROC) curve was used to screen out the optimal predictive values of ALT at different cut-off values of HBV DNA. ResultsAmong the 377 patients with hepatitis B cirrhosis, 215 tested positive and 162 tested negative by domestic HBV DNA, and among these 162 patients, 104 (64.2%) tested positive by Cobas HBV DNA detection, with a mean level of 267.5±42.3 IU/ml. After 24 weeks of antiviral therapy, the 104 patients with hepatitis B cirrhosis had significant improvements in viral replication level, ALT, and Child-Pugh score for liver function; HBV DNA decreased from 267.5±32.2 IU/ml before treatment to 59.6±7.7 IU/ml after treatment (t=3.486, P=0.002), ALT decreased from 871±10.8 U/L before treatment to 36.5±7.6 U/L after treatment (t=3.235, P=0.020), and the Child-Pugh score decreased from 6.5±0.7 before treatment to 5.7±0.5 after treatment (t=2.928, P=0.041). The ROC curve analysis of ALT in predicting HBV DNA decision point showed that an ALT level of 29 IU/L was the most sensitive cut-off value for predicting HBV DNA ＜20 IU/ml, with an area under the ROC curve of 0.904, a sensitivity of 1.0, and a specificity of 0.237. ConclusionPrecise detection helps to guarantee the precise clinical treatment of patients with hepatitis B cirrhosis and improve their treatment outcome and prognosis. An ALT level of 29 IU/L is a sensitive indicator for predicting patients with negative Cobas HBV DNA, so as to achieve individualized precise screening and treatment.

Objective:To explore the effects of planned aerobic-resistance exercise on nutritional status and intra-dialytic hypotension of maintenance hemodialysis (MHD) patients during dialysis.Methods:From January 2018 to October 2018, we selected 106 hemodialysis patients in the First Affiliated Hospital of Zhengzhou University by convenience sampling. All of patients were divided into control group and observation group with method of the random number table, 53 cases in each group. Control group carried out the routine management model. On the basis of that in control group, observation group implemented the planned aerobic-resistance exercise during dialysis for three months. We compared the hemoglobin (Hb) , serum prealbumin (PA) , body cell mass (BCM) , bone mineral content (BMC) , skeletal muscle content (SMC) , cardiopulmonary function and incidence of intra-dialytic hypotension of patients between two groups.Results:Three months after intervention, the Hb, PA, BCM, BMC and SMC of patients in observation group were (99.77±6.29) g/L, (344.55±37.12) mg/L, (31.42±3.15) kg, (3.08±0.41) kg and (27.85±2.51) kg respectively higher than those in control group with statistical differences ( P<0.05) ; the maximal oxygen uptake and left ventricular ejection fraction of observation group were (14.93±2.82) ml/ (kg·min) and (58.21±5.22) % respectively higher than those in control group with statistical differences ( P<0.05) . During intervention, the incidence of intra-dialytic hypotension of observation group was 9.05% (187/2 067) lower than that in control group [19.45% (402/2 067) ]with a statistical difference (χ 2=91.520, P<0.01) . Conclusions:Planned aerobic-resistance exercise during dialysis can improve the nutritional status, cardiopulmonary function and endurance of MHD patients, and reduce the incidence of intra-dialytic hypotension which is worthy of clinical promotion.