The liver has diverse functions such as metabolism， detoxification， and immune defense， and the maintenance of hepatic microenvironment homeostasis is crucial for overall bodily health. The hepatic microenvironment consists of the components such as parenchymal cells， non-parenchymal cells， and non-cellular components. Chronic inflammatory responses induced by various etiological factors may promote the formation and progression of liver fibrosis. During the dynamic progression of liver fibrosis， from the early to advanced stages， various components within the hepatic microenvironment undergo a series of changes， which can promote the malignant progression of liver fibrosis. An in-depth exploration of the mechanisms underlying such changes in each component of the liver fibrosis microenvironment is of great significance for understanding the pathogenesis of liver fibrosis and discovering potential treatment strategies.

ObjectiveTo investigate the changes in coagulation system in acute decompensated cirrhosis （ADC） patients with or without sepsis and the association of these changes with short-term prognosis. MethodsA prospective study was conducted among 116 ADC patients who were hospitalized in Nanfang Hospital from January 2021 to July 2023， among whom there were 86 patients with sepsis and 30 patients without sepsis， and 54 patients with sepsis alone who had no chronic liver disease were enrolled as control group. Thromboelastography （TEG） and other conventional coagulation parameters were used to comprehensively evaluate the coagulation function of patients. The data including TEG results and short-term prognosis were collected， and a correlation analysis was performed. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. The Spearman correlation coefficient was calculated to investigate the correlation between different variables. The Logistic regression model was used to perform the univariate and multivariate analyses. ResultsFor the ADC patients with sepsis， the lungs and bloodstream were the main infection sites， and bacteria were the main pathogenic microorganism. TEG results showed that compared with the patients with sepsis alone， the patients with ADC and sepsis had a significant reduction in median maximum amplitude （MA）， a significant increase in coagulation time （K time）， and a significant reduction in α angle （all P<0.05）； the patients with ADC and sepsis had a significantly longer reaction time （R time） than those with ADC alone （P=0.02）， and the patients with sepsis alone had a significantly longer R time than those with ADC and sepsis （P=0.04）. There was no correlation between MA and platelet count in the patients with ADC and sepsis （r=-0.133， P=0.057）， while there was a significant correlation between MA and platelet count in the patients with sepsis alone （r=0.595， P=0.001）. SOFA score was negatively correlated with MA in sepsis patients with or without ADC （r=-0.503 and -0.561， both P<0.001）， and for the patients with ADC and sepsis， R time， K time， and α angle were weakly correlated with SOFA score and had a relatively strong correlation with APTT （all P<0.05）. The patients with ADC alone all survived within 90 days， and compared with the death group， the patients with sepsis alone who survived had significantly higher values of MA and α angle （all P<0.05）； there was a significant difference in α angle on day 90 between the survival group and the death group， no matter whether the patients were comorbid with ADC or not （both P<0.01）， while for the patients with ADC and sepsis， there was no significant difference in MA value on day 90 between the survival group and the death group （P>0.05）. ConclusionFor ADC patients comorbid with sepsis， coagulation function assessment and monitoring should be taken seriously in clinical practice， and TEG parameters and SOFA score should be monitored when necessary to develop individualized treatment regimens.

Objective To investigate how culture duration affects the expression of immune membrane proteins in human monocyte-derived dendritic cells (DCs) and their exosomes (DEXs). Methods Human monocytes were induced with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) to differentiate into DCs and were subsequently matured with tumor necrosis factor α(TNF-α). Exosomes were isolated by ultracentrifugation, and DEXs were identified by transmission electron microscopy and Amnis imaging flow cytometry, which were also used to quantify the expression of immune membrane proteins on DCs and DEXs. Results On the 10th day of culture, DCs displayed high surface expression of CD11c, CD80, CD86, major histocompatibility complex class I (MHC-I), and MHC-II. Expression peaked at day 18(CD11c: 78.66%±20.33%, CD80: 76.41%±10.02%, CD86: 96.43%±0.43%, MHC-I: 84.71%±2.96%, MHC-II: 80.01%±7.03%). After day 24, the overall expression showed a declining trend, with statistically significant differences observed for all markers except CD80 and MHC-II. By day 30, 80% of the DCs still expressed CD80, CD86, and MHC-II. The expression of immune membrane proteins on DEX surfaces also reached its peak on day 18, followed by an overall decline with prolonged culture time, with statistically significant differences observed for all markers except CD80. Correlation analysis revealed a significant positive relationship between the expression levels of immune membrane proteins on DC and DEX surfaces (CD11c: r=0.98; CD80: r=0.65; CD86: r=0.82; MHC-I: r=0.86; MHC-II: r=0.93). Conclusion Human monocyte-derived DCs in vitro express high expression of immune membrane proteins and maintain stable expression over a specific period. The exosomes secreted by these cells similarly demonstrate high surface expression of immune membrane proteins, with temporal trends aligned with those of the parent DCs.
Humans ; Dendritic Cells/immunology* ; Exosomes/immunology* ; Monocytes/metabolism* ; Cells, Cultured ; Time Factors ; B7-1 Antigen/metabolism* ; Membrane Proteins/immunology* ; Cell Culture Techniques/methods* ; B7-2 Antigen/metabolism* ; Cell Differentiation ; CD11c Antigen/metabolism* ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology*

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

IL-2 is a multifunctional cytokine whose main functions include activating and maintaining T cell survival.Re-search has shown that the level and function of IL-2 in peripheral blood of patients with systemic lupus erythematosus(SLE)have sig-nificantly decreased,and are associated with the activity of SLE disease.In recent years,the decrease in IL-2 level has been found to play a crucial role in the occurrence and development of SLE,and is one of the important mechanisms for T cell homeostasis imba-lance and immune regulation disorders in SLE patients.The low-dose IL-2 treatment regimen for SLE based on this discovery has en-tered clinical application.However,there is still considerable controversy regarding the mechanism of decreased IL-2 level and sup-pressed functions in SLE patients.Clarifying this mechanism is of great significance for further clarifying the occurrence and develop-ment mechanism of SLE and developing new treatment regimens.

Objective:To explore the clinical characteristics of adrenal lesions in unilateral primary aldosteronism.Methods:This is a prospective study. Consecutive patients diagnosed with unilateral primary aldosteronism at the First Affiliated Hospital of Chongqing Medical University from December 2023 to November 2024 were included. Inclusion criteria：① Age is 18 to 80 years old；② The laboratory test indicators are in line with the diagnosis of primary aldosteronism；③ The auxiliary examination proved that only one side was involved；④ Patient undergo unilateral total adrenalectomy. The exclusion criteria are as follows：① Complete biochemical remission was not achieved during the 1-6 month follow-up after the surgery；② Postoperative loss to follow-up；③ No surgical specimens were received or the surgical specimens were incomplete，making continuous sectioning impossible. Patients meeting the inclusion criteria were recruited，and their clinical and biochemical data were recorded. The number of adrenal nodules visible on CT scans and the number of macroscopically visible nodules in the postoperative adrenal gross specimens were documented. Hematoxylin-eosin（HE）staining and aldosterone synthase CYP11B2 immunohistochemical staining were performed on the adrenal tissues after the operation. The number of nodules visible under the light microscope and the number of CYP11B2-positive nodules were recorded.Results:A total of 114 cases were included in this study. The age of the patients was（49.86 ± 9.80）years，the body mass index was（25.49 ± 3.40）kg/m2，the preoperative aldosterone level was 352（2012，556）pg/ml，and the direct renin concentration was 1.63（0.50，4.56）μIU/ml. The aldosterone/renin ratio was 224.9（57.1，641.6）（aldosterone concentration unit was pg/ml，renin concentration unit was μIU/ml），the minimum blood potassium concentration was 2.87（2.50，3.40）mmol/L，and the systolic blood pressure was（144.5 ± 19.5）mmHg. Among the 114 patients，105 had adrenal nodules detected by preoperative CT，of whom 2（1.75%）had multiple nodules. Postoperative gross adrenal specimen evaluation and CYP11B2 immunohistochemical staining revealed that 90 out of 114 cases were solitary nodules，2 cases had no nodules，and 22 cases（19.30%）had multiple nodules detected（17 cases had 2 nodules and 5 cases had 3 nodules）. Among them，12 cases（10.53%）presented as grossly visible multinodular lesions，while 10 cases（8.77%）appeared as solitary nodules macroscopically but demonstrated multinodular patterns on immunohistochemical staining. CYP11B2 staining showed that among the 22 patients with multiple nodules，13 had multiple CYP11B2-positive nodules，while the remaining had only one positive nodule. Among the 22 patients with multiple nodules，preoperative CT showed single nodules in 19 cases，hyperplasia in 1 case，and multiple nodules in 2 cases（9.09%）. Among the 12 patients with grossly visible multinodular lesions，preoperative CT showed single nodules in 9 cases，hyperplasia in 1 case，and multiple nodules in 2 cases（16.67%）.Conclusions:Multiple adrenal nodules associated with unilateral primary aldosteronism are relatively common，and are often not detected by preoperative CT examination. Partial adrenalectomy based solely on CT-visible nodules may fail to achieve complete remission of primary aldosteronism. This study provides evidence supporting total adrenalectomy as the preferred surgical approach for unilateral primary aldosteronism.

Objective To investigate the changes in coagulation system in acute decompensated cirrhosis(ADC)patients with or without sepsis and the association of these changes with short-term prognosis.Methods A prospective study was conducted among 116 ADC patients who were hospitalized in Nanfang Hospital from January 2021 to July 2023,among whom there were 86 patients with sepsis and 30 patients without sepsis,and 54 patients with sepsis alone who had no chronic liver disease were enrolled as control group.Thromboelastography(TEG)and other conventional coagulation parameters were used to comprehensively evaluate the coagulation function of patients.The data including TEG results and short-term prognosis were collected,and a correlation analysis was performed.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups.The Spearman correlation coefficient was calculated to investigate the correlation between different variables.The Logistic regression model was used to perform the univariate and multivariate analyses.Results For the ADC patients with sepsis,the lungs and bloodstream were the main infection sites,and bacteria were the main pathogenic microorganism.TEG results showed that compared with the patients with sepsis alone,the patients with ADC and sepsis had a significant reduction in median maximum amplitude(MA),a significant increase in coagulation time(K time),and a significant reduction in α angle(all P<0.05);the patients with ADC and sepsis had a significantly longer reaction time(R time)than those with ADC alone(P=0.02),and the patients with sepsis alone had a significantly longer R time than those with ADC and sepsis(P=0.04).There was no correlation between MA and platelet count in the patients with ADC and sepsis(r=-0.133,P=0.057),while there was a significant correlation between MA and platelet count in the patients with sepsis alone(r=0.595,P=0.001).SOFA score was negatively correlated with MA in sepsis patients with or without ADC(r=-0.503 and-0.561,both P<0.001),and for the patients with ADC and sepsis,R time,K time,and α angle were weakly correlated with SOFA score and had a relatively strong correlation with APTT(all P<0.05).The patients with ADC alone all survived within 90 days,and compared with the death group,the patients with sepsis alone who survived had significantly higher values of MA and α angle(all P<0.05);there was a significant difference in α angle on day 90 between the survival group and the death group,no matter whether the patients were comorbid with ADC or not(both P<0.01),while for the patients with ADC and sepsis,there was no significant difference in MA value on day 90 between the survival group and the death group(P>0.05).Conclusion For ADC patients comorbid with sepsis,coagulation function assessment and monitoring should be taken seriously in clinical practice,and TEG parameters and SOFA score should be monitored when necessary to develop individualized treatment regimens.

Objective To investigate the predictive value of atherosclerotic index of plasma(AIP)for the risk of coronary heart disease(CHD)in patients with nonalcoholic fatty liver disease(NAFLD).Methods A retrospective analysis was conducted in 299 patients with NAFLD.Based on presence or absence of CHD,the patients were divided into NAFLD with CHD group(n=177)and NAFLD group(n=122).Clinical data were collected from both groups,and AIP was calculat-ed.Multivariate Logistic regression analysis was performed to explore the independent risk factors for CHD in patients with NAFLD.Receiver operating characteristic(ROC)curves were plotted to evalu-ate the predictive value of AIP for the risk of CHD in patients with NAFLD.Results The NAFLD with CHD group had a higher proportion of males,smokers,and higher levels of alanine aminotrans-ferase(ALT),aspartate aminotransferase(AST),fasting plasma glucose(FPG),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),γ-glutamyltransferase(GGT),uric acid(UA),and AIP than the NAFLD group.The NAFLD with CHD group also had lower levels of high-density lipoprotein cholesterol(HDL-C)than the NAFLD group(P＜0.05).Multivariate Logistic regression analysis revealed that males(OR=2.548,95％CI,1.402 to 4.632,P=0.002),high levels of AST(OR=1.038,95％CI,1.002 to 1.077,P=0.041),high levels of LDL-C(OR=1.811,95％CI,1.242 to 2.640,P=0.002),and high AIP(OR=16.117,95％CI,1.874 to 138.609,P=0.011)were independent risk factors for CHD in patients with NAFLD(P＜0.05).ROC curve analysis showed that AIP had an area under the curve of 0.746(95％CI,0.688 to 0.804)for pre-dicting CHD in patients with NAFLD,with a sensitivity of 76.3％and a specificity of 73.0％.Conclusion AIP is an independent influencing factor for CHD in patients with NAFLD and has certain predictive value for the risk of CHD in these patients.

Objective:To evaluate the effect of perineal massage during pregnancy, when combined with Kegel exercises, on preventing perineal injury, and to provide a basis for offering safer and more effective delivery intervention measures for expectant mothers.Methods:Randomized controlled trials on perineal massage combined with Kegel exercises for preventing perineal injury were retrieved from databases such as CNKI, Wanfang database, VIP database, CBM database, PubMed, Embase, Web of Science, and Cochrane Library, from their inception to December 28, 2024. Meta-analysis was conducted using RevMan 5.3 software.Results:A total of 15 articles were included, involving 2 393 research subjects. The results of the Meta-analysis showed that there were statistically significant differences in the first stage of labor ( MD = - 1.63, 95% CI - 1.93 - - 1.30, P<0.001), the second stage of labor ( MD = - 32.58, 95% CI - 42.26 - - 22.90, P<0.01), and the third stage of labor time ( MD = - 3.41, 95% CI - 9.91 - - 2.91, P<0.001); the degree of perineal laceration Ⅱ ( OR = 0.40, 95% CI 0.28 - 0.58, P<0.001), Ⅲ( OR = 0.38, 95% CI 0.24 - 0.60, P<0.001), and Ⅳ( OR = 0.13, 95% CI 0.03 - 0.51, P = 0.003); the rate of perineal incision ( OR = 0.15, 95% CI 0.07 - 0.34, P<0.001), the rate of perineal laceration ( OR = 0.34, 95% CI 0.25 - 0.46, P<0.001), the rate of intact perineum ( OR = 6.30, 95% CI 3.20 - 12.40, P<0.001), and the amount of perineal bleeding ( MD = - 29.72, 95% CI - 43.51 - - 15.93, P<0.001), the difference was statistically significant. Conclusions:Prenatal perineal massage combined with Kegel exercises is a safe, effective and easily implementable intervention method. It is highly effective in preventing perineal injuries and shortening the duration of labor. It not only reduces the risk of postpartum complications but also helps to optimize the delivery experience. Therefore, this combined intervention method can be regarded as one of the important measures for preventing perineal injuries and should be widely promoted in clinical practice.