A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Background Per- and polyfluoroalkyl substances (PFAS), a group of persistent organic pollutants associated with adverse health effects including hepatotoxicity, immunosuppression, and carcinogenicity, have undergone risk assessments by multiple international organizations, with dietary exposure being the primary pathway. Objective To characterize the exposure to PFAS from food and drinking water sources of elderly residents in Songjiang District of Shanghai and to evaluate associated health risk and health effects. Methods A cross-sectional study was conducted from May to July 2024 in Songjiang District based on the Shanghai Suburban Adult Cohort and Biobank (SSACB) cohort. Dietary surveys were administered via face-to-face interviews among older adults aged 65 years and above, yielding 4 583 valid questionnaires. The estimated daily intake (EDI) of PFAS was calculated by integrating data from the Sixth National Dietary Survey and recent literature on PFAS concentrations in food and drinking water in Shanghai. Health risk assessment was performed using health-based guideline values (HBGV) proposed by various institutions and studies. Additionally, correlation analysis and linear regression modeling of EDI and biochemical indicators in the elderly were conducted to evaluate potential adverse health effects. Results The elderly population in Songjiang District exhibited dietary characteristics consistent with the Eastern Healthy Diet Pattern. Among PFAS compounds, PFOA showed the highest level of oral exposure [mean: 1.495 ng·(kg·d⁻¹)], followed by PFOS [mean: 0.637 ng·(kg·d⁻¹)], PFHxS [mean: 0.636 ng·(kg·d⁻¹)], and PFBS [mean: 0.273 ng·(kg·d⁻¹)]. Specifically, drinking water was the primary source of PFOA [1.415 ng·(kg·d⁻¹), accounting for 94.60%], while aquatic products were the major source of PFOS [0.278 ng·(kg·d⁻¹), accounting for 43.66%]. Using the HBGV derived by China's epidemiological studies, the mean hazard index (HI) for PFAS exposure was 1.39, indicating 54.35% of the population had potential health risks (HI>1). Following the 2024 standard established by the Food Safety Commission of Japan (FSCJ), the HI value dropped to 0.11, suggesting negligible risk. PFAS exposure was negatively associated with triglyceride levels and the indicators of liver and kidney function, but positively associated with low-density lipoprotein cholesterol (LDL-C) and lung cancer markers in the elderly residents. Conclusion PFAS exposure among the elderly residents in Songjiang District is predominantly attributed to PFOA, PFOS, PFHxS, and PFBS, with drinking water and aquatic products identified as primary exposure sources. Current exposure levels demonstrate significant associations with biomarkers of lipid metabolism and lung cancer markers, suggesting potential population health risks. These findings underscore the urgent need to establish HBGV for PFAS compounds based on Chinese population-specific metabolic characteristics.

Objective: To explore the application and clinical efficacy of red blood cell therapeutic apheresis in erythropoietic protoporphyria (EPP) and hereditary hemochromatosis (HH). Methods: 1) The EPP patient was hospitalized twice for "abdominal pain, nausea, vomiting, and brown urine". One and two sessions of red blood cell exchange/therapeutic plasma exchange (RCE/TPE) were respectively performed during the two hospitalizations. During each session, one RCE with 6-8 units of leukoreduced RBCs and 3-4 TPE procedures with 1 800-2 000 mL of frozen plasma was conducted. Biochemical parameters were monitored before and after treatment. 2) The HH patient was hospitalized for “repeatedly elevated aminotransferases”. Erythrocytapheresis was performed once, removing 550 mL of red blood cells, and venous phlebotomy was conducted once every 2 months subsequently. Blood routine and ferritin levels were assessed before and after treatment. Results: 1) During the first hospitalization, the EPP patient was relieved of the abdominal pain and brown urine after therapeutic apheresis. The total bilirubin level decreased from 141.8 μmol/L on admission to 68.6 μmol/L at discharge, with a symptom remission duration of 10 months. During the second hospitalization, the EPP patient still had recurrent abdominal pain after therapeutic apheresis. He developed psychiatric symptoms and gastrointestinal bleeding subsequently, accompanied by elevated bilirubin levels. Liver function deteriorated and the patient went into the state of the end-stage liver disease (ESLD). 2) For the HH patient, the hemoglobin level prior to erythrocytapheresis and vein phlebotomy was 150-160 g/L, with the lowest value occurring two days after erythrocytapheresis, decreasing to 107 g/L. The ferritin level before erythrocytapheresis was 2 428.08 ng/mL and it declined gradually after theraphy, with the lowest value occurring two months after erythrocytapheresis, decreasing to 1 094 ng/mL. The ferritin level was 1 114 ng/mL two months following the first vein phlebotomy, however it increased to 1 472 ng/mL two months after the second vein phlebotomy. Conclusion: RCE/TPE may alleviate protoporphyrin liver disease and help patients with bridging liver transplantation before EPP developments to ESLD. For HH patients with significantly elevated ferritin levels, erythrocytapheresis reduces serum ferritin more quickly and maintains its level longer relative to phlebotomy.

Objective: To explore the application and clinical efficacy of red blood cell therapeutic apheresis in erythropoietic protoporphyria (EPP) and hereditary hemochromatosis (HH). Methods: 1) The EPP patient was hospitalized twice for "abdominal pain, nausea, vomiting, and brown urine". One and two sessions of red blood cell exchange/therapeutic plasma exchange (RCE/TPE) were respectively performed during the two hospitalizations. During each session, one RCE with 6-8 units of leukoreduced RBCs and 3-4 TPE procedures with 1 800-2 000 mL of frozen plasma was conducted. Biochemical parameters were monitored before and after treatment. 2) The HH patient was hospitalized for “repeatedly elevated aminotransferases”. Erythrocytapheresis was performed once, removing 550 mL of red blood cells, and venous phlebotomy was conducted once every 2 months subsequently. Blood routine and ferritin levels were assessed before and after treatment. Results: 1) During the first hospitalization, the EPP patient was relieved of the abdominal pain and brown urine after therapeutic apheresis. The total bilirubin level decreased from 141.8 μmol/L on admission to 68.6 μmol/L at discharge, with a symptom remission duration of 10 months. During the second hospitalization, the EPP patient still had recurrent abdominal pain after therapeutic apheresis. He developed psychiatric symptoms and gastrointestinal bleeding subsequently, accompanied by elevated bilirubin levels. Liver function deteriorated and the patient went into the state of the end-stage liver disease (ESLD). 2) For the HH patient, the hemoglobin level prior to erythrocytapheresis and vein phlebotomy was 150-160 g/L, with the lowest value occurring two days after erythrocytapheresis, decreasing to 107 g/L. The ferritin level before erythrocytapheresis was 2 428.08 ng/mL and it declined gradually after theraphy, with the lowest value occurring two months after erythrocytapheresis, decreasing to 1 094 ng/mL. The ferritin level was 1 114 ng/mL two months following the first vein phlebotomy, however it increased to 1 472 ng/mL two months after the second vein phlebotomy. Conclusion: RCE/TPE may alleviate protoporphyrin liver disease and help patients with bridging liver transplantation before EPP developments to ESLD. For HH patients with significantly elevated ferritin levels, erythrocytapheresis reduces serum ferritin more quickly and maintains its level longer relative to phlebotomy.

ObjectiveTo analyze the prevalence and influencing factors of overweight and obesity among primary school students in a community of Fengxian District, Shanghai, and to provide references for formulating prevention and control strategies against overweight and obesity. MethodsData on height and weight of all primary school students in a community in Fengxian District, Shanghai, in 2023 were obtained by physical examination, and 1 759 primary school students were included according to the entry criteria. Overweight and obesity were determined using body mass index (BMI). Additionally, a questionnaire survey was performed to 1 045 students to collect their demographic characteristics, dietary behaviors, dietary habits, sleep and physical activity information. Chi-square test and logistic regression analysis were used to analyze the influencing factors of overweight and obesity. ResultsIn 2023, among the 1 759 primary school students in the community in Fengxian District, 923 (52.47%) were male and 836 (47.53%) were female, with an overweight/obesity detection rate of 28.08%. The detection rate of overweight and obesity was 33.37% in males and 22.25% in females, which was significantly higher in males than that in females (χ²=26.845, P<0.001). Students aged 10‒12 years had a higher overweight/obesity detection rate (32.55%) than those aged 6‒<10 years (26.53%), and the difference was statistically significant (χ²=10.925, P<0.001). Logistic regression analysis revealed that being female, with young age, parental education level of bachelor’s degree and above, a high global dietary recommendation healthy (GDR-healthy) score, preference for vegetables and sweeter home-cooked meals, and a slow eating speed were negatively correlated with overweight/obesity. Whereas, parental overweight and obesity, binge eating, and a faster eating pace than same-age, same-gender peers may be positively correlated with overweight/obesity. ConclusionThe detection rate of overweight and obesity among primary school students in the community in Fengxian District of Shanghai is higher than the national level. Gender, age, parental BMI, parental education level, dietary behaviors and habits are the main influencing factors of overweight/obesity among primary school students.

Objective To investigate the effect of miR-185-5p-mediated targeted negative regulation of transmembrane 9 superfamily member 1(TM9SF1)on proliferation,migration and autophagy in lung adenocarcinoma cells.Methods The expression of miR-185-5p in lung adenocarcinoma tissues was analyzed using dataset GSE51853 downloaded from the Gene Expression Omnibus(GEO)database.Potential target proteins of miR-185-5p were predicted using online databases(miRTargetLink,miRTarbase,and DIANA-microT-CD),and autophagy-related proteins were obtained from HADb.The intersected results from these four databases was identified,and survival curves of vascular endothelial growth factor A(VEGFA)and TM9SF1 within the overlapping candidates were analyzed using the StarBase database.TM9SF1 3'UTR wild-type(WT)or TM9SF1 3'UTR mutant(MUT)reporter plasmids were separately co-transfected with miR-185-5p control plasmid(CON)or miR-185-5p overexpression plasmid(over-miR-185-5p)into HEK-293T cells.A dual-luciferase reporter gene assay was employed to assess the binding interaction between miR-185-5p and TM9SF1 and quantify the subsequent luciferase activity.Western blotting was used to assess TM9SF1 protein expression levels in A549 cells transfected with over-miR-185-5p.A549 cells were divided into three groups:(1)CON+NC group,co-transfected with miR-185-5p control plasmid and TM9SF1 control plasmid;(2)over-miR-185-5p+NC group,co-transfected with over-miR-185-5p and TM9SF1 control plasmid;(3)over-miR-185-5p+over-TM9SF1 group,co-transfected with both miR-185-5p and TM9SF1 overexpression plasmids.EdU cell proliferation assay,wound healing assay,and Transwell migration assay were performed to validate the effects of miR-185-5p targeted binding to TM9SF1 on proliferation and migration capacities in lung adenocarcinoma.Changes in autophagic flux and mitochondrial membrane potential(MMP)of lung adenocarcinoma cells were detected using stubRFP-sensGFP-LC3 lentivirus and JC-1 assays,respectively.Results In the GSE51853 dataset,miR-185-5p expression level was significantly lower in lung adenocarcinoma tissues compared with normal lung tissues(P<0.01).qRT-PCR analysis revealed that miR-185-5p expression was downregulated in lung adenocarcinoma cell lines NCI-H1299 and A549 compared with normal lung epithelial cells BEAS-2B(P<0.01).Bioinformatics predictions using miRTargetLink,miRTarbase,DIANA-microT-CD,and HADb databases indicated that miR-185-5p could target and regulate the autophagy-related protein TM9SF1.Dual-luciferase reporter assays and Western blotting demonstrated that miR-185-5p directly bound to the 3'UTR region of TM9SF1 mRNA,and overexpression of miR-185-5p significantly reduced the expression of target protein TM9SF1(P<0.05).EdU cell proliferation,wound healing,and Transwell migration assays demonstrated that miR-185-5p overexpression inhibited proliferation and migration capacities of lung adenocarcinoma cells,whereas TM9SF1 overexpression could attenuate this inhibition effect(P<0.05).Results of stubRFP-sensGFP-LC3 for autophagic flux analysis demonstrated that overexpression of miR-185-5p enhanced autophagic flux in A549 cells,whereas co-overexpression of miR-185-5p and TM9SF1 suppressed autophagic flux.JC-1 assays showed a decreased MMP level in A549 cells after miR-185-5p overexpression,with higher MMP level observed when miR-185-5p and TM9SF1 were co-overexpressed.Conclusion miR-185-5p may suppress proliferation,migration,and autophagy capacities in lung adenocarcinoma cells by targeting TM9SF1 through negative regulation.