Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.
Reperfusion Injury/drug therapy* ; Reactive Oxygen Species/metabolism* ; Reactive Nitrogen Species/metabolism* ; Humans ; Liver/drug effects* ; Animals ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*

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

Objective:To investigate the current status and related factors of antiviral treatment for chronic hepatitis B virus (HBV) infection in rural communities in China.Methods:In 2023, 866 chronic HBV-infected individuals from rural communities in Zhangqiu District, Jinan City, were included in the study. Basic information, disease status and antiviral treatment conditions of the infected individuals were collected through questionnaires, specimen collection and laboratory tests. Univariate and multivariate logistic regression were used to analyze the related factors of the antiviral treatment rate of those who met the indications for hepatitis B antiviral treatment.Results:The median age ( Q1, Q3) of subjects was 56 (48, 66) years old, among which 436 (50.4%) were males. There were 712 (82.2%) individuals who met the indications for hepatitis B antiviral treatment, and 110 individuals received antiviral treatment with a rate of 15.5%. Multivariate logistic regression analysis showed that compared with males, families with an average monthly income per capita of <1 000 yuan, no alcohol consumption, no smoking, and a family history of HBV infection, females ( OR=4.66, 95% CI: 2.88-7.53), families with an average monthly income per capita of 1 000-1 999 yuan ( OR=1.64, 95% CI: 1.00-2.68) and ≥2 000 yuan ( OR=2.78, 95% CI: 1.54-5.03), alcohol consumption ( OR=6.42, 95% CI: 2.80-14.7), smoking ( OR=1.98, 95% CI: 1.04-3.77), and no family history of HBV infection ( OR=1.90, 95% CI: 1.16-3.09) had a lower antiviral treatment rate for chronic HBV infection. Conclusion:The antiviral treatment rate of chronic HBV-infected individuals in rural communities of Zhangqiu District, Jinan City is low, and the related factors are female, high monthly income per capita, alcohol consumption, smoking, and no family history of HBV infection.

Objective To develop four novel cocrystals of felodipine aimed at improving its poor solubility.Methods Felodipine-caproamide,felodipine-2,4-dihydroxybenzoic acid,felodipine-2,5-dihydroxybenzoic acid,and felodipine-3,5-dihydroxybenzoic acid cocrystals were prepared using the slurry method.The cocrystals were characterized by powder X-ray diffraction(PXRD),differential scanning calorimetry(DSC),thermogravimetric analysis(TGA),and Fourier-transform infrared spectroscopy(FT-IR).Stability tests and in vitro dissolution studies were conducted to assess their pharmaceutical properties.Results All four cocrystals demonstrated improved solubility and dissolution rates compared to pure felodipine.Notably,the felodipine-3,5-dihydroxybenzoic acid cocrystal showed superior stability and a marked increase in solubility.Conclusion Cocrystallization technology significantly enhanced the stability and dissolution profile of felodipine,underscoring its potential for pharmaceutical formulation development.

Objective To investigate the histological and cellular bases for the improvement of portal hypertension(PH)by observing liver histopathological changes after treatment in patients with cirrhotic portal hypertension,and to provide a basis for clinical drug development.Methods A total of 322 patients with hepatitis B cirrhosis who completed 48 weeks of antiviral therapy or combined anti-fibrotic treatment in 20 hospitals across 12 provinces in China from September 2014 to October 2018 were enrolled,and the noninvasive diagnostic criteria for clinically significant portal hypertension(CSPH)from Baveno Ⅶ were used to assess the severity of PH;43 patients with a confirmed diagnosis of CSPH were identified based on liver stiffness measurement(LSM)≥25 kPa before treatment,and according to whether the severity of PH was reduced by≥2 grades after treatment,the patients were divided into PH improvement(n=19)group and PH non-improvement group(n=24).Related data were collected,including demographic data,laboratory tests.Liver fibrosis were assessed,including HE staining and reticular fiber staining;liver microvascular lesions were assessed,including obliterative portal venopathy(OPV),nodular regenerative hyperplasia(NRH),and incomplete septal fibrosis(ISF).Single immunohistochemical staining was performed for von Willebrand factor(vWF),and fibronectin;multiplex immunohistochemical staining was performed for fibrinogen,CD32b,CD31,alpha-smooth muscle actin(α-SMA).The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between two groups.Results After 48 weeks of treatment,43 patients had significant improvements in red blood cell count,alanine aminotransferase,aspartate aminotransferase,aspartate aminotransferase-to-platelet ratio index score,liver fibrosis grade,and PH grade(all P<0.05),among whom 19 patients showed a reduction in PH severity by≥2 grades(PH improvement group),while the remaining patients were enrolled as the PH non-improvement group.There was no significant difference in the outcome of liver fibrosis between the two groups(χ2=3.380,P=0.066).Microvascular lesion assessment showed that compared with the PH non-improvement group,the PH improvement group had significantly lower OPV severity,microvascular density(the expression level of vWF),and expression of fibronectin(all P<0.05),while there were no significant differences in NRH severity,ISF severity,and the expression level of fibrinogen between the two groups(all P>0.05).Cytological evaluation showed no significant differences in the expression levels of CD32b,CD31,and α-SMA between the two groups before and after treatment(all P>0.05),and comparison of the expression levels before and after treatment showed that the PH improvement group had a significant increase in the expression level of CD32b(t=-2.007,P=0.045)and a significant reduction in the expression level of α-SMA(t=2.628,P=0.013).Conclusion The pathological features of PH improvement are associated with liver fibrosis regression and the improvement in liver microvascular lesions,and at the cellular level,PH improvement is associated with the dedifferentiation of liver sinusoidal endothelial cells and the activated phenotype of hepatic stellate cells.

BACKGROUND: The optimal antidepressant dosages remain controversial. This study aimed to analyze the efficacy of antidepressants and characterize their dose-response relationships in the treatments of major depressive disorders (MDD). METHODS: We searched multiple databases, including the Embase, Cochrane Central Register of Controlled Trials, PubMed, and Web of Science, for the studies that were conducted between January 8, 2016, and April 30, 2023. The studies are double-blinded, randomized controlled trials (RCTs) involving the adults (≥18 years) with MDD. The primary outcomes were efficacy of antidepressant and the dose-response relationships. A frequentist network meta-analysis was conducted, treating participants with various dosages of the same antidepressant as a single therapy. We also implemented the model-based meta-analysis (MBMA) using a Bayesian method to explore the dose-response relationships. RESULTS: The network meta-analysis comprised 135,180 participants from 602 studies. All the antidepressants were more effective than the placebo; toludesvenlafaxine had the highest odds ratio (OR) of 4.52 (95% confidence interval [CI]: 2.65-7.72), and reboxetine had the lowest OR of 1.34 (95%CI: 1.14-1.57). Moreover, amitriptyline, clomipramine, and reboxetine showed a linear increase in effect size from low to high doses. The effect size of toludesvenlafaxine increased significantly up to 80 mg/day and subsequently maintained the maximal dose up to 160 mg/day while the predictive curves of nefazodone were fairly flat in different dosages. CONCLUSIONS: Although most antidepressants were more efficacious than placebo in treating MDD, no consistent dose-response relationship between any antidepressants was observed. For most antidepressants, the maximum efficacy was achieved at lower or middle prescribed doses, rather than at the upper limit. REGISTRATION No. CRD42023427480; https://www.crd.york.ac.uk/prospero/display_record.php?
Humans ; Antidepressive Agents/therapeutic use* ; Depressive Disorder, Major/drug therapy* ; Dose-Response Relationship, Drug ; Randomized Controlled Trials as Topic

Fermented traditional Chinese medicine(TCM) has a long history of medicinal use, such as Sojae Semen Praeparatum, Arisaema Cum Bile, Pinelliae Rhizoma Fermentata, red yeast rice, and Jianqu. Fermentation technology was recorded in the earliest TCM work, Shen Nong's Classic of the Materia Medica. Microorganisms are essential components of the fermentation process. However, the contamination of fermented TCM by toxigenic fungi and mycotoxins due to unstandardized fermentation processes seriously affects the quality of TCM and poses a threat to the life and health of consumers. In this paper, the characteristics, microbial composition, and mycotoxin profile of fermented TCM are systematically summarized to provide a theoretical basis for its quality and safety control.
Fermentation ; Mycotoxins/analysis* ; Drugs, Chinese Herbal/analysis* ; Fungi/classification* ; Bacteria/genetics* ; Drug Contamination ; Medicine, Chinese Traditional

PURPOSE: To investigate the incidence and influencing factors of bone loss in patients with spinal cord injury (SCI). METHODS: A retrospective case-control study was conducted. Patients with SCI in our hospital from January 2019 to March 2023 were collected. According to the correlation between bone mineral density (BMD) at different sites, the patients were divided into the lumbar spine group and the hip joint group. According to the BMD value, the patients were divided into the normal bone mass group (t > -1.0 standard deviation) and the osteopenia group (t ≤ -1.0 standard deviation). The influencing factors accumulated as follows: gender, age, height, weight, cause of injury, injury segment, injury degree, time after injury, start time of rehabilitation, motor score, sensory score, spasticity, serum value of alkaline phosphatase, calcium, and phosphorus. The trend chart was drawn and the influencing factors were analyzed. SPSS 26.0 was used for statistical analysis. Correlation analysis was used to test the correlation between the BMD values of the lumbar spine and bilateral hips. Binary logistic regression analysis was used to explore the influencing factors of osteoporosis after SCI. p < 0.05 was considered statistically significant. RESULTS: The incidence of bone loss in patients with SCI was 66.3%. There was a low concordance between bone loss in the lumbar spine and the hip, and the hip was particularly susceptible to bone loss after SCI, with an upward trend in incidence (36% - 82%). In this study, patients with SCI were divided into the lumbar spine group (n = 100) and the hip group (n = 185) according to the BMD values of different sites. Then, the lumbar spine group was divided into the normal bone mass group (n = 53) and the osteopenia group (n = 47); the hip joint group was divided into the normal bone mass group (n = 83) and the osteopenia group (n = 102). Of these, lumbar bone loss after SCI is correlated with gender and weight (p = 0.032 and < 0.001, respectively), and hip bone loss is correlated with gender, height, weight, and time since injury (p < 0.001, p = 0.015, 0.009, and 0.012, respectively). CONCLUSIONS The incidence of bone loss after SCI was high, especially in the hip. The incidence and influencing factors of bone loss in the lumbar spine and hip were different. Patients with SCI who are male, low height, lightweight, and long time after injury were more likely to have bone loss.
Humans ; Spinal Cord Injuries/complications* ; Male ; Female ; Retrospective Studies ; Incidence ; Adult ; Bone Density ; Middle Aged ; Case-Control Studies ; Osteoporosis/etiology* ; Lumbar Vertebrae ; Bone Diseases, Metabolic/etiology* ; Aged ; Risk Factors

Objective:This study applies an integrated SWOT-CLPV framework combined with stakeholder analysis to systematically assess the strengths,weaknesses,opportunities,and threats of China's disease control inspector system,while identifying its control factors,leverage points,key problems,and vulnerabilities.Methods:Drawing on literature review,policy document analysis,and expert interviews with seven public health professionals,we extracted and categorized SWOT elements.A CLPV interaction analysis was conducted alongside stakeholder mapping to evaluate internal dynamics and systemic risks.Results:The inspector system demonstrates strengths in policy innovation and medical-public health integration,with external opportunities stemming from rising public health awareness and digital health advancements.However,the system faces weak endogenous momentum,limited leverage,and prominent control constraints and problem-prone areas,especially among grassroots institutions and inspectors themselves.Cross-sectoral coordination barriers and uneven local implementation contribute to significant institutional vulnerabilities.Conclusion:To enhance implementation and resilience,the system requires capacity building for key actors,improved governance structures,incentive and evaluation reforms,and strengthened coordination mechanisms to support the sustained and adaptive development of public health supervision.

Objective:To investigate the clinicopathological characteristics and prognostic factors of biliary neuroendocrine neoplasms (NENs).Methods:The retrospective cohort study was conducted. The clinicopathological data of 36 patients who underwent surgical treatment for biliary NENs at The First Hospital of Jilin University from January 2013 to December 2023 were collected. There were 22 males and 14 females, aged (59±9)years. Observation indicators: (1) clinicopatholo-gical characteristics of patients; (2) follow-up; (3) prognostic factors analysis of patients. Compari-son of measurement data with normal distribution among multiple groups was conducted using the ANOVA. Comparison of measurement data with skewed distribution among multiple groups was conducted using the Kruskal-Wallis H test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. The Kaplan-Meier method was used to calculate survival rate and plot survival curve, and Log-rank test was used for survival analysis. The Cox risk regression model was used for univariate and multivariate analyses. Results:(1) Clinicopatholo-gical characteristics of patients. None of the 36 patients with biliary NENs had carcinoid syndrome. There were 11 cases with tumor located at gallbladder, 14 cases with tumor located at bile duct, and 11 cases with tumor located at ampulla of Vater. There were significant differences in weight loss and TNM stage among biliary NENs patients with different tumor location ( χ2=9.14, 6.54, P<0.05). Of the 36 patients, there were 12 cases with neuroendocrine tumors, 16 cases with neuroendocrine carcinomas, and 8 cases with mixed neuroendocrine-non-neuroendocrine neoplasms. (2) Follow-up. All 36 patients were followed up for 39(range, 10-93)months. Of the 36 patients, 19 patients experienced tumor recurrence and 16 patients experienced tumor metastasis. There were 18 patients died. The median overall survival time of 36 patients was 30 months, with the 1-, 2-, 3-year overall survival rates of 63.9%, 51.0%, and 35.7%, respectively. The 1-, 2-, 3-year recurrence-free survival rates were 47.5%, 34.1% and 21.3%, respectively. The 1-, 2-, 3-year overall survival rates of 19 patients with tumor recurrence were 55.6%, 55.6% and 27.8%, respectively. The 1-, 2-, 3-year overall survival rates of 17 patients without tumor recurrence were 71.3%, 50.4% and 42.0%, respectively. There was no significant difference in overall survival between patients with and without tumor recurrence ( χ2=0.24, P>0.05). (3) Prognostic factors analysis of patients. Results of multivariate analysis showed that pathological type as neuroendocrine carcinomas and mixed neuroendocrine-non-neuroendocrine neoplasms, non-R 0 margin were independent risk factors influencing overall survival time of patients ( hazard ratio=5.50, 5.33, 14.04, 95% confidence interval as 1.32-23.01, 1.17-24.35, 2.67-73.79, P<0.05). Conclusions:Biliary NENs lack specific clinical manifestations. Poorly differentiated neuroendocrine carcinomas are the most common pathological type. Pathological type as neuroendocrine carcinomas and mixed neuroendocrine-non-neuroendocrine neoplasms, non-R 0 margin are independent risk factors influencing prognosis of patients.