BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

Asthma is a chronic inflammatory disease involving multiple inflammatory cells and cytokines. Its pathogenesis is complex, involving various cells and cytokines. Traditional Chinese medicine(TCM) theory suggests that the pathogenesis of asthma is closely related to the dysfunction of internal organs such as the lungs, spleen, and kidneys. In contrast, modern immunological studies have revealed the central role of T helper 1(Th1)/T helper 2(Th2) and T helper 17(Th17)/regulatory T(Treg) cellular immune imbalance in the pathogenesis of asthma. Th1/Th2 imbalance is manifested as hyperfunction of Th2 cells, which promotes the synthesis of immunoglobulin E(IgE) and the activation of eosinophil granulocytes, leading to airway hyperresponsiveness and inflammation.Meanwhile, Th17/Treg imbalance exacerbates the inflammatory response in the airways, further contributing to asthma pathology.Currently, therapeutic strategies for asthma are actively exploring potential targets for regulating the balance of Th1/Th2 and Th17/Treg immune responses. These targets include cytokines, transcription factors, key proteins, and non-coding RNAs. Precisely regulating the expression and function of these targets can effectively modulate the activation and differentiation of immune cells. In recent years,traditional Chinese medicine active ingredients have shown unique potential and prospects in the field of asthma treatment. Based on this, the present study systematically summarizes the efficacy and specific mechanisms of TCM active ingredients in treating asthma by regulating Th1/Th2 and Th17/Treg immune balance through literature review and analysis. These active ingredients, including flavonoids, terpenoids, polysaccharides, alkaloids, and phenolic acids, exert their effects through various mechanisms, such as inhibiting the activation of inflammatory cells, reducing the release of cytokines, and promoting the normal differentiation of immune cells. This study aims to provide a solid foundation for the widespread application and in-depth development of TCM in asthma treatment and to offer new ideas for clinical research and drug development of asthma.
Asthma/genetics* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Th2 Cells/drug effects* ; Th17 Cells/drug effects* ; T-Lymphocytes, Regulatory/drug effects* ; Th1 Cells/drug effects* ; Animals ; Cytokines/immunology* ; Medicine, Chinese Traditional

Objective： To analyze the symptoms, diagnosis and treatment of upper urinary tract calculi patients combined with mild and moderate benign prostatic hyperplasia (BPH) after ureteral stent implantation. Methods： One hundred and six BPH patients who were hospitalized for upper urinary tract calculi and had ureteral stents retained from January 2019 to December 2022 were selected and divided into 2 weeks group and 4 weeks group according to the time of removal of ureteral stents after surgery. Their general clinical data were analyzed and compared. International Prostatic Symptom Scale (IPSS), postoperative ureteral Stent Symptom Questionnaire (USSQ), and incidence of adverse events after ureteral stent removal were recorded before and after removal. Results： The scores of IPSS were significantly increased in all patients, and symptoms in urinary tract had improved significantly after discharge (P<0.05). Compared with the 2 weeks group, the USSQ score of the 4 weeks group was significantly increased (P<0.05). And no significant adverse event was observed in the 2 weeks group after the removal of ureteral sten. Conclusion： IPSS score and USSQ score increased significantly during stent implantation in BPH patients with lithiasis. And complications increased significantly over time. Following thorough clinical assessment, early ureteral stent removal demonstrates both safety and efficacy, representing an optimal therapeutic approach in selected cases.
Humans ; Male ; Prostatic Hyperplasia/surgery* ; Stents ; Ureter/surgery* ; Aged ; Middle Aged ; Urinary Calculi/surgery* ; Ureteral Calculi/surgery*

OBJECTIVE: To investigate the effectiveness of Xuanshen Yishen Decoction (XYD) in the treatment of hypertension. METHODS: Hospital electronic medical records from 2019-2023 were utilized to emulate a randomized pragmatic clinical trial. Hypertensive participants were eligible if they were aged ⩾40 years with baseline systolic blood pressure (BP) ⩾140 mm Hg. Patients treated with XYD plus antihypertensive regimen were assigned to the treatment group, whereas those who followed only antihypertensive regimen were assigned to the control group. The primary outcome assessed was the attainment rate of intensive BP control at discharge, with the secondary outcome focusing on the 6-month all-cause readmission rate. RESULTS: The study included 3,302 patients, comprising 2,943 individuals in the control group and 359 in the treatment group. Compared with the control group, a higher proportion in the treatment group achieved the target BP for intensive BP control [8.09% vs. 17.5%; odds ratio (OR)=2.29, 95% confidence interval (CI)=1.68 to 3.13; P<0.001], particularly in individuals with high homocysteine levels (OR=3.13; 95% CI=1.72 to 5.71; P<0.001; P for interaction=0.041). Furthermore, the 6-month all-cause readmission rate in the treatment group was lower than in the control group (hazard ratio=0.58; 95% CI=0.36 to 0.91; P=0.019), and the robustness of the results was confirmed by sensitivity analyse. CONCLUSIONS XYD could be a complementary therapy for intensive BP control. Our study offers real-world evidence and guides the choice of complementary and alternative therapies. (Registration No. ChiCTR2400086589).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antihypertensive Agents/pharmacology* ; Blood Pressure/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Hypertension/physiopathology* ; Patient Readmission ; Treatment Outcome

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective To investigate the effect of Jichuan decoction on defecation in rats with slow transit constipation(STC).Methods A total of 36 SD rats were divided into model group,experimental group and control group.Except the control group,STC rat models were established in the other two groups by gavage of 2％rhein acid suspension.The experimental group was given 170％Jichuan decoction of 10 mL·kg-1 by gavage,while the control group and model group were given with 0.9％NaCl by gavage,once a day for 30 days.Fecal dry-wet weight ratio and colon transport time were observed by fecal weighing and recording of first fecal discharge time;substance P(SP)and vasoactive peptide(VIP)contents in plasma were detected by kit;changes in intestinal flora were detected by real-time fluorescent quantitative polymerase chain reaction(qRT-PCR).Results The dry-wet ratio of feces in control group,model group and experimental group were(44.86±4.40)％,(53.44±3.52)％and(44.28±4.33)％,respectively;the colon transport time were(340.17±34.91),(424.67±37.26)and(377.36±38.87)min,respectively;plasma SP were(79.86±7.56),(60.30±2.41)and(78.84±5.83)pg·mL-1,respectively;plasma VIP were(30.56±2.87),(23.38±6.62)and(28.39±2.37)pg·mL-1,respectively;the numbers of Bifidobacterium were 7.77±0.04,5.19±0.09 and 7.45±0.03,respectively;the numbers of Lactobacillus were 6.40±0.07,4.10±0.05 and 6.36±0.08,respectively.There were statistically significant differences in the above indexes between model group and control group,and between experimental group and model group(P＜0.01,P＜0.05).Conclusion Jichuan decoction can improve the defecation of rats with slow transit constipation.

This study systematically analyzed the current status of outcomes in randomized controlled trial(RCT) of traditional Chinese medicine(TCM) treatment of diabetic kidney disease(DKD), aiming to provide a reference for constructing the core outcome set(COS) of TCM treatment of DKD. The clinical RCTs of TCM treatment of DKD that were published from January 2019 to March 2024 were retrieved from seven databases: CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, and Web of Science. The risk of bias was assessed and outcome indicators were qualitatively analyzed. A total of 323 RCTs were included, reporting 199 outcome indicators with the frequency of 3 744 in seven indicator domains: TCM syndromes(196 times, 5.24%), symptoms and signs(275 times, 7.35%), physical and chemical examinations(2 820 times, 75.32%), safety events(422 times, 11.27%), long-term prognosis(21 times, 0.56%), quality of life(9 times, 0.24%), and economic evaluation(1 time, 0.02%). The three most frequently applied outcome indicators were total clinical response rate(268 times, 82.97%), serum creatinine(251 times, 77.71%), and urea nitrogen(206 times, 63.78%). The outcomes in the studies of TCM treatment of DKD had the limitations of high risk of bias, lack of standardization of TCM syndromes and efficacy evaluation, neglect of endpoint indicators, large differences in endpoint indicators and time points of measurement, unclear primary and secondary outcomes, few application of long-term prognosis, quality of life, and economic indicators, and insufficient reporting of safety events. In the future, efforts should be made to actively promote the construction of COS in the studies about the TCM treatment of DKD and enhance the quality of the clinical studies.
Humans ; Randomized Controlled Trials as Topic ; Diabetic Nephropathies/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Treatment Outcome ; Medicine, Chinese Traditional ; Quality of Life

Objective:To explore the mechanism of Ion peptidase 1,mitochondrial(LONP1)in the progression of castration-resistant prostate cancer(CRPC). Methods:The expression levels of LONP1,N-Myc downstream-regulated gene 1(NDRG1)and androgen receptor(AR)proteins in benign prostatic hyperplasia cell line BPH-1,androgen-dependent human prostate cancer cell line LNCaP and castration-resistant prostate cancer(CRPC)cell line PC3 were examined by Western blotting.Recombinant vector carrying full-length LONP1 gene was delivered into LNCaP cells via lentiviral infection to establish stable LONP1-overexpressing(OE-LONP1)cell line,and LNCaP cells transfected with empty vector was used as the corresponding negative control(OE-NC).shRNA specifically targeting LONP1 gene(shLONP1)was delivered into PC3 cells to establish stable LONP1-silencing cell line,and PC3 cells transfected with empty shRNA vector(shNC)was used as the negative control.The effect of LONP1-overexpression and silencing on cell proliferation and invasion was analyzed by CCK-8 assay,colony formation assay and Transwell invasion assay in OE-LONP1 and shLONP1 cell lines.The effect of LONP1 on the AR/DNRG1 signaling axis was analyzed by co-immunoprecipitation assay and chromatin immunoprecipitation assay.The effect of NDRG1-silencing on the proliferation and invasion of shLONP1-expressing PC3 cells was evaluated by CCk-8 assay and Transwell assay.Tumor xenograft model was established by subcutaneously inoculating shLONP1-expressing PC3 cells and the negative control cells(PC3-shNC cells)into BALB/c nude mice.The mice were treated with DMSO or AR antagonist enzalutamide(ENZ).Then,the expression level of Ki-67 in tumor tissues was examined by immunohistochemical staining,and the cell apoptosis in tumor tissues was evaluated by TUNEL assay. Results:Compared with BPH-1 cells,LNCaP cells had lower(P＜0.05)while PC3 cells had higher(P＜0.05)expression level of LONP1 protein.The expression of AR and NDRG1 were inhibited in LNCaP cells when LONP1 was overexpressed(P＜0.05),whereas the expression of AR and NDRG1 were increased in PC3 cells when LONP1 was silenced(P＜0.05).The proliferation and invasion of LNCaP cells were promoted when LONP1 was overexpressed(P＜0.05),whereas the proliferation and invasion of PC3 cells were suppressed when LONP1 was knocked-down(P＜0.05).LONP1 can directly bind with AR to recognize the androgen response element(ARE)of NDRG1,which further inhibits the AR/NRDG1 signaling pathway to promote the progression of prostate cancer.The treatment of xenograft tumors in mouse models showed that both LONP1-silencing and ENZ application could inhibit tumor growth,and the best inhibitory effect was observed in mice treated with LONP1-silencing in combination with ENZ.The results of immunohistochemical staining and TUNEL assay indicated that the tumor tissues in the shLONP1+ENZ group had lower level of Ki-67 expression and higher level of cell apoptosis(P＜0.001). Conclusion:LONP1 is highly expressed in CRPC cell line PC3,and promotes prostate cancer progression by inhibiting AR/NDRG1 signaling transduction.

Humans ; Otosclerosis/surgery* ; Stapes ; Stapes Surgery/adverse effects* ; Arteries