Objective To investigate the effects and related mechanisms of mitochondrial-derived peptide MOTS-c on glycochenodeoxycholic acid (GCDCA)-induced injury in human hepatocytes (THLE-3 cells). Methods THLE-3 cells were cultured in vitro and treated with different concentrations of GCDCA and MOTS-c. The optimal concentrations of GCDCA and MOTS-c were determined by cell counting kit (CCK)-8 method. Subsequently, THLE-3 cells were treated or pre-treated with GCDCA (200 µmol/L), MOTS-c (15, 30, 60 µmol/L), the multidrug resistance protein 2 (MRP2) inhibitor Probenecid (500 µmol/L), and the nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML385 (10 µmol/L). Cell proliferation was assessed by CCK-8 method. Lactate dehydrogenase (LDH) levels in the culture medium were measured by biochemical method. Cell apoptosis rates were determined by flow cytometry. MRP2 messenger RNA (mRNA) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). MRP2 and Nrf2 protein expression levels were analyzed by Western blotting. Results As the concentration of GCDCA increased, the proliferation activity of THLE-3 cells gradually decreased, while LDH activity in the culture medium and apoptosis levels increased, and the expression levels of MRP2 in the cells decreased (all P<0.05). Treatment with 30 and 60 µmol/L MOTS-c significantly enhanced the proliferation activity of THLE-3 cells exposed to GCDCA, upregulated the expression of MRP2 and Nrf2, and reduced LDH activity and apoptosis levels (all P<0.05). Co-treatment with Probenecid partially reversed the protective effects of MOTS-c on GCDCA-induced THLE-3 cells injury, while co-treatment with ML385 partially inhibited the induction of MRP2 expression by MOTS-c in THLE-3 cells exposed to GCDCA. Conclusions MOTS-c may alleviate GCDCA-induced injury in human hepatocytes (THLE-3 cells), and its mechanism may be related to the upregulation of MRP2 expression mediated by Nrf2.

Dentatorubral-pallidoluysian atrophy（DRPLA） is a rare autosomal dominant neurodegenerative disease caused by CAG triplet expansion in the atrophin 1 （ATN1） gene. Up to now， the pathogenesis of DRPLA remains unclear. The main clinical features of DRPLA include myoclonus， epilepsy， ataxia， choreoathetosis， and cognitive impairment. DRPLA has great clinical heterogeneity， and the number of CAG repeats is negatively correlated with age of onset and disease severity. Some patients with late-onset DRPLA may have atypical manifestations without typical imaging changes， which brings challenges to the diagnosis of the disease. This article reviews the pathogenesis， pathological features， clinical and imaging manifestations， diagnosis， and potential treatment of DRPLA， in order to deepen the understanding of this disease.
Ataxia ; Myoclonus

Objective To evaluate the surgical efficacy of unilateral pneumonectomy for the treatment of tuberculous destroyed lung, analyze the causes of severe postoperative complications, and explore clinical management strategies. Methods A retrospective analysis was conducted on the clinical data of patients with tuberculous destroyed lung who underwent unilateral pneumonectomy at the Public Health Clinical Center of Chengdu from 2017 to 2023. Postoperative severe complications were statistically analyzed. Patients were divided into a non-severe complication group and a severe-complication group, and the causes, management, and outcomes of complications were analyzed. Results A total of 134 patients were included, comprising 69 males and 65 females, with a mean age of 17-73 (40.43±12.69) years. There were 93 patients undergoing left pneumonectomy and 41 patients undergoing right pneumonectomy. Preoperative sputum smear was positive in 35 patients, all of which converted to negative postoperatively. There were 58 patients with hemoptysis preoperatively, and none experienced hemoptysis postoperatively. Postoperative incisional infection occurred in 8 (5.97%) patients, and postoperative pulmonary infection in 26 (19.40%) patients. Severe postoperative complications occurred in 17 (12.69%) patients, including empyema in 9 (6.72%) patients, bronchopleural fistula with empyema in 1 (0.75%) patient, severe pneumonia in 3 (2.24%) patients, postpneumonectomy syndrome in 1 (0.75%) patient, chylothorax in 1 (0.75%) patient, ketoacidosis in 1 (0.75%) patient, and heart failure with severe pneumonia in 1 (0.75%) patient. Perioperative mortality occurred in 2 (1.49%) patients, both of whom underwent right pneumonectomy. Multivariate logistic regression analysis revealed that a history of ipsilateral thoracic surgery, concomitant Aspergillus infection, and greater blood loss were independent risk factors for severe complications following unilateral pneumonectomy for tuberculous destroyed lung (P<0.05). Conclusion Unilateral pneumonectomy for patients with tuberculous destroyed lung can significantly improve the clinical cure rate, sputum conversion rate, and hemoptysis cessation rate. However, there is a certain risk of severe perioperative complications and mortality, requiring thorough perioperative management and appropriate management of postoperative complications.

Background The affinity between placental transporters and perfluoroalkyl substances (PFAS) could affect the placental transport and toxicity of PFAS, while the study on the interaction between PFAS and placental transporters is limited. Objective To explore interactions between PFAS and placental transporters using molecular docking, and to provide a theoretical basis for PFAS toxicity prediction and fetal health risk assessment. Methods Fifteen PFAS compounds, each conformationally sampled and energy-minimized, and 16 placental transporters, represented by their 3D structures, were imported into a molecular docking software (MOE 20140901). For each PFAS, 30 distinct conformations were generated and docked into the active pockets of the transporters using a semi-flexible docking mode. Docking poses were primarily scored and ranked based on their calculated binding free energy (ΔG, kcal·mol⁻¹), with additional consideration given to hydrogen bonding interactions and the ligand's root mean square deviation (RMSD) at the binding site; the top 20 poses for each complex were subsequently output. Optimal binding configurations were identified as those exhibiting a relatively low binding free energy (ΔG ranging from −3 to −10 kcal·mol⁻¹), well-defined hydrogen bonds, and an RMSD ≤ 2.0 Å. The binding capabilities of the PFAS to the placental transporters were then evaluated based on these optimal docking results. Results The PFAS could bind to the placental transporters, with structural specificity. For example, the binding capabilities increased as the carbon chain length of PFAS increased, and it was also higher for PFOS alternatives than for PFOS. Besides, the binding capabilities of sulfonic PFAS with the same carbon chain length was also stronger than that of carboxylic PFAS. For example, the binding capabilities of PFOS (C8) to 15 placental transporters was higher than that of PFOA (C8), except for glucose transporter 1 (PFOS vs. PFOA: −4.14 vs. −4.14). Further, PFAS might be bound to the placental transporter through hydrogen, ionic, and hydrophobic interactions. Conclusion PFAS are able to bind the placental transporters, and its toxicity and exposure risk can’t be ignored.

Compounds isolated from Epimedium include the total flavonoids of Epimedium , icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium , its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
Male ; Epimedium/chemistry* ; Humans ; Genitalia, Male/drug effects* ; Flavonoids/therapeutic use* ; Animals

OBJECTIVE: To evaluate the efficacy and safety of a hospital-made resuscitation pack, a Chinese medicinal herbal compound formula designed to enhance recovery in post-bronchoscopy patients. METHODS: In this randomized, single-blind, placebo-controlled clinical trial, eligible patients were randomly assigned 1:1 to either the treatment or control groups. The patients in the treatment group applied the resuscitation pack, which contained aromatic compounded Chinese herbs. The patients in the control group applied a hospital-made, single herb placebo pack. Packs were placed on the Tiantu (CV 22) acupuncture point for 4 h as soon as the bronchoscopy finished. Efficacy indicators, such as recovery time, patients' symptoms including nausea and dizziness, and adverse events (AEs) were observed and compared. The outcome indices were evaluated at baseline, 1 and 24 h after the bronchoscopy. Subgroup analysis was further performed by patients' age and depth of sedation. RESULTS: When applying generalized estimating equations (GEE) to evaluate the intensity of post-bronchoscopy nausea and vomiting, the intensity was lower in the treatment group (163 cases) compared with the control group (162 cases; 95% CI: 0.004, 0.099, P=0.03]. Also, significantly lower intensity of nausea was observed in the 60-70 years of age subgroup (95% CI: 0.029, 0.169, P=0.006) and deep sedation subgroup (95% CI: 0.002, 0.124; P=0.04). There was no significant difference in dizziness between two groups by GEE (95% CI: -0.134, 0.297; P=0.459). In addition, no serious AEs were observed in either group. CONCLUSIONS Our study found that the resuscitation pack markedly improved patients' symptoms by reducing nausea and vomiting after bronchoscopy without AEs, compared with placebo in the perioperative period. (Trial registration No. ChiCTR2000038299).
Humans ; Male ; Middle Aged ; Female ; Bronchoscopy/adverse effects* ; Single-Blind Method ; Aged ; Drugs, Chinese Herbal/adverse effects* ; Treatment Outcome ; Resuscitation ; Adult ; Medicine, Chinese Traditional

Coronavirus disease 2019 (COVID-19) is an acute infectious respiratory disease that has been prevalent since December 2019. Chinese medicine (CM) has demonstrated its unique advantages in the fight against COVID-19 in the areas of disease prevention, improvement of clinical symptoms, and control of disease progression. This review summarized the relevant material components of CM in the treatment of COVID-19 by searching the relevant literature and reports on CM in the treatment of COVID-19 and combining with the physiological and pathological characteristics of the novel coronavirus. On the basis of sorting out experimental methods in vivo and in vitro, the mechanism of herb action was further clarified in terms of inhibiting virus invasion and replication and improving related complications. The aim of the article is to explore the strengths and characteristics of CM in the treatment of COVID-19, and to provide a basis for the research and scientific, standardized treatment of COVID-19 with CM.
Humans ; Drugs, Chinese Herbal/pharmacology* ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/therapy* ; Medicine, Chinese Traditional/methods* ; Antiviral Agents/pharmacology* ; Animals

OBJECTIVE: Resveratrol (Res) is a promising anticancer drug against hepatocellular carcinoma (HCC), but whether its anti-HCC effects implicate mitophagy remains unclear. Therefore, we aimed to explore the specific role of Res in mitophagy and the related mechanisms during the treatment of HCC. METHODS: HepG2 cells and tumor-grafted nude mice were used to investigate the effects of low-, middle- and high-dose of Res on HCC progression and mitophagy in vitro and in vivo, respectively. A series of approaches including cell counting kit-8, flow cytometry, wound healing and transwell assays were used to evaluate tumor cell functions. Transmission electron microscopy, immunofluorescence and Western blotting were used to assess mitophagy. Mitochondrial oxygen consumption rate, reactive oxygen species and membrane potential were used to reflect mitochondrial function. After disrupting the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), miR-143-3p, and ribonucleoside reductase M2 (RRM2), the effects of the MALAT1/miR-143-3p/RRM2 axis on cell function and mitophagy under Res treatment were explored in vitro. Additionally, dual-luciferase reporter and chromatin immunoprecipitation were used to confirm interactions between target genes. RESULTS: Res significantly inhibited the proliferation and promoted apoptosis of HCC cells in vitro, while significantly suppressing tumor growth in a dose-dependent manner and inducing mitophagy and mitochondrial dysfunction in vivo. Interestingly, MALAT1 was highly expressed in HCC cells and its knockdown upregulated miR-143-3p expression in HCC cells, which subsequently inhibited RRM2 expression. Furthermore, in nude mice grafted with HCC tumors and treated with Res, the expression of MALAT1, miR-143-3p and RRM2 were altered significantly. In vitro data further supported the targeted binding relationships between MALAT1 and miR-143-3p and between miR-143-3p and RRM2. Therefore, a series of cell-based experiments were carried out to study the mechanism of the MALAT1/miR-143-3p/RRM2 axis involved in mitophagy and HCC; these experiments revealed that MALAT1 knockdown, miR-143-3p mimic and RRM silencing potentiated the antitumor effects of Res and its activation of mitophagy. CONCLUSION Res facilitated mitophagy in HCC and exerted anti-cancer effects by targeting the MALAT1/miR-143-3p/RRM2 axis. Please cite this article as: Feng CY, Cai CS, Shi XQ, Zhang ZJ, Su D, Qiu YQ. Resveratrol promotes mitophagy via the MALAT1/miR-143-3p/RRM2 axis and suppresses cancer progression in hepatocellular carcinoma. J Integr Med. 2025; 23(1): 79-91.
Humans ; MicroRNAs/genetics* ; Liver Neoplasms/metabolism* ; Carcinoma, Hepatocellular/metabolism* ; Mitophagy/drug effects* ; Resveratrol/pharmacology* ; Animals ; Mice, Nude ; RNA, Long Noncoding/genetics* ; Hep G2 Cells ; Mice ; Disease Progression ; Mice, Inbred BALB C

Objective:To explore the risk factors for postoperative adverse events in older persons with gastrointestinal malignancies and thus provide reference for selection of surgery and evaluation of such patients.Methods:An observational study design was employed, the study cohort comprising patients aged 65 years and over with gastrointestinal malignancies who underwent elective surgery in Peking University Cancer Hospital from 2008 to 2022. In this study, we compared the clinical characteristics (disease type, tumor stage), surgical safety (combined organ resection, operation duration, comorbidities), and treatment outcomes (postoperative complications, unplanned reoperation, and perioperative mortality) of these patients. Multivariate logistic regression analysis was conducted to identify risk factors associated with adverse outcomes.Results:The study cohort comprised 10,135 patients, of whom 74.7% (7,568) were 65–75 years old (excluding 75 years old), 23.6% (2,391) 75–85 years old (excluding 85 years old), and 1.7% (176) ≥85 years old. The type of cancer was colorectal in 63.4% (6,427 patients) and gastric in 36.6% (3,708); 62.0% (6,284/10,135)of the patients had stage II or III disease. The proportion of stage III and stage IV tumors was higher in patients aged over 85 years (47.4% [73/154) and 11.0% [17/154]), respectively, than in those aged 75–85 years (41.6% [854/2 051) and 8.2% [168/2 051]), respectively, and those aged 65–75 years (40.1% [2,576/6,431) and 10.9% [700/6,431]); these differences are statistically significant (χ 2=27.95, P<0.01). Comorbidity was present in 50.6% (5,128/10,135) of the whole study cohort, comprising 58.0% (102/176) of those aged over 85 years, this being significantly higher than the 56.3% (1,346/2,391) in those aged 75–85 years and 48.6% (3,678/7,568) of those aged 65–75 years. The main comorbidities were hypertension (37.3%), diabetes (16.4%), and cardiovascular and cerebrovascular diseases (14.0%). Minimally invasive surgery was performed on 36.9% (3,740/10,135) of the whole study cohort, the 38.4% in 65–75 years old patients being significantly higher than the 32.5% in those aged 75–85 years and the 29.0% in those aged over 85 years; these differences are statistically significant (χ 2=31.97, P<0.01). Preoperative neoadjuvant therapy was administered to 9.1% (924/10,135) of the whole study cohort, the proportion of patients receiving preoperative neoadjuvant therapy being significantly higher in those aged 65–75 years (11.1%) than in those aged 75–85 years (3.4%) and over 85 years (0.6%); these differences are statistically significant (χ 2=148.98, P<0.01). Combined organ resection was performed in 4.9% (496/10,135) of the whole study cohort, the proportion undergoing combined organ resection being significantly lower in those aged over 85 years (2.3%) than in those aged 65–75 years (5.3%) and 75–85 years (3.8%); these differences are statistically significant (χ 2=11.20, P<0.01). The mean operating time was (182.2±76.8) minutes, being significantly higher in those aged 65–75 years (186.6±78.3 minutes) than in those aged 75–85 years (169.4±71.3 minutes) and over 85 years (153.2±53.7 minutes); these differences are statistically significant ( F=46.85, P<0.01). The overall incidence of postoperative complications was 10.9% (802/7,384); the incidence did not differ significantly between the three groups ( P>0.05). The incidence of unplanned reoperation was 1.9% (193/10,135) and of death during hospitalization 0.3% (32/10,135). The perioperative mortality in the three groups was 1.1%, 0.5% and 0.2% in those aged over 85, 75–85, and 65–75 years, respectively. These differences are statistically significant (χ 2=9.71, P<0.01). Among the patients with postoperative complications, 15.0% (120/802) underwent unplanned reoperation, which had a perioperative mortality of 1.0% (8/802), these rates being significantly higher than those for unplanned reoperation (1.1%, 73/6,582) and perioperative mortality (0.4%, 24/6,582) in patients without complications (all P<0.01). The median length of hospital stay was 11 days in patients aged over 85 years; this is significantly longer than the 9 days in those aged 65–75 years and 10 days in those aged 75–85 years (H=37.00, P<0.01). Multivariate logistic regression analysis showed that tumor stage IV (OR=1.56, 95%CI: 1.24–1.96, P<0.01), comorbidities (OR=1.26, 95%CI: 1.08–1.47, P<0.01), open surgery (OR=1.33, 95%CI: 1.13–1.56, P<0.01), and operation time >180 minutes (OR=1.82, 95%CI:1.53–2.15, P<0.01) were risk factors for adverse outcomes. Conclusion:Older patients with gastrointestinal tumors who have comorbidities and stage IV disease and undergo open surgery with a longer operation time are at higher risk of adverse outcomes than patients without these characteristics.

Objective·To analyse the structure of non-canonical polycomb repressive complex 1.6(PRC1.6)by negative staining and transmission electron microscopy(TEM),and obtain the three-dimensional(3D)profile information of human PRC1.6 heptameric complex.Methods·Seven PRC1.6 components,RNF2,PCGF6,RYBP,L3MBTL2,CBX3,E2F6,and TFDP1,were cloned into the pMLink vector with a 6×His-3×Flag tag at the N-terminus,respectively.The proteins were expressed in Expi293F cells grown in suspension cultures by using transfection with polyethylenimine.The tagged proteins were isolated via affinity purification with anti-DYKDDDDK G1 affinity resin,followed by gel filtration chromatography with Superdex 200 Increase 10/300 GL and glycerol density gradient centrifugation.The components of the PRC1.6 heptameric complex were confirmed by liquid chromatography-tandem mass spectrometry(LC-MS/MS).The in vitro ubiquitination activity and nucleosome-binding affinity of the purified heptameric complex were verified by the ubiquitination activity assay and the electrophoretic mobility shift assay(EMSA).The protein samples were stained by uranyl acetate and observed by TEM.The 3D information of the PRC1.6 complex was studied by single particle analysis.To predict the localization of the seven components within the structure model of PRC1.6 complex,the structure models of proteins in Protein Data Bank(PDB)were docked into the electron density map of PRC1.6 complex by using UCSF Chimera software.Results·The PRC1.6 complex with high purity and good homogeneity was obtained by eukaryotic expression,affinity purification,gel filtration chromatography and glycerol density gradient centrifugation,and confirmed as the heptameric complex by LC-MS/MS.The purified proteins showed ubiquitination activity and nucleosome-binding affinity in vitro.The 3D structure of the PRC1.6 heptameric complex with a resolution of 15.2 ?(1 ?=10-10 m)was preliminarily resolved by negative staining,TEM,and single particle analysis.The available structure models of RNF2,PCGF6,RYBP,L3MBTL2,CBX3,and DP1 proteins,as well as the predicted E2F6 structure by AlphaFold2,were docked into the reconstructed density map of PRC1.6 complex.The position of each component in the complex was preliminarily confirmed.Conclusion·The 3D structural model of the human PRC1.6 heptameric complex is obtained by negative staining,TEM,and single particle analysis.