Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

Objective To evaluate the effect of a multidisciplinary collaborative quality control management (hereinafter referred to as "QC management") on improving the performance of biological safety cabinets in hospital. Methods A total of 63 ClassⅡbiological safety cabinets in active use at Peking University Third Hospital were selected as the study subjects using the before-after study mode. Conventional management was implemented on the biological safety cabinets from 2018 to 2021. QC management was used in 2022. The compliance of biological safety cabinets management norm and performance differences under the two models were compared. Results The median and the 25th and 75th percentiles [M(P₂₅, P₇₅)] of the service life among these 63 biological safety cabinets were 3 (1,6) years. The overall performance pass rate and inflow velocity pass rate of biological safety cabinets were higher in the QC management than that in the conventional management (90.5% vs 65.1%, 96.8% vs 84.1%, both P<0.05). However, there was no significant difference in downflow velocity, high-efficiency particulate air filter integrity, cleanliness, airflow smoke pattern, noise, and illumination pass rates of biosafety cabinets before and after the implementation of QC management (79.4% vs 88.9%, 90.5% vs 100.0%, 96.8% vs 100.0%, 85.7% vs 100.0%, 100.0% vs 100.0%, and 85.7% vs 96.8%, respectively; all P>0.05). Conclusion sQC management improves the standardization of biological safety cabinet management and key performance indicators in hospital.

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: 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 investigate the associations between eight serum per- and polyfluoroalkyl substances (PFASs) and regional fat depots, we analyzed the data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 cycles. METHODS: Multiple linear regression models were developed to explore the associations between serum PFAS concentrations and six fat compositions along with a fat distribution score created by summing the concentrations of the six fat compositions. The associations between structurally grouped PFASs and fat distribution were assessed, and a prediction model was developed to estimate the ability of PFAS exposure to predict obesity risk. RESULTS: Among females aged 39-59 years, trunk fat mass was positively associated with perfluorooctane sulfonate (PFOS). Higher concentrations of PFOS, perfluorohexane sulfonate (PFHxS), perfluorodecanoate (PFDeA), perfluorononanoate (PFNA), and n-perfluorooctanoate (n-PFOA) were linked to greater visceral adipose tissue in this group. In men, exposure to total perfluoroalkane sulfonates (PFSAs) and long-chain PFSAs was associated with reductions in abdominal fat, while higher abdominal fat in women aged 39-59 years was associated with short-chain PFSAs. The prediction model demonstrated high accuracy, with an area under the curve (AUC) of 0.9925 for predicting obesity risk. CONCLUSION PFAS exposure is associated with regional fat distribution, with varying effects based on age, sex, and PFAS structure. The findings highlight the potential role of PFAS exposure in influencing fat depots and obesity risk, with significant implications for public health. The prediction model provides a highly accurate tool for assessing obesity risk related to PFAS exposure.
Humans ; Fluorocarbons/blood* ; Female ; Adult ; Middle Aged ; Male ; Environmental Pollutants/blood* ; Abdominal Fat ; Nutrition Surveys ; Alkanesulfonic Acids/blood* ; Obesity ; Environmental Exposure

Objective To explore the accumulated effects of physical activity,sedentary behavior,and sleep on cardiorespiratory fitness(CRF)among college students and provide effective measures for enhancing their CRF. Methods From May to June in 2023,223 college students aged 18 to 24 years old were recruited from Tianjin University of Science and Technology for a 24 hours activity behavior survey and CRF testing.Compositional analysis was employed to investigate the relationships of physical activity,sedentary behavior,and sleep with CRF.Isotemporal substitution models were established to predict the effects of substituting various activity behaviors on CRF.Results The proportion of time spent on moderate-to-vigorous physical activity(MVPA)was positively correlated with CRF of college students(β=6.40,P=0.002),while the proportion of time spent on sedentary behavior was negatively correlated with CRF(β=-3.02,P=0.004).Light physical activity(LPA)and sleep were not correlated with CRF(β=-1.06,P=0.504).Isotemporal substitution results for 15-min increments showed that replacing other activity behaviors with MVPA significantly increased the CRF of college students[SB:1.72 mL/(kg·min),95% CI=0.94-2.51;LPA:1.82 mL/(kg·min),95% CI=0.95-2.68;sleep:1.64 mL/(kg·min),95% CI=0.84-2.45].In the dose-response relationship from -30 min to 30 min,reallocating time from other behaviors to MVPA had greater adverse effect on CRF than reallocating time from MVPA to other behaviors.Among all the substitutions,replacing LPA with MVPA had the most beneficial effect on improving CRF.Additionally,a 5-min increment was considered the optimal tipping point for MVPA replacing other activities.Conclusions This study underscores the importance of participating in MVPA for improving the CRF of college students.The isotemporal substitution model provides clear goals for the allocation of time for these behaviors,aiding in future intervention measure development and policy-making.
Humans ; Sedentary Behavior ; Sleep ; Students ; Cardiorespiratory Fitness ; Exercise ; Young Adult ; Adolescent ; Universities ; Male ; Female

Objective To explore the effects of time reallocation among moderate-to-vigorous physical activity(MVPA),light physical activity(LPA),sedentary behavior(SB),and sleep on a body shape index(ABSI),body roundness index(BRI),conicity index(CI),and relative fat mass(RFM)of college students by the compositional isotemporal substitution method,thus providing measures for alleviating the obesity problem of college students. Methods Two hundred and ten college students(111 males and 99 females)aged 18-22 years old were recruited from Tianjin University of Science and Technology from April to June in 2023.Three-dimensional acceleration sensors were used to collect data of MVPA,LPA,SB,and sleep of college students.The body height,body weight,and waist circumference were measured,and four novel obesity indicators(ABSI,BRI,CI,and RFM)were calculated.The effects of substituting each activity behavior for 15 min on the obesity indicators were predicted,and the dose-effect relationship was explored at intervals of 5 min from -30 to 30 min.Results MVPA was negatively correlated with ABSI(β=-0.03,P=0.001),BRI(β=-0.27,P=0.049),CI(β=-0.10,P=0.001),and RFM(β=-9.95,P=0.004).LPA was negatively correlated with CI(β=-0.05,P=0.011)and RFM(β=-8.74,P=0.007).Neither SB nor sleep had correlations with ABSI,BRI,CI,and RFM.The results of 15 min isotemporal substitutions showed that increasing the MVPA time decreased the ABSI,BRI,CI,and RFM by 0.006-0.008,0.306-0.393,0.162-0.205,and 2.468-2.897,respectively.Decreasing the MVPA time increased the ABSI,BRI,CI,and RFM by 0.012-0.014,0.548-0.632,0.286-0.328,and 4.358-4.748,respectively.In the dose-effect relationship from -30 min to 30 min,MVPA was irreplaceable,and the negative benefits from substituting MVPA for other activity behaviors were much greater than the positive benefits from substituting MVPA for other activity behaviors.Conclusions Future research should take 24 hours activity behaviors as a whole.Increasing the time spent on MVPA and LPA and decreasing the time spent on SB is one of the effective ways to alleviate the obesity problem among college students.
Humans ; Male ; Students ; Female ; Young Adult ; Obesity ; Sleep ; Adolescent ; Exercise ; Universities ; Sedentary Behavior ; Body Mass Index ; Body Weight

Schistosomiasis was once hyper-endemic in Yunnan Province. Following concerted efforts for over 70 years, remarkable achievements have been made for schistosomiasis control in the province. In 2004, the Mid- and Long-term Plan for Schistosomiasis Prevention and Control in Yunnan Province was initiated in Yunnan Province, and the target for transmission control of schistosomiasis was achieved in the province in 2009. Following the subsequent implementation of the Outline for Key Projects in Integrated Schistosomiasis Control Program (2009—2015) and the 13th Five - year Plan for Schistosomiasis Control in Yunnan Province, no acute schistosomiasis had been identified in Yunnan Province for successive 12 years, and no local Schistosoma japonicum infections had been detected in humans, animals or Oncomelania hupensis snails for successive 6 years in the province by the end of 2020. The transmission of schistosomiasis was interrupted in Yunnan Province in 2020. This review summarizes the history of schistosomiasis, changes in schistosomiasis prevalence and progress of schistosomiasis control in Yunnan Province, and proposes the future priorities for schistosomiasis control in the province.

As the predominant toxic constituent within the Aconitum genus, Aconitum alkaloids (ATs) exhibit both significant pharmaceutical value and substantial toxicity, have been widely used in traditional Chinese medicine and the realm of contemporary clinical medicine. However, owing to their high toxicity, inappropriate employment of ATs in pharmaceuticals, edibles, and the environment will pose serious threats to human health, inciting a series of toxic incidents. Consequently, it is very important to develop effective analytical methods. This paper presents a comprehensive review of the advancements in research pertaining to the pretreatment and detection methods in common substrates, including high performance liquid chromatography, liquid chromatography-mass spectrometry and rapid detection methods. To explore the specific sources of ATs in actual poisoning cases, the comprehensive traceability strategy based on plant morphology, chemical fingerprint analysis and DNA barcoding technology was discussed, proposing a comprehensive prospect for the development of ATs analysis and traceability, in order to provide guidance for related research within the forensic science domain.

Objective To predict the potential geographic distribution of Oncomelania hupensis in Yunnan Province using random forest (RF) and maximum entropy (MaxEnt) models, so as to provide insights into O. hupensis surveillance and control in Yunnan Province. Methods The O. hupensis snail survey data in Yunnan Province from 2015 to 2016 were collected and converted into O. hupensis snail distribution site data. Data of 22 environmental variables in Yunnan Province were collected, including twelve climate variables (annual potential evapotranspiration, annual mean ground surface temperature, annual precipitation, annual mean air pressure, annual mean relative humidity, annual sunshine duration, annual mean air temperature, annual mean wind speed, ≥ 0 ℃ annual accumulated temperature, ≥ 10 ℃ annual accumulated temperature, aridity and index of moisture), eight geographical variables (normalized difference vegetation index, landform type, land use type, altitude, soil type, soil textureclay content, soil texture-sand content and soil texture-silt content) and two population and economic variables (gross domestic product and population). Variables were screened with Pearson correlation test and variance inflation factor (VIF) test. The RF and MaxEnt models and the ensemble model were created using the biomod2 package of the software R 4.2.1, and the potential distribution of O. hupensis snails after 2016 was predicted in Yunnan Province. The predictive effects of models were evaluated through cross-validation and independent tests, and the area under the receiver operating characteristic curve (AUC), true skill statistics (TSS) and Kappa statistics were used for model evaluation. In addition, the importance of environmental variables was analyzed, the contribution of environmental variables output by the models with AUC values of > 0.950 and TSS values of > 0.850 were selected for normalization processing, and the importance percentage of environmental variables was obtained to analyze the importance of environmental variables. Results Data of 148 O. hupensis snail distribution sites and 15 environmental variables were included in training sets of RF and MaxEnt models, and both RF and MaxEnt models had high predictive performance, with both mean AUC values of > 0.900 and all mean TSS values and Kappa values of > 0.800, and significant differences in the AUC (t = 19.862, P < 0.05), TSS (t = 10.140, P < 0.05) and Kappa values (t = 10.237, P < 0.05) between two models. The AUC, TSS and Kappa values of the ensemble model were 0.996, 0.954 and 0.920, respectively. Independent data verification showed that the AUC, TSS and Kappa values of the RF model and the ensemble model were all 1, which still showed high performance in unknown data modeling, and the MaxEnt model showed poor performance, with TSS and Kappa values of 0 for 24%(24/100) of the modeling results. The modeling results of 79 RF models, 38 MaxEnt models and their ensemble models with AUC values of > 0.950 and TSS values of > 0.850 were included in the evaluation of importance of environmental variables. The importance of annual sunshine duration (SSD) was 32.989%, 37.847% and 46.315% in the RF model, the MaxEnt model and their ensemble model, while the importance of annual mean relative humidity (RHU) was 30.947%, 15.921% and 28.121%, respectively. Important environment variables were concentrated in modeling results of the RF model, dispersed in modeling results of the MaxEnt model, and most concentrated in modeling results of the ensemble model. The potential distribution of O. hupensis snails after 2016 was predicted to be relatively concentrated in Yunnan Province by the RF model and relatively large by the MaxEnt model, and the distribution of O. hupensis snails predicted by the ensemble model was mostly the joint distribution of O. hupensis snails predicted by RF and MaxEnt models. Conclusions Both RF and MaxEnt models are effective to predict the potential distribution of O. hupensis snails in Yunnan Province, which facilitates targeted O. hupensis snail control.