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

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 investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

OBJECTIVE: To observe the clinical symptoms and MRI outcomes of patients with ruptured lumbar disc herniation(LDH) through a multicenter randomized controlled study, and to evaluate the clinical efficacy and safety of Yiqi Huoxue formula() in the treatment of this disease. METHODS: A total of 160 outpatients and inpatients with ruptured LDH admitted to 4 medical centers from January 2023 to June 2023 were selected and randomly divided into the Yiqi Huoxue formula group and the control group, with 80 patients in each group. In the Yiqi Huoxue formula group, there were 43 males and 37 females, with an age of (41.03±9.56) years and a disease duration of (10.45±25.37) days, and the patients were treated with Yiqi Huoxue formula. In the control group, there were 34 males and 46 females, with an age of (42.14±8.73) years and a disease duration of (11.31±21.14) days;during the acute phase, patients in this group could take celecoxib capsules orally, and methylcobalamin orally at the same time. The Japanese Orthopaedic Association (JOA) score, Oswestry disability index (ODI), changes in the volume of herniated disc tissue on MRI, herniation rate, and absorption rate were recorded at the time of enrollment and during follow-ups at the 3rd, 6th, and 12th month after treatment. RESULTS: A total of 156 patients completed the clinical follow-up, and 4 patients withdrew midway. The clinical symptoms of all patients who completed the study were relieved to varying degrees, and reabsorption of herniated disc tissue was observed in all patients in the Yiqi Huoxue formula group after treatment. For the JOA score:in the Yiqi Huoxue formula group, it was (10.73±2.76) points before treatment and (24.65±2.19) points at the 12th month after treatment;in the control group, it was (11.01±1.20) points before treatment and (17.07±3.26) points at the 12th month after treatment. For the ODI score:in the Yiqi Huoxue formula group, it was (26.21±3.55) points before treatment and (5.65±2.19) points at the 12th month after treatment;in the control group, it was (27.92±2.51) points before treatment and (9.09±2.15) points at the 12th month after treatment. At the 12th month after treatment, the JOA and ODI scores of both groups were better than those before treatment, and the scores of the Yiqi Huoxue formula group were better than those of the control group, with statistically significant differences (P<0.05). In terms of the herniated disc volume and herniation rate on MRI, the Yiqi Huoxue formula group was superior to the control group, with statistically significant differences(P<0.05). Reabsorption occurred in 56.96%(45/79) of patients in the Yiqi Huoxue formula group, which was significantly higher than the 37.66%(29/77) in the control group. CONCLUSION After treatment with Yiqi Huoxue formula, patients with ruptured LDH show significant improvement in clinical symptoms and a marked reduction in the volume of herniated discs. During the follow-up period, no obvious adverse drug reactions are observed in patients, and no recurrence of symptoms is found at the last follow-up, indicating that the formula has safe and reliable efficacy.
Humans ; Male ; Female ; Intervertebral Disc Displacement/drug therapy* ; Adult ; Drugs, Chinese Herbal/adverse effects* ; Middle Aged ; Lumbar Vertebrae

To compare and analyze the clinical manifestations,laboratory characteristics,imaging findings,and treatment outcomes of patients with acute and chronic brucellosis,a retrospective analysis was conducted on 258 patients with brucellosis(202 in the acute group and 56 in the chronic group)hospitalized in Xinkang Hospital in Dalad Banner,Ordos City,Inner Mongolia Autonomous Region,from November 2023 to November 2024.General data,epidemiological characteristics,clinical presentations,laboratory test results,imaging findings,treatment outcomes,and prognosis were collected.The incidences of fever(51.5%vs 7.1%),fatigue(30.2%vs 12.5%),joint pain(42.9%vs 16.1%),and muscle pain(9.9%vs.1.8%)were significantly higher in the acute phase group(all P<0.05).The incidence of osteoarthritis complications was higher in the chronic brucellosis group(51.8%vs 8.9%,χ2=75.697,P<0.01).Univariate ANOVA analysisshowed that the Serum Agglutination Tests(SAT),alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),creatinine(CRE),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),and bone destructionexhibited statistically significant differences between the acute and chronic phases of brucellosis(all P<0.05).Multivariate logistic regression analysis indicated that abnormal ALT(OR=14.18,95%CI:1.11-181.72;P=0.041)and bone destruction(OR=0.16,95%CI:0.04-0.63;P=0.009)were associated with chronic brucellosis.After treatment,all patients experienced have symptom relief in varying degrees,with 157 patients(60.9%)cured and 101 patients(39.1%)symptomatic improved(P<0.01).In conclusion,the incidences of fever,fatigue,and joint pain in patients during the acute phase is significantly higher than that those in patients during the chronic phase,while the incidence of osteoarthritis complications is higher in chronic phase patients.The incidences of abnormal SAT,ALT,AST,TBIL,CRE,CRP,and ESR,and bone destruction varies at different stages of brucellosis.Of those,abnormal ALT and bone destruction show a stronger association with,which can assist the clinical staging of brucellosis.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

To compare and analyze the clinical manifestations,laboratory characteristics,imaging findings,and treatment outcomes of patients with acute and chronic brucellosis,a retrospective analysis was conducted on 258 patients with brucellosis(202 in the acute group and 56 in the chronic group)hospitalized in Xinkang Hospital in Dalad Banner,Ordos City,Inner Mongolia Autonomous Region,from November 2023 to November 2024.General data,epidemiological characteristics,clinical presentations,laboratory test results,imaging findings,treatment outcomes,and prognosis were collected.The incidences of fever(51.5%vs 7.1%),fatigue(30.2%vs 12.5%),joint pain(42.9%vs 16.1%),and muscle pain(9.9%vs.1.8%)were significantly higher in the acute phase group(all P<0.05).The incidence of osteoarthritis complications was higher in the chronic brucellosis group(51.8%vs 8.9%,χ2=75.697,P<0.01).Univariate ANOVA analysisshowed that the Serum Agglutination Tests(SAT),alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),creatinine(CRE),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),and bone destructionexhibited statistically significant differences between the acute and chronic phases of brucellosis(all P<0.05).Multivariate logistic regression analysis indicated that abnormal ALT(OR=14.18,95%CI:1.11-181.72;P=0.041)and bone destruction(OR=0.16,95%CI:0.04-0.63;P=0.009)were associated with chronic brucellosis.After treatment,all patients experienced have symptom relief in varying degrees,with 157 patients(60.9%)cured and 101 patients(39.1%)symptomatic improved(P<0.01).In conclusion,the incidences of fever,fatigue,and joint pain in patients during the acute phase is significantly higher than that those in patients during the chronic phase,while the incidence of osteoarthritis complications is higher in chronic phase patients.The incidences of abnormal SAT,ALT,AST,TBIL,CRE,CRP,and ESR,and bone destruction varies at different stages of brucellosis.Of those,abnormal ALT and bone destruction show a stronger association with,which can assist the clinical staging of brucellosis.

OBJECTIVE: To study the impacts of varicocele (VC) and varicocelectomy (VCT) on the proteomics of rat testis tissue, and to analyze the differential proteins and signaling pathways, and observe the microstructural changes of the testis tissue. METHODS: We selected 60 male SD rats and divided them into a sham operation (SO), a VC model control, and a VCT group. We harvested the testis tissues from the rats at 4 weeks after modeling for determination of the differential protein expressions by mass spectrometry, analysis of the changes in the protein signaling pathways by KEGG pathway repolarization, and observation of the microstructural changes in the spermatogenic cells under the transmission electron microscope (TEM). RESULTS: A total of 15 clinically significant proteins were effectively identified, among which RPS24, KIFAP3, HPX, RPL38, TOP2A, PRPF19, TRPM3, RPL32, CNBP and AHSG were upregulated, while RPS9, TKFC, SH3BGRL3, ACAA2 and FABP3 downregulated. The differential pathways found included the Type-I 4-aminobutyrate degradation pathway, eIF2 signaling pathway, and Type-III glutamate degradation pathway, which were all related to the pathogenesis of testicular growth arrest. Compared with the rats in the VCT group, those of the VC group rats showed ultrastructural changes in the testis tissue under the TEM, such as mitochondrial vacuolar degeneration, dense nucleoli, invagination of cell nuclear membranes, and irregularity, which were detrimental to the survival of testicular cells. CONCLUSION VCT affects the development and growth of the testis by altering the expressions of relevant proteins and influencing the changes of the gene pathways in the testicular cells, which may be one of the causes of VC inducing testis injury and testicular spermatogenic dysfunction. The changes in these molecular pathways can provide some theoretical evidence for an insight VC as well as potential therapeutic targets for its treatment.
Male ; Animals ; Varicocele/pathology* ; Rats ; Testis/ultrastructure* ; Rats, Sprague-Dawley ; Proteomics ; Signal Transduction ; Proteome

Objective To investigate the correlation between the expression of Toll-like receptor 4(TLR4)and chitosanase 3-like protein 1(CHI3L1)in colon cancer tissue and the prognosis of patients after radical surgery.Methods A total of 152 patients who underwent radical colon cancer surgery in our hospital from January 2017 to May 2018 were collected and divided into the good prognosis group(n=97)and the poor prognosis group(n=47)according to the 5-year survival status after surgery.Immunohistochemical staining was applied to detect the expression levels of TLR4 and CHI3L1 in colon cancer tissues and adjacent tissues;the correlation between the expression of TLR4 and CHI3L1 in colon cancer tissue and the prognosis of patients was analyzed,and the influencing factors for prognosis of colon cancer patients were analyzed.Results The positive expression rates of TLR4 and CHI3L1 in colon cancer tissues were obviously higher than those in adjacent tissues(P<0.05).The expression of TLR4 in colon cancer tissue was related to the degree of tumor differentiation,clinical staging,and lymph node metastasis of colon cancer patients(P<0.05),the expression of CHI3L1 was related to the tumor diameter,degree of tumor differentiation,clinical staging,and lymph node metastasis of colon cancer patients(P<0.05).Compared with the good prognosis group,the poor prognosis group had higher proportions of patients with poorly differentiated tumor,clinical stageⅢ,lymph node metastasis,and positive expression of TLR4 and CHI3L1(P<0.05).The 5-year survival rate of patient with TLR4 positive expression was 60.38%,which was lower than that of 86.84% of patients with TLR4 negative expression(χ2=9.104,P<0.05);the 5-year survival rate of patients with CHI3L1 positive expression was 58.06%,which was lower than that of 84.31% of patients with CHI3L1 negative expression(χ2=10.935,P<0.05).The positive expression of TLR4 and CHI3L1,poorly differentiated tumor,clinical stage Ⅲ,and lymph node metastasis were the independent risk factors for the prognosis of colon cancer patients(P<0.05).Conclusion TLR4 and CHI3L1 are related to the occurrence and clinicopathological features of colon cancer,and the positive expression of TLR4 and CHI3L1 in colon cancer tissues is not conducive to the prognosis of patients,so both of them are expected to become clinical treatment targets.