Quercetin can mediate the activation of mitogen-activated protein kinase(MAPK)signaling pathways to prevent osteoporosis(OP).This paper comprehensively discusses the interrelationship between MAPK and osteoporosis-related cells based on the latest domestic and international research.Additionally,it elucidates the research progress of quercetin in mediating the MAPK signaling pathway for OP prevention.The aim is to provide an effective foundation for the clinical prevention and treatment of OP and the in-depth development of quercetin.

Objective To observe the clinical efficacy and safety of ivabredine tablets in the treatment of elderly patients with hypertension and heart failure.Methods Elderly patients with hypertension and heart failure were divided into control group and treatment group by cohort method.The control group received nifedipine controlled release tablets 30 mg per time,qd,orally+furosemide tablets 20 mg per time,qd,orally+digoxin tablets 0.5 mg per time,qd,orally.On the basis of control group,the treatment group received ivabradine 5 mg per time,bid,orally after meals.Two groups were treated for 24 weeks.The clinical efficacy,right atrial volume indexes,left ventricular ejection fraction(LVEF),serum N-terminal pro-B-type natriuretic peptide precursor(NT-proBNP)levels and safety were compared between two groups.Results Fifty-three cases were enrolled in the treatment group,45 cases were enrolled in the control group.After treatment,the total effective rates of the treatment and control groups were 88.68％(47 cases/53 cases)and 71.11％(32 cases/45 cases),with statistically significant difference(P＜0.05).After treatment,the right atrial volume indexes of treatment and control groups were(35.48±6.17)and(29.88±5.38)mL·m-2;the LVEF were(50.51±7.02)％and(43.78±6.35)％;the levels of NT-proBNP were 214(155,379)and 212(167,458)ng·mL-1,respectively,and the differences were statistically significant(all P＜0.05).The adverse drug reactions of two groups were nausea and vomiting,slow heart rate,rash and dizziness.The total incidences of adverse drug reactions in the treatment and control groups were 11.32％and 11.11％without significant difference(P＞0.05).Conclusion Ivaframine tablets have a significant clinical efficacy in the treatment of elderly patients with hypertension and heart failure,without increasing the incidence of adverse drug reactions.

ObjectiveWe conducted a drug resistance and homology analysis of diarrheagenic Escherichia coli （DEC） in Fengxian District of Shanghai in order to provide a basis for clinical rational drug use， risk monitoring and early warning. MethodsDEC were isolated from diarrheal patients in Fengxian District， Shanghai from 2019 to 2022. The minimum inhibitory concentrations （MIC） of 21 drugs to the DEC were determined. Genotyping and homology analysis were conducted with pulsed-field gel electrophoresis （PFGE）. ResultsThe DEC detection rate of diarrhea cases was 18.99% （131/690）， including enteroaggregative E.coli （EAEC） 64.89% （85/131）， enterotoxigenic E.coli （ETEC） 22.14% （29/131）， enteropathogenic E.coli （EPEC） 12.21% （16/131）， and enterohemorrhagic E.coli （EHEC） 0.76%（1/131）. The DEC detection showed obvious seasonal characteristics with a high incidence in summer. The DEC multidrug resistance rate was 66.41% with a total of 65 drug resistance profiles. The five antimicrobial drugs with the highest resistance rate were ampicillin （60.31%）， nalidixic acid （51.91%）， cefazolin （50.38%）， tetracycline （44.27%）， and cotrimoxazole （35.11%）. The rate of DEC resistance to levofloxacin was significantly increased from 2019 to 2022. Cluster analysis showed that the similarity of 85 EAEC cluster was 58.4%‒100.0%， and 69 band patterns were obtained. The similarity of 29 ETEC cluster was 58.5%‒100.0%， and 13 band patterns were obtained， including 2 dominant band types. The similarity of 16 EAEC clusters was 53.9%‒100.0%， and 15 band patterns were obtained. Five groups of homologous strains were found， consistent with the resistance phenotypes. ConclusionAmong the diarrhea cases， the DEC epidemic intensity is high， the drug resistance situation is severe， and the risk of outbreak infection is high in Fengxian District， Shanghai. Therefore， health monitoring and prevention need to be strengthened.

AIM:To investigate whether crocin alleviates right ventricular injury induced by monocrotaline(MCT)in rats with pulmonary arterial hypertension(PAH),and to explore the underlying mechanisms.METHODS:Forty male SD rats were randomly divided into 4 groups:normal group,PAH group,crocin group and sildenafil group,with 10 rats in each group.The rats in PAH,crocin and sildenafil groups received subcutaneous injection of MCT(50 mg/kg)to establish the PAH model.Starting from the day of MCT injection,the rats in crocin group received crocin(200 mg/kg),the rats in sildenafil group received sildenafil(30 mg/kg),and those in PAH and normal groups were orally gavaged with an equal volume of saline once daily.After 4 weeks,measurements of right ventricular systolic pressure(RVSP),mean pulmonary artery pressure(mPAP),right ventricular hypertrophy index(RVHI)and right ventricular mass index(RVMI)were taken for the rats in each group.Tissue staining was conducted to observe pathological changes in the right ventricle,and the expression levels of inflammatory factors(IL-1β,IL-6 and TNF-α),the p38 MAPK/NF-κB inflammato-ry pathway,CCL2,CCR2,and the macrophage marker CD68 were assessed.RESULTS:Compared with PAH group,the rats in crocin and sildenafil groups exhibited significant reductions in RVSP,mPAP,RVHI and RVMI(P＜0.05).Right ventricular tissue displayed no evident infiltration of inflammatory cells or proliferation of collagen fibers.The down-regulation of the p38 MAPK/NF-κB pathway and inflammatory factors(IL-1β,IL-6 and TNF-α)was significant(P＜0.05).Additionally,the CCL2/CCR2 pathway and the infiltration of CD68+ macrophages were markedly decreased(P＜0.05).CONCLUSION:Crocin effectively mitigates right ventricular damage in MCT-induced PAH rats,with its effica-cy comparable to that of sildenafil at the dosage utilized in this experiment.Some protective mechanisms of crocin may be attributed to its regulatory effects on inflammation.

Eleven compounds were isolated from Eucommia ulmoides by silica gel, Sephadex LH-20, HW-40C column chromatography and semi-preparative HPLC. Their structures were identified by modern spectroscopic methods as neoeucommiate A (1), (7S,8R)-dihydrodehydrodiconiferyl alcohol (2), urolignoside (3), ficusal (4), tiruneesiin (5), glochidioboside (6), forsythialansides B (7), ecdysanol B (8), (+)-syringaresinol-4-O-β-D-glucopyranoside (9), (+)-pinoresinol 4-O-[6ʹʹ-O-vanilloyl]-β-D-glucopyranoside (10), samsesquinoside (11). Compound 1 is a new compound, compounds 3-7, 10 and 11 were isolated from Eucommia ulmoides for the first time.

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Objective:To study the safety and efficiency of endovascular treatment in pediatric severe cerebral venous sinus thrombosis(CVST).Methods:This was a case series study.Data of pediatric severe CVST patients who received endovascular treatment in the Department of Neurointerventional, the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2023 were retrospectively analyzed.The technical success rate, periprocedural complications, neurologic and radiologic outcomes were collected to study the safety and efficacy of endovascular treatment in pediatric severe CVST.Results:A total of 15 patients were included in this study, including 6 males(40.0%) and 9 females(60.0%) with a mean age of(14.60±2.26) years.The modified Rankin Scale score(mRS) before endovascular treatment was(3.47±1.06) points, and the time from onset to endovascular treatment was 17(12-26) days.Thirteen patients(86.7%) received mechanical thrombectomy through catheter aspiration and/or stent-retriever thrombectomy followed or not followed by intrasinus thrombolysis(IST), and 2 patients(13.3%) received IST only.The technical success rate was 100%.Three patients(20.0%) had periprocedural complications.Ten patients(66.7%) had mRS≤2 points at discharge.Twelve patients(80.0%) had valuable neurologic and radiologic follow-ups with a duration of 9.5(3.5-19.0) months, and they all had mRS≤2 points.Among the 12 patients, 8(66.7%) had good cerebral venous recanalization.Conclusions:Endovascular treatment is technically feasible in pediatric severe CVST patients, with acceptable safety and efficacy.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Objective: To describe the distribution characteristics of hypertension among adult twins in the Chinese National Twin Registry (CNTR) and to provide clues for exploring the role of genetic and environmental factors on hypertension. Methods: A total of 69 220 (34 610 pairs) of twins aged 18 and above with hypertension information were selected from CNTR registered from 2010 to 2018. Random effect models were used to describe the population and regional distribution of hypertension in twins. To estimate the heritability, the concordance rates of hypertension were calculated and compared between monozygotic twins (MZ) and dizygotic twins (DZ). Results: The age of all participants was (34.1±12.4) years. The overall self-reported prevalence of hypertension was 3.8%(2 610/69 220). Twin pairs who were older, living in urban areas, married, overweight or obese, current smokers or ex-smokers, and current drinkers or abstainers had a higher self-reported prevalence of hypertension (P<0.05). Analysis within the same-sex twin pairs found that the concordance rate of hypertension was 43.2% in MZ and 27.0% in DZ, and the difference was statistically significant (P<0.001). The heritability of hypertension was 22.1% (95%CI: 16.3%- 28.0%). Stratified by gender, age, and region, the concordance rate of hypertension in MZ was still higher than that in DZ. The heritability of hypertension was higher in female participants. Conclusions: There were differences in the distribution of hypertension among twins with different demographic and regional characteristics. It is indicated that genetic factors play a crucial role in hypertension in different genders, ages, and regions, while the magnitude of genetic effects may vary.
Adult ; Female ; Humans ; Male ; Alcohol Drinking ; Diseases in Twins/genetics* ; Hypertension/genetics* ; Twins, Dizygotic/genetics* ; Twins, Monozygotic/genetics*