OBJECTIVE To ensure the safety of patients’ drug use and control the risk of medical insurance expenditure by upgrading the pre-prescription review system to conduct pre-review on prescriptions from internet hospitals and external prescriptions， as well as to review the payment methods of drugs （including in-hospital and external drug dispensing）. METHODS The data interfaces of prescriptions from internet hospitals and external prescriptions were integrated to achieve real-time rational drug use intervention. Additionally， an intelligent review project for payment method was added to precisely intervene in the medical insurance payment methods of drugs. The effect of the system upgrade was evaluated by comparing the qualification rates of prescriptions from internet hospitals and external prescriptions and the suspected amounts of drug violations from January to April 2025 （before the system upgrade） and May to August 2025 （after the system upgrade）. RESULTS After the upgrade of the pre-prescription review system， the qualification rates of prescriptions from internet hospitals and external prescriptions increased by 3.5% [95% confidence interval （CI）＝0.3%-6.7%， P ＝0.037 ] ； the suspected amounts of drug violations decreased to 52.9% of the pre-upgrade level （95%CI＝31.6%-88.5%， P ＝0.026）， and the average monthly sequential decrease was 29.5% （95%CI＝12.2%-43.4%， P ＝0.012）. Moreover， the addition of the intelligent review project for payment methods promoted the management of off-label drug use in our hospital. After the upgrade， a total of 79 filling valid applications for off-label drug use were received and archived. CONCLUSIONS The upgrade of the pre-prescription review system effectively improves the review qualification rates of prescriptions from internet hospitals and external prescriptions and the accuracy of medical insurance payment for drugs， and strengthens the supervision of off-label drug use， achieving dual guarantees of clinical rationality and medical insurance compliance.

Objective To investigate whether successful percutaneous coronary intervention(PCI)could improve symptoms and quality of life(QOL)in left main disease and/or 3-vessel disease patients with diabetes.Methods Patients with left main disease and/or 3-vessel disease who underwent PCI in the First Affiliated Hospital of Air Force Medical University from April 2018 to May 2021 were consecutively enrolled and subdivided into 2 groups:diabetes and no diabetes.Detailed baseline characteristics,symptoms,including dyspnea and angina,assessed with the Rose dyspnea scale(RDS),Seattle angina questionnaire(SAQ),the European quality of life-5 dimensions(EQ-5D)and 12-item short-form health survey(SF-12)questionnaire respectively,procedural details,and 1 month and 1 year follow-up data were collected.Results Among 440 left main disease and/or 3-vessel disease patients,disease was present in 176(40.00％),who had more hypertension,peripheral artery disease,and LCX lesion(all P＜0.05).The incidence of major adverse cardiovascular events(MACE)and all-cause mortality were similar between the two groups(both P＞0.05)at 1 month follow-up,while all-cause mortality in diabetes patients was significantly higher than those without diabetes at 1 year follow-up(P=0.013).Low left ventricular ejection fraction was an independent risk factor for MACE and all-cause mortality at 1 month and 1 year follow-up after successful revascularization(all P＜0.05).Most importantly,symptoms,including dyspnea and angina,and QOL were markedly improved regardless of diabetes both at 1 month and 1 year follow-up(all P＜0.05).Diabetes patients showed improved dyspnea and QOL at similar degree to the non-diabetes patients(all P＞0.05)and a more significantly relieved angina(P=0.013).Additionally,the number of chronic total occlusion(CTO)per patient was identified as an independent risk factor of dyspnea(OR 0.723,95％CI 0.525～0.997,P=0.048)and angina relief(OR 0.686,95％CI 0.473～0.995,P=0.047),and the contrast volume(OR 0.995,95％CI 0.992～0.999,P=0.008)as an independent risk factor of QOL improvement in diabetic patients.Conclusions Successful PCI is beneficial for relieving symptoms and improving quality of life in patients with diabetes who have left main disease and/or 3-vessel disease.

Aim To investigate the protective effect of Vaccarin(Va)on epithelial-mesenchymal transition(EMT)in renal fibrosis model mice through regulating STAT3,and the underlying mechanism.Methods Left ureter ligation was used to establish a mouse model of unilateral ureteral obstruction(UUO);human kid-ney tubular epithelial(HK2)cells were induced to differentiate by transforming growth factor-β(TGF-β)in vitro.HE and Masson staining were used to observe the morphological changes of renal tissue;kits were used to detect the levels of BUN,Cr,IL-1β and IL-7 in mouse serum;CCK-8 was used to detect the effect of Va on the viability of HK2 cells;RT-PCR was used to detect the levels of inflammatory factors in HK2 cells;Western blot was used to detect the expression of STAT3,p-STAT3,E-cadherin,and α-SMA proteins in renal tissue and HK2 cells;to further investigate the regulation of Va on STAT3,JAK/STAT3 pathway acti-vator RO8191 was used to treat TGF-β-induced HK2 cells,and functional loss was detected.Results Va improved the pathological damage in UUO mice,inhibi-ted the levels of BUN,Cr and inflammatory factors;Va inhibited the phosphorylation of STAT3,upregulated E-cadherin,and downregulated α-SMA protein expres-sion;RO8191 counteracted the inhibitory effect of Va on the phosphorylation of STAT3.Conclusions Va inhibits the phosphorylation of STAT3 and the release of inflammatory factors,improves EMT,thus exerting an anti-renal fibrosis effect.

Objective To explore the long-term efficacy of percutaneous pulmonary valve implantation(PPVI)and the durability of the domestic self-expanding Venus P valve.Methods A total of 8 patients with post-surgical right ventricular outflow tract(RVOT)dysfunction,who were admitted to hospital from October 2014 to July 2016 and deemed anatomically suitable for PPVI with self-expanding valve,were included prospectively.Clinical,imaging,procedural and follow-up data were analyzed.The survival rates,perioperative and long-term complication rates,long-term efficacy of PPVI,and long-term function of Venus P in 8 patients were evaluated.The immediate procedural results were evaluated by clinical implant success rate,which is defined as successful valve implantation with echocardiography-assessed pulmonary regurgitation＜moderate and peak trans-pulmonary pressure gradient＜40 mmHg.Results A total of 8 patients were included,with 7 females,aged 14 to 36 years.The initial diagnosis included post-surgical Tetralogy of Fallot(5 cases),post-surgical Trilogy of Fallot(1 case),post-surgical Quadricuspid pulmonary valve stenosis(1 case)and post-surgical Double-Outlet Right Ventricle(1 case).The indications of PPVI included RVOT-pulmonary obstruction and regurgitation(1 case)and isolated regurgitation(7 cases).Clinical implant success was achieved in all of the 8 patients with firmly fixed valve,and there were no such complications as valve detachment,displacement or stent fracture.All patients experienced significant symptom relief after the procedure.The right ventricular end-diastolic volume index(RVEDVi)measured by CMR 6 months after PPVI showed a significant decrease compared to preprocedural values[(89.99±13.85)ml/m2 vs.(144.93±11.28)ml/m2,P=0.001].Postoperative pulmonary regurgitation were significantly improved or disappeared in all patients,and there was no statistically significant difference in the average peak pressure gradient measured by echocardiogram between preoperative and the latest follow-up[(23.25±8.39)mmHg vs.(18.75±6.28)mmHg,P=0.210].Over an average follow-up period of(9.25±0.71)years,1 case of infective endocarditis occurred 5 years after PPVI.During the follow-up,no death,deterioration of heart failure,malignant arrhythmia or other serious complications were observed.All patients completed 8-year follow-up,and 3 completed 10-year follow-up.All patients were graded as NYHA functional class one at the latest follow-up.Conclusions PPVI using the domestically produced self-expanding Venus P is safe and feasible for the treatment of patients with post-surgical RVOT dysfunction and suitable anatomy.Our study confirms the long-term efficacy and durability of Venus P from multiple perspectives,and no severe stent fracture occurred without pre-stent implantation in the native RVOT.

Objective:Invasive pulmonary mucormycosis(PM)is a rare but highly lethal opportunistic infection.COVID-19 associated mucormycosis(CAM)is difficult to diagnose,often leading to misdiagnosis or missed diagnosis,and has poor treatment outcomes.This study reports a case of successfully treated CAM and explores optimized diagnostic and therapeutic strategies.Methods:A retrospective analysis of the diagnosis and treatment process in a 50-year-old female patient with COVID-19 associated with diabetic ketoacidosis(DKA)and invasive pulmonary mucormycosis was conducted.Combined with a literature review,the therapeutic efficacy of local bronchoscopic instillation in conjunction with systemic treatment using liposomal Amphotericin B(L-AmB)was specifically evaluated.Results:The patient was rapidly diagnosed with Rhizopus microsporus infection through metagenomic next-generation sequencing(mNGS).She subsequently received antifungal treatment with intravenous L-AmB combined with local bronchoscopic instillation.After treatment,the patient was significantly improved,with imaging studies showing gradual absorption of the lesions.Follow-up at six months revealed no recurrence.A literature review suggests that early diagnosis and multimodal therapy are key to improving survival rates in patients with CAM.Conclusion:mNGS can significantly improve the early diagnosis rate of CAM.The combination of local and systemic treatment with L-AmB is valuable in improving prognosis.Early diagnosis,multimodal antifungal therapy,and individualized management are key to increasing the survival rate of patients with CAM.

To investigate the molecular mechanisms underlying the mechanosensitive ion channel PI-EZO2 in osteoarthritis(OA),we developed a lentiviral vector for endogenous PIEZO2 overexpression and established a stable PIEZO2-high-expressing immortalized human primary chondrocyte line.By map-ping the open reading frame of the PIEZO2 locus and designing sequence-specific sgRNA,we employed the CRISPR/Cas9 synergistic activation mediator(SAM)system to precisely integrate transcriptional ac-tivation elements into the PIEZO2 promoter region.Lentiviral-mediated targeted genomic integration en-sured endogenous PIEZO2 overexpression,confirmed by mCherry fluorescence tracing coupled with flow cytometric sorting,which revealed membrane-specific localization of PIEZO2 protein(localization effi-ciency:78.49％).Quantitative PCR demonstrated a 17-fold upregulation of PIEZO2 mRNA,while Western blotting validated enhanced membrane-localized protein expression.Strikingly,PIEZO2-overex-pressing chondrocytes exhibited hallmark OA metabolic phenotypes compared to wild-type controls:typeⅡ collagen mRNA expression decreased to 50％of baseline levels,whereas matrix metalloproteinase 13(MMP13)mRNA surged by 20-fold.These alterations recapitulated the pathological matrix metabolic phenotype observed in biomechanical OA models induced by cyclic mechanical stress(10％strain,0.5 Hz,8 h/day for 2 consecutive days).Collectively,we successfully generated a human chondrocyte model with stable PIEZO2 overexpression,which faithfully mirrors mechanotransduction-driven OA progression.This engineered cellular system provides a robust platform for dissecting PIEZO2-mediated mechanosig-naling networks and advancing targeted therapeutic discovery.

Objective To evaluate the efficacy and safety of transcatheter aortic valve implantation(TAVI)for the treatment of primary aortic valve regurgitation(NAVR)and to compare the difference in the choice of prosthetic valve size and the difference in complications with aortic stenosis(AS).Methods According to the definition of Valve Academic Research Consortium(VARC-3),143 patients with NAVR/AS treated with TAVI and patients with NAVR treated with surgical aortic valve replacement(SAVR)at Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,China,from March 2019 to September 2024 were selected,and clinical data on baseline,perioperative,and primary endpoint events were were retrospectively collected and compared.Results Forty-three patients with NAVR were treated with TAVI,with a device success rate of 86.0％and a surgical success rate of 95.3％.Subgroup comparisons:(1)NAVR-TAVI group than NAVR-SAVR group:patients in the TAVI group had a significantly shorter operative time than those in the SAVR group(P＜0.001);complete left bundle branch block was more likely to occur after TAVI(P=0.042),and complete right bundle branch block was more likely to occur after SAVR(P=0.044).SAVR postoperatively The incidence of congestive heart failure was higher(P=0.013),and the mortality rate was significantly higher in the SAVR group than in the TAVI group(P=0.019).(2)NAVR-TAVI group than AS-TAVI group:the differences in access selection,THV size[28(22,34)mm vs.24(22,32)mm,P=0.044]and proportion of THV overdiameter[14％(7％,20％)vs.7％(3％,11％),P＜0.001]were statistically significant.patients in AS and NAVR groups had 1 case of permanent pacing after TAVI treatment.In the AS and NAVR groups,there was 1 case of permanent pacemaker implantation after TAVI.2 patients in the AS group were converted to surgical treatment,and 6 patients died.Conclusions The use of"off-label"(transfemoral)and"on-label"(transapical)TAVI devices(both from domestic sources)is safer than SAVR for the treatment of NAVR,especially in elderly and high-risk patients.Compared with patients with AS treated with TAVI,larger diameter annulas are usually selected for NAVR,with higher rates of valve migration,but overall safety and efficacy are comparable to AS.

This research aims to construct a stable epithelial cell senescence model for screening and e-valuation of senolytics.We explored the optimal conditions for doxorubicin-induced senescence of non-transformed epithelial cells MCF 10A,including the optimal induction concentration,the optimal inter-vention time,and the optimal senescence duration,and confirmed the feasibility of MCF 10A as an epi-thelial senescence model by multiple ways.The optimal condition for Doxorubicin-induced senescence of MCF 10A cells was treatment with 0.6 μmol/L Doxorubicin for 16 h to achieve the best senescence state on the 8th day.Under the optimal induction conditions,the positive rate of senescence-associated β-gal-actosidase(SA-β-gal)staining in the treated group reached 97％.At the same time,biochemical results of detecting the expression of mRNA,proteins,and immunofluorescence demonstrated that the expression levels of senescence-associated secretory phenotype(SASP),p16,p21 and p53 in the treated group were significantly higher than those in the control cells,and Lamin B1 was significantly decreased(P＜0.001),which were consistent with the specific characteristics of senescence.In summary,an epithelial senescence model was successfully induced in MCF 10A cells by Doxorubicin in this study,which will promote the screening of senolytics for senescent epithelial cells.

Objective To investigate and compare the epidemiological characteristics of common respiratory viruses among influenza-like illness(ILI)and severe acute respiratory infection(SARI)cases in Huzhou,Zhejiang Province before and after the COVID-19 pandemic,so as to provide a basis for formulating and adjusting the prevention and control strategies for viral respiratory infectious diseases.Methods ILI and SARI cases at two influenza surveillance sentinel hospitals in Huzhou and had throat swab samples collected during Nov 2017 to Feb 2020(pre-COVID-19 pandemic period)and Dec 2022 to Apr 2024(post-COVID-19 mitigation phase)were selected as the participants.Seven common viral respiratory pathogens were tested,including influenza A virus(H1N1 and H3N2 subtypes),influenza B virus(Victoria lineage,FluB),respiratory syncytial virus(RSV),rhinovirus(HRV),adenovirus(ADV),and severe acute respiratory syndrome coronavirus-2(SARS-CoV-2).The positive rates of respiratory pathogens before and after the COVID-19 pandemic were compared across different age groups and different time.Results A total of 7 948 ILI samples and 2 294 SARI samples were included.The overall positive rate of ILI samples increased from 33.6%to 47.1%,primarily due to the increase in influenza and COVID-19 infections;the overall positive rate of SARI samples decreased from 31.4%to 24.8%,mainly due to the reduction in HRV and ADV infections.During the post-COVID-19 mitigation phase,SARS-CoV-2(22.1%),H3N2(12.7%),and FluB(6.0%)were the primary pathogens in ILI samples,while RSV(7.1%),H3N2(5.3%),and HRV(4.5%)dominated in SARI samples.During the post-COVID-19 mitigation phase,the influenza virus circulation period was shortened.Before the COVID-19 pandemic,RSV was mainly detected in autumn and winter,while during the post-COVID-19 mitigation phase,out-of-season RSV epidemics were observed in spring and summer.Co-infection rate in ILI cases increased significantly in the post-COVID-19 mitigation phase,predominantly consisting of co-infections of COVID-19 and influenza A virus,while co-infection rate in SARI cases showed a decline.Conclusion We found important epidemiological changes in respiratory viruses in Huzhou during the post-COVID-19 mitigation phase compared to pre-COVID-19 period,including increased positive rates of influenza and COVID-19,and disruptions to the seasonal patterns of influenza and RSV.The prevention and control strategies should be adjusted in a timely manner based on the monitoring data.

Hypercholesterolemia is pathologically characterized by abnormal accumulation of low-density lipoprotein cholesterol,which is closely associated with metabolic dysfunction-associated fatty liver disease and increased cardiovascular risks.Hepatocytes maintain cholesterol homeostasis through LDL receptor-mediated uptake and esterification storage mechanisms.However,chronic cholesterol overload induces mitochondrial dysfunction,reactive oxygen species accumulation,and endoplasmic reticulum stress,leading to hepatocyte injury.Moreover,systemic hypercholesterolemia disrupts gut microbiota balance and impairs short-chain fatty acid and ketone metabolism,exacerbating metabolic disturbances and aggravating hepatic injury through enhanced metabolic stress.In this article,we review the advance of studies on hypercholesterolemia in recent years and summary its association with hepatic injury,which can provide theoretical support for further research.