Aim To explore the mechanism and mate-rial basis of Shenkang injection(SKI)in the treatment of renal fibrosis(RF)by bioinformatics and in vitro experiments.Methods The differentially expressed genes of RF were screened by GEO database.With the help of CMAP database,based on the similarity princi-ple of gene expression profile,the drugs that regulated RF were repositioned,and then the components of SKI potential treatment RF were screened by molecular fin-gerprint similarity analysis.At the same time,the core targets and pathways of SKI regulating RF were predic-ted based on network pharmacology.Finally,it was verified by molecular docking and cell experiments.Results Based on the GEO database,two RF-related data sets were screened,and CMAP was relocated to three common RF therapeutic drugs(saracatinib,da-satinib,pp-2).Molecular fingerprint similarity analysis showed that RF therapeutic drugs had high structural similarity with five SKI components such as salvianolic acid B and hydroxysafflor yellow A.Molecular docking results showed that salvianolic acid B,hydroxysafflor yellow A and other components had good binding abili-ty with MMP1 and MMP13,which were the core targets of SKI-regulated potential treatment of RF.Network pharmacology analysis suggested that the core targets of SKI were mainly enriched in signaling pathways such as Relaxin and AGE-RAGE.Cell experiments showed that SKI could significantly reduce the mRNA expres-sion levels of AGER,NFKB1,COL1A1,SERPINE1,VEGFC in AGE-RAGE signaling pathway and MMP1 and MMP13 in Relaxin signaling pathway in RF model cells,and significantly increase the mRNA expression level of RXFP1.Conclusions SKI can play a role in the treatment of RF by regulating Relaxin and AGE-RAGE signaling pathways,and its material basis may be salvianolic acid B,hydroxysafflor yellow A and other components.

Objective With the widespread of transcatheter aortic valve replacement(TAVR)in patients with severe symptomatic aortic stenosis(AS),the life-cycle management has become a major determinant of prognosis.Methods A total of 408 AS patients who underwent successfully TAVR from June 2021 to August 2023 were consecutively enrolled in Hospital Valve Intervention Center.Patients were assigned to the Usual Care(UC)group between June 2021 and October 2022,while patients were assigned to the Heart Multi-parameter Monitoring(HMM)group between November 2022 and August 2023.The primary endpoint was defined as composite endpoint within 6 months post-TAVR,including all-cause death,cardiovascular death,stroke/transient ischemic attack,conduction block,myocardial infarction,heart failure rehospitalization,and major bleeding events.Secondary endpoints were the time interval(in hours)from event occurrence to medical consultation or advice and patient satisfaction.Statistical analysis was performed using Kaplan-Meier and multivariable Cox proportional hazards models.Results The incidence of primary endpoint in HMM group was significantly lower than that in UC group(8.9％vs.17.7％,P=0.016),the driving event was the rate of diagnosis and recognition of conduction block.The average time intervals from event occurrence to receiving medical advice were 3.02 h in HHM group vs.97.09 h in UC group(P＜0.001).Using cardiac monitoring devices and smart healthcare platforms provided significant improving in patients long-term management(HR 0.439,95％CI 0.244-0.790,P=0.006).Conclusions The utilization of cardiac monitoring devices and smart healthcare platforms effectively alerted clinical events and improved postoperative quality of life during long-term management post TAVR.

Objective:To establish a method for detecting the binding affinity of peptides to HLA-B*1301 by HLA molecular reconstitution after weak acid treatment,and its practicality was evaluated.Methods:C1R cells overexpressing HLA-B*1301 were treated with citrate buffer of different pH for different time.After neutralization of pH,cells were resuspended in culture medium con-taining β2m and brefeldin A.Cells were incubated at 37℃with peptide(peptide group)or without peptide(blank control),after addition of anti-HLA antibody,the cells were detected by flow cytometry.Ratio of fluorescence intensity between peptide group and blank control group was used as an index to measure the level of HLA molecular remodeling,and then represented the interactions between peptide and HLA-B*1301 molecule.Results:HLA-polypeptide complex was denatalized and dissociated after being treated with pH3.0 buffer for 1 min,and only HLA heavy chain molecules were retained on the cell surface.The addition of peptides with binding force could significantly improve the level of HLA molecular remodeling,and the binding force of peptides with HLA-B*1301 could be evaluated by this method.Conclusion:HLA molecular reconstitution assay is a simple and reliable method to detect the binding of peptides to HLA-B*1301,which can also provide reference for the study of other low frequency HLA molecular antigen pre-sentation patterns.

Objective:To investigate the diagnostic performance of CT-derived fractional flow reserve (CT-FFR) derived from standard images (STD), images processed by first-generation (SSF1) and second-generation (SSF2) whole-heart motion correction algorithm, respectively.Methods:Patients who underwent both coronary CT angiography (CCTA) and invasive coronary angiography (ICA) with FFR examination within 3 months in Shanghai General Hospital, Shanghai Jiao Tong Univerisity School of Medicine from January 2020 to December 2022 were screened in this retrospective study. Totally of 121 patients (134 lesions) were finally included in the study. CCTA images were reconstructed using iterative reconstruction, iterative reconstruction plus SSF1 and SSF2 algorithms. All images were divided into three groups: STD group, SSF1 group, and SSF2 group. The image quality of the CCTA images was assessed using the Likert scale, and differences between the two groups were compared using the Mann-Whitney U and Kruskal-Wallis test. The correlation and consistency between CT-FFR and FFR were evaluated using Spearman correlation coefficient and Bland-Altman plots. The diagnostic performance of CCTA and CT-FFR from three groups was compared by receiver operating characteristic (ROC) curves. The area under the curve (AUC) was compared using the DeLong test. Results:Compared to the STD group and SSF1 group, the SSF2 group showed the best performance in image quality score (median=3.7). Best correlation ( r=0.652, P<0.001) and consistency (mean difference=0.03) between CT-FFR and FFR were observed in SSF2 group. ROC analysis results revealed that, at the per-lesion level, in the diagnosis of ischemic lesions, the diagnostic performance of CT-FFR in the SSF2 group was significantly better than that of the SSF1 group (AUC=0.88 vs. 0.76, P=0.003), while no significant difference was observed between STD group and SSF1 group ( P=0.125). At the per-patient level, the SSF2 group also demonstrated the highest diagnostic performance. Conclusion:The SSF2 algorithm significantly improved CCTA image quality and enhanced its diagnostic performance for evaluating stenosis severity and CT-FFR calculations.

This article reports a patient with hepatic coma who underwent artificial liver support therapy and liver transplantation successfully， and the patient recovered well in the later stage after active treatment. This article also discusses the timing of liver transplantation.

Objective:Operational efficiency and influencing factors of China's basic medical insurance system from 2020 to 2021 is conducted to provide reference for improving the operational efficiency and optimizing the input-output relationship.Methods:The super-efficiency SBM model based on unexpected output and the Malmquist index are used to measure the static and dynamic efficiency of resident medical insurance in 31 provinces in China,and Tobit regression analysis is employed to analyze the influencing factors.Results:The overall operational efficiency of resident medical insurance still needs improvement.The operational efficiency of resident medical insurance in the central and western regions is lower than that in the eastern region,and the gap is significant.Different levels and regions have differentiated main constraints on the operational efficiency of resident medical insurance.In terms of dynamic efficiency,the total factor productivity of resident medical insurance operation shows an increasing trend,mainly due to technological progress.In terms of influencing factors,the degree of aging,the level of medical expenses and the level of medical insurance supervision have a significant impact on the operational efficiency.Suggestions:Efforts should be made to bridge regional disparities,promote the equitable development of medical insurance,reasonably control the level of medical expenses,strengthen the supervision of medical insurance funds,and implement active aging policies.

ObjectiveTo evaluate the effect and safety of Jiuxin Pill （救心丸） on exercise tolerance and quality of life in patients with stable angina pectoris （SAP）. MethodsA randomised， double-blind， placebo-controlled， multicentre study design was used to enroll 170 patients of SAP from nine centres， which were divided into 85 patients each in the trial group and control group with 1∶1 ratio. Both groups maintained the original western medicine treatment plan， and added Jiuxin Pill or placebo respectively， 2 pills （0.05 g） each time twicely for 28 days. The main outcomes were total exercise time （TED） in the exercise treadmill test and Seattle Angina Questionnaire （SAQ） scores including physical limitation （PL）， angina stability （AS）， angina frequency （AF）， treatment satisfaction （TS）， and disease perception （DP）. The secondary outcomes were exercise treadmill test indicators including heart rate recovery in 1 min （HRR1）， metabolic equivalents （METs）， maximum magnitude of ST-segment depression， and the Borg rating of perceived exertion scale， the average number of angina attacks per week， withdrawal and reduction rate of nitroglycerin， traditional Chinese medicine syndrome scores， incidence of major adverse cardiovascular events. Safety indicators were evaluated and the occurrence of adverse events during the trial was recorded. Data was collected before treatment， day 28±2 in treatment period， and follow-up at day 56 which is 28±2 days after treatment period finished. ResultsEighty-four and eighty-five patients respectively from trial group and control group were included to the full analysis set （FAS） and safety analysis set （SS）. Compared with the group before treatment and with the control group after treatment， the trial group had higher TED， HRR1， and METs， and lower maximum magnitude of ST-segment depression and Borg rating of perceived exertion scores after treatment （P＜0.01）. Compared with the group before treatment and with the control group after treatment and at follow-up， the total SAQ score and scores of AS， AF， TS and DP of the trial group after treatment and at follow-up elevated， while the average number of angina attacks per week and traditional Chinese medicine syndrome scores reduced （P＜0.01）. There was no statistically significant difference in the withdrawal and reduction rate of nitroglycerin between groups （P＞0.05）. Major adverse cardiovascular events occurred in 1 case （1/84， 1.19%） in the trial group and 1 case （1/85， 1.18%） in the control group， and the difference between groups was not statistically significant （P＞0.05）. A total of 3 cases of adverse events occurred in the trial group （3/84， 3.57%）， and a total of 6 cases of adverse events occurred in the control group （6/85， 7.06%）， and there was no statistically significant difference in the incidence of adverse events between groups （P＞0.05）. ConclusionIn the treatment of SAP， Jiuxin Pill combined with conventional western medicine can further enhance exercise tolerance， improve quality of life， and demonstrate great safety.

Objective This study aims to assess the role of DNA methylation changes in tongue cancer through a comprehensive analysis of global DNA methylation alterations during experimental lingual carcinogenesis.Methods C57BL/6J mice were subjected to 16-week oral administration of 4-nitroquinoline-1-oxide(4NQO,50 mg/L).Lingual mucosa samples,being representative of normal tissue(week 0)and early(week 12)and advanced(week 28)tumorigen-esis,were harvested for microarray and methylated DNA immunoprecipitation sequencing(MeDIP-Seq).The mRNA and promoter methylation of transforming growth factor-beta-signaling protein 1(SMAD1)were evaluated with real-time quantitative reverse transcription polymerase chain reaction and Massarray in human lingual mucosa and tongue cancer cell lines.Results The cytosine guanine island(CGI)methylation level observed at 28 weeks surpassed that of both 12 weeks and 0 weeks.The promoter methylation level at 12 weeks exceeded that at 0 weeks.Notably,208 differentially expressed genes were negatively correlated to differential methylation in promoters among 0,12,and 28 weeks.The mRNA of SMAD1 was upregulated,con-current with a decrease in promoter methylation levels in cell lines compared to normal mucosa.Conclusion DNA methylation changed during lingual carcinogenesis.Overexpression of SMAD1 was correlated to promoter hypomethyl-ation in tongue cancer cell lines.

Objective:Osteosarcoma is the most common malignant bone tumor in children and adolescents,characterized by a high potential for proliferation and metastasis.Patients with osteosarcoma who have distant metastases generally have a poor prognosis.Challenges in treatment include incomplete resection of tumor and chemotherapy resistance,with no effective cure currently available.Recent studies suggest that β-1,4-N-acetyl-galactosaminyltransferase 1(B4GALNT1)plays a role in the progression of various malignant tumors.However,the function of B4GALNT1 in osteosarcoma cells has not been reported.This study aims to investigate the expression of B4GALNT1 in osteosarcoma tissues compared to normal tissues and to explore its effects on the proliferation,migration,and invasion of osteosarcoma cells,thereby providing new theoretical foundations and directions for the treatment of osteosarcoma patients. Methods:Tumor tissues and corresponding normal tissue samples were collected from 16 osteosarcoma patients who underwent tumor resection at the Second Xiangya Hospital of Central South University.The patients'ages ranged from 8 to 17 years(median age 12 years).The expression of B4GALNT1 mRNA in osteosarcoma tissues,corresponding normal tissues,3 osteosarcoma cell lines(MG63,Saos-2,and U2OS),and human fetal osteoblastic cells(hFOB)was detected using real-time reverse transcription PCR(real-time RT-PCR).The effects of B4GALNT1 knockdown on the proliferation of osteosarcoma cells Saos-2 and U2OS were analyzed using cell counting kit-8(CCK-8)assays and colony formation assays.The effects of B4GALNT1 knockdown on the migration and invasion abilities of Saos-2 and U2OS cells were evaluated using Transwell migration and invasion assays.Western blotting analysis was performed to assess the impact of B4GALNT1 knockdown on the expression of epithelial-mesenchymal transition(EMT)and invasion-related proteins in Saos-2 and U2OS cells. Results:Real-time RT-PCR results showed that B4GALNT1 mRNA expression levels were significantly higher in osteosarcoma tissues and the 3 osteosarcoma cell lines compared to normal tissues and hFOB cells(all P＜0.0 1).CCK-8 and colony formation assays indicated that B4GALNT1 knockdown significantly reduced the proliferation rate of osteosarcoma cells compared to the control group(all P＜0.05).Transwell migration and invasion assays demonstrated that B4GALNT1 knockdown significantly decreased the number of migrating and invading osteosarcoma cells(all P＜0.01).Western blotting analysis revealed that B4GALNT1 knockdown inhibited the expression of N-cadherin,Snail,Vimentin,and matrix metalloproteinase 9(MMP9)compared to the control group(all P＜0.01). Conclusion:B4GALNT1 is upregulated in osteosarcoma tissues and cell lines,and its knockdown suppresses the malignant phenotype of osteosarcoma cells.B4GALNT1 may function as an oncogene in the proliferation and metastasis of osteosarcoma cells.

With the recent ongoing autumn/winter 2022 COVID-19 wave and the adjustment of public health control measures, there have been widespread SARS-CoV-2 infections in Chinese mainland. Here we have analyzed 369 viral genomes from recently diagnosed COVID-19 patients in Shanghai, identifying a large number of sublineages of the SARS-CoV-2 Omicron family. Phylogenetic analysis, coupled with contact history tracing, revealed simultaneous community transmission of two Omicron sublineages dominating the infections in some areas of China (BA.5.2 mainly in Guangzhou and Shanghai, and BF.7 mainly in Beijing) and two highly infectious sublineages recently imported from abroad (XBB and BQ.1). Publicly available data from August 31 to November 29, 2022 indicated an overall severe/critical case rate of 0.035% nationwide, while analysis of 5706 symptomatic patients treated at the Shanghai Public Health Center between September 1 and December 26, 2022 showed that 20 cases (0.35%) without comorbidities progressed into severe/critical conditions and 153 cases (2.68%) with COVID-19-exacerbated comorbidities progressed into severe/critical conditions. These observations shall alert healthcare providers to place more resources for the treatment of severe/critical cases. Furthermore, mathematical modeling predicts this autumn/winter wave might pass through major cities in China by the end of the year, whereas some middle and western provinces and rural areas would be hit by the upcoming infection wave in mid-to-late January 2023, and the duration and magnitude of upcoming outbreak could be dramatically enhanced by the extensive travels during the Spring Festival (January 21, 2023). Altogether, these preliminary data highlight the needs to allocate resources to early diagnosis and effective treatment of severe cases and the protection of vulnerable population, especially in the rural areas, to ensure the country's smooth exit from the ongoing pandemic and accelerate socio-economic recovery.