Humans ; Mitral Valve Stenosis/surgery* ; Transcatheter Aortic Valve Replacement ; Dilatation ; Catheterization ; Aortic Valve Stenosis/surgery* ; Aortic Valve/surgery* ; Treatment Outcome ; Heart Valve Prosthesis ; Heart Valve Prosthesis Implantation

Humans ; Mitral Valve Stenosis/surgery* ; Transcatheter Aortic Valve Replacement ; Dilatation ; Catheterization ; Aortic Valve Stenosis/surgery* ; Aortic Valve/surgery* ; Treatment Outcome ; Heart Valve Prosthesis ; Heart Valve Prosthesis Implantation

The development of broad-spectrum antivirals against human coronaviruses (HCoVs) is critical to combat the current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, as well as future outbreaks of emerging CoVs. We have previously identified a polyethylene glycol-conjugated (PEGylated) lipopeptide, EK1C4, with potent pan-CoV fusion inhibitory activity. However, PEG linkers in peptide or protein drugs may reduce stability or induce anti-PEG antibodies in vivo. Therefore, we herein report the design and synthesis of a series of dePEGylated lipopeptide-based pan-CoV fusion inhibitors featuring the replacement of the PEG linker with amino acids in the heptad repeat 2 C-terminal fragment (HR2-CF) of HCoV-OC43. Among these lipopeptides, EKL1C showed the most potent inhibitory activity against infection by SARS-CoV-2 and its spike (S) mutants, as well as other HCoVs and some bat SARS-related coronaviruses (SARSr-CoVs) tested. The dePEGylated lipopeptide EKL1C exhibited significantly stronger resistance to proteolytic enzymes, better metabolic stability in mouse serum, higher thermostability than the PEGylated lipopeptide EK1C4, suggesting that EKL1C could be further developed as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases.

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.
China ; Gastrointestinal Agents/therapeutic use* ; Gastrointestinal Neoplasms ; Humans ; Pharmaceutical Preparations ; United States ; United States Food and Drug Administration

Objective: To evaluate the reliability and validity of the Chinese Criteria of Health Scale for the elderly people. Methods: A cross-sectional study was performed among older adults of Meiyuan Community in Haidian District, Beijing and Nanwangkong Village in Qingzhou City,Shandong Province during July 2021. Using a cluster sampling method, totally 667 elderly people were investigated by face-to-face interview, using the scale which was formulated after two rounds of the Delphi method and pilot study. The overall scale includes physical health, mental health and social health subscales, including 9, 52 and 15 items, respectively. Four weeks after the survey, 56 elderly people were randomly selected and repeated the survey with the same method. The test-retest reliability, split-half reliability and internal consistency reliability of the scale were evaluated, and the validity was evaluated at the same time, including construct validity and content validity. Results: A total of 710 questionnaires were distributed and 667 valid questionnaires were obtained, with a total effective rate of 93.94%. The score of the overall scale was 79.79±16.22, the scores of the physical health, mental health, social health sub-scores were 41.64±9.76, 26.82±3.92 and 11.34±5.19, respectively. The scale had excellent reliability. In the test-retest reliability, the intraclass correlation coefficient (ICC) of the overall scale and each subscale were 0.766-0.861, and the weighted Kappa values were 0.762-0.817. The Spearman-Brown coefficient of the overall scale and each subscale in the split-half reliability were 0.722-0.855 (all P<0.001). The Cronbach's α coefficients of the overall scale of internal consistency reliability and each subscale were 0.748-0.899, and the Cronbach's α coefficients of each dimension were from 0.709 to 0.963(all P<0.001). At the same time, the scale had good construct validity and content validity. The correlation coefficients between the score of each dimension and its sub-scale were larger, from 0.641 to 0.873 (all P<0.05). The cumulative variance contribution rates of the scale and three subscales were all more than 50% of the approved standard. A total of 11 common factors were extracted, and all the load values of each item on the corresponding factors were ≥0.04. Conclusion: The Chinese Criteria of Health Scale for the elderly people has good validity and excellent reliability. It can be used as a basis for the scientific division of the health status of the elderly, the formulation of relevant policies by the government and the provision of appropriate health services for the elderly.
Humans ; Aged ; Reproducibility of Results ; Cross-Sectional Studies ; Pilot Projects ; East Asian People ; Surveys and Questionnaires ; Psychometrics/methods* ; China

Objective:To compare the left ventricular (LV) reverse remodeling after transcatheter aortic valve replacement (TAVR) between patients with bicuspid aortic valve (BAV) stenosis and tricuspid aortic valve (TAV) stenosis.Methods:The data of patients who underwent TAVR procedure from March 2013 to December 2018 in the Second Affiliated Hospital of Zhejiang University were retrospectively reviewed. The patients were divided into BAV group and TAV group according to cardiac computed tomography. Echocardiographic parameters, including aortic valve peak velocity (Vmax), mean gradient (PGmean), effective orifice area(EOA), interventricular septum diastolic thickness (IVSd), left ventricular posterior wall diastolic thickness (LVPWd), left ventricular end diastolic diameter( LVEDd), LV mass index (LVMI), ΔLVMI%, left ventricular ejection fraction( LVEF) of the two groups at baseline, 1 week, 1 month and 1 year post TAVR procedure were obtained and compared.Results:①Compared with preoperative measurements, both groups showed decreases in Vmax, PGmean and increase in EOA at 1 week, 1 month, 1 year follow-ups(all P<0.05). No significant differences were found in Vmax, PGmean, EOA, moderate/sever perivalvular leakage(PVL), moderate/sever prosthetic-patient mismatch(PPM) between BAV group and TAV group at 1 year. ②Both groups showed decreases in IVSd, LVPWd, LVEDd at 1 month, 1 year post TAVR compared with those before the procedure (all P<0.05), as well as increases in LVEF at 1 week, 1 month, 1 year (all P<0.05). Downward trends of LVMI were detected in both groups within 1 year follow-up( P<0.05). ③Compared to TAV group, BAV group showed smaller baseline LVMI( P<0.05), while there were no significant differences in ΔLVMI% post TAVR for all follow-up times of the two groups(all P>0.05). Repeated measures analysis of variance also showed no significant differences in downward trend of LVMI between the two groups after TAVR within 1 year( P>0.05). Conclusions:Left ventricular reverse remodeling can be detected in both BAV and TAV patients after TAVR, which starts from 1 week and can be lasted for 1 year post procedure. Patients with bicuspid morphology might experience similar reverse LV remodeling post TAVR versus patients with tricuspid morphology.

Aortic Valve/surgery* ; Aortic Valve Insufficiency/surgery* ; Aortic Valve Stenosis/surgery* ; Heart Valve Prosthesis ; Humans ; Perioperative Period ; Severity of Illness Index ; Transcatheter Aortic Valve Replacement ; Treatment Outcome

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome