Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.

With the development of molecular pharmacognosy, the advantages of DNA molecular markers in the identification of original plants of Chinese medicinal materials are becoming increasingly significant. To compensate for the limitations of existing markers in the quality supervision of Chinese medicinal materials, our team has independently designed a new molecular marker named DNA signature sequence(DSS). This marker is a nucleotide sequence that only appears in a specific taxonomic unit, with a length of 40 bp and high identification accuracy. This article aims to screen and verify the DSS markers that can accurately identify the original plants of the medicinal materials included in the volume one of the Chinese Pharmacopoeia, establish the operating procedure for developing standard nucleotide sequences, and lay a foundation for the widespread application of polymerase chain reaction in the quality supervision of traditional Chinese medicine. Firstly, the Chloroplast Genome Information Resource(CGIR) was searched for the chloroplast genome sequences of the test samples, species of the same genus, and common background species. IdenDSS was used to obtain the DSS tags and specific identification primers of the tested species. After DNA extraction, PCR amplification, sequencing, and sequence alignments, a total of 203 DSS markers of Chinese medicinal materials were obtained for validation. The above sequences were uploaded to the Traditional Chinese Medicine Molecular Identification Platform(www.herbsdna.com), and a standard DSS library was established for identifying the original plants of medicinal materials, serving as an important tool for quality supervision of Chinese materia medica. On this basis, an operating procedure for DSS development is formed, laying a foundation for further DSS screening and application based on more diverse genome sequences.
Plants, Medicinal/classification* ; DNA, Plant/genetics* ; Drugs, Chinese Herbal ; Pharmacopoeias as Topic ; Genetic Markers ; Medicine, Chinese Traditional

Acute lung injury (ALI), as a common clinical emergency, is pulmonary edema and diffuse lung infiltration caused by inflammation. The lack of non-invasive alert strategy, resulting in failure to carry out preventive treatment, means high mortality and poor prognosis. Stimulator of interferon genes (STING) is a key molecular biomarker of innate immunity in response to inflammation, but there is still a lack of STING-targeted strategy. In this study, a novel STING-targeted PET tracer, [¹⁸F]FBTA, was labeled with high radiochemical yield (79.7 ± 4.3%) and molar activity (32.5 ± 2.9 GBq/μmol). We confirmed that [¹⁸F]FBTA has a strong STING binding affinity (K_d = 26.86 ± 6.79 nmol/L) and can be used for PET imaging in ALI mice to alert early lung inflammation and to assess the efficacy of drug therapy. Our STING-targeted strategy also reveals that [¹⁸F]FBTA can trace ALI before reaching the computed tomography (CT) diagnostic criteria, and demonstrates its better specificity and distribution than [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG).

Objective: To compare the prognosis of mildly or severely symptomatic patients with obstructive hypertrophic cardiomyopathy (OHCM) who underwent alcohol septal ablation (ASA). Methods: This retrospective study cohort consisted of patients with OHCM who received ASA treatment in Beijing Anzhen Hospital, Capital Medical University from March 2001 to August 2021. These patients were divided into mildly and severely symptomatic groups according to the severity of clinical symptoms. Long-term follow-up was conducted, and the following data were collected: duration of follow-up, postoperatire treatment, New York Heart Association (NYHA) classification, arrhythmia events and pacemaker implantation, echocardiographic parameters, and cause of death. Overall survival and survival free from OHCM-related death were observed, and the improvement of clinical symptoms and resting left ventricular outflow tract gradient (LVOTG) and the incidence of new-onset atrial fibrillation were evaluated. The Kaplan-Meier method and log-rank test were used to determine and compare the cumulative survival rates of the different groups. Cox regression analysis models were used to determine predictors of clinical events. Results: A total of 189 OHCM patients were included in this study, including 68 in the mildly symptomatic group and 121 in the severely symptomatic group. The median follow-up of the study was 6.0 (2.7, 10.6) years. There was no statistical difference in overall survival between the mildly symptomatic group (5-year and 10-year overall survival were 97.0% and 94.4%, respectively) and the severely symptomatic group (5-year and 10-year overall survival were 94.2% and 83.9%, respectively, P=0.405); there was also no statistical difference in survival free from OHCM-related death between the mildly symptomatic group (5-year and 10-year survival free from HCM-related death were 97.0% and 94.4%, respectively) and the severely symptomatic group (5-year and 10-year survival free from HCM-related death were 95.2% and 92.6%, respectively, P=0.846). In the mildly symptomatic group, NYHA classification was improved after ASA (P<0.001), among which 37 patients (54.4%) were in NYHA class Ⅰ, and the resting left ventricular outflow tract gradient (LVOTG) decreased from 67.6 (42.7, 90.1) mmHg (1 mmHg=0.133 kPa) to 24.4 (11.7, 35.6) mmHg (P<0.001). In severely symptomatic group, NYHA classification was also improved post ASA (P<0.001), among which 96 patients (79.3%) improved by at least one NYHA classification, and the resting LVOTG decreased from 69.6 (38.4, 96.1) mmHg to 19.0 (10.6, 39.8) mmHg (P<0.001). The incidence of new-onset atrial fibrillation was similar between the mildly and severely symptomatic groups (10.2% vs. 13.3%, P=0.565). Cox multivariate regression analysis showed that age was an independent predictor of all-cause mortality in OHCM patients post ASA (HR=1.068, 95%CI 1.002-1.139, P=0.042). Conclusions: Among patients with OHCM treated with ASA, overall survival and survival free from HCM-related death were similar between mildly symptomatic group and severely symptomatic group. ASA therapy can effectively relieve resting LVOTG and improve clinical symptoms in mildly or severely symptomatic patients with OHCM. Age was an independent predictor of all-cause mortality in OHCM patients post ASA.
Humans ; Retrospective Studies ; Atrial Fibrillation ; Heart Septum/surgery* ; Treatment Outcome ; Cardiomyopathy, Hypertrophic/surgery*

Aim To investigate the possible mechanism of quercetin in promoting apoptosis of breast cancer cells. Methods Breast cancer cells MCF-7 were treated with quercetin. Cell viability was detected by MTT assay, cell proliferation and cloning ability were measured by plate colony formation assay, and cell apoptosis was examined by Annexin V-FITC/PI double staining assay. Meanwhile, MCF-7 cells were treated with quercetin (40, 80, 160 μmol · L

Objective: To determine the prevalence and determinants of folic acid (FA) supplementation in Chinese couples planning for pregnancy and in women during early pregnancy. Methods: This was a cross-sectional study based on the Shanghai PreConception Cohort (SPCC) study. Data on FA supplementation and socio-demographic features were collected using questionnaires. Couples visiting clinics for pre-pregnancy examination and pregnant women at < 14 gestational weeks were recruited in Shanghai, China, between March 2016 and September 2018. Results: Among the pregnancy planners, 42.4% (4,710/11,099) women and 17.1% (1,377/8,045) men used FA supplements, while 93.4% (14,585/15,615) of the pregnant women used FA supplements. FA supplement use was higher in female pregnancy planners who were older ( : 1.13, 95% : 1.08-1.18), had higher education ( : 1.71, 95% : 1.53-1.92), and were residing in urban districts ( : 1.06, 95% : 1.01-1.11) of FA supplementation; female pregnancy planners with alcohol consumption ( : 0.95, 95% : 0.90-0.99) had lower odds of FA supplementation. In early pregnancy, women with higher educational level ( : 1.04, 95% : 1.03-1.06), who underwent pre-pregnancy examination ( : 1.02, 95% : 1.01-1.03) had higher odds of using an FA supplement; older aged ( : 0.99, 95% : 0.98-0.99), and multigravida ( : 0.97, 95% : 0.96-0.98) had lower odds of FA supplementation. Conclusion Although the majority of pregnant women took FA supplements, more than half of the women planning for pregnancy did not. Urgent strategies are needed to improve pre-conception FA supplementation.
Adult ; China ; Cohort Studies ; Cross-Sectional Studies ; Diet ; Dietary Supplements ; analysis ; Female ; Folic Acid ; administration & dosage ; Humans ; Male ; Pregnancy ; Surveys and Questionnaires ; Vitamin B Complex ; administration & dosage ; Young Adult

Tung tree (Vernicia fordii) is an economically important woody oil plant that produces tung oil rich in eleostearic acid. Here, we report a high-quality chromosome-scale genome sequence of tung tree. The genome sequence was assembled by combining Illumina short reads, Pacific Bio-sciences single-molecule real-time long reads, and Hi-C sequencing data. The size of tung tree gen-ome is 1.12 Gb, with 28,422 predicted genes and over 73％ repeat sequences. The V. fordii underwent an ancient genome triplication event shared by core eudicots but no further whole-genome duplication in the subsequent ca. 34.55 million years of evolutionary history of the tung tree lineage. Insertion time analysis revealed that repeat-driven genome expansion might have arisen as a result of long-standing long terminal repeat retrotransposon bursts and lack of efficient DNA deletion mechanisms. The genome harbors 88 resistance genes encoding nucleotide-binding sites;17 of these genes may be involved in early-infection stage of Fusarium wilt resistance. Further, 651 oil-related genes were identified, 88 of which are predicted to be directly involved in tung oil biosynthesis. Relatively few phosphoenolpyruvate carboxykinase genes, and synergistic effectsbetween transcription factors and oil biosynthesis-related genes might contribute to the high oil content of tung seed. The tung tree genome constitutes a valuable resource for understanding genome evolution, as well as for molecular breeding and genetic improvements for oil production.

Objective To assess the limit of detection(LOD),sensitivity and specificity of collodial gold immunochrom-atography(GICA)products purchased from two manufacturers under special environmental conditions.Methods The sensitivity and specificity of GICA made in InTec Products, INC.and Beijing WANTAI Biological Pharmacy Enterprise Co., LTD.for detecting HBsAg, anti-HCV and anti-Treponema pallidum(TP)serum samples were evaluated under different conditions(conventional facilities,simulated hot and humid environments and simulated low pressure and hypoxia environments)according to the protocol of kits.LOD was estimated by detecting the standard materials obtained from the National Center for Clinical Laboratory(NCCL)of China.Results LOD for syphilis improved from 2 NCU to 1 NCU using GICA from InTec Products in hot and humid environments.The extreme conditions did not influence the specificity of GICA from the two manufacturers in the course of detection of clinical samples,but the sensitivity of detection was affected.For InTec Products,the sensitivity of hepatitis B virus and syphilis detection was improved in hot and humid environments,but was reduced in low pressure and hypoxia environments.In addition,the sensitivity of hepatitis C virus detection by InTec Products decreased in hot and humid environments.As for WANTAI products,the sensitivity of hepatitis B virus detection was reduced under extreme conditions and that of hepatitis C virus was only influenced by hot and humid environments. Interestingly, extreme conditions had no impact on the sensitivity of syphilis.Conclusion LOD of InTec Products is better than that of the WANTAI products for detection of standard materials from blood-borne diseases.In the process of detecting clinical samples,the sensitivity of the two manufacturers′GICA is influenced by extreme conditions, with the specificity unchanged.Overall, WANTAI products are more stable than those of InTec, and are also less influenced by extreme conditions.

Objective To study the damage propagation and evolution mechanism of cartilage under compressive load. Methods The fiber-reinforced porous elastic model of cartilage with micro-defect was established by using finite element method, and the process of damage evolution under compressive load was simulated and analyzed with parameters. The patterns of stress and strain distributions on cartilage matrix and collagen fiber at different damage extension stage were obtained. Results The strain in surface and the forefront of cartilage damage increased significantly with the increase of compression displacement, and they were obviously in positive correlation; in the process of damage evolution, there was a trend that cartilage extended to the deep and both sides simultaneously; cracks and damage in cartilage extended preferentially along the fiber tangent direction. With the aggravation of cartilage damage, the lateral extension speed was significantly faster than the longitudinal extension speed. Conclusions The process of cartilage damage extension has a close relationship with the distribution of fibers. And the damage in matrix and fiber promote each other. The evolution speed and degree of cartilage vary constantly in different layers and at different stages. These results can provide the qualitative reference for prediction and repair of cartilage damage, as well as the theoretical basis for explaining clinical pathological phenomena of damage degeneration and treatment.