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.

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

In the clinical practice, Professor Jiang Liangduo, a national senior Chinese medicine doctor, has created the theory of "sanjiao meridian stasis" from the theory of meridian dialectics and from the overall state. In this paper, the traditional Chinese medicine and Western medicine clinical characteristics of sanjiao meridian stasis theory which is often used by Professor Jiang Liangduo in the treatment of out-patient syndrome differentiation, were first studied and summarized to investigate its inherent regularity. First, the source of data and research methods were introduced, and then the Traditional Chinese Medicine Inheritance Support System was used with the method of data mining to retrospectively analyze the disease characteristics of Chinese and Western medicine in 279 patients with sanjiao meridian stasis diagnosed by Professor Jiang in 2014. Then the following main conclusions were made after research: sanjiao meridian stasis was more common in women as well as young and middle-aged population. Often manifested by prolonged treatment course, red tongue with yellowishfur, with good correlation between modern Western medicine diagnosis and TCM differentiation syndrome. The symptoms of sanjiao meridian stasis syndrome are mostly of heat syndromes, and middle-aged patients are the most common patients with stasis and stasis of sanjiao. Related information of Western medicine diagnosis can help to diagnose the "sanjiao meridian stasis".

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.

AIM To optimize the aqueous extraction for polysaccharides from Astragali Radix and to evaluate the in vitro antitumor activity.METHODS With extraction temperature,extraction time and solid-liquid ratio as influencing factors,extraction rate of polysaccharides as an evaluation index,the extraction was optimized by uniform design.The effect of polysaccharides on the proliferation of non-small cell lung cancer NCI-H460 cells,the apoptosis rate and cell cycle of NCI-H460 cells,and the expressions of Caspase-3,Bax and Bcl-2 were detected by MTT assay,flow cytometry and Western blot,respectively.RESULTS The optimal conditions were determined to be 100 ℃ for extraction temperature,1 h for extraction time,and 1 ∶ 35 for solid-liquid ratio,the extraction rate of polysaccharides was 3.62％.Compared with the control group,the proliferation of NCI-H460 cells was significandy inhibited in a dose-dependent manner (P ＜ 0.01),the S phase ratio,early apoptosis rate,late apoptosis rate and total apoptosis rate were markedly increased (P ＜ 0.01),and the Caspase-3 expression and Bax/Bcl-2 ratio were also obviously increased (P ＜ 0.01) in the polysaccharides group.CONCLUSION This fast,stable and reliable method can be used for the aqueous extraction for polysaccharides from Astragali Radix,which can significantly inhibit the proliferation of NCI-H460 cells and induce apoptosis of NCI-H460 cells.

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 loads.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 loads was simulated and analyzed with parameters.The patterns of stress and strain distributions on cartilage matrix and collagen fiber at different damage extension stages were obtained.Results The strain in the surface and 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.The damages 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 pathological phenomena of damage degeneration and its clinic treatment.

Objective To investigate the clinical application of measurements of neutrophil gelatinase associated lipocalin in serum (sN-GAL) and urine(uNGAL),cystatin C(CysC) and serum creatinine(sCr) in diagnosis of acute kidney injury(AKI) patients secondary to liver cirrhosis (LC).Methods A total of 260 liver cirrhosis patients without AKI (LC group),207 liver cirrhosis patients with AKI (AKI group)and 106 healthy controls(HC group)were included in the study.The levels of sNGAL,uNGAL,serum creatinine(sCr) and cystatin C (CysC) were determined,respectively.The estimated glomerular filtration rate (eGFR) were calculated base on sCr and CysC,named as c-aGFR and CysC-eGFR.The differences and correlation of each observed parameters among the various groups were statistically analyzed,and the effectiveness of these parameters as biomarkers for predicting the development of AKI in these patients with liver cirrhosis were assessed.Results Compared with LC group and healthy control group,the levels of sNGAL,uNGAL,sCr and CysC in AKI group were significantly increased(all P ＜0.01),while the levels of c-aGFR and CysC-eGFR were significantly decreased(all P ＜ 0.01).Along with the progression of AKI stages,the levels of sNGAL,uNGAL,sCr and CysC in the patients were increasing(all P ＜ 0.01),while the levels of c-aGFR and CysC-eGFR were decreasing(all P ＜0.01).Correlation analysis showed that the levels of sNGAL,uNGAL and CysC were positively correlated with sCr(r =0.662,0.672,0.726,all P ＜0.01)and negatively correlated with c-aGFR(r =-0.639,-0.661,-0.732,all P ＜ 0.01).On the contrary,CysC was negatively correlated with sCr (r =-0.711,P ＜ 0.01)and positively correlated with c-aGFR (r =0.736,P ＜ 0.01).ROC curve analysis showed that the area under the curve (AUC) of uNGAL was maximum (0.995) which were significantly higher than that of sNGAL,sCr,c-aGFR,CysC and CysCeGFR(all P ＜ 0.01).The AUC of sNGAL did not present marked difference with that of sCr and CysC (P ＞ 0.05),but-was barely higher than that of c-aGFR and CysC-eGFR (P ＜ 0.05).The diagnostic effectiveness of uNGAL was maximum (0.962),followed by sNGAL(0.920).Conclusion For diagnosis of the development of AKI in the patients with liver cirrhosis,NGAL may be more reliable marker than sCr and CysC,and the detection of uNGAL could be more effective than sNGAL for the diagnosis.

OBJECTIVETo study the mechanism of interleukin 7/interleukin 7 receptor (IL-7/IL-7R) in promoting cell proliferation and inducing lymphangiogenesis of non-small cell lung cancer (NSCLC) in vivo and in vitro.

METHODSImmunohistochemical study for IL-7, IL-7R, cyclin D1 and vascular endothelial growth factor-D (VEGF-D) was carried out in NSCLC tissues from 95 patients. The relationship between IL-7/IL-7R expression and various parameters was analyzed. The mechanism of IL-7/IL-7R in promoting cell proliferation and inducing lymphangiogenesis was studied by methylthiazolyldiphenyl-tetrazolium bromide, fluorescence-activated cell sorting, reverse transcriptase-PCR, Western blot, co-immunoprecipitation, chromatin immunoprecipitation and nude mice experiments with xenograft tumors.

RESULTSIL-7 (63.2%, 60/95), IL-7R (61.1%, 58/95), cyclin D1 (52.6%, 50/95) and VEGF-D (58.9%, 56/95) showed that high level of expression in NSCLC. IL-7/IL-7R over-expression correlated with cyclin D1 expression (P < 0.01, P < 0.01), VEGF-D expression (P < 0.01, P < 0.01), increased lymphovascular density (P = 0.005, P = 0.013), advanced clinical stage (P = 0.008, P = 0.005) and presence of lymph node metastasis (P < 0.01, P < 0.01). IL-7/IL-7R could promote proliferation of A549 cell, increase cyclin D1 and VEGF-D expression, and enhance c-Fos/c-Jun expression and phosphorylation, resulting in formation of heterodimer. Furthermore, IL-7/IL-7R could induce binding of c-Fos/c-Jun to cyclin D1/VEGF-D promoters and regulate their transcription. IL-7/IL-7R could also promote proliferation and lymphangiogenesis of lung cancer xenograft tumors.

CONCLUSIONSIL-7/IL-7R promotes c-Fos/c-Jun expression and activity in NSCLC. This further facilitates cyclin D1 expression and accelerates proliferation of cells and VEGF-D-induced lymphovascular formation.

Animals ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Cyclin D1 ; metabolism ; Female ; Humans ; Interleukin-7 ; metabolism ; physiology ; Lung Neoplasms ; metabolism ; pathology ; Lymphangiogenesis ; Lymphatic Metastasis ; Male ; Mice ; Mice, Nude ; Middle Aged ; Neoplasm Staging ; Neoplasm Transplantation ; Proto-Oncogene Proteins c-fos ; metabolism ; Proto-Oncogene Proteins c-jun ; metabolism ; Receptors, Interleukin-7 ; metabolism ; physiology ; Vascular Endothelial Growth Factor D ; metabolism