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.

In order to investigate the effect of Shouwu Shudi Yin on dopaminegic neurons in MPTP induced Parkinson's disease mouse model and the possible mechamism, the experimental mice were randomly divided into 4 groups: control, Shouwu Shudi Yin, MPTP and the treatment (MPTP+Shouwu Shudi Yin) groups. The number of tyrosine hydroxylase (TH) positive cells in the substantia nigra was measured by immunohistochemistry, and mRNA expression of TH and glutathione peroxidase (GPX) were detected by PCR. The results showed that the number of TH positive cells and mRNA expression of TH were significantly reduced in MPTP group compared with the control (P<0.05), and pretreated with Shouwu Shudi Yin didn't show protective effect. Compared to MPTP group, the mRNA expression of four subtypes of GPX were increased in various degrees in the treatment group pretreated with Shouwu Shudi Yin, although the difference was not statistically significant. These indicated that the preventive medication of Shouwu Shudi Yin don't have protective effect on the mice with Parkinson' s disease induced by MPTP, but it may enhance the antioxidant capacity through increasing the expression of GPX.

OBJECTIVETo compare the value of CT and mediastinoscopy in assessment of mediastinal lymph node status in potentially operable non-small cell lung cancer (NSCLC).

METHODSFrom Oct. 2000 to Jun. 2007, 152 consecutive patients with pathologically proven and stage I to approximately III NSCLC were enrolled into the study. Of the 152 cases, there were 118 males and 34 females, with a median age of 58 years (range, 24 to approximately 79 years). Compared with the final pathology, the sensitivity, specificity, positive and negative predictive values and accuracy of CT and mediastinoscopy for preoperative evaluation of mediastinal lymph node status were calculated, respectively. The accuracy and diagnostic efficacy of CT and mediastinoscopy was compared by Pearson chi(2) test and ROC curve, respectively.

RESULTSThe sensitivity, specificity, positive predictive value, negative predictive value and accuracy of detection of mediastinal metastasis was 73.8%, 70.1%, 64.9%, 78.2% and 71.7% by CT, respectively, versus 83.1%, 100.0%, 100.0%, 88.8% and 92.8% by mediastinoscopy, respectively. Both the accuracy and diagnostic efficacy of mediastinoscopy were superior to CT (Pearson chi(2) test, P < 0.001; Z test of the areas under the ROC curve, P < 0.001). The complication rate of mediastinoscopy was 4.6%, and the false negative rate was 7.2%.

CONCLUSIONMediastinoscopy is safe and effective in preoperative assessment of mediastinal lymph node status in potentially operable NSCLC, while CT alone is inadequate.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; diagnostic imaging ; pathology ; False Negative Reactions ; Female ; Humans ; Lung Neoplasms ; diagnostic imaging ; pathology ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; diagnostic imaging ; pathology ; Male ; Mediastinoscopy ; Mediastinum ; Middle Aged ; Prospective Studies ; ROC Curve ; Sensitivity and Specificity ; Tomography, X-Ray Computed ; Young Adult

OBJECTIVETo investigate the effects of the self-developed anti-heparanase polypeptide antibodies on growth and invasion of human hepatocellular carcinoma HCCLM6 cells.

METHODSUsing MTT, flow cytometry, plate clone formation, transwell invasion and heparan degrading enzyme assay, the growth and invasion changes of human hepatocellular carcinoma HCCLM6 cells by co-culture with each of three self-developed rabbit anti-heparanase polyclonal antibodies were detected.

RESULTSCompared with normal rabbit IgG, in the presence of each anti-heparanase polypeptide antibody, the growth, cell cycle and clone formation remained unchanged, and under the P1 or P2 anti-heparanase polypeptide antibody (with final concentration 100 microg/ml), the cell invasiveness was inhibited by 52.5% and 36.6%, respectively, and the heparanase activity was inhibited by 42.9% and 39.1%, respectively.

CONCLUSIONThe P1 and P2 anti-heparanase polypeptide antibodies can effectively inhibit the invasion ability and heparanase activity of liver cancer HCCLM6 cells. However, All the three antibodies have no effects on its growth, cell cycle and clone formation.

Antibodies ; pharmacology ; Carcinoma, Hepatocellular ; enzymology ; pathology ; Cell Adhesion ; Cell Differentiation ; Cell Line, Tumor ; Cell Movement ; Coculture Techniques ; Enzyme Activation ; Glucuronidase ; immunology ; metabolism ; Humans ; Liver Neoplasms ; enzymology ; pathology ; Neoplasm Invasiveness

OBJECTIVETo discuss the strategy of mediastinoscopy for the evaluation of mediastinal lymph node status (metastasis or not) of non-small cell lung cancer (NSCLC) prior to surgery.

METHODSFrom October 2000 to June 2007, 152 consecutive NSCLC cases pathologically proven and clinically staged I-III were enrolled in the study. Of the 152 cases, there were 118 males and 34 females. Age ranged 24-79 years old and the median age was 58. All cases underwent CT and mediastinoscopy for the evaluation of mediastinal lymph node status prior to surgery. Compared with the results of final pathology, the positive rate of mediastinoscopy and the prevalence of mediastinal lymph node metastasis were calculated in the NSCLC patients with negative mediastinal or hilar lymph nodes on CT scan (the shortest axis of mediastinal or hilar lymph nodes <1 cm). Clinical characteristics used as predictive factor including sex, age, cancer location, type of pathology, T status, cancer type (central or peripheral), size of mediastinal lymph nodes (the shortest axis <1 cm or >1 cm) on CT scan and serum CEA level were analyzed by univariate and multivariate analysis with Binary logistic regression model to identify risk factors of mediastinal metastasis.

RESULTSThe positive rate of mediastinoscopy was 11.6% (8/69) and the prevalence of mediastinal metastasis was 20.1% (14/69) in NSCLC with negative mediastinal or hilar lymph nodes on CT scan respectively. In clinical stage I (cT1-2N0M0) NSCLC the positive rate of mediastinoscopy was 11.3% (7/62), N2 accounting for 6.5% (4/62) and N3 4.8% (3/62), respectively; and the prevalence of mediastinal lymph node metastasis was 19.4% (12/62), N2 ccounting for 14.6% (9/62) and N3 4.8% (3/62), respectively. In the whole group both univariate and multivariate analysis showed that adenocarcinoma or mediastinal lymph nodes > or =1 cm in the shortest axis on CT scan was an independent risk factor to predict mediastinal lymph node metastasis. In NSCLC with negative mediastinal or hilar lymph nodes on CT scan both univariate and multivariate analysis showed that adenocarcinoma was a predictor of mediastinal lymph node metastasis. Conclusion We recommend the policy of routine mediastinoscopy in NSCLC prior to surgery if the mediastinal staging was only based on CT scan. Mediastinal lymph nodes > or =1 cm in the shortest axis on CT scan mandates preoperative mediastinoscopy. Adenocarcinoma also indicates mandatory mediastinoscopy even with negative mediastinal or hilar lymph nodes on CT scan.

Adenocarcinoma ; diagnostic imaging ; pathology ; surgery ; Adult ; Aged ; Carcinoembryonic Antigen ; blood ; Carcinoma, Non-Small-Cell Lung ; diagnostic imaging ; pathology ; surgery ; Female ; Humans ; Logistic Models ; Lung Neoplasms ; diagnostic imaging ; pathology ; surgery ; Lymph Nodes ; diagnostic imaging ; pathology ; surgery ; Lymphatic Metastasis ; diagnostic imaging ; pathology ; Male ; Mediastinoscopy ; Mediastinum ; Middle Aged ; Neoplasm Staging ; Preoperative Period ; Risk Factors ; Tomography, X-Ray Computed ; Young Adult

OBJECTIVETo analyze the patterns of serum soluble CD14 (sCD14) and C-reactive protein (CRP) alterations in patients with chronic heart failure (CHF) and investigate the correlations of sCD14 variation to the etiology, clinical symptoms, and the number of mononuclear cells in these patients.

METHODSThis study involved 246 CHF patients stratified according to their etiology and clinical symptoms, with 107 normal individuals serving as the control group. Blood samples were collected from these patients the next day after admission and also from the control subjects for measuring serum sCD14 and CPR levels using enzyme-linked immunosorbent assay (ELISA) and rate nephelometry, respectively.

RESULTSThe CHF patients had significantly higher serum levels of sCD14 and CRP than the control subjects (P<0.01). In the CHF patients, serum sCD14 and CRP levels differed significantly in the patients with clinical symptoms of different severities (F=3.787, P=0.024), and those with moderate and severe symptoms had significantly higher levels than the asymptomatic patients (P<0.05). The difference in etiologies also resulted in significant difference in sCD14 levels (P<0.05), which were significantly lower in coronary artery disease group than in hypertension group (P<0.05). Significant positive correlations were found between sCD14 and the CRP levels in the CHF patients (r=0.227, P=0.018) and between sCD14 level and the clinical symptoms (r=0.206, P=0.001), but sCD14 level was not correlated to the absolute or relative number of mononuclear cells.

CONCLUSIONSSerum sCD14 and CRP levels are significantly elevated in CHF patients, but this condition may vary as the etiologies and clinical symptoms differ. Increased mononuclear cells do not contribute to the elevation of serum sCD14.

Adult ; Aged ; Aged, 80 and over ; C-Reactive Protein ; metabolism ; Chronic Disease ; Enzyme-Linked Immunosorbent Assay ; Female ; Heart Failure ; blood ; Humans ; Lipopolysaccharide Receptors ; blood ; Male ; Middle Aged

Objective To study the prognostic value of circumferential resection margin(CRM)status. Methods Specimens of 62 patients with rectal cancer,who underwent total mesorectal excision from December,2001 to June,2002,were examined using whole-mount sections.All patients were followed up for 4～60 months. Results Circumferential resection margin involvement(CRMI)was identified in 12 specimens.while only 4 of them were cancer positive in the resection margin.Analyzed by logistic regression test,the occurrence of CRMI was related to tumor differentiation [ P=0.015,Exp(B)=0.131]and lymph node metastases[P=0.013,Exp(B)=7.488 ],but not tumor distance to anal verge(P=0.246).The difference in local recurrence rate,overall recurrence rate,disease-free survival rate and overall survival rate between CRMI and that of CRM negative,were significant(P=0.002,0.000,0.000 and 0.003,respectively). Conclusions CRMI is an accurate prognostic factor of recurrence and postoperative survival,and its occurrence is mainly determined by biologic characteristics of the tumor.TME could decrease the incidence of CRMI.

Using the amino acids 1-147 of the yeast transcriptional activator GAL4 as the DNA-binding domain and four tandem repeats of the 12-aa peptide (DALDDFDLDMLG) of the herpesvirus as the activation domain, an artificial transcription factor, GVP4,was constructed via the linkage of the nuclear localization signal sequence of SV40. And then, GVP4 was cloned into expression vector pcDNA3 . 1/Hygro ( + ) . Various amounts of targeting sites of artificial transcription factor were linked to the upstream of promoter CMV in exogenous gene expression vector pcDNA3.1 ( + ) that separately harbored EGFP cDNA and t-PA cDNA.The CHO cells were then co-transfected with GVP4 expression vector and EGFP or t-PA expression vector. The effect of GVP4 on exogenous gene expression was evaluated by measuring the fluorescence intensity of EGFP in CHO cells and the concentration of t-PA in the supernatant. GVP4 showed positive effect on the enhancement of exogenous gene expression in CHO cells integrated with targeting sites of artificial transcription factor. And, CHO cells integrated with 10 targeting sites of GVP4 was more favorable to foreign gene expression, which resulted in 2-3-fold increase in both EGFP and t-PA expressions. These results indicated that artificial transcription factor is potent in the enhancement of exogenous gene expression in mammalian cells.
Amino Acid Sequence ; Animals ; CHO Cells ; Cricetinae ; Cricetulus ; Flow Cytometry ; Gene Expression Regulation ; Genetic Vectors ; genetics ; Green Fluorescent Proteins ; genetics ; metabolism ; Tissue Plasminogen Activator ; genetics ; metabolism ; Transcription Factors ; genetics ; metabolism ; Transcriptional Activation ; Transfection

OBJECTIVETo evaluate the clinical effect of transrectal high-intensity focused ultrasound (HIFU) in the treatment of prostate cancer (PCa).

METHODSA total of 57 PCa patients, 27 localized and 30 advanced, underwent transrectal HIFU with the Sonab- late 500, the localized group treated by transrectal HIFU only, while the advanced group by transrectal HIFU combined with androgen ablation.

RESULTSFor the HIFU treatment, the mean operating time, hospital stay and follow-up were 111 mm (ranging from 86 to 153 mm), 3.2 days (ranging from 2 to 18 days) and 18 months (ranging from 6 to 30 months), respectively. The biochemical disease-free rates at 1, 2 and 3 years in the localized group were 86%, 81% and 79%, respectively. While in the advanced group, the serum prostate specific antigen (PSA) was < 4.0 microg/L in 26 cases ( < 0.51 microg/L in 20) and the prostate volume decreased more than 50% in 21 cases after treated for an average of 8 months (ranging from 3 to 24 months). After transrectal HIFU prostate ablation, the prostate volume reduced, serum PSA lowered, Qmax raised and IPSS improved significantly (P < 0.05). No serious complications occurred including severe urethrorectal fistula and incontinence.

CONCLUSIONTransrectal HIFU is a safe, effective and minimally invasive therapy for patients with prostate cancer.

Aged ; Aged, 80 and over ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; blood ; pathology ; therapy ; Treatment Outcome ; Ultrasound, High-Intensity Focused, Transrectal