Standard Operating Procedures for Chinese Medicine Data Monitoring Committees of Clinical Studies.

Although there is guidance from different regulatory agencies, there are opportunities to bring greater consistency and stronger applicability to address the practical issues of establishing and operating a data monitoring committee (DMC) for clinical studies of Chinese medicine. We names it as a Chinese Medicine Data Monitoring Committee (CMDMC). A panel composed of clinical and statistical experts shared their experience and thoughts on the important aspects of CMDMCs. Subsequently, a community standard on CMDMCs (T/CACM 1323-2019) was issued by the China Association of Chinese Medicine on September 12, 2019. This paper summarizes the key content of this standard to help the sponsors of clinical studies establish and operate CMDMCs, which will further develop the scientific integrity and quality of clinical studies.

Establish a Real-time Responsible Home Quarantine and Monitoring Management mHealth Platform.

Due to the global spreading of the COVID-19 virus, countries all over the world are faced with the need to conduct centralized quarantine or home quarantine for "persons who have been in contact with individuals diagnosed with the COVID-19 virus" and "visitors who have travel histories via COVID-19 hot zones". We have presented the community home quarantine service platform design that was utilized in Nanjing, China when the first wave of citizens returns to work after the Chinese New Year holidays on 10th Feb 2020. The main functions of the home quarantine monitoring system include (1) community grid management,(2) GPS positioning application in home isolation movement management,(3) Bluetooth body temperature patch data transmission integration, (4) health assessment scale (physical and mental health state) and (5) multilingual language options.

Developing Mobile Health Management System for Patients with Musculoskeletal Tumor.

This research provided a postoperative system for osteosarcoma which is seperated into two parts, Bone Patient and Bone Care. We focus on using smartphone features and proper interface design to facilitate self-monitoring, health analysis, and to make appointments. It achieves the effects of shared decision making (SDM). During the two weeks of research, we achieved satisfied with 4.03 ± 0.67 TAM score.

MiR-345 suppresses proliferation, migration and invasion by targeting Smad1 in human prostate cancer.

INTRODUCTION: The roles of dysregulated microRNAs in prostate cancer metastasis are still unknown. In this study, we found that the expression of miR-345 was significantly downregulated in prostate cancer and clinical prostate cancer tissues. MATERIALS, METHODS AND RESULTS: Overexpression of miR-345 in prostate cancer cells suppressed proliferation, migration and invasion. Using nude mice model, we revealed that miR-345 inhibits the growth of prostate cancer cells in vivo and in vitro. Furthermore, we identified and validated Smad1 as a direct target of miR-345. Ectopic expression of Smad1 without its 3'-UTR rescued miR-345-induced cell migration and invasion inhibition. CONCLUSION: Taken together, our data suggest that miR-345 exerts a suppressive effect on prostate cancer proliferation, invasion and migration through downregulation of Smad1.

MiR-378 suppresses prostate cancer cell growth through downregulation of MAPK1 in vitro and in vivo.

Prostate cancer is one of the biggest health problems for the aging male. To the present, the roles of dysregulated microRNAs in prostate cancer are still unclear. Here, we evaluated the anti-proliferative role of miR-378 in prostate cancer. And, we found that the expression of miR-378 was significantly downregulated in clinical prostate cancer tissues. In vitro assay suggested that overexpression of miR-378-suppressed prostate cancer cell migration and invasion promoted cell apoptosis. Furthermore, we identified and validated MAPK1 as a direct target of miR-378. Ectopic expression of MAPK1 rescues miR-378-suppressed cell migration and invasion. In vivo assay demonstrated that the stably miR-378-overexpressed prostate cancer cells displayed a significantly reduction in tumor growth. Taken together, our data suggested that miR-378 may act as a potential therapeutic target against human prostate cancer.

Danhong injection in the treatment of chronic stable angina: study protocol for a randomized controlled trial.

BACKGROUND: Chronic stable angina is a leading cause of death worldwide. Danhong injection, a complementary alternative medicine for chronic stable angina, has been demonstrated to be effective in numerous studies and is widely prescribed to patients. However, the methodological quality of most prior studies was found to be, in general, low. Therefore, we designed this randomized controlled trial to evaluate the efficacy and safety of using Danhong injection to treat chronic stable angina. METHODS/DESIGN: This is a randomized multicentre, double-blind, placebo-controlled, adaptive clinical trial. A total of 870 patients meeting the eligibility criteria will be randomly assigned into either the Danhong injection or the placebo group in a 2:1 ratio. Participants will then undergo a 2-week treatment regimen and a 76-day follow-up period. Because this is an adaptive trial, two interim analyses are prospectively planned. These will be performed after one-third and two-thirds of the patients, respectively, have completed the trial. Based on the results of these interim analyses, a data monitoring committee will determine how to modify aspects of the study without undermining the validity and integrity of the trial. The primary outcome measure is the proportion of patients who show a clinically significant change, which is defined as at least a 20-point improvement in angina frequency score on the Seattle Angina Questionnaire, which will be administered on day 30. Other secondary efficacy and safety outcomes will also be assessed. DISCUSSION: This trial will provide high-quality evidence regarding the use of Danhong injection to treat chronic stable angina. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01681316 .

Dynamic Changes in Phenotypic Groups in Patients with Stable Angina Pectoris after Treatment with Xinxuekang Capsule: A Randomized Controlled Trial.

OBJECTIVE: To reveal the cutoff point and influencing factors in the dynamic change in phenotypic group in patients with stable angina pectoris (SAP) after Xinxuekang capsule treatment. METHODS: Five hundred and seventy-six SAP patients were randomly assigned to receive Xinxuekang (XXK) capsules or Compound Danshen (CDS) tablets for 8 weeks. Global similarity degree analysis and nonlinear mixed effects modeling (NONMEM) were employed to reveal the cutoff points and influencing factors in dynamic changes in the SAP phenotypic group. The phenotypic group was defined as the six phenotypes in SAP, including angina, choking sensation in the chest, palpitations, dark purple lips, ecchymosis on the tongue, and fine-choppy pulse, which were quantitatively evaluated on Days 0, 14, 28, 42, and 56. RESULTS: Variation in the six individual phenotypes and distribution of the SAP phenotypic profile were similar between the two experimental groups, but cutoff points for changes in the SAP phenotypic group were 7.28 and 10.73 weeks in XXK and CDS groups, respectively. Degree of severity of SAP as well as study site significantly affected the tendency for change in the SAP Xueyu Zheng in both XXK and CDS treatment groups. Different Chinese patent drugs affected the tendency for change in phenotypic group in patients with SAP. XXK was superior to CDS in controlling a clinical phenotypic group. CONCLUSION: Based on global similarity degree analysis and NONMEM, the cutoff point and influencing factors in phenomic variation of SAP may be determined, to improve the development and modification of treatment regimens.

Overexpression of RIN1 associates with tumor grade and progression in patients of bladder urothelial carcinoma.

Ras and Rab interactor 1 (RIN1) is an effector of H-Ras, which plays an important role in the development and progression of carcinomas, but it has not been reported in bladder cancer. Hence, the association of RIN1 expression with prognosis of bladder urothelial carcinoma (UC) was examined. RIN1 mRNA and protein expression in 20 paired UCs and the adjacent normal tissues was detected by quantitative reverse transcription polymerase chain reaction and Western blot. The expression of RIN1 protein in 96 specimens of UCs and 22 specimens of adjacent normal bladder tissues were analyzed by immunohistochemistry. The overall survival (OS) was assessed by univariate and multivariate analysis. Moreover, the progression-free survival (PFS) and recurrence-free survival (RFS), classified by the clinicopathologic features with RIN1 expression, were assessed by multivariate analysis. RIN1 mRNA and protein level was higher in UCs than in the adjacent normal tissues (P < 0.01). Enhanced RIN1 immunoexpression was associated with high histologic grades (P = 0.046), cancer progression (P = 0.047) as well as Ki-67 expression (P = 0.023). Furthermore, the 5-year survival rate was 29% in the subgroup with high level of RIN1 expression, while it was 43% in the subgroup with normal level of RIN1 expression (P < 0.05). Importantly, RIN1 level was revealed as the significant independent prognostic factor for death (P = 0.023) and progression (P = 0.003), but a weak contribution for recurrence (P = 0.063). Collectively, RIN1 expression could be a potential prognostic predictor for UC patients.

The role of zinc transporter ZIP4 in prostate carcinoma.

OBJECTIVE: Normal prostate tissues have a unique function of accumulating high levels of zinc. This capability is lost during the early stage in the development of prostate malignancy. ZIP4 is an important zinc transporter. In this study, we explore the expression of ZIP4 in prostate carcinoma and invest the functional contributions of ZIP4 to cancer growth in vitro. METHODS: ZIP4 expression was detected in 14 prostate carcinoma and 20 BPH tissues by real-time RT-PCR and western blot. To invest the biological function of ZIP4 in prostate carcinoma cells, ZIP4 stable over-expression in cells was established in prostate carcinoma cell line DU145 (DU145-ZIP4) and ZIP4 short hairpin RNA(shRNA) expression in stable cells was also established in prostate carcinoma cell line 22RV1(22RV1-shRNA). The proliferation, migration, and invasion ability of the prostate carcinoma cells were detected. RESULTS: The expression of ZIP4 mRNA and protein are significantly down-regulated in prostate carcinoma tissues compared with that in BPH tissues. However, we found that there was no correlation between the ZIP4 expression and the pathologic grade of prostate carcinoma. In in vitro studies, over-expression of ZIP4 not only inhibits the proliferation but also inhibits the invasive ability of prostate carcinoma cell line DU145-ZIP4. At the same time, we found silencing of ZIP4 was associated with increased cell proliferation and invasion ability in 22RV1-shRNA cell line. However, both DU145-ZIP4 and 22RV1-shRNA cells showed a significant reduction on cell migration ability compared with the control. CONCLUSION: The results indicate that ZIP4 expression is down-regulated in prostate carcinoma and it may serve as a promising biomarker for prostate carcinoma. ZIP4 has an inhibitory effect on prostate carcinoma cell proliferation and invasion. It suggests that ZIP4 may be a tumor suppressor gene and down-regulation of ZIP4 may be a critical early event in the development of prostate carcinoma.

[Effects of inhibiting RhoA by Stealth RNA on high glucose-induced RhoA/ROCK signaling pathway in human mesangial cells].

OBJECTIVE: To observe the effect of small interference RNA (Stealth RNAiTM siRNA) of RhoA on the inflammatory response and fibrosis in human mesangial cell (HMC) and explore the role of RhoA/ROCK signaling pathway in the process of diabetic nephropathy. METHODS: Synchronized HMC were divided into several groups. Lipofectamine(TM)2000 was employed to transfect RhoA-siRNA and RhoA-negative siRNA into the above cells. RhoA-siRNA could inhibit the expression of RhoA. The expressions of RhoA, ROCK-I, fibronectin (FN), connective tissue growth factor (CTGF) and tumor necrosis factor-alpha (TNF-α) were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR) and ELISA (enzyme-linked immunosorbent assay). RESULTS: (1) The expressions of RhoA, ROCK-I and CTGF mRNA were inhibited by RhoA siRNA transfection in high glucose-induced HMC. The expression of each mRNA was reduced 26% - 60% as compared with the high glucose-induced group (P < 0.05); (2) After RhoA siRNA transfection and culturing with high glucose for 48 h, FN, the secretions of CTGF and TNF-α significantly declined [FN: (1.99 ± 0.04) mg/L vs. (4.31 ± 0.13) mg/L, CTGF:(4.98 ± 0.17) mg/L vs. (6.06 ± 0.09) mg/L; TNF-α: (61.17 ± 2.59) ng/L vs.(91.76 ± 2.27) ng/L, all P < 0.05]. The levels of FN and CTGF almost decreased to those of normal glucose-induced HMC. CONCLUSION: The levels of FN, CTGF and TNF-α in high glucose-induced HMC may be lowered by inhibiting RhoA through RNA interference and reducing the accumulation of extracellular matrix, glomerular fibrosis and inflammation. Thus it provides a new intervention target for the prevention of diabetic nephropathy.

[Establishment of non-parametric probabilistic model for evaluation of Chinese dietary exposure].

OBJECTIVE: To establish a non-parametric probabilistic model for evaluation of Chinese dietary exposure and to improve the assessment accuracy while integrating into the global risk assessment on food safety. METHODS: Contamination data was from the national food contamination monitoring program during 2000 - 2006, including heavy metals, pesticides and mycotoxins, amounting to 135 contaminants with 499 commodities and 487 819 samples. Food consumption data was obtained from the national diet and nutrition survey conducted in 2002 with three consecutive days by 24-hour recall method, and 66 172 consumers were included. Monte Carlo simulation was applied to derive the intake distribution, and the uncertainty of each percentile was estimated using the Bootstrap sampling. RESULTS: Different non-parametric probabilistic models for dietary exposure evaluation on heavy metals, pesticides and some of the toxins were established for Chinese people, and intake distributions with 95% confidence intervals of these contaminants were estimated. Taking acephate as an example, the results of its model shows that, for the 7 - 10 year-old children, the median dietary exposure in urban and rural areas were 1.77 microg x kg(-1) x d(-1) and 2.48 microg x kg(-1) x d(-1) respectively, with a 95% confidence interval of (1.59 - 2.06) microg x kg(-1) x d(-1) and (2.33 - 2.80) microg x kg(-1) x d(-1) respectively. CONCLUSION: The non-parametric probabilistic model can quantify the variability and uncertainty of exposure assessment and improve the assessment accuracy.

Comparison of second-trimester maternal serum free-beta-human chorionic gonadotropin and alpha-fetoprotein between normal singleton and twin pregnancies: a population-based study.

BACKGROUND: The second-trimester maternal serum screening in twin pregnancy is still controversial, as the serum marker levels in twins are not as clear as those in singletons. This study aimed to evaluate the relationship between the levels of the second-trimester maternal serum free beta-human chorionic gonadotropin (free beta-HCG) and alpha-fetoprotein (AFP) in normal twin and singleton pregnancies and to estimate feasible analysis methods for utilizing these markers in second trimester screening for twin pregnancy. METHODS: On the basis of a prospective population-based study of second-trimester maternal serum screening, the concentrations of maternal serum AFP and free beta-HCG of 195 normal twin pregnancy and 26,512 singleton controls at gestational weeks 15 to 20 were measured by time-resolved fluoroimmunoassay in one laboratory. The levels of markers were compared between the twins and singletons using weight-correction and gestational age-specific model. RESULTS: According to the research protocol, 95 communities were randomly sampled, which covered the whole Jiangsu province, the east of China. A total of 26 803 pregnant women (98%), from the target population accepted prenatal screening for maternal serum AFP, beta-HCG detection, and all babies were followed up for at least six months. There were 197 (0.73%) twin pregnancies, of which one case had fetal trisomy 18, and one case with fetal anencephaly. The others were normal twin pregnancy. From a total enrollment of 26 803 women participants, 26 512 women with normal singleton pregnancies were selected as the model controls. The other 291 pregnancies, including trisomy 21, neural tube defect (NTD), trisomy 18, and other fetal abnormalities, were excluded. No significant differences were found in the medians of gestational age-specific maternal serum free beta-hCG and AFP in normal twin pregnancy comparing with twice those in model controls with the exception of the medians for free beta-hCG during the 16th gestational week (P = 0.012). CONCLUSION: The weight-correction and gestational age-specific levels of Chinese Han population maternal serum free beta-hCG and AFP in normal twins were twice the levels as those in the singleton controls during the 17-19 gestational weeks.

[Investigation and confirmatory factor analysis of information collected with the four diagnostic methods in patients with bronchial asthma].

OBJECTIVE: To investigate the information acquired through the four diagnostic methods of traditional Chinese medicine in patients with bronchial asthma, and to classify the syndrome types. METHODS: Four hundred and thirty patients with bronchial asthma were randomly investigated. The information acquired through the four diagnostic methods was recorded and the database was established by Amos software, and then the data were analyzed by confirmatory factor analysis (CFA). RESULTS: After analyzing the data with 4 factors, 5 factors and 6 factors, we found that the results of CFA with 6 factors were in accordance with clinical practical experience. CONCLUSION: According to the results of CFA with 6 factors and with the standard regression coefficient 0.4 as primary and secondary critical points, the syndromes in patients with bronchial asthma can be classified into 5 types, which are syndromes of cold fluid retained in lung, phlegm-heat obstructing lung, wind-phlegm blocking lung, qi deficiency of lung and kidney and qi deficiency of spleen.