Geliang Yang

Comparison of registered and published primary outcomes in randomized controlled trials of gastroenterology and hepatology

Abstract Objectives. The need for trial registration as well as the benefits it has brought for the transparency of medical research has been recognized for years. Trial registration has turned from an exception to a mandatory guideline in recent years. The present study aimed to examine the characteristics of registered randomized controlled trials (RCTs) in a sample of recently published gastroenterology RCTs, and to assess the consistency of registered and published primary outcome (PO) in RCTs. Methods. Articles published in the top five “general and internal journals” and top five “gastroenterology and hepatology journals” categories between 2009 and 2012 were searched in PubMed. Basic characteristics and the registration information were identified and extracted from the included RCTs. PO consistency analysis was conducted to compare between the registered and published format. Results. A total of 305 RCTs were included; among them 252 could be identified with a registration number. Nearly half of these RCTs were funded solely by industry (141/305, 46.3%). ClinicalTrials.gov was the most popular registry for these RCTs (214/252, 84.9%). A total of 155 RCTs were included in the PO consistency analysis. Among them, 22 (14.2%) RCTs had discrepancies between POs registered in the trial registry compared to the published article. Conclusions. Based on the results of the present study, selective outcome reporting of gastroenterology RCTs published in leading medical journals has been much improved over the past years. However, there might be a sampling bias to say that consistency of registered and published POs of gastroenterology RCTs has been better than before.

Corosolic acid analogue, a natural triterpenoid saponin, induces apoptosis on human hepatocarcinoma cells through mitochondrial pathway in vitro.

abstract Context 2a,-3a,-24-Trihydroxyurs-12-en-28-oic acid (TEO, a corosolic acid analogue) is a triterpenoid saponin isolated from Actinidia valvata Dunn (Actinidiaceae), a well-known traditional Chinese medicine. Objective This study investigated the anti-proliferation and inducing apoptosis effects of TEO in three human hepatocellular carcinoma (HCC) cell lines. Materials and methods Cytotoxic activity of TEO was determined by the MTT assay at various concentrations from 2.5 to 40 μg/mL in BEL-7402, BEL-7404 and SMMC-7721 cell lines. Cell morphology was assessed by acridine orange/ethidium bromide and 4′-6-diamidino-2-phenylindole dihydrochloride staining and fluorescence microscopy. Cell-cycle distribution and DNA damage were determined by flow cytometry and comet assay. Mitochondrial dysfunction was assessed by JC-1 staining and transmission electron microscopy. Apoptosis changes were explored by Western blot, TNF-α and caspase-3, -8, -9 assays. Results TEO exhibited inhibition effects on BEL-7402, BEL-7404 and SMMC-7721 cells treated for 24 h, the IC50 values were 34.6, 30.8 and 30.5 μg/mL, respectively. TEO (40 μg/mL)-treated three cell lines increased by more than 21% in the G1 phase and presented the morphological change and DNA damage. TEO also declined the mitochondrial membrane potential and altered mitochondrial ultra-structure. Furthermore, caspase-3, caspase-8, caspase-9 and TNF-α were also activated. Mechanism investigation showed that TEO could decrease anti-apoptotic Bcl-2 protein expression, increase proapoptotic Bax and Bid proteins expressions and increase Bax/Bcl-2 ratio. Conclusion Our results demonstrate for the first time that TEO inhibited growth of HCC cell lines and induced G1 phase arrest. Moreover, proapoptotic effects of TEO were mediated through the activation of TNF-α, caspases and mitochondrial pathway.

National survey of China's oncologists' knowledge, attitudes, and clinical practice patterns on complementary and alternative medicine

It is common for cancer patients to use complementary and alternative medicine (CAM). This study was designed to explore Chinas oncologists’ knowledge, attitudes and clinical practices regarding CAM use by their patients. An online survey was conducted of Chinas oncologists. Among 11,270 participants who completed the online survey, 6,007 (53.3%) were identified as oncologists. Most were men (75.2%), with a mean age of 33.4 (standard deviation: 6.5) years. The 6,007 oncologists discussed with 36.5% of their patients about CAM. Most of them (75.6%) did not want to initiate discussions due to lack of knowledge on CAM. Oncologists estimated that 40.0% of their patients used CAM treatments. Oncologists reported that 28.7% of their patients underwent anticancer therapy with the concurrent use of CAM. Four out of five of the responding oncologists self-reported inadequate knowledge and only 22.0% reported receiving professional education on CAM. Nearly half (44.9%) of the oncologists believed CAM treatment was effective for symptoms and treatment of cancer. Physician factors associated with initiating discussions with patients about CAM use included sex, age (≥ 33 years), medical license for traditional Chinese medicine, enough knowledge and professional education experience. Chinas oncologists infrequently discussed with their patients about CAM due to lack of knowledge. Most of the oncologists did not encourage CAM use.

Bufalin-loaded bovine serum albumin nanoparticles demonstrated improved anti-tumor activity against hepatocellular carcinoma: preparation, characterization, pharmacokinetics and tissue distribution

Objective To prepare and evaluate the liver-targeted drug delivery system of Bufalin with higher liver uptake and stronger antitumor activity against hepatocellular carcinoma. Methods Bufalin-loaded bovine serum albumin nanoparticle was prepared by desolvation method, to investigate the in vitro release performance and to evaluate the pharmacokinetic and tissue distribution. The antitumor activity against hepatocellular carcinoma was evaluated in vitro and in vivo, respectively. Results The Bufalin-loaded bovine serum albumin nanoparticle with an average particle size of 125.1 nm exhibited a sustained release behavior in vitro. The half-life, blood plasma area under the curve and apparent volume of distribution of Bufalin-loaded bovine serum albumin nanoparticle were significantly higher than that of Bufalin, whereas the clearance rate was lower than Bufalin group. The uptake of liver for Bufalin-loaded bovine serum albumin nanoparticle was 352.045 ± 35.665 ng/g while for Bufalin was 164.465 ± 48.080 ng/g (P < 0.01) at 5 min. The uptake of tumor for Bufalin-loaded bovine serum albumin nanoparticle was significantly higher than that of Bufalin both at 5 min (50.169 ± 11.708 ng/g, 93.415±13.828 ng/g, P < 0.01) and 15 min (43.683 ± 11.499 ng/g, 64.219 ± 17.684 ng/g, P > 0.05). Bufalin-loaded bovine serum albumin nanoparticle and Bufalin have similar antitumor activity in vitro. The tumor inhibition effect of Bufalin-loaded bovine serum albumin nanoparticle was stronger than that of Bufalin alone in vivo. Conclusion Bufalin-loaded bovine serum albumin nanoparticle is a promising liver-targeted drug delivery system with higher liver uptake and stronger antitumor activity against hepatocellular carcinoma.OBJECTIVE To prepare and evaluate the liver-targeted drug delivery system of Bufalin with higher liver uptake and stronger antitumor activity against hepatocellular carcinoma. METHODS Bufalin-loaded bovine serum albumin nanoparticle was prepared by desolvation method, to investigate the in vitro release performance and to evaluate the pharmacokinetic and tissue distribution. The antitumor activity against hepatocellular carcinoma was evaluated in vitro and in vivo, respectively. RESULTS The Bufalin-loaded bovine serum albumin nanoparticle with an average particle size of 125.1 nm exhibited a sustained release behavior in vitro. The half-life, blood plasma area under the curve and apparent volume of distribution of Bufalin-loaded bovine serum albumin nanoparticle were significantly higher than that of Bufalin, whereas the clearance rate was lower than Bufalin group. The uptake of liver for Bufalin-loaded bovine serum albumin nanoparticle was 352.045 ± 35.665 ng/g while for Bufalin was 164.465 ± 48.080 ng/g (P < 0.01) at 5 min. The uptake of tumor for Bufalin-loaded bovine serum albumin nanoparticle was significantly higher than that of Bufalin both at 5 min (50.169 ± 11.708 ng/g, 93.415±13.828 ng/g, P < 0.01) and 15 min (43.683 ± 11.499 ng/g, 64.219 ± 17.684 ng/g, P > 0.05). Bufalin-loaded bovine serum albumin nanoparticle and Bufalin have similar antitumor activity in vitro. The tumor inhibition effect of Bufalin-loaded bovine serum albumin nanoparticle was stronger than that of Bufalin alone in vivo. CONCLUSION Bufalin-loaded bovine serum albumin nanoparticle is a promising liver-targeted drug delivery system with higher liver uptake and stronger antitumor activity against hepatocellular carcinoma.

How do systematic reviews of acupuncture for pain relief incorporate risk of bias assessments into the synthesis? A methodological study

Objective By reviewing the assessment of internal validity in relevant systematic reviews (SRs), the aim of this study was to identify how critical appraisals of risk of bias (RoB) inform the synthesis of evidence in SRs of acupuncture for pain relief. Methods SRs were searched in Medline, EMBASE, and the Cochrane Database of SRs from their inception to 30 December 2014. Only SRs of acupuncture for pain relief were included. Basic information, types of RoB appraisal tool, whether or not there was domain-level assessment of RoB, whether or not the reviews ranked studies by RoB, plus whether or not (and, if so, how) RoB appraisal was incorporated into the synthesis were determined. Results A total of 91 SRs met the inclusion criteria and were included in the final analysis. Over half of the SRs (85, 64.8%) used standard tools, such as the Jadad quality score and the Cochrane RoB tool, followed by adapted tools (n=23, 25.3%). Of the 85 SRs that assessed RoB, 29 (34.1%) presented domain-level assessment and 71 SRs (83.5%) included ranking of the studies based on RoB assessment. Of these 71, 35 (49.4%) used a cut-off threshold score and 26 (36.6%) required all criteria sum-up. Of the 85 SRs that assessed RoB, 48 (56.5%) incorporated RoB appraisal into the data synthesis. Conclusions Although most SRs of acupuncture for pain relief conducted some form of RoB assessment, nearly half of them failed to incorporate the RoB assessment into the synthesis.

Discrepant Views of Oncologists and Cancer Patients on Complementary and Alternative Medicine in a Chinese General Hospital

Purpose: Complementary and alternative medicine (CAM) has been widely used by cancer patients but rarely discussed by oncologists. This study was designed to evaluate the communication gap between China’s oncologists and cancer patients on CAM. Methods: Two parallel cross-sectional studies assessed 83 oncologists and 402 cancer patients on CAM communication between patients and oncologists, and attitudes toward CAM use and clinical decisions about CAM. Results: A majority (75.1%) of the cancer patients (302/402) were identified as CAM users within the most recent three months while 77.6% of the cancer patients (312/402) were identified as CAM users since diagnosis of cancer. Oncologists and patients responded differently (P < .001) on CAM communications. Both oncologists and patients expected that CAM could improve the immune system. They both agreed that oncologists usually discouraged their patients from using CAM. Regarding the effectiveness of CAM, cancer patients were more likely to believe that CAM was effective while oncologists had more concerns about adverse effects of CAM use. CAM use by patients was predicted by disease duration (≥9 months) in the multivariable logistic regression model. Conclusion: China’s oncologists and cancer patients may hold discrepant views on CAM. China’s oncologists are encouraged to improve their knowledge on CAM and to initiate more discussions with their patients regarding effective and the safe use of CAM.

Characteristic Analysis of Complementary and Alternative Medicine in Randomized Controlled Trials of Oncology: A Comparison of Published Studies

Background: Complementary and alternative medicine (CAM) has been widely used by cancer patients and oncologists in the past decades. The present study aimed to examine and compare the characteristics and registration status of published studies in a sample of recently published CAM randomized controlled trial (RCT) reports of oncology in leading journals of 3 categories: general and internal medicine (GIM), clinical oncology (CO), and CAM. Methods: Articles published in the top 5 journals of the 3 categories from 2006 to 2015 were searched in PubMed. Basic characteristics, registration information, impact factor, and citations were identified and extracted from the included RCTs. Data were summarized by frequency, mean, and median and compared using χ2 test and Kruskal-Wallis H test. Results: A total of 59 RCTs were included; among them, 34 (58%) could be identified with a registration number. GIM journals (15) enjoyed the highest average number of citations per article, followed by CO (12) and CAM (3) journals (P < .0001). ClinicalTrials.gov was the most popular registry for these RCTs. Of the RCTs registered in ClinicalTrials.gov, 24% (4/17) of the published studies in CO journals put their results in the registry; however, no study in GIM and CAM journals put the result in the registry (P = .372). Conclusion: The top GIM, CO, and CAM journals rarely published CAM RCTs of oncology from 2006 to 2015, and the CAM articles of oncology were less cited. However, there was a clear improvement in the trial registration rate over the past decades.

China's growing contribution to military Chinese medicine (2005-2014): a ten-year literature survey.

OBJECTIVE In China, people have relied on traditional Chinese medicine (TCM) for thousands of years to keep healthy and treat diseases. TCM also plays an important role in military health services and now forms a new discipline called military Chinese medicine (MCM). However, the type, quality and focus of research articles about MCM have not been reported. The present study was performed to analyze the growing trends of MCM and investigate Chinas contribution to military health services. METHODS Chinas MCM publications were retrieved from the PubMed database, as well as China National Knowledge Infrastructure, Wanfang Data and Chongqing VIP database from 2005 to 2014. RESULTS The study found that the number of published articles increased markedly from 2005 to 2014. Basic research studies comprised a small percentage of the literature. Among these studies, military training injury and special military environmental medicine were the most common research subjects in MCM. Military hospitals were the main institutions generating MCM literature. CONCLUSION The quality of MCM research is generally low, as indicated by the proportion of publications in core journals. Studies on MCM still lack high-quality publications and international cooperation.

The application status of Chinese herbal medicine in military health service in China.

Military medicine has had a long history in China since the emergence of the war. Chinese medicine, especially Chinese herbs, was widely used in China as well as other Asian countries for the prevention and treatment of diseases in the military for hundreds of years. However, the use of Chinese medicine in military health service has never been well studied. In this article, we briefly summarize the application status of Chinese herbal medicine in military health service in China, putting particular emphasis on special military environment, in an attempt to build a bridge between Chinese medicine and military health service and promote the quality of health service for the military and maintain world peace.