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Angiogenesis is a major pathologic characteristic of glioblastoma, which is one aggressive primary brain tumor. MicroRNA‐221/222 (miR‐221/222) cluster has been previously reported to function importantly in malignant glioma biological process. The current study aims at evaluating the effects of miR‐221/222 cluster on angiogenesis of glioblastoma cells. Microarray data were analyzed to select glioblastoma‐associated differentially expressed genes, and dual‐luciferase reporter assay was performed to assess targeting correlation between miR‐221/222 cluster and suppressor of cytokine signaling‐3 (SOCS3). Subsequently, the expression patterns of miR‐221 and miR‐222 in glioblastoma cells were identified. miR‐221 and miR‐222 were overexpressed or silenced in glioblastoma cells to identify the effect of miR‐221/222 cluster in cell invasion, migration, proliferation, and angiogenesis. To define downstream pathway of miR‐221/222 cluster or SOCS3 in glioblastoma, levels of Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway‐related proteins were assessed. Additionally, the functions of miR‐221/222 on glioblastoma cell angiogenesis were measured in vivo with microvessel density assayed. miR‐221 and miR‐222 were expressed at a high level and SOCS3 was at a low level in glioblastoma. Downregulation of the miR‐221/222 cluster diminished the invasion, migration, proliferation, and angiogenesis with reduced protein levels of matrix metalloproteinase‐2 (MMP‐2), MMP‐9, and vascular endothelial growth factor in glioblastoma cells. Also, silencing miR‐221/222 cluster reduced p‐JAK2/JAK2 and p‐STAT3/STAT3. Consistently, the inhibitory role of silencing miR‐221/222 cluster on tumorigenesis of glioblastoma cells was confirmed in vivo. Collectively, the inhibition of miR‐221/222 cluster could attenuate the glioblastoma angiogenesis through inactivation of the JAK/STAT pathway by upregulating SOCS3. [ABSTRACT FROM AUTHOR]

Objective Comparing the essential medicine lists for children and China national essential medicine list 2012, to provide the evidence for establishing essential medicine list for children in China. Methods Search the official websites of WHO and some other countries' ministry of health to get essential medicine lists for children (EMLc) that have already established. Compare the situation of updating, the number and classification of medicines, and the dosage forms in essential medicine lists for children and China national essential medicine list 2012. Results By December 2013, the WHO, India, and South Africa have established EMLc. The list of China was for people in all ages, so the number of medicines ranked first in four lists. WHO, India, and China classified the medicines by pharmacologic action, South Africa classified by ATC classification. Except for WHO, India, South Africa, and China did not have specific medicines for neonatal care or medicines for diseases of joints. The main administration routes in these four lists were oral administration, injection, and topical application. There were medicine restrictions in lists of WHO and India, but there were no medicine restrictions in the lists of South Africa and China. Conclusion Compared with EMLs for children, the 2012 National Essential Medicine List for China is not suitable for children in China. Development of Chinese EMLc should be based on the burden of diseases for children, and should select applicable dosage forms and specifications. [ABSTRACT FROM AUTHOR]

Objective To compare the effects of misoprostol versus ergometrine-oxytocin for postpartum haemorrhage (PPH) prevention, and provide important evidence to choose optimal agents for preventing PPH in developing countries. Methods The Cochrane Central Register of Controlled Trials, PubMed, EMbase, and were searched from inception to 1st January 2016. Two authors independently extracted data and assessed risk of bias of studies according to Cochrane Handbook5.1.0. Meta-analysis was performed using RevMan5.2.4 software. Results A total of 4034 women from six randomized controlled trials (RCTs) were included. Meta-analyses showed that the PPH rate (7.6% vs. 4.2%, RR = 1.81, 95%CI (1.40, 2.35), P < 0.01), and the additional uterotonic therapy (19.2% vs. 10.5%, RR = 1.83, 95%CI (1.57, 2.14), P < 0.01) for misoprostol group were significantly higher than ergometrine-oxytocin group, respectively. But there was no significant difference of severe PPH rate between two groups (1.2% vs. 0.76%, RR = 1.55, 95%CI (0.78, 3.07), P = 0.21). The need for manual removal of placenta in misoprostol was only about one-third of ergometrine-oxytocin (0.5% vs. 1.4%, RR = 0.33, 95%CI (0.15, 0.76), P < 0.01). Conclusions Misoprostol can be used in the third stage of labor for preventing PPH where sterilized syringe and trained midwife were absent, and ergoetrine-oxytocin could be deemed as alternative agent in low-resource setting due to recognized effect. As a result of limited evidence about these uterotonic agents, the more high-quality RCTs are needed to determine the potentials and harms of various uterotonic agents for preventing PPH in developing countries. [ABSTRACT FROM AUTHOR]

Objective To investigate the incidence of severe maternal morbidities ( SMM) in China and explore effects of medical co-morbidities on SMM. Design Proactive multicenter clinic register collaboration. Setting Data on all deliveries at eight hospitals in Sichuan province, China, collected from 1 January 2009 to 12 December 2010. Population 33 993 delivering women and 34 547 live births. Methods We defined SMM as a combination indicator of severe maternal complications, critical interventions, admission to the intensive care unit and maternal near-miss instances. We randomly selected 80% of the data from the entire database to build a logistic regression model. The remaining 20% were used to test the predictive power of the model. Main outcome measures SMM incidence, adjusted odds ratios ( aORs), and area under a receiver operating characteristic ( ROC) curve. Results Severe maternal morbidities incidence was 43.4/1000 live births [confidence interval ( CI) 41.24-45.56]. Fifteen variables were independent contributors to the model. Seven medical co-morbidities significantly affected the occurrence of SMM, including iron-deficiency anemia ( aOR 3.07, CI 2.47-3.83) and other hematological diseases ( aOR 5.82, CI 3.50-9.69), hepatitis-B virus infection ( aOR 1.48, CI 1.12-1.97) and other hepatic diseases ( aOR 3.81, CI 1.61-9.04), cardiopathy ( aOR 3.59, CI 2.62-4.93), hypertension ( aOR 5.23, CI 4.06-6.75), and respiratory diseases ( aOR 2.10, CI 1.25-3.52). The area under the ROC curve was 0.8127. Conclusions The incidence of SMM was typical of a low resource area. There is a need to identify medical co-morbidities and to adopt prophylactic measures and interventions. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the quality of pancreatic cancer guidelines with evidence-based methods based on the global burden of disease and to explore its status, distribution, characteristics of theme, and the difference of recommended therapies among various qualities of guidelines, so as to provide a reference for clinical decision. Methods The PubMed, The Cochrane Library (Issue 11, 2013), Chinese Biomedical Database, China National Knowledge Infrastructure, and VIP databases, as well as the website of National Guidelines Clearinghouse, Guidelines International Network, and National Institute for Clinical Excellence were systematically reviewed through November 2013 for pancreatic cancer guidelines. The Appraisal of Guidelines for Research and Evaluation (AGREE II) were applied to assess the methodological quality of the guidelines. Results A total of 14 relevant guidelines (including 5 evidence-based ones) were identified, involving four continents (Asia, Europe, North America, and Oceania), seven counties, and four international organizations. There were only two domains, namely 'scope and purpose' and 'clarity of presentations', getting high average scores (more than 60%) among all 14 guidelines. The mean AGREE domain score in guidelines varies among different areas, and the quality of 5 evidence-based guidelines was superior to that established by consensus. According to AGREE II, 11 guidelines were weakly recommended, while 3 were not recommended due to poor methodological quality. Their subjects of 14 guidelines covered six treatment categories, including chemotherapy, surgery, radiotherapy, support therapy, radiotherapy, and interventional therapy. Conclusion The overall methodological quality of pancreatic cancer guidelines is suboptimal among different countries or regions. The qualities of evidence-based guidelines are significantly superior to consensus. The chemotherapy, surgery, radiotherapy, and support therapy were the predominant choices by guidelines. [ABSTRACT FROM AUTHOR]

Objective To explore the efficacy and safety of high-intensity focused ultrasound combined with other physical therapies for the treatment of pancreatic cancer, so as to provide reference for clinical application. Methods The PubMed, EMbase, The Cochrane Library (Issue 11, 2013), CBM, CNKI, and WanFang databases were systematically searched up to November 2013. The randomized controlled trials and clinical controlled trials about the treatment of high-intensity focused ultrasound were included. According to the inclusion and exclusion criteria, two reviewers independently screened the studies, exacted the data, and assessed the quality. The meta-analysis was performed by using the RevMan 5.0 software. Results A total of 23 studies including 19 randomized controlled trials and four clinical controlled trials were included. Of which 14 studies reported the safety. The results of meta-analyses showed that: the survival rate at 6 months and 12 months, overall efficacy, and clinical benefit rate in high-intensity focused ultrasound plus radiation and chemotherapy group were significantly higher than those in groups treated with three-dimensional conformal radiation therapy (P < 0.05), gemcitabine (P < 0.05), gemcitabine plus cisplatin (P < 0.05), and gemcitabine plus 5-fluorouracil (P < 0.05). The adverse effect caused by high-intensity focused ultrasound plus other therapy was equal to those in the control group. The major high-intensity focused ultrasound-related adverse effect was skin damage and fever. Conclusion The current evidence suggested that the efficacy of high-intensity focused ultrasound for pancreatic cancer was superior to other therapies. However, the poor quality of trails may reduce the reliability of outcome to some extent. The current evidence suggested that the efficacy of HIFU for pancreatic cancer was superior to other therapies, but with poor quality. Therefore, a standard and unified criterion for the diagnosis and outcome measures of pancreatic cancer is needed, and the quality of study design and implementation should be bettered, so as to improve the high quality of evidence for its clinical application. [ABSTRACT FROM AUTHOR]

Objectives Helical tomotherapy (HT) can be applied to treat complex malignant cancer with high-precise radiotherapy, and it can reduce the damage to normal tissues and improve treatment effects. But the procurement of HT must be approved by relevant departments of administration affairs. This study, appointed by the National Health and Family Planning Commission of China and undertook by the National Health Development Research Center and the Chinese Evidence-Based Medicine Centre, was aimed to rapidly assess the effectiveness, safety, costs, and applicability of HT, so as to provide currently available best evidence for decision-makers of health policies. Methods We electronically searched databases including PubMed, EMbase, The Cochrane Library, CNKI, WanFang Data, VIP, CBM, and other professional websites. Two reviewer independently screened literature according to the inclusion and exclusion criteria, extracted data, assessed quality, and then performed descriptive analysis. Results (i) We finally included 150 studies, encompassing 5 HTAs, 18 CCTs, and 127 observational studies. (ii) The included HTAs were published during 2006-2009, providing fairly less evidence of low quality and the results of 145 primary studies showed that: HT had been used mainly in the treatments of 14 kinds of cancer, with low total toxicity and high survival rates. Although the quality of the included studies was poor, there was much evidence about prostate cancer, head and neck cancer, nasopharynx cancer, cervical cancer, lung cancer and liver cancer, with enough sample and fairly reliable results in HT efficacy and safety. And (iii) a total of 56 clinical trials were registered in , most of which were registered by the occident. Among them, 9 were completed but the results had not been published yet. Conclusions The evidence of this study showed that, HT is safe and effective in clinic. But the abovementioned conclusion needs to be verified by conducting more high-quality studies with long-term follow-up. The costs of HT in procurement, maintenance, and application are high; and the skills, training, and qualification of operators are required. We suggest that the procurement of HT should be reduced; it should be allocated rationally and effectively used after comprehensive assessment in China's cancer epidemiology characteristics, health resource allocation, disease burden, medical service level, etc.; and also high-quality studies with long-term follow-up should be financially supported on the basis of establishing projects, so as to provide local evidence and consistently guide and improve scientific decision-making. [ABSTRACT FROM AUTHOR]

Objectives To systematically review the effects of tolerogenic dendritic cells (Tol-DCs) induced by different methods on liver transplantation and their possible mechanisms of action. Methods PubMed and EMbase were searched for relevant articles through 31 December 2013. The effects of Tol-DCs on liver allograft survival were semiquantitatively evaluated, and the possible mechanisms by which Tol-DCs prolong graft survival were analyzed. Results Seven articles were included, and classified according to methods of induction, sources, and methods of infusing Tol-DCs. Tol-DCs induced from immature DCs (imDCs), with cytokines, and by gene modification induced liver transplant tolerance for 33.1 ± 32.5 days (2.7-fold vs. control), 26.17 ± 16.20 days (1.8-fold vs. control), and 11.7 ± 1.6 days (2.3-fold vs. control), respectively. DCs derived from recipient bone marrow, donor bone marrow, and donor spleen induced liver transplant tolerance for 51.0 ± 0.0 days (5.9-fold vs. control), 21.4 ± 26.8 days (2.4-fold vs. control), and 15.0 ± 0.0 days (2.3-fold vs. control), respectively. The primary mechanisms by which Tol-DCs induce liver transplant tolerance were the induction of T-cell hyporeactivity and Th2 differentiation. Conclusions Tol-DCs induced by three different methods could extend liver allograft survival, with imDCs showing optimal results. The optimal infusion method was intravenous injection of 1-2 × 106 Tol-DC, similar to findings in renal transplantation. Tol-DCs prolonged liver transplant tolerance more than renal transplant tolerance. [ABSTRACT FROM AUTHOR]

Objectives Capsule endoscopy (CE) has been widely used in the diagnosis of small bowel disease (SBD) in the world. To bring CE into the national health insurance directory, and intensify its popularization in primary hospital, the government needs high-quality HTA evidence for decision makers. We were appointed by the National Health and Family Planning Commission of China to evaluate the effectiveness, safety, economy, and applicability of CE in the diagnosis of SBD, to provide the best currently available evidence for decision making. Methods We searched the Cochrane Library (Issue 8, 2013), PubMed, EMbase, INAHTA, VIP, CBM, CNKI and WanFang Data. All confirmed or suspected SBD patients with diagnosis by CE versus other alternative therapies were considered. Health technology assessments (HTAs), systematic reviews (SRs), meta-analyses, randomized controlled trials (RCTs), guidelines and economic studies were included. Two investigators selected studies, assessed the quality and extracted data independently, and a descriptive analysis was used. Results We included 4 HTAs, 11 SRs/meta-analyses, 2 RCTs, 5 guidelines, and 10 economic studies for assessment. The results showed that the disease detection rate of CE was higher than that of many other traditional technologies and that the main adverse event for CE was retention (0.7% to 3.0%). These results were consistent with those of the guidelines. Comprehensive results of economic studies showed the superiority of CE compared with other technologies. As the first choice, CE can decrease potential costs, especially when used in outpatients. Conclusions (i) CE has advantages in diagnostic yield, safety, and cost in the diagnosis of SBD, but some limitations exist. It still needs more high-quality evidence on CE diagnosis accuracy. (ii) When the government approves the introduction of CE in a hospital, many factors must be considered, such as the local disease burden, clinical demand, ability to pay, and staff. At the same time, it is necessary to standardize training for operating physicians, to reduce economic losses caused by poor technical ability of the medical staff. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to systematically review the effects of transfusing Tol-DCs induced by different methods on renal transplantation and survival time. Method PubMed and EMbase were searched for relevant articles from inception to July 20th, 2013. Renal allograft survival time was regarded as the endpoint outcome. The effects of Tol-DCs on renal transplantation were evaluated semi-quantitatively. Results Sixteen articles were included. There were three sources of Tol-DCs, including bone marrow, spleen, and thoracic duct lymph node. Rats were administrated cells intravenously and 83% of mice through the portal vein. Four subtypes of bone marrow Tol-DCs enhanced renal allograft time: immature DCs enhanced allograft survival 4.9-fold in rats and 2.0-fold in mice, gene modified DCs enhanced allograft survival 4.4-fold in rats and 2.2-fold in mice, and drug and cytokine induced enhanced allograft survival 2.9-fold and 2.7-fold, respectively, in rats. Tol-DCs from the spleen and thoracic duct lymph nodes prolonged allograft survival 2.7-fold and 1.8-fold, respectively, in rats. 1-2×106 doses of Tol-DCs extended the survival time of rats following renal transplantation. The key mechanisms by which Tol-DCs enhance allograft and overall survival included: (i) inducing T-cell hyporeactivity; (ii) reducing the effects of cytotoxic lymphocytes; and (iii) inducing Th2 differentiation. Conclusion Bone marrow Tol-DCs can extend allograft survival and induce immune tolerance in fully MHC-mismatched renal transplantation in rats and mice. The effects of imDCs and gene modified Tol-DCs in mice are less marked. In conclusion, a single-injection of 1-2×106 doses of bone marrow Tol-DCs (i.v.), in combination with an immune-suppressor, a co-stimulator, and accessory cells can significantly extend renal allograft survival. [ABSTRACT FROM AUTHOR]

Objective To explore the relationship between macro-economic indicators and incidences of adverse events linked to intrauterine devices (IUDs). Methods Data on IUD-associated adverse events were collected from a cohort study conducted between September 2005 and December 2006. Regional economic data were from the 2006 National Economic and Social Development Statistical Bulletins and Statistical Yearbooks of various regions. A total of 20,220 IUD users in 236 towns in Jiangsu, Shanghai, Guangdong, Anhui, Sichuan, and Chongqing provinces in China were included in this study. Linear correlation and regression analyses were used to analyze the relationships between regional income and total incidences of adverse events, incidences of mild adverse events, and incidences of severe adverse events. Results Incidences of total adverse events and mild adverse events were positively correlated with regional economic level (rs= 0.336, p < 0.05; rs= 0.272, p < 0.05), while incidences of severe adverse events were not correlated with regional economic level. Conclusions The positive relationship between regional economic level and reported IUD-associated mild adverse events likely reflects income-related disparities in women seeking care and receiving treatment for mild adverse events. This points to a need to improve both public health education and the quality of health services, particularly in poorer areas. [ABSTRACT FROM AUTHOR]

Background While reporting of adverse drug events (AE) and adverse drug reactions (ADR) following Chinese materia medica (CM) injection is becoming more common, the reporting quality is of concern. Methods A checklist about the reporting quality of AE/ADR was set up, and the ADR/AE reporting of Herba Houttuyniae injection was chosen as an example. Electronic databases Chinese Journal Net (1994-2009) and Chinese Science and Technological Journal Net (VIP) (1989-2009) were searched for target literature. Results Based on our search strategy, 210 articles were included, with 175 articles reporting single or several cases of ADR/AE following Herba Houttuyniae injection (type I report). There were seven reports from regional or national ADR monitoring centers (type II report), and 28 summary reports from a single hospital or medical center (type III report). All 210 papers mentioned 'adverse effect,''safety' or related meaning words in their titles, but 199 articles did not have abstract. Patient demographic characteristics were not fully reported in these articles. In type I articles, only 97 cases (43.11%) mentioned whether patients had or did not have a history of allergies, whereas 128 cases (56.89%) in type II papers and 14 (50%) type III papers, did not mention allergic history of patients. Only three articles (3/210, 1.43%), all of them type I, mentioned the syndrome type in Chinese medicine. None of the papers gave clear indications of the type and grade of ADR/AE of patients. Most papers did not report details of the CM injection procedure, such as the drug company, product serial number, or the drug's validity period. Data about the occurrence time and management of ADR/AE was also inadequately reported. Conclusion and recommendations The current reporting format of ADR/AE in clinical CM injections is not standardized. Much fundamental information of ADR/AE following CM injection is therefore missing. A standard reporting format for ADR should be developed, and should include the following: (1) a title mentioning adverse effects and safety; (2) a structured abstract including adequate information about the patient and the disease treated, the drug used, the specific ADR/AE, physician response to the ADR/AE, and result of management; (3) demographic characteristic of the patients (gender, age, etc.); (4) clinical characteristics of patients (disease, syndrome, etc); (5) allergic history of patients; (6) diagnosis and syndrome based on Chinese medicine theory; (7) detailed information about the CM intervention (the manufacturer of the drug, series number, valid dates, dosage, route of administration, menstruum, dripping speed, etc.); (8) concomitant drug use; (9) time and symptoms of ADR/AE; (10) type and grading of ADR/AE; (11) physiological systems affected by ADR/AE; (12) specific treatment and prognosis for ADR/AE; (13) evidence of the cause and effect of ADR/AE; and (14) any other possibility of ADR/AE. Also, a ADR/AE registration system should be established. [ABSTRACT FROM AUTHOR]

Objective To compare the relative effectiveness and side effects of two intrauterine devices (IUDs), TCu380A and Multiload Cu375 (MLCu375). Methods We searched PubMed, EMBASE, the Cochrane Library, POPLINE, SCOPUS, and the Chinese Biomedical Literature Database in all languages, along with reference lists of retrieved papers. Randomized controlled trials comparing TCu380A with MLCu375 were included. The outcomes examined were pregnancy, continuation, removal, expulsion, infection, pain, abnormal menstruation, uterine perforation, and other adverse events. Two reviewers independently extracted the data. Data from the trials were combined to calculate relative risks (RRs) along with 95% confidence intervals (CIs). Results Sixteen trials were included, involving 15236 participants. Generally the methodological quality was poor. Compared to MLCu375, TCu380A was associated with less pregnancy and expulsion at five years with (RR: 0.49, 95% CI: 0.33 to 0.72; RR: 0.63, 95% CI: 0.45 to 0.89; respectively), as well as more removals for bleeding and/or pain at three years and pelvic infection disease over the whole study period (RR: 1.83, 95% CI: 1.28 to 2.62; RR: 1.47, 95% CI: 1.03 to 2.11; respectively). There were no statistical differences at all time intervals to 5 years in continuation rates or rates of uterine perforation. Conclusions While there was some variability between study results, we found evidence that TCu380A is more effective than MLCu375, with a similar side-effect profile. [ABSTRACT FROM AUTHOR]

Objective: To explore the relationship between macro-economic indicators and incidences of adverse events linked to intrauterine devices (IUDs)., Methods: Data on IUD-associated adverse events were collected from a cohort study conducted between September 2005 and December 2006. Regional economic data were from the 2006 National Economic and Social Development Statistical Bulletins and Statistical Yearbooks of various regions. A total of 20,220 IUD users in 236 towns in Jiangsu, Shanghai, Guangdong, Anhui, Sichuan, and Chongqing provinces in China were included in this study. Linear correlation and regression analyses were used to analyze the relationships between regional income and total incidences of adverse events, incidences of mild adverse events, and incidences of severe adverse events., Results: Incidences of total adverse events and mild adverse events were positively correlated with regional economic level (rs= 0.336, p < 0.05; rs= 0.272, p < 0.05), while incidences of severe adverse events were not correlated with regional economic level., Conclusions: The positive relationship between regional economic level and reported IUD-associated mild adverse events likely reflects income-related disparities in women seeking care and receiving treatment for mild adverse events. This points to a need to improve both public health education and the quality of health services, particularly in poorer areas., (© 2011 Blackwell Publishing Asia Pty Ltd and Chinese Cochrane Center, West China Hospital of Sichuan University.)