Research space telescope deployable mechanism variable diameter internal drive device elastic collision contact characteristics in the inter-stage transition.

To address the problem of elastic contact discrepancies between a variable-diameter internal drive device and a non-continuous surface during the transition, caused by the vibrations resulting from elastic collision impact when the motion speed of the elastic body increases, the following steps were taken. First, we established models for elastic collision, impact, and vibration during the inter-stage transition to analyze how motion speed and preload affect the elastic contact characteristics between the two components. Subsequently, we employed the finite element method to further analyze the elastic contact state, using identical loads but varying motion speeds and radial preloads as boundary conditions. Finally, an experimental prototype was developed to validate the elastic contact state of the elastic body during the inter-stage transition. The results indicated that the amplitude of elastic body vibration increased with higher motion speed, while it decreased with higher radial preload. Therefore, it is necessary to adjust radial preload at different times to ensure effective elastic contact between the elastic body and the non-continuous surface during the inter-stage transition. This approach not only enhances deployment speed but also guarantees the stability of the inter-stage transition.

High-grain diet feeding alters ileal microbiota and disrupts bile acid metabolism in lactating dairy cows.

Bile acids (BAs) play an important role in the regulation of lipid metabolic homeostasis, but little is known about their metabolism in dairy cows fed a high-grain (HG) diet. In the present study, we examined the bacterial community, BA profile, and the FXR/FGF19 signaling pathway in the ileum and liver to investigate the gut microbe-BA metabolism interactions response to HG diet and the changes in the subsequent enterohepatic circulation of dairy cows. The results showed that the ileal bacterial community was altered, with an increase of Paraclostridium, Anaerobutyricum, Shuttleworthia, and Stomatobaculum in the relative abundance in the HG group. Moreover, real-time polymerase chain reaction (PCR) showed that the abundance of total bacteria and bacterial bile-salt hydrolase (BSH) genes was increased in the ileal digesta in the HG group. Meanwhile, HG feeding also decreased the total BA content in the digesta of jejunum and ileum and in feces. HG feeding altered the BA profile in the ileal digesta by increasing unconjugated BAs and decreasing conjugated BAs. In addition, the intestinal FXR/FGF19 signaling pathway was activated. The expression of CYP7A1 (cholesterol 7α-hydroxylase) was depressed, which inhibited BAs synthesis in the liver of cows fed HG. Overall, HG feeding altered the ileal bacterial community and BA profile, and activated FXR/FGF19 signaling pathway, resulting in a decrease of BA level in the ileal digesta via the inhibition of hepatic BA synthesis. The findings provided novel insights into understanding the relationship between gut microbiota and the homeostasis of BAs in dairy cows fed a HG diet.

Bile acids plays an important role in regulating lipids metabolism in animals and human. Dairy cows fed high-grain (HG) diet generally suffer abnormal lipids metabolism. However, if there is a relationship between the bile acids metabolism and abnormal lipids metabolism in dairy cows fed HG diet is unclear. This study found that HG diet altered the bacterial community and bile aids composition in the ileum of dairy cows. HG also activated the FXR/FGF19 signaling pathway in the ileum, and inhibited the bile acid synthesis in the liver, which might be the reason for the reduced level of bile acid in the digesta of small intestine. The reduced bile acid level in the small intestine might affect the digestion and absorption of the dietary lipids in dairy cows fed HG diet.

Effects of hypoxia-inducible factor prolyl hydroxylase inhibitors versus erythropoiesis-stimulating agents on iron metabolism and inflammation in patients undergoing dialysis: A systematic review and meta-analysis.

Aims: This study aimed to evaluate the effects of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) on iron metabolism and inflammation in dialysis-dependent chronic kidney disease (DD-CKD) patients. Methods: PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov websites were searched for randomized controlled trials (RCTs) investigating HIF-PHIs versus ESAs for DD-CKD patients. Key findings: Twenty studies with 14,737 participants were included in the meta-analysis, which demonstrated no significant difference in the effect of transferrin saturation and ferritin between HIF-PHIs and the ESAs group (MD, 0.65; 95%CI, -0.45 to 1.75; very low certainty; SMD, -0.03; 95% CI, -0.13 to 0.07; low certainty). However, HIF-PHIs significantly increased the iron (MD, 2.30; 95% CI, 1.40 to 3.20; low certainty), total iron-binding capacity (SMD, 0.82; 95% CI, 0.66 to 0.98; low certainty), and transferrin (SMD, 0.90; 95%CI, 0.74 to 1.05; moderate certainty) levels when compared with the ESAs group. In contrast, the hepcidin level and dosage of intravenous iron were significantly decreased in the HIF-PHIs group compared with the ESAs group (MD, -15.06, 95%CI, -21.96 to -8.16; low certainty; MD, -18.07; 95% CI, -30.05 to -6.09; low certainty). The maintenance dose requirements of roxadustat were independent of baseline CRP or hsCRP levels with respect to the effect on inflammation. Significance: HIF-PHIs promote iron utilization and reduce the use of intravenous iron therapy. Furthermore, HIF-PHIs, such as roxadustat, maintain the erythropoietic response independent of the inflammatory state. Thus, HIF-PHIs may be an alternative treatment strategy for anemia in DD-CKD patients, where ESA is hyporesponsive due to iron deficiency and inflammation.

Cardiac and Kidney Adverse Effects of HIF Prolyl-Hydroxylase Inhibitors for Anemia in Patients With CKD Not Receiving Dialysis: A Systematic Review and Meta-analysis.

RATIONALE & OBJECTIVE: Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are novel, orally administered agents for anemia management in chronic kidney disease (CKD). We evaluated the cardiac and kidney-related adverse effects of HIF-PHIs among patients with CKD and anemia. STUDY DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). SETTING & STUDY POPULATIONS: Patients with anemia and CKD not receiving maintenance dialysis. SELECTION CRITERIA FOR STUDIES: RCTs comparing HIF-PHIs to placebo or an erythropoiesis-stimulating agent (ESA) with primary outcomes of cardiac and kidney-related adverse events (AEs). DATA EXTRACTION: Two independent reviewers evaluated RCTs for eligibility and extracted relevant data. ANALYTICAL APPROACH: Dichotomous variables were pooled using the Mantel-Haenszel method and presented as risk ratios (RRs). Subgroup analyses evaluated different intervention times and HIF-PHIs, as well as phase 2 versus phase 3 trials. The certainty of findings was rated according to GRADE criteria. RESULTS: Twenty-three studies with 15,144 participants were included. No significant difference in the risk of cardiac AEs was observed between the HIF-PHIs group and the placebo (RR, 1.02 [95% CI, 0.89-1.16]; moderate certainty) or ESA (RR, 1.06 [95% CI, 0.98-1.14]; low certainty) groups. No significant difference in the risk of kidney-related AEs was observed between the HIF-PHIs group and the placebo (RR, 1.09 [95% CI, 0.98-1.20]; moderate certainty) or ESA (RR, 1.00 [95% CI, 0.94-1.06]; low certainty) groups. The occurrence of hypertension and hyperkalemia was higher in the HIF-PHIs group than in the placebo group (RRs of 1.35 [95% CI, 1.14-1.60] and 1.25 [95% CI, 1.03-1.51], respectively; both findings had high certainty). The occurrence of hypertension was lower in the HIF-PHIs group than in the ESA group (RR, 0.89 [95% CI, 0.81-0.98]; moderate certainty). LIMITATIONS: The reporting criteria of cardiac and kidney-related AEs and dosage of HIF-PHIs were inconsistent across trials. CONCLUSIONS: The occurrence of cardiac or kidney-related AEs in the HIF-PHI groups were not different compared with placebo or ESA groups. REGISTRATION: Registered at PROSPERO with registration number CRD42021228243.

Genome-centric investigation of bile acid metabolizing microbiota of dairy cows and associated diet-induced functional implications.

Although the importance of bile acid (BA)-related microbial strains and enzymes is increasingly recognized for monogastric animals, a lack of knowledge about BA metabolism in dairy cows limits functional applications aimed at the targeted modulation of microbe-host interactions for animal production and health. In the present study, 108 content samples from six intestinal regions of dairy cows were used for shotgun metagenomic sequencing. Overall, 372 high-quality metagenome-assembled genomes (MAGs) were involved in BA deconjugation, oxidation, and dehydroxylation pathways. Furthermore, the BA-metabolizing microbiome predominately occurred in the large intestine, resulting in the accumulation of secondary unconjugated BAs. Comparative genomic analysis revealed that the bile salt hydrolase (BSH)-carrying microbial populations managed with the selective environment of the dairy cow intestine by adopting numerous host mucin glycan-degrading abilities. A sequence similarity network analysis classified 439 BSH homologs into 12 clusters and identified different clusters with diverse evolution, taxonomy, signal peptides, and ecological niches. Our omics data further revealed that the strains of Firmicutes bacterium CAG-110 processed the increased abundance of BSHs from Cluster 1, coinciding with the changes in the colon cholic acid concentration after grain introduction, and were intricately related to intestinal inflammation. This study is the first to use a genome-centric approach and whole intestine-targeted metabolomics to reveal microbial BA metabolism and its diet-induced functional implications in dairy cows. These findings provide insight into the manipulation of intestinal microorganisms for improving host health.

Integrated analyses of brain and platelet omics reveal their common altered and driven molecules in Alzheimer's disease.

Platelets may serve as a perfect peripheral source for exploring diagnostic biomarkers for Alzheimer's disease (AD); however, the molecular linkage between platelet and the brain is missing. To find the common altered and driving molecules in both brain and the platelet, we performed an integrated analysis of our platelet omics and brain omics reported in the literature, and analyzed their correlations with AD-specific pathology and cognitive impairment. By integrating the gene and protein expression profiles from 269 AD patients, we deduced 239 differentially expressed proteins (DEPs) appeared in both brain and the platelet, and 70.3% of them had consistent changes. Further analysis demonstrated that the altered brain and peripheral regulations were pinpointed into 10 imbalanced pathways. We also found that 117 DEPs, including ADAM10, were closely associated to the AD-specific ß-amyloid and tau pathologies; and the changes of IDH3B and RTN1 had a potential diagnostic value for cognitive impairment analyzed by machine learning. Finally, we identified that HMOX2 and SERPINA3 could serve as driving molecules in neurodegeneration, and they were increased and decreased in AD patients, respectively. Together, this integrated brain and platelet omics provides a valuable resource for establishing efficient peripheral diagnostic biomarkers and potential therapeutic targets for AD.

[Application status and thinking of acupuncture and moxibustion therapy for assisted reproductive field in the United States].

The application status of acupuncture and moxibustion therapy for assisted reproductive field in the United States was analyzed, and the existing problems and future development directions were discussed. According to the survey on the 456 websites of assisted reproductive clinic in the United States mentioned in the report of U.S. Centers for Disease Control and Prevention (CDC), 111 clinics among 456 assisted reproductive clinics recommend and used acupuncture and moxibustion therapy, accounting for 24.3%. Acupuncture and moxibustion therapy had obvious effect, good safety and low cost, and the assisted reproductive institutions in the United States had a high degree of application and recognition to acupuncture and moxibustion therapy. However, some problems, such as immature treatment scheme, unclear mechanism and imperfect insurance policies, still existed. In the future, the advantages of Chinese traditional acupuncture and moxibustion should combine with international modern assisted reproductive technology, and multi-center and large-sample clinical randomized controlled trials and basic experimental research on the mechanism of acupuncture and moxibustion for assisted reproduction should be carried out.

[Application of Tiaojing Cuyun acupuncture in treatment of diseases with ovarian function decline].

Taking regulating the thoroughfare vessel and the conception vessel, tonifying liver and kidney, calming mind as the treatment principle, Tiaojing Cuyun acupuncture (acupuncture for regulating menstruation and promoting pregnancy) is commonly used in clinical treatment of diseases with ovarian function decline, and recommends full cycle acupuncture treatment. Clinical research shows that Tiaojing Cuyun acupuncture can improve menstruation and ovulation, increase the reserve function and response of ovary as well as endometrial receptivity, so as to improve the pregnancy outcome. It can also improve the related symptoms caused by negative emotions and low estrogen, and comprehensively enhance the health related quality of life in patients. The mechanism of Tiaojing Cuyun acupuncture mainly involves 2 aspects, i.e. overall regulation on hypothalamus-pituitary-ovary (HPO) axis and the local regulation on FSH/cAMP signal transduction in ovarian granulosa cells.

Effect of acupuncture for diminished ovarian reserve: study protocol for a randomized controlled trial.

BACKGROUND: Diminished ovarian reserve (DOR) is a condition in which the ovary loses its normal reproductive potential, compromising fertility. Although the prevalence and incidence of DOR is increasing, there are currently no effective treatments for this condition. Acupuncture has been reported as an alternative therapy for female infertility. The purpose of this study is to investigate the effect of acupuncture for women with DOR. METHODS/DESIGN: In this randomized controlled trial, a total of 120 women with DOR will be randomly assigned to receive either acupuncture or sham acupuncture for 12 weeks. The primary outcome will be determined by the mean change from baseline in the antral follicle count (AFC) at week 12. Secondary outcomes include serum levels of FSH, LH, E2, and AMH, the length of menstrual cycle, and the score of Self-Rating Anxiety Scale (SAS). DISCUSSION: This study is expected to investigate the effectiveness of acupuncture versus sham acupuncture in improving ovarian reserve for women with DOR. TRIAL REGISTRATION: Acupuncture-Moxibustion Clinical Trial Registry ChiCTR1800014988 . Registered on 6 February 2018.

Controlled ovarian hyperstimulation for poor ovarian responders undergoing in vitro fertilisation/intracytoplasmic sperm injection: a protocol for systematic review and Bayesian network meta-analysis.

INTRODUCTION: Controlled ovarian hyperstimulation (COH) is the routine regimen used to generate a sufficient number of follicles during in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatment. Poor ovarian response is a challenge encountered by many clinicians during COH and poor ovarian responders (PORs) usually have higher follicle stimulating hormone levels, lower levels of anti-Mullerian hormone and few oocytes retrieved, which have been attributed mainly to advanced maternal age and poor follicle reserve or other reasons that could impair ovarian response during ovarian stimulation. Over the last few decades, researchers have proposed a series of strategies and ovarian stimulation protocols to improve pregnancy outcomes in patients with POR during their IVF/ICSI treatment. However, clinical decisions regarding COH protocols in PORs during IVF/ICSI treatment remain controversial. Traditional pairwise meta-analysis only allows the direct comparison of two protocols in COH for patients with POR. However, many of these COH protocols have not been compared directly in randomised controlled trials (RCTs). Thus, we aim to use network meta-analysis (NMA) to assess the clinical effectiveness and safety of COH protocols and to generate treatment rankings of these COH protocols for the most clinically important and commonly reported outcomes events. METHODS AND ANALYSIS: The PubMed, Embase, Cochrane Library, Web of Science, SinoMed, CNKI, WanFang database and Chongqing VIP information databases will be searched for all RCTs of COH for POR women during IVF/ICSI from inception to 31 March 2020. Primary outcomes will include live birth rate and number of oocytes retrieved. Secondary outcomes will include ongoing pregnancy rate, clinical pregnancy rate, miscarriage rate, ovarian hyperstimulation syndrome rate, multiple pregnancy rate and cycle cancellation rate. Pairwise meta-analysis and Bayesian NMA will be conducted for each outcome. Subgroup analysis, meta-regression, and sensitivity analysis will be performed to assess the robustness of the findings. The generation of NMA plots and subsequent results will be performed by using R V.4.0.1. The assessment of confidence in network estimates will use the Confidence in Network Meta-Analysis)web application (see https://cinema.ispm.unibe.ch/). ETHICS AND DISSEMINATION: This review does not require ethics approval and the results of the NMA will be submitted to a peer-review journal.

The efficacy and safety of roxadustat for anemia in patients with chronic kidney disease: a meta-analysis.

BACKGROUND: Chronic kidney disease (CKD) is an increasing public health issue. Anemia, which is a complication of CKD, is associated with reduced quality of life and increased morbidity and mortality. Currently quite a few clinical studies have been conducted to compare roxadustat with epoetin alfa [all for dialysis-dependent (DD) patients] or placebo [all for nondialysis-dependent (NDD) patients]. Our meta-analysis aimed to investigate the efficacy and safety of roxadustat for anemia in patients with CKD. METHODS: We thoroughly searched eight electronic resource databases for randomized controlled trials (RCTs) comparing the efficacy and safety between roxadustat versus epoetin alfa or placebo for the treatment of anemia in patients with CKD. RESULTS: Four Phase 2 and two Phase 3 studies with 1010 participants were included. Hemoglobin (Hb) and transferrin levels were increased significantly in the roxadustat group versus those in the placebo {standard mean difference [SMD] 1.57 [95% confidence interval (CI) 1.17-1.98]; SMD 1.81 [95% CI 1.53-2.08]; respectively, both low-quality evidence} or epoetin alfa group [SMD 0.47 (95% CI 0.02-0.93), very low-quality evidence; SMD 1.05 (95% CI 0.81-1.29), low-quality evidence; respectively]. Hepcidin levels were reduced significantly in the roxadustat group versus those in the placebo [SMD -1.72 (95% CI -3.03 to -0.41), very low-quality evidence] or epoetin alfa group [SMD -0.23 (95% CI -0.43 to -0.02), low-quality evidence]. Ferritin and serum transferrin saturation (TSAT) levels were reduced significantly in the roxadustat group versus those in the placebo group [SMD -0.82 (95% CI -1.31 to -0.33); SMD -0.54 (95% CI -0.76 to -0.32), respectively; both low-quality evidence] and ferritin and TSAT levels in the roxadustat group were comparable to those in the epoetin alfa group [SMD 0.02 (95% CI -0.18-0.21); SMD 0.15 (95% CI -0.04-0.35), respectively, both low-quality evidence]. As for safety, the incidence of adverse events (AEs) in the roxadustat group was insignificantly different from that of the placebo group [risk ratio (RR) 0.99 (95% CI 0.83-1.18); P = 0.89, very low-quality evidence]. But the incidence of AEs in the roxadustat group was significantly higher than that in the epoetin alfa group [RR 1.25 (95% CI 1.01-1.54); P = 0.04, low-quality evidence]. There was no significant association between roxadustat and the incidence of serious AEs (SAEs) for both NDD and DD patients [RR 1.08 (95% CI 0.51-2.28) and RR 1.43 (95% CI 0.85-2.40), respectively, both very low-quality evidence]. CONCLUSION: In this meta-analysis of RCTs, we found evidence that after the oral administration of roxadustat, NDD patients' Hb levels were increased effectively and DD patients' Hb levels were maintained effectively. The risk of SAEs was not observed with the short-term use of roxadustat. These findings support roxadustat for the treatment of anemia in patients with CKD.

Effect of acupuncture on women with poor ovarian response: a study protocol for a multicenter randomized controlled trial.

BACKGROUND: Poor ovarian response (POR), a manifestation of low ovarian reserve and ovarian aging, leads to a significant reduction in the pregnancy rate after in vitro fertilization-embryo transfer. Acupuncture has increasingly been used to improve the ovarian reserve. The purpose of this study will be to evaluate the effect of acupuncture on increasing the number of retrieved oocytes after controlled ovarian hyperstimulation in women with POR. METHODS: This will be a multicenter randomized controlled trial. A total of 140 women with POR will be randomly assigned to receive acupuncture or nontreatment for 12 weeks before controlled ovarian hyperstimulation. The primary outcome will be the number of retrieved oocytes. The secondary outcomes will be antral follicle counts, serum levels of anti-Müllerian hormone, basal serum levels of follicle stimulating hormone, luteinizing hormone and estradiol levels, scores from the self-rating anxiety scale, fertilization rates, cleavage rates, available embryo rates, and high-quality embryo rates. The safety of acupuncture will also be assessed. DISCUSSION: The results of this trial will help to determine the effectiveness of acupuncture in the treatment of POR. This may provide a new treatment option for patients with POR and their physicians. TRIAL REGISTRATION: AMCTR-IPR-18000198 . Registered on 10 August 2018.

[Discussion on contents and methods of quality control for acupuncture registry study].

To explore the basic principles and methods of quality control of clinical registry research in the field of acupuncture. This study drawed on the data quality control methods of clinical trials in the United States and combined clinical practice experience, based on the "International Patient Registry Platform of Acupuncture and Moxibustion", and the registry study of acupuncture treatment for early-onset ovarian insufficiency as a model. The principles of accuracy, authenticity, consistency and completeness were followed. A remote and on-site quality control method with remote quality control as the main and on-site quality control as the supplement is formed, with a view to providing ideas and reference for the quality control of registry research.

Efficacy and safety of HIF prolyl-hydroxylase inhibitor vs epoetin and darbepoetin for anemia in chronic kidney disease patients not undergoing dialysis: A network meta-analysis.

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are a new class of oral medicines being developed for the treatment of anemia in chronic kidney disease (CKD) patients. This study aimed to compare the efficacy and safety of HIF-PHI vs epoetin and darbepoetin in CKD patients with anemia not undergoing dialysis. The PubMed, Embase, Cochrane Library, Web of Science, and clinicaltrials.gov databases were searched from inception to October 2019 for randomized controlled trials investigating different agents (six HIF-PHIs, epoetin, darbepoetin, and placebo) for treating CKD patients with anemia that did not undergo dialysis. The outcomes included a change in hemoglobin (Hb) levels and all-cause mortality. A total of 19 studies were included. Compared with the placebo, except for vadadustat (mean differences: 1.12, 95 % confidence interval [CI]: ‒0.11-2.35), the other drugs significantly increased Hb levels, with mean differences of 2.46 (95 % CI: 0.93-3.99) for desidustat, 1.81 (0.87-2.75) for enarodustat, 1.68 (0.64-2.72) for molidustat, 1.66 (0.89-2.44) for epoetin, 1.63 (0.69-2.56) for darbepoetin, 1.61 (0.99-2.22) for roxadustat, and 1.55 (0.74-2.36) for daprodustat. No differences were found in the Hb level elevations among these eight drugs. Compared with the placebo, there also was no significant association between the drugs and all-cause mortality (molidustat of RR, 0.39 [95 % CI, 0.06-2.59]; roxadustat, 0.40 (0.06-2.84); enarodustat, 0.33 (0.01-16.25); desidustat, 0.34 (0.01-17.00); epoetin, 0.50 (0.18-1.42); daprodustat, 0.54 (0.09-3.31); darbepoetin, 1.03 (0.65-1.65); and vadadustat, 1.43 (0.15-13.27)). No differences were observed in the all-cause mortality among the drugs. In conclusion, these HIF-PHIs are effective and relatively tolerant for treating anemia patients with CKD not undergoing dialysis. Further research should consider the limitations of our study to evaluate the value of these HIF-PHIs in clinical settings.

Efficacy of Intermittent or Continuous Very Low-Energy Diets in Overweight and Obese Individuals with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analyses.

OBJECTIVE: This study is aimed at investigating the efficacy of a very low-energy diet (VLED) in overweight and obese individuals with type 2 diabetes mellitus (T2DM). METHODS: We thoroughly searched eight electronic resource databases of controlled studies concerning the efficacy and acceptability of intermittent or continuous VLEDs in patients with T2DM compared with other energy restriction interventions. RESULTS: Eighteen studies (11 randomized and seven nonrandomized controlled trials) with 911 participants were included. The meta-analyses showed that compared with a low-energy diet (LED) and mild energy restriction (MER), VLED is superior in the reduction of body weight (mean difference (MD) MDLED = -2.77, 95% confidence interval (CI) CILED = -4.81 to - 0.72, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39, I 2 = 0%) and TG level (MD = -0.25, 95%CI = -0.55 to 0.06, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39, I 2 = 0%) and TG level (MD = -0.25, 95%CI = -0.55 to 0.06, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39. CONCLUSION: Dietary intervention through VLEDs is an effective therapy for rapid weight loss, glycemic control, and improved lipid metabolism in overweight and obese individuals with T2DM. Thus, VLEDs should be encouraged in overweight and obese individuals with T2DM who urgently need weight loss and are unsuitable or unwilling to undergo surgery. As all outcome indicators have low or extremely low quality after GRADE evaluation, further clinical trials that focus on the remission effect of VLEDs on T2DM are needed.

Efficacy and Safety of Daprodustat for Anemia Therapy in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis.

Objective: Daprodustat is a novel oral agent in treating anemia of chronic kidney disease (CKD), and several clinical trials have been conducted to compare daprodustat with recombinant human erythropoietin (rhEPO) or placebo. Our systematic review aimed to investigate the efficacy and safety of daprodustat for anemia treatment in both dialysis-dependent (DD) and non-dialysis-dependent (NDD) patients. Methods: Six databases were searched for randomized controlled trials (RCTs) reporting daprodustat vs. rhEPO or placebo for anemia patients in CKD. The outcome indicators were focused on hemoglobin (Hb), ferritin, transferrin saturation (TSAT), total iron-binding capacity (TIBC), vascular endothelial growth factor (VEGF), and serious adverse events (SAEs). Results: Eight eligible studies with 1,516 participants were included. For both NDD and DD patients, changes in Hb levels from baseline were significantly higher in daprodustat group than that in the placebo (mean difference (MD) = 1.73, [95% confidence interval (CI), 0.34 to 3.12], p = 0.01; MD = 1.88, [95% CI, 0.68 to 3.09], p = 0.002; respectively), and there was no significant difference between daprodustat and rhEPO group (MD = 0.05, [95% CI, -0.49 to 0.59], p = 0.86; MD = 0.12, [95% CI, -0.28 to 0.52], p = 0.55; respectively). The indexes of iron metabolism were improved significantly in the daprodustat group compared to placebo- or rhEPO-treated patients, while there was no similar change in terms of TSAT for DD patients. Furthermore, no trend of increasing plasma VEGF was observed in daprodustat-treated subjects. As for safety, there was no significant difference in the incidence of SAEs between daprodustat and placebo treatment, while the incidence of SAEs in the daprodustat group was significantly lower than that in the rhEPO group. Conclusion: Daprodustat was efficacious and well tolerated for anemia in both NDD and DD patients in the short term based on current RCTs. And daprodustat may become an effective alternative for treatment of anemia with CKD. Since the application of daprodustat is still under exploration, future researches should consider the limitations of our study to evaluate the value of daprodustat.

Comparative efficacy of 13 immunosuppressive agents for idiopathic membranous nephropathy in adults with nephrotic syndrome: a systematic review and network meta-analysis.

OBJECTIVES: This study aimed to compare the effectiveness of 13 types of immunosuppressive agents used to treat idiopathic membranous nephropathy (IMN) in adults with nephrotic syndrome. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: PubMed, EMbase, Cochrane Library, Web of Science, Clinical trials, SinoMed, Chinese Biomedicine, CNKI, WanFang and Chongqing VIP Information databases were comprehensively searched until February 2018. ELIGIBILITY CRITERIA: Randomised clinical trials (RCTs) comparing the effects of different immunosuppressive treatments in adult patients with IMN and nephrotic syndrome were included, and all included RCTs had a study-duration of at least 6 months. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened articles, extracted data and assessed study quality. Standard pairwise meta-analysis was performed using DerSimonian-Laird random-effects model. RESULTS: This study ultimately included 48 RCTs with 2736 patients and 13 immunosuppressive agents. The network meta-analysis results showed that most regimens, except for leflunomide (LEF), mizoribine (MZB) and steroids (STE), showed significantly higher probabilities of total remission (TR) when compared with non-immunosuppressive therapies (the control group),with risk ratios (RRs) of 2.71 (95% CI) 1.81 to 4.06)for tacrolimus+tripterygium wilfordii (TAC+TW), 2.16 (1.27 to 3.69) foradrenocorticotropic hormone, 2.02 (1.64 to 2.49) for TAC, 2.03 (1.13 to3.64) for azathioprine (AZA), 1.91 (1.46 to 2.50) for cyclosporine (CsA), 1.86 (1.44 to2.42) for mycophenolate mofetil (MMF), 1.85 (1.52 to 2.25) for cyclophosphamide (CTX),1.81 (1.10 to 2.98) for rituximab (RIT), 1.80 (1.38 to 2.33) for TW, 1.72 (1.35 to 2.19) for chlorambucil. As for 24 hours UTP, the direct andindirect comparisons showed that AZA (standard mean difference (SMD), -1.02(95% CI -1.90 to -0.15)), CsA (SMD, -0.70 (95% CI -1.33 to -0.08)),CTX (SMD, -1.01 (95% CI -1.44 to -0.58)), MMF (SMD, -0.98 (95% CI -1.64 to -0.32)), MZB (SMD, -0.97 (95% CI -1.90 to-0.04]), TAC (SMD, -1.16 (95% CI -1.72 to -0.60)) and TAC+TW(SMD, -2.03 (95% CI -2.94 to -1.12)) could significantly superior thancontrol, except for chlorambucil, LEF, RIT and STE. Thechanges of serum creatinine (Scr) was not significantly different between eachtreatments of immunosuppressive agents and the control, except for STE whichhas the possibility of increasing Scr (SMD, 1.00 (95% CI 0.36 to 1.64)).Comparisons among all treatments of immunosuppressive agents showed nostatistical significance in the outcome of relapse. A drenocorticotropichormone (85.1%) showed the lowest probability of relapse under the cumulativeranking curve values among all immunosuppressants. Infection,gastrointestinal symptoms, and bone marrow suppression were the common adverseevents associated with most of the immunosuppressive therapies. CONCLUSIONS: This study demonstrates that TAC+TW, TAC and CTX are superior to other immunosuppressive agents in terms of TR and 24 hours UTP. Moreover, they are all at risk of infection, gastrointestinal symptoms, and myelosuppression. Furthermore, TAC could increase the risk of glucose intolerance or new-onset diabetes mellitus. Conversely, STE alone, LEF and MZB seem to have little advantage in clinical treatment of IMN. PROSPERO REGISTRATION NUMBER: CRD42018094228.

[Network meta-analysis on the effects of the acupuncture-related therapy on ovulation rate and pregnancy rate in patients with polycystic ovary syndrome].

OBJECTIVE: To review systematically the safety and effectiveness of acupuncture-related therapies on ovulation rate and pregnancy rate in patients with polycystic ovary syndrome (PCOS). METHODS: From PubMed, EMbase, the Cochrane Library, China Biology Medicine disc (CBM), China National Knowledge Infrastructure (CNKI), Wanfang database and VIP database, the randomized controlled trials (RCTs) on PCOS were retrieved in the period from the date of database establishment to January 8, 2018. Two researchers screened the articles, extracted the data and assessed the bias risk of the eligible trials independently. Using Stata 13.0 and WinBUGS 1.4.3 software, the data were analyzed. RESULTS: A total of 39 RCTs were collected, including 4605 cases of PCOS and 14 kinds of acupuncture-related therapies and the comprehensive therapies. The short-term therapeutic effects were observed. The results of mesh meta-analysis showed: regarding the ovulation rate, the effects of the acupuncture-medication therapy were better than western medication. The top 6 therapeutic measures were the treatment with acupoint thread-embedding therapy and medication (93.3%), the treatment with moxibustion and Chinese herbal medicine (91.4%), moxibustion (74.5%), the treatment with acupuncture and medication (65.7%), the treatment with acupuncture-moxibustion and auricular point therapy (61.9%) and the treatment with acupuncture and auricular point therapy (49.6%). Regarding the pregnancy rate, the effects of the acupuncture-medication therapy were better than western medication. The top 6 therapeutic measures were the treatment with acupuncture and auricular point therapy (91.5%), the treatment with moxibustion and Chinese herbal medication (86.9%), the treatment with acupuncture-moxibustion and auricular point therapy (81.1%), the treatment with acupoint thread-embedding therapy and medication (69.4%), the treatment with acupuncture and medication (66.1%) and the treatment with placebo and western medication (58.7%). CONCLUSION: Among acupuncture-related therapies, the combined treatment is more advantageous than single therapy and its safety is superior to western medication. The combined therapies are various in advantages. Because of the limitation of the present researches, it needs a large scale of RCTs with rational design, high quality and proper methods to verify this research conclusion.

Acupuncture and Related Therapies for Obesity: A Network Meta-Analysis.

Obesity is a worldwide public health problem. Currently, increasing evidence suggests acupuncture and related therapies are effective for obesity. This network meta-analysis (NMA) was performed to compare the effectiveness of different acupuncture and related therapies. We searched potential randomized controlled trials (RCTs) in three international databases. Thirty-four trials involving 2283 participants were included. Pairwise meta-analysis showed that acupuncture and related therapies were superior to lifestyle modification and placebo in reducing weight and body mass index (BMI). Based on decreases in body weight, results from NMA showed that acupoint catgut embedding (standard mean difference [SMD]: 1.26; 95% credible interval [95% CI], 0.46-2.06), acupuncture (SMD: 2.72; 95% CrI, 0.06-5.29), and combination of acupuncture and related theories (SMD: 3.65; 95% CrI, 0.96-6.94) were more effective than placebo. Another NMA result indicated that acupoint catgut embedding (SMD: 0.63; 95% CI, 0.25-1.11), acupuncture (SMD: 1.28; 95% CrI, 0.43-2.06), combination of acupuncture and related therapies (SMD: 1.44; 95% CrI, 0.64-2.38), and electroacupuncture (SMD: 0.60; 95% CrI, 0.03-1.22) were superior to lifestyle modification in decreasing BMI. Combination of acupuncture and related therapies was ranked the optimal method for both reducing weight and BMI. Further studies will clarify which combination of acupuncture and related therapies is better.