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The etiology for a considerable proportion of patients with congenital radioulnar synostosis (RUS) remains unclear. This study aimed to investigate the genetic cause of RUS without a known cause.Patients with RUS were investigated. Exome sequencing and/or Sanger sequencing was performed. Bioinformatics analysis was also performed. Pathogenicity was evaluated for variants of interest.We identified unique missense variants in MECOM (encodes EVI1) associated with RUS in 8 families. Of them, 6 families had variants in residue R781, including 3 families with R781C (c.2341CT), 2 families with R781H (c.2342GA), and 1 family with R781L (c.2342GT). Another 2 variants included I783T (c.2348TC) in 1 family and Q777E (c.2329CG) in 1 family. All these variants were clustered within the ninth zinc finger motif of EVI1. Phenotype evaluation identified that most of these patients with RUS harboring mutant MECOM had finger malformations, but none of them had identifiable hematological abnormalities. Functional experiments showed that MECOM R781C led to alterations in TGF-β-mediated transcriptional responses.This study examined MECOM variants by focusing on RUS instead of hematological abnormalities. The R781 residue in EVI1 is a hotspot for human RUS variants. Mutant MECOM is the second most common cause for familial RUS.

Purpose In the Guidelines for the Prevention and Control of Type 2 Diabetes in China (2017 edition), intensive lifestyle interventions are recommended for preventing the progression of impaired glucose tolerance (IGT) to type 2 diabetes mellitus. Acarbose and metformin can also be considered if intensive lifestyle modification has been ineffective for 6 months. But the effects of intensive lifestyle modification and glucose-lowering drug interventions that work best in the population with IGT are unclear. This network meta-analysis assessed the effectiveness of intensive lifestyle modification, acarbose, and metformin in treating populations with IGT. Methods We systematically searched both Chinese- and English-language databases, including China Knowledge, the Cochrane Library, Embase, PubMed, VIP, and Wanfang, for articles published between database inception and September 2019. Randomized, controlled clinical trials in patients with IGT treated with acarbose, metformin, and intensive lifestyle modification were assessed for eligibility. The data from all included studies were evaluated by 2 reviewers independently in accordance with the Cochrane Handbook for Systematic Reviews of Intervention version 6.0. A network meta-analysis was performed by using R software version 3.6.1. Findings The data from 53 randomized controlled trials were included in the review, with a sample size of 21,208 patients. Compared with the control group, the use of acarbose, metformin, and/or intensive lifestyle modification was associated with reduced rates of progression to diabetes (relative risks [RRs] [95% credible intervals]: acarbose, 0.37 [0.29–0.47]; metformin, 0.39 [0.30–0.50]; intensive lifestyle modification, 0.61 [0.50–0.73]). The surface under the cumulative ranking (SUCRA) value of acarbose was 88.35%, supporting that acarbose was more effective in reducing the rate of progression to diabetes compared with controls. With acarbose, metformin, and intensive lifestyle modification, the rates of achieving a normal glucose level were increased by RR = 2.1, 1.7, and 1.2, respectively when compared with control group. The SUCRA value of acarbose was 99.69%, supporting the optimal effect of acarbose in achieving a normal blood glucose level. Implications In this meta-analysis in patients with IGT, compared with controls, acarbose and metformin were associated with decreased rates of progression to diabetes and increased rates of achieving a normal glucose level. Acarbose use was associated with an increased rate of achieving a normal glucose level, while intensive lifestyle modification was not.

Background: The maintenance treatment of ESRD puts a great burden on individual patients, society, and the country of China as a whole. Hemoperfusion plus hemodialysis (HP + HD) in ESRD patients can yield modified outcomes such as prolonged life expectancy and improved dialysis quality and quality of life. This study aimed to systematically analyze the effect of HP + HD on the overall survival (OS) rates of ESRD patients and to provide support for clinical decision-making. Methods: A computerized search was performed in the PubMed, Embase, Cochrane Library, CNKI, WanFang Data and SinoMed databases for relevant original research articles. Studies were included or excluded based on their compliance with predefined selection criteria. Results: Twelve studies were included in the qualitative synthesis and quantitative synthesis (meta-analysis). The meta-analysis showed that the 1-year OS rate (odds ratio [OR]: 3.35, 95% CI: 1.89, 5.91, p < 0.05), 2-year OS rate (OR: 2.88, 95% CI: 1.84, 4.53, p < 0.05), and 5-year OS rate (χ2 = 4.3092, p < 0.05) of patients with ESRD treated with HP + HD were better than those treated with HD, but there was no significant difference in 3-year OS rate (OR: 1.97, 95% CI: 0.76, 5.06, p > 0.05). Subgroup analysis showed the same outcomes in different study designs (1-year OS rate: randomized controlled trials [RCTs]: OR: 4.38, 95% CI: 1.61, 11.88, p < 0.05; cohort studies: OR: 2.90, 95% CI: 1.44, 5.85, p < 0.05; 2-year OS rate: RCTs: OR: 2.99, 95% CI: 1.84, 4.84, p < 0.05) and different age-groups (1-year OS rate: 45–50 years: OR: 3.19, 95% CI: 1.55, 6.57, p < 0.05; 55–60 years: OR: 3.37, 95% CI: 1.07, 10.61, p < 0.05; 2-year OS rate: 50–55 years: OR: 2.86, 95% CI: 1.59, 5.16, p < 0.05: 60–65 years: OR: 4.41, 95% CI: 1.19, 16.30, p < 0.05). Conclusions: This meta-analysis suggests that the OS rates of ESRD patients treated with HP + HD were better than those of patients treated with HD. A speculative hypothesis for why this is the case may be that HP + HD can achieve the complementary elimination of metabolites, effectively preventing and treating complications caused by long-term dialysis and prolonging life expectancy. Therefore, HP + HD should be widely used in ESRD patients.

Background SMAD6 variants have been reported in patients with radioulnar synostosis (RUS). This study aimed to investigate the genotypes and phenotypes for a large cohort of patients with RUS having mutant SMAD6. Methods Genomic DNA samples were isolated from 251 RUS sporadic patients (with their parents) and 27 RUS pedigrees. Sanger sequencing was performed for the SMAD6 coding regions. For positive probands, co‐segregation and parental‐origin analysis of SMAD6 variants and phenotypic re‐evaluation were performed for their family members. Results We identified 50 RUS probands with SMAD6 variants (13 co‐segregated with RUS in pedigrees and 37 in RUS‐sporadic patients). Based on the new and previous data, we identified SMAD6 mutated in 16/38 RUS pedigrees and 61/393 RUS sporadic patients, respectively. Overall, 93 SMAD6 mutant patients with RUS were identified, among which 29 patients had unilateral RUS, where the left side was more involved than the right side (left:right = 20:9). Female protective effects and non‐full penetrance were observed, in which only 6.90% mothers (vs. ~50% fathers) of SMAD6 mutant RUS probands had RUS. Pleiotropy was observed as a re‐evaluation of SMAD6 mutant families identified: (a) three families had axial skeletal malformations; (b) two families had polydactyly; and (c) eight families had other known malformations. Conclusion SMAD6 was mutated in 42.11% RUS pedigrees and 15.52% RUS sporadic patients. The RUS patients with SMAD6 variants exhibit both non‐full‐penetrance, variable expressivity, pleiotropy, female protective effects, and the left side is more susceptible than the right side., Radioulnar synostosis is a rare disorder with the genetic basis keeping unknown for several 100 of years. We recently identified SMAD6 and NOG are two disease genes for it, but the data are still limited. For using such advances in clinic, we further analyzed a large cohort of patients and provided a systemic data for SMAD6 and the disease.

Up to 84% of patients with congenital pseudarthrosis of the tibia (CPT) present with neurofibromatosis type 1 (NF1) (NF1-CPT). However, the etiology of CPT not fulfilling the NIH diagnostic criteria for NF1 (non-NF1-CPT) is not well understood. Here, we collected the periosteum tissue from the pseudarthrosis (PA) site of 43 non-NF1-CPT patients and six patients with NF1-CPT, together with the blood or oral specimen of trios (probands and unaffected parents). Whole-exome plus copy number variation sequencing, multiplex ligation-dependent probe amplification (MLPA), ultra-high amplicon sequencing, and Sanger sequencing were employed to identify pathogenic variants. The result showed that nine tissues of 43 non-NF1-CPT patients (21%) had somatic mono-allelic NF1 inactivation, and five of six NF1-CPT patients (83.3%) had bi-allelic NF1 inactivation in tissues. However, previous literature involving genetic testing did not reveal somatic mosaicism in non-NF1-CPT patients so far. In NF1-CPT patients, when the results from earlier reports and the present study were combined, 66.7% of them showed somatic NF1 inactivation in PA tissues other than germline inactivation. Furthermore, no diagnostic variants from other known genes (GNAS, AKT1, PDGFRB, and NOTCH3) related to skeletal dysplasia were identified in the nine NF1 positive non-NF1-CPT patients and six NF1-CPT patients. In conclusion, we detected evident somatic mono-allelic NF1 inactivation in the non-NF1-CPT. Thus, for pediatric patients without NF1 diagnosis, somatic mutations in NF1 are important.

Background This study evaluates the cost-effectiveness of hemodialysis (HD) plus hemoperfusion (HP) with HD alone in adult patients with end-stage renal disease (ESRD) in China. Methods A Markov model was constructed to assess the cost-effectiveness of interventions over a lifetime horizon. Model parameters were informed by the HD/HP trial, the first randomized, open-label multicenter trial comparing survival outcomes and incidence of cardiovascular disease (CVD) for HD + HP versus HD alone, and supplemented by published literature and expert opinion. The primary outcome was the incremental cost-effectiveness ratio (ICER) with respect to quality adjusted life-years (QALY). The robustness of the results was examined in extensive sensitivity analyses. Analyses were conducted from a healthcare perspective. Costs were reported in both Chinese Renminbi (RMB) and US Dollars (USD) in 2019 values. Results The base case ICER of HD + HP is RMB 174,486 (USD 25,251) per QALY, which is lower than the RMB 212,676 (USD 30,778) willingness-to-pay threshold of three times Gross Domestic Product. This conclusion is sensitive to the mortality for patients with no severe CVD events, the incidence of CVD events, and the cost of HP and HD. At a willingness-to-pay threshold of RMB 212,676 (USD 30,778) per QALY gained, the probability that HD + HP is cost-effective is 58%. Conclusions Our results indicate a potential for HD + HP to be cost-effective for patients with ESRD. Further evidence on the longer-term impact of HD + HP on CVD event rates and mortality unrelated to CVD is needed to robustly demonstrate the cost-effectiveness of HD + HP. Trial registration The HD/HP trial was registered with the Chinese Clinical Trial Registry (ChiCTR-IOR-16009332).

Objectives: To evaluate the cost-effectiveness of olmesartan/amlodipine fixed-dose combination vs olmesartan and amlodipine free combination, amlodipine single drug, and valsartan/amlodipine fixed-dose combination in the treatment of hypertensive patients from payer perspective in China. Methods: A Markov model was constructed, which included five health states of hypertensive patients who are aged 35–84 years at baseline and free of cardiovascular disease. Clinical data were obtained from a network meta-analysis. Epidemiology data, adverse events (AEs), cost, and utility data were obtained from the literature. The cost associated with AEs was estimated based on the cost of same symptoms of hypertensive patients in an electric medical record database. The model projected quality-adjusted life years (QALYs) gained, total costs per patient in a 20-year time horizon, and incremental cost-effectiveness ratios. Probability sensitivity analyses (PSA) and one-way sensitivity analyses were conducted for the main parameters to test the robustness of the model. Results: Compared to olmesartan and amlodipine free combination, amlodipine, and valsartan/amlodipine fixed-dose combination, treatment with olmesartan/amlodipine fixed-dose combination led to fewer CVD events and deaths; resulted in an incremental cost of ¥−5,439 ($−791.36), ¥6,530 ($950.09), and ¥−1,019 ($−148.26) and gained additional QALYs of 0.052, 0.094, and 0.037 per patient, respectively. Compared with olmesartan and amlodipine free combination and valsartan/amlodipine fixed-dose combination, olmesartan/amlodipine fixed-dose combination was dominant. Compared with amlodipine alone, the incremental cost-effectiveness ratios were below the WHO recommended cost-effectiveness threshold, indicating the olmesartan/amlodipine fixed-dose combination was a cost-effective option for hypertensive patients in China. The 10-years’ time horizon scenario analysis showed similar results to the 20-years’ time horizon. Probabilistic sensitivity analysis and one-way sensitivity analyses showed the robustness of the model results. Conclusions: Olmesartan/amlodipine fixed-dose combination confers better health outcomes and costs less compared with olmesartan and amlodipine free combination and valsartan/amlodipine fixed-dose combination, and is cost-effective compared to amlodipine for hypertension treatment in China.

In this paper, the commercial software CFD was used to solve problems by solving the Navier-Stokes equatlon with the model and VOF method. Firstly, the author computed and simulated the sailing of the experimential amphibious weapon running on the water. Secondly the resistance results reasonably compared with the test data from the towing tank, showing that the technology can play an important role in the research of fluid dynamic performance of an amphibious weapon, At the same time, an apparent discrepancy in conculated and test results at high speed shows that the application or parameter itself should be improved.