颈腰椎慢性筋骨病损临床实践指南和专家共识的方法学质量评价

目的 评价国内外颈腰椎慢性筋骨病损相关的临床实践指南和专家共识的方法学质量。方法 检索中国知网、维普、万方、中国生物医学文献数据库、PubMed、国际指南网、英国国家卫生与临床优化研究所、国际指南中心网,收集有关颈腰椎慢性筋骨病损相关的临床实践指南和专家共识。检索时限为建库至2022年7月31日。2名研究者按照纳入排除标准独立筛选指南并提取相关信息,4名研究者使用AGREE II评价工具对指南进行质量评价,并采用组内相关系数(ICC)评价其一致性。结果 本研究共纳入23篇临床实践指南和专家共识,其中21篇为临床实践指南,2为篇专家共识。AGREE II 6个领域得分率中位数和四分位间距分别为:范围和目的 84.72%(69.44%,88.89%)、参与人员59.72%(38.89%,75.00%)、严谨性71.88%(45.83%,81.77%)、清晰性81.94%(73.61%,87.50%)、应用性56.25%(30.21%,65.63%)、独立性79.17%(30.25%,85.42%)。总体评价一致性ICC为0.769。结论 现有证据表明国内颈腰椎慢性筋骨病损相关临床指南较国外总体质量相对一般,需对临床问题构建、证据检索和综合,以及患者价值与意愿和利益声明方面进一步完善,并建议基于此构建以中医证据为主体的中医骨伤疾病相关临床指南。

Comparison of intraosseous access and central venous catheterization in Chinese adult emergency patients: A prospective, multicenter, and randomized study

BACKGROUND: It is challenging to establish peripheral intravenous access in adult critically patients. This study aims to compare the success rate of the first attempt, procedure time, operator satisfaction with the used devices, pain score, and complications between intraosseous(IO) access and central venous catheterization(CVC) in critically ill Chinese patients.METHODS: In this prospective clustered randomized controlled trial, eight hospitals were randomly divided into either the IO group or the CVC group. Patients who needed emergency vascular access were included. From April 1, 2017 to December 31, 2018, each center included 12 patients. We recorded the data mentioned above.RESULTS: A total of 96 patients were enrolled in the study. There were no statistically significant differences between the two groups regarding sex, age, body mass index, or operator satisfaction with the used devices. The success rates of the first attempt and the procedure time were statistically significant between the IO group and the CVC group(91.7% vs. 50.0%, P<0.001;52.0 seconds vs. 900.0 seconds, P<0.001). During the study, 32 patients were conscious. There was no statistically significant difference between the two groups regarding the pain score associated with insertion. There were statistically significant differences between the two groups regarding the pain score associated with IO or CVC infusion(1.5 vs. 0.0, P=0.044). Complications were not observed in the two groups.CONCLUSIONS: IO access is a safe, rapid, and effective technique for gaining vascular access in critically ill adults with inaccessible peripheral veins in the emergency departments.

Analysis of risk factors for early stent thrombosis in the Chinese population:A multicenter restrospective study

BACKGROUND:The predictive scoring systems for early stent thrombosis(EST)remains blank in China.The study aims to evaluate the risk factors and conduct a prediction model of EST in the Chinese population.METHODS:EST was defined as thrombosis that occurs within the first 30 days after primary percutaneous coronary intervention(PCI).Patients from ten Chinese hospitals diagnosed as stent thrombosis(ST)from January 2010 to December 2016 were retrospectively included as the study group.A control group(1 case:2 controls)was created by including patients without ST,major adverse cardiovascular events,or cerebrovascular events during follow-up.The present study evaluated 426 patients with single-vessel lesions and ultimately included 40 patients with EST and 80 control patients,who were included to identify factors that predicted EST and to develop a prediction scoring system.The other 171 patients without integrated 1:2 pair were used for external validation.RESULTS:EST was independently associated with a low hemoglobin concentration(adjusted odds ratio[OR]0.946,95%confi dence interval[95%CI]0.901-0.993,P=0.026),a high pre-PCI Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery(SYNTAX)score(OR 1.166,95%CI 1.049-1.297,P=0.004),and a DAPT(DAPT)duration of<30 days(OR 28.033,95%CI 5.302-272.834,P<0.001).The simple EST prediction score provided an area under the curve(AUC)of 0.854(95%CI 0.777-0.932,P<0.001)with 70.0%sensitivity and 90.0%specifi city,and 0.742(95%CI 0.649-0.835,P<0.001)with 54.5%sensitivity and 81.0%specifi city for external validation dataset.CONCLUSIONS:EST may be independently associated with DAPT discontinuation within 30 days,a low hemoglobin concentration,and a high SYNTAX score.The scoring system also has a good ability to predict the risk of EST and may be useful in the clinical setting.

Mechanism and therapeutic strategy of hepatic TM6SF2-deficient non-alcoholic fatty liver diseases via in vivo and in vitro experiments

BACKGROUND The lack of effective pharmacotherapies for nonalcoholic fatty liver disease(NAFLD)is mainly attributed to insufficient research on its pathogenesis.The pathogenesis of TM6SF2-efficient NAFLD remains unclear,resulting in a lack of therapeutic strategies for TM6SF2-deficient patients.AIM To investigate the role of TM6SF2 in fatty acid metabolism in the context of fatty liver and propose possible therapeutic strategies for NAFLD caused by TM6SF2 deficiency.METHODS Liver samples collected from both NAFLD mouse models and human participants(80 cases)were used to evaluate the expression of TM6SF2 by using western blotting,immunohistochemistry,and quantitative polymerase chain reaction.RNA-seq data retrieved from the Gene Expression Omnibus database were used to confirm the over-expression of TM6SF2.Knockdown and overexpression of TM6SF2 were performed to clarify the mechanistic basis of hepatic lipid accumulation in NAFLD.MK-4074 administration was used as a therapeutic intervention to evaluate its effect on NAFLD caused by TM6SF2 deficiency.RESULTS Hepatic TM6SF2 levels were elevated in patients with NAFLD and NAFLD mouse models.TM6SF2 overexpression can reduce hepatic lipid accumulation,suggesting a protective role for TM6SF2 in a high-fat diet(HFD).Downregulation of TM6SF2,simulating the TM6SF2 E167K mutation condition,increases intracellular lipid deposition due to dysregulated fatty acid metabolism and is characterized by enhanced fatty acid uptake and synthesis,accompanied by impaired fatty acid oxidation.Owing to the potential effect of TM6SF2 deficiency on lipid metabolism,the application of an acetyl-CoA carboxylase inhibitor(MK-4074)could reverse the NAFLD phenotypes caused by TM6SF2 deficiency.CONCLUSION TM6SF2 plays a protective role in the HFD condition;its deficiency enhanced hepatic lipid accumulation through dysregulated fatty acid metabolism,and MK-4074 treatment could alleviate the NAFLD phenotypes caused by TM6SF2 deficiency.

Safety, pharmacokinetics, and biomarkers of F-652, a recombinant human interleukin-22 dimer, in healthy subjects

F-652 is a recombinant fusion protein consisting of two human interleukin-22(IL-22)molecules linked to an immunoglobulin constant region(IgG 2-Fc).IL-22 plays critical roles in promoting tissue repair and suppressing bacterial infection.The safety,pharmacokinetics(PK),tolerability,and biomarkers of F-652 were evaluated following a single dose in healthy male volunteers in a randomized,double-blind,placebo-controlled study.Following single-dose subcutaneous(SC)injection of F-652 at 2.0µg/kg into healthy subjects,six out of six subjects experienced delayed injection site reactions,which presented as erythematous and/or discoid eczematous lesions 10 to 17 days post-dosing.F-652 was then administered to the healthy subjects via an intravenous(IV)infusion at 2.0,10,30,and 45µg/kg.No severe adverse event(SAE)was observed during the study.Among the IV-dosed cohorts,eye and skin treatment emergent adverse events(TEAEs)were observed in the 30 and 45µg/kg cohorts.F-652 IV dosing resulted in linear increases in C max and AUC(0–t),and the T 1/2 ranged from 39.4 to 206h in the cohorts.An IV injection of F-652 induced dose-dependent increases in serum marker serum amyloid A,C-reactive protein,and FIB,and decreased serum triglycerides.The serum levels of 36 common pro-inflammatory cytokines/chemokines were not altered by the treatment of F-652 at 45μg/kg.In conclusion,IV administration of F-652 to healthy male volunteers is safe and well-tolerated and demonstrates favorable PK and pharmacodynamic properties.These results warrant further clinical development of F-652 to treat inflammatory diseases.

Development of an Eight-gene Prognostic Model for Overall Survival Prediction in Patients with Hepatocellular Carcinoma

Background and Aims:The overall survival(OS)of hepatocellular carcinoma(HCC)remains dismal.Bioinformatic analysis of transcriptome data could identify patients with poor OS and may facilitate clinical decision.This study aimed to develop a prognostic gene model for HCC.Methods:GSE14520 was retrieved as a training set to identify differential expressed genes(DEGs)between tumor and adjacent liver tissues in HCC patients with different OS.A DEG-based prognostic model was then constructed and the TCGA-LIHC and ICGC-LIRI datasets were used to validate the model.The area under the receiver operating characteristic curve(AUC)and hazard ratio(HR)of the model for OS were calculated.A model-based nomogram was estab-lished and verified.Results:In the training set,differential expression analysis identified 80 genes dysregulated in oxidation-reduction and metabolism regulation.After univariate Cox and LASSO regression,eight genes(LPCAT1,DHRS1,SORBS2,ALDH5A1,SULT1C2,SPP1,HEY1 and GOLM1)were selected to build the prognostic model.The AUC for 1-,3-and 5-year OS were 0.779,0.736,0.754 in training set and 0.693,0.689,0.693 in the TCGA-LIHC validation set,respectively.The AUC for 1-and 3-year OS were 0.767 and 0.705 in the ICGC-LIRI validation set.Multivariate analysis confirmed the model was an independent prognostic factor(training set:HR=4.422,p<0.001;TCGA-LIHC validation set:HR=2.561,p<0.001;ICGC-LIRI validation set:HR=3.931,p<0.001).Furthermore,a nomogram combining the model and AJCC stage was established and validated,showing increased OS predictive efficacy compared with the prognostic model(p=0.035)or AJCC stage(p<0.001).Conclusions:Our eight-gene prognostic model and the related nomogram represent as reliable prognostic tools for OS prediction in HCC patients.