Atherosclerosis (AS) is the major form of cardiovascular disease and the leading cause of morbidity and mortality in countries around the world. Atherosclerosis combines the interactions of systemic risk factors, haemodynamic factors, and biological factors, in which biomechanical and biochemical cues strongly regulate the process of atherosclerosis. The development of atherosclerosis is directly related to hemodynamic disorders and is the most important parameter in the biomechanics of atherosclerosis. The complex blood flow in arteries forms rich WSS vectorial features, including the newly proposed WSS topological skeleton to identify and classify the WSS fixed points and manifolds in complex vascular geometries. The onset of plaque usually occurs in the low WSS area, and the plaque development alters the local WSS topography. low WSS promotes atherosclerosis, while high WSS prevents atherosclerosis. Upon further progression of plaques, high WSS is associated with the formation of vulnerable plaque phenotype. Different types of shear stress can lead to focal differences in plaque composition and to spatial variations in the susceptibility to plaque rupture, atherosclerosis progression and thrombus formation. WSS can potentially gain insight into the initial lesions of AS and the vulnerable phenotype that gradually develops over time. The characteristics of WSS are studied through computational fluid dynamics (CFD) modeling. With the continuous improvement of computer performance-cost ratio, WSS as one of the effective parameters for early diagnosis of atherosclerosis has become a reality and will be worth actively promoting in clinical practice. The research on the pathogenesis of atherosclerosis based on WSS is gradually an academic consensus. This article will comprehensively review the systemic risk factors, hemodynamics and biological factors involved in the formation of atherosclerosis, and combine the application of CFD in hemodynamics, focusing on the mechanism of WSS and the complex interactions between WSS and plaque biological factors. It is expected to lay a foundation for revealing the pathophysiological mechanisms related to abnormal WSS in the progression and transformation of human atherosclerotic plaques.

ObjectiveThe purpose of this study is to evaluate the optimal dose of tirzepatide (TZP) for the treatment of type 2 diabetes mellitus (T2DM) by meta-analysis and trial sequential analysis (TSA).MethodsClinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022. Mean differences (MD) and 95% confidence intervals (95%CI) were used for continuous variables, and relative risk (RR) and 95%CI were used for dichotomous variables.ResultsCompared with TZP 5 mg, meta-analysis showed that TZP 10 mg significantly reduced glycosylated hemoglobin type A1c (HbA1c) (MD −0.24, 95%CI −0.31~-0.17, P < 0.00001), fasting serum glucose (FSG) (MD −5.82, 95%CI −8.35~-3.28, P < 0.00001) and weight (MD −2.47, 95%CI −2.95~-1.98, P < 0.00001), and TZP 15 mg significantly reduced HbA1c (MD −0.37, 95%CI −0.44~-0.29, P < 0.00001), FSG (MD −8.52, 95%CI −11.07~-5.98, P < 0.00001) and weight (MD −4.63, 95%CI −5.45~-3.81, P < 0.00001). Compared with TZP 10 mg, TZP 15 mg dramatically reduced HbA1c (MD −0.12, 95%CI −0.19~-0.05, P = 0.001), FSG (MD −2.73, 95%CI −5.29~-0.17, P = 0.04) and weight (MD −2.18, 95%CI −2.67~-1.70, P < 0.00001). The TSA indicated that the benefits observed in the current information set were conclusive, except for the FSG of “TZP 15 mg vs. TZP 10 mg”. In terms of safety endpoints, meta-analysis revealed that there was no significant difference in the serious adverse events (AEs), major adverse cardiovascular events-4 (MACE-4), cardiovascular death, hypertension, cancer and hypoglycemic of the three dose groups of TZP. Compared with TZP 5 mg, TZP 10 mg increased total adverse events (RR 1.06, 95%CI 1.01~1.11, P = 0.03) and gastrointestinal (GI) AEs (RR 1.17, 95%CI 1.03~1.33, P = 0.02), and TZP 15 mg increased total AEs (RR 1.10, 95%CI 1.05~1.15, P = 0.0001). There were no significant differences in total AEs and GI AEs for TZP 15 mg compared to TZP 10 mg. The TSA demonstrated that the total AEs of “TZP 15 mg vs. TZP 5 mg” were conclusive.ConclusionsTZP 15 mg >TZP 10 mg > TZP 5 mg in terms of lowering glycemia and reducing weight. TZP 5 mg > TZP 10 mg = TZP 15 mg in terms of safety. On this basis, we recommend TZP 5 mg as the first-choice dose for patients with T2DM to minimize AEs while reducing glycemia and weight. If patients cannot effectively control their glycemia after taking TZP 5 mg, it is recommended to take TZP 15 mg directly to achieve the best effect of glycemic reduction. However, most of the included studies have the background of basic medication, the independent efficacy and safety of different doses of TZP still need to be tested.Systematic review registrationUnique Identifier: CRD42022341966.

ObjectiveTo evaluate the efficacy and safety of dorzagliatin in the treatment of type 2 diabetes mellitus (T2DM) by using meta-analysis and trial sequential analysis (TSA).MethodSearch for clinical trials of dorzagliatin for T2DM in eight databases, with a time limit of build to July 2022. The included studies that met the requirements were carried out for meta-analysis and TSA.ResultsIn terms of efficacy endpoints, meta-analysis showed that dorzagliatin decreased glycated hemoglobin A1c(HbA1c) [mean difference (MD) −0.65%, 95% confidence interval (CI) −0.76 ~ −0.54, P < 0.00001], fasting plasma glucose (FPG) (MD −9.22 mg/dL, 95% CI −9.99 ~ −8.44, P < 0.00001), 2 h postprandial glucose (2h-PPG) (MD −48.70 mg/dL, 95% CI −55.45 ~ −41.96, P < 0.00001), homeostasis model assessment 2 of insulin resistance (HOMA2-IR) (MD −0.07, 95% CI −0.14 ~ −0.01, P = 0.03) and increased homeostasis model assessment 2 of ß-cells function (HOMA2-β) (MD 2.69, 95% CI 1.06 ~ 4.31, P = 0.001) compared with placebo. And TSA revealed that the benefits observed for the current information set were conclusive, except for HOMA2-IR. In comparison with placebo, dorzagliatin increased triglyceride(TG) (MD 0.43 mmol/L, 95% CI 0.30 ~ 0.56, P < 0.00001), total cholesterol (TC) (MD 0.13 mmol/L, 95% CI 0.05 ~ 0.21, P = 0.001), body weight (MD 0.38 kg, 95% CI 0.12–0.63, P = 0.004) and body mass index (BMI) (MD 0.14 kg/m2, 95% CI 0.05–0.24, P = 0.003), while low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were comparable. And TSA demonstrated that TG, TC, body weight, and BMI were conclusive. In terms of safety endpoints, dorzagliatin increased total adverse events (AEs) [risk ratio (RR) 1.56, 95% CI 1.06 ~ 2.30, P = 0.03], while serious AEs, hyperlipidemia, and hypoglycaemia were all comparable. And TSA indicated that the results need to be confirmed by additional studies. Harbord regression showed no publication bias.ConclusionDorzagliatin was effective in lowering glycemia, reducing insulin resistance and improving islet ß-cells function without affecting blood pressure, LDL-C, and HDL-C. Although dorzagliatin caused a mild increase in TG and TC, it did not increase the incidence of hyperlipidemia, and the small increases in body weight and BMI were not clinically significant enough. In terms of safety, the total AEs caused by dorzagliatin may be a cumulative effect of single AEs, with no drug-related adverse event being reported at a higher incidence than placebo alone. Dorzagliatin's serious AEs, hyperlipidemia, and hypoglycemia are comparable to that of placebo, and dorzagliatin has a good safety profile.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=371802 identifier: CRD42022371802.

Background: Although anti-inflammatory and immunomodulatory measures have delayed the progression of ulcerative colitis (UC) to a certain extent, the adverse drug reactions and recurrence after recovery still trouble clinicians. Acupoint catgut embedding is a possible alternative strategy for the treatment of UC, but its clinical efficacy remains controversial. Therefore, this study systematically evaluated the clinical efficacy and safety of acupoint catgut embedding compared with conventional western medicine in the treatment of UC.Methods: VIP, Wanfang, China National Knowledge Infrastructure, China Biology Medicine, PubMed, Embase, Web of Science, the Cochrane Library databases were searched. And the publication time of the literature was limited from the time that the database was established to February 2022. Two researchers independently screened the literature, extracted data, and assessed risk of bias as required. Meta-analysis was performed with Revman 5.3. Trial sequential analysis (TSA) was performed with TSA 0.9.5.10 Beta. Publication bias was assessed by Stata 15.0. And evidence quality was appraised with GRADEpro3.6.Results: A total of 10 studies were listed, with a total sample size of 782 cases. Meta-analysis showed that compared with conventional western medicine, acupoint catgut embedding can effectively improve the total effective rate of clinical symptoms (relative risk [RR] = 1.16, 95% confidence interval [CI] = [1.09,1.24], P < .00001), endoscopic total effective rate (RR = 1.16, 95%CI = [1.08,1.25], P < .0001), clinical symptom cure rate (RR = 1.80, 95%CI = [1.37,2.38], P < .0001), and endoscopic cure rate (RR = 1.97, 95%CI = [1.36,2.86], P = .0004) of UC, but the adverse event rate (RR = 0.20, 95%CI = [0.01,4.00], P = .29) was similar. Trial sequential analysis indicated that the efficacy endpoint was conclusive. Harbord test confirmed no significant publication bias. The quality of evidence for these outcomes ranges from low to medium. Conclusion:The clinical efficacy of acupoint catgut embedding in the treatment of UC is superior to that of conventional western medicine, and the safety may be equivalent to that of conventional western medicine, which has the value of further research and exploration.