Efficacy and safety of esketamine for pediatric gastrointestinal endoscopy: a meta-analysis and trial sequential analysis.

Objective: The role of esketamine in pediatric gastrointestinal endoscopy is still unclear. This study aims to evaluate the efficacy and safety of esketamine for pediatric gastrointestinal endoscopy. Methods: Clinical trials of esketamine for pediatric gastrointestinal endoscopy were searched in eight common databases, up to October 2023. These clinical trials were included in the meta-analysis and trial sequential analysis (TSA). The risk ratio (RR) and weighted mean difference (WMD) were used as the effect sizes for dichotomous variables and continuity variables, respectively. When the heterogeneity test showed I2 < 50%, the fixed effects model was used for the meta-analysis and TSA; Otherwise, the random effects model was used for them. Results: In terms of efficacy endpoints, the meta-analysis showed that compared with placebo or blank, esketamine significantly decreased recovery time by 2.34 min (WMD -2.34; 95% Confidence interval [CI] -3.65, -1.02; p = 0.0005) and propofol consumption by 0.70 mg/kg (WMD -0.70; 95% CI -0.98, -0.43; p < 0.00001), and increased mean heart rate by 4.77 beats/min (WMD 4.77; 95% CI 2.67, 6.87; p < 0.00001) and mean arterial pressure by 3.10 mmHg (WMD 3.10; 95% CI 1.52, 4.67; p = 0.0001), while induction time and mean blood oxygen remained comparable. TSA indicated conclusive evidence for these benefits. In terms of safety endpoints, the meta-analysis revealed that esketamine significantly reduced involuntary movements by 59% (RR 0.41; 95% CI 0.22, 0.76; p = 0.005) and choking by 51% (RR 0.49; 95% CI 0.26, 0.92; p = 0.03), while significantly increasing dizziness by 98% (RR 1.98; 95% CI 1.11, 3.56; p = 0.02) and there were no significant differences in total adverse events, respiratory depression, and vomiting. TSA demonstrated conclusive evidence for involuntary movements and dizziness. Low-dose analysis showed that esketamine at ≤0.3 mg/kg significantly reduced recovery time, propofol consumption and involuntary movements, and significantly increasing mean heart rate, with no increase in dizziness. The Begg's test (p = 0.327) and the Egger's test (p = 0.413) indicated no significant publication bias, yet the funnel plot suggested potential publication bias. Conclusion: Esketamine is an effective adjuvant anesthesia for children undergoing gastrointestinal endoscopy. However, the general dose of esketamine may increase the risk of dizziness, which can be avoided by administering a low dose (≤0.3 mg/kg).

Love-hate relationship between hepatitis B virus and type 2 diabetes: a Mendelian randomization study.

Objective: The impact of hepatitis B virus (HBV) on the risk of type 2 diabetes (T2D) remains a controversial topic. This study aims to analyze the causal relationship between HBV and T2D using Mendelian randomization (MR). Methods: Single nucleotide polymorphisms on chronic hepatitis B (CHB), liver fibrosis, liver cirrhosis, and T2D were obtained from BioBank Japan Project, European Bioinformatics Institute, and FinnGen. Mendelian randomization was utilized to evaluate exposure-outcome causality. Inverse variance weighted was used as the primary method for MR analysis. To assess horizontal pleiotropy and heterogeneity, we conducted MR-Egger intercept analysis and Cochran's Q test, and the robustness of the MR analysis results was evaluated through leave-one-out sensitivity analysis. Results: MR analysis revealed that CHB was associated with a decreased genetic susceptibility to T2D (OR, 0.975; 95% CI, 0.962-0.989; p < 0.001) while liver cirrhosis (OR, 1.021; 95% CI, 1.007-1.036; p = 0.004) as well as liver cirrhosis and liver fibrosis (OR, 1.015; 95% CI, 1.002-1.028; p = 0.020) were associated with an increased genetic susceptibility to T2D. MR-Egger intercept showed no horizontal pleiotropy (p > 0.05). Cochran's Q showed no heterogeneity (p > 0.05). Leave-one-out sensitivity analysis showed that the results were robust. Conclusion: CHB has the potential to act as a protective factor for T2D, but its effectiveness is constrained by viral load and disease stage. This protective effect diminishes or disappears as viral load decreases, and it transforms into a risk factor with the progression to liver fibrosis and cirrhosis.

Effect of viral hepatitis on type 2 diabetes: A Mendelian randomization study.

BACKGROUND: The effects of viral hepatitis (VH) on type 2 diabetes (T2D) remain controversial. AIM: To analyze the causal correlation between different types of VH and T2D using Mendelian randomization (MR). METHODS: Single nucleotide polymorphisms of VH, chronic hepatitis B (CHB), chronic hepatitis C (CHC) and T2D were obtained from the BioBank Japan Project, European Bioinformatics Institute, and FinnGen. Inverse variance weighted, MR-Egger, and weighted median were used to test exposure-outcome associations. The MR-Egger intercept analysis and Cochran's Q test were used to assess horizontal pleiotropy and heterogeneity, respectively. Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results. RESULTS: The MR analysis showed no significant causal relationship between VH and T2D in Europeans [odds ratio (OR) = 1.028; 95% confidence interval (CI): 0.995-1.062, P = 0.101]. There was a negative causal association between CHB and T2D among East Asians (OR = 0.949; 95%CI: 0.931-0.968, P < 0.001), while there was no significant causal association between CHC and T2D among East Asians (OR = 1.018; 95%CI: 0.959-1.081, P = 0.551). Intercept analysis and Cochran's Q test showed no horizontal pleiotropy or heterogeneity (P > 0.05). Sensitivity analysis showed that the results were robust. CONCLUSION: Among East Asians, CHB is associated with a reduced T2D risk, but this association is limited by HBV load and cirrhosis. Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D, focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHC-mediated pathways of hepatic steatosis, liver fibrosis, and cirrhosis.

A strategic study of acupuncture for diabetic kidney disease based on meta-analysis and data mining.

Objective: The specific benefit and selection of acupoints in acupuncture for diabetic kidney disease (DKD) remains controversial. This study aims to explore the specific benefits and acupoints selection of acupuncture for DKD through meta-analysis and data mining. Methods: Clinical trials of acupuncture for DKD were searched in eight common databases. Meta-analysis was used to evaluate its efficacy and safety, and data mining was used to explore its acupoints selection. Results: Meta-analysis displayed that compared with the conventional drug group, the combined acupuncture group significantly increased the clinical effective rate (risk ratio [RR] 1.35, 95% confidence interval [CI] 1.20 to 1.51, P < 0.00001) and high-density lipoprotein cholesterol (mean difference [MD] 0.36, 95% CI 0.27 to 0.46, P < 0.00001), significantly reduced the urinary albumin (MD -0.39, 95% CI -0.42 to -0.36, P < 0.00001), urinary microalbumin (MD -32.63, 95% CI -42.47 to -22.79, P < 0.00001), urine ß2-microglobulin (MD -0.45, 95% CI -0.66 to -0.24, P < 0.0001), serum creatinine (MD -15.36, 95% CI -21.69 to -9.03, P < 0.00001), glycated hemoglobin A1c (MD -0.69, 95% CI -1.18 to -0.19, P = 0.006), fasting blood glucose (MD -0.86, 95% CI -0.90 to -0.82, P < 0.00001), 2h postprandial plasma glucose (MD -0.87, 95% CI -0.92 to -0.82, P < 0.00001), total cholesterol (MD -1.23, 95% CI -2.05 to -0.40, P = 0.003), triglyceride (MD -0.69, 95% CI -1.23 to -0.15, P = 0.01), while adverse events were comparable. Data mining revealed that CV12, SP8, SP10, ST36, SP6, BL20, BL23, and SP9 were the core acupoints for DKD treated by acupuncture. Conclusion: Acupuncture improved clinical symptoms, renal function indices such as uALB, umALB, uß2-MG, and SCR, as well as blood glucose and blood lipid in patients with DKD, and has a favorable safety profile. CV12, SP8, SP10, ST36, SP6, BL20, BL23, and SP9 are the core acupoints for acupuncture in DKD, and this program is expected to become a supplementary treatment for DKD.

Research status and hotspots of autoimmune gastritis: A bibliometric analysis.

BACKGROUND: As an emerging potential risk factor for gastric cancer, autoimmune gastritis (AIG) has garnered increasing attention from researchers. AIM: To analyze the research overview and popular topics in the field of AIG using bibliometrics. METHODS: Relevant publications on AIG in the Web of Science Core Collection were collated, and data visualization and analysis of the number of publications, countries, institutions, journals, authors, keywords, and citations were performed using software such as VOSviewer, CiteSpace, and Scimago Graphic. RESULTS: In total, 316 relevant articles were included in the analysis. From 2015 to 2022, the number of publications increased annually. The countries, institutions, authors, and journals with the highest number of publications in this field were Italy, Monash University, Toh BH, and Internal Medicine. The main keywords used in this field of research were pathogenesis, Helicobacter pylori, autoantibody, parietal cell antibody, atrophic gastritis, classification, diagnosis, autoimmune disease, risk, cancer, gastric cancer, vitamin B12 deficiency, and pernicious anemia. The following directions may be popular for future research: (1) The role of Helicobacter pylori in the pathogenesis of AIG; (2) diagnostic criteria for AIG and reference values for serum antibodies; (3) comorbidity mechanisms between AIG and other autoimmune diseases; (4) specific risks of AIG complicating gastric and other cancers; and (5) the role of vitamin B12 supplementation in patients with early-stage AIG. CONCLUSION: This bibliometric analysis reported on popular topics and emerging trends in AIG, with diagnosis and prognosis being research hotspots in this field.

Is acupoint injection the optimal way to administer mecobalamin for diabetic peripheral neuropathy? A meta-analysis and trial sequential analysis.

Objective: Mecobalamin is a commonly used drug in the treatment of diabetic peripheral neuropathy (DPN). This study aimed to systematically evaluate the efficacy and safety of acupoint injection of mecobalamin for DPN. Methods: Relevant clinical trials on acupoint injection of mecobalamin for DPN published before 31 January 2023 were searched in eight commonly used databases. After screening and confirming the included studies, meta-analysis and trial sequential analysis were performed. Results: A total of 10 relevant studies were confirmed, and the total sample size was 927 cases. On the efficacy endpoints, meta-analysis showed that compared with other administration methods, acupoint injection of mecobalamin significantly increased the clinical effective rate by 27% [RR = 1.27, 95% CI = (1.19, 1.36), P < 0.00001], motor nerve conduction velocity (median nerve) by 5.93 m/s [MD = 5.93, 95% CI = (4.79, 7.07), P < 0.00001], motor nerve conduction velocity (common peroneal nerve) by 5.66 m/s [MD = 5.66, 95% CI = (2.89, 8.43), P < 0.0001], sensory nerve conduction velocity (median nerve) by 4.83 m/s [MD = 4.83, 95% CI = (3.75, 5.90), P < 0.00001], and sensory nerve conduction velocity (common peroneal nerve) by 3.60 m/s [MD = 3.60, 95% CI = (2.49, 4.71), P < 0.00001], and trial sequential analysis showed these benefits were conclusive. In terms of safety endpoints, meta-analysis indicated that the total adverse events for acupoint injection were comparable to other methods of administration, and trial sequential analysis suggested that the results needed to be validated by more studies. Subgroup analysis demonstrated that the benefits of acupoint injections of mecobalamin were not limited by the dose, duration of treatment, or number of acupoints reported in the included studies. Harbord's test showed no significant publication bias (P = 0.106). Conclusion: The efficacy of acupoint injection of mecobalamin for DPN was significantly better than other administrations, and its safety was comparable to other administrations. Therefore, acupoint injection may be the optimal method of mecobalamin for DPN. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=454120, identifier: CRD42023454120.

Gastrointestinal adverse events of tirzepatide in the treatment of type 2 diabetes mellitus: A meta-analysis and trials sequential analysis.

BACKGROUND: Tirzepatide (TZP) is a novel drug for type 2 diabetes mellitus (T2DM), but the gastrointestinal (GI) adverse events (AEs) is a limiting factor in clinical application. Therefore, this study systematically evaluated the GI AEs of TZP for T2DM. METHODS: Clinical trials of TZP for T2DM were retrieved from eight databases published only from the establishment of the database to February 2023. Revman5.3 and TSA0.9.5.10 Beta were used for meta-analysis and trials sequential analysis (TSA). RESULTS: Meta-analysis showed that compared with placebo, total GI AEs, nausea, decreased appetite, constipation and vomiting were significantly higher in all dose groups of TZP (P < .05), while abdominal pain and abdominal distension were comparable (P > .05). TSA showed that the differences in total GI AEs, nausea, decreased appetite and constipation were conclusive. Compared with insulin, nausea, diarrhea, vomiting and decreased appetite were significantly increased in all doses of TZP (P < .05), and dyspepsia was significantly increased with TZP 15 mg (P < .05). TSA showed that these differences were all conclusive. Compared with GLP-1 RA, decreased appetite was significantly higher with TZP 5 mg, total GI AEs, decreased appetite and diarrhea were significantly higher with TZP 10 mg (P < .05), while nausea, vomiting, dyspepsia and constipation were significantly different in all dose groups, abdominal pain were not significantly different (P < .05) and TSA showed no conclusive results in this group. CONCLUSION: The GI AEs of TZP were significantly higher than those of placebo and insulin, but comparable to GLP-1 RA. Nausea, diarrhea and decreased appetite are very common GI AEs of TZP, and the incidence is positively correlated with dose. GI AEs of TZP decrease gradually over time, so long-term steady medication may be expected to reduce GI AEs.

Influence of TiN Inclusions and Segregation Bands on the Mechanical Properties and Delayed Crack in Thick NM550 Wear-Resistant Steel.

The formation mechanism of the delayed crack after flame cutting and mechanical properties in thick NM550 wear-resistant steel are studied by optical microscopy, scanning electron microscopy, energy dispersive spectroscopy, X-ray diffraction, and an electron backscattered diffractometer. The delayed crack is formed at the segregation zone (SZ) located in the center of the 65 mm thick steel plate. The strength of the non-segregation zone (NSZ) with a martensite microstructure is slightly higher than that of SZ with a mixture microstructure of martensite plus bainite, and the plasticity of NSZ is significantly better than that of SZ. There exists a more severe segregation in the SZ, and only a slight segregation in the NSZ. The average grain sizes of the segregation bands in the NSZ and SZ are 15.72 µm and 6.76 µm, respectively. The number density of TiN larger than 5 µm in the NSZ and SZ is 0.031 and 1.156 number/mm2, respectively. Therefore, a high hardness segregation band with fine grains and a high dislocation density, along with the large number of coarse TiN inclusions within it, results in delayed cracking. For TiN inclusions close to the crack, microvoids or microcracks around the TiN are formed, and the delayed crack will propagate along the edge of the TiN or through the TiN inclusions.

Effect of tea intake on genetic predisposition to gout and uric acid: a Mendelian randomization study.

Objective: The effect of tea on gout and uric acid is still controversial. This study aims to analyze the effect of tea intake on genetic predisposition to gout, idiopathic gout, gout due to impairment of renal function as well as uric acid by Mendelian randomization (MR). Methods: Forty independent single nucleotide polymorphisms (SNPs) associated with tea intake were selected from UK Biobank. SNPs for uric acid were obtained from BioBank Japan, SNPs for gout were obtained from UK Biobank, and SNPs for gout due to impairment of renal function and idiopathic gout were derived from FinnGen. The causal relationship of exposure-outcome was tested using inverse variance weighted, MR-Egger and weighted median. MR-Egger intercept was employed to assess horizontal pleiotropy, Cochran's Q test was used to assess heterogeneity, and leave-one-out sensitivity analysis was utilized to analyze the stability of the results. Results: The results of MR analysis showed that tea intake was negatively associated with gout due to impairment of renal function (OR 0.997, 95% CI 0.994 to 0.999, P = 0.017), whereas there was no causal association with gout, idiopathic gout, and uric acid (P > 0.05), for which sensitivity analysis suggested that these results were robust. Conclusions: There was a genetic predisposition effect of increased tea intake on the reduced risk of gout due to impairment of renal function, whereas there was no such effect on gout, idiopathic gout, and uric acid. Tea intake may become an important option in the dietary treatment of gout due to impairment of renal function.

Efficacy and safety of dorzagliatin for type 2 diabetes mellitus: A meta-analysis and trial sequential analysis.

Objective: To 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). Method: Search 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. Results: In 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-ß) (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. Conclusion: Dorzagliatin 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 registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=371802 identifier: CRD42022371802.