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Objective By summarizing the clinical characteristics and follow-up outcomes of 5 patients with immune checkpoint inhibitor induced diabetes mellitus (ICI-DM) and reviewing the relevant literatures, the article aims at providing reference to clinicians in the diagnosis and treatment of the ICI-DM. Methods Clinical data of 5 patients with ICI-DM who were admitted to Peking Union Medical College Hospital from December 2018 to February 2023 and did retrospectively analyzed. Results Five patients with a mean age of (65±7)years received treatment by the programmed cell death 1 (PD-1) or its ligand inhibitor (PD-L1). The median time from the first immunotherapy to the discovery of elevated plasma glucose was 100 (43, 210)days, and the median cycle of immunotherapy was 7 (2.5, 10.5). The onset of the illness of all the 5 patients started with diabetic ketosis or ketoacidosis. At the onset, urine ketone bodies were positive, random plasma glucose was (36.36±15.89)mmol/L, glycosylated hemoglobin A1c (HbA1c)was (8.6%±0.66%), arterial blood pH was (7.28±0.16), and the median fasting C-peptide level was 0.09 (0.05, 0.32)μg/L. Five patients had an onset plasma glucose level of grade 3 or 4.Then, ICI treatment was discontinued in all patients and insulin therapy started. The daily dosage of insulin was (56±20)IU, supplemented with hypoglycemic drugs. After treatment, urine ketone body turned negative, pH value increased to normal range, and random plasma glucose decreased significantly (the median difference of random blood glucose before and after treatment was 21.30 mmol/L, P=0.043) showing that the treatment was effective. During the follow-up, all patients continued to use insulin. The PD-1 or PD-L1 inhibitors were restarted after hyperglycemia remission. The tumor condition was under control. Conclusions ICI-DM mainly occurs in patients who receive treatment with PD-1 or PD-L1 inhibitors usually with acute hyperglycemia whose laboratory tests indicate insulin secretion defects. Some patients had positive islet cell antibodies, glutamic acid decarboxylase antibodies and autoantibodies.Patients with positive autoantibodies needed early diagnosis and continuous insulin treatment. ICI treatment can be restarted after endocrinologists brought the blood glucose under control.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), as a kind of novel hypoglycemic agent, are widely used in patients with type 2 diabetes. GLP-1RAs are effective in glycemic control with low risk of hypoglycemia, significant weight loss, and cardiovascular benefit and renal protection. The most common adverse effects of GLP-1RAs are mild to moderate gastrointestinal symptoms, which generally resolve over time. The use of GLP-1RAs also increases the risk of gallbladder or biliary diseases, especially when used at higher doses, for longer durations, and for weight loss, but the absolute risk of gallbladder or biliary tract disease is small. Clinicians and patients need to carefully weigh the benefits and risks of GLP-1RAs to make decisions for the rational use of GLP-1RAs.

Aiming at exhaust pipe cracking failure of a single cylinder diesel engine, thermo-mechanical coupling approach based on equivalent vibration and material temperature effect was presented, and then varied stress was simulated using Finite Element Method. According to the modified Miner law and linear cumulative damage theory, considering stress gradient, surface roughness and temperature, dangerous position of exhaust pipe structure is predicted. The results show that exhaust pipe cracking is due to lack of stiffness in upper and lower direction. There is a risk of thermal modal resonance, and insufficient safety factor causes failure. Fatigue safety factor of original and support improved is 1.06 and 1.6, respectively. The predicted results agree well with measurements.

Objective To identify the relationship between physical activity,insulin resistance and cardiovascular risk in individuals with different glucose tolerance status and to provide evidence for exercise intervention in people with different glucose tolerance status. Methods A total of 691 patients with different glucose metabolism status were recruited as subjects of the research. Spearman correlation analysis was used to study the relationship between exercise frequency and insulin resistance, insulin sensitivity, neck circumference (NC) and neck circumference height ratio (NHtR) in the subjects with different glucose metabolism status, the relationship between NC and insulin resistance and insulin sensitivity in different glucose metabolism groups. Results 171(62.9%) Subjects with diabetes were intervened by exercised every day. Spearman correlation analysis showed the correlation between exercise frequency and tri-glyceride triglyceride-glucose index (TyG index) (r=-0.120, P＜0.05) and NC (r=-0.168, P＜0.05) were negatively correlated. In subjects with diabetes, NC was positively correlated with triglycerides(TG) (r=-0.100, P＜0.05), homeostasis model assessment of insulin resistance(HOMA-R) (r=-0.163, P＜0.05), total cholesterol/high-density lipoprotein(TC/HDL-C)(r=-0.214, P＜0.05) and TyG index (r=-0.156, P＜0.05). Conclusions Increased frequency of exercise is associated with reduced NC, improved insulin resistance, and cardiovascular risk factors in subjects of our team with newly diagnosed diabetes. Exercise has no significant effect on insulin resistance of subjects with normal glucose tolerance and pre-diabetes.

Background: To systematically analyze differences in atherosclerotic cardiovascular disease (ASCVD) burden between young and older adults. Methods: We estimated the prevalence, mortality, and disability-adjusted life years (DALYs) of ASCVD, including ischemic heart disease (IHD), ischemic stroke (IS), and peripheral artery disease (PAD), in individuals aged 20–54 and > 55 years from 1990–2019, utilizing data from the 2019 Global Burden of Disease Study. The annual percentage changes (EAPCs) for age-specific prevalence, mortality, or DALY rates were calculated to quantify the temporal trends of ASCVD burden. We also analyzed population attribution fractions (PAF) of premature ASCVD mortality and DALYs for different risk factors and compared the burden of extremely premature, premature, and non-premature ASCVD cases based on clinical classifications. Results: From 1990–2019, the global prevalence rates of IHD, IS, and PAD in the 20–54 years age group increased by 20.55% (from 694.74 to 837.49 per 100,000 population), 11.50% (from 439.48 to 490.03 per 100,000 population), and 7.38% (from 384.24 to 412.59 per 100,000 population), respectively. Conversely, the ASCVD prevalence in > 55years age group decreased. Adverse outcome burdens, including mortality and DALYs, varied among ASCVD subtypes. The decrease in the mortality/DALY burden of IHD and IS was lower in the 20–54 years group than in the > 55 years group. For PAD, DALYs among those aged 20–54 increased but decreased among those aged > 55 years. When grouped according to socio-demographic index (SDI) values, lower SDI regions exhibited a higher proportion of young ASCVD burden. The prevalence of young IHD, IS, and PAD in low SDI regions reached 20.70%, 40.05%, and 19.31% in 2019, respectively, compared with 12.14%, 16.32%, and 9.54%, respectively, in high SDI regions. Metabolic risks were the primary contributors to the ASCVD burden in both age groups. Increased susceptibility to ambient particulate matter pollution and inadequate control of high body-mass index and high fasting plasma glucose in young individuals may partially explain the differing temporal trends between young and older individuals. Conclusions: The ASCVD burden in young individuals may become a growing global health concern, especially in areas with lower socioeconomic development levels that require more effective primary prevention strategies. [ABSTRACT FROM AUTHOR]

CO oxidation at mild condition is significant for industrial process but still challenging nowadays, especially for the non-noble metal catalysts. The preparation method significant affect the catalytic activity of the catalyst. Comparing with cobalt supported on tantalum oxide prepared by impregnation method, Co/Ta2O5 prepared by deposition–precipitation method with urea in this study has smaller particle size, higher specific surface area and better redox properties, and these features make the catalyst exhibit higher catalytic activity for CO oxidation at mild condition. 90% CO conversion was achieved at 130 ℃, and CO was fully converted at 150 ℃. The XPS and DRIFTs results show that Co/Ta2O5 has more oxygen vacancies, and the absorbed CO will react with oxygen. The study may provide a new thought for the preparation of catalysts with high activity at mild condition. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the impact of a dual glucose‐dependent insulinotropic peptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) receptor agonist tirzepatide (TZP), and its potential dose‐response effect, on heart rate. Methods: Articles were searched from PubMed, Web of Science, Embase, Cochrane Library, and clinical trials registries (ClinicalTrials.gov) databases. Randomized controlled trials (RCTs) comparing TZP at doses of 5, 10 and 15 mg in adults with type 2 diabetes were included. Six study arms were summarized from original research (TZP 5, 10 and 15 mg, GLP‐1 receptor agonists [GLP‐1RAs], insulin, placebo). The GLP‐1RA and non‐GLP‐1RA groups were combined to form a control group. Two reviewers independently extracted data and assessed the quality of each study. Mean differences (MDs) were calculated as effect estimates for continuous outcomes. Pairwise meta‐analyses and network meta‐analyses were conducted. The study protocol was prospectively registered (PROSPERO ID: CRD42023418551). Results: Eight articles were included in this systematic review and meta‐analysis. The mean baseline heart rate ranged from 65.2 to 75.7 beats per minute. Pairwise meta‐analysis showed that, compared with combined the control group, there were significantly greater increases in heart rates in the TZP group (MD 1.82, 95% confidence interval [CI] 0.75, 2.89). Similar significant rises were identified when comparing TZP with GLP‐1RAs and non‐GLP‐1RAs (GLP‐1 RAs: MD 2.29, 95% CI 1.00, 3.59; non‐GLP‐1RAs: MD 1.58, 95% CI 0.26, 2.91). TZP 5 mg was associated with smaller increases in heart rates compared to TZP 10 mg and TZP 15 mg (TZP 10 mg: MD −0.97, 95% CI −1.79, −0.14; TZP 15 mg: MD −2.57, 95% CI −3.79, −1.35). TZP 10 mg increased heart rate less than TZP 15 mg (MD −1.5, 95% CI −2.38, −0.82). Network meta‐analysis indicated that TZP 15 mg was associated with significant increases in heart rate compared with TZP 5 mg (MD 2.53, 95% CI 1.43, 3.62), TZP 10 mg (MD 1.44, 95% CI 0.35, 2.53), GLP‐1RAs (MD 3.46, 95% CI 1.67, 5.25), insulin (MD 2.86, 95% CI 1.32, 4.41) and placebo (MD 2.96, 95% CI 1.36, 4.57). Conclusions: Our study showed not only that there was a greater increase in heart rate in the TZP group than in the control, GLP‐1RA and non‐GLP‐1RA groups, but also that the 15‐mg dose of TZP had the strongest impact on increasing heart rates compared with the other five inventions, with a TZP dose‐response impact on heart rate. Further research on the effects of TZP treatment‐related increases in heart rate is required. [ABSTRACT FROM AUTHOR]