Ferulic Acid Inhibits Arsenic-Induced Colon Injury by Improving Intestinal Barrier Function.

The prolonged exposure to arsenic results in intestinal barrier dysfunction, which is strongly concerned with detrimental processes such as oxidative stress and the inflammatory response. Ferulic acid (FA), as a phenolic acid, possesses the capability to mitigate arsenic-induced liver damage and cardiotoxic effects dependent on inhibition of oxidative stress and inflammatory responses. FA can mitigate testicular tissue damage and alveolar epithelial dysfunction, the mechanism of which may rely on nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) activation and nuclear factor-kappa B (NF-κB) pathway blocking. Based on the antioxidant and anti-inflammatory properties of FA, we speculated that FA might have the potential to inhibit arsenic-induced intestinal damage. To confirm this scientific hypothesis, mice exposed to sodium arsenite were treated with FA to observe colonic histopathology and TJ protein levels, and oxidative stress and TJ protein levels in Caco-2 cells exposed to sodium arsenite were assessed after FA intervention. In addition, molecular levels of NF-κB and Nrf2/HO-1 pathway in colon and Caco-2 cells were also detected. As shown in our data, FA inhibited arsenic-induced colon injury, which was reflected in the improvement of mucosal integrity, the decrease of down-regulated expression of tight junction (TJ) proteins (Claudin-1, Occludin, and ZO-1) and the inhibition of oxidative stress. Similarly, treatment with FA attenuated the inhibitory effect of arsenic on TJ protein expression in Caco-2 cells. In addition to suppressing the activation of NF-κB pathway, FA retrieved the activation of Nrf2/HO-1 pathway in colon and intestinal epithelial cells induced by arsenic. In summary, our findings propose that FA has the potential to mitigate arsenic-induced intestinal damage by preserving the integrity of intestinal epithelial TJs and suppressing oxidative stress. These results lay the groundwork for the potential use of FA in treating colon injuries caused by arsenic.

Dipeptidyl peptidase-4 inhibitors and the risk of infection: A systematic review and meta-analysis of cardiovascular outcome trials.

BACKGROUND: Since adverse events during treatment affect adherence and subsequent glycemic control, understanding the safety profile of oral anti-diabetic drugs is imperative for type 2 diabetes mellitus (T2DM) therapy. AIM: To evaluate the risk of infection in patients with T2DM treated with dipeptidyl-peptidase 4 (DPP-4) inhibitors. METHODS: Electronic databases were searched. The selection criteria included randomized controlled trials focused on cardiovascular outcomes. In these studies, the effects of DPP-4 inhibitors were directly compared to those of either other active anti-diabetic treatments or placebo. Six trials involving 53616 patients were deemed eligible. We calculated aggregate relative risks employing both random-effects and fixed-effects approaches, contingent upon the context. RESULTS: The application of DPP-4 inhibitors showed no significant link to the overall infection risk [0.98 (0.95, 1.02)] or the risk of serious infections [0.96 (0.85, 1.08)], additionally, no significant associations were found with opportunistic infections [0.69 (0.46, 1.04)], site-specific infections [respiratory infection 0.99 (0.96, 1.03), urinary tract infections 1.02 (0.95, 1.10), abdominal and gastrointestinal infections 1.02 (0.83, 1.25), skin structure and soft tissue infections 0.81 (0.60, 1.09), bone infections 0.96 (0.68, 1.36), and bloodstream infections 0.97 (0.80, 1.18)]. CONCLUSION: This meta-analysis of data from cardiovascular outcome trials revealed no heightened infection risk in patients undergoing DPP-4 inhibitor therapy compared to control cohorts.

Triceps skinfold thickness trajectories and the risk of all-cause mortality: A prospective cohort study.

BACKGROUND: The measurement of triceps skinfold (TSF) thickness serves as a noninvasive metric for evaluating subcutaneous fat distribution. Despite its clinical utility, the TSF thickness trajectories and their correlation with overall mortality have not been thoroughly investigated. AIM: To explore TSF thickness trajectories of Chinese adults and to examine their associations with all-cause mortality. METHODS: This study encompassed a cohort of 14747 adults sourced from the China Health and Nutrition Survey. Latent class trajectory modeling was employed to identify distinct trajectories of TSF thickness. Subjects were classified into subgroups reflective of their respective TSF thickness trajectory. We utilized multivariate Cox regression analyses and mediation examinations to explore the link between TSF thickness trajectory and overall mortality, including contributory factors. RESULTS: Upon adjustment for multiple confounding factors, we discerned that males in the 'Class 2: Thin-stable' and 'Class 3: Thin-moderate' TSF thickness trajectories exhibited a markedly reduced risk of mortality from all causes in comparison to the 'Class 1: Extremely thin' subgroup. In the mediation analyses, the Geriatric Nutritional Risk Index was found to be a partial intermediary in the relationship between TSF thickness trajectories and mortality. For females, a lower TSF thickness pattern was significantly predictive of elevated all-cause mortality risk exclusively within the non-elderly cohort. CONCLUSION: In males and non-elderly females, lower TSF thickness trajectories are significantly predictive of heightened mortality risk, independent of single-point TSF thickness, body mass index, and waist circumference.

Impact of a dual glucose-dependent insulinotropic peptide/glucagon-like peptide-1 receptor agonist tirzepatide on heart rate among patients with type 2 diabetes: A systematic review and pairwise and network meta-analysis.

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.

Leukocyte telomere length independently predicts hyperuricemia risk in a longitudinal study of the Chinese population.

BACKGROUND AND AIMS: Leukocyte telomere length (LTL) has been correlated with uric acid levels, although results are inconsistent, and prospective studies are lacking. In this longitudinal, prospective cohort study, we aimed to assess whether a shorter LTL predicts the risk of hyperuricemia. METHODS AND RESULTS: We conducted a longitudinal study in a Chinese cohort of 599 participants. Of these, 266 participants completed a 5.9-year follow-up from June 2014 to December 2021. LTL was assessed at baseline using real-time polymerase chain reaction. Hyperuricemia was defined as serum uric acid ≥420 mmol/L according to Chinese guidelines for diagnosis and treatment of hyperuricemia and gout. Participants who had developed hyperuricemia during follow-up (n = 17) had shorter LTL at baseline. Baseline LTL was independently associated with the development of hyperuricemia at follow-up after adjusting for conventional hyperuricemia risk factors (odds ratio [OR] 2.347 [95% confidence interval [CI] 1.123, 4.906]; P = 0.023). After grouping according to LTL tertiles, the incidence of hyperuricemia was 18.334-fold higher for the first than for the third tertile (OR 18.334 [95%CI 1.786, 191.272]; P = 0.014, P for trend = 0.050). CONCLUSION: Our findings in a prospective cohort suggest that LTL could predict hyperuricemia risk, which might inform the timely prevention and treatment of hyperuricemia.

Effects of online continuing medical education on perspectives of shared decision-making among Chinese endocrinologists.

BACKGROUND: Shared decision-making (SDM) may influence the clinical outcomes of patients with endocrine disorders. There are few studies describing perspectives towards SDM among endocrinologists in China. METHODS: In the first stage, we conducted a national survey using an online questionnaire about SDM among endocrinologists in China. The national survey focused on attitude and propensity, potential barriers, and the effectiveness of SDM implementation strategies. In the second stage, survey participants were further recruited to participate in a prospective cohort study in the online continuing medical education (CME) program of Peking Union Medical College Hospital in Beijing. The Shared Decision-Making Questionnaire (SDM-Q-Doc) was employed to assess the effects of online CME on physicians' perspectives during the process of SDM, which was conducted before and after the CME course was provided. RESULTS: In the national survey, 280 endocrinologists (75.7% female, mean age 38.0 ± 4.5 years, 62.5% with a duration of practice of more than ten years) completed the questionnaire. Participants had a generally positive attitude towards SDM in clinical practice. The main perceived barriers included time consumption, information inequality between doctors and patients, and a lack of technical support and training for SDM. The main uncertainties of implementation steps included inviting patients to participate in SDM (16.3%), assisting in decision-making (15.3%), facilitating deliberation and decision-making (13.7%), and providing information on benefits and risks (12.6%). Of the physicians who participated in the national survey, 84 registered for the eight-day online CME course. The SDM-Q-Doc score increased from 87.3 ± 18.2 at baseline to 93.0 ± 9.3 at the end of the 8-day online CME training (p = 0.003, paired t test). The participants' age, sex, education level, practice duration, the annual number of patients with rare endocrine diseases, and the annual number of patients requiring MDT or CME were not significantly related to increased SDM-Q-Doc scores after online CME (all p > 0.05). CONCLUSIONS: Chinese endocrinologists had a generally positive attitude towards SDM in clinical practice. There were also several uncertainties in the implementation steps of SDM. Regardless of a physician's educational background or prior professional experience, CME may help to improve their perspectives regarding SDM.

Tumor necrosis factor-alpha mediates the negative association between telomere length and kidney dysfunction.

Aim/hypothesis: The relationship between peripheral blood leukocyte telomere length (LTL) and kidney dysfunction, especially in people with hypertension, remains unclear. No clinical study has explored the role of inflammation and oxidative stress in the relationship between LTL and kidney dysfunction. Therefore, we examined the relationship between baseline LTL and albuminuria progression and/or rapid renal function decline in Chinese patients with or without hypertension and investigated whether inflammation and oxidative stress played a mediating role in this relationship. Methods: We conducted a prospective study including 262 patients in a 7-year follow-up period from 2014 to 2021. Data on LTL, inflammation, oxidative markers, renal function, and urine protein levels were assessed. Kidney dysfunction was defined as either albuminuria progression, rapid decline in renal function, or the composite endpoint (albuminuria progression and rapid decline in renal function). Logistic regression and simple mediation models were used for the analysis. Results: In this cohort (mean age, 54.3±9.7 years; follow-up period, 5.9±1.1 years), 42(16.0%), 21(8.0%), and 59(22.5%) patients developed albuminuria progression, rapid eGFR decline, and the composite endpoint of kidney dysfunction, respectively. Logistic regression analysis showed that each standard deviation decrease of baseline LTL and the lower quartile (Q) of baseline LTL were significantly correlated with an increased risk of rapid decline in renal function (OR=1.83 [95% CI 1.07, 3.27] per 1SD, P=0.03; OR=7.57 [95% CI 1.25, 145.88] for Q1 vs. Q4, P for trend=0.031); and the composite endpoint of kidney dysfunction (OR=1.37 [95% CI 0.97, 1.96] per 1SD, borderline positive P=0.072; OR=2.96[95% CI 1.15, 8.2] for Q1 vs. Q4, P for trend=0.036). The mediating analysis showed that tumor necrosis factor (TNF)-a partly mediated the relationship between LTL and rapid decline in renal function (direct effect: ß=0.046 95%CI [0.006, 0.090],P=0.02; indirect effect: ß=0.013 95%CI [0.003, 0.020]), and the mediating proportion was 22.4%.In subgroup analyses, LTL was inversely associated with rapid decline in renal function or the composite endpoint of kidney dysfunction only in patients with hypertension (OR=49.07[3.72,211.12] vs.1.32[0.69,2.58] per 1SD, P for interaction=0.045;OR=3.10 [1.48, 7.52] vs.1.08[0.92,1.63] per 1SD, P for interaction=0.036). Conclusion: Baseline LTL could independently predict kidney dysfunction at follow-up, especially in participants with hypertension. TNF-a partially mediated the negative association between LTL and kidney dysfunction.

The Dof transcription factor COG1 acts as a key regulator of plant biomass by promoting photosynthesis and starch accumulation.

Photosynthetic efficiency is the primary determinant of crop yield, including vegetative biomass and grain yield. Manipulation of key transcription factors known to directly control photosynthetic machinery can be an effective strategy to improve photosynthetic traits. In this study, we identified an Arabidopsis gain-of-function mutant, cogwheel1-3D, that shows a significantly enlarged rosette and increased biomass compared with wild-type plants. Overexpression of COG1, a Dof transcription factor, recapitulated the phenotype of cogwheel1-3D, whereas knocking out COG1 and its six paralogs resulted in a reduced rosette size and decreased biomass. Transcriptomic and quantitative reverse transcription polymerase chain reaction analyses demonstrated that COG1 and its paralogs were required for light-induced expression of genes involved in photosynthesis. Further chromatin immunoprecipitation and electrophoretic mobility shift assays indicated that COG1 can directly bind to the promoter regions of multiple genes encoding light-harvesting antenna proteins. Physiological, biochemical, and microscopy analyses revealed that COG1 enhances photosynthetic capacity and starch accumulation in Arabidopsis rosette leaves. Furthermore, combined results of bioinformatic, genetic, and molecular experiments suggested that the functions of COG1 in increasing biomass are conserved in different plant species. These results collectively demonstrated that COG1 acts as a key regulator of plant biomass by promoting photosynthesis and starch accumulation. Manipulating COG1 to optimize photosynthetic capacity would create new strategies for future crop yield improvement.

Clopidogrel as a Distinctive Cause of Insulin Autoimmune Syndrome: A Systematic Case Review.

The sulfhydryl group of clopidogrel metabolite could induce insulin autoimmune syndrome (IAS) with hypoglycemia as the major symptom. For patients with cardiovascular disease taking clopidogrel for vascular protection, this adverse event hypoglycemia increases the risk of cardiovascular events. However, discontinuing clopidogrel leaves patients without appropriate antiplatelet therapy. Treating IAS with glucocorticoids is also risky for these patients' primary cardiovascular diseases. Early recognition and appropriate treatment of clopidogrel-induced IAS (CIAS) would be beneficial for patients. This research aimed to discover the clinical features and investigate optimal therapeutic management of CIAS. We systematically searched for cases of CIAS in PubMed and Embase and performed data mining in Food and Drug Administration Adverse Event Reporting System (FAERS). In the CIAS series, clinical features were summarized and compared to 287 IAS cases, including demographic information, HLA alleles, onset, and symptoms. The therapeutic effect of glucocorticoids was compared between the receiving group and the not-receiving group. The possibilities of common antiplatelet drugs to induce hypoglycemia/IAS were investigated with chemical structure and FAERS reports. A CIAS series of 51 patients was established. CIAS had an onset age of 74.8±8.6 years old, 92.2% male, and a balanced proportion of East Asians and non-East Asians. Confusion occurred more frequently in CIAS than in IAS from various causes, while the other symptoms and hypoglycemia types were similar. The recovery time was approximately the same whether using glucocorticoids/immunotherapy in CIAS or not. Among common antiplatelet drugs, ticagrelor and rivaroxaban were unlikely to induce hypoglycemia/IAS. Clopidogrel is a distinctive cause of IAS featuring an elderly male presenting confusion as the symptom of hypoglycemia. Glucocorticoids/immunotherapy might not be necessary for the long-term recovery of CIAS. To balance the risks of hypoglycemia and cardiovascular events, substituting clopidogrel with ticagrelor and rivaroxaban might be considered.

Glucose-Histidine Heyns compound: Preparation, characterization and fragrance enhancement.

N-(2-Deoxy-D-glucos-2-yl)-L-histidine (Glu-His), one of Heyns rearrangement products (HRPs), was prepared by condensation, dehydration and rearrangement using l-Histidine and d-Fructose as raw materials with methanol as solvent. The response surface method (RSM) was used to improve yield of product and the optimal reaction condition was as following: the original ratio of Fru:His was 1.2:1 and the temperature and time of reaction was 73.2 °C and 4.7 h, and the yield of final product was 74.10% with the purity of 99.7%. The structure of product was identified by IR, NMR and conformed as C12H19N3O7 (317.1 Da) by high-resolution mass spectrometry (HRMS) and UPLC-MS/MS. The pyrolysis behavior of Glu-His showed that its initial pyrolysis temperature was 145.2 °C and the total weight loss reached 70.61% at 800 °C. The number of pyrolysis products increased with the increase of temperature, and the main pyrolysis products were pyrans, furans, pyrazines, pyrroles, pyridines, indoles and etc. with burnt-sweet, baking, nutty, sweet and floral aroma features. At last, the fragrance enhancement effect of Glu-His in the preparation of reconstructed tobacco stem (RTS) was investigated and the result of sensory evaluation showed that the smoke of RTS cigarettes brought about more sweet and moist, less irritation, better flavor and comfort with the addition of Glu-His (0.25%, w/w).

SAA1 exacerbates pancreatic ß-cell dysfunction through activation of NF-κB signaling in high-fat diet-induced type 2 diabetes mice.

Insufficient decompensated insulin secretion and insulin resistance caused by pancreatic ß-cell dysfunction are the pathological bases of type 2 diabetes mellitus (T2DM). Glucolipotoxicity in pancreatic ß-cells is an important factor leading to their dysfunction, closely related to inflammatory signals, oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum stress (ERs). However, there may be other unproven regulatory mechanisms that govern pancreatic ß-cell dysfunction. Therefore, further elucidation of the underlying mechanisms that lead to pancreatic ß-cells dysfunction will provide a sufficient theoretical basis for the more effective prevention and treatment of T2DM. As a stress protein with pro-inflammatory properties, Serum Amyloid 1 (SAA1) promotes the progression of metabolic syndrome-related diseases by activating immune cells and damaging endothelial cells. In the development of T2DM, the activation of nuclear factor-kappa B (NF-κB) signaling aggravates pancreatic ß-cells dysfunction under the stimulation of free fatty acids (FFAs), inflammatory factors, and chemokines. Moreover, the facilitating effect of SAA1 on the activation of the NF-κB signaling pathway has been demonstrated in other studies. In the present study, we demonstrated that SAA1 inhibits insulin secretion and promotes apoptotic molecular expression in pancreatic cells and islets and that NF-κB signaling inhibitors could reduce this effect of SAA1. SAA1 deficiency improved high-fat diet (HFD)-induced pancreatic ß-cell dysfunction and decreased expression of NF-κB signaling molecules. Our findings suggested that HFD-induced SAA1 might exacerbate T2DM by enhancing pancreatic ß-cell dysfunction; such a function of SAA1 might depend on NF-κB signaling activation.

Clinical Features and Outcome Analysis of Type B Insulin Resistance Syndrome: A Single-Center Study in China.

CONTEXT: Type B insulin resistance syndrome (TBIRS) is a rare condition, for which effective treatment remains challenging. OBJECTIVE: This work aimed to summarize the clinical characteristics of TBIRS and explore effective therapeutic strategies. METHODS: The clinical manifestations, biochemical indices, and treatment of 8 patients (3 men and 5 women) with TBIRS from Peking Union Medical College Hospital were retrospectively analyzed and their clinical outcomes were evaluated. RESULTS: The average age of the patients was 49.5 ± 16.5 years, and the duration of the disease ranged from 2 months to 1 year. Seven patients with hyperglycemia had normal/lower triglycerides (TGs) and lower insulin-like growth factor 1 (IGF-1) levels. One patient complained of intractable hypoglycemia. Five patients had accompanied systemic lupus erythematosus, 2 had mixed connective tissue disease, and 1 had undifferentiated connective tissue disease. Five patients had acanthosis nigricans and 3 women of child-bearing age had hyperandrogenism. All 8 patients were treated with glucocorticoids combined with immunosuppressants, among whom, 5 received high-dose glucocorticoid pulse therapy followed by conventional-dose glucocorticoid therapy, all of whom achieved partial remission within 2 to 4 weeks. Among the 3 patients receiving conventional glucocorticoid therapy, 2 achieved partial remission within 2 to 4 weeks. Six patients were tracked for 10 weeks to 4 years; 4 and 2 achieved complete and partial remission, respectively. CONCLUSION: Decreased serum complement 3 and IGF-1 levels and normal/decreased TG levels act as striking biochemical features of TBIRS. High-dose glucocorticoid pulse therapy followed by conventional-dose long-term therapy combined with immunosuppressants achieves good clinical efficacy.

Creation of a watermelon haploid inducer line via ClDMP3-mediated single fertilization of the central cell.

The use of doubled haploids is one of the most efficient breeding methods in modern agriculture. Irradiation of pollen grains has been shown to induce haploids in cucurbit crops, possibly because it causes preferential fertilization of the central cell over the egg cell. Disruption of the DMP gene is known to induce single fertilization of the central cell, which can lead to the formation of haploids. In the present study, a detailed method of creating a watermelon haploid inducer line via ClDMP3 mutation is described. The cldmp3 mutant induced haploids in multiple watermelon genotypes at rates of up to 1.12%. These haploids were confirmed via fluorescent markers, flow cytometry, molecular markers, and immuno-staining. The haploid inducer created by this method has the potential to greatly advance watermelon breeding in the future.

RANKL inhibition: a new target of treating diabetes mellitus?

Accumulating evidence demonstrates the link between glucose and bone metabolism. The receptor activator of nuclear factor-kB ligand (RANKL)/the receptor activator of NF-κB (RANK)/osteoprotegerin (OPG) axis is an essential signaling axis maintaining the balance between bone resorption and bone formation. In recent years, it has been found that RANKL and RANK are distributed not only in bone but also in the liver, muscle, adipose tissue, pancreas, and other tissues that may influence glucose metabolism. Some scholars have suggested that the blockage of the RANKL signaling may protect islet ß-cell function and prevent diabetes; simultaneously, there also exist different views that RANKL can improve insulin resistance through inducing the beige adipocyte differentiation and increase energy expenditure. Currently, the results of the regulatory effect on glucose metabolism of RANKL remain conflicting. Denosumab (Dmab), a fully human monoclonal antibody that can bind to RANKL and prevent osteoclast formation, is a commonly used antiosteoporosis drug. Recent basic studies have found that Dmab seems to regulate glucose homeostasis and ß-cell function in humanized mice or in vitro human ß-cell models. Besides, some clinical data have also reported the glucometabolic effects of Dmab, however, with limited and inconsistent results. This review mainly describes the impact of the RANKL signaling pathway on glucose metabolism and summarizes clinical evidence that links Dmab and DM to seek a new therapeutic strategy for diabetes.

Nickel-catalyzed stereoselective reductive cross-coupling of gem-difluoroalkenes with alkenyl electrophiles.

Herein we develop a Ni-catalyzed defluorinative cross-electrophile coupling of gem-difluoroalkenes with alkenyl electrophiles that allowed the generation of C(sp2)-C(sp2) bonds. The reaction provided various monofluoro 1,3-dienes with broad functional group compatibility and excellent stereoselectivity. Synthetic transformations and applications to the modification of complex compounds were also demonstrated.

Evaluating the Clinical Accuracy of a Non-invasive Single-Fasting-Calibration Glucometer in Patients with Diabetes: A Multicentre Study.

INTRODUCTION: The aim of this study was to evaluate the stability and accuracy of glucose measurements determined using the metabolic heat conformation (MHC)-based non-invasive glucometer in a multicentre, self-controlled clinical trial. This device is the first to obtain a medical device registration certificate awarded by the National Medical Products Administration of China (NMPA). METHODS: The multicentre clinical study was conducted at three sites and enrolled 200 subjects whose glucose was measured with a non-invasive glucometer (the Contour Plus blood glucose monitoring system) and by venous plasma glucose (VPG) measurements, in a fasted state and at 2 and 4 h after meals. RESULTS: Based on both the non-invasive and VPG measurements, 93.9% (95% confidence interval 91.7-95.6%) of the blood glucose (BG) values fell within consensus error grid (CEG) zones A + B. The measurements obtained in a fasted state and at 2 h after meals were more accurate, with 99.0% and 97.0% of the BG values, respectively, falling within zones A + B. Compared to those subjects who received insulin, the proportion of values in zones A + B and the correlation coefficients were 3.1% and 0.0596 higher, respectively. The accuracy of the non-invasive glucometer was influenced by the level of insulin resistance calculated by the homeostatic model assessment method, which had a correlation coefficient with the mean absolute relative difference of - 0.1588 (P = 0.0001). CONCLUSION: The MHC-based non-invasive glucometer assessed in the present study demonstrates generally high stability and accuracy in the glucose monitoring of people with diabetes. The calculation model needs to be further explored and optimised for patients with different diabetes subtypes, levels of insulin resistance and insulin secretion capacity. CLINICAL TRIAL REGISTRY NUMBER: ChiCTR1900020523.

Efficacy of unblinded and blinded intermittently scanned continuous glucose monitoring for glycemic control in adults with type 1 diabetes.

Objective: Intermittently scanned continuous glucose monitoring (isCGM) is used for unblinded or blinded monitoring of interstitial glucose. We aimed to compare the efficacy of blinded and unblinded isCGM with the FreeStyle Libre system for glycemic control in adults with type 1 diabetes (T1D). Research design and methods: This randomized clinical trial conducted between October 2018 and September 2019 across four endocrinology practices in China included 273 adults aged ≥18 years with T1D, who were randomly divided in a 2:1 ratio into the unblinded (n = 199) or blinded isCGM group (n = 78). In the blinded group, the clinician used FreeStyle Libre Pro system for monitoring, but self-monitoring was also performed by the patients. Results: Two hundred sixteen (78%) participants completed the study (152 [75%] in the unblinded and 64 [82%] in the blinded group). At 12 weeks, a significant increase in TIR (3.9-10.0 mmol/L) was only observed in the unblinded group, along with a significant decrease in hyperglycemia (>13.9 mmol/L), hypoglycemia (<3.0 mmol/L), glycemic variability. Further, the mean HbA1c reduction from baseline to 12 weeks was 0.5% in the unblinded isCGM group and 0.4% in the blinded isCGM group respectively (P < 0.001), but the significance did not remain after adjustment for between-group differences. Finally, 99.5% of the blinded isCGM values and 93.8% the of unblinded isCGM values were obtained at the final visit. Conclusions: The unblinded isCGM system was associated with benefits for glucose management, but nearly 100% of the attempted profiles were obtained successfully with the blinded isCGM system. Thus, combining real-time and retrospective data with isCGM might be the most impactful way to utilize flash glycemic monitoring devices.

Hypoglycemia as a potential risk for patients taking clopidogrel: A systematic review and meta-analysis.

Background: Clopidogrel is a cornerstone antiplatelet drug used in cardiovascular, cerebrovascular, and peripheral artery diseases. The sulfhydryl group of clopidogrel metabolite could induce insulin autoimmune syndrome (IAS) with hypoglycemia as the major symptom. Discontinuing clopidogrel and substituting it with ticagrelor has been revealed as an effective treatment in previous studies. Since hypoglycemia serves as a risk factor for cardiovascular and cerebrovascular events, we aimed to determine the association between hypoglycemia/IAS and clopidogrel and to investigate whether clopidogrel is a modifiable and causal risk factor of hypoglycemia/IAS. Methods: MEDLINE, Embase, Cochrane databases, and clinical trial registries were searched for randomized controlled trials (RCTs) of clopidogrel from inception to 28 February 2022. RCTs comparing clopidogrel with placebo or other antiplatelet drugs were eligible if meeting the inclusion criteria: 1) clopidogrel was administrated 75 mg qd orally as a long-term antiplatelet prescription at least for months, and 2) hypoglycemia-inducible drugs were not used in the control arm. One investigator abstracted articles and performed a quality assessment. Uncertainties were resolved by discussions with two investigators independently. Odds ratio (OR) and risk difference (RD) were calculated and performed with subgroup analyses. The pre-specified protocol was registered in PROSPERO (CRD42022299622). Results: Six trials with 61,399 participants in total fulfilled the criteria and were included in the meta-analysis. Clopidogrel might not be associated with higher hypoglycemia odds (OR 0.95, 95% CI 0.65 to 1.40). However, Asian participants (p = 0.0437) seemed more likely to develop clopidogrel-associated hypoglycemia. Clopidogrel-associated hypoglycemia occurred at the highest rate of 0.03% (RD -0.00023, 95% CI -0.00077 to 0.00031), and this increased to 0.91% (RD 0.00210, 95% CI -0.00494 to 0.00914) in an aging population and to 0.18% (RD 0.00040, 95% CI -0.00096 to 0.00177) when Asian ratio of the population was elevated. Conclusions: We raise the concern that clopidogrel might be a modifiable and causal risk factor of hypoglycemia. The Asian population might be more vulnerable and need additional care. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42022299622.

Clinical expert consensus on the assessment and protection of pancreatic islet ß-cell function in type 2 diabetes mellitus.

Islet ß-cell dysfunction is a basic pathophysiological characteristic of type 2 diabetes mellitus (T2DM). Appropriate assessment of islet ß-cell function is beneficial to better management of T2DM. Protecting islet ß-cell function is vital to delay the progress of type 2 diabetes mellitus. Therefore, the Pancreatic Islet ß-cell Expert Panel of the Chinese Diabetes Society and Endocrinology Society of Jiangsu Medical Association organized experts to draft the "Clinical expert consensus on the assessment and protection of pancreatic islet ß-cell function in type 2 diabetes mellitus." This consensus suggests that ß-cell function can be clinically assessed using blood glucose-based methods or methods that combine blood glucose and endogenous insulin or C-peptide levels. Some measures, including weight loss and early and sustained euglycemia control, could effectively protect islet ß-cell function, and some newly developed drugs, such as Sodium-glucose cotransporter-2 inhibitor and Glucagon-like peptide-1 receptor agonists, could improve islet ß-cell function, independent of glycemic control.

Development and validation of questionnaire-based machine learning models for predicting all-cause mortality in a representative population of China.

Background: Considering that the previously developed mortality prediction models have limited applications to the Chinese population, a questionnaire-based prediction model is of great importance for its accuracy and convenience in clinical practice. Methods: Two national cohort, namely, the China Health and Nutrition Survey (8,355 individual older than 18) and the China Health and Retirement Longitudinal Study (12,711 individuals older than 45) were used for model development and validation. One hundred and fifty-nine variables were compiled to generate predictions. The Cox regression model and six machine learning (ML) models were used to predict all-cause mortality. Finally, a simple questionnaire-based ML prediction model was developed using the best algorithm and validated. Results: In the internal validation set, all the ML models performed better than the traditional Cox model in predicting 6-year mortality and the random survival forest (RSF) model performed best. The questionnaire-based ML model, which only included 20 variables, achieved a C-index of 0.86 (95%CI: 0.80-0.92). On external validation, the simple questionnaire-based model achieved a C-index of 0.82 (95%CI: 0.77-0.87), 0.77 (95%CI: 0.75-0.79), and 0.79 (95%CI: 0.77-0.81), respectively, in predicting 2-, 9-, and 11-year mortality. Conclusions: In this prospective population-based study, a model based on the RSF analysis performed best among all models. Furthermore, there was no significant difference between the prediction performance of the questionnaire-based ML model, which only included 20 variables, and that of the model with all variables (including laboratory variables). The simple questionnaire-based ML prediction model, which needs to be further explored, is of great importance for its accuracy and suitability to the Chinese general population.