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Abstract Background Chronic insomnia is a common yet often overlooked issue in primary health care. This study investigated the knowledge, attitude, and practices of chronic insomnia management among general practitioners (GPs). Methods A cross-sectional online survey was conducted among GPs providing routine care to adults with insomnia in health facilities at all levels in Sichuan Province, China. Additionally, we designed an online questionnaire that included basic information and knowledge, attitudes, and practices regarding chronic insomnia management. Results We included 420 GPs, 66.2% of whom were female and 58.1% were from community health service centers. Total 198 (47.1%) GPs had received specific training and only 2 GPs (0.5%) correctly answered the knowledge-related questions. Furthermore, only 44 GPs (10.5%) demonstrated excellent practice behaviors, while most GPs (70.2%) expressed high demand for training in insomnia management. Insomnia training experience was associated with higher practice scores (β = 3.318, p

Abstract Background Diabetes mellitus (DM) and Helicobacter pylori infection (HPI) pose increasing public health challenges in aging societies, sharing common pathophysiological mechanisms, and linked to significant health risks. Our study examines their respective impacts on all-cause and cardiovascular mortalities in a comprehensive longitudinal population-based analysis. Methods The study analyzed data from the National Health and Nutrition Examination Survey (NHANES) database conducted between 1999 and 2019, which included information on Diabetes mellitus status and Helicobacter pylori infection status. Mortality data were obtained from the same database mentioned above. Results Among the 2719 participants, 1362 (50.1%) were free of both diabetes mellitus (DM) and Helicobacter pylori infection (HP) (DM −/HP −), 140 (5.1%) had DM alone (DM +/HP −), 1011 (37.2%) had HP alone (DM −/HP +), and 206 (7.6%) had both DM and HP (DM +/HP +). Compared to the DM −/HP − group, the DM +/HP − and DM + /HP + groups demonstrated increased all-cause mortality with adjusted hazard ratios (HRs) of 1.40 (95% [CI] 1.07–1.78) and 1.46 (95% CI 1.15–1.84), respectively. For diabetic mortality, DM +/HP– group and DM + /HP + group showed increased HR of 6.30 (95% CI 1.30–30.43) and 8.56 (95% CI 1.98–36.94), respectively. For cardiovascular mortality, the DM + /HP– group and DM + /HP + group exhibited increased HR of 1.75 (95% CI 1.14–2.69) and 1.98 (95% CI 1.40–2.79), respectively. The DM + /HP + cohort displayed the highest risk of overall mortality (p for trend = 0.003), diabetic mortality (p for trend

BackgroundOsteoporosis (OP) and sarcopenia are prevalent musculoskeletal conditions among the elderly. Nevertheless, the causal relationship between sarcopenia and OP remains a subject of controversy and uncertainty. In this study, we employed cross-sectional analysis and Mendelian randomization (MR) to investigate the intricate relationship between sarcopenia and OP.MethodsThe cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999-2020, which involved in 116,876 participants. It assessed the correlation between sarcopenia, osteoporosis (OP), and bone mineral density (BMD) using Chi-square tests, T-tests, and a multiple logistic regression model. Additionally, we conducted Mendelian randomization (MR) analysis to investigate the causal effects of sarcopenia-related characteristics (ALM) on OP. We employed IVW, sensitivity analysis, heterogeneity testing, and other methods for MR. The ALM data was sourced from the UK Biobank (n=450,243), while the aggregated data on OP was obtained from GWAS statistics (n=53,236).ResultsIn this cross-sectional analysis, we observed that in the multivariate logistic regression model, without adjusting for any variables, OP emerged as a risk factor for sarcopenia [OR 95% CI = 1.90 (1.13-3.18), P = 0.02]. Following adjustments for gender, age, BMI, and biochemical variables, OP retained its status as a risk factor for sarcopenia [OR 95% CI = 3.54 (1.91-6.54), P < 0.001]. Moreover, after accounting for all variables, OP emerged as an independent risk factor for sarcopenia [OR 95% CI = 4.57 (1.47-14.22), P = 0.01].In the MR analysis, we uncovered that femoral neck BMD (FN BMD), lumbar spine BMD (LS BMD), and forearm bone mineral density (FA BMD) exerted a direct causal influence on ALM [FA BMD: OR 95% CI = 1.028 (1.008, 1.049), p = 0.006; FN BMD: OR (95% CI) = 1.131 (1.092, 1.170), p = 3.18E-12; LS BMD: OR (95% CI) = 1.080 (1.062, 1.098), p = 2.86E-19].ConclusionOur study has revealed a positive correlation between OP and the prevalence of sarcopenia. It suggests a potentially robust causal relationship between OP and sarcopenia. Notably, OP appears to be associated with a higher likelihood of losing ALM, and a significant loss of ALM may contribute to a decline in LS BMD.

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease characterized by irreversible progressive airflow limitation, often manifested by persistent cough, sputum production and other respiratory symptoms that pose a serious threat to human health and affect the quality of life of patients. The disease is associated with chronic inflammation, which is associated with the onset and progression of COPD, but anti-inflammatory therapy is not first-line treatment. Inflammation has multiple manifestations and phenotypes, and this heterogeneity reveals different patterns of inflammation, making treatment difficult. This paper aims to explore the direction of more effective anti-inflammatory treatment by analyzing the nature of inflammation and the molecular mechanism of disease occurrence and development in COPD patients, and to provide new ideas for the treatment of COPD patients.

Abstract Vaccines have proven effective in protecting populations against COVID-19, including the recombinant COVID-19 vaccine (Sf9 cells), the first approved recombinant protein vaccine in China. In this positive-controlled trial with 85 adult participants (Sf9 cells group: n = 44; CoronaVac group: n = 41), we evaluated the safety, immunogenicity, and protective effectiveness of a heterologous boost with the Sf9 cells vaccine in adults who had been vaccinated with the inactivated vaccine, and found a post-booster adverse events rate of 20.45% in the Sf9 cells group and 31.71% in the CoronaVac group (p = 0.279), within 28 days after booster injection. Neither group reported any severe adverse events. Following the Sf9 cells vaccine booster, the geometric mean titer (GMT) of binding antibodies to the receptor-binding domain of prototype SARS-CoV-2 on day 28 post-booster was significantly higher than that induced by the CoronaVac vaccine booster (100,683.37 vs. 9,451.69, p

BackgroundOxidative Balance Score (OBS) is a novel indicator of the overall antioxidant/oxidant balance, providing a comprehensive reflection of the body’s overall oxidative stress status, with higher OBS suggesting more substantial antioxidant exposures. We aimed to investigate the possible relationship between OBS with serum uric acid (SUA) and hyperuricemia.MethodsData utilized in this study were sourced from the 2011–2018 National Health and Nutrition Examination Survey (NHANES). Participants under 18 years old, those with ≤16 complete data out of 20 OBS components, incomplete serum uric acid data, and missing covariates were excluded from the analysis. OBS was computed by evaluating 16 nutrients and 4 lifestyle factors, encompassing 5 pro-oxidants and 15 antioxidants, guided by a priori knowledge of their relationship with oxidative stress.ResultsA total of 1,5096 individuals were included in our analysis with 49.7% being male, and an average age of 49.05 ± 17.56 years. The mean OBS was 19.76 ± 7.17. Hyperuricemia was present in 19.28% of participants. Due to the right-skewed distribution of the OBS, a natural log transformation was applied to address this issue, and Quartiles of lnOBS 1, 2, 3, and 4 were 1.10–2.56 (N=3526), 2.64–2.94 (N=3748), 3.00–3.22 (N=4026), and 3.26–3.61 (N=3796), respectively. Multivariable logistic regression showed that higher lnOBS quantiles were correlated with lower serum uric acid levels. Compared with the lowest lnOBS quantile, participants in the highest lnOBS quantile had a significant serum uric acid decrease of 16.94 μmol/L for each unit increase in lnOBS (β=-16.94, 95% CI: -20.44, -13.45). Similar negative associations were observed in the second-highest (β=-8.07, 95% CI: -11.45, -4.69) and third-highest (β=-11.69, 95% CI: -15.05, -8.34) lnOBS quantiles. The adjusted odds ratios (ORs) for hyperuricemia in Quartiles 1, 2, 3, and 4 were 1.00, 0.84 (95% CI: 0.75, 0.95), 0.78 (95% CI: 0.69, 0.88), and 0.62 (95% CI: 0.55, 0.71), respectively. Compared to Quartile 1, participants in Quartile 4 had a 38% lower prevalence of hyperuricemia. Subgroup analysis and interaction test showed that there was a significant dependence of sex between OBS and serum uric acid (p for interaction 0.05). Subgroup analysis stratified by age, BMI, hypertension, diabetes, and hyperlipidemia showed there is no significant dependence on these negative correlations (all p for interaction >0.05).ConclusionsThe serum uric acid levels and prevalence of hyperuricemia in US adults exhibited a negative association with OBS. By exploring this connection, our research aims to gain a better understanding of how oxidative balance affects the prevalence of hyperuricemia. This could provide valuable insights for developing preventive strategies and interventions for hyperuricemia. Additional large-scale prospective studies are required to explore the role of OBS in hyperuricemia further.

Abstract Background The insufficient number of general practitioners (GPs) is a major challenge facing China’s healthcare system. The purpose of the GP transfer training programme was to provide training for experienced doctors to transition to general practice. However, research on the competencies of GP transfer training trainers in teaching skills in China is limited. This cross-sectional study aimed to examine the baseline familiarity with teaching skills among Chinese GP transfer training trainers. Methods An online survey was conducted among trainers who participated in the 2021 Sichuan Province General Practice Training Trainer Program. The survey collected data on participants’ characteristics and familiarity with 20 skills in three essential teaching knowledge areas: the core functions of primary care (five questions), preparation for lesson plan (four questions), and teaching methods (11 questions). Results In total, 305 participants completed the survey. Familiarity rates were generally low across all three essential teaching knowledge areas. No significant differences were observed in familiarity rates between the tertiary and secondary hospitals. Conclusion This study revealed gaps in the teaching skills of GP transfer training trainers in China. These results suggest the necessity for targeted training programs to enhance the teaching skills and competencies of trainers.

Renal hypouricemia (RHUC) is a rare autosomal recessive disorder characterized by impaired renal tubular uric acid reabsorption and abnormally high uric acid clearance, which may be manifested by reduced serum uric acid (SUA) levels and elevated fractional excretion of uric acid (FE-UA >10%). Most RHUC patients are often asymptomatic or have accidentally decreased SUA levels during health examinations, while others develop kidney stones and exercise-induced acute kidney injury (EIAKI). We now report a case of RHUC complicated with an asymptomatic kidney stone, and we identified a heterozygous mutation of c.269G > A (p.R90H) and a novel heterozygous mutation of c.674C > G (p.T225R) in the SLC22A12 gene in the patient through whole exon gene detection (NGS method). This case offers valuable insights into the mechanisms, clinical management, and prognosis of RHUC and its associated complications.

Abstract Age-associated bone diseases such as osteoporosis (OP) are common in the elderly due to skeletal ageing. The process of skeletal ageing can be accelerated by reduced proliferation and osteogenesis of bone marrow mesenchymal stem cells (BM-MSCs). Senescence of BM-MSCs is a main driver of age-associated bone diseases, and the fate of BM-MSCs is tightly regulated by histone modifications, such as methylation and acetylation. Dysregulation of histone modifications in BM-MSCs may activate the genes related to the pathogenesis of skeletal ageing and age-associated bone diseases. Here we summarize the histone methylation and acetylation marks and their regulatory enzymes that affect BM-MSC self-renewal, differentiation and senescence. This review not only describes the critical roles of histone marks in modulating BM-MSC functions, but also underlines the potential of epigenetic enzymes as targets for treating age-associated bone diseases. In the future, more effective therapeutic approaches based on these epigenetic targets will be developed and will benefit elderly individuals with bone diseases, such as OP.

Abstract To enhance the control effect of intelligent transportation system (ITS) of expressway, avoid blind travel causing traffic congestion, improve road capacity, and achieve the purpose of smooth and efficient operation of the network, 3σ criterion and 2σ cycle removal criterion were used to eliminate the abnormal data of travel time. Thereafter, a combined prediction model of Long Short‐Term Memory (LSTM) based on the complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) algorithm and attention mechanism is proposed. Travel time data, collected from the real world, is decomposed into several Intrinsic Mode Functions (IMFs) and a residue with the CEEMDAN. Then, the decomposed sub‐sequence is predicted and the final prediction result is obtained by comprehensive superposition. The results indicate that: the CEEMDAN algorithm has significantly improved the prediction performance. Compared with the AT‐LSTM model, mean absolute percentage error (MAPE) is reduced by 10.75%, 24.84%, 31.80%, 24.98%, 14.29%, and 31.42% when the time window was 3, 6, 9, 12, 15, and 18, respectively, in the dataset of Yaxi expressway. In the dataset of Chengnan expressway, the number of error points with MAPE greater than 40% is significantly reduced after the adoption of the LSTM model. After the introduction of CEEMDAN algorithm, the error at each time point is controlled within 30%. The proposed model controls the error at each time point within 25%. In different datasets, the proposed model has better prediction ability for highly non‐linear travel time, and can better capture the trend abrupt characteristics of rush hour traffic flow.

Abstract Skeletal muscle makes up 30–40% of the total body mass. It is of great significance in maintaining digestion, inhaling and exhaling, sustaining body posture, exercising, protecting joints and many other aspects. Moreover, muscle is also an important metabolic organ that helps to maintain the balance of sugar and fat. Defective skeletal muscle function not only limits the daily activities of the elderly but also increases the risk of disability, hospitalization and death, placing a huge burden on society and the healthcare system. Sarcopenia is a progressive decline in muscle mass, muscle strength and muscle function with age caused by environmental and genetic factors, such as the abnormal regulation of protein post‐translational modifications (PTMs). To date, many studies have shown that numerous PTMs, such as phosphorylation, acetylation, ubiquitination, SUMOylation, glycosylation, glycation, methylation, S‐nitrosylation, carbonylation and S‐glutathionylation, are involved in the regulation of muscle health and diseases. This article systematically summarizes the post‐translational regulation of muscle growth and muscle atrophy and helps to understand the pathophysiology of muscle aging and develop effective strategies for diagnosing, preventing and treating sarcopenia.

The simultaneous determination of multi-mycotoxins in food commodities are highly desirable due to their potential toxic effects and mass consumption of foods. Herein, liquid chromatography-quadrupole exactive orbitrap mass spectrometry was proposed to analyze multi-mycotoxins in commercial vegetable oils. Specifically, the method featured a successive liquid–liquid extraction process, in which the complementary solvents consisted of acetonitrile and water were optimized. Resultantly, matrix effects were reduced greatly. External calibration approach revealed good quantification property for each analyte. Under optimal conditions, the recovery ranging from 80.8% to 109.7%, relative standard deviation less than 11.7%, and good limit of quantification (0.35 to 45.4 ng/g) were achieved. The high accuracy of proposed method was also validated. The detection of 20 commercial vegetable oils revealed that aflatoxins B1 and B2, zearalenone were observed in 10 real samples. The as-developed method is simple and low-cost, which merits the wide applications for scanning mycotoxins in oil matrices.

The implementation of shared decision making (SDM) in management of sarcopenia is still in its nascent stage, especially compared to other areas of medical research. Accumulating evidence has highlighted the importance of SDM in older adults care. The current study overviews general SDM practices and explores the potential advantages and dilemmas of incorporating these concepts into sarcopenia management. We present common patient decision aids available for sarcopenia management and propose future research directions. SDM can be effectively integrated into daily practice with the aid of structured techniques, such as the “seek, help, assess, reach, evaluate” approach, “making good decisions in collaboration” questions, “benefits, risks, alternatives, doing nothing” tool, or “multifocal approach to sharing in shared decision making.” Such techniques fully consider patient values and preferences, thereby enhancing adherence to and satisfaction with the intervention measures. Additionally, we review the barriers to and potential solutions to SDM implementation. Further studies are required to investigate measurement and outcomes, coordination and cooperation, and digital technology, such as remote SDM. The study concludes that sarcopenia management must go beyond the single dimension of “Paternalism” choice. Integrating SDM into clinical practice offers promising opportunities to improve patient care, with patient-centered care and partnership of care approaches positively impacting treatment outcomes.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly defined as non-alcoholic fatty liver disease (NAFLD), is a disorder marked by the excessive deposition of lipids in the liver, giving rise to a spectrum of liver pathologies encompassing steatohepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma. Despite the alarming increase in its prevalence, the US Food and Drug Administration has yet to approve effective pharmacological therapeutics for clinical use. MASLD is characterized by the accretion of lipids within the hepatic system, arising from a disarray in lipid provision (whether through the absorption of circulating lipids or de novo lipogenesis) and lipid elimination (via free fatty acid oxidation or the secretion of triglyceride-rich lipoproteins). This disarray leads to the accumulation of lipotoxic substances, cellular pressure, damage, and fibrosis. Indeed, the regulation of the lipid metabolism pathway is intricate and multifaceted, involving a myriad of factors, such as membrane transport proteins, metabolic enzymes, and transcription factors. Here, we will review the existing literature on the key process of lipid metabolism in MASLD to understand the latest progress in this molecular mechanism. Notably, de novo lipogenesis and the roles of its two main transcription factors and other key metabolic enzymes are highlighted. Furthermore, we will delve into the realm of drug research, examining the recent progress made in understanding lipid metabolism in MASLD. Additionally, we will outline prospective avenues for future drug research on MASLD based on our unique perspectives.

BackgroundSalmonella Dublin is a zoonotic pathogen that is associated with invasive infections and high morbidity and mortality rates. Here we present the case of a 78-year-old man with a rare manifestation of a paravertebral abscess in the thoracolumbar spine caused by Salmonella Dublin.Case presentationThe patient had a history of spinal tuberculosis and poorly controlled diabetes. The abscess was successfully managed by drainage, and a 12-week course of moxifloxacin resulted in complete recovery. Salmonella Dublin was identified using culture-based serotyping. The patient resided in an environment where cattle farming is common; he consumed raw beef and unpasteurized milk, suggesting a potential source of infection.DiscussionIncreasing the awareness of Salmonella Dublin as a potential cause of spinal abscesses is important, particularly in patients with structural spinal abnormalities. The timely initiation of appropriate antimicrobial therapy based on susceptibility testing is recommended. This case highlights the pathogenic potential of Salmonella Dublin and emphasizes the importance of effectively managing invasive Salmonella infections.

BackgroundDepression and the increased risk of sarcopenia are prevalent among the elderly population. However, the causal associations between these factors remain unclear. To investigate the potential association between depression and the risk of sarcopenia in older adults, this study was performed.MethodsIn the baseline survey, a total of 14,258 individuals aged 40 and above from the China Health and Retirement Longitudinal Study (2015) participated. We initially described the baseline prevalence of the disease. Then, logistic regression and restricted cubic spline (RCS) regression were conducted to assess the relationship between depression and sarcopenia. Subgroup analysis was performed to validate the robustness of the findings. Additionally, we conducted Mendelian randomization analysis using the inverse variance weighting estimator to assess the causal relationship between depression and sarcopenia. Furthermore, we adopted six methods, including MR-Egger, simple median, weighted median, maximum likelihood, robust adjusted profile score (RAPS), and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO), for sensitivity analyses.ResultsDepression patients exhibited higher risks of sarcopenia in all five models adjusting for different covariates (P < 0.05). The RCS analysis demonstrated a linear relationship between depression and sarcopenia (P < 0.05). In the subgroup analysis, increased risk was observed among participants aged 60−70, married or cohabiting individuals, non-smokers, non-drinkers, those with less than 8 h of sleep, BMI below 24, and individuals with hypertension (all P < 0.05). Mendelian randomization results revealed that genetically proxied depression led to a reduction in appendicular skeletal muscle mass (all P < 0.05).ConclusionOur study provides observational and causal evidences that depression can lead to sarcopenia. This finding emphasizes the importance of timely identification and management of depression, as well as implementing targeted educational programs as part of comprehensive strategies to prevent sarcopenia.

PurposeA systematic review and meta-analysis was conducted to synthesize the available data from clinical trials and assess the safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes (T2D) and obesity.MethodsA systematic search was conducted in three electronic databases, namely Embase, PubMed, and the Cochrane Library, up until March 1, 2023, to identify randomized controlled trials (RCTs) comparing tirzepatide to either placebo or active hypoglycemic drugs in individuals with T2D and obesity. Heterogeneity was assessed using the I2 value and Cochran’s Q test, and a fixed effects model was employed to estimate the safety profile of tirzepatide. The safety outcomes of interest, including pancreatitis, the composite of gallbladder or biliary diseases, cholecystitis, and cholelithiasis and biliary diseases, were evaluated. (The composite of gallbladder or biliary diseases incorporated cholelithiasis, cholecystitis, other gallbladder disorders, and biliary diseases.)ResultsA total of nine trials with 9871 participants (6828 in the tirzepatide group and 3043 in the control group) that met the pre-specified criteria were included. When compared to all control groups consisting of basal insulin (glargine or degludec), selective GLP1-RA (dulaglutide or semaglutide once weekly), and placebo, an increased risk of pancreatitis was not found to be significantly associated with tirzepatide (RR 1.46, [95% CI] 0.59 to 3.61; I2 = 0.0%, p = 0.436). For gallbladder or biliary disease, the composite of gallbladder or biliary disease was significantly associated with tirzepatide compared with placebo or basal insulin (RR 1.97, [95% CI] 1.14 to 3.42; I2 = 0.0%, p = 0.558), but not with the risk of cholelithiasis, cholecystitis or biliary diseases.ConclusionBased on the currently available data, tirzepatide appears to be safe regarding the risk of pancreatitis. However, the increased risk of the composite outcome of gallbladder or biliary diseases observed in RCTs warrants further attention from physicians in clinical practice.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42023412400.

We aimed to determine the utility of biopsy data and anemia for the prediction of renal outcomes in Chinese patients with type 2 diabetes. In total, 441 Chinese patients with type 2 diabetes and biopsy-confirmed diabetic nephropathy (DN) were enrolled in a retrospective study. Their renal pathology was assessed using the Renal Pathology Society system. Cox proportional hazards models were used to estimate hazard ratios (HRs) for end-stage renal disease (ESRD), and immunofluorescence staining was used to assess the expression of hypoxia-inducible factor (HIF)-α in patients’ kidneys. We found that glomerular pathology classification was an independent pathological predictor of low hemoglobin concentration, according to linear and logistic regression analyses. Each 1 g/dL decrease in baseline hemoglobin concentration was associated with a 42% higher risk of an adverse renal outcome, after adjustment for clinical and pathologic covariates. In patients with severe glomerular lesions, the risk of progression to ESRD was significantly higher if mild or moderate/severe anemia was present, but in patients with mild glomerular lesions, the risk was only significantly higher in those with moderate or severe anemia than in the absence of anemia. Harrell’s C Concordance was improved, but the Akaike information criterion was worsened by adding the glomerular pathology classification to the use of anemia status and clinical data. Immunofluorescence staining revealed that renal HIF-1α and HIF-2α expression was significantly higher in classes II–IV than class I. Thus, the addition of glomerular pathology classification increases the value of anemia status for the prediction of the progression to ESRD.

Abstract Background This study probes into the function and mechanism of bone marrow mesenchymal stem cell (BMSC)-derived exosomes loaded with miR-150-5p in mechanical allodynia. Methods BMSCs were infected with miR-150-5p inhibition lentiviruses to obtain exosomes with low miR-150-5p expression. A L5 spinal nerve ligation (SNL) model was established in rats where exosomes, NOTCH2 overexpression/inhibition plasmids, or microglial cells were intrathecally administered. Hind paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) of rats were measured. TUNEL staining was used to measure the apoptotic rate in rat spinal dorsal horn (SDH), ELISA to evaluate pro-inflammatory factor levels, and RT-qPCR, western blotting, and immunohistochemistry to detect miR-150-5p and NOTCH2 expression. Immunofluorescence was used for localizing exosomes and NOTCH2 and detecting the expression of OX42, a maker for microglia. Dual luciferase reporter and RNA pull down assays were performed to validate the putative binding between miR-150-5p and NOTCH2. Results NOTCH2 expressed at a high level and miR-150-5p was downregulated in SDH of SNL rats. Exosomes injected were localized in rat SDH. BMSC-exosomes or NOTCH2 downregulation increased PWT and PWL of SNL rats and reduced apoptosis and inflammation in SDH. In contrast, NOTCH2 overexpression aggravated mechanical allodynia and SDH injury. Moreover, inhibiting miR-150-5p in BMSC-exosomes offset the therapeutic effects of BMSC-exosomes. Microglia activation induced mechanical allodynia in wild rats, while intrathecal injection of microglial cells incubated with BMSC-exosomes showed alleviated mechanical allodynia in SNL rats. NOTCH2 was targeted by miR-150-5p. Conclusion BMSC-derived exosomal miR-150-5p alleviates mechanical allodynia by targeting NOTCH2 in microglial cells.

Sarcopenia is a syndrome characterized by a decline in muscular mass, strength, and function with advancing age. The risk of falls, fragility, hospitalization, and death is considerably increased in the senior population due to sarcopenia. Although there is no conclusive evidence for drug treatment, resistance training has been unanimously recognized as a first-line treatment for managing sarcopenia, and numerous studies have also pointed to the combination of nutritional supplementation and resistance training as a more effective intervention to improve quality of life for people with sarcopenia. People with both malnutrition and sarcopenia have a higher mortality rate, so identifying people at risk of malnutrition and intervening early is extremely important to avoid sarcopenia and its associated problems. This article provides important information for dietary interventions in sarcopenia by summarizing the discoveries and developments of nutritional supplements such as protein, leucine, β-hydroxy-β-methylbutyric acid, vitamin D, vitamin C, vitamin E, omega-3 fatty acids, creatine, inorganic nitrate, probiotics, minerals, collagen peptides, and polyphenols in the management of sarcopenia.

Abstract Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on the backbones or amino acid side chains of proteins and expand the diversity of proteins, which provides the basis for the emergence of organismal complexity. To date, more than 650 types of protein modifications, such as the most well‐known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short‐chain and long‐chain acylation modifications, redox modifications, and irreversible modifications, have been described, and the inventory is still increasing. By changing the protein conformation, localization, activity, stability, charges, and interactions with other biomolecules, PTMs ultimately alter the phenotypes and biological processes of cells. The homeostasis of protein modifications is important to human health. Abnormal PTMs may cause changes in protein properties and loss of protein functions, which are closely related to the occurrence and development of various diseases. In this review, we systematically introduce the characteristics, regulatory mechanisms, and functions of various PTMs in health and diseases. In addition, the therapeutic prospects in various diseases by targeting PTMs and associated regulatory enzymes are also summarized. This work will deepen the understanding of protein modifications in health and diseases and promote the discovery of diagnostic and prognostic markers and drug targets for diseases.

Abstract Background The triglyceride and glucose index (TyG) and triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) are substitute markers of insulin resistance (IR). In a retrospective cross-sectional study, the authors aimed to compare the efficacy of the two indicators in diagnosing metabolic-associated fatty liver disease (MAFLD) to construct a novel disease diagnosis model. Methods Overall, 229 patients (97 MAFLD and 132 Non-MAFLD at West China Hospital of Sichuan University were included. MAFLD was diagnosed using ultrasonography. Biochemical indexes were collected and analyzed by logistic regression to screen out indicators that were expressed differently in MAFLD patients and healthy controls, which were incorporated into a diagnostic model. Results After adjusting for age, sex, and body mass index (BMI), serum alanine transaminase (ALT), aspartate transaminase (AST), AST/ALT (A/A), fasting plasma glucose (FPG), cystatin C (Cys-C), uric acid (URIC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), non-HDL-C, LDL-C/HDL-C, non-HDL-C/HDL-C, TG/HDL-C, TC/HDL-C, TyG, and TyG-BMI were risk factors for MAFLD. The odds ratio of TG/HDL-C and TyG were 5.629 (95%CI: 3.039–10.424) and 182.474 (95%CI: 33.518–993.407), respectively. In identifying MAFLD, TyG, TyG-BMI, TG, and TG/HDL-C were found to be the most vital indexes based on the random forest method, with the area under the curve (AUC) greater than 0.9. In addition, the combination of BMI, ALT, and TyG had a high diagnostic efficiency for MAFLD. Conclusions TyG and TG/HDL-C were potential risk factors for MAFLD, and the former performed better in diagnosing MAFLD. The combination of BMI, ALT, and TyG improved the diagnostic capability for MAFLD.

Travel time is the basis for intelligent emergency control and guidance in expressway networks. To realize its accurate prediction and improve the expressway service level during emergencies, this study uses a combined model to predict the short-term travel time of expressway sections based on the expressway gantry data of Sichuan Province. First, the travel time series was extracted using a data matching algorithm, and the double standard deviation-cyclic elimination (2SD-CE) algorithm was used to clean the data. Then, combined with the complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) algorithm, the travel time subsequence was extracted, and the frequency of the subsequence was divided by Sample entropy (SampEn) algorithm. Based on this, bidirectional long short-term memory (BiLSTM), long short-term memory (LSTM), and vanilla recurrent neural network (vanilla RNN) models were used to construct prediction combination model 1 (CM1) under the condition of a single feature. Subsequently, the CEEMDAN and empirical mode decomposition (EMD) algorithms were combined with the LSTM algorithm to obtain the combination models (CM2 and CM3) without frequency division. The example calculation and analysis show that under different time granularities (5 min, 10 min, and 15 min) and different highway sections, the combined model can integrate the advantages of all prediction models and has higher prediction accuracy and stability, among which the prediction effect of CM1 can reduce the prediction value of the root mean squared error (RMSE) by 18.8~26.4%, 0.8~41%, 4.1~13.3%.

Abstract Mental disorders are associated with dysregulated metabolism, but comprehensive investigations of their metabolic similarities and differences and their clinical relevance are few. Here, based on the plasma metabolome and lipidome of subcohort1, comprising 100 healthy participants, 55 cases with anxiety, 52 persons with depression, and 41 individuals with comorbidity, which are from WCHAT, a perspective cohort study of community‐dwelling older adults aged over 50, multiple metabolites as potential risk factors of mental disorders were identified. Furthermore, participants with mental illnesses were classified into three subtypes (S1, S2, and S3) by unsupervised classification with lipidomic data. Among them, S1 showed higher triacylglycerol and lower sphingomyelin, while S2 displayed opposite features. The metabolic profile of S3 was like that of the normal group. Compared with S3, individuals in S1 and S2 had worse quality of life, and suffered more from sleep and cognitive disorders. Notably, an assessment of 6,467 individuals from the WCHAT showed an age‐related increase in the incidence of depression. Seventeen depression‐related metabolites were significantly correlated with age, which were validated in an independent subcohort2. Collectively, this work highlights the clinical relevance of metabolic perturbation in mental disorders, and age‐related metabolic disturbances may be a bridge‐linking aging and depressive.

BackgroundUneven distribution of health resources is higher in Tibet than in other regions. The development of core professional capability for general practitioners (GPs) is the main goal of continuing medical education (CME) training programs.AimThis study aimed to explore the needs of CME for GPs and provide advice for the development of policy, practice, and CME curriculums.MethodsWe conducted a cross-sectional online survey among GPs in Tibet Autonomous Region, China. We designed an online questionnaire including the demographic section, training contents, and training formats about CME.ResultsA total of 108 questionnaires were included in this study. Notably, 79 (73.15%) were women and 56 participants (51.85%) were working in primary care settings. We developed a curriculum priority: first-choice, major alternatives, and secondary considerations. The topics identified as first-choice for CME were related to “cardiovascular disease” (85.19%), “respiratory disease” (81.48%), and “digestive disease” (80.56%). Major alternatives included two essential knowledge and eight clinical skill items. We rated 10 items as secondary considerations. Only 39.81% ranked mental health as an essential priority; bedside teaching (51.85%) was the first choice.ConclusionWe presented priority areas identified in this study to focus on CME for GPs in Tibet. The 23 topics may reflect the features of general practice, which increasingly require common disease management skills, while a demand-oriented curriculum and staged training plans should be adopted. CME programs should be adapted dynamically to respond to evolving needs.

IntroductionModified electroconvulsive therapy (MECT) is a viable therapeutic option for patients with mood disorders and schizophrenia. We found that there is a relationship between MECT and leukocytosis. To the best of our knowledge, this is the first case of this problem. There are no relevant guidelines recommending the risk of leukocytosis caused by MECT, nor the method to reduce the risk. We hope to share this case to provide a reference for the prevention and treatment of similar patients with leukocytosis during or after MECT and remind psychiatrists to pay attention to this risk of leukocytosis before making the decision of MECT while knowing how to deal with it.Case presentationWe describe a case of a 24-year-old woman diagnosed with Paranoid personality disorder (PPD) whose symptoms began at 19 years old. Her main clinical manifestations are feeling targeted, cheated, tracked, misunderstood, and repeating action. Since antipsychotic treatment was ineffective, we considered MECT. After MECT, the patient’s body temperature increased, and leukocytosis was found. After excluding infection and other possibilities, we added 1,000 ml physiological saline to the patient through the vein. The white blood cell (WBC) count returned to normal in a short time.ConclusionBefore MECT, it is necessary to screen blood cytology. During and after MECT, we should be alert to leukocytosis that may be related to MECT and deal with it correctly in time.

Abstract Background Emerging studies have explored the prognostic value of MIR31HG in cancers, but its role remains elusive. Herein, we aimed to summarize the prognostic potential of MIR31HG in this study. Methods Several databases were searched for literature retrieval on Dec 5, 2019. Overall and subgroup analyses were conducted to measure the relationship between MIR31HG expression and clinical outcomes. Moreover, GEPIA was applied for validation of prognostic value of MIR31HG in tumor patients in TCGA dataset. Results Overall, seventeen studies with 2573 patients were enrolled. Compared to counterparts, those patients with high MIR31HG expression tended to have shorter RFS. Notably, MIR31HG overexpression predicted unfavorable OS in lung cancer. By contrast, gastrointestinal cancer patients with elevated MIR31HG expression predicted better OS and disease-free survival. Additionally, MIR31HG overexpression was significantly associated with worse clinicopathological features including advanced tumor stage and LNM in lung cancer, but favorable clinical characteristics in gastrointestinal cancer. Moreover, the positive association between MIR31HG and OS in lung cancer was further confirmed in TCGA dataset. Conclusion Overexpression of MIR31HG suggested remarkable association with poor prognosis in terms of OS, tumor stage, and LNM in lung cancer, but favorable prognosis in gastrointestinal cancer. Therefore, MIR31HG may serve as a promising prognostic biomarker in multiple cancers.

Background OIP5-AS1 has been reported to be aberrantly expressed in multiple cancers and associated with clinical outcomes. We conducted this study to assess the generalized prognostic value of OIP5-AS1 in cancers.Methods PubMed, Web of science, and Cochrane Library were searched for eligible studies. Hazards ratios (HRs) or odd ratios (ORs) with 95% confidence intervals (CIs) were pooled to estimate the prognostic value of OIP5-AS1 in cancers, including overall survival (OS), age, gender, tumor size, clinical stage, and lymph node metastasis (LNM). Publication bias was measured by Begg’s test and funnel plot. Sensitivity analysis were used to detect the stability of pooled results.Results Overall, eleven studies containing 713 patients were eventually enrolled. The pooled results showed that high OIP5-AS1 expression was correlated with shorter OS (HR = 0.48, 95%CI: 0.35–0.64), regardless of the sample size, tumor type and follow-up time. Furthermore, elevated expression of OIP5-AS1 indicated advanced clinical stage (OR = 2.12, 95% CI: 1.06–4.23), but not associated with age, gender, tumor size and LNM. No publication bias was detected.Conclusion High expression of lncRNA OIP5-AS1 may predict a poor OS and advanced clinical stage, implicating that OIP5-AS1 may be a possible prognostic factor in cancers.

Background: Hyperuricemia is involved in the risk of chronic kidney disease (CKD). However, whether urate-lowering therapy (ULT) can influence the progression of kidney function in patients with asymptomatic hyperuricemia is still controversial. We conducted a systematic review and meta-analysis to evaluate the effect of ULT on the progression of kidney function in asymptomatic hyperuricemia patients.Methods: The MEDLINE, EMBASE and Cochrane databases were searched without language, national or ethnic restrictions for randomized controlled trials published prior to November 30, 2020, that compared ULT with controlled therapy in patients with asymptomatic hyperuricemia.Results: Eleven studies were included for qualitative synthesis. ULT did not ameliorate eGFR slopes (WMD 0.36 ml/min/1.73 m2 per year, 95% CI: −0.31, 1.04), or lead to reductions in kidney events (RR 1.26; 95% CI: 0.80, 2.00) or all-cause mortality (RR 1.00; 95% CI: 0.65, 1.55), although ULT resulted in a decrease in serum uric acid levels (WMD −2.73 mg/dl; 95% CI: −3.18, −2.28) and lowered the incidence of gout episodes (0.9 vs 2.7%, RR 0.38; 95% CI: 0.17, 0.86).Conclusion: In patients with asymptomatic hyperuricemia, ULT did not decay the progression of kidney function. Long-term and larger sample studies are needed to verify the results.Systematic Review Registration: [www.crd.york.ac.uk/PROSPERO/#recordDetails], identifier [CRD42020204482].

The prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM) is increasing and there is an urgent need for new treatment strategy to prevent progression of hepatic steatosis and fibrosis. We have performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the treatment of hepatic steatosis and fibrosis in patients with T2DM and NAFLD. The PubMed, Web of Science, Scopus, Embase and Cochrane Central Register of Controlled Trials databases were searched for articles that met the eligibility criteria to explore the efficacy and safety of GLP-1RAs in patients with T2DM and NAFLD. We assessed pooled data using a random/fixed-effects model according to the I2 and p-values. Eight trials that included a total of 468 participants were eligible for inclusion in the review. For primary outcomes, administration of GLP-1RAs significantly decreased the content of intrahepatic adipose (IHA)[p=0.007, weight mean difference (WMD) -3.01, 95% confidence interval (CI) -4.75, -1.28], subcutaneous adipose tissue (SAT) (p

BackgroundDiabetes is prevalent worldwide including hospitalized patients with heart failure with reduced ejection fraction (HFrEF). This retrospective study investigated the association of diabetes with in-hospital adverse events in patients with HFrEF.MethodsWe analyzed data from electronic medical records of patients hospitalized with HFrEF in West China Hospital of Sichuan University from January 1, 2011, to September 30, 2018. Propensity score matching balances the baseline characteristics between patients with and without diabetes. Logistic and Poisson regressions investigated the association of diabetes with risks of intubation, cardiogenic shock, acute kidney injury (AKI), intensive care unit (ICU) admission and death during hospitalization, and length of ICU and hospital stay in the matched cases.ResultsAmong 6,022 eligible patients (including 1,998 with diabetes), 1,930 patient pairs with and without diabetes were included by propensity score matching. Patients with diabetes had a significantly increased risk of intubation (odds ratio [OR], 2.69; 95% confidence interval [CI], 2.25–3.22; P

Detrital zircon of clastic rocks has been widely recognized as a powerful tool for the study of crustal uplift, which is of great significance for understanding multi-sphere interaction. However, young detrital zircons can only roughly constrain the depositional time of the strata, and commonly used zircon age probability density and kernel density estimations cannot provide sufficient evidence to reveal spatio-temporal differences in tectonic uplift. The basins developed in active continental margins usually contain abundant magmatic rocks, which can provide insights into basin evolution and crustal deformation when combined with sedimentary characteristics. In this study, we report detrital zircon ages of Late Mesozoic clastic rocks from the Boli Basin, being part of the Great Sanjiang Basin Group in eastern NE China, which is strongly affected by the Paleo-Pacific subduction. In conjunction with the age data of coeval magmatic rocks and potential sedimentary sources of basement rocks adjacent to the basin, the geochronologic results of this study provide solid evidence for the formation of the Boli Basin and the spatio-temporal evolution of the crustal uplift in northeastern China. The Boli Basin went through multi-phase tectonic evolution of syn-rift and post-rift stages, based on the zircon age data of clastic and igneous rocks. When the geographical distribution characteristics of potential sedimentary sources and their percentages of contribution are taken into account, two stages of eastward migration of the crustal uplift and two episodes of basin destruction caused by the tectonic extension and subsequent compression can be proposed for the Boli Basin. These processes were caused successively by the rolling back of the subducted Paleo-Pacific slab, the docking of the Okhotomorsk block along the eastern continental margin of East Asia, and the transition of the subduction zone by the collision of the Okhotomorsk block.

The entropy weight method (EWM) was developed and used to integrate multiple quality indexes of pork to generate a comprehensive measure of quality. The Arrhenius equation and chemical kinetic reaction were used to fit and generate the shelf life prediction model. The pork was stored at the temperatures of 7 °C, 4 °C, 1 °C and −1 °C. Quality indexes, such as drip loss, color, shear force, pH, TAC, TVB-N and TBARS were measured. The results show that low temperatures effectively delay microbial growth and lipid oxidation. The regression coefficients (R2) for the comprehensive scores at each temperature were greater than 0.973 and the activation energy Ea was 9.7354 × 104 kJ mol−1. The predicted shelf life of pork stored at 7 °C, 4 °C, 1 °C and −1 °C was 4.35 d, 6.85 d, 10.88 d and 14.90 d, respectively. In conclusion, EWM is an effective method to predict the shelf life of chilled/supercooled pork.

Background. Long noncoding RNAs (lncRNAs) have critical regulatory functions in biological and pathological activities during osteosarcoma progression. It is important to elucidate the expression pattern and reveal the underlying mechanisms of the newly identified lncRNAs. Methods. Herein, we screened the differentially expressed lncRNAs in osteosarcoma tumors and cell lines using lncRNA microarray. The candidate lncRNA was further verified by qRT-PCR, and the association of gene expression with clinicopathological features was evaluated by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The targeting miRNA was identified using starBase analysis, and the competing endogenous RNA (ceRNA) network was established by STRING. Overexpression and silence of RNA were detected by qRT-PCR. Osteosarcoma cell proliferation was measured with CCK-8 assay, and the migration and invasion were evaluated with Transwell assay. Colony formation assay was observed. Flow cytometry evaluated the cell cycle. Western blot was performed to detect the mitotic markers and apoptosis-related proteins. A nude mouse tumor formation experiment was used to evaluate osteosarcoma progression in vivo. Cooverexpressing miR-34b-3p with RAD51 reversed the miR-34b-3p-induced changes in proliferation, the cell cycle, the expression of H2A.X, and that of apoptosis-related proteins. Results. HCG9 was identified as osteosarcoma-associated lncRNA. Osteosarcoma tissues and cell lines expressed higher levels of HCG9 as compared to normal tissues and osteoblasts, and high expression of HCG9 was further proved to be related to metastasis and the grade of osteosarcoma in clinical cases. Knockdown of HCG9 inhibited the proliferation, migration, and invasion of osteosarcoma cells. miR-34b-3p was identified as the target of HCG9, and RAD51 acted as a potential target of miR-34b-3p. Cooverexpressing miR-34b-3p with HCG9 partially suppressed the HCG9-stimulated proliferation, migration, and invasion of osteosarcoma cells in vitro and delayed the tumor progression in vivo. Conclusion. We discovered that lncRNA HCG9 promoted the proliferation of osteosarcoma cells via suppressing miR-34b-3p. Our study provides novel biomarkers and potential therapeutic targets for osteosarcoma treatment.

The vertical curve is a major factor affecting vehicle exhaust (CO2, CO, NOx, PM2.5) emissions. This article takes a heavy-duty diesel truck as a typical vehicle, combining instantaneous speed, acceleration and the vehicle-specific power VSP to divide the operating mode, and the exhaust emission of a heavy-duty diesel truck is then calculated by using MOVES. Finally, the environmental modification factors (EMFs) are used to evaluate the influence of curvature change on the exhaust emissions. The results show that CO2 and PM2.5 emissions of heavy-duty diesel trucks are increasing with the curvature of the crest vertical curve changing; with the increase and decrease of curvature K of the crest vertical curve by 50%, CO and NOx emissions showed an increasing trend. Among the four main emissions, CO2 emission amount is the largest, followed by NOx, CO and PM2.5. The emission rates of CO2 and PM2.5 increase with the increase of curvature of the crest vertical curve, and the minimum values of CO2 and PM2.5 emission rates are 46.7 g/s and 0.022 g/s, respectively. The emission rates of CO and NOx increase with the increase of curvature. The minimum point of emission rates of CO and NOx are 0.042 g/s and 0.259 g/s, respectively.

The low temperature is an effective method for postharvest fruits preservation. However, the ice crystal nucleation caused by low temperature significantly decreases the quality of fruits. In this paper, the effects of alternating magnetic field (AMF) on the ice nucleation temperature of grape were investigated, and the AMF continued treatment and AMF intermittent treatment (20 Gs, 60 Hz) assisted near-freezing temperature (AMCT/AMIT-NFT) were used to store grapes at (−2.5 ± 0.2)°C. Compared with the untreated group, AMF decreased the ice nucleation temperature of grape by 1°C. Meanwhile, Results demonstrated that AMCT/AMIT-NFT storage improved sensory properties and antioxidant capacity of grapes, with the overall effect of AMIT treatment being the most favorable. After 9 days of storage, the color difference and polyphenol oxidase (PPO) activity of AMIT treatment were reduced by 17% and 12%, respectively, compared with the untreated group, and it effectively slowed down malonaldehyde (MDA) accumulation. These conclusions show that AMCT/AMIT-NFT storage is an effective tool for prolonging the shelf life of grapes.

The purpose of this work was to develop a highly selective, sensitive, and reliable method for multi-residual analysis. A three-dimensional microporous reduced graphene oxide/polypyrrole nanotube/magnetite hydrogel (3D-rGOPFH) composite was synthesized and utilized as a magnetic solid-phase extraction (MSPE) sorbent to preconcentrate thirteen insecticides, including five organophosphorus (isocarbophos, quinalphos, phorate, chlorpyrifos, and phosalone), two carbamates (pirimor and carbaryl), two triazoles (myclobutanil and diniconazole), two pyrethroids (lambda-cyhalothrin and bifenthrin), and two organochlorines (2, 4′-DDT and mirex), from vegetables, followed by gas chromatography-tandem mass spectrometry. This method exhibited several major advantages, including simultaneous enrichment of different types of insecticides, no matrix effect, high sensitivity, and ease of operation. This is ascribed to the beneficial effects of 3D-rGOPFH, including the large specific surface (237 m2 g−1), multiple adsorption interactions (hydrogen bonding, electrostatic, π–π stacking and hydrophobic interaction force), appropriate pore size distribution (1–10 nm), and the good paramagnetic property. Under the optimal conditions, the analytical figures of merit were obtained as: linear dynamic range of 0.1–100 ng g−1 with determination coefficients of 0.9975–0.9998; limit of detections of 0.006–0.03 ng g−1; and the intra-day and inter-day relative standard deviations were 2.8–7.1% and 3.5–8.8%, respectively. Recoveries were within the range of 79.2 to 109.4% for tomato, cucumber, and pakchoi samples at the fortification levels of 5, 25, and 50 ng g−1. This effective and robust method can be applied for determining multi-classes of insecticide residues in vegetables.

The avalanche photodiode is a highly sensitive photon detector with wide applications in optical communication and single photon detection. ZnO is a promising wide band gap material to realize a UV avalanche photodiode (APD). However, the lack of p-type doping, the strong self-compensation effect, and the scarcity of data on the ionization coefficients restrain the development and application of ZnO APD. Furthermore, ZnO APD has been seldom reported before. In this work, we employed a p-Si/i-ZnO/n-AZO structure to successfully realize electron avalanche multiplication. Based on this structure, we investigated the band structure, field profile, Current–Voltage (I-V) characteristics, and avalanche gain. To examine the influence of the width of the i-ZnO layer on the performance, we changed the i-ZnO layer thickness to 250, 500, and 750 nm. The measured breakdown voltages agree well with the corresponding threshold electric field strengths that we calculated. The agreement between the experimental data and calculated results supports our analysis. Finally, we provide data on the impact ionization coefficients of electrons for ZnO along the (001) direction, which is of great significance in designing high-performance low excess noise ZnO APD. Our work lays a foundation to realize a high-performance ZnO-based avalanche device.

Purpose: A systematic review and meta-analysis was conducted to synthesize the available data from clinical trials and assess the safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes (T2D) and obesity. Methods: A systematic search was conducted in three electronic databases, namely Embase, PubMed, and the Cochrane Library, up until March 1, 2023, to identify randomized controlled trials (RCTs) comparing tirzepatide to either placebo or active hypoglycemic drugs in individuals with T2D and obesity. Heterogeneity was assessed using the I2 value and Cochran's Q test, and a fixed effects model was employed to estimate the safety profile of tirzepatide. The safety outcomes of interest, including pancreatitis, the composite of gallbladder or biliary diseases, cholecystitis, and cholelithiasis and biliary diseases, were evaluated. (The composite of gallbladder or biliary diseases incorporated cholelithiasis, cholecystitis, other gallbladder disorders, and biliary diseases.) Results: A total of nine trials with 9871 participants (6828 in the tirzepatide group and 3043 in the control group) that met the pre-specified criteria were included. When compared to all control groups consisting of basal insulin (glargine or degludec), selective GLP1-RA (dulaglutide or semaglutide once weekly), and placebo, an increased risk of pancreatitis was not found to be significantly associated with tirzepatide (RR 1.46, [95% CI] 0.59 to 3.61; I2 = 0.0%, p = 0.436). For gallbladder or biliary disease, the composite of gallbladder or biliary disease was significantly associated with tirzepatide compared with placebo or basal insulin (RR 1.97, [95% CI] 1.14 to 3.42; I2 = 0.0%, p = 0.558), but not with the risk of cholelithiasis, cholecystitis or biliary diseases. Conclusion: Based on the currently available data, tirzepatide appears to be safe regarding the risk of pancreatitis. However, the increased risk of the composite outcome of gallbladder or biliary diseases observed in RCTs warrants further attention from physicians in clinical practice. [ABSTRACT FROM AUTHOR]