Obstructive sleep apnea (OSA) is associated with increased risk of early-onset sarcopenia and sarcopenic obesity: Results from NHANES 2015-2018.

OBJECTIVE: This study aims to estimate the prevalence of early-onset sarcopenia and sarcopenic obesity in the United States and its relative risk due to obstructive sleep apnea (OSA). METHODS: Data in this cross-sectional study were extracted from the National Health and Nutritional Examination Survey (NHANES) 2015-2018. Weighted multistage stratified probability sampling design was considered to estimate the prevalence of early-onset sarcopenia and sarcopenic obesity. Weighted multivariable logistic regression analyses and weighted multivariable mediation models were performed to evaluate the association between OSA and early-onset sarcopenia. RESULTS: The prevalence of early-onset sarcopenia and early-onset sarcopenic obesity was estimated to be 5.5% and 4.6%, respectively. A higher prevalence of sarcopenia (12% V.S. 5.5%, P < 0.01) and sarcopenic obesity (10.3% V.S. 4.0%, P < 0.01) was observed among participants with OSA than those without OSA. Multivariable logistic regression models suggested that participants with OSA had higher odds ratios of suffering from early-onset sarcopenia [Odds Ratio (OR): 1.5, 95% confidence interval (CI):1.1-2.7] and early-onset sarcopenic obesity [OR: 1.8, 95% CI: 1.1-3.1] after adjusting for potential confounding variables. Mediation analyses suggested serum chronic reaction protein (CRP) mediated 23.7% (P < 0.01) & 26.2% (P < 0.01), homeostasis model assessment insulin resistance index (HOMA-IR) mediated 24.8% (P < 0.01) & 20.7% (P < 0.05), body mass index (BMI) mediated 46.4% (P < 0.05) & 49.9% (P < 0.01), HEI-2015 mediated 23.3% (P < 0.01) & 25.6% (P < 0.01), and Vitamin D mediated 7.5% (P < 0.01) & 8.5% (P < 0.01) of the potential effects of OSA on early-onset sarcopenia and sarcopenic obesity, respectively. CONCLUSION: Early-onset sarcopenia and sarcopenic obesity were prevalent among young adults in the US. OSA is a significant independent risk factor and may induce muscle loss by unhealthy diet habits, higher BMI, chronic inflammation, insulin resistance, and Vitamin D. It was essential for clinicians to arrange appropriate screening and interventions for patients with OSA to prevent muscle loss as early as possible.

Structure-based design and synthesis of anti-fibrotic compounds derived from para-positioned 3,4,5-trisubstituted benzene.

Liver fibrosis is an abnormal wound-healing response to liver injuries. It can lead to liver cirrhosis, and even liver cancer and liver failure. There is a lack of treatment for liver fibrosis and it is of great importance to develop anti-fibrotic drugs. A pivotal event in the process of developing liver fibrosis is the activation of hepatic stellate cells (HSCs), in which the nuclear receptor Nur77 plays a crucial role. This study aimed to develop novel anti-fibrotic agents with Nur77 as the drug target by modifying the structure of THPN, a Nur77-binding and anti-melanoma compound. Specifically, a series of para-positioned 3,4,5-trisubstituted benzene ring compounds with long-chain backbone were generated and tested for anti-fibrotic activity. Among these compounds, compound A8 was with the most potent and Nur77-dependent inhibitory activity against TGF-ß1-induced activation of HSCs. In a crystal structure analysis, compound A8 bound Nur77 in a peg-in-hole mode as THPN did but adopted a different conformation that could interfere the Nur77 interaction with AKT, which was previous shown to be important for an anti-fibrotic activity. In a cell-based assay, compound A8 indeed impeded the interaction between Nur77 and AKT leading to the stabilization of Nur77 without the activation of AKT. In a mouse model, compound A8 effectively suppressed the activation of AKT signaling pathway and up-regulated the cellular level of Nur77 to attenuate the HSCs activation and ameliorate liver fibrosis with no significant toxic side effects. Collectively, this work demonstrated that Nur77-targeting compound A8 is a promising anti-fibrotic drug candidate.

Surplus fatty acid synthesis increases oxidative stress in adipocytes and lnduces lipodystrophy.

Adipocytes are the primary sites for fatty acid storage, but the synthesis rate of fatty acids is very low. The physiological significance of this phenomenon remains unclear. Here, we show that surplus fatty acid synthesis in adipocytes induces necroptosis and lipodystrophy. Transcriptional activation of FASN elevates fatty acid synthesis, but decreases NADPH level and increases ROS production, which ultimately leads to adipocyte necroptosis. We identify MED20, a subunit of the Mediator complex, as a negative regulator of FASN transcription. Adipocyte-specific male Med20 knockout mice progressively develop lipodystrophy, which is reversed by scavenging ROS. Further, in a murine model of HIV-associated lipodystrophy and a human patient with acquired lipodystrophy, ROS neutralization significantly improves metabolic disorders, indicating a causal role of ROS in disease onset. Our study well explains the low fatty acid synthesis rate in adipocytes, and sheds light on the management of acquired lipodystrophy.

Comparisons of clinical outcomes between newly diagnosed early- and late-onset T2DM: a real-world study from the Shanghai Hospital Link Database.

Objective: The aim of this study was to compare the differences in incident population, comorbidities, and glucose-lowering drug prescriptions between newly diagnosed patients with early-onset type 2 diabetes mellitus (T2DM) and those with late-onset T2DM to provide real-world evidence for clinical practice. Methods: This study was based on the Shanghai Hospital Link Database (SHLD). Anonymized electronic medical record (EHR) data from 2013 to 2021 were included in this study. Newly diagnosed patients with T2DM were defined as those without related diagnostic records or glucose-lowering medicine prescriptions in the past 3 years. Early-onset T2DM was defined as patients who were aged 18-40 years old at the first visit for T2DM to represent those who were born after the 1980s. And late-onset T2DM was defined as those aged 65-80 years old to represent those who were born in a relatively undeveloped period. Descriptive statistical analyses were performed to describe their incidence number, glucose-lowering drug prescriptions, and comorbidities at the first visit to the hospital between two T2DM groups. Results: There were a total of 35,457 newly diagnosed patients with early-onset T2DM and 149,108 newly diagnosed patients with late-onset T2DM included in this study. Patients with late-onset T2DM constituted the majority and their number increased by 2.5% on average by years, while the number of patients with early-onset T2DM remained stable each year. Compared with late-onset T2DM patients, more early-onset T2DM patients had dyslipidemia at the first visit to hospitals (9.5% vs 7.7%, P < 0.01) despite their significant age differences. Patients with early-onset T2DM were more likely to use metformin (74.8% vs 46.5, P < 0.01), dipeptidyl peptidase-4 inhibitors (DDP-4i) (16.7% vs 11.2%, P < 0.01), thiazolidinediones (TZD) (14.9% vs 8.4%, P < 0.01), sodium glucose cotransporter 2 inhibitors (SGLT2-i) (0.8% vs 0.3%, P < 0.01), and glucagon-like peptide 1 receptor agonists (GLP-1 RA) (3.7% vs 0.5%, P < 0.01) at their first visit to the hospital. Conclusions: Different characteristics were observed between patients with early-onset T2DM and those with late-onset T2DM. Compared with patients with late-onset T2DM, those with early-onset T2DM were more prone to dyslipidemia and had novel organ-protective drugs prescribed.

Fat-free mass index is a feasible predictor of insulin resistance in women with polycystic ovary syndrome: Evidence from a cross-sectional study.

BACKGROUND: Insulin resistance (IR) and adipose tissue amplify the metabolic and reproductive outcomes in women with polycystic ovary syndrome (PCOS). It has been widely discussed that body composition influences metabolic health. Still, limited studies were focused on the role of the fat-free mass index (FFMI) in assessing IR in PCOS women. AIMS: We aimed to explore the associations between FFMI/fat mass index (FMI) and IR in women with PCOS and assess the role of FFMI in predicting IR in women with PCOS. METHODS: In the current cross-sectional study, women with PCOS aged between 18 and 40 years were enrolled from October 2018 to July 2022. Baseline demographic information was obtained using standardized self-administered questionnaires. Anthropometric, biochemical, and hormonal information was measured and recorded by investigators. Pearson's correlation and multivariable logistical regression were used to analyze the associations of FFMI/FMI and IR. In addition, receiver operating characteristic (ROC) curves were implied to measure the predictive role of FFMI/FMI for IR in women with PCOS. RESULTS: A total of 371 women with PCOS, reproductive age (27.58 ± 4.89) were enrolled. PCOS women with IR have higher levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), homeostatic model assessment of insulin resistance (HOMA-IR), FMI, and FFMI than that without IR. FMI (r = 0.492, p < 0.001) and FFMI (r = 0.527, p < 0.001) were positively associated with IR. After adjusting for potential confounders, FMI and FFMI were significantly associated with IR in PCOS women, and the OR was 1.385 (95%CI: 1.212-1.583) and 2.306 (95%CI: 1.675-3.174), respectively. Additionally, the FFMI (0.847, 95%CI: 0.784-0.888) has a larger area of ROC (AUC) than the FMI (0.836, 95%CI: 0.799-0.896), while there is no difference in predicting IR (95%CI: -0.18-0.41, p = 0.456). CONCLUSION: These results indicated that FFMI and FMI could significantly increase the risk of IR, both of which could be feasible predictors of IR in PCOS women.

The causal effects of leisure screen time on irritable bowel syndrome risk from a Mendelian randomization study.

Associations between leisure sedentary behavior (especially leisure screen time, LST) and irritable bowel syndrome (IBS) have been reported, but causality is unclear. Here, the two-sample Mendelian randomization was performed to investigate the causal association between LST and IBS. Two recently published genome-wide association studies (GWASs) including a total of 1,190,502 people from Europe were used as our data source. Inverse variance weighting (OR = 1.120, 95% CI 1.029-1.219) and weighted median (OR = 1.112, 95% CI 1.000-1.236) analyses revealed a causal effect between LST and IBS. There was no evidence of pleiotropy in the sensitive analysis (MR-Egger, p = 0.139). After removing potentially confounding single nucleotide polymorphisms (SNPs), similar results were found using inverse variance weighting (OR = 1.131, 95% CI 1.025-1.248) and weighted median (OR = 1.151, 95% CI 1.020-1.299), as well as in the validation analyses using inverse variance weighting (OR = 1.287, 95% CI 0.996-1.662). This study provided support for a possible causal relationship between leisure screen time and IBS.

Associations of Oral Contraceptive Use With Cardiovascular Disease and All-Cause Death: Evidence From the UK Biobank Cohort Study.

Background The associations of oral contraceptive (OC) use with cardiovascular disease (CVD) and all-cause death remains unclear. We aimed to determine the associations of OC use with incident CVD and all-cause death. Methods and Results This cohort study included 161 017 women who had no CVD at baseline and reported their OC use. We divided OC use into ever use and never use. Cox proportional hazard models were used to calculate hazard ratios and 95% CIs for cardiovascular outcomes and death. Overall, 131 131 (81.4%) of 161 017 participants reported OC use at baseline. The multivariable-adjusted hazard ratios for OC ever users versus never users were 0.92 (95% CI, 0.86-0.99) for all-cause death, 0.91 (95% CI, 0.87-0.96) for incident CVD events, 0.88 (95% CI, 0.81-0.95) for coronary heart disease, 0.87 (95% CI, 0.76-0.99) for heart failure, and 0.92 (95% CI, 0.84-0.99) for atrial fibrillation. However, no significant associations of OC use with CVD death, myocardial infarction, or stroke were observed. Furthermore, the associations of OC use with CVD events were stronger among participants with longer durations of use (P for trend<0.001). Conclusions OC use was not associated with an increased risk of CVD events and all-cause death in women and may even produce an apparent net benefit. In addition, the beneficial effects appeared to be more apparent in participants with longer durations of use.

Staying up late increases cardiovascular disease risk in women with polycystic ovary syndrome.

STUDY QUESTION: What is the association between late bedtime, night sleep duration, and lifetime cardiovascular disease (CVD) risk in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Both late bedtime (≥1:00) and short sleep duration (<7 h/night) were independently associated with a high-lifetime CVD risk among women with PCOS. WHAT IS KNOWN ALREADY: Previous studies indicated that sleep disturbances, including altered sleep duration and staying up late (SUL), occurred more frequently among women with PCOS compared to women without PCOS. Studies have shown that both PCOS and sleep disturbances are associated with deterioration in cardiometabolic health in the longer term. However, there are limited data regarding the possible association between sleep disturbances and CVD risk among reproductive-aged women with PCOS. STUDY DESIGN, SIZE, DURATION: From the original 393 women identified at our center, a total of 213 women with PCOS aged 18-40 years were enrolled in a cross-sectional study between March 2020 and July 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Bedtime and night sleep duration were obtained from a standardized self-administered questionnaire. The prediction for atherosclerotic CVD risk in the China risk model was applied to estimate the lifetime CVD risk in the PCOS population. Restricted cubic spline regression was applied to explore the non-linear association between sleep duration and lifetime CVD risk in a series of models. Multivariable logistic regression analyses were performed to determine the association between bedtime, night sleep duration, and lifetime CVD risk. MAIN RESULTS AND THE ROLE OF CHANCE: In our study, we found that the proportion of SUL was 94.25% and the mean (±SD) of night sleep duration was 7.5 ± 1.1 h in women with PCOS. Restricted cubic spline regression analysis showed a U-shaped relation between sleep duration and lifetime CVD risk. After adjusting for occasional drinking, fasting insulin, triglyceride, low-density lipoprotein cholesterol, and testosterone in multivariable logistic analyses, compared with going to bed at 23-24 o'clock, those who went to bed after 1 o'clock were independently associated with high-lifetime CVD risk [odds ratio (OR) = 3.87, 95% CI: 1.56-9.62]; compared with optimal sleep duration (7-8 h/night), short sleep (<7 h/night) was also independently associated with high-lifetime CVD risk (OR = 2.46, 95% CI: 1.01-5.97). LIMITATIONS, REASONS FOR CAUTION: Inferring causality is limited owing to the cross-sectional design. All sleep variables data were obtained from a standardized self-administered questionnaire rather than measurements using objective approaches. Even after adjusting for potential confounders, we still cannot completely rule out the possibility of residual confounding from unmeasured factors such as socioeconomic status. Future studies with larger sample sizes are needed to further explore the relation between long sleep duration and lifetime CVD risk. Although these findings are not generalizable to non-SUL PCOS populations, they could be used for guiding multidimensional treatment. Lastly, there is no non-PCOS group in the current cross-sectional study, which limits the interpretation of the findings from the PCOS group. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to report that both late bedtime (≥1:00) and short sleep duration (<7 h/night) were independently associated with a high-lifetime CVD risk among reproductive-aged women with PCOS, in a sample of Chinese adults. Predicting cardiovascular risk and examining the association between sleep disturbances and predicted CVD risk among women with PCOS help to highlight the need for early interventions on sleep to improve their cardiovascular outcomes. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Natural Science Foundation of Fujian Province (No. 2020J011242), the Fujian provincial health technology project (No. 2022CXB016), the Joint Research Projects of Health and Education Commission of Fujian Province (No. 2019-WJ-39), and the Medical and Health project of Xiamen Science & Technology Bureau (No. 3502Z20214ZD1001). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Intestinal Epithelial Cell-specific Deletion of Cytokine-inducible SH2-containing Protein Alleviates Experimental Colitis in Ageing Mice.

BACKGROUND AND AIMS: The incidence of inflammatory bowel disease [IBD] in the elderly has increased in recent years. However, the mechanisms underlying the ageing-related IBD susceptibility remain elusive. Cytokine-inducible SH2-containing protein [CISH] is involved in regulating metabolism, the expansion of intestinal tuft cells and type-2 innate lymphoid cells, and ageing-related airway inflammation. Here, we investigated the role of CISH in ageing-related colitis susceptibility. METHODS: CISH and phosphorylated signal transducer and activator of transcription-3 [p-STAT3] levels were evaluated in the colons of ageing mice and older ulcerative colitis [UC] patients. Mice with intestinal epithelial cell-specific knockout of Cish [CishΔIEC] and Cish-floxed mice were administered dextran sodium sulphate [DSS] or trinitrobenzene sulphonic acid [TNBS] to induce colitis. Colonic tissues were analysed in quantitative real-time polymerase chain reaction, immunoblotting, immunohistochemical, and histological staining experiments. Differentially expressed genes from colonic epithelia were analysed by RNA sequencing. RESULTS: Ageing increased the severity of DSS-induced colitis and the expression of colonic epithelial CISH in mice. CishΔIEC prevented DSS- or TNBS-induced colitis in middle-aged mice but not in young mice. RNA-sequencing analysis revealed that CishΔIEC significantly suppressed DSS-induced oxidative stress and proinflammatory responses. During ageing in the CCD841 cell model, knockdown of CISH decreased ageing-induced oxidative stress and proinflammatory responses, whereas these effects were compromised by knocking down or inhibiting STAT3. The increase in CISH expression was higher in the colonic mucosa of older patients with UC than in that of healthy controls. CONCLUSIONS: CISH might be a proinflammatory regulator in ageing; therefore, targeted therapy against CISH may provide a novel strategy for treating ageing-related IBD.

Comparative Effectiveness of Team-Based Care With and Without a Clinical Decision Support System for Diabetes Management : A Cluster Randomized Trial.

BACKGROUND: Uncontrolled hyperglycemia, hypercholesterolemia, and hypertension are common in persons with diabetes. OBJECTIVE: To compare the effectiveness of team-based care with and without a clinical decision support system (CDSS) in controlling glycemia, lipids, and blood pressure (BP) among patients with type 2 diabetes. DESIGN: Cluster randomized trial. (ClinicalTrials.gov: NCT02835287). SETTING: 38 community health centers in Xiamen, China. PATIENTS: 11 132 persons aged 50 years or older with uncontrolled diabetes and comorbid conditions, 5475 receiving team-based care with a CDSS and 5657 receiving team-based care alone. INTERVENTION: Team-based care was delivered by primary care physicians, health coaches, and diabetes specialists in all centers. In addition, a computerized CDSS, which generated individualized treatment recommendations based on clinical guidelines, was implemented in 19 centers delivering team-based care with a CDSS. MEASUREMENTS: Coprimary outcomes were mean reductions in hemoglobin A1c (HbA1c) level, low-density lipoprotein cholesterol (LDL-C) level, and systolic BP over 18 months and the proportion of participants with all 3 risk factors controlled at 18 months. RESULTS: During the 18-month intervention, HbA1c levels, LDL-C levels, and systolic BP significantly decreased by -0.9 percentage point (95% CI, -0.9 to -0.8 percentage point), -0.49 mmol/L (CI, -0.53 to -0.45 mmol/L) (-19.0 mg/dL [CI, -20.4 to -17.5 mg/dL]), and -9.1 mm Hg (CI, -9.9 to -8.3 mm Hg), respectively, in team-based care with a CDSS and by -0.6 percentage point (CI, -0.7 to -0.5 percentage point), -0.32 mmol/L (CI, -0.35 to -0.29 mmol/L) (-12.5 mg/dL [CI, -13.6 to -11.3 mg/dL]), and -7.5 mm Hg (CI, -8.4 to -6.6 mm Hg), respectively, in team-based care alone. Net differences were -0.2 percentage point (CI, -0.3 to -0.1 percentage point) for HbA1c level, -0.17 mmol/L (CI, -0.21 to -0.12 mmol/L) (-6.5 mg/dL [CI, -8.3 to -4.6 mg/dL]) for LDL-C level, and -1.5 mm Hg (CI, -2.8 to -0.3 mm Hg) for systolic BP. The proportion of patients with controlled HbA1c, LDL-C, and systolic BP was 16.9% (CI, 15.7% to 18.2%) in team-based care with a CDSS and 13.0% (CI, 11.7% to 14.3%) in team-based care alone. LIMITATION: There was no usual care control, and clinical outcome assessors were unblinded; the analysis did not account for multiple comparisons. CONCLUSION: Compared with team-based care alone, team-based care with a CDSS significantly reduced cardiovascular risk factors in patients with diabetes, but the effect was modest. PRIMARY FUNDING SOURCE: Xiamen Municipal Health Commission.

Nanoengineered Spintronic-Metasurface Terahertz Emitters Enable Beam Steering and Full Polarization Control.

The demand for emerging applications at the terahertz frequencies motivates the development of novel and multifunctional devices for the generation and manipulation of terahertz waves. In this work, we report the realization of multifunctional spintronic-metasurface emitters, which allow simultaneous beam-steering and full polarization control over a broadband terahertz beam. This is achieved through engineering individual meta-atoms with nanoscale magnetic heterostructures and, thus, implementing microscopical control over the laser-induced spin and charge dynamics. By arranging the spintronic meta-atoms in the metagrating geometry, the generated terahertz beam can be flexibly steered in space between different orders of diffraction. Furthermore, we demonstrate a simultaneous control over the terahertz polarization states at different emission angles and show that the two control capabilities are mutually independent of each other. The nanoengineered multifunctional terahertz emitter demonstrated in this work can provide a solution to the challenge associated with a growing variety of applications of terahertz technology.

Sleep disturbances, sleep quality, and cardiovascular risk factors in women with polycystic ovary syndrome: Systematic review and meta-analysis.

Objectives: (1) To establish the prevalence of sleep disorders in women with PCOS. (2) To establish the association between sleep disturbance and cardiovascular risk factors in women with PCOS. Methods: The electronic databases PubMed and EMBASE were searched for observational studies of individuals with PCOS published in English from inception to 21 October 2021. The dichotomous outcome measure was presented as odds ratio (OR) and 95% confidence interval (CI). The mean difference (MD) in continuous variables was expressed for each study. Results: A total of 18 articles were included in this meta-analysis, with a total of 16,152 participants from nine different countries. Women with PCOS had a high prevalence of sleep disturbance (OR = 6.22; 95% CI: 2.77, 13.97; p < 0.001), higher PSQI scores (MD = 2.10; 95% CI: 0.29, 3.90; p = 0.02), and shorter duration of sleep (MD = -15.65 min; 95% CI: -27.18, -4.13; p = 0.008). We found that body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol (LDL-c), fasting glucose, 2-h glucose, and waist circumference (WC) levels were significantly higher and high-density lipoprotein cholesterol (HDL-c) was significantly lower in PCOS with sleep disturbance than in PCOS without sleep disturbance. Conclusions: The current study shows a high prevalence of sleep disturbance in women with PCOS and provides evidence of an association between cardiovascular risk factors and sleep disturbance among this population. Increased attention should be paid to sleep management in clinical guidelines for PCOS.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022298040.

Case Report: Anti-TNF Treatment Failure in a Patient With Immune Checkpoint Inhibitor-Induced Severe Colitis.

Immune checkpoint inhibitor (ICI)-induced colitis is one of the known complications of therapies targeting cytotoxic programmed cell death protein 1 (PD-1), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), and programmed cell death ligand 1 (PD-L1). ICI-associated colitis is routinely treated with immunosuppressive therapy, including corticosteroids and/or agents targeting tumor necrosis factor-α (TNF-α). In this report, a 69-year-old male patient developed severe ICI-induced colitis 2 weeks after anti-PD-L1 mAb (i.e., durvalumab) treatment; unexpectedly failed to respond to systemic corticosteroid, anti-TNF, and anti-integrin agents; and unfortunately died in 1 month. This case reminds clinical physicians to be on the alert for early-onset acute ICI-induced colitis and emphasizes that urgent optimized rescue measures are required for patients with severe ICI-induced colitis.

Relationship between diabetes and risk of gastric cancer: A systematic review and meta-analysis of cohort studies.

Patients with diabetes mellitus (DM) are at increased risk of developing several cancers; however, there is a lack of consensus on the relationship between gastric cancer (GC) and DM. This study aimed to explore the association between GC and DM based on the type and duration of DM. We searched nine databases from inception to December 1, 2021, and 40 cohort studies that evaluated the relationship between DM and the incidence of GC were included in this review. The summary relative ratios for the relationship of GC incidence with type 1 DM (T1DM) and type 2 DM (T2DM) were estimated using the fixed-effect and random-effect models, respectively. The risk of GC was 46% and 14% higher in individuals with T1DM and T2DM, respectively, than in those without diabetes. The risk of GC development in patients with diabetes showed a U-shape curve of change with DM duration. Our meta-analysis suggested that both T1DM and T2DM present a higher risk of GC development. The risk of GC may be influenced by the different time windows following the onset of diabetes. Future studies are required to explore the mechanism by which the duration of DM, antidiabetic medication use, and sex affect this association.

miR-31-5p-DMD axis as a novel biomarker for predicting the development and prognosis of sporadic early-onset colorectal cancer.

The incidence of colorectal cancer (CRC) is increasing in young adults, but knowledge regarding the molecular features of sporadic early-onset colorectal cancer (SEOCRC) is limited. The objective of the present study was to investigate potential key tumorigenesis-associated genes and their regulatory microRNAs (miRNAs) in SEOCRC. Using miRNA and mRNA expression screening of SEOCRC and sporadic late-onset colorectal cancer (SLOCRC) by next generation sequencing (NGS) and bioinformatics, the SEOCRC-associated miRNAome and transcriptome were analyzed. In SEOCRC miRNA and mRNA expression profiles, the tumorigenesis-associated genes and their regulatory miRNAs were analyzed according to the miRTarBase database, and specific miRNA-mRNA pairs were selected as the candidate biomarkers in SEOCRC, which were further verified in another cohort of SEOCRC and SLOCRC patients' colon cancer and paracancerous tissues using reverse transcription-quantitative PCR and immunohistochemistry. Moreover, the clinical relevance of these paired signatures to clinicopathological features was determined in 80 patients with SEOCRC. The expression of dystrophin (DMD) was downregulated and that of miR-31-5p was upregulated in SEOCRC tissue compared with adjacent peritumoral tissue. While DMD and miR-31-5p were not differentially expressed in SLOCRC tissues compared with that in adjacent peritumoral tissues. The miR-31-5p-DMD axis was identified as the key regulatory axis specific to SEOCRC, and DMD expression was closely associated with TNM stage and lymph node metastasis. Importantly, Kaplan-Meier analysis revealed that patients with low DMD expression had significantly poorer overall survival, cancer specific survival and recurrence free survival compared with those with high expression of DMD. In conclusion, the miR-31-5p-DMD axis may serve as a novel biomarker in predicting the development of SEOCRC, and DMD can be used as a promising biomarker for the prognosis of SEOCRC.

Nurse-led care versus usual care on cardiovascular risk factors for patients with type 2 diabetes: a systematic review and meta-analysis.

OBJECTS: This study aims to systematically evaluate the effectiveness of nurse-led cares on cardiovascular risk factors among individuals with type 2 diabetes mellitus. DESIGN: Systematic review and meta-analysis. METHODS: The electronic databases PubMed, EMBASE, CINAHL and Cochrane Library databases were searched for randomised controlled trials of nurse-led care for individuals with type 2 diabetes mellitus (T2DM) published in English from inception to 23 December 2021. Random effects models were used to calculate weighted mean differences (WMD) with 95%CI. RESULTS: 13 articles were included in the meta-analysis, with a total of3757 participants. Considering baseline measurements, pooled analysis showed that nurse-led care significantly decreased the glycosylated haemoglobin (HbA1c) (WMD=-0.68 mmol/L; 95% CI -0.85 to -0.52; p<0.001), body mass index (BMI) (WMD=-0.54 kg/m2; 95% CI: -0.97 to -0.11; p=0.01) and systolic blood pressure (SBP) (WMD=-1.17 mmHg; 95% CI: -2.11 to -0.22; p=0.02) for patients with T2DM. But there was no difference in low-density lipoprotein cholesterol (LDL-c) (WMD=-2.50 mg/dL ; 95% CI: -5.07 to 0.08; p=0.06) between the nurse-led and control groups. CONCLUSION: Nurse-led care is an effective and accessible intervention that could improve HbA1c, SBP, BMI levels among individuals with T2DM. PROSPERO REGISTRATION NUMBER: CRD42021248275.

Visceral Adipose Tissue Indices Independently Correlated with Obstructive Sleep Apnea in Patients with Type 2 Diabetes.

AIMS: We aimed to explore whether visceral adiposity indices were significantly associated with obstructive sleep apnea (OSA) in type 2 diabetes (T2DM) patients. METHODS: 100 patients with T2DM who underwent overnight polysomnography were analyzed in this study. Anthropometric data, lipid profiles, and glycemic parameters were recorded. Body fat percentage (BFP) and visceral adipose tissue area (VAT area) were collected from a whole body scan using dual-energy X-ray absorptiometry (DXA). Multivariate logistic regression analysis was performed to explore the associations of AHI with BFP, VAT area, and CVAI. RESULTS: The prevalence rate of OSA was 80%, and the mean (±SD) of age was 47.0 ± 13.6 years. Apnea-hypopnea index (AHI) was significantly and positively associated with either VAT area (r = 0.433, p ≤ 0.001) or Chinese visceral adiposity index (CVAI) (r = 0.355, p ≤ 0.001) but not for BFP (r = 0.107, p = 0.294). Multivariate logistic regression analyses showed that VAT area and CVAI were significantly associated with increased risk of OSA, and the adjusted ORs were (95% CI) 1.025 (1.003-1.047, p = 0.023) and 1.018 (1.002-1.034, p = 0.030), respectively. However, there was no significant association between BFP and increased risk of OSA. CONCLUSIONS: VAT area and CVAI were independent risk factors of OSA in the patients with T2DM.

Association between intrahepatic triglyceride content in subjects with metabolically healthy abdominal obesity and risks of pre-diabetes plus diabetes: an observational study.

OBJECTIVE: We aimed to evaluate the association of intrahepatic triglyceride (IHTG) content in subjects with metabolically healthy abdominal obesity (MHAO) on risks of pre-diabetes plus diabetes. DESIGN: Cross-sectional survey. SETTING: Lianqian community, the First Affiliated Hospital of Xiamen University, Xiamen, China. PARTICIPANTS: Among 1523 community-living healthy adults aged 40 years or older with abdominal obesity recruited at baseline, 428 subjects who underwent IHTG content measurement were selected. OUTCOME MEASURES: Risk of pre-diabetes plus diabetes. RESULTS: Non-alcoholic fatty liver disease (NAFLD) was diagnosed as 203 (69.1%) in MHAO and 121 (90.3%) in metabolically unhealthy abdominal obesity (MUAO) (p<0.001). The prevalence rates of pre-diabetes plus diabetes were 81.1%, 88.8% and 90.9% across the tertiles of IHTG content (p=0.037). Both MUAO (vs MHAO) and NAFLD (vs non-NAFLD) were independently associated with increased risks of pre-diabetes plus diabetes, the adjusted ORs (95% CIs) were 10.90 (3.15 to 37.69, p<0.001) and 3.02 (1.47 to 6.20, p=0.003), respectively. Higher IHTG content was significantly associated with increased risk of pre-diabetes plus diabetes with the adjusted OR (95% CI) of per SD increase of IHTG content of 1.62 (1.07 to 2.46, p=0.024). And there was a significantly positive trend between increasing categories of IHTG content tertiles and excessive risks of pre-diabetes plus diabetes (trend test p value=0.011). Stratified analyses showed similar results on the associations of NAFLD and IHTG content with risks of pre-diabetes plus diabetes for subjects with MHAO but not for those with MUAO. CONCLUSIONS: NAFLD and higher IHTG content were independently associated with increased risks of pre-diabetes plus diabetes in MHAO subjects. NAFLD or quantity of liver fat should be considered as additional criterion when defining and diagnosing MHO. Screening of NAFLD and intervention to reduce liver fat should be strengthened even for those seemly metabolically healthy obese.

Time-restricted feeding improves metabolic and endocrine profiles in mice with polycystic ovary syndrome.

Objectives: Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathy disorders in premenopausal women, which is characterized by hyperandrogenemia, anovulation, and polycystic ovarian morphology (PCOM). Time-restricted feeding (TRF) is a new intermittent restriction dietary pattern, which has been shown to have positive benefits on obesity and glycolipid metabolism disorders. We aimed to explore the effect of the feeding regimen (ad libitum vs. TRF) on the glycolipid metabolism and reproductive endocrine disorders in a PCOS mouse model. Methods: PCOS mouse model was induced by continuous subcutaneous administration of dihydrotestosterone for 21 days. Mice were fed a high-fat diet (HFD) for 8 weeks on an ad libitum or time- restricted diet (from 10:30 p.m. to 6:30 a.m.). Results: Compared to control mice, PCOS mice that received TRF treatment had significantly lower body weight, reduced adiposity, lower area under the curve (AUC) of glucose response in the oral glucose tolerance test (OGTT), and lower AUC in the insulin tolerance test (ITT). TRF also ameliorated lipid metabolism, as shown by a reduction in plasma lipid profiles (triglycerides and cholesterol) and the triglyceride content in the liver of PCOS mice. In terms of reproduction, the plasma androgen level, plasma estrogen (E2) level, and luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio in PCOS mice were significantly reduced after 8 weeks of TRF treatment. In addition, ovarian histology showed that TRF inhibits cyst formation and promotes corpus luteum formation. Conclusion: In conclusion, TRF improved metabolic and endocrine profiles in mice with PCOS.