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BACKGROUND: Dulaglutide, a subcutaneously administered glucagon-like peptide 1 receptor agonist, has been hypothesized to lead to weight loss in patients with Type 2 diabetes mellitus (T2DM). However, the consequences of its prescription on body weight (BW) and other anthropometric indices, for example, body mass index (BMI) or waist circumference (WC), have not been completely clarified. Therefore, we aimed to assess the effects of subcutaneous dulaglutide administration on BW, BMI and WC values in T2DM subjects by means of a systematic review and meta-analysis of RCTs. METHODS: We computed a literature search in five databases (PubMed/Medline, Web of Science, EMBASE, Scopus and Google Scholar) from their inception to February 2023 to identify RCTs that examined the influence of subcutaneous dulaglutide on obesity indices. We calculated effect sizes using the random-effects model (using DerSimonian-Laird method). Results were derived across weighted mean differences (WMD) and 95% confidence intervals (CI). Subgroup analyses were applied to explore possible sources of heterogeneity among the RCTs. The current systematic review and meta-analysis was conducted in compliance with The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: In total, 18 studies with 33 RCT arms (BW = 33 RCT arms, 14,612 participants, 7869 cases and 6743 controls; BMI = 10 RCT arms, 14,612 subjects, 7869 cases and 6743 controls; WC = 10 RCT arms, 1632 participants, 945 cases and 687 cases) were included in the meta-analysis. BW (WMD: -0.86 kg, 95% CI: -1.22, -0.49, p < 0.001), BMI (WMD: -0.68 kg/m2 , 95% CI: -0.88, -0.49, p < 0.001) and WC (WMD: -1.23 cm, 95% CI: -1.82, -0.63, p < 0.001) values decreased notably following subcutaneous dulaglutide administration versus placebo. BW notably decreased in RCTs lasting >18 weeks (WMD: -1.42 kg, 95% CI: -1.90, -0.94, p < 0.001), whereas notable reductions in WC were seen in RCTs lasting ≤18 weeks (WMD: -1.78 cm, 95% CI: -2.59, -0.98, p < 0.001). Dulaglutide dosages >1 mg/day significantly decreased BW (WMD: -1.94 kg, 95% CI: -2.54, -1.34, p < 0.001), BMI (WMD: -0.80 kg/m2 , 95% CI: -1.07, -0.54, p < 0.001) and WC (WMD: -1.47 cm, 95% CI: -1.80, -1.13, p < 0.001). BW decreased particularly following dulaglutide prescription in individuals with obesity (WMD: -1.05 kg, 95% CI: -1.28, -0.82, p < 0.001) versus overweight. The dose-response meta-analysis revealed that BW decreased significantly when dulaglutide was prescribed in doses ≤3 mg/day versus >3 mg/day. CONCLUSIONS: Subcutaneous dulaglutide administration in T2DM reduces BW, BMI and WC. The decrease in BW and WC was influenced by the dose and the duration of dulaglutide administration. The reduction in BMI was only influenced by the dosage of dulaglutide. Moreover, T2DM patients who suffered from obesity experienced a notable decrease in BW versus T2DM subjects without obesity.
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Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Fragmentos Fc de Inmunoglobulinas , Proteínas Recombinantes de Fusión , Humanos , Peso Corporal , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Suplementos Dietéticos , Péptidos Similares al Glucagón/análogos & derivados , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Pérdida de PesoRESUMEN
BACKGROUND: Certain occupations may predispose individuals to urolithiasis, a multi-factorial disease. The study aimed to evaluate the prevalence and related factors of nephrolithiasis in medical staff in Qingdao, China. METHODS: Physical examination results of 5115 in-service medical staff aged 22-60 years old were retrospectively analyzed. Multivariable logistic regression analysis and stratified analyses by age and gender were applied to explore the related factors of nephrolithiasis in these medical staff. RESULTS: The overall nephrolithiasis prevalence in medical staff in Qingdao, China was 4.65%. Doctors were more prone to nephrolithiasis than nurses (5.63% vs. 3.96%, P = 0.013) and the peak prevalence (6.69%) was observed in medical staff working in the emergency department (ED). Male gender (OR = 1.615, 95% CI = 1.123-2.323, P = 0.010), overweight or obesity (OR = 1.674, 95% CI = 1.266-2.214, P < 0.001), work seniority ≥ 10 years (OR = 2.489, 95%CI = 1.675-3.699, P < 0.001) and working in the ED (OR = 1.815, 95% CI = 1.202-2.742, P = 0.005) were independent predictors for nephrolithiasis in medical staff based on the results of multivariate logistic regression analysis. The associations between overweight or obesity and nephrolithiasis risk as well as between work seniority ≥ 10 years and nephrolithiasis risk in medical staff were independent of age or gender in stratified analysis. CONCLUSIONS: Nephrolithiasis prevalence in medical staff in Qingdao, China seemed not to be higher than that in the general population. Medical staff with work seniority ≥ 10 years and working in the ED should pay abundant attention to take measures to modify their nephrolithiasis risk.
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Nefrolitiasis , Humanos , Masculino , Adulto , Femenino , China/epidemiología , Nefrolitiasis/epidemiología , Estudios Retrospectivos , Prevalencia , Persona de Mediana Edad , Estudios Transversales , Adulto Joven , Factores de Riesgo , Enfermedades Profesionales/epidemiología , Cuerpo Médico/estadística & datos numéricosRESUMEN
Hippocampal neuronal damage likely underlies cognitive impairment in vascular dementia (VaD). PPARγ coactivator-1α (PGC-1α) is a master regulator of mitochondrial biogenesis. However, the role and the precise mechanism of how PGC-1α alleviates hippocampal neuronal injury remain unknown. To address this question, HT-22 cells, an immortalized hippocampal neuron cell line, with or without PGC-1α overexpression were subjected to oxygen-glucose deprivation (OGD), which mimics the circumstance of chronic cerebral hypoperfusion in VaD. After OGD, cell viability was assessed using the MTS assay. The mitochondrial function and reactive oxygen species (ROS) were both detected. ChIP-Seq analysis was employed to discover the underlying molecular mechanism of PGC-1α-mediated neuroprotective effects. Our results showed that mitochondrial membrane potentials were increased and ROS production was decreased in PGC-1α overexpressing cells, which increased cell viability. The further bioinformatics analysis from ChIP-Seq data indicated that PGC-1α may participate in the regulation of apoptosis, autophagy, and mitophagy pathways in HT-22 cells. We found that PGC-1α promoted the LC3-II formation and reduced the neuronal apoptosis determined by TUNEL staining. In addition, PGC-1α upregulated the expressions of mitochondrial antioxidants, including SOD2, Trx2, and Prx3. In summary, our findings indicate that PGC-1α may attenuate OGD-induced hippocampal neuronal damage by regulating multiple mechanisms, like autophagy and mitochondrial function. Thus, PGC-1α may be a potential therapeutic target for hippocampal damage associated with cognitive impairment.
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Glucosa , Oxígeno , Glucosa/metabolismo , Hipocampo/metabolismo , Neuronas/metabolismo , Oxígeno/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Regulación hacia ArribaRESUMEN
BACKGROUND Activation of AKT pathway attenuates brain damage and neuronal apoptosis during cerebral ischemia/reperfusion (I/R) injury. SC79 is a novel, selective and highly-efficient Akt activator. This study aimed to investigate the neuroprotective effect of SC79 against cerebral I/R injury in a rat model, and to explore the possible underlying mechanisms. MATERIAL AND METHODS Male Sprague-Dawley rats received cerebral ischemia for 1 hour, followed by brain reperfusion for 0.5-24 hours. The cerebral I/R injury animal model were treated with SC79 alone or SC79 in combination with LY294002. Western blots were used to detect the levels of expression of phosphatidylinositol AKT (p-Akt), Bax, and bcl-2. Twenty-four hours after cerebral I/R, the degree of brain injury was evaluated by detecting the neurological deficit score (NDS). The infarct rate of brain tissue was observed by TTC (2, 3, 5-triphenyltetrazolium chloride) staining. TUNEL (terminal deoxynucleotidyl transferase-mediated UTP nick end labeling) staining was used to detect cell apoptosis. RESULTS p-Akt was activated during early cerebral I/R at 0.5 hours, and reached the highest levels at 4 hours, then gradually decreased from 6 hours, and reached and maintained the lowest levels at 12-24 hours. Bax expression was gradually increased from 6 hours and reached the highest level at 24 hours. However, bcl-2 expression was gradually increased and reached the highest levels at 4 hours, then gradually decreased from 6 hours, and reached the lowest levels at 24 hours. Administration of SC79 decreased infarct volumes and improved neurological function significantly. LY294002 in combination with SC79 lost the capability of SC79 to resist the cerebral I/R injury. SC79 treatment alone activated p-Akt and promoted anti-apoptotic bcl-2 and inhibited anti-apoptotic Bax expression in middle cerebral artery occlusion (MCAO) mice. However, combined SC79 and LY294002 treatment abolished SC79-induced p-Akt activity, inhibited anti-apoptotic bcl-2 and promoted anti-apoptotic Bax expression in MCAO mice. Furthermore, SC79 treatment alone attenuated apoptotic neuronal cell death, but abolished this effect in SC79 in combination with LY294002 treated groups. CONCLUSIONS SC79 significantly increased Akt activation and reduced infarct volume and subsequently improved neurological function in ischemic brain after cerebral I/R injury in rats. These findings suggested that SC79 may be as a neuroprotective drug to be potentially used in the clinic.
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Acetatos/farmacología , Benzopiranos/farmacología , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & control , Animales , Apoptosis/efectos de los fármacos , Encéfalo/metabolismo , Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatología , Muerte Celular/efectos de los fármacos , Cromonas/farmacología , Modelos Animales de Enfermedad , Infarto de la Arteria Cerebral Media/metabolismo , Masculino , Morfolinas/farmacología , Fármacos Neuroprotectores/farmacología , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacosRESUMEN
OBJECTIVE: Little evidence exists on the effect of 17beta-estradiol plus norethisterone acetate on all the anthropometric indices. Hence, this systematic review and meta-analysis of Randomized Controlled Trials was conducted to give an evidence-based report on the effect of 17beta-estradiol plus norethisterone acetate on anthropometric indices. METHODS: The literature search was executed in databases including PubMed/Medline, Web of Science, Scopus, Embase, and Google Scholar to recognize clinical trials that examined the influence of 17beta-estradiol plus norethisterone acetate on obesity indices from database inception to Jan 2023. RESULTS: Combined findings were generated from 20 eligible articles. The meta-analysis showed that body weight (Weighted Mean Difference (WMD): -0.47 kg, 95% CI: -1.32, 0.37, p = 0.274), body fat (WMD: 0.16 kg, 95% CI: -1.26, 1.59, p = 0.821), WHR (WMD: 0.001 kg, 95% CI: -0.006, 1.15, p = 0.872), and LBM (WMD: -0.02 kg, 95% CI: -1.19, 1.15, p = 0.970) were not modified in DHEA group compared to the control, but BMI levels were significantly reduced in 17beta-estradiol plus norethisterone acetate group (WMD: -0.15 kg/m2, 95% CI: -0.30, -0.008, p = 0.039). Moreover, based on intervention duration (months), a more significant reduction in BMI was found in trials that were performed on studies with Ë3 months duration (WMD: -0.176 kg/m2) than studies with ≤ 3 months (WMD: 0.05 kg/m2). CONCLUSION: Administration of 17beta-estradiol plus norethisterone acetate for more than 3 months results in a decrease in BMI, which helps to reduce cardiovascular disease risk.
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Estradiol , Obesidad , Humanos , Acetato de Noretindrona , Ensayos Clínicos Controlados Aleatorios como Asunto , Peso Corporal , Suplementos Dietéticos/análisisRESUMEN
Objective: To assess the effect of gender factors on serum leptin levels in patients with diabetes mellitus. Methods: To remove any studies that indicated a relationship between leptin-based inflammatory variables and the prevalence of type 2 diabetes in particular patient categories, a comprehensive search of all articles published between July 2019 and June 2021 was performed on PubMed/MEDLINE, Web of Science, Scopus, and EBSCO Host, including Academic Search Premier, Africa-Wide Information, and Cumulative Index to Nursing and Allied Health Literature. A summary description of the combined analysis across multiple centers, regions, and continents will help us better understand the effect of gender on serum leptin levels in patients with diabetes. The meta-analysis was performed using RevMan 5.2 software on the literature that satisfied the inclusion and exclusion criteria. Results: Plasma CRP levels in women with type 2 diabetes were found to be no different from those in males with type 2 diabetes, with an OR of 0.12, 95 percent confidence interval (CI) of 0.12 to 0.12, P = 0.01. There was no statistically significant difference in the plasma level of interleukin-6 (IL-6) between women with type 2 diabetes and males with type 2 diabetes However, the "inverted funnel" diagram is asymmetrical, indicating a publication bias in the included studies, despite the fact that there was no statistically significant difference in abnormal leptin levels between men with type 2 diabetes and women patients (OR = -0.69, 95 percent CI (0.88, 1.00), P < 0.05). Conclusion: Gender factors did not affect the level of inflammatory factors and leptin level in type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Leptina , África , Femenino , Humanos , Interleucina-6 , Masculino , PrevalenciaRESUMEN
This study was designed to investigate cardiac injury after acute carbon monoxide poisoning and its clinical treatment scheme. Seventy patients with moderate and severe acute carbon monoxide poisoning (ACOP) admitted from January 2017 to December 2018 into The Affiliated Hospital of Qingdao University were regarded as a research group (RG), and another 30 healthy adults undergoing physical examination in the hospital during the same period were selected as a control group (CG). Thirty-five patients in the RG who received hyperbaric oxygen therapy were considered as group A, and 35 patients who received extracorporeal membrane oxygenation therapy were considered as group B. The effective rates and complications of the two groups after treatment were compared. The concentrations of creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH) of myocardial enzymes at different time points before and after treatment were detected. Expression of miR-30a in the blood of experimental subjects was detected by time-fluorescence quantitative PCR, and the relationship between miR-30a expression and ACOP patients was analyzed. Patients in groups A and B achieved obvious efficacy, but the effective rate and incidence rate of complications in the extracorporeal membrane oxygenation (ECMO) group were better than those in the hyperbaric oxygen group. The concentrations of CK-MB and LDH in group A and group B were significantly higher than those in control group (P<0.01). The expression level of miR-30a in the RG was significantly higher than that in the control group (P<0.05). Both hyperbaric oxygen therapy and ECMO therapy have obvious efficacy on ACOP patients, but the latter is better than the former. The expression level of miR-30a in blood of ACOP patients increased significantly, which is positively correlated with myocardial injury, and it decreased after treatment. It is believed that miR-30a can provide a reference index for early diagnosis and prediction of disease progression and prognosis in cardiac injury of ACOP.
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UNLABELLED: Background- AIMS: Little is known about the prognostic significance of elevated serum relaxin in acute myocardial infarction (AMI) patients. The present study is designed to investigate the potential association between serum relaxin levels and the risk of AMI. MATERIALS AND METHODS: We measured circulating relaxin levels in 80 patients (median age 62.3 years) who presented with first-time AMI 8 hours after the incident. The circulating relaxin-2 levels in 80 healthy volunteers (median age 61.5 years) was also measured. Relaxin-2 was detected using enzyme immunoassay in both groups. RESULTS: Serum relaxin levels were significantly higher in patients with AMI (27.4 ± 6.3 ng/ml) compared to controls (9.2 ± 2.3 ng/ml) (P < 0.01). We found that a relaxin level > 13.8 ng/ml had a sensitivity of 79% and a specificity of 86% for predicting AMI. Relaxin revealed the higher sensitivity and specificity for diagnosing AMI. CONCLUSIONS: Elevated relaxin in plasma may be a novel biomarker for early detection of AMI.