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AIM/HYPOTHESIS: Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may exert positive effects in patients with depression. Our aim was to conduct a systematic review and meta-analysis to examine the antidepressant effects of GLP-1RAs. METHODS: Randomized controlled trials and prospective cohort studies investigating the effects of GLP-1RAs versus placebo or other antidiabetic therapies on depressive symptoms were searched for using multiple electronic sources (CENTRAL, PubMed, EMBASE, PsycINFO, World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, China Network Knowledge Infrastructure, China Biomedical Database, Wan Fang data, and Chinese Scientific Journals Database) from inception to February 16, 2023. We utilized a random effects model to analyze standardized mean differences for the change in depression rating scales comparing GLP-1RA treated groups with control treated groups. RESULTS: The meta-analysis comprising 2,071 participants included 5 randomized controlled trials and 1 prospective cohort study. The meta-analysis indicated that the change from baseline in depression rating scale scores decreased significantly when patients received treatment with GLP-1RAs compared to control treatments (SMD = -0.12, 95% CI [-0.21, -0.03], pSMD <0.01, I2 = 0%, pQ = 0.52). The subgroup analysis showed that the effects of GLP-1RAs on depressive symptoms were consistent in patients with Type 2 diabetes mellitus (SMD = -0.12, 95% CI [-0.21, -0.03], pSMD <0.01, I2 = 2%, pQ = 0.40). CONCLUSIONS: Adults treated with GLP-1RAs showed significant reductions in the depression rating scale scores compared to those treated with control substances. Our findings suggest that GLP-1RAs may be a potential treatment for alleviating depressive symptoms in humans.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon , Estudos Prospectivos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Antidepressivos/farmacologia , Antidepressivos/uso terapêuticoRESUMO
BACKGROUND: Prior to Wuhan lock-down in 2020, chunyun, the largest population mobility on this planet, had begun. We quantified impact of Wuhan lock-down on COVID-19 spread during chunyun across the nation. METHODS: During the period of January 1 to February 9, 2020, a total of 40,278 confirmed COVID-19 cases from 319 municipalities in mainland China were considered in this study. The cross-coupled meta-population methods were employed using between-city Baidu migration index. We modelled four scenarios of geographic spread of COVID-19 including the presence of both chunyun and lock-down (baseline); lock-down without chunyun (scenario 1); chunyun without lock-down (scenario 2); and the absence of both chunyun and lock-down (scenario 3). RESULTS: Compared with the baseline, scenario 1 resulted in 3.84% less cases by February 9 while scenario 2 and 3 resulted in 20.22 and 32.46% more cases by February 9. The geographic distribution of cases revealed that chunyun facilitated the COVID-19 spread in the majority but not all cities, and the effectiveness of Wuhan lock-down was offset by chunyun. Impacts of Wuhan lock-down during chunyun on the COVID-19 spread demonstrated heterogenetic geographic patterns. CONCLUSION: Our results strongly supported the travel restriction as one of the effective responses and highlighted the importance of developing area-specific rather than universal countermeasures.
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COVID-19 , Epidemias , China/epidemiologia , Cidades , Controle de Doenças Transmissíveis , Humanos , SARS-CoV-2RESUMO
Pentacene is a small molecule organic semiconductor and has high absorption in the UV and visible region. In this work, we report the channel-length-dependent performance of bottom-gate top-contact photosensitive organic field-effect transistors based on pentacene with different channel lengths ranging from 25 to 150 µm. The results show that, for a given drain voltage, the photoresponsivity, external quantum efficiency, and specific detectivity decrease with increasing channel length. For a given channel length and gate voltage, the photoresponsivity, external quantum efficiency, and specific detectivity increase with drain voltages, and then tend to saturate at high drain voltages.
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Erectile dysfunction (ED) is one of the most common male sexual dysfunctions and is related to many pathogenic factors. However, first-line treatment, represented by phosphodiesterase 5 inhibitors, is unable to maintain long-term efficacy. Extracellular vesicles (EVs) have recently attracted the attention of researchers in the fields of cardiovascular disease, neurologic disease, and regenerative medicine and may become a treatment for ED. This article reviews recent applications of EVs in the treatment of ED from the aspects of the source, the therapeutic mechanism, and the strategies to enhance therapeutic efficacy. These research advances lay the foundation for further research and provide references for in-depth understanding of the therapeutic mechanism and possible clinical application of EVs in ED.
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Disfunção Erétil , Vesículas Extracelulares , Humanos , Disfunção Erétil/terapia , Disfunção Erétil/tratamento farmacológico , MasculinoRESUMO
A novel layered magnesium phosphate (MgP) was synthesised from a MgO-P2 O5 -choline chloride-oxalic acid dihydrate system using an ionothermal approach. Single crystal samples of MgP were obtained following introduction of diethylamine (DEA) to the reaction system. Its structure revealed that both the layer and the sheets contained Mg octahedra. Interestingly, adding the layered material to lithium grease resulted in superior lubrication with higher load-carrying, anti-wear and friction reduction capacities compared with the typical lubricant MoS2 ; the PB value of base grease was increased from 353 to 1078 and 549â N, the wear scar diameter was decreased from 0.50 to 0.34 and 0.46â mm, and the friction coefficient was decreased from 0.082 to 0.056 and 0.075, respectively. We also discuss the lubrication mechanism of layered materials based on the crystal structure and resource endowment. The findings could assist the development of new high-efficiency solid lubricants.
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BACKGROUND: Maturity-onset diabetes of the young 10 caused by the c.4G>A (p.Ala2Thr) mutation is extremely rare, with only two reported studies to date. Herein, we report another case that differs from previous cases in phenotype. CASE SUMMARY: The proband developed diabetes at the age of 27 years, despite having a normal body mass index (BMI). She exhibited partial impairment of islet function, tested positive for islet antibodies, and required high doses of insulin. Her sister also carried the c.4G>A (p.Ala2Thr) mutation, and their mother was strongly suspected to carry the mutated gene. Her sister developed diabetes around 40 years of age and required high doses of insulin, while the mother was diagnosed in her 20s and was managed with oral hypoglycemic agents; neither of them were obese. CONCLUSION: p.Ala2Thr mutation carriers often experience relatively later onset and normal BMI. Treatment regimens vary between individuals.
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Background: Cavernous nerve injury (CNI) is the leading cause of erectile dysfunction (ED) after radical prostatectomy and pelvic fracture. Transplantation of human adipose-derived stem cells (ASCs) has been widely used to restore erectile function in CNI-ED rats and patients. Umbilical cord blood-derived MSCs (CBMSCs) are similarly low immunogenic but much primitive compared to ASCs and more promising in large-scale commercial applications due to the extensive establishment of cord blood banks. However, whether CBMSCs and ASCs have differential therapeutic efficacy on CNI-ED and the underlying mechanisms are still not clear. Materials and methods: A bilateral cavernous nerve injury (BCNI) rat model was established by crushing the bilateral cavernous nerves. After crushing, ASCs and CBMSCs were intracavernously injected immediately. Erectile function, Masson staining, and immunofluorescence analyses of penile tissues were assessed at 4 and 12 weeks. PKH-26-labeled ASCs or CBMSCs were intracavernously injected to determine the presence and differentiation of ASCs or CBMSCs in the penis 3 days after injection. In vitro experiments including intracellular ROS detection, mitochondrial membrane potential assay, EdU cell proliferation staining, cell apoptosis assay, and protein chip assay were conducted to explore the underlying mechanism of CBMSC treatment compared with ASC treatment. Results: CBMSC injection significantly restored erectile function, rescued the loss of cavernous corporal smooth muscles, and increased the ratio of smooth muscle to collagen. PKH-26-labeled CBMSCs or ASCs did not colocalize with endothelial cells or smooth muscle cells in the corpus cavernosum. Moreover, the conditioned medium (CM) of CBMSCs could significantly inhibit the oxidative stress and elevate the mitochondria membrane potential and proliferation of Schwann cells. Better therapeutic effects were observed in the CBMSC group than the ASC group both in vivo and in vitro. In addition, the content of neurotrophic factors and matrix metalloproteinases in CBMSC-CM, especially NT4, VEGF, MMP1, and MMP3 was significantly higher than that of ASC-CM. Conclusion: Intracavernous injection of CBMSCs exhibited a better erectile function restoration than that of ASCs in CNI-ED rats owing to richer secretory factors, which can promote nerve regeneration and reduce extracellular matrix deposition. CBMSC transplantation would be a promising therapeutic strategy for CNI-ED regeneration in the future.
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OBJECTIVE: We aim to explore and compare the effect of global travel restrictions and public health countermeasures in response to COVID-19 outbreak. DESIGN: A data-driven spatio-temporal modelling to simulate the spread of COVID-19 worldwide for 150 days since 1 January 2020 under different scenarios. SETTING: Worldwide. INTERVENTIONS: Travel restrictions and public health countermeasures. MAIN OUTCOME: The cumulative number of COVID-19 cases. RESULTS: The cumulative number of COVID-19 cases could reach more than 420 million around the world without any countermeasures taken. Under timely and intensive global interventions, 99.97% of infections could be avoided comparing with non-interventions. The scenario of carrying out domestic travel restriction and public health countermeasures in China only could contribute to a significant decrease of the cumulative number of infected cases worldwide. Without global travel restriction in the study setting, 98.62% of COVID-19 cases could be avoided by public health countermeasures in China only compared with non-interventions at all. CONCLUSIONS: Public health countermeasures were generally more effective than travel restrictions in many countries, suggesting multinational collaborations in the public health communities in response to this novel global health challenge.
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COVID-19 , Pandemias , China/epidemiologia , Humanos , Saúde Pública , SARS-CoV-2 , ViagemRESUMO
AIMS: The purpose of this study was to explore the clinical significance of telomerase reverse transcriptase (TERT) promoter mutations in gliomas. METHODS AND RESULTS: We used DNA sequencing data to analyze 887 gliomas for TERT promoter mutations based on histological and genetic backgrounds. TERT promoter mutations were detected in 39.6% of low-grade gliomas, 40.3% of anaplastic gliomas, 44.7% of primary glioblastomas, 29.4% of secondary glioblastomas, and in 29.7% of Proneural, 38.6% of Neural, 41.8% of Classical, and 41.6% of Mesenchymal subtypes. Frequency of C250T mutation in recurrent gliomas was approximately half that in newly diagnosed gliomas. TERT exhibited improved prognosis when co-occurred with isocitrate dehydrogenase 1 (IDH1) and 1p19q alteration, but experienced inverse survival in the Mesenchymal subtype or tumor protein p53 (TP53) and epidermal growth factor receptor (EGFR) alteration. Furthermore, the five subtypes were classified based on the prognostic impact of the TERT mutation with different genetic backgrounds of glioma. CONCLUSION: We describe the TERT promoter mutation spectrum according to the histological, genetic, and molecular subtypes of glioma, which may aid in glioma subtype classification and have clinical implications.