The Therapeutic Effect of Exogenous Melatonin on Depressive Symptoms: A Systematic Review and Meta-Analysis.

Background: Depression-related mortality and morbidity pose growing public health burdens worldwide. Although the therapeutic effect of exogenous melatonin on depression has been investigated, findings remain inconsistent. We conducted this systematic review and meta-analysis to clarify the effectiveness of melatonin in the treatment of depression, including primary and secondary depression symptoms. Methods: We searched the online databases of PubMed, EMBASE, and the Cochrane Library for original studies published up to May 2021. We used STATA 14.0 software to synthesize the results of included studies. To evaluate the effectiveness of melatonin, we calculated the standardized mean differences (SMDs) and 95% confidence intervals (CIs) of depression scores between the melatonin and placebo groups. Results: Our literature search returned 754 publications, among which 19 studies with 1,178 patients (715 women, 463 men; mean age: 56.77 years) met inclusion criteria. Melatonin dosages ranged from 2 to 25 mg per day; treatment durations were between 10 days and 3.5 years. Our synthesized results showed that melatonin was not found significantly beneficial for alleviating depressive symptoms (SMD = -0.17, 95% CI = [-0.38, 0.05]). Subgroup analysis demonstrated that the decrease in depression scores measured with the Beck Depression Inventory (BDI) was significant (SMD = -0.52, 95% CI = [-0.73, -0.31]). Conclusions: There is very limited evidence for effects of melatonin on depression.

Arbidol is associated with increased in-hospital mortality among 109 patients with severe COVID-19: A multicenter, retrospective study.

BACKGROUND: The antiviral therapy has been considered as an ordinary intervention for COVID-19 patients. However, the effectiveness of antiviral therapy is uncertain. This study was designed to determine the association between the antiviral therapy and in-hospital mortality among severe COVID-19 patients. METHODS: This study enrolled severe COVID-19 patients admitted to four designated hospitals in Wuhan, China. The use of antiviral treatments, demographics, laboratory variables, co-morbidities, complications, and other treatments were compared between survival and fatal cases. The association between antiviral agents and in-hospital mortality were analyzed. RESULTS: In total, 109 severe COVID-19 patients (mean age 65.43) were enrolled for analysis, among which, 61 (56.0%) patients were discharged alive, and 48 (44.0%) died during hospitalization. We found no association between lopinavir/ritonavir (LPV/r) treatment and the in-hospital mortality (odds ratio (OR) = 0.195, 95% confidence interval (CI) = 0.023-1.679). Besides, ribavirin (OR = 0.738, 95% CI = 0.344-1.582), oseltamivir (OR = 0.765, 95% CI = 0.349-1.636), and interferon-alpha (IFN-α) (OR = 0.371, 95% CI = 0.112-1.236) were not associated with the in-hospital mortality. However, arbidol monotherapy (OR = 5.027, 95% CI = 1.795-14.074) or the combination of arbidol and oseltamivir (OR = 5.900, 95% CI = 1.190-29.247) was associated with an increased in-hospital mortality. In addition, the multiple logistic regression identified a significant association between the use of arbidol and the in-hospital mortality (adjusted OR = 4.195, 95% CI = 1.221-14.408). CONCLUSIONS: Our findings indicated that LPV/r, IFN-α, ribavirin, or oseltamivir have no beneficial effects on the prognosis of severe COVID-19 patients, whereas the use of arbidol is associated with increased in-hospital mortality.

The Burden of Alzheimer's Disease Mortality in the United States, 1999-2018.

BACKGROUND: The increasing prevalence of Alzheimer's disease (AD), along with the associated burden on healthcare systems, presents a substantial public health challenge. OBJECTIVE: This study aimed to investigate trends in AD mortality and the relevant burden across the United States (U.S.) from 1999 to 2018 and to predict mortality trends between 2019 and 2023. METHODS: Data on AD-related deaths between 1999 and 2018 were collected from the WONDER database administered by the U.S. Centers for Disease Control and Prevention (CDC). The Joinpoint Regression Program was used to analyze mortality trends due to AD. Years of life lost (YLL) were calculated to explore the burden of AD deaths. An autoregressive integrated moving average (ARIMA) model was employed to forecast mortality trends from 2019 to 2023. RESULTS: Over a recent 20-year period, the number of AD deaths in the U.S. increased from 44,536 (31,145 females and 13,391 males) to 122,019 (84,062 females and 37,957 males). The overall age-adjusted mortality rate increased from 16.5/100,000 in 1999 to 30.5/100,000 in 2018. AD mortality is projected to reach 42.40/100000 within the year 2023. Overall, AD resulted in 322,773.00 YLL (2.33 per 1000 population) in 1999 and 658,501.87 YLL (3.68 per 1000 population) in 2018. CONCLUSION: Our findings demonstrate an increase in AD mortality in the U.S. from 1999 to 2018 as well as a rapid increase from 2019 to 2023. The high burden of AD deaths emphasizes the need for targeted prevention, early diagnosis, and hierarchical management.

Association between night-shift work and level of melatonin: systematic review and meta-analysis.

BACKGROUNDS: Night-shift workers are exposed to nocturnal light and are more prone to circadian rhythm disorders. Although night-shift work is thought to be associated with the decrease in melatonin secretion, studies have shown inconsistent results. METHODS: This systematic review and meta-analysis studied the association between night-shift work and melatonin levels. Pubmed and Embase databases were used for literature searching. The pooled standardized mean differences (SMDs) and 95% confidence intervals (CIs) were used to compare the differences between night-shift workers and the controls. RESULTS: Thirty-three studies reported in 25 articles (1845 night-shift workers and 3414 controls, mean age 45.12 years) were included after a systematic literature review. Data of circulating melatonin levels and its metabolites, 6-sulfatoxymelatonin (aMT6s) in urine were collected for meta-analysis. The results showed that the first morning-void aMT6s level in night-shift workers was significantly lower than in day workers (SMD = -0.101, 95% CI = -0.179 to -0.022, P = 0.012). The level of mean 24-h urinary aMT6s was lower in night-shift workers than day workers (SMD: -0.264, 95% CI: -0.473 to -0.056, P = 0.013). Among fixed night-shift workers, the level of circulating melatonin, as well as first morning-void aMT6s was lower than that of day workers. CONCLUSION: Our findings indicate that experience of night-shift work is associated with suppression of melatonin production, especially among fixed night-shift workers.

Glycomics: Immunoglobulin G N-Glycosylation Associated with Mammary Gland Hyperplasia in Women.

Mammary gland hyperplasia (MGH) is very common, especially among young and middle-aged women. New diagnostics and biomarkers for MGH are needed for rational clinical management and precision medicine. We report, in this study, new findings using a glycomics approach, with a focus on immunoglobulin G (IgG) N-glycosylation. A cross-sectional study was conducted in a community-based population sample in Beijing, China. A total of 387 participants 40-65 years of age were enrolled in this study, including 194 women with MGH (cases) and 193 women who had no MGH (controls). IgG N-glycans were characterized in the serum by ultra-performance liquid chromatography. The levels of the glycan peaks (GPs) GP2, GP5, GP6, and GP7 were lower in the MGH group compared with the control group, whereas GP14 was significantly higher in the MGH group (p < 0.05). A predictive model using GP5, GP21, and age was established and a receiver operating characteristic curve analysis was performed. The sensitivity and specificity of the model for MGH was 61.3% and 63.2%, respectively, likely owing to receptor mechanisms and/or inflammation regulation. To the best of our knowledge, this is the first study reporting on an association between IgG N-glycosylation and MGH. We suggest person-to-person variations in IgG N-glycans and their combination with multiomics biomarker strategies offer a promising avenue to identify novel diagnostics and individuals at increased risk of MGH.