Importance: Coronavirus disease 2019 (COVID-19) is a pandemic with no specific drugs and high mortality. The most urgent thing is to find effective treatments. Objective: To determine whether hydroxychloroquine application may be associated with a decreased risk of death in critically ill COVID-19 patients and what is potential mechanism. Design, Setting and Patients: This retrospective study included all 568 critically ill COVID-19 patients who were confirmed by pathogen laboratory tests despite antiviral treatment and had severe acute respiratory distress syndrome, PAO2/FIO2 <300 with need of mechanical ventilation in Tongji Hospital, Wuhan, between February 1 of 2020 to April 8 of 2020. All 568 patients received comparable basic treatments including antiviral drugs and antibiotics, and 48 of them additionally received oral hydroxychloroquine (HCQ) treatment (200 mg twice a day for 7-10 days). Primary endpoint is mortality of patients, and inflammatory cytokines levels were compared between hydroxychloroquine and non-hydroxychloroquine (NHCQ) treatments. MAIN OUTCOMES AND MEASURES: In-hospital death and hospital stay time (day) were obtained, level of inflammatory cytokine (IL-6) was measured and compared between HCQ and NHCQ treatments. RESULTS: The median age of 568 critically ill patients is 68 (57, 76) years old with 37.0% being female. Mortalities are 18.8% (9/48) in HCQ group and 45.8% (238/520) in NHCQ group (p<0.001). The time of hospital stay before patient death is 15 (10-21) days and 8 (4 - 14) days for the HCQ and NHCQ groups, respectively (p<0.05). The level of inflammatory cytokine IL-6 was significantly lowered from 22.2 (8.3-118.9) pg/mL at the beginning of the treatment to 5.2 (3.0-23.4) pg/ml (p<0.05) at the end of the treatment in the HCQ group but there is no change in the NHCQ group. CONCLUSIONS AND RELEVANCE: Hydroxychloroquine treatment is significantly associated with a decreased mortality in critically ill patients with COVID-19 through attenuation of inflammatory cytokine storm. Therefore, hydroxychloroquine should be prescribed for treatment of critically ill COVID-19 patients to save lives. Key Points: Question: Could hydroxychloroquine administration be beneficial in the treatment of critically ill patients with COVID-19? Findings: In this retrospective study, a total of 568 critically ill patients with COVID-19 all received basic therapy and additionally 48 of them received hydroxychloroquine for 7–10 days (200 mg twice per day). Hydroxychloroquine treatment is significantly associated with a decreased mortality in critically ill COVID-19 patients and attenuated inflammatory cytokine IL-6 level. Meaning: Our data suggest that hydroxychloroquine could be used to treat critically ill patients with COVID-19 which may save a lot of lives.

Marfan syndrome (MFS) is a life-threatening autosomal dominant genetic disorder of connective tissue caused by the pathogenic mutation of FBN1. Whole exome sequencing and Sanger sequencing were performed to identify the pathogenic mutation. The transcriptional consequence of the splice-altering mutation was analyzed via minigene assays and reverse-transcription PCR. We identified a novel pathogenic mutation (c.8051+1G>C) in the splice site of exon 64 of the FBN1 gene in an MFS-pedigree. This mutation was confirmed to cause two different truncated transcripts (entire exon 64 skipping; partial exon 64 exclusion). We also systematically summarized previously reported transcriptional studies of pathogenic splice-altering mutations in the FBN1 gene to investigate the clinical and transcriptional consequences. In conclusion, we reported for the first time that a splice-altering mutation in the FBN1 gene leads to two abnormal transcripts simultaneously.

The coronavirus disease (COVID-19) pandemic has continued for 5 years. Sporadic cases continue to occur in different locations. Type 2 diabetes mellitus (T2DM) is associated with a high risk of a poor prognosis in patients with COVID-19. Successful control of blood glucose levels can effectively decrease the risks of severe infections and mortality. However, the effects of different treatments were reported differently and even adversely. This retrospective study included 4,922 patients who have been diagnosed as COVID-19 and T2DM from 138 Hubei hospitals. The clinical characteristics and outcomes were compared and calculated their risk for death using multivariate Cox regression and Kaplan–Meier curves. After adjustment of age, sex, comorbidities, and in-hospital medications, metformin and alpha-glucosidase inhibitor (AGI) use performed lower all-cause mortality (adjusted hazard ratio [HR], 0.41; 95% confidence interval [CI]: 0.24–0.71; p = 0.001 for metformin; 0.53, 0.35–0.80, p = 0.002 for AGIs), while insulin use was associated with increased all-cause mortality (adjusted HR, 2.07, 95% CI, 1.61–2.67, p < 0.001). After propensity score-matched (PSM) analysis, adjusted HRs for insulin, metformin, and AGIs associated with all-cause mortality were 1.32 (95% CI, 1.03–1.81; p = 0.012), 0.48 (95% CI, 0.23–0.83, p = 0.014), and 0.59 (95% CI, 0.35–0.98, p = 0.05). Therefore, metformin and AGIs might be more suitable for patients with COVID-19 and T2DM while insulin might be used with caution.

As next-generation sequencing develops, there are significant associations between glucokinase regulatory protein (GCKR) variants and many diseases, especially metabolic diseases. However, there is a lack of solid descriptions and summaries of how GCKR variants lead to diseases and a lack of successful translations of drugs targeting this molecular variant. We searched literature datasets, mainly including PubMed and Web of Science, with “GCKR” or “GKRP”, “Variants”, “Hypertriglyceridemia”, “NAFLD”, and “Metabolic diseases” as the search terms. Our review firstly introduces the biological function of the GCKR gene and its encoding protein GKRP and then describes the GCKR variants in different diseases, such as hypertriglyceridemia and NAFLD, revealing that GCKR/GKPR is strongly associated with metabolic diseases. GKPR might be a potential target for T2D and other metabolic diseases. One drug for interfering with the GCK-GKRP complex has been developed and has shown its effectiveness in preclinical studies, with some possible side effects. More and more different-structured drugs should be developed to improve side effects, and more clinical trials should be carried out to determine the best intervention window and timing points to improve prognosis. Taken together, these insights show that GCKR/GKRP is significantly associated with many metabolic diseases via its complex metabolism system and is a potential target in many metabolic diseases.

Objective: This study aimed to analyze the global, regional, and national burden of acute glomerulonephritis (AGN) from 1990 to 2021 and project its trends through 2036 using data from the Global Burden of Disease (GBD) study.Methods: Using the GBD 2021 dataset, we evaluated the burden of AGN in terms of incidence, mortality, and disability-adjusted life years (DALYs). Age-standardized rates (ASRs) were calculated, and trends were assessed using the Estimated Annual Percentage Change (EAPC) measure. Decomposition analysis quantified the contributions of population growth, aging, and epidemiological changes. Projections for AGN burden were modeled using the Auto-Regressive Integrated Moving Average (ARIMA) approach.Results: From 1990 to 2021, the global age-standardized incidence rate (ASIR) of AGN declined by 46.09%, and the age-standardized DALY rate decreased by 65.87%. Middle-Socio-Demographic Index (SDI) regions exhibited the highest burden, while high-SDI regions showed increasing trends in mortality and DALY, potentially linked to autoimmune and systemic conditions. Decomposition analysis highlighted the role of epidemiological improvements, balanced by the impacts of population growth and aging. Projections indicate a continued global decline, with a 43.81% reduction in the ASIR and a 62.92% decline in the age-standardized DALY rate by 2036.Conclusion: Despite significant global progress, disparities persist, particularly in low- and middle-income regions. Targeted interventions, enhanced diagnostic capabilities, and strategies that address socioeconomic determinants are essential to achieving a equitable reduction in the AGN burden. This study emphasizes the importance of global and regional strategies in improving AGN outcomes worldwide.