Serum homocysteine concentration as a marker for advanced diabetic nephropathy in a cohort of elderly patients.

BACKGROUND: Hyperhomocysteinemia has been linked with chronic kidney disease (CKD). The present study investigated whether homocysteine (Hcy) serum levels might serve as a marker for the advancement of diabetic nephropathy (DN). METHODS: Clinical and laboratory indicators including Hcy, vitamin D (VD), urine protein, estimated glomerular filtration rate (eGFR) and the urinary protein/creatinine ratio in subjects > 65 years with DN (n = 1,845), prediabetes (n = 1,180) and in a non-diabetes (control) group (n = 28,720) were analyzed. RESULTS: DN patients had elevated Hcy concentrations, decreased VD and higher urinary protein levels, a reduced eGFR and a higher urinary protein/creatinine ratio compared with prediabetic and control subjects. After correcting for urinary protein quantitation, multivariate analysis revealed that both the Hcy concentration (P < 0.010) and urinary protein/creatinine ratio (P < 0.001) were risk factors, while the VD2 + VD3 serum concentration (P < 0.001) was a protective factor for DN. Moreover, Hcy > 12 µmol/L was a cut-off value for predicting advanced DN. CONCLUSION: Hcy serum concentration is a potential marker for the advancement of CKD in DN but not prediabetes patients.

Case report of pyogenic meningitis after tooth extraction in an elderly diabetic patient.

INTRODUCTION: Among elderly diabetic patients with comorbid conditions, the clinical characteristics of suppurative meningitis may not be typical, which is easy to cause misdiagnosis and delayed treatment. CASE PRESENTATION: In this report, we described the case of a 65-year-old elderly diabetic male who developed purulent meningitis after tooth extraction. The patient developed repeated infections (fever, headache and other symptoms) and was diagnosed with pyogenic meningitis by combining clinical manifestations and cerebrospinal fluid testing. The patient was treated with intracranial pressure reduction, nutritional support and anti-infection drugs, and recovered and was discharged after 15 days. CONCLUSIONS: The atypical clinical presentation and insidious onset of the disease in this patient could easily lead to missed diagnosis and misdiagnosis. We emphasize that we should be vigilant with purulent meningitis and active treatment and prevention should be implemented in this subgroup of patients. During treatment, active anti-infection and nutritional support should be provided on the basis of blood glucose control.

Clinical progression and outcomes of 260 patients with severe COVID-19: an observational study.

This paper presents the results of an observational, prospective study of the clinical progression and outcomes of patients with severe COVID-19. Overall, 260 patients with severe COVID-19 were included. The median age of the patients was 61 years (IQR 42.0-73.0), and 119 (45.8%) patients had one or more medical comorbidities. The median time from initial onset of symptoms to hospital admission was 8 days (IQR 6.0-11.0). Varying degrees of abnormalities in blood biochemical results were detected in most patients. All patients received supportive therapy and antiviral treatment. All patients were administered empirical antibiotic treatment with a median time of 5 days (IQR 3-7). Mechanical ventilation was required in accordance with respiratory conditions. At the data cutoff, 183 (70.4%) patients had been discharged, and 17 (6.5%) patients had been transferred to the intensive care unit (ICU). Twenty-five (9.6%) patients had died, and 35 (13.5%) patients were still in the hospital. During follow-up, 7 patients with fever were negative for SARS-Cov-2 antigens upon retest. The implications of the results are discussed for clinical features and the management of patients with severe COVID-19.

Neurocognitive Outcomes in Adult Quasi -Moyamoya Disease: A Prospective Analysis of Consecutive Cases.

BACKGROUND: This study aimed to evaluate and compare the neurocognitive outcomes of adult quasi-moyamoya disease (quasi-MMD) patients with autoimmune diseases (AIDs) to help better manage these patients. METHODS: We performed a structured battery of neurocognitive tests to analyze and compare the neurocognitive outcomes of adult quasi-MMD patients with AID in our hospital from October 2000 to September 2015. RESULTS: Overall, 27.3% of the neuropsychological test comparisons indicated a significant improvement in cognition, and a significant decline was found in 6%. In 47.4% of comparisons, the observed difference did significantly change the reliable change indices (RCI) before and after anti-autoimmune treatment. We found that the number of patients showing significant improvements, and no change in cognitive outcomes did differ between quasi-MMD and MMD (31.8% vs 14.9% with p = 0.006 and 50.0% vs 66.8% with p = 0.031, respectively; Chi-squared test). The incidence of cognitive decline in quasi-MMD patients (18.2%) did not significantly differ from that in MMD patients (18.3%) (p = 0.982). After adjusting for covariates, including sex, age, type 2 diabetes mellitus, risk factors, other comorbidities, and AID, multiple logistic regression analysis suggested that AID was more likely to aggravate the neurocognitive outcome of quasi-MMD patients (p = 0.042, odds ratio (OR) 6.78, 95% confidence interval (CI) 1.31-62.71). CONCLUSIONS: AID was more likely to aggravate the neurocognitive outcome of quasi-MMD patients, and anti-autoimmune treatment could improve long-term neurocognitive outcomes. These findings indicated that AID seemed to be an independent risk factor for the pathological and physiological mechanisms of quasi-MMD.

Relationship of gender and age on thyroid hormone parameters in a large Chinese population

ABSTRACT Objective This study aimed to present the impact of age and gender on thyroid hormone levels in a large Chinese population with sufficient iodine intake. Subjects and methods A total of 83643 individuals were included and were stratified by age and gender. The median, 2.5th and 97.5th of thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4) and FT3/FT4 ratio were calculated for both genders for every decade from 18 to over 80 years. TSH, FT3, FT4, FT3/FT4 distribution in each age group was evaluated for females and males using smoothing splines in the generalized additive models (GAM). TSH concentrations were compared in the different age groups in gender. Results In the over 80s age group, the TSH level (median: 2.57 mIU/L, 2.5th-97.5th: 0.86-7.56 mIU/L) was significantly higher than other age groups, irrespective to gender (P<0.001). Females had a higher TSH value than males in all age groups (P<0.001). Results of the smoothing curves showed that TSH increased with age, FT3 concentration was higher in males than in females and the tendency of the FT3/FT4 ratio was basically similar to that of FT3. TSH concentration in the 50s age group (median 2.48 mIU/L for females versus 2.00 mIU/L for males) was significantly higher than that in the 30s age group (median 2.18 mIU/L for females versus median 1.85 mIU/L for males). Conclusions In accord with increasing TSH values during aging, females and older adults have lower FT3 values and lower FT3/FT4 ratios, while the FT4 values remain stable.

Relationship of gender and age on thyroid hormone parameters in a large Chinese population.

Objective This study aimed to present the impact of age and gender on thyroid hormone levels in a large Chinese population with sufficient iodine intake. Subjects and methods A total of 83643 individuals were included and were stratified by age and gender. The median, 2.5th and 97.5th of thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4) and FT3/FT4 ratio were calculated for both genders for every decade from 18 to over 80 years. TSH, FT3, FT4, FT3/FT4 distribution in each age group was evaluated for females and males using smoothing splines in the generalized additive models (GAM). TSH concentrations were compared in the different age groups in gender. Results In the over 80s age group, the TSH level (median: 2.57 mIU/L, 2.5th-97.5th: 0.86-7.56 mIU/L) was significantly higher than other age groups, irrespective to gender (P<0.001). Females had a higher TSH value than males in all age groups (P<0.001). Results of the smoothing curves showed that TSH increased with age, FT3 concentration was higher in males than in females and the tendency of the FT3/FT4 ratio was basically similar to that of FT3. TSH concentration in the 50s age group (median 2.48 mIU/L for females versus 2.00 mIU/L for males) was significantly higher than that in the 30s age group (median 2.18 mIU/L for females versus median 1.85 mIU/L for males). Conclusions In accord with increasing TSH values during aging, females and older adults have lower FT3 values and lower FT3/FT4 ratios, while the FT4 values remain stable.

PIWIL1 suppresses circadian rhythms through GSK3ß-induced phosphorylation and degradation of CLOCK and BMAL1 in cancer cells.

Circadian rhythms are maintained by series of circadian clock proteins, and post-translation modifications of clock proteins significantly contribute to regulating circadian clock. However, the underlying upstream mechanism of circadian genes that are responsible for circadian rhythms in cancer cells remains unknown. PIWIL1 participates in many physiological processes and current discoveries have shown that PIWIL1 is involved in tumorigenesis in various cancers. Here we report that PIWIL1 can suppress circadian rhythms in cancer cells. Mechanistically, by promoting SRC interacting with PI3K, PIWIL1 can activate PI3K-AKT signalling pathway to phosphorylate and inactivate GSK3ß, repressing GSK3ß-induced phosphorylation and ubiquitination of CLOCK and BMAL1. Simultaneously, together with CLOCK/BMAL1 complex, PIWIL1 can bind with E-BOX region to suppress transcriptional activities of clock-controlled genes promoters. Collectively, our findings first demonstrate that PIWIL1 negatively regulates circadian rhythms via two pathways, providing molecular connection between dysfunction of circadian rhythms and tumorigenesis.

[Mutation analysis of a family affected with isolated proteinuria].

OBJECTIVE: To analyze the clinical characteristics and genetic features of a family affected with isolated proteinuria. METHODS: Clinical data of the family was collected. Mutations of 191 renal disease-related genes in the proband were screened with next generation sequencing (NGS). Sanger sequencing was used to verify suspected mutations in his family members and 100 healthy controls. The impact of the mutation was predicted with online software SIFT. Frequency of the mutation was searched in databases including 1000 Genomic Project, ESP and ExAC. RESULTS: NGS and Sanger sequencing showed that the proband harbored compound heterozygous mutations of ADCK4 gene including c.748C>G (p.Asp250His) and c.1041G>T (p.Cys347*), which were respectively inherited from his mother and father whom were both non-symptomatic. CONCLUSION: The proband may have ADCK4-associated glomerulopathy due to the compound heterozygous mutations of the ADCK4 gene.

Vitamin D status is associated with 1,5-anhydro-d-glucitol status in patients with type 2 diabetes mellitus.

Serum 1,5-anhydro-d-glucitol (1,5-AG) concentrations are short-term hyperglycemia indicators and were used to estimate the effects of serum vitamin D concentrations on glycemic control in patients with type 2 diabetes mellitus (T2DM). Serum concentrations of 1,5-AG, 25-hydroxyvitamin D2 (25-OH-D2), and 25-hydroxyvitamin D3 (25-OH-D3) from 11 026 patients with T2DM, hospitalized in the Department of Endocrinology, Shanghai Central Hospital of Xuhui District, from January 2012 to June 2015, were retrospectively analyzed. Correlation analyses revealed correlations between 1,5-AG and 25-OH-D3 (r = 0.05, P < 0.001), age (r = 0.05, P < 0.001), and 25-OH-D2 + 25-OH-D3 (25-OH-D2/D3) (r = 0.05, P < 0.001). Linear regression analyses revealed associations between 1,5-AG and 25-OH-D2/D3 (adjusted R2 = 0.003) as well as 25-OH-D3 (adjusted R2 = 0.002). In males with 1,5-AG levels ≤11.55 mg/L, serum concentrations of 25-OH-D2 (P < 0.001) and 25-OH-D3 (P = 0.001) were significantly lower than those in diabetic males with 1,5-AG levels >11.55 mg/L. Serum concentrations of 25-OH-D2/D3 in patients with T2DM were associated with 1,5-AG retention, suggesting involvement in glycemic control.