Aims: Studies have indicated that chloroquine (CQ) shows antagonism against COVID-19 in vitro. However, evidence regarding its effects in patients is limited. This study aims to evaluate the efficacy of hydroxychloroquine (HCQ) in the treatment of patients with COVID-19. Main methods: From February 4 to February 28, 2020, 62 patients suffering from COVID-19 were diagnosed and admitted to Renmin Hospital of Wuhan University. All participants were randomized in a parallel-group trial, 31 patients were assigned to receive an additional 5-day HCQ (400 mg/d) treatment, Time to clinical recovery (TTCR), clinical characteristics, and radiological results were assessed at baseline and 5 days after treatment to evaluate the effect of HCQ. Key findings: For the 62 COVID-19 patients, 46.8% (29 of 62) were male and 53.2% (33 of 62) were female, the mean age was 44.7 (15.3) years. No difference in the age and sex distribution between the control group and the HCQ group. But for TTCR, the body temperature recovery time and the cough remission time were significantly shortened in the HCQ treatment group. Besides, a larger proportion of patients with improved pneumonia in the HCQ treatment group (80.6%, 25 of 31) compared with the control group (54.8%, 17 of 31). Notably, all 4 patients progressed to severe illness that occurred in the control group. However, there were 2 patients with mild adverse reactions in the HCQ treatment group. Significance: Among patients with COVID-19, the use of HCQ could significantly shorten TTCR and promote the absorption of pneumonia. Significance: Among patients with COVID-19, the use of HCQ could significantly shorten TTCR and promote the absorption of pneumonia. Trial registration: URL: https://www.clinicaltrials.gov/ . The unique identifier: ChiCTR2000029559.

Key Points: Diabetic kidney disease progression was associated with increased Piezo1 expression in podocytes. Specific Piezo1 deletion alleviated podocyte injury in diabetic models. Piezo1 contributes to podocyte injury through nuclear factor of activated T cell cytoplasmic 1–transient receptor potential cation channel 6 signaling. Background: Diabetic kidney disease (DKD) is characterized by progressive injury to glomerular podocytes due to sustained mechanical stress within the glomerulus. Piezo proteins, acting as cellular mechanosensors, play a pivotal role in mechanotransduction by sensing mechanical forces and regulating intracellular ion flux. This study investigates the role of Piezo1 in the progression of DKD and its mechanistic involvement in podocyte injury. Methods: Podocyte-specific Piezo1 knockout mice were generated using the streptozotocin plus high-fat diet model of DKD. In vitro studies included the use of Piezo1 inhibitors to assess calcium influx, podocyte cytoskeletal rearrangement, and apoptosis under stiff matrix conditions. In addition, NF of activated T-cell cytoplasmic 1 (NFATc1) and transient receptor potential cation channel 6 (TRPC6) signaling pathways were explored to establish their role in Piezo1-mediated podocyte injury. Adeno-associated virus TRPC6 was used to overexpress TRPC6 in podocyte-specific Piezo1 knockout mice to assess the in vivo interaction between Piezo1 and TRPC6. Results: Podocyte-specific deletion of Piezo1 significantly ameliorated the progression of DKD in diabetic mice. Inhibition of Piezo1 reduced calcium influx, cytoskeletal rearrangement, and podocyte apoptosis in vitro . Mechanistically, Piezo1 activation triggered a signaling loop involving NFATc1 and TRPC6, leading to increased calcium influx, perpetuating podocyte injury. TRPC6 overexpression in vivo counteracted the protective effects of Piezo1 deletion, confirming the critical role of the Piezo1/NFATc1/TRPC6 axis in DKD progression. Conclusions: Piezo1 plays a key mechanosensory role in podocyte injury during DKD progression by mediating calcium influx and activating the NFATc1/TRPC6 signaling pathway.

Background. Perirenal fat (PRF) has multiple effects on the kidney through its physical structure and adipocytokine-secreting ability. The present study explored the relationship between PRF thickness and the onset and progression of albuminuria in patients with diabetes. Methods. In the cross-sectional analysis, we screened 959 patients from 8764 subjects with type 2 diabetes mellitus (T2DM) who met the inclusion criteria and measured their perirenal fat thickness (PFT) using color Doppler ultrasound. A group of laboratory indexes were included in the analysis models. In a longitudinal study, a total of 218 patients with a baseline UACR <30 mg/g were included in the follow-up study. Results. In a cross-sectional analysis, patients with diabetes and higher PFT presented with higher albuminuria. Multiple logistic regression analysis indicated that PFT was an independent risk factor for the degree of albuminuria in patients with T2DM (odds ratio = 4.186, 95%CI: 2.290–7.653, < 0.001). In a longitudinal study, 218 albuminuria-free patients with T2DM at the baseline were followed up for a mean of 12.3 months. Based on the cutoff value from the ROC diagnostic test in the cross-sectional study, patients were divided into two groups: higher PFT (H-PFT) and lower PFT (L-PFT). Kaplan–Meier survival curve analysis showed that H-PFT was associated with a higher incidence of albuminuria than L-PFT (log-rank test, χ2 = 4.522, = 0.033). Cox regression analysis showed that PFT was a risk factor for the earlier onset of albuminuria (hazard ratio 2.83, 95% CI: 1.34–4.88, < 0.001). Conclusions. PRF evaluated by color Doppler ultrasound is an easy and reliable tool for predicting the onset and progression of albuminuria in patients with T2DM.

Background: With the emergence of 4 ^rd generation transmission, the prevention and treatment of the novel coronavirus disease 2019 (COVID-19) has entered a new period. We aimed to report several changes in the clinical characteristics at admission of patients with COVID-19. Methods: Clinical records and laboratory results of patients suffering from COVID-19 were retrospectively reviewed and matched with the admission dates to analyze the changes in characteristics at the onset of illness. Results: Of the 89 affected patients, 31 [34.8%] patients were admitted from January 16 to 22, and 58 [65.2%] were admitted from January 23 to 29. Patients were admitted with more systemic symptoms, such as fever (21 [67.7%] of 31), fatigue (13 [41.9%] of 31), and myalgia (7 [22.6%] of 31), before January 23. More patients (10 [32.3%] of 31) admitted before January 23 had a small amount of sputum production compared with a smaller proportion (4 [6.9%] of 58) of the patients admitted after January 23. Other symptoms, such as cough, nausea, diarrhea, and chest tightness, were not significantly different between the two groups. In addition, the group admitted before January 23 had a larger proportion of patients with reduced lymphocyte (13 [54.2%] of 24), CD3 (11 [54.4%] of 21), and CD8 (9 [42.9%] of 21) counts and elevated serum amyloid A (SAA, 18 [75%] of 24). Conclusions: The initial symptoms of recently infected patients seem more insidious, indicating that the new coronavirus may gradually evolve into a virus similar to influenza and latent in asymptomatic carriers for a long time. Summary: Compared with the cases admitted earlier, more hidden initial symptoms and improved immune system disorders appeared in COVID-19 patients infected recently.