A 3-month-old neonatal rhesus macaque HFMD model caused by coxsackievirus B1 infection and viral tissue tropism.

Coxsackievirus B1 (CVB1), an enterovirus with multiple clinical presentations, has been associated with potential long-term consequences, including hand, foot, and mouth disease (HFMD), in some patients. However, the related animal models, transmission dynamics, and long-term tissue tropism of CVB1 have not been systematically characterized. In this study, we established a model of CVB1 respiratory infection in rhesus macaques and evaluated the clinical symptoms, viral load, and immune levels during the acute phase (0-14 days) and long-term recovery phase (15-30 days). We also investigated the distribution, viral clearance, and pathology during the long-term recovery period using 35 postmortem rhesus macaque tissue samples collected at 30 days postinfection (d.p.i.). The results showed that the infected rhesus macaques were susceptible to CVB1 and exhibited HFMD symptoms, viral clearance, altered cytokine levels, and the presence of neutralizing antibodies. Autopsy revealed positive viral loads in the heart, spleen, pancreas, soft palate, and olfactory bulb tissues. HE staining demonstrated pathological damage to the liver, spleen, lung, soft palate, and tracheal epithelium. At 30 d.p.i., viral antigens were detected in visceral, immune, respiratory, and muscle tissues but not in intestinal or neural tissues. Brain tissue examination revealed viral meningitis-like changes, and CVB1 antigen expression was detected in occipital, pontine, cerebellar, and spinal cord tissues at 30 d.p.i. This study provides the first insights into CVB1 pathogenesis in a nonhuman primate model of HFMD and confirms that CVB1 exhibits tissue tropism following long-term infection.

The effects of sacubitril/valsartan on heart failure with preserved ejection fraction: a meta-analysis.

BACKGROUND: Compared with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, Sacubitril/Valsartan has been reported to have superior results. However, the effects of sacubitril/valsartan on heart failure with preserved ejection fraction (HFpEF) are still in dispute. OBJECTIVES: This study aims to evaluate the effects of sacubitril/valsartan on the treatment of HFpEF patients. METHODS: PubMed, Embase, Web of Science, Cochrane Library, and Clinicaltrials.gov were used to search for randomised controlled trials of sacubitril/valsartan in HFpEF patients from inception to 7 December 2020. RESULTS: Four studies, with a total of 7739 participants, met the inclusion criteria. The present meta-analysis results showed that compared with the control group, sacubitril/valsartan reduced the hospitalisation rate of HF in HFpEF patients [Risk Ratio(RR): 0.85; 95% confidence interval (CI): 0.79-0.93; p = 0.0002). Regarding all-cause mortality, cardiovascular mortality, and the improvement in NYHA class, sacubitril/valsartan did not show apparent advantages. Although sacubitril/valsartan was linked to increasing the risk of symptomatic hypotension (RR: 1.44; 95% CI: 1.25-1.66; p﹤0.00001), there was no evidence supporting the incidence of renal function worsening and hyperkalemia. CONCLUSION: Our study shows that compared with valsartan or individualised medical therapy (IMT), there were not different between the two groups except for the hospitalisation rate which was favoured by Sacubitril/Valsartan treatment group for HFpEF patients.

Clinical efficacy and safety of mesenchymal stem cell transplantation for osteoarthritis treatment: A meta-analysis.

PURPOSE: The aim of this study was to evaluate the therapeutic efficacy and safety of mesenchymal stem cells (MSCs) for the treatment of patients with knee osteoarthritis (OA). MATERIALS: We performed a meta-analysis of relevant published clinical studies. An electronic search was conducted for randomized controlled trials (RCTs) of MSC-based therapy in knee OA. The visual analogue scale (VAS), International Knee Documentation Committee (IKDC) form, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lequesne algofunctional indices (Lequesne), Lysholm knee scale (Lysholm), Tegner activity scale (Tegner) and adverse events (AEs) were evaluated. RESULTS: Eleven eligible trials with 582 knee OA patients were included in the present meta-analysis. We demonstrated that MSC treatment could significantly decrease VAS and increase IKDC scoresafter a 24-month follow-up compared with controls (P<0.05). MSC therapy also showed significant decreases in WOMAC and Lequesne scores after the 12-month follow-up (P<0.01). Analysis of Lysholm (24-month) and Tegner (12- and 24-month) scores also demonstrated favorable results for MSC treatment (P<0.05). CONCLUSION: Overall, MSC transplantation treatment was shown to be safe and has great potential as an efficacious clinical therapy for patients with knee OA.

Intercellular adhesion molecule-1 E469K gene polymorphism and coronary artery disease in the Chinese population: a meta-analysis involving 3065 subjects.

BACKGROUND: The intercellular adhesion molecule-1 (ICAM-1) E469K gene polymorphism has been implicated in increased coronary artery disease (CAD) susceptibility, but the individual study results are still controversial. HYPOTHESIS: The ICAM-1 E469K gene polymorphism may be associated with CAD risk. METHODS: The current meta-analysis involving 3065 subjects and 11 separate studies was conducted to explore the relationship between the ICAM-1 E469K gene polymorphism and CAD in the Chinese population. The pooled odds ratio (ORs) for the distribution of K allele frequency of ICAM-1 E469K gene and its corresponding 95% confidence interval (CI) was assessed by random effect model. RESULTS: The distribution of the K allele frequency was 0.67 for the CAD group and 0.60 for the control group. The pooled OR for the distribution of the K allele frequency of the ICAM-1 E469K gene was 1.32 (95% CI, 1.02-1.72; P(heterogeneity) < 0.00001; inconsistency index I(2) = 81.8%). The association between the ICAM-1 E469K gene polymorphism and CAD in the Chinese population was significant (P = 0.04). CONCLUSIONS: In the Chinese population, the distribution of the K allele frequency of the ICAM-1 E469K gene was indicated to be associated with CAD risk. The K allele of the ICAM-1 E469K gene might predispose to the CAD susceptibility.