查看更多>>摘要：We aimed to investigate the safety and efficacy of nirmatrelvir/ritonavir(Paxlovid)therapy for hemodialysis-dependent patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Thirteen hemodialysis patients infected with the Omicron variant of SARS-CoV-2 from April 3 to May 30,2022,were recruited.Laboratory parameters and chest CT(computed tomography)imaging were analyzed.The treatment group included six patients who received 150 mg/100 mg of Paxlovid orally once daily for 5 days,whereas the control group included seven patients who received basic treatment.No serious adverse reactions or safety events were recorded.Four control patients progressed to moderate disease,and none in the treatment group showed progression of chest CT findings(P＜0.05).Paxlovid therapy tended toward early viral clearance and low viral load on Day 8.Moreover,83.3％ of the patients in the treatment group and 57.1％ of the patients in the control group turned negative within 22 days.In the Paxlovid treatment group,we found significantly increased levels of lymphocytes(P=0.03)and eosinophils(P=0.02)and decreased levels of D-dimer on Day 8 compared with those on Day 1.Paxlovid therapy showed a potential therapeutic effect with good tolerance in hemodialysis patients.The optimal dose and effectiveness evaluation must be further investigated in a largeer cohort.
查看更多>>摘要：Lipin proteins including Lipin 1-3 act as transcriptional co-activators and phosphatidic acid phosphohydrolase enzymes,which play crucial roles in lipid metabolism.However,little is known about the function of Lipin3 in triglyceride(TG)metabolism.Here,we identified a novel mutation(NM_001301860:p.1835A＞T/p.D612V)of Lipin3 in a large family with hypertriglyceridemia(HTG)and obesity through whole-exome sequencing and Sanger sequencing.Functional studies revealed that the novel variant altered the half-life and stability of the Lipin3 protein.Hence,we generated Lipin3 heterozygous knockout(Lipin3-heKO)mice and cultured primary hepatocytes to explore the pathophysiological roles of Lipin3 in TG metabolism.We found that Lipin3-heKO mice exhibited obvious obesity,HTG,and non-alcoholic fatty liver disorder.Mechanistic study demonstrated that the haploinsufficiency of Lipin3 in primary hepatocytes may induce the overexpression and abnormal distribution of Lipin1 in cytosol and nucleoplasm.The increased expression of Lipin1 in cytosol may contribute to TG anabolism,and the decreased Lipin1 in nucleoplasm can reduce PGC1α,further leading to mitochondrial dysfunction and reduced TG catabolism.Our study suggested that Lipin3 was a novel disease-causing gene inducing obesity and HTG.We also established a relationship between Lipin3 and mitochondrial dysfunction.
查看更多>>摘要：Malnutrition in early life increases the risk of osteoporosis,but the association of early-life undernutrition combined with adulthood obesity patterns with low-energy fracture remains unknown.This study included 5323 community-dwelling subjects aged ≥40 years from China.Early-life famine exposure was identified based on the participants'birth dates.General obesity was assessed using the body mass index(BMI),and abdominal obesity was evaluated with the waist-to-hip ratio(WHR).Low-energy fracture was defined as fracture occurring after the age of 40 typically caused by falls from standing height or lower.Compared to the nonexposed group,the group with fetal,childhood,and adolescence famine exposure was associated with an increased risk of fracture in women with odds ratios(ORs)and 95％confidence intervals(CIs)of 3.55(1.57-8.05),3.90(1.57-9.71),and 3.53(1.05-11.88),respectively,but not in men.Significant interactions were observed between fetal famine exposure and general obesity with fracture among women(P for interaction=0.0008).Furthermore,compared with the groups with normal BMI and WHR,the group of women who underwent fetal famine exposure and had both general and abdominal obesity had the highest risk of fracture(OR,95％CI:3.32,1.17-9.40).These results indicate that early-life famine exposure interacts with adulthood general obesity and significantly increases the risk of low-energy fracture later in life in women.
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