Objective To investigate the relationship and mechanism between the serum level of high mobility group box protein-1(HMGB1)and the mortality rate in patients with sepsis.Methods The serum levels of HMGB1,superoxide dismutase(SOD)and malondialdehyde(MDA)in 48 patients with sepsis were determined.The clinical outcomes in those patients were recorded and anlyzed.Results After the onset of sepsis,the serum HMGB1 levels of both death group and survival group were increased gradually and peaked at 72h after the onset of the disease.The semm HMGB1 levels of death group were much higher than those of survival group except at 24h(t=6.07,6.20,24.43,all P＜0.05).The activity of serum SOD of death group was markedly lower than that of survival group at 12h,24h,48h and 72h(t=10.24,20.61,11.67,33.33,all P＜0.05),and the level of serum MDA of death group was significantly higher than those of survival group at all time points(t=26.06,22.17,23.86,9.49,5.95,all P＜0.05).There was a significantly positive correlation between the serum HMGB1 and MDA level.Conlusioa The increase in serum HMGB1 level may be the important reasoll for the increased mortality rate in patients with sepsis;Oxidant/antioxidant imbalance may be olle reason for the increase in serum HMGB1 level.

Objective:To analyze the correlation betWeen clinical features at admission and recent prognostic outcome in patients With acute myocardial infarction (AMI).Methods:The data of 108 patients admitted because of primary AMI Were retrospectively analyzed.According to occurrence of major adverse cardiovascular events (MACE)or not after discharge,they Were divided into event group (n=61)and non-event group (n=47).Clinical features such as Gender,age etc.of tWo groups Were collected,analyzed and compared.After one-year folloW-up,correlations betWeen clinical feature indexes and MACE incidence Were analyzed.Results:Compared With non-event group, there Were significant increase in mean age,mean arterial pressure (MAP),left ventricular end-diastolic dimension (LVEDd),percentage of> Killip class 2,Grace score and multi-vessel coronary disease,and significant decrease in left ventricular ejection fraction (LVEF)in event group,P<0.05~<0.01. Single factor correlation analysis indi-cated that age,MAP,LVEF,percentage of > Killip class 2,Grace score and multi-vessel coronary disease rate Were correlated With MACE incidence rate (P<0.05~<0.01);multi-factor Logistic regression analysis indicated that age (OR=0.827),LVEF (OR=0.624),Grace score (OR=0.589)and multi-vessel coronary disease rate (OR=0.461)Were risk factors for MACE in AMI patients,P<0.05 all.Conclusion:Advanced age,loW left ven-tricular ejection fraction,higher Grace score and more multi-vessel coronary disease are high risk factors for recent occurrence of major adverse cardiovascular events in patients With acute myocardial infarction.

Objective To evaluate the clinical efficacy of early diagnosis by contrast-enhanced ultrasound (CEUS) combined with mesenchymal stem cell (MSC) therapy in the treatment of biliary ischemia after liver transplantation. Methods Clinical data of 9 recipients presenting with biliary ischemia detected by CEUS within 4 weeks after liver transplantation and diagnosed with non-anastomotic biliary stricture (NAS) within postoperative 1 year were retrospectively analyzed. In the conventional treatment group, 4 recipients were treated with conventional treatment including liver protection, cholagogic therapy and interventional therapy. In MSC treatment group, 5 recipients received intravenous infusion of MSC at 1, 2, 4, 8, 12 and 16 weeks after biliary ischemia detected by CEUS on the basis of conventional therapy. The interventional treatment and clinical prognosis within 1 year after liver transplantation were analyzed between two groups. Results Two recipients in the MSC treatment group required interventional therapy, which was initially given at 7-9 months after liver transplantation for 1-2 times. All recipients in the conventional treatment group required interventional therapy, which was initially delivered at postoperative 1-3 months for 2-6 times, earlier than that in the MSC treatment group. Within 1 year following liver transplantation, diffuse bile duct injury occurred in 2 recipients in MSC treatment group, and no graft dysfunction was observed. In the conventional treatment group, all recipients developed diffuse bile duct injury, and 2 recipients presented with graft dysfunction. Conclusions Early diagnosis of biliary ischemia after liver transplantation by CEUS combined with MSC therapy may delay and reduce the requirement of interventional therapy for NAS, and also improve clinical prognosis of the recipients.

Objective:To observe and investigate the related factors that might affect clinical features of familial exudative vitreoretinopaty (FEVR) patients.Methods:A retrospective chart study. From January 2012 and December 2021, 42 patients with 84 eyes with a diagnosis of FEVR from Department of Ophthalmology, Peking University People's Hospital were included in the study. The patients came from 42 separate families. There were 31 males and 11 females, with an average age of first diagnosis was 16.6±33.7 months. There were 21 patients referred from other hospitals for the fundus disease found in eye screening after birth, 21 patients were first seen in our hospital. There were 4 and 38 premature and full-term infants, respectively. Two patients with a positive family history of FEVR. All patients are FEVR stages 1-5. The wide-angle digital pediatric retinal imaging system after general anesthesia for fluorescein fundus angiography (FFA) examination were performed for patients aged <5 years. If patients ≥ 5 years old, routine FFA examination was performed. Sixty-eight first-degree relatives from 28 families undergo routine fundus examinations and FFA examination. Genetic examination was performed for 26 families, including 26 probands and 57 first-degree relatives. Genetic examination were performed on gene the coreceptor of low density lipoprotein receptor-associated protein 5 ( LRP5), Wnt receptor coiled protein 4 ( FZD4), Norrie disease ( NDP), tetraporin 12 ( TSPAN12), catenin β1 ( CTNNB1) genes known to be involved in FEVR. The clinical features and the genotype of FEVR were observed in relation to the clinical phenotype. Results:Among the 42 patients, 13 patients were first observed by strabismus and nystagmus, with the median age of 12 months. Eight patients were complained non-chasing or vision-related symptoms. Among the 84 eyes, FEVR stage 1 or 2, 3 or 4, and 5 were 50 (59.5%, 50/84), 31 (36.9%, 31/84), and 3 (3.6%, 3/84) eyes, respectively. Among the 23 patients who were > 3 months at first diagnosis, 16 patients had at least one eye severer than stage 3 (69.6%, 16/23). Of the 68 first-degree relatives, 22 (32.4%, 22/68) had FEVR-like changes. Among the 26 families that underwent genetic detection, 13 families (50%, 13/26) of 16 variants of FEVR-related genes were detected, of which 10 mutations of LRP5 gene were the most common. There were 10 families with single gene mutations, including 6, 2 and 2 families of LRP5, FZD4 and CTNNB1 genes, respectively. One family of LRP5 gene mutations were compound heterozygous mutations, 1 family with LRP5 gene mutaition combined with NDP gene mutation, and 1 family with LRP5 and TSPAN12 gene mutation. Among the proband with FEVR pathogenic genes, 6 cases with similiar stage of both eyes, and 7 cases with inconsistent disease stages, and there was no obvious correlation between gene mutations and clinical phenotypes. Conclusion:In addition to the age of first diagnosis, no exact factors affecting the clinical manifestations of FEVR are found, and the association between clinical phenotypic and genetic heterogeneity still needs to be further explored.

Despite the continuous improvement and development of modern cataract surgery technology, posterior capsule opacification (PCO) is still the common long-term complication causing secondary visual acuity decline after cataract surgery.Previous studies have shown that the occurrence of PCO is closely related to the proliferation, migration, epithelial-mesenchymal transition (EMT) and myofibroblast fibrosis of lens epithelial cells in the anterior capsule and lens equator.In terms of pathogenesis, recent research focuses on the role of cytokines, especially various growth factors.Vascular endothelial growth factor (VEGF) is a kind of growth factor that can promote vascular endothelial cell proliferation and migration, extracellular matrix degeneration and angiogenesis.In addition, there is increasing evidence showing that VEGF plays an important role in fibrosis, inflammation, neuroprotection and other aspects.In recent years, VEGF has been found to promote PCO formation directly or cooperatively with transforming growth factor-β2.Based on the function of VEGF and the relationship between VEGF and EMT, this paper mainly reviewed the advances in the role of VEGF in the eye and the pathogenesis of posterior capsule opacification.

Werner syndrome (WS) is a premature aging disorder that mainly affects tissues derived from mesoderm. We have recently developed a novel human WS model using WRN-deficient human mesenchymal stem cells (MSCs). This model recapitulates many phenotypic features of WS. Based on a screen of a number of chemicals, here we found that Vitamin C exerts most efficient rescue for many features in premature aging as shown in WRN-deficient MSCs, including cell growth arrest, increased reactive oxygen species levels, telomere attrition, excessive secretion of inflammatory factors, as well as disorganization of nuclear lamina and heterochromatin. Moreover, Vitamin C restores in vivo viability of MSCs in a mouse model. RNA sequencing analysis indicates that Vitamin C alters the expression of a series of genes involved in chromatin condensation, cell cycle regulation, DNA replication, and DNA damage repair pathways in WRN-deficient MSCs. Our results identify Vitamin C as a rejuvenating factor for WS MSCs, which holds the potential of being applied as a novel type of treatment of WS.
Animals ; Ascorbic Acid ; pharmacology ; Cell Cycle Checkpoints ; drug effects ; Cell Line ; Cellular Senescence ; drug effects ; DNA Damage ; DNA Repair ; drug effects ; DNA Replication ; drug effects ; Disease Models, Animal ; Heterochromatin ; metabolism ; pathology ; Humans ; Mesenchymal Stem Cells ; metabolism ; pathology ; Mice ; Nuclear Lamina ; metabolism ; pathology ; Reactive Oxygen Species ; metabolism ; Telomere Homeostasis ; drug effects ; Werner Syndrome ; drug therapy ; genetics ; metabolism