Mesangial cell proliferation is an early pathological indicator of diabetic nephropathy (DN). Growing evidence highlights the pivotal role of paired-related homeobox 1 (Prrx1), a key regulator of cellular proliferation and tissue differentiation, in various disease pathogenesis. Notably, Prrx1 is highly expressed in mesangial cells under DN conditions. Both in vitro and in vivo studies have demonstrated that Prrx1 overexpression promotes mesangial cell proliferation and contributes to renal fibrosis in db/m mice. Conversely, Prrx1 knockdown markedly suppresses hyperglycemia-induced mesangial cell proliferation and mitigates renal fibrosis in db/db mice. Mechanistically, Prrx1 directly interacts with the Yes-associated protein 1 (YAP) promoter, leading to the upregulation of YAP expression. This upregulation promotes mesangial cell proliferation and exacerbates renal fibrosis. These findings emphasize the crucial role of Prrx1 upregulation in high glucose-induced mesangial cell proliferation, ultimately leading to renal fibrosis in DN. Therefore, targeting Prrx1 to downregulate its expression presents a promising therapeutic strategy for treating renal fibrosis associated with DN.

Butyrylation(Kbu),as an important post-translational modification(PTM)of proteins,precisely regu-lates various biological behaviors of tumor cells by modulating the structure and function of proteins.Abnormal bu-tyrylation promotes tumor cell proliferation and migration by regulating protein stability,enzyme activity,cell signa-ling pathways,chromatin structure and gene expression,and further participates in tumor occurrence and develop-ment.This review focuses on the role of butyrylation modification in the occurrence and development of various hu-man tumors,aiming to summarize the research progress of butyrylation modification in the field of tumors,and to provide new directions for tumor treatment through the intervention strategies of butyrylation modification.

Cirrhotic portal hypertension (CPH) is a manifestation of decompensated liver cirrhosis, with ascites, portal collateral circulation formation, hypersplenism and splenomegaly as the typical clinical symptoms. In recent years, the incidence of CPH has been increasing year by year, and the treatment of CPH has gradually become a hot issue in medical research. In order to further explore the diagnosis and treatment scheme of CPH. We briefly describe the pathophysiological mechanism and diagnosis of CPH, and the current situation of CPH treatment and the new progress of internal and external treatment were reviewed.

Anesthesia, General/adverse effects* ; Hypertension/etiology* ; Humans

Objective:To study development problems and countermeasures of the health emergency management system in a city based on the grounded theory, for references on the construction of a new round of urban health emergency management system.Methods:From June 2020 to April 2021, 61 health emergency management personnel were selected using the objective sampling method from the municipal health commission and disease prevention and control center of a city, and from 11 district health bureaus and disease prevention and control centers, for semi-structured interviews. Grounded theory method was used to analyze the interview data.Results:288 concepts, 79 initial categories, 15 sub-categories, and 5 main categories were extracted from the interview materials. The urban health emergency management system was affected by a variety of constraints such as the weak construction of public health talent team, non-standard plan management, and limited information sharing. There was a fragmentation dilemma in structure and mechanism. It was necessary to strengthen policy support and emergency resource allocation to promote the reconstruction of the health emergency response system. Among them, policy support and emergency resource allocation were prerequisites, and the remodeling of health emergency system was the core process.Conclusions:There were problems such as insufficient resource supply and weak plan management in the construction of the city′s health emergency management system. We should establish a high-level driven policy system, strengthen the resource allocation of peacetime and wartime, and reshape the system and mechanism of coordination and integration, so as to continue to promote the continuous development of the health emergency management system.

Helicobacter pylori (Hp) is a Gram-negative bacterium selectively colonized in gastric mucosa, and is one of the main factors inducing chronic gastritis and even gastric cancer. Recent studies have shown that Hp infection induces various stress responses, including oxidative stress, nitrosative stress and endoplasmic reticulum stress. Hp can stimulate neutrophils, macrophages and gastric epithelial cells to express reactive oxygen species and reactive nitrogen species, resulting in excessive accumulation of reactive oxygen species and reactive nitrogen species, aggravating inflammation and damage to gastric mucosa. Such long-term inflammation and oxidative stress may increase the risk of cancer. In addition, Hp induced endoplasmic reticulum stress plays an important role in the early stages of precancerous lesion formation. This article reviewed the research progress of role of stress response induced by Hp infection in gastric mucosal diseases.

Adult ; Female ; Humans ; Liver ; pathology ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease ; pathology ; Obesity ; pathology ; Young Adult

OBJECTIVETo develop and evaluate a mouse model of nonalcoholic steatohepatitis (NASH) induced by a high-fat and high-fructose (HFHFr) diet.

METHODSSix-week-old C3H mice were randomly divided into groups for HFHFr diet experimental modeling, high fat-only (HF) diet controls, high fructose-only (HFr) diet controls, and standard chow (SC) diet controls. The standard HFHFr diet was modified so that it consisted of 76.5% standard chow, 12% lard, 1% cholesterol, 5% egg yolk powder, 5% whole milk powder, and 0.5% sodium cholate, along with 20% fructose drinking water. At the end of experimental weeks 4, 8, and 16, measurements were taken for the NASH-related parameters of body mass, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), lipid profile, and wet liver weight (upon sacrifice). In addition, histological changes in the liver were evaluated by hematoxylin-eosin (HE) and oil red O staining. The significance of differences between groups was assessed by statistical analysis, using the

METHODSof t-test, Wilcoxon rank sum test, x2 test, F test or Fisher's test as appropriate.

RESULTSAs compared to the mice in the SC group at the corresponding time points, the mice in the HFHFr and HF groups showed significantly higher body mass and wet liver weight, as well as more extensive and robust lipid disposition in hepatic tissues as evidenced by oil red O staining. However, HE staining indicated that the HFHFr and HF groups had different degrees of macrosteatosis accompanied with intralobular inflammatory foci, with the former showing more remarkable NASH-related histological changes. Analysis at the end of week 16 showed that about 80% of the mice in the HFHFr group had developed NASH [nonalcoholic fatty liver disease (NAFLD) activity score (NAS): less than 5]. The levels of low-and high-density lipoprotein (LDL and HDL) cholesterol, as well as the levels of ALT and AST, were increased from the end of week 4 to the end of week 8 for the HFHFr and HF groups. At the end of week 16, the two groups differed in the extent of increase in total cholesterol and LDL and HDL cholesterol, with only the HFHFr group showing statistically significant changes. Specifically, at the end of week 16, the HFHFr group showed ALT levels of 108.5 +/- 93.34 U/L (F=5.099, P =0.005 vs. HF group: 44.30 +/- 35.71 U/L, HFr group: 46.70 +/- 17.95 U/L, SC group: 24.70 +/- 6.57 U/L), AST levels of 316.30 +/- 208.98 U/L (F=6.654, P=0.001 vs. HF: 132.12 +/- 75.43 U/L, HFr: 143.30 +/- 38.53 U/L, SC: 122.60 +/- 12.76 U/L), total cholesterol levels of 5.18 +/- 0.58 mmol/L (F=72: 470, P =0.000 vs. HF: 3.94 +/- 0.75 mmol/L, HFr: 2.30 +/- 0.50 mmol/L, SC: 2.02 +/- 0.24 mmol/L), HDL cholesterol levels of 3.05 +/- 0.49 mmol/L (F=25.413, P =0.000 vs. HF: 2.65 +/- 0.54 mmol/L HFr: 1.77 +/- 0.47 mmol/L, SC: 1.58 +/- 0.16 mmol/L), LDL cholesterol levels of 1.11 +/- 0.23 mmol/L (F =83.297, P =0.000 vs. HF: 0.72 +/- 0.17 mmol/L, HFr: 0.27 +/- 0.04 mmol/L, SC: 0.20 +/- 0.05 mmol/ L).

CONCLUSIONThe present study suggests that a mouse model of NASH can be successfully induced by a 16-week modified HFHFr diet.

Animals ; Diet, High-Fat ; Disease Models, Animal ; Fructose ; administration & dosage ; Male ; Mice ; Mice, Inbred C3H ; Non-alcoholic Fatty Liver Disease