Study of liver cirrhosis over twenty consecutive years in adults in Southern China.

BACKGROUND: Liver cirrhosis (LC) is a prevalent and severe disease in China. The burden of LC is changing with widespread vaccination of hepatitis B virus (HBV) and antiviral therapy. However, the recent transition in etiologies and clinical features of LC cases requiring hospitalization is unclear. AIM: To identify the transition in etiologies and clinical characteristics of hospitalized LC patients in Southern China. METHODS: In this retrospective, cross-sectional study we included LC inpatients admitted between January 2001 and December 2020. Medical data indicating etiological diagnosis and LC complications, and demographic, laboratory, and imaging data were collected from our hospital-based dataset. The etiologies of LC were mainly determined according to the discharge diagnosis, and upper gastrointestinal bleeding, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatocellular carcinoma (HCC), portal vein thrombosis, hepatorenal syndrome, and acute-on-chronic liver failure (ACLF) were considered LC-related complications in our study. Changing trends in the etiologies and clinical characteristics were investigated using logistic regression, and temporal trends in proportions of separated years were investigated using the Cochran-Armitage test. In-hospital prognosis and risk factors associated with in-hospital mortality were also investigated. RESULTS: A total of 33143 patients were included in the study [mean (SD) age, 51.7 (11.9) years], and 82.2% were males. The mean age of the study population increased from 51.0 years in 2001-2010 to 52.0 years in 2011-2020 (P < 0.001), and the proportion of female patients increased from 16.7% in 2001-2010 to 18.2% in 2011-2020 (P = 0.003). LC patients in the decompensated stage at diagnosis decreased from 68.1% in 2001-2010 to 64.6% in 2011-2020 (P < 0.001), and the median score of model for end-stage liver disease also decreased from 14.0 to 11.0 (P < 0.001). HBV remained the major etiology of LC (75.0%) and the dominant cause of viral hepatitis-LC (94.5%) during the study period. However, the proportion of HBV-LC decreased from 82.4% in 2001-2005 to 74.2% in 2016-2020, and the proportion of viral hepatitis-LC decreased from 85.2% in 2001-2005 to 78.1% in 2016-2020 (both P for trend < 0.001). Meanwhile, the proportions of LC caused by alcoholic liver disease, autoimmune hepatitis and mixed etiology increased by 2.5%, 0.8% and 4.5%, respectively (all P for trend < 0.001). In-hospital mortality was stable at 1.0% in 2011-2020, whereas HCC and ACLF manifested the highest increases in prevalence among all LC complications (35.8% to 41.0% and 5.7% to 12.4%, respectively) and were associated with 6-fold and 4-fold increased risks of mortality (odds ratios: 6.03 and 4.22, respectively). CONCLUSION: LC inpatients have experienced changes in age distribution and etiologies of cirrhosis over the last 20 years in Southern China. HCC and ACLF are associated with the highest risk of in-hospital mortality among LC complications.

The p75 neurotrophin receptor regulates cranial irradiation-induced hippocampus-dependent cognitive dysfunction.

Cognitive deficits, characterized by progressive problems with hippocampus-dependent learning, memory and spatial processing, are the most serious complication of cranial irradiation. However, the underlying mechanisms remain obscure. The p75 neurotrophin receptor (p75NTR) is involved in a diverse arrays of cellular responses, including neurite outgrowth, neurogenesis, and negative regulation of spine density, which are associated with various neurological disorders. In this study, male Sprague-Dawley (SD) rats received 10 Gy cranial irradiation. Then, we evaluated the expression of p75NTR in the hippocampus after cranial irradiation and explored its potential role in radiation-induced synaptic dysfunction and memory deficits. We found that the expression of p75NTR was significantly increased in the irradiated rat hippocampus. Knockdown of p75NTR by intrahippocampal infusion of AAV8-shp75 ameliorated dendritic spine abnormalities, and restored synapse-related protein levels, thus preventing memory deficits, likely through normalization the phosphor-AKT activity. Moreover, viral-mediated overexpression of p75NTR in the normal hippocampus reproduced learning and memory deficits. Overall, this study demonstrates that p75NTR is an important mediator of irradiation-induced cognitive deficits by regulating dendritic development and synapse structure.

Adsorption and separation of proteins by collagen fiber adsorbent.

The separation of proteins is a key step in biomedical and pharmaceutical industries. In the present investigation, the collagen fiber adsorbent (CFA) was exploited as column packing material to separate proteins. Bovine serum albumin (BSA), bovine hemoglobin (Hb) and lysozyme (LYS) that have different isoelectric points (pIs) were selected as model proteins to investigate the separation ability of CFA to proteins. In batch adsorption, the adsorption behaviors of these proteins on CFA under different pHs and ionic strengths indicated that the electrostatic interaction plays a predominant role in the adsorption of proteins on CFA. CFA exhibited high adsorption capacity to Hb and LYS. In column separation, the proteins were completely separated by adjusting pH and ionic strength of the eluent. The increase of flow rate could reduce the separation time with no influence on the recovery of protein in the experimental range. The protein recovery was higher than 90% even when the CFA column was re-used for 4 times in separation of BSA and LYS, and the retention time of BSA or LYS was almost constant during the repeated applications. In addition, as a practical application, LYS was successfully separated from chicken egg white powder by CFA column.

Molecular cloning and characterization of a matrix metalloproteinase, from Caenorhabditis elegans: employed to identify homologous protein from Angiostrongylus cantonensis.

Matrix metalloproteinases (MMPs) are a class of zinc-binding endopeptidases mainly responsible for degrading extracellular matrix constituent components, which also serve as effectors of leukocyte recruitment, cytotoxicity, cytokine and chemokine processing, and defensin activation involved in multiple mechanisms of immunomodulation. MMPs are a conserved proteolytic enzyme family participating in normal physiological function. In the present study, we have cloned a gene named CEMMP62 from Caenorhabditis elegans, the putative 62-kDa protein that contained 579 residues with MMP-conserved catalytic domain known as ZnMc_MMP and showed high identities with MMPs from other nematodes, and demonstrated that the recombinant CEMMP62 (rCEMMP62) expressed and purified from Escherichia coli could have weak proteolytic activity on swine gelatin; Western blot analysis revealed that sera from BALB/c mice immunized by recombinant protein could recognize excretory-secretary antigens from Angiostrongylus cantonensis third-stage larvae (L3). Also, the antiserum can recognize larval soluble antigens of L4 coming from mice (nonpermissive host) infected with A. cantonensis while it cannot recognize larval soluble antigens of L4 coming from rats (permissive host) infected with A. cantonensis. The results implied that probably CEMMP62 has homologous proteins which exist in A. cantonensis, and the potential MMP may play an important role in A. cantonensis infection and pathogenic process.