A systematic review and meta-analysis of severe risk in patients with common chronic diseases and coronavirus disease 2019 / 中华传染病杂志

Objective:To systematically review the severe risk in common chronic diseases and coronavirus disease 2019 (COVID-19) cases.Methods:PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, China Biology Medicine disc, medRxiv, SSRN and ChinaXiv were searched for clinical and epidemiological studies that reported chronic diseases in patients with COVID-19. Only studies of severe COVID-19 in comparison with non-severe controls were included. The prevalence rates of chronic diseases including chronic obstructive pulmonary disease (COPD), diabetes mellitus, hypertension, malignant tumor, cardiovascular diseases, cerebrovascular disease, chronic kidney disease, and chronic liver disease were estimated. Pooled odds ratio ( OR) with 95% confidence interval ( CI) between patients with severe COVID-19 and non-severe groups were calculated. R 3.6.3 software was used for meta-analysis. Results:The search yielded 2 455 articles. A total of 19 eligible comparative studies with 4 792 patients were included in a quantitative analysis. Meta-analysis showed that there was a proportion of 55.0% (95% CI 40.0%-80.0%) male among patients with COVID-19, and the overall pooled prevalence of any chronic diseases in COVID-19 cases was 30.4% (95% CI 24.0%-37.0%). The most prevalent comorbidity was hypertension (16.9%(95% CI 14.0%-20.0%)), followed by diabetes mellitus (8.3%(95% CI 8.0%-9.0%)). The proportion of male patients with severe COVID-19 was higher than that of male patients with non-severe COVID-19 (64.4% vs 52.8%, OR=1.49, 95% CI 1.08-2.05, Z=4.63, P<0.01). The prevalence rates of COPD, cerebrovascular disease, diabetes mellitus, chronic kidney disease, hypertension, cardiovascular diseases and malignant tumor in severe COVID-19 patients were higher than those of non-severe patients ( OR=5.77, 95% CI 3.80-8.74; OR=4.47, 95% CI 2.71-7.38; OR=3.55, 95% CI 2.86-4.40; OR=3.05, 95% CI=1.76-5.28; OR=2.82, 95% CI=1.96-3.97; OR=2.39, 95% CI=1.77-3.23; OR=2.15, 95% CI 1.27-3.66, respectively, Z=8.37, 6.01, 11.60, 4.20, 5.46, 5.71, 3.12, all P<0.01). There was no significant difference in the prevalence of chronic liver disease between severe and non-severe patients ( OR=1.35, 95% CI 0.84-2.17, P=0.11). Conclusion:COVID-19 patients with chronic diseases have higher risk of developing severe disease, and the ORs from high to low are COPD, cerebrovascular disease, diabetes mellitus, chronic kidney disease, hypertension, cardiovascular diseases and malignant tumor.

Expression of thymidylate synthase in salivary adenoid myoepithelial cells and its clinical significance / 南方医科大学学报

OBJECTIVE@#To evaluate the expression of thymidylate synthase (TS) in myoepithelial cells (MECs) of salivary adenoid tissues and explore its clinical significance.@*METHODS@#Immunohistochemical staining EnVision method was used to detect the expression of TS, P63, Calponin, CK5/6 and S-100 in 32 salivary gland specimens, including 10 non-neoplastic and salivary inflammation specimens, 11 mixed tumor specimens, 5 basal cell carcinoma specimens and 6 adenoid cyst carcinoma specimens. The specificity and sensitivity of TS as a specific molecular marker of salivary muscle epithelial cells were evaluated in comparison with P63, Calponin, CK5/6 and S-100.@*RESULTS@#The expression pattern of TS in all the salivary gland tissue specimens was identical with that of p63. TS and P63 both showed strong immunohistochemical expressions in MECs of salivary adenoid tissue specimens. Calponin, CK5/6, and S-100 showed cytoplasmic/membranous expressions in the MECs. In addition, TS exhibited weak or moderate cytoplasmic expression in a few salivary gland epithelial cells, cancer cells and scattered stromal cells, with negative expression in the cell nuclei. The expression of TS in the MECs of all the salivary adenoid specimens was highly consistent with those of P63, Calponin, CK5/6 and S-100 (>0.05) Except for CK5/6 expression in Salivary inflammation and Salivary gland specimens. Kappa>0.75. The specificity and sensitivity of TS as a molecular marker of MECs were both 100%.@*CONCLUSIONS@#TS is a new specific marker of MECs for differential diagnosis of salivary gland tumors.

Generation of a novel HBeAg transgenic mice using CRISPR/Cas9 technique / 南方医科大学学报

OBJECTIVE@#To generate a new strain of HBeAg transgenic mice using CRISPR/Cas9 technique.@*METHODS@#Hepatitis B virus (HBV) HBeAg gene was cloned and inserted in the pliver-HBeAg expression frame at the site of Rosa26 gene using CRISPR/Cas9 and homologous recombination techniques to construct the pliver-HBeAg expression vector containing HBeAg gene. The linear DNA fragment containing HBeAg gene was obtained by enzyme digestion. Cas9 mRNA, gRNA and the donor vector were microinjected into fertilized eggs of C57BL/6J mice, which were then transplanted into the uterus of C57BL/6J female surrogate mice to obtain F0 generation mice. The F0 generation mice were identified by long fragment PCR to obtain F0 transgenic mice with HBeAg gene. The positive F0 generation mice were bred with wild-type C57BL/6J mice to produce the F1 mice, which were identified by PCR and sequencing. The positive F1 transgenic mice carrying HBeAg gene were backcrossed until the homozygous offspring transgenic mice were obtained. The genotypes of the offspring mice were identified. The expressions of HBeAg and HBeAb in the heterozygous and homozygous HBeAg transgenic mice were detected by automatic chemiluminescence immunoassay, immune colloidal gold technique and immunohistochemistry method.@*RESULTS@#A total of 56 F0 mice were obtained, and 2 of them carried homologous recombined HBeAg gene. Six positive F1 mice were obtained, from which 22 homozygous and 29 heterozygous F2 generation HBeAg transgenic mice were obtained. High concentration of HBeAg protein was detected in the peripheral blood of all the positive HBeAg transgenic mice without HBeAb expression. HBeAg expression was detected in the hepatocytes of HBeAg transgenic mice.@*CONCLUSIONS@#We obtained a new strain of HBeAg transgenic mice with stable expression of HBeAg in the hepatocytes and immune tolerance to HBeAg using CRISPR/Cas9 technique, which provide a new animal model for studying HBV.

Calcium channel blocker diltizem transiently inhibits migration and up-regulates metadherin expression in hepatocellular carcinoma cells / 南方医科大学学报

OBJECTIVE@#To investigate the effect of calcium channel blocker diltizem in reversing multi-drug resistance (MDR) and on metadherin expression in hepatocellular carcinoma cells and explore the molecular mechanism.@*METHODS@#Hepatocellular carcinoma MHCC97H and 7402 cells were treated with diltiazem hydrochloride, a calcium channel blocker (0, 25, 50, 100, 200, and 400 μmol/L), for 12, 24, or 48 h. Wound healing assay was employed to assess the changes in the mobility and migration of the cells following the treatments, and the changes in the expression levels of metadherin mRNA and protein and P-gp protein were determined using RT-PCR and immunocytochemistry.@*RESULTS@#Diltiazem hydrochloride could transiently inhibit the migration and movement of MHCC97H and 7402 cells in a time-and concentration-dependent manner ( < 0.05). Diltiazem hydrochloride at different concentrations also transiently up-regulated the expressions of metadherin mRNA and protein but did not inhibit the expression of P-gp protein in MHCC97H and 7402 cells.@*CONCLUSIONS@#Calcium channel blocker can transiently inhibit the migration of hepatocellular carcinoma cells and up-regulate the expression of metadherin mRNA and protein through a feedback mechanism, suggesting the potential risk of calcium channel blockers for promoting tumor progression during the treatment of malignant tumors.

Research progress in liver targeted therapy for nonalcoholic fatty liver disease / 临床肝胆病杂志

Nonalcoholic fatty liver disease (NAFLD)is the most common progressive liver disease worldwide.Currently,there is no satisfy-ing treatment for NAFLD.Research progress in fatty acid bile acid conjugates (FABACs)and ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE),which are two novel liver targeted drugs with anti-NAFLD effects,is reviewed.FABACs,which reduce liver fat in pa-tients with NAFLD induced by high-fat diet by regulating lipid metabolism,have been proved effective in preventing and treating NAFLD. The safety and efficacy of FABACs in NAFLD patients have been confirmed in a phase II,randomized,double-blind,placebo-controlled trial.UDCA-LPE can not only reduce liver fat in NAFLD patients,but also inhibit mitochondrial damage and apoptosis and promote hepa-tocyte regeneration,with a marked anti-inflammatory effect during the development of NAFLD.Therefore,FABACs and UDCA-LPE hold promise for preventing and treating NAFLD.

Detection of the serum free insulin-like growth factor 1 in patients with chronic severe hepatitis and its implication / 解放军医学杂志

Objective To evaluate the relationship between the serum free IGF-1 level and the severity and prognosis in patients with chronic severe hepatitis. Methods Serum free IGF-1 was assessed by ELISA in 44 patients with chronic severe hepatitis, 43 chronic viral hepatitis, 46 liver cirrhosis. At the same time the liver function, prothrombin activity and cholinesterase were also determined. Results Serum free IGF-1 in patients with chronic severe hepatitis, liver cirrhosis and chronic viral hepatitis was 0.24?0.15,0.33?0.17 and 1.06?0.70 (ng/ml), respectively. IGF-1 was significantly decreased in patients with chronic severe hepatitis and liver cirrhosis. IGF-1 level in patients with chronic severe hepatitis at early, middle and advanced stages was 0.28?0.07, 0.27?0.19 and 0.16?0.06 (ng/ml), respectively. The reduction in the value showed a positive correlation with different stages of chronic severe hepatitis. Patients with chronic severe hepatitis having a serum free IGF-1 below 0.2ng/ml had a higher mortality, and those with the value above 0.35ng/ml had a better chance to survive during the follow-up period. There was a significant positive correlation between serum free IGF-1 and prothrombin activity. Conclusion Serum free IGF-1 was decreased in the patients with chronic severe hepatitis. The clinical observation suggested that the serum free IGF-1 might be an important prognostic indicator in patients with chronic severs hepatitis.

The Immune Role in Central Nervous System (CNS) Injury and its Rehabilitation / 中国康复理论与实践

@#The most Cytokines are found to be produced and functional in both of immune systemsand nervous system, which become a foundation of interaction between nervous and immune system.Macrophage and microglia may play an important role in the study of CNS injury and regeneration.

A Experimental Study on Pharmacokinetics of Cefazolinum in Rats with Paraplegia / 中国康复理论与实践

@#Wistar male rats were divided into two grorps, The experimental group was madethe paraplegia model. BOth groups were received cefazolinum 250 mg through single-dosed intra-venous injection. The concentration was measured by HPLC. The result implied that a).the concentra-tion of cefazolinum in paraplegic group was higher than that in control group either the distributingphase or the eliminating phase(p<0. 001);b). the pharmacokinetic parameters showed that the apparent vlumeof distribution:(v1,v2)was decreased and the elimination. half-life(t1/2β)was more length-y in paraplegia group. So that the drug concentration increased. The conclusion is that the dosege on thepatients with paraplegia should be clinically monitored,especilly following hepatic and renal disfunctionand with the drugs with narrowed safety range.