Diagnosis and treatment of 4 cases imported severe malaria and COVID-19 co-infection / 中国热带医学

@#Abstract: To explore the clinical characteristics, diagnosis and treatment of imported severe malaria and COVID-19 co-infection cases, and to provide scientific basis for epidemic prevention and control measures. The epidemiological characteristics, clinical manifestations, laboratory tests, treatment process and prognosis of 4 cases of severe malaria and COVID-19 co-infection with confirmed diagnosis were analyzed retrospectively. Four cases of severe malaria were African returnees of the same batch, male, aged 40-54 years old, with the same journey track. They all had African work and life history and acute onset. The main clinical manifestations were fever (4/4), chills (3/4), chills (3/4), nausea and vomiting (3/4), diarrhea (4/4), fatigue and anorexia (4/4). Two cases had headache and dizziness, confusion, muscle aches, two cases had cough, one cases had sputum, sore throat and runny urine. All 4 cases were confirmed by positive nucleic acid detection of the new coronavirus (2019-nCOV) in throat swabs. Plasmodium falciparum was found by microscopic examination of peripheral blood smears of all patients, and all of them were consistent with high altitude helminthiasis. All cases were accompanied by abnormal liver function and severe hypoproteinemia, two cases were hyperbilirubinemia, three cases were dyslipidemia, three cases were involved in abnormal tertiary hemogram with different degrees of elevation of procalcitonin, two cases were lactic acid poisoning, and one case was hypoglycemia. One case showed viral pneumonia on chest CT. All cases were treated individually according to the different conditions and were discharged after improvement, and were rechecked for 2019-nCOV nucleic acid and microscopic examination of blood smear negative for Plasmodium.During the global COVID-19 epidemic, the emergence of coinfection cases of con-infection of imported malaria parasites and severe acuterespiratory syndrome coronavirus 2 (SARS-CoV-2) makes the clinical diagnosis and treatment more complicated. It is important to establish the awareness of simultaneous prevention and diagnosis of COVID-19 and malaria for local prevention and control and early warning of severe cases, and timely and effective formulation of treatment plan to improve the comprehensive treatment efficiency.

Transformation of berberine to its demethylated metabolites by the CYP51 enzyme in the gut microbiota / 药物分析学报

Berberine(BBR)is an isoquinoline alkaloid extracted from Coptis chinensis that improves diabetes,hyperlipidemia and inflammation.Due to the low oral bioavailability of BBR,its mechanism of action is closely related to the gut microbiota.This study focused on the CYP51 enzyme of intestinal bacteria to elucidate a new mechanism of BBR transformation by demethylation in the gut microbiota through multiple analytical techniques.First,the docking of BBR and CYP51 was performed;then,the pharma-cokinetics of BBR was determined in ICR mice in vivo,and the metabolism of BBR in the liver,kidney,gut microbiota and single bacterial strains was examined in vitro.Moreover,16S rRNA analysis of ICR mouse feces indicated the relationship between BBR and the gut microbiota.Finally,recombinant E.coli con-taining cyp51 gene was constructed and the CYP51 enzyme lysate was induced to express.The metabolic characteristics of BBR were analyzed in the CYP51 enzyme lysate system.The results showed that CYP51 in the gut microbiota could bind stably with BBR,and the addition of voriconazole(a specific inhibitor of CYP51)slowed down the metabolism of BBR,which prevented the production of the demethylated metabolites thalifendine and berberrubine.This study demonstrated that CYP51 promoted the deme-thylation of BBR and enhanced its intestinal absorption,providing a new method for studying the metabolic transformation mechanism of isoquinoline alkaloids in vivo.

Influencing factors of the accuracy of digital surgical implant-guide plate / 口腔疾病防治

@#With the increasing development of digital technologies, digital surgical templates have been widely used in stomatology. However, the accuracy of digital surgical templates is always a consideration for many researchers and dentists. This article analyzed the factors affecting the accuracy of digital surgical templates and found that errors arise from six factors, including the design and manufacture of the templates, implant guide support, implant systems and guide systems, implant length, bone density and the clinical experience of the operator; this literature review aims to reduce or eliminate human factors and improve accuracy, objectivity and security in implant placement.

Berberine is a new mechanism drug against energy metabolic disorder / 中国药理学与毒理学杂志

Berberine (BBR) is a natural compound isolated from Coptis chinensis and for decades an over-the-count medicine in China for bacterial-caused diarrhea. We have identified BBR to be an effective drug in treating hyperlipidemia as well as hyperglycemia. Clinical studies showed that oral administration of BBR caused significant reduction of blood cholesterol, LDL-c, triglyceride, as well as glucose and HbA1c in patients with hyperlipidemia or T2D. A small % of patients have minor and transient side- effect in the GI system. The cholesterol- lowering effect was associated with the ERK mediated LDLR mRNA up-regulation; the glucose-lowering effect mainly resulted from PKD-mediated insulin receptor expression as well as activation of AMPK. The clinical efficacy of BBR were verified by a large number of independent clinical groups in and outside China. For BBR absorption mechanism, we showed that BBR was first converted into dhBBR by nitroreductase in the gut microbiota, promoting BBR enter into intestinal well, where it was oxidized back to BBR, and then got into blood. Our recent study showed that BBR could also promote gut microbiota pathways to make SCFAs (such as butyrate), which entered blood and reduced blood lipids and glucose, suggesting a newly identified MOA of BBR. BBR is now in clinical trial in China. We consider it a multiple-target drug for metabolic disorders in clinic.

GATA3-IL-13 pathway gene polymorphisms are associated with serum IL-13 and asthma / 中国免疫学杂志

Objective:Asthma is a chronic inflammatory respiratory disease .The data show that involvement of the GATA 3-IL-13 gene in asthma is biologically plausible .The objective of this study is investigated the association of GATA 3-IL13 gene polymorphisms and IL-13 levels with asthma;assess the correlations between GATA 3-IL-13 gene SNPs polymorphisms and serum levels of IL-13 in population of Xinjiang (China).Methods:A case group of 279 patients and 277 healthy controls were genotyped to perform using the MassARRAY SNP genotyping system.In 279 asthma patients and 277 controls,IL-13 levels were measured by ELISA.Data were analyzed using the statistical package for social science (SPSS) 22.0 (IBM,NY,USA) and Graph Pad Prism 6.0.Results:Patients were found that IL-13 levels were associated with asthma in asthmatic and the IL-13 ( rs2066960 AA ) , GATA3 ( rs3781093 CC) genotype was associated with a notably increased risk of asthma compared with the CC (rs2066960),TT (rs3781093) genotype (P<0.05).Similarly,IL-13(rs2066960) C-A alleles were significantly associated with risk of asthma (P<0.05).However,the rs3781093 C-T alleles had no obvious differences (P>0.05).In addition,the patients carrying the rs2066960 AA genotype presented with higher IL-13 levels compared to the CC group .Conclusion:This result suggests that the rs 2066960 C-A variant is associated with IL-33 levels in patients with asthma .

Establishment and application of high throughput screening model for hepatitis C virus NS3-4A protease inhibitors in vitro / 中国医学科学院学报

<p><b>OBJECTIVE</b>To establish fluorescence resonance energy transfer (FRET) assay method of detecting proteolytic activity of non-structural protein 3-4A (NS3-4A) serine protease of hepatitis C virus (HCV) for high throughput screening inhibitors against HCV in vitro.</p><p><b>METHODS</b>HCV recombinant plasmid pMAL~c2/NS3-4A was transformed into the E.coli strain K12TB1. Maltose-binding-protein (MBP) NS3-4A fusion protein expression was induced by adding isopropyl-β-D-thiogalacto-pyranoside (IPTG) and purified by affinity chromatography. The proteolytic activity of MBP-NS3-4A protease was analyzed by FRET with the special protease substrate. The reaction system in this model was optimized, and the reliability of the model was evaluated.</p><p><b>RESULTS</b>High throughput screening model for HCV NS3-4A protease inhibitors was established, and the best concentrations of enzyme and substrate were optimized. In the model, the Km value of protease was 4.74 μmol/L, Z factor was up to 0.80, and coefficient of variation (CV) was 1.91%. BILN 2061, one of the known HCV protease inhibitors, was measured with the Ki of 0.30 nmol/L.</p><p><b>CONCLUSION</b>The assay model using FRET method for HCV NS3 4A serine protease is stable and reliable, and the model is suitable for high throughput screening for HCV NS3 4A protease inhibitors.</p>

Silencing effect of recombinant plasmids PPARgamma-pSUPER-EGFP on the expression of peroxisome proliferator-activated receptor gamma / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the silencing effect of gene encoding peroxisome proliferator-activated receptor gamma (PPARgamma) on the expression of tumor necrosis factor alpha (TNFalpha) by constructing vectors for RNA interference in RAW264.7 cells.</p><p><b>METHODS</b>The pSUPER-EGFP vectors were used to transcribe functional small interfering RNA (siRNA). Four pairs of oligonucleotides (64 nt) targeting PPARgamma gene were inserted into the downstream of the H1 promotor, with their veracity confirmed by double digestion and sequencing. Western blotting and immunofluorescence assay were used to examine the silencing effect of PPARgamma gene in RAW264.7 cells. Meanwhile, the TNFalphalevel was determined by Sandwich ELISA.</p><p><b>RESULTS</b>Compared with other recombinant pSUPER-EGFP vectors (R-pSUPER.EGFP), R-pSUPER.EGFP2 induced the best silencing effect on the expression of PPARgamma in RAW264.7 cells, which played an obvious inhibitory role in down-regulating the TNFalphaexpression after the curcumin and lipopolysaccharide (LPS) stimulation.</p><p><b>CONCLUSIONS</b>PPARgamma-pSUPER-EGFP inducing a silencing effect on the expression of PPARgamma can efficiently play a negative role in controlling the inflammatory responses of RAW264.7 cells.</p>