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Objective:To explore the relationship between serum retinol binding protein(RBP)and metabolic-associated fatty liver disease(MAFLD)in elderly patients with type 2 diabetes mellitus(T2DM)and possible underlying metabolic mechanisms.Methods:A total of 3384 elderly T2DM patients hospitalized and with complete clinical records at the Department of Endocrinology and Metabolism, Sixth People's Hospital Affiliated to Shanghai Jiao Tong University between January 2003 and December 2012 were recruited in this retrospective study.Patients were divided into four groups according to the quartiles of serum RBP levels: the first quartile of serum RBP levels(<35 mg/L, 844 cases), the second quartile of serum RBP levels(35 mg/L≤ RBP ≤41 mg/L, 773 cases), the third quartile of serum RBP levels(42 mg/L≤ RBP ≤51 mg/L, 902 cases), and the fourth quartile of serum RBP levels(RBP>51 mg/L, 865 cases). Clinical data and laboratory test results were collected.Differences in the prevalence of MAFLD were compared between the four groups.The association between RBP and MAFLD was analyzed via binary logistic regression.Results:After adjusting for age and sex, the proportion of obesity( χ2=15.222, P<0.01), the percentage using lipid-lowering drugs( χ2=88.552, P<0.01), systolic blood pressure( F=12.002, P<0.01), diastolic blood pressure( F=6.872, P<0.01), waist circumference( F=9.563, P<0.01), waist-hip ratio( F=7.972, P<0.01), body mass index( F=9.057, P<0.01), serum creatinine( χ2=185.445, P<0.01), serum uric acid( χ2=314.691, P<0.01), 24-hour urinary albumin( χ2=91.012, P<0.01), alanine aminotransferase( χ2=17.049, P=0.003), γ-glutamyl transpeptidase( χ2=50.514, P<0.01), total cholesterol( F=45.669, P<0.01), triglycerides( χ2=361.269, P<0.01), low-density lipoprotein( F=8.772, P<0.01), fasting C-peptide( χ2=165.756, P<0.01), 2h postprandial C-peptide( χ2=120.690, P<0.01), and the homeostasis model assessment of insulin resistance(HOMA2-IR)( χ2=148.884, P<0.01)in elderly patients with T2DM all showed a clear upward trend.The prevalence of MAFLD also gradually increased across the quartiles of serum RBP levels[26.5%(224/844), 30.1%(233/773), 36.6%(330/902), and 41.8%(362/865)], respectively( χ2=52.526, P<0.01). Elderly T2DM patients with MAFLD had a significantly higher value of HOMA2-IR than those without MAFLD[2.0(1.31-2.8) vs.1.39(0.86-2.06), F=220.826, P<0.01]. After correcting for other confounding factors, binary logistic regression showed that serum RBP was strongly associated with the presence of MAFLD in elderly patients with T2DM( β=0.209, 95% CI: 1.079-1.408, OR=1.232, χ2=9.441, P<0.01). Conclusions:Elevated serum RBP levels are an independent risk factor for the development of MAFLD in elderly T2DM patients, possibly through increased insulin resistance induced by RBP.
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Primary liver cancer includes three types: Hepatocellular carcinoma, intrahepatic cholangiocarcinoma, mixed hepatocellular carcinoma and cholangiocarcinoma. Among them, hepatocellular carcinoma accounts for 75% to 85%, posing a serious threat to human life and health. The screening and monitoring of high-risk populations for hepatocellular carcinoma is crucial for early detection, diagnosis, and treatment, as well as for improving the prognosis of liver cancer. Serum biomarkers play an important role in monitoring and diagnosing hepatocellular carcinoma. In recent years, new serum biomarkers such as AFP heterogeneity, abnormal prothrombin/de-γ-carboxyprothrombin, Golgi protein 73, Dickkopf-associated protein 1, aldehyde ketone reductase-AKR1B10, gypican 3, liquid biopsies and microRNAs have been recommended for screening and monitoring hepatocellular carcinoma, and some have been included as auxiliary diagnostic measures in liver cell carcinoma guidelines. This article summarizes the progress of relevant basic research and clinical evaluation of these novel biomarkers, which may provide a reference for future clinical application.
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In recent years, with the progress of research on the molecular mechanism of cell death, it has been discovered that there are many new types of programmed cell death, including non-apoptotic (10 types) and apoptotic (2 types), which are widely involved in the pathogenesis of infectious diseases and tumors. It is also a frontier research topic and provides new ideas for disease prevention and treatment. This article reviews the published literature on programmed cell death, focusing on the characteristics of cell necrosis, apoptosis, pyroptosis, ferroptosis, neutrophil inflammatory cell death (NETosis), cuproptosis, and widespread apoptosis (PANoptosis), as well as their relationship with infectious diseases.
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In recent years, great progress has been made in small molecule therapeutic drugs and monoclonal neutralizing antibody preparations against 2019-nCoV. At least 5 oral drugs (Monupavir, AT-527, Proclutamide, Paxlovid and S-217622) and 2 monoclonal antibodies (Ambavirumab/Romisevirumab combination and Sotrovimab) have completed phase Ⅲ clinical trials exhibiting excellent antiviral effects. This article reviews the research progress of these 7 drugs to provide reference for clinical application.
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This article reviews the status quo of new antimicrobial agents that have been approved or undergoing phase Ⅱ/Ⅲ clinical trials in last five years at home and abroad, including new β-lactamase inhibitors and their compound preparations, oxazolidinones, tetracyclines, aminoglycosides, glycopeptides, quinolones, new antifungal agents, cyclic lipopeptides and new anti-mycobacterial agents. The antibacterial activities, main mechanisms of drug resistance, and progress of clinical studies of 27 new drugs were introduced to provide a reference for their clinical application.
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During the treatment of critically ill COVID-19 patients it has been revealed that the neutralizing monoclonal antibodies against 2019-nCoV have the advantages of high specificity, high purity, and can be prepared in a large scale, which are expected to be a effective preparation for clinical use. This article introduces the way of 2019-nCoV invasion into the host cells, the major variants of novel coronavirus, and the mechanism of action of anti-2019-nCoV monoclonal antibodies, as well as the progress of research and development of their preparation in major pharmaceutical companies, to provide reference for scientific research and clinical application.
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At present, drug therapies for hepatitis C patients are using a large variety of direct-acting antiviral agents (DAAs). In order to facilitate clinicians for selection of appropriate therapeutic agents, the author recommends Zepatier or Gilead third-generation (Epdusa) for treatment, and G/P cocktail (Maviret) therapy for patients with failure of other DAAs treatments. In this article, the author also discusses the safety and resistance rate of these small molecule drugs to provide reference for clinicians.
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2019-nCoV has a up to 96% homology with the gene sequence of a bat coronavirus. By comparing its 7 conserved non-structural proteins, it is found that 2019-nCoV belongs to SARS related coronaviruses(SARSr-CoV). The receptor for 2019-nCoV entering cells is the same as that for SARSr-CoV, and angiotensin-converting enzyme 2 (ACE2) is a common cross-genus receptor. This article first elaborates the interspecies transmission and genetic variation, then briefly discusses the receptors on the surface of human cells (such as ACE2 and APP4), which cause human infection and encode five proteins in the viral genome, therefore are important targets for development of antiviral drugs. The article reviews eight promising anti-coronavirus drugs, including three anti-HIV drugs (Lopinavir/Ritonavir, Danoprevir/Ritonavir, Darunavir), two anti-Ebola virus drugs (Remdesivir, Galidesivir), two anti-influenza virus drugs (Arbidol, Favipiravir) and one anti-malarial drug (chloroquine phosphate). Among them, Remdesivir, Abidol and Favipiravir have strong inhibitory effects on 2019-nCoV, they may be the most promising drugs under investigation.
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Coronaviruses widely exist in the nature.The domestic animals, poultry, rodents, and wild mammals, especially bats are the natural reservoir hosts of various coronaviruses , which spread infectious agents causing epidemics of animal or human diseases .Six coronaviruses have been found to cause disease in human, including SARS-CoV and MERS-CoV which cause high mortality rates.Due to the extensive hosts and the genomic characteristics , coronavirus is prone to gene recombination and mutation in the course of evolution, showing genetic diversity.New subtypes and new coronaviruses continue to emerge during this process, making it possible for cross-species infections, which bring great difficulties in the prevention and treatment of the disease.The article reviews and discusses the morphological structure , classification, genome and cross-species infection, pathogenicity of coronavirus as well as the prevention and control measures of its infection.
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In recent years,the rabies virus(RV)has been studied in more depth, including wild virus,vaccine strain, and the gene structure, replication, gene function and expression regulation of the newly identified isolates from bats.According to the homology of N protein base,the human pathogenic RV can be divided into 7 genotypes, which belong to the genetic pedigree Ⅰ,Ⅱ,Ⅲ, respectively.The pathogenesis of human rabies has not been fully understood,no breakthrough has been made in the treatment of rabies, and the Milwaukee protocol has not been recognized by expert consensus.From the current research progress of animal models,the development of novel therapeutic vaccines and drugs to inhibit viral replication and diffusion are promising for cure of rabies.This article reviews some new discoveries and information of rabies, including the characteristics of RV, the pathogenic mechanisms and the progress of treatments after onset,which would provide reference for prevention and control of human rabies.
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In recent years,great progress has been made in treatment of patients with HCV infection with direct-acting antiviral agents (DAAs).Up to now,twelve kinds of oral DAAs and three kinds of combination regimens have been approved by the U.S.Food and Drug Administration and European Medicines Agency to treat chronic HCV infection.This article reviews the research progress of DAAs in treatment of hepatitis C,including the name of DAAs,drug targets,therapy regimen,clinical efficacy and adverse effects.
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HBV infection is a major public health threat around the world.At present, clinical anti-HBV drugs,including nucleoside/nucleotide analogues (NAs) and PegIFNα, can only directly or indirectly inhibit viral replication rather than viral elimination.In recent years, medical researchers and pharmaceutical enterprises are extensively researching and developing new drugs for treatment of HBV, and a variety of drugs have entered the stage of clinical trials.This article reviews the research progress on characteristics,safety and clinical trials,as well as the development trends of several currently available anti-HBV drugs, focusing on the target points and life cycle of HBV.
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Zika virus was named after the Ugandan forest where it was first isolated in a rhesus monkey in 1947, and the first confirmed human case was reported in 1954 in Nigeria.The incidence of Zika virus disease is very low.In the year 2014, Zika virus infection appeared in the Western hemisphere, and then the virus rapidly spread to Americas, Caribbean and Pacific island countries.Currently more than 30 countries have reported Zika virus infection, and officials estimate there will be 4 million Zika infections. Zika virus disease is a self-limited disease with mild symptoms, however, Zika virus is neuroinvasive.It can be transmitted to infants from mothers who infected in the early months of pregnancy, and may cause microcephaly, retinae macula and optic nerve abnormalities.Guillain-Barré syndrome is also found as a complication of Zika virus infection in some cases.Zika virus is mainly transmitted by aedes mosquito, and no vaccine is available at present, so the prevention of its infection is difficult.This paper reviews the research progress of Zika virus infection, including virus characteristics, epidemiology and clinical feature of Zika infection in human.
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Recently,a new species of Cardiovirus was isolated from human beings,named Saffold virus (SAFV).SAFV can be divided into 11 genotypes,and its infection usually occurs in children aged ≤6 years.SAFV is spread by fecal-oral route or from respiratory tract.It can induce acute gastroenteritis,respiratory tract infection and central nerve system infection,and the latter one may result in severe encephalitis.This article reviews the characteristics of SAFV and its infection in human beings.
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The origin,diversity,hemagglutinin protein and mutations of avian influenza A (H7N9) virus are widely studied recently.Although this virus is low-pathogenic in domestic poultry,it becomes highly pathogenic in human when gene mutations occur.The available evidence has revealed that the novel avian influenza A (H7N9) virus is a multiple gene reassortment,and virus shedding in quail and chickens is much higher than in other species.When human infected with H7N9 virus,immune responses will be activated,and massive cytokines and chemokine are produced,which may result in secondary hemophagocytic syndrome and multiple organ dysfunction.The prognosis of H7N9 viral infection may be associated with high level of angiotensin Ⅱ in plasma and the genetic trait of individuals (carrying rs12252-C/C genotype IFITM3).This paper reviews the recent progress on H7N9 virus infection,to provide reference for the control of human infection with H7N9 avian influenza virus and the management of severe cases.
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<p><b>OBJECTIVE</b>To investigate the status of the drug resistance and the ampC gene expression of Enterobacter cloacae.</p><p><b>METHODS</b>Disk diffusion tests were made for detecting the susceptibility of antimicrobial agents against Enterobacter cloacae. AmpC gene was amplified by polymerase chain reaction (PCR) and verified by DNA sequencing. AmpC gene expression was analyzed according to antimicrobial agent sensitive phenotype.</p><p><b>RESULTS</b>The sensitivity rates of 144 strains to imipenam, cefepime and cefoperazone/sulbactam were 98.61%, 65.97% and 63.89%, respectively. The sensitivity rates of 144 strains to other antimicrobial agents were lower. Among the 144 strains 120 were found to be positive by PCR for ampC. The PCR product showed high homology to the GenBank ampC sequence. Stably derepressed strains, hyperinducible strains and unexpressing or lower level expressing strains accounted for 30.0% (36/120), 37.5% (45/120), and 32.5% (39/120), respectively. Fifty-six out of 120 strains (46.67%) also produced extended spectrum beta-lactamases (ESBLs). The hyperinducible strains were highly sensitive to all the antimicrobial agents except amoxicillin/clavulanic acid and cefuroxime, while the stably derepressed strains were only sensitive to imipenam and cefepime. However, sensitivity to cefepime decreased if the strains also produced ESBLs.</p><p><b>CONCLUSIONS</b>The drug resistant status of Enterobacter cloacae is severe. Clearing out the expressive status of ampC gene will be helpful in selection of antimicrobial agents in the treatment of clinical infection.</p>
Subject(s)
Cefoperazone , Pharmacology , Drug Resistance, Bacterial , Enterobacter cloacae , Genetics , Gene Expression , Genes, Bacterial , Genetics , Imipenem , Pharmacology , Microbial Sensitivity Tests , Polymerase Chain Reaction , Sulbactam , Pharmacology , beta-LactamasesABSTRACT
<p><b>OBJECTIVE</b>To investigate the epidemiological status of extended-spectrum beta-lactamase (ESBL) producing Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) and the drug resistance profiles of such organisms.</p><p><b>METHODS</b>A total of 282 clinical isolates of E. coli and 180 of K. pneumoniae were collected from different districts of Zhejiang Province. Inhibitor potentiated broth dilution tests were performed for detecting extended-spectrum beta-lactamases. Etests were performed to detect the drug resistance of these strains against nine commonly used antibiotics.</p><p><b>RESULTS</b>The prevalence of extended-spectrum beta-lactamases in E. coli and K. pneumoniae was 34.0% and 38.3%, respectively. The average prevalence of extended-spectrum beta-lactamases in E. coli and K. pneumoniae was 35.7%. The resistance prevalence of extended spectrum beta-lactamase producing strains to ceftazidime and cefotaxime was 40% and 26% respectively, so were those to cefepime, cefoxitin, piperacillin-tazobactam, cefoperazone-sulbactam, amikacin and ciprofloxacin. All these strains were sensitive to imipenem.</p><p><b>CONCLUSION</b>The results in this study showed that the prevalence of extended-spectrum beta-lactamases was high, while extended-spectrum beta-lactamase producing strains were resistant to most antimicrobial agents except imipenem.</p>
Subject(s)
Humans , Drug Resistance, Bacterial , Escherichia coli , Klebsiella pneumoniae , Microbial Sensitivity Tests , beta-LactamasesABSTRACT
<p><b>OBJECTIVE</b>To analyze the epidemiology of hospital and community-acquired infections caused by Klebsiella pneumoniae (K. pneumoniae) and risk factors for infections caused by resistant strains.</p><p><b>METHODS</b>A retrospective observational study was performed to analyze the relationship between antimicrobial use and bacterial resistance.</p><p><b>RESULTS</b>A K. pneumoniae infection was diagnosed in 0.47% of patients (169 of 36 179) admitted to the hospital between 1 March 1999 and 31 August 2000. Of the 169 isolates, 166 (98.2%) were resistant to at least one antimicrobial and 91.1% (154/169) to two or more antibiotics. 98% were resistant to ampicillin, 77% to piperacillin, 64% to cephalothin, 60% to ampicillin/sulbactam, 59% to cefoperazone, 57% to cefazolin, 55% to cefuroxime, 51% to TMP-SMZ, 51% to tobramycin, 50% to gentamicin, 49% to aztreonam, cefetaxime and ceftriaxone respectively, 47% to ceftazidime, 47% to cefepime, 46% to ciprofloxacin, 46% to ticarcillin/clavulanate, 44% to amikacin, 38% to cefoxitin, 22% to piperacillin/tazobactam, while all strains were tested susceptible to imipenem.</p><p><b>CONCLUSIONS</b>Prior receipt of amtimicrobial therapy was significantly associated with infection caused by a resistant organism and most strains were resistant to multiple antibiotics.</p>
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Drug Resistance, Bacterial , Klebsiella Infections , Drug Therapy , Epidemiology , Klebsiella pneumoniae , Risk FactorsABSTRACT
Objective To diagnose the infection of Pseudomonas aeruginosa early. Methods Polymerase chain reaction (PCR) was used to amplify the fragment of Pseudomonas aeruginosa OprI gene. The fragment was determined by HaeⅢ and PvuⅡ digestion, and sequencing analyses. Results It showed that 96 of 223 specimens were cultured to be positive with Pseudomonas aeruginosa, 96 of which had expectant streaks. Otherwise the other specimens had no positive streaks. The procedure needed only 4 hours. The PCR products were determined by ribonuclease HaeⅢ and PvuⅡ , and resulted in two small fragments with 49bp and 112bp separately. By automatic sequencing analysis, the coincidence rate with the gene bank was 100%. Conclusions The results indicates that the OprI gene detection by PCR is a specific, sensitive and quick technique for the diagnosis of Pseudomonas aeruginosa infection.
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Aim To obtain the encoding gene sequences of TEM-type ?-lactamases produced by 4-strain Klebsiella pneumoniae in Zhejian g Province, identify their genotypes and study some properties of these TEM-typ e ?-lactamases.Methods The encoding genes of TEM-type ?-la ctamases produced by 4 isolates were amplified by PCR. The purified PCR products were ligated with pGEM-T easy vectors, expressed in E. coli DH 5?, and sequenced by Sanger's dideoxy chain termin ation composition method. Compared with anino acid sequences in the GenBank,TEM -types of the ?-lactamases was determined. The genes of TEM ?-lactamases were ligated with pET-28 c vector to express recombinant proteins in E. coli DH 5?. Plasmids were extracted from the p ronucleus expression strains and PCR was performed to determine whether the pron ucleus expression was successful or not. Their phenotypes were determined by ESB Ls phenotype affirmative test. The isoelectric points (pIs) of the recombinant p roteins were determined by isoelectric focus. Conjugation test was performed to determine whether their genes existed in plasmid or chromosome. Results The encoding genes of ?-lactamases were determined as TEM by PCR. It s PCR product had 1 009 nucleotides. The pI of the novel TEM ?-lactamase was 5.4. The enzyme was determined as non-ESBLs by ESBLs phenotype affirmative tes t.Transconjugants were successfully selected from the paternal producers in conj ugation tests. The TEM-type ?-lactamase produced by 4 strains was determined as TEM-105(AF516720) by GenBank. Conclusion The ?-lactamase produced by 4-strain K. pneumoniae from 4 patients in Zhejiang Province was TEM-105. It was the first report of TEM-105 type ?-lactamase produced by 4-st ain K. pneumoniae from China in the world.