[Drug resistance and molecular typing of diarrheagenic escherichia coli from the diarrhea clinics in Qingpu District, Shanghai City from 2015 to 2019].

Objective: To analyze the drug resistance and multilocus sequence typing of five types of diarrheagenic Escherichia coli (DEC) isolated from diarrhea outpatients of diarrhea comprehensive monitoring designated hospital in Qingpu District, Shanghai City from 2015 to 2019. Methods: From January 2015 to December 2019, five types of DEC, isolated and identified from diarrhea outpatient cases' anal swabs of the Qingpu branch of Zhongshan Hospital were collected to determine the minimal inhibitory concentration by using the micro broth dilution susceptibility test. The strains, resistant to the third-generation cephalosporins or carbapenems, or producing ESBLs, were selected based on the results of sensitivity tests and determined by WGS. The MLST typing of DEC was analyzed based on the WGS technology and the minimum spanning tree was constructed by BioNumerics 7.6 software to analyze the local dominant flora. Results: A total of 513 strains of DEC were detected and isolated from 4 494 anal swabs, with a detection rate of 11.42%. About 500 strains were tested for drug sensitivity to nine antibiotics in four classes, including 330 strains of enterotoxigenic E.coli (ETEC), 72 strains of enteroaggregative E.coli (EAEC), 95 strains of enteropathogenic E.coli (EPEC), 1 strain of enterohemorrhagic E.coli (EHEC), and 2 strains of enteroinvasive E.coli (EIEC). From 2015 to 2019, the resistance rate of cefotaxime-clavulanic acid was significantly different (P<0.05). The resistance rate of virulence types of DEC to nalixic acid was significantly different (P<0.05). About 71 strains of DEC were determined by WGS, and 77 drug-resistant genes were detected. Strains were classified into 32 ST subtypes, with the dominant genotypes being ST-1491 (29.6%, 21/71) and ST-10 Complex (23.9%, 17/71). All ST-1491 produced ESBLs, which were blaCTX-M gene mutant strains. The dominant type of ST-10 complex was ST-218 (35.3%, 6/17). In addition, 8 strains of EAEC, 14 strains of EPEC and 49 strains of ETEC were classified into 7, 14 and 18 ST subtypes, respectively. Conclusion: The drug resistance of DEC strains from the diarrhea outpatient case of Qingpu District is serious. The ST types of EAEC and EPEC are highly polymorphic. The dominant ST types of DEC are basically consistent with the common genotypes in southeast China.

[Drug resistance and molecular typing of diarrheagenic escherichia coli from the diarrhea clinics in Qingpu District, Shanghai].

Objective: To analyze the drug resistance and multilocus sequence typing of five types of diarrheagenic Escherichia coli (DEC) isolated from diarrhea outpatients of diarrhea comprehensive monitoring designated hospital in Qingpu District, Shanghai from 2015 to 2019. Methods: From January 2015 to December 2019, five types of DEC, isolated and identified from diarrhea outpatient cases' anal swabs of the Qingpu branch of Zhongshan Hospital were collected to determine the minimal inhibitory concentration by using the micro broth dilution susceptibility test. The strains, resistant to the third-generation cephalosporins or carbapenems, or producing ESBLs, were selected based on the results of sensitivity tests and determined by WGS. The MLST typing of DEC was analyzed based on the WGS technology and the minimum spanning tree was constructed by BioNumerics 7.6 software to analyze the local dominant flora. Results: A total of 513 strains of DEC were detected and isolated from 4 494 anal swabs, with a detection rate of 11.42%. About 500 strains were tested for drug sensitivity to nine antibiotics in four classes, including 330 strains of enterotoxigenic E.coli (ETEC), 72 strains of enteroaggregative E.coli (EAEC), 95 strains of enteropathogenic E.coli (EPEC), 1 strain of enterohemorrhagic E.coli (EHEC), and 2 strains of enteroinvasive E.coli (EIEC). From 2015 to 2019, the resistance rate of cefotaxime-clavulanic acid was significantly different (P<0.05). The resistance rate of virulence types of DEC to nalixic acid was significantly different (P<0.05). About 71 strains of DEC were determined by WGS, and 77 drug-resistant genes were detected. Strains were classified into 32 ST subtypes, with the dominant genotypes being ST-1491 (29.6%, 21/71) and ST-10 Complex (23.9%, 17/71). All ST-1491 produced ESBLs, which were blaCTX-M gene mutant strains. The dominant type of ST-10 complex was ST-218 (35.3%, 6/17). In addition, 8 strains of EAEC, 14 strains of EPEC and 49 strains of ETEC were classified into 7, 14 and 18 ST subtypes, respectively. Conclusion: The drug resistance of DEC strains from the diarrhea outpatient case of Qingpu District is serious. The ST types of EAEC and EPEC are highly polymorphic. The dominant ST types of DEC are basically consistent with the common genotypes in southeast China.

[Drug selection for simultaneous treatment of tuberculosis combined with hepatitis C virus infection].

Clinically, patients with tuberculosis (TB) combined with hepatitis C virus (HCV) infection often require simultaneous treatment. Consequently, when anti-HCV and TB drugs are used in combination drug-drug interactions (DDIs), anti-TB drug-induced hepatotoxicity, and liver disease states need to be considered. This paper focuses on discussing the metabolic mechanisms of commonly used anti-TB and HCV drugs and the selection options of combined drugs, so as to provide rational drug use for TB patients combined with HCV infection.

[Analysis of eight-year follow-up data of plateau workers by color doppler echocardiography].

Objective: To analyze the heart rate changes and risk factors, as a result of high altitude. Methods: Retrospective analysis of echocardiographic data of plateau workers at a railway maintenance company from 2006 to 2013. The survival curve method was used to analyze the abnormal rate of the heart. Kaplan-Meier method and Cox proportional hazards regression model were used to analyze the influencing factors. Results: In the first occurrence of cardiac abnormalities, the main types of abnormalities were right atrium enlargement (53.47%) , right ventricle enlargement (17.36%) , and tricuspid regurgitation (16.67%) . Cox regression analysis showed that workplace altitude and first physical examination age are two influencing factors of cardiac abnormalities, and their relative risk was 1.661 and 1.039. At high altitudes (3 600~4 000 m) , nearly 40% of workers heart has not changed. But this adaptation does not observed in the ultra-high altitudes (≥4 000 m) . Conclusion: There are individual differences in human adaptability to high altitude. We should take more stringent measures of health care for older people and those who work at more than 4000m. And we should abide by the rotation system for railways that are suitable for the plateau.

[Prevalence of inpatients with liver disease in infectious diseases department of three comprehensive hospitals in Yunnan: a multi-center retrospective analysis].

Objective: To study the constitutional features of diseases spectrum of inpatients with liver disease in infectious diseases department of three comprehensive hospitals to provide resource allocation proposition for the construction of Department of Infectious Diseases. Methods: Inpatients data were extracted from the department of infectious diseases of three comprehensive hospitals (Kunming General Hospital of the People's Liberation Army, Yuxi People's Hospital and Dali People's Hospital) between January 2010 to December 2015, and were retrospectively analyzed. The distribution of patients with viral hepatitis (A, B, C, E) and severe liver disease (Severe hepatitis, cirrhosis, liver cancer) was further analyzed in hospitalized patients. Data were analyzed by one-way analysis of variance. A chi-squared test was used for comparison between groups. The change trends of disease constituent ratio in different years were checked by 2 test. Results: Liver disease, tuberculosis and AIDS were the three common diseases of three comprehensive hospitals in Yunnan, accounting for 58.61% of all admissions. However, an inpatients with liver diseases (17.25%, 3555/20606, 95% CI 16.73%-17.77%) were significantly lower than tuberculosis inpatients (33.98%, 7002/20606, 95% CI 33.34%-34.62%). An observations from different hospitals and at different time points showed that the proportion of patients with liver disease was lower than that of tuberculosis patients. The proportion of inpatients with HBV infection showed a downward trend (P < 0.001), whereas the proportions of inpatients with HCV and severe liver diseases showed an increased trend over time (P < 0.001). Conclusion: The proportion of inpatients with liver diseases was lower than tuberculosis inpatients in the Department of Infectious Diseases of three comprehensive hospitals. Hence, the paucity of the disease spectrum should be considered for resource allocation in the construction of infectious disease department.

[Recovery of hemoglobin level and blood pressure in workers unfit for duties at high altitude following relocation].

Objective: To determine the hemoglobin level and blood pressure and the factors that influence their recovery in relocated workers who were unfit for duties at high altitude. Methods: The physical examination data of 693 relocated workers who previously worked at high altitude were dynamically monitored from January 2006 to June 2015 in order to examine the recovery of hemoglobin level and blood pressure. Results: The rate of hemoglobin recovery was 81.37% among the 161 relocated workers with abnormal hemoglobin levels, and the rate of blood pressure recovery was 69.51% among the 164 relocated workers with abnormal blood pressure. The rates of hemoglobin and blood pressure recovery were decreased in individuals aged 40 years and older. The peak recovery time of hemoglobin was 11-15 months following relocation, and that of blood pressure was 5-7 months and 11-13 months following relocation. The half-year blood pressure recovery rate and 2-year hemoglobin recovery rate following relocation were significantly higher in workers who worked at 2500-3000 m altitude than in those at ≥3000 m (P<0.05) . Total cholesterol and educational level were factors that influence the half-year blood pressure recovery in relocated workers (P<0.05) . Conclusion: The rate of hemoglobin and blood pressure recovery are high among relocated workers who previously worked at high altitude. Factors that influence blood pressure, such as total cholesterol, should be closely monitored so that high-altitude workers with abnormal blood pressure and hemoglobin level can be relocated as early as possible.

[Research advances in the role of interleukin-21 in chronic hepatitis B virus infection].

Interleukin-21 (IL-21) is a cytokine mainly secreted by activated CD4+ T cells and natural killer T cells and has multiple effects. It is involved in innate and adaptive immune responses. Recent studies have shown that IL-21 can promote functional activation of various immune cells in the process of hepatitis B virus (HBV) infection, and the gene polymorphisms of IL-21 is associated with the susceptibility to HBV. In addition, the expression of IL-21 is closely associated with HV genotype, HBV clearance, HBeAg seroconversion, HBV-related liver cirrhosis, liver failure, liver cancer, and autoimmune disease. This article reviews the research advances in clinical trials with reference to the aspects above.

Molecular epidemiological features of Mycobacterium tuberculosis in an endemic region of Henan Province, China.

Henan Province is one of the regions with the highest tuberculosis (TB) burden in China. Among isolates collected from Zhongmou County, Henan, 21.28% (10/47) of those from 2001 and 22.95% (10/61) from 2007 were resistant to at least one drug (isoniazid, rifampicin, ethambutol or streptomycin); 90.74% (98/108) of the isolates were from the Beijing family, and 108 exhibited 105 different mycobacterial interspersed repetitive units-variable number of tandem repeats patterns. This study preliminarily reveals that Henan Province is still a high prevalence region for drug-resistant TB, and strains collected from local TB cases have diverse genotypes, of which the Beijing family type is predominant.

The use of chloroplast microsatellite markers for assessing cytoplasmic variation in a watermelon germplasm collection.

Fifteen chloroplast microsatellite (cpSSR) markers were tested to analyze cytoplasmic variation in a set of watermelon accessions containing 67 Chinese watermelon germplasms (CWGs) and 19 non-Chinese watermelon germplasms (NCGs), and 11 were polymorphic. These polymorphic cpSSR markers detected 2-4 alleles (mean = 2.8) in all the accessions, with diversity values ranging from 0.047 to 0.427 (mean = 0.252). Based on the polymorphic cpSSR loci, 17 distinct haplotypes were identified, of which six were from CWGs, seven were from NCGs, and four were shared by both of them. Most haplotypes from CWGs were nearly identical at the 11 cpSSR loci, but those from NCGs revealed higher variations. Of the haplotypes from CWGs, a predominant haplotype was found in 76.1% of CWGs, indicating that CWGs suffered a cytoplasmic bottleneck in domestication process and lost most of their cytoplasmic variability. To analyze the relationships among these 17 haplotypes, a dendrogram was constructed based on the cpSSR data using the unweighted pair-group method with arithmetic average (UPGMA). Three distinct groups were generated, revealing a genetic divergence between CWGs and NCGs. From this analysis, we obtained five rare haplotypes which had quite low genetic similarity to the others and would be useful for watermelon breeding in China. The results enriched the knowledge in genetic diversity of CWGs and could be informative for broadening the genetic base of watermelon.

Ethyl carbamate in fermented foods and beverages: dietary exposure of the Hong Kong population in 2007-2008.

To evaluate the potential public health risk of ethyl carbamate (EC), EC exposure from fermented foods and beverages for Hong Kong population was estimated. In 276 samples analysed, EC was detected (limit of detection (LOD) at 0.4 µg kg(-1)) in 202 samples (73%), with higher levels in fermented red bean curd (150-650 µg kg(-1)) and yellow wine (140-390 µg kg(-1)), while low or non-detected (ND) in preserved vegetables (ND-10 µg kg(-1)) and fermented tea (ND-15 µg kg(-1)). The estimated dietary exposure from all fermented foods and beverages was 8.27 ng kg(-1) bw day(-1), while exposure excluding alcoholic beverages was 5.42 ng kg(-1) bw day(-1), with calculated margins of exposure (MOEs) at 3.6 × 10(4) and 5.5 × 10(4) respectively. The risk of adverse health effects was low for the average population but higher (MOE of 10(3)) for high consumers of alcoholic beverages especially habitual drinkers of alcoholic types with high EC contents.

A study of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and polychlorinated biphenyls (PCBs) in the livestock waste compost of Hong Kong, PR China.

Composting is one of the waste disposal methods adopted for disposal of livestock waste in Hong Kong. The composting livestock waste normally undergoes 6-8 weeks fermentation, followed by 16-20 weeks maturation. The matured compost is sold as soil conditioner in the local market. In 2006, feedstock material and a time-series of compost samples were collected throughout the fermentation and maturation process from the Sha Ling Composting Plant in the New Territories. The feedstock material and compost samples were analyzed for contents of three unintentional persistent organic pollutants (POPs), i.e. dioxins/furans, dioxin-like PCBs and total PCBs. These POPs are unintentionally produced by-products of chemical industrial processes and combustion processes. Selected heavy metals were also analyzed, which served as conservative tracers to determine potential mass loss during the composting process. Levels of contamination by these POPs were found to be low in the matured compost for sale. The mean concentrations (lower-upper bound) of total dioxins/furans, total dioxin-like PCBs and total PCBs were 2.01-2.05 ng I-TEQ/kg dw, 0.04-0.05 ng WHO-TEQ/kg dw and 1.55-1.55 microg/kg dw, respectively. Progressively elevated levels of these POPs were observed in the compost samples during the fermentation process. Analysis of the congener profiles revealed that the heptaCDD and octaCDD were the main contributors to the observed increase in dioxin/furan content. The possible sources of dioxins/furans in the compost were discussed. The study results established a local dioxins/furans emission factor specific to the trade and provided a better estimate of the annual dioxins/furans emission for the livestock waste composting activity in Hong Kong.

Design of novel peptide ligands which have opioid agonist activity and CCK antagonist activity for the treatment of pain.

Disease states such as neuropathic pain offer special challenges in drug design due to the system changes which accompany these diseases. In this manuscript we provide an example of a new approach to drug design in which we have modified a potent and selective peptide ligand for the CCK-2 receptor to a peptide which has potent agonist binding affinity and bioactivity at delta and mu opioid receptors, and simultaneous antagonist activity at CCK receptors. De novo design based on the concept of overlapping pharmacophores was a central hypothesis of this design, and led to compounds such as H-Tyr-DPhe-Gly-DTrp-NMeNle-Asp-Phe-NH(2) (i.e., RSA 601) which have the designed properties.

Transgenic plants expressing autoantigens fed to mice to induce oral immune tolerance.

Oral administration of protein can induce antigen-specific immune hyporesponsiveness. However, the utility of oral tolerance to autoantigens in the treatment of autoimmune diseases may be limited when candidate autoantigens cannot be produced by conventional systems in quantities sufficient for clinical studies. Plants may be ideally suited for this purpose, as they can synthesize, glycosylate and assemble mammalian proteins to provide huge quantities of relatively low cost soluble proteins. Furthermore, edible transgenic plants could provide a simple and direct method of autoantigen delivery for oral tolerance. Therefore, the aim of this study was to determine whether a transgenic plant expression system was capable of synthesizing the diabetes-associated autoantigen, glutamic acid decarboxylase (GAD) in an immunogenic form and whether the oral administration of an autoantigen expressed by a plant could directly induce protective immune responses in a mouse model of diabetes. We show that a GAD-expressing transgenic plant, given as a dietary supplement, inhibits the development of diabetes in the non-obese diabetic (NOD) mouse.

Tramadol, M1 metabolite and enantiomer affinities for cloned human opioid receptors expressed in transfected HN9.10 neuroblastoma cells.

Tramadol hydrochloride is a centrally acting synthetic analgesic in widespread clinical use. Despite different degrees of opioid-like characteristics in preclinical tests, it is characterized by lack of full naloxone reversibility or naloxone-precipitated withdrawal in humans. To investigate this apparent discrepancy, the present study measured the affinity of tramadol (and its enantiomers) and an active O-desmethyl metabolite (M1) (and its enantiomers) to cloned human opioid receptors of the mu, delta and kappa type stably expressed in HN9.10 neuroblastoma cells. At mu sites, the Ki values for tramadol, its (+) and (-) enantiomers, M1, and its (+) and (-) enantiomers were 17000, 15700, 28800, 3190, 153 and 9680 nM, respectively, compared to 7.1 nM for morphine. These results are consistent with the suggestion of a non-opioid contribution to the clinical profile of tramadol.

Pharmacological characterization of the cloned kappa opioid receptor as a kappa 1b subtype.

Substantial pharmacological evidence in vitro and in vivo has suggested the existence of subtypes of the kappa opioid receptor. Quantitative radioligand binding techniques resolved the presence of two high affinity binding sites for the kappa 1 ligand [3H]U69,593 in mouse brain membranes, termed kappa 1a and kappa 1b, respectively. Whereas the kappa 1a site has high affinity for fedotozine and oxymorphindole and low affinity for bremazocine and alpha-neoendorphin, site kappa 1b has high affinity for bremazocine and alpha-neoendorphin and low affinity for fedotozine and oxymorphindole. CI-977 and U69,593 bind equally well at both sites. To determine the relationship between these kappa 1 receptor subtypes and the recently cloned mouse kappa 1 receptor (KOR), we examined [3H]U69,593 binding to the KOR in stably transfected cells (KORCHN-8). Competition of [3H]U69,593 binding to the KOR by bremazocine, alpha-neoendorphin, fedotozine and oxymorphindole resolved a single class of binding sites at which these agents had binding affinities similar to that of the kappa 1b site present in mouse brain. These results suggest that the cloned KOR corresponds to the kappa 1 site in mouse brain defined as kappa 1b.

Transient myeloproliferative disorder and acute myeloid leukemia: study of six neonatal cases with long-term follow-up.

Six neonates with hematological and clinical pictures indistinguishable from acute myeloid leukemia were studied. Two patients had Down syndrome and three others had either +21 or i(21q) chromosomal abnormalities in their blood cells at presentation. Granulocyte-macrophage colony-forming unit assays performed in bone marrow and peripheral blood mononuclear cells revealed abnormal growth patterns in two patients; both died of progressive disease of acute myeloid leukemia. All the other four neonates with normal in vitro cell growth pattern had spontaneous remission within 7 months. Of these four patients, one remains well and in remission for 8 years and the other three developed acute myeloid leukemia at the ages of 15, 32 and 19 months, respectively. We conclude that the in vitro cell growth pattern is helpful to distinguish transient myeloproliferative disorder from congenital acute myeloid leukemia and that patients with the former condition are at risk to develop acute myeloid leukemia subsequently.

Cloning and sequence analysis of a p40 structural protein gene of Helicoverpa zea nuclear polyhedrosis virus.

A gene encoding an occluded virion structural protein was isolated from an expression library constructed from the Helicoverpa zea S-type nuclear polyhedrosis virus (NPV) isolate HzS-15 using both polyclonal and monoclonal antibody screening. The gene was located within a Pstl-Sall fragment of the HzS-15 genome spanning from 96.5 to 97.3 m.u. Sequencing analyses revealed a long open reading frame of 927 nucleotides that predicted a protein of 37 kDa in size. Immunoblot analyses using the monoclonal antibody ENV409 demonstrated that the gene corresponded to a 40-kDa protein (p40) in SDS-polyacrylamide gels that was present exclusively in enveloped occluded virions but not in extracellular budded virions or envelope-stripped nucleocapsids. A p40 protein-specific transcript was detected at 16 hr postinfection in HzS-15-infected Hz 1075/UND-K cells and remained until 22 hr. Primer extension analyses demonstrated that the p40 protein-specific transcript started at -49 nucleotides from the ATG start codon within an ATAAG consensus pentamer found in late protein genes of Baculoviruses. The deduced amino acid sequence of the HzS-15 p40 protein gene shared 44 and 45% sequence homology with the p40 proteins of Bombyx mori NPV and Autographa californica NPV, respectively.