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1.
J Hazard Mater ; 409: 124921, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33421874

RESUMO

The discovery of plasmid-mediated tet(X) variants and efflux pump gene tmexCD1-toprJ1 conferring bacteria resistance to tigecycline has compromised glycylcycline as the last line of defense against infection, which poses serious threat to public health. Herein, real-time quantitative PCR was used to detect the abundance of seven tigecycline resistance genes (TRGs), including six tet(X) variants and tmexCD1-toprJ1, and insertion sequences ISCR2 and IS26. Then, the concentrations of nine antibiotics were quantified in fecal samples collected from 157 livestock farms in four Chinese provinces. TRGs, especially tet(X4), tmexCD1-toprJ1, and insertion sequences ISCR2 and IS26, were more abundant in chicken feces than in pig and cattle feces, suggesting the greater risk for the propagation of TRGs in chicken feces. Positive correlations (ρ = 0.3741-0.8275, P < 0.0001) between ISCR2/IS26 and TRGs (except tet(X1)) further demonstrated that ISCR2 mediates the transfer of tet(X3), tet(X4), and tet(X5) and that IS26 plays a certain role for the mobilization of tet(X4) and tmexCD1-toprJ1. Tetracyclines had no positive correlation with the abundance of TRGs (except tet(X1)), meanwhile florfenicol and tiamulin were positively correlated with TRGs. However, further research is needed to confirm whether or not florfenicol and tiamulin are potential driving factors of TRG accumulation.

2.
Food Chem ; 334: 127598, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32707363

RESUMO

A multi-residue method has been developed for the identification and quantification of 78 compounds from seven different classes of veterinary drugs in eggs. This method was based on dispersive solid phase extraction where mixed-mode cation exchange sorbent was used to combine the isolation of compounds and sample purification. The analysis was performed using ultra-high performance liquid chromatography-tandem mass spectrometry, and the chromatographic run time of one injection was 9.5 min. The mean recovery ranged from 70.5% to 119.2% and inter-day relative standard deviation was less than 17.0%. The limit of quantification ranged between 0.1 and 1 µg/kg, which was sufficient to support surveillance monitoring. Lastly, the method was successfully used to detect residues of veterinary drug in real samples. The dietary exposure risk was subsequently assessed using the results of the survey, indicating that the evaluated daily intake and percentage of acceptable daily intake were at toxicologically acceptable levels.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ovos/análise , Contaminação de Alimentos/análise , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Drogas Veterinárias/análise , Animais , China , Exposição Dietética/análise , Análise de Alimentos/métodos , Humanos , Limite de Detecção , Nível de Efeito Adverso não Observado , Reprodutibilidade dos Testes
3.
Steroids ; : 108774, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33285175

RESUMO

Giosgenin is a naturally steroidal saponin exhibiting a variety of biological activities including antitumor ones. A series of novel diosgenyl quaternary ammonium derivatives were designed and synthesized to develop potential anti-tumor agents in our research. All novel derivatives were characterized by 1H NMR, 13C NMR and HR-MS, and evaluated for their in vitro anti-proliferative activities using MTT assay. The human cancer cell lines were A549 (Human lung cancer cell), H1975 (Human lung adenocarcinoma cell), A431 (Human skin squamous cell carcinoma), HCT-116 (Human colorectal adenocarcinoma cell), Aspc-1 (Human metastatic pancreatic cancer cell), Ramos (Human B lymphoma cell), HBE (Human bronchial epithelioid cell) and LO2 (Human normal hepatocyte).

4.
Environ Int ; 146: 106217, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33129001

RESUMO

BACKGROUND: Previous studies of the health impact of ambient and household air pollution (AAP/HAP) have chiefly relied on self-reported and/or address-based exposure modelling data. We assessed the feasibility of collecting and integrating detailed personal exposure data in different settings and seasons. METHODS/DESIGN: We recruited 477 participants (mean age 58 years, 72% women) from three (two rural [Gansu/Henan] and one urban [Suzhou]) study areas in the China Kadoorie Biobank, based on their previously reported fuel use patterns. A time-resolved monitor (PATS+CO) was used to measure continuously for 120-hour the concentration of fine particulate matter (PM2.5) at personal and household (kitchen and living room) levels in warm (May-September 2017) and cool (November 2017-January 2018) seasons, along with questionnaires on participants' characteristics (e.g. socio-demographic, and fuel use) and time-activity (48-hour). Parallel local ambient monitoring of particulate matter (PM1, PM2.5 and PM10) and gaseous pollutants (CO, ozone, nitrogen oxides) was conducted using regularly-calibrated devices. The air pollution exposure data were compared by study sites and seasons. FINDINGS: Overall 76% reported cooking at least weekly (regular-cooks), and 48% (urban 1%, rural 65%) used solid fuels (wood/coal) for cooking. Winter heating was more common in rural sites than in urban site (74-91% vs 17% daily), and mainly involved solid fuels. Mixed use of clean and solid fuels was common for cooking in rural areas (38%) but not for heating (0%). Overall, the measured mean PM2.5 levels were 2-3 fold higher in the cool than warm season, and in rural (e.g. kitchen: Gansuwarm_season = 142.3 µg/m3; Gansucool_season = 508.1 µg/m3; Henanwarm_season = 77.5 µg/m3; Henancool_season = 222.3 µg/m3) than urban sites (Suzhouwarm_season = 41.6 µg/m3; Suzhoucool_season = 81.6 µg/m3). The levels recorded tended to be the highest in kitchens, followed by personal, living room and outdoor. Time-resolved data show prominent peaks consistently recorded in the kitchen at typical cooking times, and sustained elevated PM2.5 levels (> 100 µg/m3) were observed in rural areas where use of solid fuels for heating was common. DISCUSSION: Personal air pollution exposure can be readily assessed using a low-cost time-resolved monitor in different settings, which, in combination with other personal and health outcome data, will enable reliable assessment of the long-term health effects of HAP/AAP exposures in general populations.

5.
BMC Psychiatry ; 20(1): 499, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33036580

RESUMO

BACKGROUND: The 5-hydroxytryptamine 1B receptor (5-HT1B) plays an essential role in the serotonin (5-HT) system and is widely involved in a variety of brain activities. HTR1B is the gene encoding 5-HT1B. Genome-wide association studies have shown that HTR1B polymorphisms are closely related to multiple mental and behavioral disorders; however, the functional mechanisms underlying these associations are unknown. This study investigated the effect of several HTR1B haplotypes on regulation of gene expression in vitro and the functional sequences in the 5' regulatory region of HTR1B to determine their potential association with mental and behavioral disorders. METHODS: Six haplotypes consisting of rs4140535, rs1778258, rs17273700, rs1228814, rs11568817, and rs130058 and several truncated fragments of the 5' regulatory region of HTR1B were transfected into SK-N-SH and HEK-293 cells. The relative fluorescence intensities of the different haplotypes and truncated fragments were detected using a dual-luciferase reporter assay system. RESULTS: Compared to the major haplotype T-G-T-C-T-A, the relative fluorescence intensities of haplotypes C-A-T-C-T-A, C-G-T-C-T-A, C-G-C-A-G-T, and C-G-T-A-T-A were significantly lower, and that of haplotype C-G-C-A-G-A was significantly higher. Furthermore, the effects of the rs4140535T allele, the rs17273700C-rs11568817G linkage combination, and the rs1228814A allele made their relative fluorescence intensities significantly higher than their counterparts at each locus. Conversely, the rs1778258A and rs130058T alleles decreased the relative fluorescence intensities. In addition, we found that regions from - 1587 to - 1371 bp (TSS, + 1), - 1149 to - 894 bp, - 39 to + 130 bp, + 130 to + 341 bp, and + 341 to + 505 bp upregulated gene expression. In contrast, regions - 603 to - 316 bp and + 130 to + 341 bp downregulated gene expression. Region + 341 to + 505 bp played a decisive role in gene transcription. CONCLUSIONS: HTR1B 5' regulatory region polymorphisms have regulatory effects on gene expression and potential correlate with several pathology and physiology conditions. This study suggests that a crucial sequence for transcription is located in region + 341 ~ + 505 bp. Regions - 1587 to - 1371 bp, - 1149 to - 894 bp, - 603 to - 316 bp, - 39 to + 130 bp, and + 130 to + 341 bp contain functional sequences that can promote or suppress the HTR1B gene expression.

6.
J Orthop Surg Res ; 15(1): 469, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046099

RESUMO

An amendment to this paper has been published and can be accessed via the original article.

7.
Cell ; 183(2): 490-502.e18, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33002410

RESUMO

The non-receptor protein tyrosine phosphatase (PTP) SHP2, encoded by PTPN11, plays an essential role in RAS-mitogen-activated protein kinase (MAPK) signaling during normal development. It has been perplexing as to why both enzymatically activating and inactivating mutations in PTPN11 result in human developmental disorders with overlapping clinical manifestations. Here, we uncover a common liquid-liquid phase separation (LLPS) behavior shared by these disease-associated SHP2 mutants. SHP2 LLPS is mediated by the conserved well-folded PTP domain through multivalent electrostatic interactions and regulated by an intrinsic autoinhibitory mechanism through conformational changes. SHP2 allosteric inhibitors can attenuate LLPS of SHP2 mutants, which boosts SHP2 PTP activity. Moreover, disease-associated SHP2 mutants can recruit and activate wild-type (WT) SHP2 in LLPS to promote MAPK activation. These results not only suggest that LLPS serves as a gain-of-function mechanism involved in the pathogenesis of SHP2-associated human diseases but also provide evidence that PTP may be regulated by LLPS that can be therapeutically targeted.

8.
J Hematol Oncol ; 13(1): 119, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883331

RESUMO

Tumor metastasis accounts for the majority of cancer-related deaths; it is therefore important to develop preclinical models that faithfully recapitulate disease progression. Here, we generated paired organoids derived from primary tumors and matched liver metastases in the same colorectal cancer (CRC) patients. Despite the fact that paired organoids exhibit comparable gene expression and cell morphology, organoids from metastatic lesions demonstrate more aggressive phenotypes, tumorigenesis, and metastatic capacity than those from primary lesions. Transcriptional analyses of the paired organoids reveal signature genes and pathways altered during the progression of CRC, including SOX2. Further study shows that inducible knockdown of SOX2 attenuated invasion, proliferation, and liver metastasis outgrowth. Taken together, we use patient-derived paired primary and metastatic cancer organoids to model CRC metastasis and illustrate that SOX2 is associated with CRC progression and may serve as a potential prognostic biomarker and therapeutic target of CRC.

9.
Environ Int ; 144: 106005, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32739516

RESUMO

Cumulative research on resistomes and microbiomes from aquatic environments has revealed that both integrated freshwater and monoculture freshwater aquaculture systems can cause the development and dissemination of antibiotic resistance genes (ARGs) and associated mobile genetic elements (MGEs). However, few studies have examined differences in resistomes between the different aquaculture modes, and those that do have focused on antibiotic residues or individual resistance genes. In the current study, we collected 44 environmental samples from two monoculture freshwater aquaculture farms and four integrated farms (two duck and fish farms, two laying duck and fish farms) in Guangdong, China, in 2018. After measuring the concentrations of antibiotic residues in the samples, we characterized MGEs and ARGs and examined their association with potential bacterial hosts in the microbial communities using high-throughput sequencing-based metagenomic and network analyses. We then compared the resistome profiles of the different aquaculture models. We found that the number and total relative abundance of ARG and MGE subtypes in the integrated (fish and duck/laying duck) farm samples were significantly higher than those in samples from monoculture freshwater aquaculture farms. Specifically, both the mobile colistin resistance genes mcr variants and tigecycline resistance gene tet(X) variants in integrated farms exhibited higher total relative abundance than that in monoculture farms. Moreover, the interrelationships among ARGs and microbial taxa, ARGs and MGEs, and MGEs and microbial taxa in the integrated farm samples were also more complex than those observed in monoculture freshwater aquaculture farm samples. Meanwhile, the species of Acinetobacter and Escherichia were identified to be the possible host of tet(X) and ESBL gene blaCTX-M in aquaculture, respectively. To the best of our knowledge, this is the first metagenomic study to analyze differences in resistome profiles between integrated and monoculture ponds. Overall, integrated aquaculture systems exhibited a higher prevalence of resistance genes compared with monoculture freshwater aquaculture farms. Therefore, additional antimicrobial resistance surveillance should be focused on this type of freshwater aquaculture system.

10.
Stem Cell Res Ther ; 11(1): 366, 2020 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-32831148

RESUMO

BACKGROUND: Significant progress has been made in cell replacement therapy for neural retinal diseases using retinal cells differentiated from human pluripotent stem cells. Low tumorigenicity and the ability to mature to form synaptic junctions make precursor cells a promising donor source. Here, we attempted to improve the yield of photoreceptor precursor cells in three-dimensional retinal organoids from human embryonic stem cells (hESCs). METHODS: A CRX-tdTomato-tagged hESC line was generated to track retinal precursors in 3D retinal organoids. COCO, a multifunctional antagonist of the Wnt, TGF-ß, and BMP pathways, was employed to 3D organoid differentiation schemes for enhanced photoreceptor precursor cells. Organoid fluorescence intensity measurement was used to monitor retinalization tendency with the number of precursors further checked by flow cytometry. Signature gene expression during organoid differentiation were assessed by qPCR and immunocytochemistry after COCO supplementation. RESULTS: CRX-positive cells can be spatiotemporally tracked by tdTomato without affecting retinalization during retinal organoid differentiation. Fluorescence intensity of organoids, which turned out highly consistent with flow cytometry measurement, allowed us to determine the differentiation efficiency of precursors during organoid culturing directly. Using COCO as an auxiliary supplement, rather than alone, can yield an increased number of photoreceptor precursors in the early stage of organoid differentiation. Over a longer time-frame, photoreceptor precursors enhanced their fate of cones and decreased fate of rods after treatment with COCO. CONCLUSIONS: Tracing with the CRX-reporter system showed that in retinal organoids derived from human pluripotent stem cells, COCO increased the differentiation efficiency of photoreceptor precursors and cones.

11.
BMC Med Genet ; 21(1): 159, 2020 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-32770953

RESUMO

BACKGROUND: The CACNA1C gene was defined as a risk gene for schizophrenia in a large genome-wide association study of European ancestry performed by the Psychiatric Genomics Consortium. Previous meta-analyses focused on the association between the CACNA1C gene rs1006737 and schizophrenia. The present study focused on whether there was an ancestral difference in the effect of the CACNA1C gene rs1006737 on schizophrenia. rs2007044 and rs4765905 were analyzed for their effect on the risk of schizophrenia. METHODS: Pooled, subgroup, sensitivity, and publication bias analysis were conducted. RESULTS: A total of 18 studies met the inclusion criteria, including fourteen rs1006737 studies (15,213 cases, 19,412 controls), three rs2007044 studies (6007 cases, 6518 controls), and two rs4765905 studies (2435 cases, 2639 controls). An allele model study also related rs2007044 and rs4765905 to schizophrenia. The overall meta-analysis for rs1006737, which included the allele contrast, dominant, recessive, codominance, and complete overdominance models, showed significant differences between rs1006737 and schizophrenia. However, the ancestral-based subgroup analysis for rs1006737 found that the genotypes GG and GG + GA were only protective factors for schizophrenia in Europeans. In contrast, the rs1006737 GA genotype only reduced the risk of schizophrenia in Asians. CONCLUSIONS: Rs1006737, rs2007044, and rs4765905 of the CACNA1C gene were associated with susceptibility to schizophrenia. However, the influence model for rs1006737 on schizophrenia in Asians and Europeans demonstrated both similarities and differences between the two ancestors.


Assuntos
Canais de Cálcio Tipo L/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único/genética , Esquizofrenia/genética , Adulto , Alelos , Feminino , Frequência do Gene/genética , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Viés de Publicação , Fatores de Risco , Adulto Jovem
12.
Curr Med Sci ; 40(4): 767-772, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32862389

RESUMO

The optimal assisted reproductive treatment strategy for infertile women with unilateral tubal obstruction remains uncertain. To investigate the role of intrauterine insemination (IUI) in the treatment of infertile women with unilateral tubal occlusion, the data of 148 couples were retrospectively collected and analyzed. Seventy-eight infertile women with unilateral occlusion diagnosed by hysterosalpingography (HSG) were categorized as the study group and 70 others with unexplained infertility as the control group. The study group was divided into a proximal occlusion subgroup and a mid-distal occlusion subgroup for further analysis. The main outcomes, namely the clinical pregnancy rate (CPR), ongoing pregnancy rate (OPR), and live birth rate (LBR) per cycle, were analyzed. Our results showed a tendency of lower CPR, OPR, and LBR in the study group than in the control group, without statistical significance. Further investigations revealed that the unilateral proximal occlusion subgroup had similar CPR, OPR, and LBR as the control group, while the unilateral mid-distal occlusion subgroup had significantly lower CPR (5.1% vs. 20.0%, P=0.035), OPR (5.1% vs. 20.0%, P=0.035), and LBR (5.1% vs. 20.0%, P=0.035) than the control group. In conclusion, the clinical outcomes of IUI were worse in patients with unilateral tubal occlusion than in those with unexplained infertility. This might be primarily caused by the worse outcome of patients with unilateral mid-distal tubal occlusion instead of proximal occlusion.

13.
BMC Nephrol ; 21(1): 349, 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807121

RESUMO

BACKGROUND: Plasma fibrinogen is significantly associated with cardiovascular (CV) events and mortality in the general population. However, the association between plasma fibrinogen and mortality in patients undergoing peritoneal dialysis (PD) is unclear. METHODS: This was a prospective cohort study. A total of 1603 incident PD patients from a single center in South China were followed for a median of 46.7 months. A Cox regression analysis was used to evaluate the independent association of plasma fibrinogen with CV and all-cause mortality. Models were adjusted for age, sex, smoking, a history of CV events, diabetes, body mass index, systolic blood pressure, hemoglobin, blood platelet count, serum potassium, serum albumin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, hypersensitive C-reactive protein, estimated glomerular filtration rate, antiplatelet agents and lipid-lowering drugs. RESULTS: The mean age was 47.4 ± 15.3 years, 955 (59.6%) patients were male, 319 (19.9%) had a history of CV events, and 410 (25.6%) had diabetes. The average plasma fibrinogen level was 4.12 ± 1.38 g/L. Of the 474 (29.6%) patients who died during follow-up, 235 (49.6%) died due to CV events. In multivariable models, the adjusted hazard ratios (HRs) for quartile 1, quartile 3, and quartile 4 versus quartile 2 were 1.18 (95% confidence interval [CI], 0.72-1.95, P = 0.51), 1.47 (95% CI, 0.93-2.33, P = 0.10), and 1.78 (95% CI, 1.15-2.77, P = 0.01) for CV mortality and 1.20 (95% CI, 0.86-1.68, P = 0.28), 1.29 (95% CI, 0.93-1.78, P = 0.13), and 1.53 (95% CI, 1.12-2.09, P = 0.007) for all-cause mortality, respectively. A nonlinear relationship between plasma fibrinogen and CV and all-cause mortality was observed. CONCLUSIONS: An elevated plasma fibrinogen level was significantly associated with an increased risk of CV and all-cause mortality in patients undergoing PD.

14.
Neuropsychiatr Dis Treat ; 16: 1519-1532, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606704

RESUMO

Background: Epidemiological studies have shown that genetic factors are among the causes of schizophrenia. Galanin receptor 1 is an inhibitory receptor of galanin that is widely distributed in the central nervous system. This study mainly explored the relationship between polymorphisms of the 5' region of the GALR1 gene and schizophrenia in the northern Chinese Han population. Methods: A 1545 bp fragment of the 5' regulatory region of the GALR1 gene was amplified and sequenced in 289 schizophrenia patients and 347 healthy controls. Results: Among the haplotypes composed of the 16 detected SNPs, the haplotype H3 was identified as conferring a risk of schizophrenia (p=0.011, OR=1.430, 95% CI=1.084-1.886). In addition, the haplotypes H4 and H7 were both protective against schizophrenia (p=0.024, OR=0.526, 95% CI=0.298-0.927; p=0.037, OR=0.197, 95% CI=0.044-0.885, respectively). In the subgroup analysis by sex, it was found that seven SNP alleles (rs72978691, rs11662010, rs11151014, rs11151015, rs13306374, rs5373, rs13306375) conferred a risk of schizophrenia in females (p<0.05), while allele G of rs7242919 (p=0.007) was protective against schizophrenia in females. Moreover, the rs72978691 AA+AC genotype (p=0.006, OR=1.874, 95% CI=1.196-2.937, power=0.780), rs7242919 CC+CG genotype (p=0.002, OR=2.027, 95% CI=1.292-3.180, power=0.861), rs11151014 GG+GT genotype (p=0.008, OR=1.834, 95% CI=1.168-2.879, power=0.735), rs11151015 GG+AG genotype (p=0.002, OR=2.013, 95% CI =1.291-3.137, power=0.843), rs13306374 CC+AC genotype (p=0.006, OR=1.881, 95% CI=1.198-2.953, power=0.788), and rs13306375 GG+AG genotype (p=0.006, OR=1.868, 95% CI=1.194-2.921, power=0.770) increased the risk of schizophrenia in females. The haplotype FH2 consisting of rs72978691, rs11662010, rs7242919, rs11151014, rs11151015, rs13306374, rs5373, and rs13306375 may also be associated with the risk of schizophrenia in females (p=0.024). Conclusion: This study identified an association between polymorphisms in the 5' region of the GALR1 gene and schizophrenia, especially in females.

15.
BMC Genet ; 21(1): 79, 2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32689951

RESUMO

BACKGROUND: The HTR1B gene encodes the 5-hydroxytryptamine (5-HT1B) receptor, which is involved in a variety of brain activities and mental disorders. The regulatory effects of non-coding regions on genomic DNA are one of many reasons for the cause of genetic-related diseases. Post-transcriptional regulation that depends on the function of 3' regulatory regions plays a particularly important role. This study investigated the effects, on reporter gene expression, of several haplotypes of the HTR1B gene (rs6297, rs3827804, rs140792648, rs9361234, rs76194807, rs58138557, and rs13212041) and truncated fragments in order to analyze the function of the 3' region of HTR1B. RESULTS: We found that the haplotype, A-G-Del-C-T-Ins-A, enhanced the expression level compared to the main haplotype; A-G-Del-C-G-Ins-A; G-G-Del-C-G-Ins-G decreased the expression level. Two alleles, rs76194807T and rs6297G, exhibited different relative luciferase intensities compared to their counterparts at each locus. We also found that + 2440 ~ + 2769 bp and + 1953 ~ + 2311 bp regions both had negative effects on gene expression. CONCLUSIONS: The 3' region of HTR1B has a regulatory effect on gene expression, which is likely closely associated with the interpretation of HTR1B-related disorders. In addition, the HTR1B 3' region includes several effector binding sites that induce an inhibitory effect on gene expression.

16.
J Hazard Mater ; 399: 123059, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-32516648

RESUMO

Livestock and poultry manures are major reservoirs of antibiotic-resistant bacteria and antibiotic resistance genes (ARGs). Linezolid is a clinical medicine for humans and has never been approved for use in livestock. Interestingly, three linezolid resistance genes (cfr, optrA, and poxtA) have been detected in bacteria of animal origin, arousing public concern. This study investigated the abundance of three ARGs, cfr, optrA, and poxtA, in manures from 157 large-scale farms in China using real-time quantitative polymerase chain reaction. The residual concentrations of linezolid, florfenicol, tiamulin, and valnemulin were determined using ultra-high performance liquid chromatography-tandem mass spectrometry. A total of 140 livestock farms were tested positive for ARGs, and the positive detection rate was 89.17 %. OptrA was the most commonly detected ARG. The diversity and abundance of ARGs were significantly higher in poultry and swine manure than in bovine manure. Redundancy analysis presented a strong association between florfenicol and all the three ARGs targeted in the study, and tiamulin showed a significant correlation with optrA. Our results indicated that the residual concentration of florfenicol had a major effect on the distribution of the three ARGs in livestock manures, and extensive use of florfenicol may lead to the production of linezolid resistance genes.

17.
Lancet Infect Dis ; 20(10): 1161-1171, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32505232

RESUMO

BACKGROUND: Following the discovery and emergence of the plasmid-mediated colistin resistance gene, mcr-1, the Chinese government formally banned colistin as an animal growth promoter on April 30, 2017. Herein, we report patterns in colistin resistance and mcr-1 abundance in Escherichia coli from animals and humans between 2015 and 2019, to evaluate the effects of the colistin withdrawal. METHODS: We did an epidemiology comparative study to investigate: annual production and sales of colistin in agriculture across mainland China according to data from the China Veterinary Drug Association from 2015 to 2018; the prevalence of colistin-resistant E coli (CREC) in pigs and chickens in 23 Chinese provinces and municipalities as reported in the China Surveillance on Antimicrobial Resistance of Animal Origin database from Jan 1, 2015, to Dec 31, 2016, and Jan 1, 2017, to Dec 31, 2018; the presence of residual colistin and mcr-1 in faeces from 118 animal farms (60 pig, 29 chicken, and 29 cattle) across four provinces over July 1, 2017, to August 31, 2017, and July 1, 2018 to August 31, 2018; the prevalence of mcr-1-positive E coli (MCRPEC) carriage in healthy individuals attending routine hospital examinations across 24 provinces and municipalities from June 1 to July 30, 2019, comparing with equivalent 2016 data (June 1 to September 30) from our previous study in the same hospitals; and the patterns in CREC prevalence among hospital E coli infections across 26 provinces and municipalities from Jan 1, 2015, to Dec 31, 2016, and Jan 1, 2018, to Dec 31, 2019, reported on the China Antimicrobial Surveillance Network. FINDINGS: After the ban on colistin as a growth promoter, marked reductions were observed in the production (27 170 tonnes in 2015 vs 2497 tonnes in 2018) and sale (US$71·5 million in 2015 vs US$8·0 million in 2018) of colistin sulfate premix. Across 118 farms in four provinces, mean colistin residue concentration was 191·1 µg/kg (SD 934·1) in 2017 versus 7·5 µg/kg (50·0) in 2018 (p<0·0001), and the median relative abundance of mcr-1 per 16S RNA was 0·0009 [IQR 0·0001-0·0059] in 2017 versus 0·0002 [0·0000-0·0020] in 2018 (p=0·0001). Across 23 provinces and municipalities, CREC was identified in pig faeces in 1153 (34·0%) of 3396 samples in 2015-16 versus 142 (5·1%) of 2781 in 2017-18 (p<0·0001); and in chickens in 474 (18·1%) of 2614 samples in 2015-16 versus 143 (5·0%) of 2887 in 2017-18 (p<0·0001). In hospitals across 24 provincial capital cities and municipalities, human carriage of MCRPEC was identified in 644 (14·3%) of 4498 samples in 2016 versus 357 (6·3%) of 5657 in 2019 (p<0·0001). Clinical CREC infections in 26 provinces and municipalities comprised 1059 (1·7%) of 62 737 E coli infections in 2015-16 versus 794 (1·3%) of 59 385 in 2018-19 (p<0·0001). INTERPRETATION: The colistin withdrawal policy and the decreasing use of colistin in agriculture have had a significant effect on reducing colistin resistance in both animals and humans in China. However, continuous colistin monitoring is essential, in particular to act as an early warning system for colistin stewardship in Chinese hospitals. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, and UK Medical Research Council.


Assuntos
Colistina/farmacologia , Farmacorresistência Bacteriana/genética , Proteínas de Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Ração Animal/análise , Animais , Antibacterianos/farmacologia , China , Colistina/administração & dosagem , Regulação Bacteriana da Expressão Gênica , Humanos , Legislação de Medicamentos
18.
J Int Med Res ; 48(6): 300060520932801, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32567430

RESUMO

OBJECTIVE: Schizophrenia is a severe neurodevelopmental disorder with a complex genetic and environmental etiology. The gene encoding EF-hand domain-containing protein D2 (EFHD2) may be a genetic risk locus for schizophrenia. METHODS: We genotyped four EFHD2 single-nucleotide polymorphisms (281 schizophrenia cases [SCZ], 321 controls) from northern Chinese Han individuals using Sanger sequencing and polymerase chain reaction-restriction fragment length polymorphism analysis. Differences existed in genotype, allele, and haplotype frequency distributions between SCZ and control groups. RESULTS: The rs2473357 genotype and allele frequency distributions differed between SCZ and controls; however, this difference disappeared after Bonferroni correction. Differences in rs2473357 genotype and allele frequency distributions between SCZ and controls were more pronounced in men than in women. The G allele increased schizophrenia risk (odds ratio = 1.807, 95% confidence interval = 1.164-2.803). Among six haplotypes (G-, A-, G-insC, A-C, G-C, and G-T), the G- haplotype frequency distribution differed between SCZ and controls in women; the A-C and G-C haplotype frequency distributions differed between SCZ and controls in men. CONCLUSIONS: EFHD2 may be involved in schizophrenia. Sex differences in EFHD2 genotype and allele frequency distributions existed among schizophrenia patients. Further research is needed to determine the role of EFHD2 in schizophrenia.

19.
Perit Dial Int ; 40(6): 573-580, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32489134

RESUMO

BACKGROUND: Few studies evaluated over 5-year outcomes of dialysis patients. This study examined 10-year all-cause mortality and death-censored technique failure in a cohort of incident peritoneal dialysis (PD) individuals. METHODS: Five hundred and thirty-three incident PD individuals from 2006 to 2008 were prospectively followed up for more than 10 years until 2018. Clinical characteristics at PD initiation were collected. The primary outcome was all-cause mortality, and the secondary outcome was death-censored technique failure. Cox hazards models were fit using clinical characteristics at PD initiation. RESULTS: The mean age starting PD for these participants was 48 ± 16 years; 130 (24%) patients had diabetic nephropathy. During follow-up, 208 patients died, and 84 patients experienced technique failures. The 1, 3, 5, and 10 years' survival rates for incident PD patients were 93%, 81%, 64%, and 36%, respectively, and the technical survival rates were 98%, 93%, 85%, and 62%, respectively. Mortality risk was much higher after 3 years on PD. The peritonitis rate was 0.19 episodes per patient-year, and 7 (1.3%) patients had encapsulating peritoneal sclerosis (EPS) giving an incidence rate of 3.1 of 1000 patient-years. The main causes of death were cardiovascular events (97 of 208, 47%), and technique failure was mainly due to peritonitis (41 of 84, 49%). Older age, higher Charlson comorbidity index, and lower level of education were strongly associated with mortality, and diabetic nephropathy was an independent risk factor for technique failure. CONCLUSIONS: The 10-year's survival and technique survival rates of incident PD patients were 36% and 62%. Long-term PD can be continued successfully with improved outcomes and low risk for EPS.

20.
Dig Liver Dis ; 52(10): 1076-1079, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32507692

RESUMO

Objective: To explore the clinical characteristics of Coronavirus Disease (COVID-19) patients with gastrointestinal symptoms. Methods: The clinical data of 164 COVID-19 patients with gastrointestinal symptoms were extracted and analysed retrospectively. Results: In total, 505 COVID-19 patients were divided into two groups: those with gastrointestinal symptoms (G group) and those without gastrointestinal symptoms (NG group). Common gastrointestinal symptoms included inappetence, diarrhoea, nausea, abdominal pain, and vomiting. Significantly higher proportions of patients with fever, dizziness, myalgia, and fatigue were noted in group G than in group NG. Compared with patients without fever, there was a significant difference between G group and NG group in moderate fever or above, while there was no significant difference between the two groups in low fever. The laboratory results showed that patients in the G group had significantly higher C-reactive protein, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase levels than those in the NG group. Moreover, the proportion of patients with severe pneumonia was significantly higher in the G group than in the NG group. Conclusion: In Wuhan, the proportion of COVID-19 patients who experience gastrointestinal symptoms is relatively high. Patients who experience gastrointestinal symptoms are more likely to suffer from severe pneumonia, which may help clinicians identify patients at high risk of COVID-19 and thus reduce the incidence of this condition.


Assuntos
Dor Abdominal/fisiopatologia , Anorexia/fisiopatologia , Infecções por Coronavirus/fisiopatologia , Diarreia/fisiopatologia , Náusea/fisiopatologia , Pneumonia Viral/fisiopatologia , Vômito/fisiopatologia , Dor Abdominal/etiologia , Dor Abdominal/metabolismo , Adulto , Idoso , Anorexia/etiologia , Anorexia/metabolismo , Betacoronavirus , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Infecções por Coronavirus/complicações , Infecções por Coronavirus/metabolismo , Diarreia/etiologia , Diarreia/metabolismo , Tontura/etiologia , Tontura/fisiopatologia , Fadiga/etiologia , Fadiga/fisiopatologia , Feminino , Febre/etiologia , Febre/fisiopatologia , Humanos , Hidroxibutirato Desidrogenase/metabolismo , L-Lactato Desidrogenase/metabolismo , Masculino , Pessoa de Meia-Idade , Mialgia/etiologia , Mialgia/fisiopatologia , Náusea/etiologia , Náusea/metabolismo , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/metabolismo , Estudos Retrospectivos , Índice de Gravidade de Doença , Vômito/etiologia , Vômito/metabolismo
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