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Prevalence and drug resistance characteristics of carbapenem-resistant Enterobacteriaceae in Hangzhou

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《医学前沿（英文）》 2018年第12卷第2期页码 182-188 doi: 10.1007/s11684-017-0529-4

摘要：

With the abuse of antimicrobial agents in developing countries, increasing number of carbapenem-resistant Enterobacteriaceae (CRE) attracted considerable public concern. A retrospective study was conducted based on 242 CRE strains from a tertiary hospital in Hangzhou, China to investigate prevalence and drug resistance characteristics of CRE in southeast China. Bacterial species were identified. Antimicrobial susceptibility was examined by broth microdilution method or epsilometer test. Resistant β-lactamase genes were identified by polymerase chain reaction and sequencing. Genotypes were investigated by phylogenetic analysis. and were the most prevalent types of species, with occurrence in 71.9% and 21.9% of the strains, respectively. All strains exhibited high resistance (>70%) against β-lactam antibiotics, ciprofloxacin, trimethoprim–sulfamethoxazole, and nitrofurantoin but exhibited low resistance against tigecycline (0.8%) and minocycline (8.3%). A total of 123 strains harbored more than two kinds of β-lactamase genes. , , , and were the predominant genotypes, with detection rates of 60.3%, 61.6%, 43.4%, and 16.5%, respectively, and were highly identical with reference sequences in different countries, indicating potential horizontal dissemination. IMP-4 was the most frequent class B metallo-lactamases in this study. In conclusion, continuous surveillance and effective prevention should be emphasized to reduce spread of CRE.

关键词： Enterobacteriaceae carbapenem β-lactamase genes phylogenetic analysis

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头孢他啶-阿维巴坦耐药革兰氏阴性菌的流行病学特征及耐药机制 Review

徐婷婷, 郭育奇, 姬扬, 王保红, 周凯

《工程（英文）》 2022年第11卷第4期页码 138-145 doi: 10.1016/j.eng.2020.11.004

摘要：

细菌的碳青霉烯耐药性是全球公共健康面临的一个重大挑战，由碳青霉烯耐药菌（CRO）引起的临床感染通常有很高的发病率和死亡率。头孢他啶-阿维巴坦（CAZ-AVI）是一种新型头孢菌素/β-内酰胺酶抑制剂，为临床治疗CRO感染提供了一项重要选择。据报道，CAZ-AVI 能够抑制Ambler A类、C类以及部分D类酶的活性。然而，这种药物在临床使用后不久，细菌的耐药性就已经出现，并且呈上升趋势。了解细菌对CAZ-AVI 的耐药机制，对于指导开发新型治疗方法、帮助预测潜在的耐药机制至关重要。本文旨在系统总结CAZ-AVI 耐药菌株的流行病学发展过程和最近发现的CAZ-AVI 耐药机制；将重点关注β-内酰胺酶突变体的产生、β-内酰胺酶高表达、细胞表面通透性降低以及药物外排泵的过表达。短时间内多种CAZ-AVI耐药机制的产生，强调了临床合理用药的重要性以及监测CAZ-AVI 耐药性病原体的必要性。

关键词：头孢他啶-阿维巴坦耐药机制碳青霉烯耐药性 β-内酰胺/β-内酰胺酶抑制剂

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碳青霉烯类耐药性在人源和动物源产NDM酶大肠埃希菌间的传播 Article

沈应博, 胡付品, 王永强, 尹丹丹, 杨璐, 陈义强, 许春燕, 李基云, 蒋君瑶, 王雪杨, 付玉林, 邵东延, 刘德俊, 马藤菲, 蔡畅, 沈张奇, 王少林, 李娟, 张嵘, 柯跃斌, 吴聪明, 沈建忠, Timothy R. Walsh, 汪洋

《工程（英文）》 2022年第15卷第8期页码 24-33 doi: 10.1016/j.eng.2021.07.030

摘要：

Although carbapenem use is prohibited in animals in China, carbapenem-resistant Escherichia coli (CREC), especially New Delhi metallo-β-lactamase (NDM)-producing strains, are widely prevalent in foodproducing animals. At present, the impact of livestock-associated CREC strains on human populations at the national level is unknown. Here, we conduct a retrospective cross-sectional study to investigate the prevalence of CREC from clinical settings across 22 Chinese provinces or municipalities and analyze anthropogenic factors associated with their presence. We also ascertain the bla_NDM and bla_KPC abundance among pig and chicken farms and present a detailed genomic framework for CREC of animal and human origin. Overall, 631/29799 (2.1%) clinical Escherichia coli (E. coli) isolates were identified as CREC. Multivariable analysis revealed that being male, an age below 1, an age between 13 and 18, provinces with greater chicken production, and provinces with higher pig production were associated with higher odds of CREC infection. In general, 73.8% (n = 45/61) of pig farms and 62.2% (n = 28/45) of chicken farms had a bla_NDM abundance of 1×10^－5 to 1×10^－3 and 1×10－3 to 1×10^－2, respectively. Among all the Chinese NDM-positive E. coli (n = 463) available at the National Center for Biotechnology Information (NCBI), the genomic analysis revealed that bla_NDM-5 and IncX3 were the predominant carbapenemase gene-plasmid combination, while a highly homogeneous relationship between NDM-positive isolates from humans and animals was demonstrated at the plasmid and core genome levels. All the findings suggest frequent CREC transmission between humans and animals, indicating that further discussions on the use of antibiotics in animals and humans are needed, both in China and across the globe.

关键词： Carbapenem resistance Escherichia coli bla^NDM-5 One Health Antimicrobial resistance transmission

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Prevalence of antifolate drug resistance markers in in China

《医学前沿（英文）》 2022年第16卷第1期页码 83-92 doi: 10.1007/s11684-021-0894-x

摘要： The dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes of Plasmodium vivax and antifolate resistance-associated genes were used for drug resistance surveillance. A total of 375 P. vivax isolates collected from different geographical locations in China in 2009–2019 were used to sequence Pvdhfr and Pvdhps. The majority of the isolates harbored a mutant type allele for Pvdhfr (94.5%) and Pvdhps (68.2%). The most predominant point mutations were S117T/N (77.7%) in Pvdhfr and A383G (66.8%) in Pvdhps. Amino acid changes were identified at nine residues in Pvdhfr. A quadruple-mutant haplotype at 57, 58, 61, and 117 was the most frequent (57.4%) among 16 distinct Pvdhfr haplotypes. Mutations in Pvdhps were detected at six codons, and the double-mutant A383G/A553G was the most prevalent (39.3%). Pvdhfr exhibited a higher mutation prevalence and greater diversity than Pvdhps in China. Most isolates from Yunnan carried multiple mutant haplotypes, while the majority of samples from temperate regions and Hainan Island harbored the wild type or single mutant type. This study indicated that the antifolate resistance levels of P. vivax parasites were different across China and molecular markers could be used to rapidly monitor drug resistance. Results provided evidence for updating national drug policy and treatment guidelines.

关键词： drug resistance antifolates molecular markers Plasmodium vivax China

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Metagenomic analysis on resistance genes in water and microplastics from a mariculture system

《环境科学与工程前沿（英文）》 2022年第16卷第1期页码 4-4 doi: 10.1007/s11783-021-1438-y

摘要：

Microplastics existing widely in different matrices have been regarded as a reservoir for emerging contaminants. Mariculture systems have been observed to host microplastics and antibiotic resistance genes (ARGs). However, more information on proliferation of ARGs and metal resistance genes (MRGs) in mariculture system at the presence of microplastics is needed.

关键词： Antibiotic resistance genes Metal resistance genes Metagenomic analysis Microplastics Mariculture

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Taking advantage of drug resistance, a new approach in the war on cancer

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《医学前沿（英文）》 2018年第12卷第4期页码 490-495 doi: 10.1007/s11684-018-0647-7

摘要：

Identification of the driver mutations in cancer has resulted in the development of a new category of molecularly targeted anti-cancer drugs. However, as was the case with conventional chemotherapies, the effectiveness of these drugs is limited by the emergence of drug-resistant variants. While most cancer therapies are given in combinations that are designed to avoid drug resistance, we discuss here therapeutic approaches that take advantage of the changes in cancer cells that arise upon development of drug resistance. This approach is based on notion that drug resistance comes at a fitness cost to the cancer cell that can be exploited for therapeutic benefit. We discuss the development of sequential drug therapies in which the first therapy is not given with curative intent, but to induce a major new sensitivity that can be targeted with a second drug that selectively targets the acquired vulnerability. This concept of collateral sensitivity has hitherto not been used on a large scale in the clinic and holds great promise for future cancer therapy.

关键词： cancer drug resistance genetic screens senescence targeted therapy

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Targeting apoptosis to manage acquired resistance to third generation EGFR inhibitors

《医学前沿（英文）》 2022年第16卷第5期页码 701-713 doi: 10.1007/s11684-022-0951-0

摘要： A significant clinical challenge in lung cancer treatment is management of the inevitable acquired resistance to third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs), such as osimertinib, which have shown remarkable success in the treatment of advanced NSCLC with EGFR activating mutations, in order to achieve maximal response duration or treatment remission. Apoptosis is a major type of programmed cell death tightly associated with cancer development and treatment. Evasion of apoptosis is considered a key hallmark of cancer and acquisition of apoptosis resistance is accordingly a key mechanism of drug acquired resistance in cancer therapy. It has been clearly shown that effective induction of apoptosis is a key mechanism for third generation EGFR-TKIs, particularly osimertinib, to exert their therapeutic efficacies and the development of resistance to apoptosis is tightly associated with the emergence of acquired resistance. Hence, restoration of cell sensitivity to undergo apoptosis using various means promises an effective strategy for the management of acquired resistance to third generation EGFR-TKIs.

关键词： acquired resistance EGFR inhibitor apoptosis lung cancer

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Transmission of antibiotic resistance genes in agroecosystems: an overview

Jizheng HE, Zhenzhen YAN, Qinglin CHEN

《农业科学与工程前沿（英文）》 2020年第7卷第3期页码 329-332 doi: 10.15302/J-FASE-2020333

摘要：

The use of antibiotics in human medicine and animal husbandry has resulted in the continuous release of antibiotics into the environment, which imposes high selection pressure on bacteria to develop antibiotic resistance. The spread and aggregation of antibiotic resistance genes (ARGs) in multidrug-resistant pathogens is one of the most intractable clinical challenges. Numerous studies have been conducted to profile the patterns of ARGs in agricultural ecosystems, as this is closely related to human health and wellbeing. This paper provides an overview of the transmission of ARGs in agricultural ecosystems resulting from the application of animal manures and other organic amendments. The future need to control and mitigate the spread of antibiotic resistance in agricultural ecosystems is also discussed, particularly from a holistic perspective, and requires multiple sector efforts to translate fundamental knowledge into effective strategies.

关键词： agroecosystem antibiotic resistance public health soil-plant system

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swine manure with sulfamethoxazole and norfloxacin: Dynamics of microbial communities and evolution of resistance

《环境科学与工程前沿（英文）》 2021年第15卷第5期 doi: 10.1007/s11783-020-1342-x

摘要：

• SMX addition had negative effect on acetoclastic methanogens in mesophilic AD.

关键词： Pig manure Antibiotics Anaerobic digestion Resistance genes Microbial community

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Degradation of extracellular genomic, plasmid DNA and specific antibiotic resistance genes by chlorination

Menglu Zhang, Sheng Chen, Xin Yu, Peter Vikesland, Amy Pruden

《环境科学与工程前沿（英文）》 2019年第13卷第3期 doi: 10.1007/s11783-019-1124-5

摘要：

Extracellular DNA structure damaged by chlorination was characterized.

Integrity of extracellular ARG genetic information after chlorination was determined.

Typical chlorine doses will likely effectively diminish extracellular DNA and ARGs.

Plasmid DNA/ARGs were less readily broken down than genomic DNA.

The Bioanalyzer methodology effectively documented damage incurred to DNA.

关键词： Antibiotic resistance Antibiotic resistance genes (ARGs) Extracellular DNA/ARGs Chlorination

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Insulin resistance and the metabolism of branched-chain amino acids

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《医学前沿（英文）》 2013年第7卷第1期页码 53-59 doi: 10.1007/s11684-013-0255-5

摘要：

Insulin resistance (IR) is a key pathological feature of metabolic syndrome and subsequently causes serious health problems with an increased risk of several common metabolic disorders. IR related metabolic disturbance is not restricted to carbohydrates but impacts global metabolic network. Branched-chain amino acids (BCAAs), namely valine, leucine and isoleucine, are among the nine essential amino acids, accounting for 35% of the essential amino acids in muscle proteins and 40% of the preformed amino acids required by mammals. The BCAAs are particularly responsive to the inhibitory insulin action on amino acid release by skeletal muscle and their metabolism is profoundly altered in insulin resistant conditions and/or insulin deficiency. Although increased circulating BCAA concentration in insulin resistant conditions has been noted for many years and BCAAs have been reported to be involved in the regulation of glucose homeostasis and body weight, it is only recently that BCAAs are found to be closely associated with IR. This review will focus on the recent findings on BCAAs from both epidemic and mechanistic studies.

关键词： branched-chain amino acids leucine isoleucine valine insulin resistance

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Immunometabolism: a new dimension in immunotherapy resistance

《医学前沿（英文）》 2023年第17卷第4期页码 585-616 doi: 10.1007/s11684-023-1012-z

摘要： Immune checkpoint inhibitors (ICIs) have demonstrated unparalleled clinical responses and revolutionized the paradigm of tumor treatment, while substantial patients remain unresponsive or develop resistance to ICIs as a single agent, which is traceable to cellular metabolic dysfunction. Although dysregulated metabolism has long been adjudged as a hallmark of tumor, it is now increasingly accepted that metabolic reprogramming is not exclusive to tumor cells but is also characteristic of immunocytes. Correspondingly, people used to pay more attention to the effect of tumor cell metabolism on immunocytes, but in practice immunocytes interact intimately with their own metabolic function in a way that has never been realized before during their activation and differentiation, which opens up a whole new frontier called immunometabolism. The metabolic intervention for tumor-infiltrating immunocytes could offer fresh opportunities to break the resistance and ameliorate existing ICI immunotherapy, whose crux might be to ascertain synergistic combinations of metabolic intervention with ICIs to reap synergic benefits and facilitate an adjusted anti-tumor immune response. Herein, we elaborate potential mechanisms underlying immunotherapy resistance from a novel dimension of metabolic reprogramming in diverse tumor-infiltrating immunocytes, and related metabolic intervention in the hope of offering a reference for targeting metabolic vulnerabilities to circumvent immunotherapeutic resistance.

关键词： immune cell immunometabolism metabolic reprogramming immunotherapy resistance tumor microenvironment immune checkpoint inhibitor

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Characteristics of two transferable aminoglycoside resistance plasmids in

Chengjun Pu, Xiaoyan Gong, Ying Sun

《环境科学与工程前沿（英文）》 2019年第13卷第3期 doi: 10.1007/s11783-019-1119-2

摘要：

pRKZ3 is a non-conjugative IncQ plasmid, while pKANJ7 is a conjugative IncX plasmid.

The optimal mating time of pKANJ7 varied under different conditions.

Both of the two transferable ARPs had little impact on the growth of their hosts.

A relatively high level of fitness cost was observed for pKANJ7.

The fitness cost of ARPs depended on their hosts.

关键词： Escherichia coli Characteristics Aminoglycoside resistance plasmids Transfer Persistence

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Correlation between tension softening relation and crack extension resistance in concrete

Xiufang ZHANG , Shilang XU ,

《结构与土木工程前沿（英文）》 2009年第3卷第3期页码 323-329 doi: 10.1007/s11709-009-0041-2

摘要： Changes of the material fracture energy consumption with crack propagation can be described by a crack extension resistance curve, one of the fundamental fracture criteria in crack mechanics. Recently, experimental observation of the fracture behavior in concrete was used to develop a new fracture criterion, the crack extension resistance curve, to analyze crack propagation during the entire concrete fracture process. The variation of the crack extension resistance is mainly associated with the energy consumption in the fracture process zone ahead of the stress-free crack tip. The crack extension resistance is then a function of the softening curve, which is a basic mechanical property in the fracture process zone. The relationship between the softening curve and the crack extension resistance curve is then analyzed based on results of three-point bending beams tests. The results indicate that the characteristic points of the crack extension resistance curve is closely related to the characteristic point on used tension softening curve.

关键词： concrete fracture process zone crack extension G_R resistance tension softening curve