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Medical image segmentation is the most widely used technique in diagnostic and clinical research. However, accurate segmentation of target organs from blurred border regions and low-contrast adjacent organs in Computed tomography (CT) imaging is crucial for clinical diagnosis and treatment.In this article, we propose a Multi-Scale Feature Pyramid Fusion Network (MS-Net) based on the codec structure formed by the combination of Multi-Scale Attention Module (MSAM) and Stacked Feature Pyramid Module (SFPM). Among them, MSAM is used to skip connections, which aims to extract different levels of context details by dynamically adjusting the receptive fields under different network depths; the SFPM including multi-scale strategies and multi-layer Feature Perception Module (FPM) is nested in the network at the deepest point, which aims to better focus the network's attention on the target organ by adaptively increasing the weight of the features of interest.Experiments demonstrate that the proposed MS-Net significantly improved the Dice score from 91.74% to 94.54% on CHAOS, from 97.59% to 98.59% on Lung, and from 82.55% to 86.06% on ISIC 2018, compared with U-Net. Additionally, comparisons with other six state-of-the-art codec structures also show the presented network has great advantages on evaluation indicators such as Miou, Dice, ACC and AUC.The experimental results show that both the MSAM and SFPM techniques proposed in this paper can assist the network to improve the segmentation effect, so that the proposed MS-Net method achieves better results in the CHAOS, Lung and ISIC 2018 segmentation tasks.

In lung adenocarcinoma (LUAD), the appearance of morphologically diverse tumor regions, termed histological patterns, is closely associated with disease progression and lymph node metastasis. However, the molecular characteristics of the histological patterns in LUAD and the underlying molecular evolutionary mechanisms between the histological patterns in primary tumors and lymph node metastases are poorly understood. Here, we re-analyzed the large TCGA-LUAD dataset and depicted a comprehensive profiling of the genome and transcriptome across the histological patterns in LUAD. Tumor phylogenetic trajectory analysis suggested that the complex glands is more apt to metastasize to the lymph node. Further deconvolution of the tumor microenvironment demonstrated that the complex glands had a higher infiltration of cancer-associated fibroblasts (CAFs). Single-cell transcriptome profiling of complex glands pattern identified a novel CAF subtype co-expressing fibroblast activation protein-alpha (FAP) and stimulator of interferon genes (STING). Moreover, our data demonstrated that FAP is an important downstream effector of STING in CAFs. In summary, our results provide the basis for the development of innovative therapeutic guidelines and intervention strategies for LUAD patients.

Introduction Clostridioides (Clostridium) difficile infection, the leading cause of healthcare-associated diarrhea, represents a significant burden on global healthcare systems. Despite being a global issue, information on C. difficile from a global perspective is lacking. The aim of this study is to model the global phylogeography of clinical C. difficile. Methods Using samples collected from the MODIFY I and II studies (NCT01241552, NCT01513239), we performed whole-genome sequencing of 1501 clinical isolates including 37 novel sequence types (STs), representing the largest worldwide collection to date. Results Our data showed ribotypes, multi-locus sequence typing clades, and whole-genome phylogeny were in good accordance. The clinical C. difficile genome was found to be more conserved than previously reported (61% core genes), and modest recombination rates of 1.4-5.0 were observed across clades. We observed a significant continent distribution preference among five C. difficile clades (Benjamini-Hochberg corrected Fisher's exact test P

Background COVID-19 (coronavirus disease 2019) has caused a major epidemic worldwide; however, much is yet to be known about the epidemiology and evolution of the virus partly due to the scarcity of full-length SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) genomes reported. One reason is that the challenges underneath sequencing SARS-CoV-2 directly from clinical samples have not been completely tackled, i.e., sequencing samples with low viral load often results in insufficient viral reads for analyses. Methods We applied a novel multiplex PCR amplicon (amplicon)-based and hybrid capture (capture)-based sequencing, as well as ultra-high-throughput metatranscriptomic (meta) sequencing in retrieving complete genomes, inter-individual and intra-individual variations of SARS-CoV-2 from serials dilutions of a cultured isolate, and eight clinical samples covering a range of sample types and viral loads. We also examined and compared the sensitivity, accuracy, and other characteristics of these approaches in a comprehensive manner. Results We demonstrated that both amplicon and capture methods efficiently enriched SARS-CoV-2 content from clinical samples, while the enrichment efficiency of amplicon outran that of capture in more challenging samples. We found that capture was not as accurate as meta and amplicon in identifying between-sample variations, whereas amplicon method was not as accurate as the other two in investigating within-sample variations, suggesting amplicon sequencing was not suitable for studying virus-host interactions and viral transmission that heavily rely on intra-host dynamics. We illustrated that meta uncovered rich genetic information in the clinical samples besides SARS-CoV-2, providing references for clinical diagnostics and therapeutics. Taken all factors above and cost-effectiveness into consideration, we proposed guidance for how to choose sequencing strategy for SARS-CoV-2 under different situations. Conclusions This is, to the best of our knowledge, the first work systematically investigating inter- and intra-individual variations of SARS-CoV-2 using amplicon- and capture-based whole-genome sequencing, as well as the first comparative study among multiple approaches. Our work offers practical solutions for genome sequencing and analyses of SARS-CoV-2 and other emerging viruses.

Understanding the impacts of nitrogen (N) deposition on soil respiration (Rs) and its components (autotrophic respiration (Ra) and heterotrophic respiration (Rh)) in urban forests is crucial for predicting the soil carbon dioxide (CO2) emission and evaluating carbon (C) budget in changing environments. In this study, a three-year-long field manipulation experiment was conducted in two urban forests to assess the effect of N application at three rates (0, 50, and 100 kg N·ha−1·year−1) on Rs components. N application did not alter the seasonal dynamics of Rs and its components. Rs and its components showed nonlinear responses to N application; both Rs and Rh increased in year 1 of N application but decreased in year 3. The Ra/Rs ratio increased by 21% in the low N (50 kg N·ha−1·year−1) plots. The mechanism varied across the years of N application; soil temperature and moisture substantially influenced Ra and Rh under N application. Our results indicated that increasing atmospheric N deposition may inhibit soil CO2 emission, and a higher proportion of soil C is released due to root activities. Interannual variations in temperature and rainfall may help predict the efflux of soil CO2 in urban forests in response to atmospheric N deposition.

In modern industrial systems, high-dimensional process data provide rich information for process monitoring. To make full use of local information of industrial process, a distributed robust dictionary pair learning (DRDPL) is proposed for refined process monitoring. Firstly, the global system is divided into several sub-blocks based on the reliable prior knowledge of industrial processes, which achieves dimensionality reduction and reduces process complexity. Secondly, a robust dictionary pair learning (RDPL) method is developed to build a local monitoring model for each sub-block. The sparse constraint with l2,1 norm is added to the analytical dictionary, and a low rank constraint is applied to the synthetical dictionary, so as to obtain robust dictionary pairs. Then, Bayesian inference method is introduced to fuse local monitoring information to global anomaly detection, and the block contribution index and variable contribution index are used to realize anomaly isolation. Finally, the effectiveness of the proposed method is verified by a numerical simulation experiment and Tennessee Eastman benchmark tests, and the proposed method is then successfully applied to a real-world aluminum electrolysis process.

Identifying active prophages is critical for studying coevolution of phage and bacteria, investigating phage physiology and biochemistry, and engineering designer phages for diverse applications. We present Prophage Hunter, a tool aimed at hunting for active prophages from whole genome assembly of bacteria. Combining sequence similarity-based matching and genetic features-based machine learning classification, we developed a novel scoring system that exhibits higher accuracy than current tools in predicting active prophages on the validation datasets. The option of skipping similarity matching is also available so that there's higher chance for novel phages to be discovered. Prophage Hunter provides a one-stop web service to extract prophage genomes from bacterial genomes, evaluate the activity of the prophages, identify phylogenetically related phages, and annotate the function of phage proteins. Prophage Hunter is freely available at https://pro-hunter.bgi.com/.

Reference genomes are essential for metagenomic analyses and functional characterization of the human gut microbiota. We present the Culturable Genome Reference (CGR), a collection of 1,520 nonredundant, high-quality draft genomes generated from >6,000 bacteria cultivated from fecal samples of healthy humans. Of the 1,520 genomes, which were chosen to cover all major bacterial phyla and genera in the human gut, 264 are not represented in existing reference genome catalogs. We show that this increase in the number of reference bacterial genomes improves the rate of mapping metagenomic sequencing reads from 50% to >70%, enabling higher-resolution descriptions of the human gut microbiome. We use the CGR genomes to annotate functions of 338 bacterial species, showing the utility of this resource for functional studies. We also carry out a pan-genome analysis of 38 important human gut species, which reveals the diversity and specificity of functional enrichment between their core and dispensable genomes., A resource of >1,500 bacterial reference genomes sheds light on the human gut microbiome.

Mutations are an important origin of antibiotic resistance in bacteria. While there is increasing evidence showing promoted resistance mutations by environmental stresses, no retrospective research has yet been conducted on this phenomenon and its mechanisms. Herein, we summarized the phenomena of stress-elevated resistance mutations in bacteria, generalized the regulatory mechanisms and discussed the environmental and human health implications. It is shown that both chemical pollutants, such as antibiotics and other pharmaceuticals, biocides, metals, nanoparticles and disinfection byproducts, and non-chemical stressors, such as ultraviolet radiation, electrical stimulation and starvation, are capable of elevating resistance mutations in bacteria. Notably, resistance mutations are more likely to occur under sublethal or subinhibitory levels of these stresses, suggesting a considerable environmental concern. Further, mechanisms for stress-induced mutations are summarized in several points, namely oxidative stress, SOS response, DNA replication and repair systems, RpoS regulon and biofilm formation, all of which are readily provoked by common environmental stresses. Given bacteria in the environment are confronted with a variety of unfavorable conditions, we propose that the stress-elevated resistance mutations are a universal phenomenon in the environment and represent a nonnegligible risk factor for ecosystems and human health. The present review identifies a need for taking into account the pollutants' ability to elevate resistance mutations when assessing their environmental and human health risks and highlights the necessity of including resistance mutations as a target to prevent antibiotic resistance evolution.

Background: K. pneumoniae can cause a wide range of diseases, and is highly associated with antimicrobial-resistant infections in hospitals. We aimed to characterize a five-year collection of K. pneumoniae genomes, and identify transmission events that were not identified by conventional typing approaches. Methods: From January 5, 2013 to July 24, 2018, 3,061 K. pneumoniae isolates were unbiasedly collected, and sequenced. The earliest strain recovered for each patient was retrospectively analyzed for the genomic epidemiology. Pairwise core-genome single-nucleotide polymorphism (cgSNP) distances were measured. An F1 score well differentiating isolates from the same ward and collected within 180 days was calculated. The best distance cutoffs, and the spatial-temporal information of each clone were combined to define transmission sub-lineages. Findings: A sum of 2,193 non-duplicated genomes was clustered into four species complexes. 93% (n = 2,035) was KpI with its largest clonal group being CG11 (20%, n = 406; 393 were ST11). 92% (n = 374) CG11 carried the carbapenem-resistant gene blaKPC-2. Four transmission sub- lineages (ST307-neo, ST20-neo, ST25-neo, and ST25-icu) were confidently identified by the integrated epidemiological-genomic method. None was from the high-endemic-risk clone CG11. Interpretation: Strain transmissions by low-endemic-risk clones are easy to be neglected by routine surveillance. Whole-genome sequencing analysis identified four episodes of within-ward transmissions of those neglectable clones: three in a neonatal ward, and one in ICU. Both wards are full of vulnerable patients. Thus, this study highlights the importance of including high-resolution typing technologies in infection surveillance, particularly for the neonates and critically-ill patients. Funding Information: This work was supported by National Natural Science Foundation of China [grant number 81672066 to WL]. This work was also supported by China National GeneBank (CNGB). Declaration of Interests: We declare no competing interests. Ethics Approval Statement: This study was approved by the ethics committees under tracking numbers 201806861 and BGI‐IRB 18061.

Additional file 2: Fig. S1. Correlation of estimated alternative allele frequencies between metatranscriptomic and hybrid capture data. Fig. S2. Correlation of estimated minor alternative allele frequencies between biological replicates. Fig. S3. Correlation between sequencing depth and detected iSNVs. Fig. S4. Number of iSNV among three codon positions. Fig. S5. Haplotype frequency of proximal iSNVs within the gastrointestinal tract of patient P01.

Advances in synthetic genomics have led to a great demand for genetic manipulation. Trimming any process to simplify and accelerate streamlining of genetic code into life holds great promise for synthesizing and studying organisms. Here, we develop a simple but powerful stepping-stone strategy to promote genome refactoring of viruses in one pot, validated by successful cross-genus and cross-order rebooting of 90 phages infecting 4 orders of popular pathogens. Genomic sequencing suggests that rebooting outcome is associated with gene number and DNA polymerase availability within phage genomes. We integrate recombineering, screening, and rebooting processes in one pot and demonstrate genome assembly and genome editing of phages by stepping-stone hosts in an efficient and economic manner. Under this framework

BackgroundSince early February 2021, the causative agent of COVID-19, SARS-CoV-2, has infected over 104 million people with more than 2 million deaths according to official reports. The key to understanding the biology and virus-host interactions of SARS-CoV-2 requires the knowledge of mutation and evolution of this virus at both inter- and intra-host levels. However, despite quite a few polymorphic sites identified among SARS-CoV-2 populations, intra-host variant spectra and their evolutionary dynamics remain mostly unknown.MethodsUsing high-throughput sequencing of metatranscriptomic and hybrid captured libraries, we characterized consensus genomes and intra-host single nucleotide variations (iSNVs) of serial samples collected from eight patients with COVID-19. The distribution of iSNVs along the SARS-CoV-2 genome was analyzed and co-occurring iSNVs among COVID-19 patients were identified. We also compared the evolutionary dynamics of SARS-CoV-2 population in the respiratory tract (RT) and gastrointestinal tract (GIT).ResultsThe 32 consensus genomes revealed the co-existence of different genotypes within the same patient. We further identified 40 intra-host single nucleotide variants (iSNVs). Most (30/40) iSNVs presented in a single patient, while ten iSNVs were found in at least two patients or identical to consensus variants. Comparing allele frequencies of the iSNVs revealed a clear genetic differentiation between intra-host populations from the respiratory tract (RT) and gastrointestinal tract (GIT), mostly driven by bottleneck events during intra-host migrations. Compared to RT populations, the GIT populations showed a better maintenance and rapid development of viral genetic diversity following the suspected intra-host bottlenecks.ConclusionsOur findings here illustrate the intra-host bottlenecks and evolutionary dynamics of SARS-CoV-2 in different anatomic sites and may provide new insights to understand the virus-host interactions of coronaviruses and other RNA viruses.

As of middle May 2020, the causative agent of COVID-19, SARS-CoV-2, has infected over 4 million people with more than 300 thousand death as official reports1,2. The key to understanding the biology and virus-host interactions of SARS-CoV-2 requires the knowledge of mutation and evolution of this virus at both inter- and intra-host levels. However, despite quite a few polymorphic sites identified among SARS-CoV-2 populations, intra-host variant spectra and their evolutionary dynamics remain mostly unknown. Here, using deep sequencing data, we achieved and characterized consensus genomes and intra-host genomic variants from 32 serial samples collected from eight patients with COVID-19. The 32 consensus genomes revealed the coexistence of different genotypes within the same patient. We further identified 40 intra-host single nucleotide variants (iSNVs). Most (30/40) iSNVs presented in single patient, while ten iSNVs were found in at least two patients or identical to consensus variants. Comparison of allele frequencies of the iSNVs revealed genetic divergence between intra-host populations of the respiratory tract (RT) and gastrointestinal tract (GIT), mostly driven by bottleneck events among intra-host transmissions. Nonetheless, we observed a maintained viral genetic diversity within GIT, showing an increased population with accumulated mutations developed in the tissue-specific environments. The iSNVs identified here not only show spatial divergence of intra-host viral populations, but also provide new insights into the complex virus-host interactions.

COVID-19 has caused a major epidemic worldwide, however, much is yet to be known about the epidemiology and evolution of the virus. One reason is that the challenges underneath sequencing HCoV-19 directly from clinical samples have not been completely tackled. Here we illustrate the application of amplicon and hybrid capture (capture)-based sequencing, as well as ultra-high-throughput metatranscriptomic (meta) sequencing in retrieving complete genomes, inter-individual and intra-individual variations of HCoV-19 from clinical samples covering a range of sample types and viral load. We also examine and compare the bias, sensitivity, accuracy, and other characteristics of these approaches in a comprehensive manner. This is, to date, the first work systematically implements amplicon and capture approaches in sequencing HCoV-19, as well as the first comparative study across methods. Our work offers practical solutions for genome sequencing and analyses of HCoV-19 and other emerging viruses.

Additional file 2: Fig. S1. Normalized coverage across SARS-CoV-2 genomes of serial dilutions of the cultured isolate sequenced by multiple approaches. Fig. S2. Sanger sequencing results of SNVs in clinical samples. Fig. S3. Box-plot of allele frequencies against SARS-CoV-2 genome copies per mL. Fig. S4. Taxonomy of clinical samples by unbiased metatranscriptomic sequencing. Table S2. Capture sequencing data summary of serial dilutions of the cultured isolate and eight SARS-CoV-2 positive clinical samples collected from Guangzhou (PE100). Table S3. Amplicon sequencing data summary of serial dilutions of the cultured isolate and eight SARS-CoV-2 positive clinical samples collected from Guangzhou (SE400). Table S4. Estimated minimum amount of sequencing data required to achieve ≥10X sequencing depth and ≥ 95% coverage for different methods. Table S5. Estimated minimum amount of sequencing data required to achieve high-confidence variants calling analyses for different methods. Table S6. Bioinformatic tools and parameters used in this study.

Food preservatives are important for the storage of foods, and natural polyphenols with antioxidant and antibacterial effects are often effective as food preservatives. In this study, we systemically investigated the phenolic composition, antioxidant and antibacterial effects of 28 pigmented edible bean coat extracts. Most of these bean coat extracts had a relatively high level of total phenolic content, mainly flavonoids and proanthocyanidins, and they also exhibited much higher antioxidant effect than most common fruits, vegetables and cereal grains. In addition, most of them showed antibacterial effects, mainly against gram-positive bacteria, higher than the effect of phenol. Correlation analysis and principal component analysis indicated that flavonoids and proanthocyanidins were mostly responsible for the antioxidant and antibacterial effects of these bean coat extracts. Therefore, the pigmented bean coats rich in polyphenols with antioxidant and antibacterial effects are potential candidates as food preservatives.

Bacterial multidrug efflux pumps belong to a class of membrane transporter proteins that dedicate to the extrusion of a diverse range of substances out of cells including all classes of currently available antibiotics. They constitute an important mechanism of bacterial antibiotic and multidrug resistance. Since many ecological niches of bacteria and the infection foci in animal host display low oxygen tension under which condition bacterial pathogens undergo fundamental changes on their metabolic modes, it is necessary to study the expression profiles of drug efflux pumps under these physiologically and clinically relevant conditions. In this chapter, we first introduce procedures to culture bacteria under anaerobic conditions, which is achieved using screw-capped Pyrex culture tubes without agitation. We then introduce β-galactosidase activity assay using promoter-lacZ (encoding the β-galactosidase enzyme) fusion to measure the expression of efflux pumps at transcriptional level, and Western blot using chromosomal FLAG-tagged construct to examine the expression of these proteins at translational level. Applications of these gene expression studies to reveal the regulatory mechanisms of efflux genes expression as well as their physiological functions are also discussed.

Bacterial multidrug efflux pumps belong to a class of membrane transporter proteins that dedicate to the extrusion of a diverse range of substances out of cells including all classes of currently available antibiotics. They constitute an important mechanism of bacterial antibiotic and multidrug resistance. Since many ecological niches of bacteria and the infection foci in animal host display low oxygen tension under which condition bacterial pathogens undergo fundamental changes on their metabolic modes, it is necessary to study the expression profiles of drug efflux pumps under these physiologically and clinically relevant conditions. In this chapter, we first introduce procedures to culture bacteria under anaerobic conditions, which is achieved using screw-capped Pyrex culture tubes without agitation. We then introduce β-galactosidase activity assay using promoter-lacZ (encoding the β-galactosidase enzyme) fusion to measure the expression of efflux pumps at transcriptional level, and Western blot using chromosomal FLAG-tagged construct to examine the expression of these proteins at translational level. Applications of these gene expression studies to reveal the regulatory mechanisms of efflux genes expression as well as their physiological functions are also discussed.

Gastric duplication cyst is a very rare gastrointestinal tract malformation that accounts for 2%-4% of alimentary tract duplications. It is a diagnostic dilemma for doctors because its clinical and radiological manifest is usually nonspecific. At the present stage, it can only rely on surgery. We should pay attention to ectopic pancreas resection and ligation of pancreatic duct during operation. There was one case of gastric duplication cyst with ectopic pancreas in adults from the Second Affiliated Hospital of Nanchang University.胃重复囊肿是非常少见的胃肠道畸形，占整个消化道畸形发生率的2%~4%。因为该病的临床及影像学表现非特异性，诊断较为困难，现阶段只能依靠手术切除治疗，术中应注意异位胰腺的合并切除并结扎胰腺管道。南昌大学第二附属医院胃肠外科收治1例成人胃重复囊肿伴异位胰腺，给予胃部分切除术后治愈出院。.

To evaluate the safety, feasibility and effectiveness of laparoscopic-assisted resection of colorectal cancer without incision at abdomen vs the traditional laparoscopic resection. Methods: We retrieved literature published from August, 2005 to August, 2015 to compare laparoscopic-assisted resection for colorectal cancer without incision at abdomen with the traditional laparoscopic resection. The clinical indicators were extracted from literature met inclusion criteria. The RevMan 5.3 software with a Meta-analysis was used. Results: Seven literature with a total of 621 patients, including 262 in laparoscopic-assisted resection of colorectal cancer without auxiliary incision at abdomen group (NOSE group) and 359 in conventional laparoscopic colorectal resection group (LAP group), were enrolled. The Meta-analysis showed that the total complication rate in the NOSE group was significantly less than that in the LAP group (OR=0.31, 95% CI 0.18 to 0.53, P0.05). Complications of incision in the NOSE group were less than those in the LAP group (OR= 0.15, 95% CI 0.05 to 0.40, P=0.0002). Postoperative bleeding (OR=1.52, 95% CI 0.38 to 6.18, P=0.55), intestinal obstruction (OR= 0.30, 95% CI 0.09 to 0.98, P=0.05), anastomotic complications (OR=0.92, 95% CI 0.28 to 3.07, P=0.89), and other related complications (OR=0.63, 95% CI 0.23 to 1.66, P=0.35) showed no significant difference between the 2 groups (P0.05). Hospitalization (MD=-0.66, 95% CI -1.33 to 0.01, P=0.05), duration of surgery (MD=14.78, 95% CI -1.75 to 31.31, P=0.08), bleeding amount (MD=-12.81, 95% CI -40.36 to 14.74, P=0.36), the tumor size (SMD=-0.40, 95% CI -0.87 to 0.08, P=0.10), the number of lymph node dissection (MD=-0.49, 95% CI 1.80 to 0.82, P=0.46), and the recurrence of 2-year follow-up (OR=1.15, 95% CI 0.38 to 3.50, P=0.81) were not statistically significant between the 2 groups. Time of gas passage (SMD=-0.62, 95% CI -0.82 to -0.42, P0.001) and time of regular diet after surgery (SMD=-0.60, 95% CI -1.15 to 0.05, P=0.03) in the NOSE group were earlier than those in the LAP group. The postoperative pain score (MD=-1.49, 95% CI -1.97 to -1.01, P0.001) in the NOSE group was significantly lower than that in the LAP group. Cosmetic surgery in the NOSE group had a higher index (MD=1.37, 95% CI 0.59 to 2.14, P=0.0005) compared with that in the LAP group. Conclusion: Laparoscopic-assisted resection for colorectal cancer without auxiliary incision at abdomen can obviously reduce the incidence of incision complications, and the patients can recover early and incision is showed more cosmetic. The method is safe, feasible, and effective.目的：评价腹腔镜下腹部无切口结直肠癌切除术较之传统腹腔镜下结直肠癌切除术的可行性和安全性。方法：检索2005年8月至2015年8月公开发表的腹腔镜下腹部无切口结直肠癌切除对比传统腹腔镜下结直肠癌切除术应用情况的文献。按纳入标准筛选后进行质量评分，提取临床效应指标，采用Review Maneger 5.3软件对所纳入的数据进行Meta分析。结果：最终纳入7项研究，共621例患者，其中无辅助切口组(NOSE组)262例，传统腹腔镜组(LAP组)359例。Meta分析结果显示总并发症发生率的对比NOSE组明显较LAP组少(OR=0.31，95% CI：0.18~0.53，P0.05)。对并发症进行亚组分析，其中切口并发症NOSE组较LAP组少(OR=0.15，95% CI：0.05~0.40，P=0.0002)；术后出血(OR=1.52，95% CI：0.38~6.18，P=0.55)、肠梗阻(OR=0.30，95% CI：0.09~0.98，P=0.05)、吻合口相关并发症(OR=0.92，95% CI：0.28~3.07，P=0.89)、其他相关并发症(OR=0.63，95% CI：0.23~1.66，P=0.35)等亚组两组比较差异无统计学意义；住院时间(MD=–0.66，95% CI：–1.33~0.01，P=0.05)、手术持续时间(MD=14.78，95% CI： –1.75~31.31，P=0.08)、术中出血量(MD=–12.81，95% CI：–40.36~14.74，P=0.36)、切除肿瘤大小(SMD=–0.40，95% CI：–0.87~0.08，P=0.10)、淋巴结清扫(MD=–0.49，95% CI：1.80~0.82，P=0.46)、随诊2年肿瘤复发(OR=1.15，95% CI：0.38~3.50，P=0.81)等指标NOSE组与LAP组比较差异均无统计学意义；术后肛门首次排气时间(SMD=–0.62，95% CI：–0.82~–0.42，P0.001)及术后恢复进食时间(SMD=–0.60，95% CI：–1.15~–0.05，P=0.03)NOSE组均较LAP组更早；术后疼痛指数(MD=–1.49，95% CI：–1.97~–1.01，P0.001)NOSE组较LAP组明显较低；且NOSE组具有更好的美容效果(MD=1.37，95% CI：0.59~2.14，P=0.0005)。结论：腹腔镜辅助腹部无辅助切口结直肠癌切除可显著减少患者切口并发症的发生，并可减轻患者疼痛，加快术后恢复，具有更好的美容效果，是治疗结直肠癌安全、可行、有效的 方法。.

Multidrug resistance (MDR) refers to the capability of bacterial pathogens to withstand lethal doses of structurally diverse drugs which are capable of eradicating non-resistant strains. MDR has been identified as a major threat to the public health of human being by the World Health Organization (WHO). Among the four general mechanisms that cause antibiotic resistance including target alteration, drug inactivation, decreased permeability and increased efflux, drug extrusion by the multidrug efflux pumps serves as an important mechanism of MDR. Efflux pumps not only can expel a broad range of antibiotics owing to their poly-substrate specificity, but also drive the acquisition of additional resistance mechanisms by lowering intracellular antibiotic concentration and promoting mutation accumulation. Over-expression of multidrug efflux pumps have been increasingly found to be associated with clinically relevant drug resistance. On the other hand, accumulating evidence has suggested that efflux pumps also have physiological functions in bacteria and their expression is subject tight regulation in response to various of environmental and physiological signals. A comprehensive understanding of the mechanisms of drug extrusion, and regulation and physiological functions of efflux pumps is essential for the development of anti-resistance interventions. In this review, we summarize the development of these research areas in the recent decades and present the pharmacological exploitation of efflux pump inhibitors as a promising anti-drug resistance intervention.

As organisms are typically exposed to chemical mixtures over long periods of time, chronic mixture toxicity is the best way to perform an environmental risk assessment (ERA). However, it is difficult to obtain the chronic mixture toxicity data due to the high expense and the complexity of the data acquisition method. Therefore, an approach was proposed in this study to predict chronic mixture toxicity. The acute (15 min exposure) and chronic (24 h exposure) toxicity of eight antibiotics and trimethoprim to Vibrio fischeri were determined in both single and binary mixtures. The results indicated that the risk quotients (RQs) of antibiotics should be based on the chronic mixture toxicity. To predict the chronic mixture toxicity, a docking-based receptor library of antibiotics and the receptor-library-based quantitative structure-activity relationship (QSAR) model were developed. Application of the developed QSAR model to the ERA of antibiotic mixtures demonstrated that there was a close affinity between RQs based on the observed chronic toxicity and the corresponding RQs based on the predicted data. The average coefficients of variations were 46.26 and 34.93 % and the determination coefficients (R (2)) were 0.999 and 0.998 for the low concentration group and the high concentration group, respectively. This result convinced us that the receptor library would be a promising tool for predicting the chronic mixture toxicity of antibiotics and that it can be further applied in ERA.

The gadE-mdtEF operon encodes a central acid resistance regulator GadE and two multidrug efflux proteins MdtEF. Although transcriptional regulation of gadE in the context of acid resistance under the aerobic growth environment of Escherichia coli has been extensively studied, regulation of the operon under the physiologically relevant environment of anaerobic growth and its effect on the expression of the multidrug efflux proteins MdtEF in the operon has not been disclosed. Our previous study revealed that anaerobic induction of the operon was dependent on ArcA, the response regulator of the ArcBA two-component system, in the M9 glucose minimal medium. However, the detailed regulatory mechanism remains unknown. In this study, we showed that anaerobic activation of mdtEF was driven by the 798 bp unusually long gadE promoter. Deletion of evgA, ydeO, rpoS, and gadX which has been shown to activate the gadE expression during acid stresses under aerobic condition did not have a significant effect on the anaerobic activation of the operon. Rather, anaerobic activation of the operon was largely dependent on the global regulator ArcA and a GTPase MnmE. Under aerobic condition, transcription of gadE was repressed by the global DNA silencer H-NS in M9 minimal medium. Interestingly, under anaerobic condition, while ΔarcA almost completely abolished transcription of gadE-mdtEF, further deletion of hns in ΔarcA mutant restored the transcription of the full-length PgadE-lacZ, and P1- and P3-lacZ fusions, suggesting an antagonistic effect of ArcA on the H-NS mediated repression. Taken together, we conclude that the anaerobic activation of the gadE-mdtEF was primarily mediated by the two-component system ArcBA through antagonizing the H-NS mediated repression.

During the past two decades, the phenomenon of hormesis has gained increasing recognition in environmental and toxicological communities. However, the mechanistic understanding of hormesis, to date, is extremely limited. Herein is proposed a novel parametric model with a mechanistic basis and two model-based parameters for hormesis that was successfully applied to the hormetic dose-response observed in the chronic toxicity of sulfonamides on Photobacterium phosphoreum. On the basis of the methods of molecular docking and quantitative structure-activity relationships (QSARs), we proposed a mechanistic hypothesis for hormesis that introduces for the first time the concept of quorum sensing in toxicological studies and explains the mechanism at the level of the receptors. The mechanistic hypothesis stated that (1) specific target binding like interaction with LuxR may contribute to transcriptional activation leading to enhanced luciferase activity at low dose exposure of sulfonamides, and (2) as the dose of sulfonamides increases, more sulfonamides competitively bind to dihydropteroate synthase, which inhibit the biosynthesis of folic acid and thus provoke toxicity. This mechanistic hypothesis, which explains both the dose-dependent and time-dependent features of hormesis, could give new insight into the mechanistic study of hormesis.

The determination of the hormetic effects of a mixture is quite difficult because of the moderate simulation and the complexity of measurement in low doses. In the present study, two typical models for mixture toxicity prediction, concentration additive (CA) and independent action (IA), were used to predict the hormetic effects of mixtures. The predictive power of those models was validated by the hormetic effects (24-h exposure) of antibiotic's binary mixtures to Vibrio fischeri. The results showed that CA and IA were unable to predict the hormetic dose-response of mixture, especially those of the interactive mixtures. As an alternative, a novel model, which was named as "six-point" and developed based on the quantitative features in the determined dose-response curve and on the Quantitative Structure Activity Relationships (QSARs) approach, was proposed for predicting the hormetic effects of mixtures in low dose. The results indicated that the "six-point" model can accurately predict the mixture hormetic effects in low dose, not only for non-interactive mixtures but also for interactive mixtures. Therefore, the "six-point" model is a powerful tool to predict the mixture hormetic effects at low dose, and may offer an important approach in the environment risk assessment of mixtures.