An Epidemiological Study of Drug Resistance and Resistance Genes in Bovine Escherichia coli Isolates in Heilongjiang Province of China

Background: To explore the epidemiology of bovine multidrug-resistant Escherichia coli isolates and resistance genes in Heilongjiang province of China. This study examined the prevalence of genes in bovine E. coli isolates, which confer resistance to antibiotics that are commonly used in the clinic, in regions of Baiquan, Shangzhi, and Songbei of Harbin. The purpose of the study was to investigate the epidemiology of the main resistance genes of bovine E. coli isolates in clinical veterinary medicine, and to provide a theoretical basis for preventing the spread of drug-resistant bacteria, as well as for rational drug use.Materials, Methods & Results: The sensitivity of 105 isolates to 22 antibiotics was determined using the KirbyBauer disk diffusion method, and the distribution of 19 kinds of common drug resistance genes was investigated using Polymerase Chain Reaction. The results showed that the resistance rate to nine antibiotics was over 50%, including rifampin (84.76%), ampicillin (73.58%), tetracycline (69.52%), and sulfisoxazole (59.05%). In total, 105 strains of bovine E. coli presented 21 spectra of drug resistance, including eight strains (7.62%, 8/105) that were resistant to one antibiotic and four strains (3.81%, 4/105) that were resistant to 21 antibiotics. The resistance gene detection results showed that the streptomycin-resistance gene strA was found in 73 isolates, accounting for 69.52% of the isolates, followed by the sulfanilamide-resistance genes sul3/sul2 and the aminoglycoside-resistance gene aphA, which accounted for 57.14%, 51.43%, and 50.48%, respectively, of the isolates.Discussion: This study revealed serious drug resistance of bovine E. coli isolates in some areas of Heilongjiang province. Of 105 E. coli isolates, more than 50% were resistant to the following antibacterial drugs: rifampicin, ampicillin, tetracycline, sulfisoxazole, and cephalothin. The isolates were the most sensitive to amikacin, with a sensitivity of 84.76%, followed by sensitivity to ofloxacin, ciprofloxacin, norfloxacin, cefoxitin, and tobramycin. Drug sensitivity tests showed that the drug resistance spectra of the bovine E. coli isolates was different in different regions, indicating that there were multidrug-resistant bovine E. coli isolates in different regions of Heilongjiang province, and that drug resistance differed among different regions. This may be due to prolonged use or overuse of antibiotics in a particular locality. Additionally, because of different management modes of livestock farms, the application of antimicrobial drugs in some farms may have imposed selective pressure on the intestinal flora including E. coli, resulting in the horizontal transmission of drug resistance among the bacteria. The study found that some strains had a resistance phenotype, but no resistance gene, while some had a resistance gene without expressing a resistance phenotype, which is consistent with relevant reports in the literature. This may be related to the same genotype corresponding to different resistance phenotypes, or different levels of gene expression, or different drug metabolic rates. In our study, some strains with certain drug resistance genes were sensitive to the corresponding drug, which may be due to mutations of drug-resistance genes, the loss of a strains resistance phenotype, or the loss of gene function. These issues require further study. This study revealed serious drug resistance of bovine E. coli isolates in some areas of Heilongjiang province. Of 105 E. coli isolates, more than 50% were resistant to the following antibacterial drugs: rifampicin, ampicillin, tetracycline, sulfisoxazole, and cephalothin. The isolates were the most sensitive to amikacin, with a sensitivity of 84.76%, followed by sensitivity to ofloxacin, ciprofloxacin, norfloxacin, cefoxitin, and tobramycin

Baseline Peripheral Blood Leukocytosis Is Negatively Correlated With T-Cell Infiltration Predicting Worse Outcome in Colorectal Cancers

We aimed to explore the prognostic value of blood leukocyte and to generate a predictive model to refine risk stratification for colorectal cancers. 6,558 patients with colorectal cancers were identified eligible respectively in Fudan University Shanghai Cancer Center (FUSCC) between May, 2008 and October, 2016. Then the entire set is divided into a training set and a testing set. The prognostic value of pretreatment white blood cell count and clinicopathologic parameters in the context of tumor-infiltrating lymphocytes (TIL) and neutrophils was investigated. Conventional leukocytosis (≥10,000/μl) was significantly associated with decreased overall survival (OS) and disease-free survival (DFS) (p < 0.05). In fact, moderately elevated leukocyte (≥7,500/μl) has also been identified as an independent prognostic factor for survivals in the training, testing, and entire sets, respectively. And leukocytosis correlated with advanced T-stage (p < 0.001), M-stage (p < 0.001), poor differentiation tumor (p = 0.023) and Glasgow prognostic score, even predicted for worse relapse postoperatively (p = 0.001) and resistance to chemotherapy. In addition, nomograms on OS and DFS were established according to leukocytosis and other significant factors, demonstrating a great prediction accuracy. Importantly, pretreatment leukocytosis had a significantly lower intra-tumor CD3+ and CD8+ TIL infiltration (p < 0.001 and p = 0.033), whereas low CD3+ and CD8+ TIL expression in tumor were associated with worse OS and DFS (p = 0.02 and p = 0.015). In conclusion, our study validates leukocytosis as an independent prognostic factor in colorectal cancers. Our data provide for the first-time vital insight on the correlation of peripheral pretreatment leukocytosis with the tumor-infiltrating cells contexture and might be relevant for future risk stratification

Retinal alterations in evaluation of rheumatoid arthritis with chloroquine treatment: A new approach

Objective: To evaluate the effect of hydroxychloroquine on conjunctival and retinal microvascular density in rheumatoid arthritis (RA) patients. Methods: Ten healthy controls, 10 RA patients who had not been treated with hydroxychloroquine, and 10 RA patients who had been treated with chloroquine for more than 5 years were recruited. Optical coherence tomography (OCTA) was used to examine the conjunctival and superficial and deep retinal microvascular density and compared the differences in microvascular density between the three groups. Results: The vascular density in RA group in superficial microvascular was significantly lower than that in control group (p < 0.001). Compared with RA group, the chloroquine group showed statistically significantly lower microvascular (p < 0.001) and deep microvascular (p = 0.018). Superficial microvascular was positively correlated with conjunctival vessel density in RA patients (r = 0.868, p = 0.0048). Conclusions: The use of chloroquine could further reduce the vascular density in the absence of statistical difference in the course of the disease

Inhibited Endogenous H2S Generation and Excessive Autophagy in Hippocampus Contribute to Sleep Deprivation-Induced Cognitive Impairment

Background and Aim: Sleep deprivation (SD) causes deficit of cognition, but the mechanisms remain to be fully established. Hydrogen sulfide (H2S) plays an important role in the formation of cognition, while excessive and prolonged autophagy in hippocampus triggers cognitive disorder. In this work, we proposed that disturbances in hippocampal endogenous H2S generation and autophagy might be involved in SD-induced cognitive impairment.Methods: After treatment of adult male wistar rats with 72-h SD, the Y-maze test, object location test (OLT), novel object recognition test (NORT) and the Morris water maze (MWM) test were performed to determine the cognitive function. The autophagosome formation was observed with electron microscope. Generation of endogenous H2S in the hippocampus of rats was detected using unisense H2S microsensor method. The expressions of cystathionine-β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MST), beclin-1, light chain LC3 II/LC3 I, and p62 in the hippocampus were assessed by western blotting.Results: The Y-maze, OLT, NORT, and MWM test demonstrated that SD-exposed rats exhibited cognitive dysfunction. SD triggered the elevation of hippocampal autophagy as evidenced by enhancement of autophagosome, up-regulations of beclin-1 and LC3 II/LC3 I, and down-regulation of p62. Meanwhile, the generation of endogenous H2S and the expressions of CBS and 3-MST (H2S producing enzyme) in the hippocampus of SD-treated rats were reduced.Conclusion: These results suggested that inhibition of endogenous H2S generation and excessiveness of autophagy in hippocampus are involved in SD-induced cognitive impairment

Statistical considerations for the HPTN 052 Study to evaluate the effectiveness of early versus delayed antiretroviral strategies to prevent the sexual transmission of HIV-1 in serodiscordant couples

The HIV Prevention Trial Network (HPTN) 052 Study is a Phase III, two-arm, controlled, open-labeled, randomized clinical trial designed to determine whether early antiretroviral therapy (ART) can prevent the sexual transmission of human immunodeficiency virus type 1 (HIV-1). A total of 1,763 couples in which one partner was HIV-1-positive and the other was HIV-1-negative were enrolled in four continents, nine countries and thirteen study sites. The HIV-1-positive partner was randomly assigned to either of the two arms: “immediate” (early) therapy with ART initiated upon enrollment plus HIV primary care, or “delayed” therapy with HIV primary care but ART initiated when the index case would have two consecutive measurements of a CD4+ cell count within or below the range of 200–250 cells/mm3, or develop an AIDS-defining illness. In this paper, we describe several key statistical considerations for the design of this landmark study. Despite that the observed event rates were lower than expected, which might have compromised the study power, an early release of the trial results in May 2011 showed an overwhelming 96% risk reduction for the immediate therapy in the prevention of genetically linked HIV-1 incident transmissions. Nevertheless, the durability of its long-term effectiveness is yet to be assessed. The HPTN 052 Study is still ongoing and will not complete till 2015

Transcriptome profiling and digital gene expression by deep-sequencing in normal/regenerative tissues of planarian Dugesia japonica

AbstractPlanarians exhibit an extraordinary ability to regenerate lost body parts which is attributed to an abundance of pluripotent somatic stem cells called neoblasts. In this article, we report a transcriptome sequence of a Planaria subspecies Dugesia japonica derived by high-throughput sequencing. In addition, we researched transcriptome changes during different periods of regeneration by using a tag-based digital gene expression (DGE) system. Consequently, 11,913,548 transcriptome sequencing reads were obtained. Finally, these reads were eventually assembled into 37,218 unique unigenes. These assembled unigenes were annotated with various methods. Transcriptome changes during planarian regeneration were investigated by using a tag-based DGE system. We obtained a sequencing depth of more than 3.5million tags per sample and identified a large number of differentially expressed genes at various stages of regeneration. The results provide a fairly comprehensive molecular biology background to the research on planarian development, particularly with regard to its regeneration progress

21-Gene Recurrence Score Assay Could Not Predict Benefit of Post-mastectomy Radiotherapy in T1-2 N1mic ER-Positive HER2-Negative Breast Cancer

Introduction: It is still controversial whether post-mastectomy radiotherapy (PMRT) is necessary for women with T1-2 N1mic ER-positive HER2-negative breast cancer. The 21-gene recurrence score (RS) assay has been validated in T1-2 N1 breast cancer to be prognostic of locoregional recurrence (LRR) and overall survival (OS). This study aims to evaluate the predict value of 21-gene recurrence score assay for the benefit of PMRT in T1-2 N1mic ER-positive HER2-negative breast cancer.Methods: A population-based cohort study was performed on women with T1-2 N1mic ER-positive HER2-negative breast cancer who underwent mastectomy and were evaluated using the 21-gene RS in the Surveillance, Epidemiology, and End Results (SEER) registry between 2004 and 2015. Clinical characteristics as well as OS and breast cancer-specific survival (BCSS) were compared between patients with and without PMRT in patients with a Low-, Intermediate-, and High-RS. Multivariate COX regression analysis was performed to investigate if the 21-gene RS assay could predict benefit of PMRT in this group of breast cancer patients.Results: A total of 1571 patients met the criteria of our study and were enrolled, including 970 patients in the Low-Risk group (score &lt;18), 508 in the Intermediate-Risk group (score 18–30), and 93 patients in the High-Risk group (score &gt;30). In the High-Risk group, there were more patients with age ≥50 (87.0 vs. 64.3%, P = 0.040) and received chemotherapy with a borderline significance (91.3 vs. 72.9%, P = 0.066) in the PMRT subgroup than in the no PMRT subgroup. In all three groups, OS was comparable between the PMRT subgroup and the no PMRT subgroup. Furthermore, multivariate analysis did not show any OS benefit for PMRT based on the 21-gene recurrence score.Conclusion: This study showed that the 21-gene RS assay was not able to predict the benefit of PMRT for OS in women with T1-2 N1mic ER-positive HER2-negative breast cancer. However, further prospective larger sample-size trials are warranted to determine if a benefit exists

Prediction model of ocular metastasis from primary liver cancer: Machine learning‐based development and interpretation study

Background: Ocular metastasis (OM) is a rare metastatic site of primary liver cancer (PLC). The purpose of this study was to establish a clinical predictive model of OM in PLC patients based on machine learning (ML). Methods: We retrospectively collected the clinical data of 1540 PLC patients and divided it into a training set and an internal test set in a 7:3 proportion. PLC patients were divided into OM and non‐ocular metastasis (NOM) groups, and univariate logistic regression analysis was performed between the two groups. The variables with univariate logistic analysis p < 0.05 were selected for the ML model. We constructed six ML models, which were internally verified by 10‐fold cross‐validation. The prediction performance of each ML model was evaluated by receiver operating characteristic curves (ROCs). We also constructed a web calculator based on the optimal performance ML model to personalize the risk probability for OM. Results: Six variables were selected for the ML model. The extreme gradient boost (XGB) ML model achieved the optimal differential diagnosis ability, with an area under the curve (AUC) = 0.993, accuracy = 0.992, sensitivity = 0.998, and specificity = 0.984. Based on these results, an online web calculator was constructed by using the XGB ML model to help clinicians diagnose and treat the risk probability of OM in PLC patients. Finally, the Shapley additive explanations (SHAP) library was used to obtain the six most important risk factors for OM in PLC patients: CA125, ALP, AFP, TG, CA199, and CEA. Conclusion: We used the XGB model to establish a risk prediction model of OM in PLC patients. The predictive model can help identify PLC patients with a high risk of OM, provide early and personalized diagnosis and treatment, reduce the poor prognosis of OM patients, and improve the quality of life of PLC patients

Management of granulomatous lobular mastitis: an international multidisciplinary consensus (2021 edition)

Granulomatous lobular mastitis (GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions, etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology. The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidence-based consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM.Improving the Ability of Diagnosis and Treatment of Difficult Disease