批准用于奶牛的抗菌药物分析

我国奶牛养殖规模不断扩大,奶业产值比重逐步提高,给奶牛疫病防治带来巨大压力。奶牛乳房炎及细菌性肺炎等呼吸系统疾病和细菌性肠炎等消化系统疾病最为常见,抗菌药物的使用成为主要防治手段。但抗菌药物的不当使用易使细菌产生耐药性,增加临床治疗的成本和难度,危害我国奶牛产业发展。本文对截至2021年7月我国和美国、英国、日本、欧盟批准用于奶牛的抗菌药物产品进行整理、统计与分析,包括抗菌药物的分类、剂型以及适应证等,旨在为我国奶牛用抗菌药物管理、合理用药和新兽药开发提供参考。     

How can hospitals change practice to better implement smoking cessation interventions? A systematic review

Smoking cessation reduces the risk of death, improves recovery, and reduces the risk of hospital readmission. Evidence and policy support hospital admission as an ideal time to deliver smoking-cessation interventions. However, this is not well implemented in practice. In this systematic review, the authors summarize the literature on smoking-cessation implementation strategies and evaluate their success to guide the implementation of best-practice smoking interventions into hospital settings. The CINAHL Complete, Embase, MEDLINE Complete, and PsycInfo databases were searched using terms associated with the following topics: smoking cessation, hospitals, and implementation. In total, 14,287 original records were identified and screened, resulting in 63 eligible articles from 56 studies. Data were extracted on the study characteristics, implementation strategies, and implementation outcomes. Implementation outcomes were guided by Proctor and colleagues' framework and included acceptability, adoption, appropriateness, cost, feasibility, fidelity, penetration, and sustainability. The findings demonstrate that studies predominantly focused on the training of staff to achieve implementation. Brief implementation approaches using a small number of implementation strategies were less successful and poorly sustained compared with well resourced and multicomponent approaches. Although brief implementation approaches may be viewed as advantageous because they are less resource-intensive, their capacity to change practice in a sustained way lacks evidence. Attempts to change clinician behavior or introduce new models of care are challenging in a short time frame, and implementation efforts should be designed for long-term success. There is a need to embrace strategic, well planned implementation approaches to embed smoking-cessation interventions into hospitals and to reap and sustain the benefits for people who smoke.     

Pure laparoscopic living donor liver transplantation: Dreams come true

Minimally invasive approaches are increasingly being applied in surgeries and have recently been used in living donor hepatectomy. We have developed a safe and reproducible method for minimally invasive living donor liver transplantation, which consists of pure laparoscopic explant hepatectomy and pure laparoscopic implantation of the graft, which was inserted through a suprapubic incision. Pure laparoscopic explant hepatectomy without liver fragmentation was performed in a 60-year-old man with alcoholic liver cirrhosis and hepatocellular carcinoma. The explanted liver was retrieved through a suprapubic incision. A modified right liver graft, procured from his 24-year-old son using the pure laparoscopic method, was inserted through a suprapubic incision, and implantation was performed intracorporeally throughout the procedure. The time required to remove the liver was 369 min, and the total operative time was 960 min. No complications occurred during or after the surgery. The patient recovered well, and his hospital stay was of 11 days. Pure laparoscopic living donor liver transplantation from explant hepatectomy to implantation was performed successfully. It is a feasible procedure when performed by a highly experienced surgeon and transplantation team. Further studies with larger sample sizes are needed to confirm its safety and feasibility.

     

半夏泻心汤对DSS诱导的溃疡性结肠炎小鼠肠道微生态及Th17/Treg细胞平衡的影响＊

目的 观察半夏泻心汤对饮用葡聚糖硫酸钠（DSS）诱导建立的溃疡性结肠炎（UC）模型小鼠Th17/Treg细胞平衡及肠道微生态的影响，从免疫失衡及菌群紊乱角度分析半夏泻心汤治疗UC的作用机制。方法 将40只C57BL/6J雄性小鼠随机分为空白组、模型组、阳性药（美沙拉嗪）组及半夏泻心汤组，除空白组外的各小鼠采用2.5% DSS水溶液自由饮用7天诱导建立UC小鼠模型。自实验第8日起，分别采用灭菌水、美沙拉嗪水溶液、半夏泻心汤水溶液给上述各组别小鼠灌胃。采用HE染色观察结肠组织病理学变化，ELISA方法检测组织炎症因子含量，流式细胞术检测Th17及Treg细胞的相对数量，16S rRNA测序技术进一步检测模型小鼠粪便中菌群的变化。结果 与空白组比较，模型组小鼠结肠损伤严重，血清炎症因子含量显著升高（P<0.01）；与模型组比较，中药干预组小鼠结肠损伤减轻，血清TNF-α、IFN-γ含量显著下降（P<0.05）。较空白组小鼠相比，模型组小鼠Th17细胞百分比显著升高（P<0.01），而Treg细胞百分比显著降低（P<0.01）。经半夏泻心汤干预后，其小鼠Th17细胞数量均显著降低（P<0.05），Treg细胞数量则显著升高（P<0.05）。同时，半夏泻心汤可升高门水平上Firmicutes、属水平上Lachnospiraceae_NK4A136_group、unclassified_f_Lachnospiraceae、Prevotellaceae_UCG-001、Alistipes；降低门水平上Actinobacteriota，科水平上Bifidobacteriaceae、Atopobiaceae、Clostridiaceae，属水平上Clostridium_sensu_stricto_1、Coriobacteriaceae_UCG-002、Bifidobacterium的相对丰度。结论 半夏泻心汤可使Treg细胞相对数量升高、Th17细胞相对数量降低，以维持Th17/Treg细胞动态平衡；同时可降低有害菌Clostridium_sensu_stricto_1、Coriobacteriaceae_UCG-002的相对丰度，升高产短链脂肪酸类菌Lachnospiraceae_NK4A136_group、Prevotellaceae_UCG-001、unclassified_f_Lachnospiraceae等菌属的相对丰度，调控肠道微生物结构及动态平衡，从而发挥治疗UC的作用。     

Arterial spin labeling MR image denoising and reconstruction using unsupervised deep learning

Arterial spin labeling (ASL) imaging is a powerful magnetic resonance imaging technique that allows to quantitatively measure blood perfusion non-invasively, which has great potential for assessing tissue viability in various clinical settings. However, the clinical applications of ASL are currently limited by its low signal-to-noise ratio (SNR), limited spatial resolution, and long imaging time. In this work, we propose an unsupervised deep learning-based image denoising and reconstruction framework to improve the SNR and accelerate the imaging speed of high resolution ASL imaging. The unique feature of the proposed framework is that it does not require any prior training pairs but only the subject's own anatomical prior, such as T1-weighted images, as network input. The neural network was trained from scratch in the denoising or reconstruction process, with noisy images or sparely sampled k-space data as training labels. Performance of the proposed method was evaluated using in vivo experiment data obtained from 3 healthy subjects on a 3T MR scanner, using ASL images acquired with 44-min acquisition time as the ground truth. Both qualitative and quantitative analyses demonstrate the superior performance of the proposed txtc framework over the reference methods. In summary, our proposed unsupervised deep learning-based denoising and reconstruction framework can improve the image quality and accelerate the imaging speed of ASL imaging.     

Viral hepatitis: Past,present, and future

Each hepatitis virus—Hepatitis A, B, C, D, E, and G—poses a distinct scenario to the patient and clinician alike. Since the discovery of each virus, extensive knowledge regarding epidemiology, virologic properties, and the natural clinical and immunologic history of acute and chronic infections has been generated. Basic discoveries about host immunologic responses to acute and chronic viral infections, combined with virologic data, has led to vaccines to prevent Hepatitis A, B, and E and highly efficacious antivirals for Hepatitis B and C. These therapeutic breakthroughs are transforming the fields of hepatology, transplant medicine in general, and public and global health. Most notably, there is even an ambitious global effort to eliminate chronic viral hepatitis within the next decade. While attainable, there are many barriers to this goal that are being actively investigated in basic and clinical labs on the local, national, and international scales. Herein, we discuss pertinent clinical information and recent organizational guidelines for each of the individual hepatitis viruses while also synthesizing this information with the latest research to focus on exciting future directions for each virus.     

Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible.