A pilot phase Ⅱ study of neoadjuvant triplet chemotherapy regimen in patients with locally advanced resectable colon cancer

Objective： This study aims to investigate the feasibility, safety and efficacy of triplet regimen of neoadjuvant chemotherapy in patients with locally advanced resectable colon cancer.Methods： Patients with clinical stage IIIb colon cancer received a perioperative triple chemotherapy regimen（oxaliplatin 85 mg/m2 and irinotecan 150 mg/m2, combined with folinic acid 200 mg, 5-fluorouracil 500 mg bolus and then 2,400 mg/m2 by 44 h infusion or capecitabine 1 g/m2 or S-1 40–60 mg b.i.d orally d 1–10, repeated at 2-week intervals） for 4 cycles. Complete mesocolic excision was scheduled 2–6 weeks after completion of neoadjuvant treatment and followed by a further 6 cycles of FOLFOXIRI or XELOX. Primary outcome measures of this stage II trial were feasibility, safety, tolerance and efficacy of neoadjuvant treatment.Results： All 23 patients received neoadjuvant chemotherapy and underwent surgery. Twenty-one patients（91.3%） had reductions in tumor volume after neoadjuvant treatment, and 13 patients（56.5%） had grade 3–4toxicity. No patients had severe complications from surgery. Preoperative therapy resulted in significant downstaging of T-stage and N-stage compared with the baseline clinical stage including one pathological complete response.Conclusions： Neoadjuvant triple chemotherapy has high activity and acceptable toxicity and perioperative morbidity, and is feasible, tolerable and effective for locally advanced resectable colon cancer.

Interaction between the gut microbiome and mucosal immune system

The gut microbiota, the largest symbiotic ecosystem with the host, has been shown to play important roles in maintaining intestinal homeostasis. Dysbiosis of the gut microbiome is caused by the imbalance between the commensal and pathogenic microbiomes. The commensal microbiome regulates the maturation of the mucosal immune system, while the pathogenic microbiome causes immunity dysfunction, resulting in disease development.The gut mucosal immune system, which consists of lymph nodes, lamina propria and epithelial cells, constitutes a protective barrier for the integrity of the intestinal tract. The composition of the gut microbiota is under the surveillance of the normal mucosal immune system. Inflammation, which is caused by abnormal immune responses,influences the balance of the gut microbiome, resulting in intestinal diseases. In this review, we briefly outlined the interaction between the gut microbiota and the immune system and provided a reference for future studies.

Protective effect of hydroxychloroquine on rheumatoid arthritis-associated atherosclerosis

Background: Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease. We examined the effect of gut microbiota in a mouse model of RA that develops atherosclerosis. Methods: We created three groups of K/BxN female mice that were positive for the anti‐glucose‐6‐phosphate isomerase (GPI) antibody: control diet (CD), high fat diet (HFD), and HFD with hydroxychloroquine (HFD + HCQ). Serological tests were used to detect the serum levels of total cholesterol (TCHO), low‐density lipoprotein cholesterol (LDL‐C), triglyceride (TG), high‐density lipoprotein cholesterol (HDL‐C), anti‐ GPI antibody titers, and serum cytokines. Atherosclerotic plaque was determined by histological analysis, and gut microbiota were determined by 16sV4 sequencing. Results: Relative to mice given the CD, those receiving the HFD had increased serum levels of LDL‐C, TCHO, and TG, decreased serum levels of HDL‐C, increased atherosclerotic lesions in the aortic root, and altered gut microbiota. Addition of HCQ to HFD decreased the serum levels of LDL‐C, TCHO, and TG, increased serum levels of HDL‐C, and decreased the atherosclerotic lesions in the aortic root. Mice receiving HFD + HCQ also had the greatest bacterial diversity among the three experimental groups. Moreover, HCQ treatment significantly increased the abundance of Akkermansia and Parabacteroides, and decreased the abundance of Clostridium sensu stricto cluster 1, and therefore may be responsible for the reduced RA‐associated atherosclerosis and dyslipidemia. Conclusion: Our mouse model of RA indicated that HFD increased ankle width and aggravated a therosclerosis a nd d yslipidemia, a nd t hat H CQ a lleviated t he d yslipidemia and atherosclerosis, but had no effect on ankle width.

The status,limitation and improvement of adoptive cellular immunotherapy in advanced urologic malignancies

In recent years, immunotherapy has been gradually established as the fourth frequently adopted antitumor therapy, following surgery, chemotherapy and radiotherapy, for advanced urologic malignancies with an improved understanding of theoretical basis, such as molecular biology and immunology. Thereinto, adoptive cellular immunotherapy （ACI） has become one of the hotspots, which comprises a variety of treatment approaches, such as TIL, CIK cell, ~＇~ T cell, CAR-engineered T cell and Allogeneie stem cell transplantation （alloSCT）. Although preclinical efficacy has been demonstrated remarkably, clinical trials could not consistently show the benefit due to multi-factors in complex immnnosuppressive microenvironment in vivo compared to that of in vitro. Here we review some timely aspects of ACI for advanced urologic malignancies, and describe the current status and limitation of immunotherapy from the cellular level. It＇s our expectation to provide prompting consideration of novel combinatorial ACI strategies and a resurgence of interest in ACI for advanced urologic malignancies.

Monogenic deficiency in murine intestinal Cdc42 leads to mucosal inflammation that induces crypt dysplasia

CDC42 controls intestinal epithelial(IEC)stem cell(IESC)division.How aberrant CDC42 initiates intestinal inflammation or neoplasia is unclear.We utilized models of inflam-matory bowel diseases(IBD),colorectal cancer,aging,and IESC injury to determine the loss of intestinal Cdc42 upon inflammation and neoplasia.Intestinal specimens were collected to determine the levels of CDC42 in IBD or colorectal cancer.Cdc42 floxed mice were crossed with Villin-Cre,Villin-CreERT2 and/or Lgr5-eGFP-IRES-CreERT2,or Bmi1-CreERT2 mice to generate Cdc42 deficient mice.Irradiation,colitis,aging,and intestinal organoid were used to evaluate CDC42 upon mucosal inflammation,IESC/progenitor regenerative capacity,and IEC repair.Our studies revealed that increased CDC42 in colorectal cancer correlated with lower survival;in contrast,lower levels of CDC42 were found in the inflamed IBD colon.Colonic Cdc42 depletion significantly reduced Lgr5+IEsCs,increased progenitors'hyperplasia,and induced mucosal inflammation,which led to crypt dysplasia.Colonic Cdc42 depletion markedly enhanced irra-diation-or chemical-induced colitis.Depletion or inhibition of Cdc42 reduced colonic Lgr5+IESC regeneration.In conclusion,depletion of Cdc42 reduces the IESC regeneration and IEC repair,leading to prolonged mucosal inflammation.Constitutive monogenic loss of Cdc42 in-duces mucosal inflammation,which could result in intestinal neoplasia in the context of aging.

Application of 5G telesurgery in urology

The fifth generation of mobile communication technology(5G technology)features large system capacity,fast data transmission rate,support for large-scale device connection,low latency,and high reliability.With the development and popularization of 5G technology,it is also widely used in medicine.In recent years,5G telesurgery has been paid attention to and made continuous progress,and the research related to its combination with urology has also made significant achievements.We collect the combination of 5G technology and urology improves the uneven distribution of medical resources,provides timely,highquality remote surgical interventions for urology patients,reduces the financial burden on patients,surgical complications,and the difficulty of accessing medical care from a distance,and brings new opportunities for medical development.

微生物组测序与分析专家共识

在过去的十几年,微生物组相关研究和应用持续升温。微生物组逐渐成为生命科学、环境科学和医学等领域的研究焦点。与此同时,全球多个国家和组织也都积极发起各自的微生物组计划,进行多方面的布局,力争在这一具有广阔前景的领域获得战略地位。此外,无论是科研还是产业应用已经迎来了研究高潮和投融资热潮,微生物组相关产品和服务也不断出现。然而,行业在快速发展的同时,也存在一些不足。由于微生物组测序和分析相关技术和方法发展迅速,各国研究和应用尚未在技术、方案和数据等标准上达成统一,国内行业参与者对微生物组也存在认识不足,对微生物组相关新方法、新技术、新理论等还未能充分掌握和使用。除此之外,已有的一些标准和指南,内容过于简单,实操性也不足,这不仅给科研数据的整合造成了困难和资源浪费,还给相关企业进行不良竞争、以次充好提供了机会。更重要的是,我国尚缺乏微生物组相关的国家标准,国家微生物组计划仍处于筹备过程。在此背景下,中国生物工程学会、中国科学院微生物研究所于2019年6月至2020年3月,共同设立了“微生物组测序与分析专家共识”专项研究课题。中国生物工程学会组织了微生物组相关领域的27位专家以及来自行业内的30多位专业人员,通过分成4个项目小组、召开4轮研讨会后,最终形成了涵盖从微生物采集与保存、DNA提取与建库、高通量基因测序和数据分析以及质控标准品等全流程的“微生物组测序与分析专家共识”。本专家共识具有较强可参考性和可操作性,不仅能指导国内科研和产业机构规范进行微生物组相关产、学、研,还能为国家相关职能部门提供可参考的技术依据,保障规模型和规范化的企业利益,加强行业自律,避免不规范的企业扰乱市场,最终促进微生物组相关产业的良性发展。

Self-crosslinkable chitosan-hyaluronic acid dialdehyde nanoparticles for CD44-targeted siRNA delivery to treat bladder cancer

Bladder cancer is one of the concerning malignancies worldwide,which is lacking effective targeted therapy.Gene therapy is a potential approach for bladder cancer treatment.While,a safe and effective targeted gene delivery system is urgently needed for prompting the bladder cancer treatment in vivo.In this study,we confirmed that the bladder cancer had CD44 overexpression and small interfering RNAs(siRNA)with high interfere to Bcl2 oncogene were designed and screened.Then hyaluronic acid dialdehyde(HAD)was prepared in an ethanol-water mixture and covalently conjugated to the chitosan nanoparticles(CS-HAD NPs)to achieve CD44 targeted siRNA delivery.The in vitro and in vivo evaluations indicated that the siRNA-loaded CS-HAD NPs(siRNA@CS-HAD NPs)were approximately 100 nm in size,with improved stability,high siRNA encapsulation efficiency and low cytotoxicity.CS-HAD NPs could target to CD44 receptor and deliver the therapeutic siRNA into T24 bladder cancer cells through a ligand-receptor-mediated targeting mechanism and had a specific accumulation capacity in vivo to interfere the targeted oncogene Bcl2 in bladder cancer.Overall,a CD44 targeted gene delivery system based on natural macromolecules was developed for effective bladder cancer treatment,which could be more conducive to clinical application due to its simple preparation and high biological safety.

Applications of Next-generation Sequencing in Systemic Autoimmune Diseases

Systemic autoimmune diseases are a genetic and environmental factors. Although group of heterogeneous disorders caused by both numerous causal genes have been identified by genome-wide association studies （GWAS）, these susceptibility genes are correlated to a relatively low disease risk, indicating that environmental factors also play an important role in the pathogen- esis of disease. The intestinal microbiome, as the main symbiotic ecosystem between the host and host-associated microorganisms, has been demonstrated to regulate the development of the body＇s immune system and is likely related to genetic mutations in systemic autoimmune diseases. Next-generation sequencing （NGS） technology, with high-throughput capacity and accuracy, provides a powerful tool to discover genomic mutations, abnormal transcription and intestinal microbiome identification for autoimmune diseases. In this review, we briefly outlined the applications of NGS in systemic autoimmune diseases. This review may provide a reference for future studies in the pathogenesis of systemic autoimmune diseases.