Polo-like kinase 1 as a biomarker predicts the prognosis and immunotherapy of breast invasive carcinoma patients

Invasive breast carcinoma(BRCA)is associated with poor prognosis and high risk of mortality.Therefore,it is critical to identify novel biomarkers for the prognostic assessment of BRCA.Methods:The expression data of polo-like kinase 1(PLK1)in BRCA and the corresponding clinical information were extracted from TCGA and GEO databases.PLK1 expression was validated in diverse breast cancer cell lines by quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting.Single sample gene set enrichment analysis(ssGSEA)was performed to evaluate immune infiltration in the BRCA microenvironment,and the random forest(RF)and support vector machine(SVM)algorithms were used to screen for the hub infiltrating cells and calculate the immunophenoscore(IPS).The RF algorithm and COX regression model were applied to calculate survival risk scores based on the PLK1 expression and immune cell infiltration.Finally,a prognostic nomogram was constructed with the risk score and pathological stage,and its clinical potential was evaluated by plotting calibration charts and DCA curves.The application of the nomogram was further validated in an immunotherapy cohort.Results:PLK1 expression was significantly higher in the tumor samples in TCGA-BRCA cohort.Furthermore,PLK1 expression level,age and stage were identified as independent prognostic factors of BRCA.While the IPS was unaffected by PLK1 expression,the TMB and MATH scores were higher in the PLK1-high group,and the TIDE scores were higher for the PLK1-low patients.We also identified 6 immune cell types with high infiltration,along with 11 immune cell types with low infiltration in the PLK1-high tumors.A risk score was devised using PLK1 expression and hub immune cells,which predicted the prognosis of BRCA patients.In addition,a nomogram was constructed based on the risk score and pathological staging,and showed good predictive performance.Conclusions:PLK1 expression and immune cell infiltration can predict post-immunotherapy prognosis of BRCA patients.

负载无定型钌纳米簇的原子级钴掺杂一维碳纳米笼增强析氢催化性能

析氢反应是电解水产制氢的关键反应之一.在碱性条件下,由于催化剂表面与反应过程中产生的氧物种、氢物种与催化剂的吸附未处于最佳状态,析氢反应动力学往往比较缓慢,比在酸性条件下慢2-3个数量级.目前,铂基纳米催化剂被认为是最优的析氢催化剂,但因价格昂贵、稳定性较差,限制了其在电解水器件上的大规模应用.因此,设计一种价格较为低廉、活性高和稳定性好的碱性析氢催化剂尤为必要.钌作为铂族金属之一,其价格约为铂的三分之一,但其与氢的结合能却与铂类似.因此,钌基催化剂被认为是有望替代铂作为析氢催化剂.本文结合模板法、静电纺丝和碳化热解策略构筑了一种负载无定型钌纳米簇的原子级钴掺杂一维碳纳米笼催化剂,有效提升了碱性条件下析氢反应性能.该催化剂具有较高的比表面积,丰富的缺陷结构,原子级分散的金属Co掺杂以及无定型钌纳米簇结构,并在碱性条件下催化析氢反应时,表现出了低起始过电位,低Tafel斜率(62 mV dec^(-1))和高稳定性.X射线衍射(XRD)结果表明,该催化剂中钌和钴以无定型形式存在.选区电子衍射结果表明了无定型结构的存在,并且钌以纳米簇形式存在,其平均粒径为1.48 nm.X射线光电子能谱结果表明该催化剂含有较高的氮掺杂,拉曼光谱证明了其存在碳缺陷结构.进一步通过X射线近边吸收谱和扩展边精细结构谱研究了钌和钴的配位环境,结果发现,钌带轻微正电荷,并且存在Ru-Ru键;钴带正电荷,价态介于0与+2价之间,其主要与N配位.在1 mol/L氢氧化钾电解液中,该杂化催化剂的电催化活性明显高于没有钴掺杂的催化剂以及商业化铂/碳催化剂.在电流密度为10 mA cm^(-2)时,过电位仅为40 mV,在过电位为100 mV时,该催化剂的质量催化活性达到了3.77 mAμg_(Ru)^(-1),远超商业化铂/碳(2.01 mAμg_(Ru)^(-1))和钌/碳(1.66 mAμg_(Ru)^(-1)).该催化剂也表现出了优异的析氢催化稳定性,5000圈循环后,10 mA cm^(-2)下的过电位仅增加了2 mV,在恒电流测试中,10 h后电位仅下降了95 mV.

Repair of a small and crooked vesicovaginal fistula using electrocauterization

Dear Editor,Vesicovaginal fistula(VVF)is an abnormal opening between the urinary bladder and the vagina.The condition has an immense psychological effect on patients due to the continuous leakage of urine or watery vaginal discharge.The wet feeling and foul smell associated with leakage of urine cause social outcasting of the patients.This leads to immense emotional trauma and makes life miserable for the patient.The most common etiology for VVF in developing countries is obstructed labour[1],and in developed countries,it is abdominal hysterectomy[2].VVF poses a challenging problem to the surgeon.The location and the size of the fistula determine the extent of the patients’symptoms.

共价有机框架材料在质子交换膜中的应用

共价有机框架(COFs)作为一种新型有机多孔材料,具有高度结晶性、有序的多孔排列、功能可修饰性、结构可调性以及较高稳定性。COFs规整的孔道可以容纳多种质子载流子和质子供体,构建连续稳定的质子传输通道,在含水质子传导与无水质子传导中均发挥巨大的作用,将COFs应用到质子交换膜领域具有重要的研究意义和价值。本文分别从COFs作为低温燃料电池质子交换膜和高温燃料电池质子交换膜两方面,总结了COFs固态电解质膜、COFs与高分子基质复合膜、COFs自支撑膜等不同种类质子交换膜的特点以及提高COFs质子交换膜性能的改性方法,综述了近年来COFs在燃料电池质子交换膜领域的相关代表性研究。最后,对COFs质子交换膜的应用前景进行了讨论与展望。

Prevalence and risk evaluation of cardiovascular disease in the newly diagnosed prostate cancer population in China:A nationwide,multi-center,population-based cross-sectional study

Background:Cardiovascular disease(CVD)has emerged as the leading cause of death from prostate cancer(PCa)in recent decades,bringing a great disease burden worldwide.Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy(ADT).The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China.Methods:Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling.CVD was defined as myocardial infarction,arrhythmia,heart failure,stroke,ischemic heart disease,and others.CVD risk was estimated by calculating Framingham risk scores(FRS).Patients were accordingly divided into low-,medium-,and high-risk groups.χ2 or Fisher’s exact test was used for comparison of categorical variables.Results:A total of 4253 patients were enrolled in the present study.A total of 27.0%(1147/4253)of patients had comorbid PCa and CVD,and 7.2%(307/4253)had two or more CVDs.The enrolled population was distributed in six regions of China,and approximately 71.0%(3019/4253)of patients lived in urban areas.With imaging and pathological evaluation,most PCa patients were diagnosed at an advanced stage,with 20.5%(871/4253)locally progressing and 20.5%(871/4253)showing metastasis.Most of them initiated prostatectomy(46.6%,1983/4253)or regimens involving ADT therapy(45.7%,1944/4253)for prostate cancer.In the present PCa cohort,43.1%(1832/4253)of patients had hypertension,and half of them had poorly controlled blood pressure.With FRS stratification,as expected,a higher risk of CVD was related to aging and metabolic disturbance.However,we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT.This was in accordance with clinical practice,i.e.,aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery.Among patients who underwent medical castration,only 4.0%(45/1118)received gonadotropin releasing hormone antagonists,in stark contrast to the grim situation of CVD prevalence and risk.Conclusions:PCa patients in China are diagnosed at an advanced stage.A heavy CVD burden was present at the initiation of treatment.Patients who accepted ADT-related therapy showed an original higher risk of CVD,but the awareness of cardiovascular protection was far from sufficient.

Synthesis of covalent organic framework materials and their application in the field of sensing

Covalent organic frameworks(COFs)are an emerging type of porous crystalline polymers formed by combining strong covalent bonds with organic building blocks.Due to their large surface area,high intrinsic pore space,good crystallization properties,high stability,and designability of the resultant units,COFs are widely studied and used in the fields of gas adsorption,drug transport,energy storage,photoelectric catalysis,electrochemistry,and sensors.In recent years,the rapid development of the Internet of Things and people’s yearning for a better life have put forward higher and more requirements for sensors,which are the core components of the Internet of Things.Therefore,this paper reviews the recent progress of COFs in synthesis methods and sensing applications,especially in the last five years.This paper first introduces structure,properties,and synthesis methods of COFs and discusses advantages and disadvantages of different synthesis methods.Then,the research progress of COFs in different sensing fields,such as metal ion sensors,gas sensors,biomedical sensors,humidity sensors,and pH sensors,is introduced systematically.Conclusions and prospects are also presented in order to provide a reference for researchers concerned with COFs and sensors.

舒林酸联合双歧杆菌三联活菌治疗家族性腺瘤性息肉病的作用及其机制初探

目的探讨舒林酸联合双歧杆菌三联活菌(培菲康)治疗家族性腺瘤性息肉病(FAP)的疗效及其机制。方法收集2013年1月1日至2022年1月1日在上海交通大学医学院附属瑞金医院就诊的FAP患者,采用随机数字表法,将经胃肠镜检查及组织病理学检查确诊的这些FAP患者,分为舒林酸组、培菲康组、舒林酸联合培菲康组3组。舒林酸组口服舒林酸400 mg/d,疗程为1年;培菲康组口服培菲康6粒/d,疗程1年;舒林酸联合培菲康组,口服舒林酸400 mg/d+6粒培菲康/d,疗程1年。每4个月结肠镜复查1次,观察每组患者一般情况,腺瘤的病理类型、大小、数目。采用16sRNA高通量测序分析患者粪便菌群变化Western blot检测凋亡抑制蛋白Bcl-2的表达。结果入组患者共90例,每组30例,舒林酸联合培菲康组于治疗后4、8、12个月腺瘤的病理类型:管状腺瘤分别占活检腺瘤总数分别为90.5%、94.4%、99.2%;绒毛管状腺瘤占9.5%、5.6%、0.8%;舒林酸组分别为85.3%、90.4%、95.2%,培菲康组分别为80.5%、85.3%、90.2%。舒林酸+培菲康组与培菲康组、舒林酸组比较,差异有统计学意义(P<0.05)16sRNA测序提示舒林酸联合培菲康组厚壁菌门和放线菌门比例增加,而拟杆菌门比例降低。Western blot显示舒林酸联合培菲康组Bcl-2表达显著较其它组降低(P<0.05)。结论舒林酸联合培菲康能有效的治疗FAP,其疗效优于单纯服用舒林酸组和培菲康组。可能的机制与降低Bcl-2,减少对凋亡的抑制,促进了腺瘤的凋亡,同时改善了肠内环境菌群有关。

Increasing prevalence of antibiotic resistance genes in manured agricultural soils in northern China

Land application of manure tends to result in the dissemination of antibiotic resistance in the environment.In this study,the influence of long-term manure application on the enrichment of antibiotic resistance genes(ARGs)and mobile genetic elements(MGEs)in agricultural soils was investigated.All the analyzed eight ARGs(tetA,tetW,tetX,sull,sulll,ermF,aac(6')-Ib-cr and blaTEM)and two MGEs(intJJ and Tn916/1545)were detected in both the manured and control soils,with relative abundances ranging from 10^-6 to 10^-2 Compared with the control soil,the relative abundances of ARGs and MGEs in manured soils were enriched 1.0-18.1 fold and 0.6-69.1 fold,respectively.High-throughput sequencing analysis suggested that at the phylum level,the bacteria carrying intll and ermF might be mainly affiliated with Proteobacteria and Bacteroides,respectively.The dominant genera carrying intll and ermF cow\d be Pseudomonas and Bacteroides,independent of manure application.Correlation analysis revealed that ARGs had strong links with soil physicochemical properties(TC,TN,and OM),heavy metals(Cu,Zn and Pb)and MGEs,indicating that the profile and spread of ARGs might be driven by the combined impacts of multiple factors.In contrast,soil pH and C/N exhibited no significant relationships with ARGs.Our findings provide evidence that long-term manure application could enhance the prevalence and stimulate the propagation of antibiotic resistance in agricultural soils.

Clinical efficacy of comprehensive therapy based on traditional Chinese medicine patterns on patients with pneumoconiosis: a pilot double-blind, randomized, and placebo-controlled study

Effective therapy options for pneumoconiosis are lacking.Traditional Chinese medicine(TCM)presents a favorable prospect in the treatment of pneumoconiosis.A pilot study on TCM syndrome differentiation can evaluate the clinical efficacy and safety of TCM and lay a foundation for further clinical research.A double-blind,randomized,and placebo-controlled trial was conducted for 24 weeks,in which 96 patients with pneumoconiosis were randomly divided into the control and treatment groups.Symptomatic treatment was conducted for the two groups.The treatment group was treated with TCM syndrome differentiation,and the control group was treated with placebo.The primary outcomes were the six-minute walking distance(6MWD)and the St.George Respiratory Questionnaire(SGRQ)score.The secondary outcomes were the modified British Medical Research Council Dyspnea Scale(mMRC),Chronic Obstructive Pulmonary Disease Assessment Test(CAT),Hospital Anxiety and Depression Scale(HADS),and pulmonary function.Only 83 patients from the 96 patients with pneumoconiosis finished the study.For the primary outcome,compared with the control groups,the treatment group showed a significantly increased 6MWD(407.90 m vs.499.51 m;95%confidence interval(CI)47.25 to 135.97;P<0.001)and improved SGRQ total score(44.48 vs.25.67;95%CI 27.87 to 9.74;P<0.001).The treatment group also significantly improved compared with the control group on mMRC score(1.4 vs.0.74;95%CI 1.08 to 0.23;P=0.003),CAT score(18.40 vs.14.65;95%CI 7.07 to 0.43;P=0.027),and the total symptom score(7.90 vs.5.14;95%CI 4.40 to 1.12;P<0.001).No serious adverse events occurred.This study showed that TCM syndrome differentiation and treatment had a favorable impact on the exercise endurance and quality of life of patients with pneumoconiosis.

An in-situ NH_(4)^(+)-etched strategy for anchoring atomic Mo site on ZnIn_(2)S_(4) hierarchical nanotubes for superior hydrogen photocatalysis

Atomic sites co-catalyst (ASC) on photocatalytic materials possesses an attractive prospect to promote charge carrier separation and tune surface reaction kinetics,yet the synthesis of earth-abundant ASC under low temperature remains a great challenge.Here,a novel in-situ NH_(4)^(+)-etched strategy to anchor atomic Mo sites on ZnIn_(2)S_(4)hierarchical nanotubes (HNTs) with abundant mesopores under mild conditions for promoting charge carrier separation and enhancing light multi-reflections is developed for efficient photocatalytic H_(2) evolution.Density functional theory calculations and linear sweep voltammetry demonstrate that the well-defined Mo-S_(2)O_(1) sites with distinctive coordination configuration and electronic property contribute to the enhanced separation of photo-generated charge carriers and reduced Gibbs free energy for H_(2) evolution.Consequently,the well-defined MoSA-ZIS HNTs present an excellent photocatalytic activity with a rate of 29.9μmol h^(-1)(5.98 mmol g^(-1)h^(-1)),which is 7.3 times higher than that of ZnIn_(2)S_(4)nanosheets (NSs),to be among the best ZnIn_(2)S_(4)-based photocatalysts.The present strategy breaks the high-temperature limitation of conventional top-down thermal dissociation/emitting approach for anchoring non-noble metal atomic sites on catalyst support.