Prostate cancer in Asia:A collaborative report

The incidence of prostate cancer(PCa)within Asian population used to be much lower than in the Western population;however,in recent years the incidence and mortality rate of PCa in some Asian countries have grown rapidly.This collaborative report summarized the latest epidemiology information,risk factors,and racial differences in PCa diagnosis,current status and new trends in surgery management and novel agents for castration-resistant prostate cancer.We believe such information would be helpful in clinical decision making for urologists and oncologists,health-care ministries and medical researchers.

The Efficacy and Safety of Triazavirin for COVID-19: A Trial Protocol

根据2019年12月的报道,新冠病毒肺炎(coronavirus disease 2019, COVID-19)是由一种新型冠状病毒引起的肺炎。到目前为止,还没有发现能够治疗这种病毒的有效药物。本研究是一项在黑龙江省10个研究中心正在进行的多中心双盲随机对照试验(randomized controlled trial, RCT),其目的是研究与安慰剂相比,特力阿扎维林(triazavirin, TZV)治疗COVID-19患者的疗效和安全性。共计划招募240名COVID-19患者参加这项试验。咽拭子病毒核酸检测为阳性的受试者被随机(1∶1)分为两组:使用标准治疗加TZV或标准治疗加安慰剂,进行为期7 d的治疗和为期21 d的随访。主要结局是受试者临床改善的时间。次要结局包括临床改善率、退热时间、肺内炎症明显吸收的平均时间和人数比例、病毒核酸转阴率、病死率以及重症和危重症患者的转化率。整个试验过程将对不良事件,严重不良事件,肝功能、肾功能以及合并用药进行监测和记录。本试验的结果可为临床医生治疗COVID-19提供循证医学的证据和建议。

Efficacy and Safety of Triazavirin Therapy for Coronavirus Disease 2019:A Pilot Randomized Controlled Trial

目前,尚无有效疗法可治愈由严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)引起的新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)。为了评估抗病毒药物特力阿扎维林治疗COVID-19的有效性和安全性,本研究针对感染COVID-19的成年住院患者开展了一项随机双盲对照试验。本研究从10个分中心招募COVID-19患者,并将患者按1:1的比例随机分为两组。试验组的患者每天服用250 mg的特力阿扎维林药物3~4次,对照组患者则服用安慰剂,为期共7 d。主要结局指标为临床改善时间,临床改善时间的定义为随机分组28d内患者的体温、呼吸频率、血氧饱和度、咳嗽频率和肺CT(计算机断层扫描,computed tomography)所显示的肺部感染吸收情况全部恢复正常的时间。次要结局指标包括主要结局指标的5个组成指标,及肺部感染吸收的平均时间和吸收比例,以及用咽拭子采样法连续两次SARS-CoV-2核酸检测阴性的转阴率。与此同时,记录合并的治疗药物、不良事件和严重不良事件。由于需要进行住院治疗的新增感染病例的减少,本研究在招募52名患者后便停止招募。将52名受试者随机分为服用特力阿扎维林药物的试验组(n=26)和服用安慰剂的对照组(n=26)。结果显示,两组临床改善时间并无明显差异[中位数,7 d vs.12 d;风险比(RR)为2.0;95%置信区间(CI)为0.7~5.6;p=0.2]。服用特力阿扎维林的试验组中有10名患者发生临床改善,服用安慰剂的对照组中有6名患者出现临床改善(38.5%vs.23.1%,RR为2.1;95%CI为0.6~7.0;p=0.2)。除了肺部感染的吸收情况外(试验组50.0%,对照组26.1%),其余主要结局所观察指标均在28 d内恢复正常。此外,试验组的患者在呼吸系统、心脏、肾、肝或凝血功能等方面的合并治疗较对照组少。尽管特力阿扎维林药物对COVID-19患者的疗效尚未达到统计学上的显著性水平,但本研究结果表明,由于特力阿扎维林药物具有抗病毒作用,将其用于COVID-19的治疗也可能具有一定的疗效。对此,需要进一步的研究进行验证。

Themechanism of resistance to CDK4/6 inhibition and novel combination therapy with RNR inhibition for chemo-resistant bladder cancer

Bladder cancer(BCa)is the most prevalent urological cancer worldwide[1].A significant proportion of BCa(89%)exhibits molecular alterations in the cell cycle pathway,and targeting cyclin-dependent kinases 4 and 6(CDK4/6)is deemed as a promising therapeutic strategy[2].Selective inhibitors of CDK4/6(CDK4/6is)have been approved by the US Food and Drug Administration(FDA)[3].

Clinical practice guideline on bladder cancer(Part Ⅰ)

Bladder cancer represents one of the most prevalent malignant tumors affecting the urinary system.As per data disclosed by the National Cancer Registration Center of China in 2019,the incidence of bladder cancer was 5.80 per 100,000 in 2015,placing it as the thirteenth most common systemic malignancy.Bladder cancer poses a substantial threat to public health in China,underlining the critical importance of standardizing diagnosis and treatment to enhance clinical outcomes.This clinical practice guideline for bladder cancer centers on the etiologies,clinical presentations,and diagnostic procedures for suspected bladder cancer,in addition to the histopathology and staging of urothelial bladder cancer.

Clinical practice guideline on bladder cancer(Part Ⅲ)

Bladder cancer(BC)has become a significantly prevalent disease in China,with an incidence rate of 5.80 per 100000 in 2015,ranking it as the thirteenth most common type of cancer within the nation.This illness presents a serious public health concern,highlighting the imperative need to unify the standards for diagnosis and treatment to improve patient outcomes.The section of the clinical practice guideline in question is dedicated to addressing muscle-invasive bladder cancer(MIBC)and metastatic BC.The primary treatment strategies for MIBC are well-defined:preoperative(neoadjuvant)chemotherapy combined with radical cystectomy stands as the conventional treatment protocol.For patients with locally advanced MIBC,integrating systemic and local therapies is advocated to enhance treatment effectiveness.In cases of metastatic BC,the focus shifts to systemic treatment supplemented by supportive care measures.The guideline also succinctly presents the pros and cons of various urinary diversion surgeries,which are critical considerations following radical cystectomy.It provides an in-depth exploration of the treatment modalities for metastatic urothelial carcinoma of the bladder.Additionally,this part delves into the integrated approach to treatment and the use of radiotherapy in bladder preservation for localized disease.Moreover,it offers a concise overview of the classification,diagnosis,and therapeutic approaches for nonurothelial carcinoma of the bladder.Lastly,this part emphasizes the importance of recommended posttreatment follow-up for MIBC patients to ensure comprehensive and ongoing care management.

Consensus on safety management of novel hormonal therapy for advanced prostate cancer

Prostate cancer(PCa)is one of the most prevalent malignant tumors in men,accompanied by high incidence and mortality rates.Novel hormonal therapy(NHT)has emerged as the primary treatment for advanced PCa,providing noticeable clinical benefits.However,the diverse range of adverse events(AEs)associated with NHT may influence both treatment efficacy and patients'quality of life.In light of the latest international clinical research evidence and recommendations from domestic and foreign guidelines,this consensus aims to provide a comprehensive overview of the common AEs experienced during NHT for advanced PCa patients.Additionally,it seeks to develop a hierarchical approach to more efficiently manage AEs,presenting valuable insights for clinical medication and adverse reaction management.

Clinical practice guideline on bladder cancer(PartⅡ)

Bladder cancer(BC)is an increasingly common malignancy in China,with an incidence rate of 5.80 per 100000 in 2015,making it the thirteenth most common cancer in the country.This trend underscores the urgent need for standardized diagnosis and treatment protocols.In terms of treatment,approaches for bladder cancer vary based on the cancer's stage and pathology,as well as the patient's overall health.Notably,non-muscleinvasive BC(NMIBC)confined to the mucosa(Ta)and lamina propria(T1)without invading the muscle represents about 75%of all BC cases.Succeeding the first part of the guideline,this part of the clinical practice guideline focuses on NMIBC.It details risk classifications and treatment options,including both surgical procedures and posttransurethral resection of the bladder tumor intravesical instillations.Special attention is given to the treatment strategies for carcinoma in situ.The guideline also covers the recommended follow-up procedures for patients with NMIBC,underscoring the need for thorough and continuous care management.

Coronavirus transmissible gastroenteritis virus antagonizes the antiviral effect of the microRNA miR-27b via the IRE1 pathway

Although the functional parameters of micro RNAs(mi RNAs)have been explored to some extent,the roles of these molecules in coronavirus infection and the regulatory mechanism of mi RNAs in virus infection are still unclear.Transmissible gastroenteritis virus(TGEV)is an enteropathgenic coronavirus and causes high morbidity and mortality in suckling piglets.Here,we demonstrated that microRNA-27b-3p(miR-27b-3p)suppressed TGEV replication by directly targeting porcine suppressor of cytokine signaling 6(SOCS6),while TGEV infection downregulated miR-27b-3p expression in swine testicular(ST)cells and in piglets.Mechanistically,the decrease of miR-27b-3p expression during TGEV infection was mediated by the activated inositolrequiring enzyme 1(IRE1)pathway of the endoplasmic reticulum(ER)stress.Further studies showed that when ER stress was induced by TGEV,IRE1 acted as an RNase activated by autophosphorylation and unconventionally spliced m RNA encoding a potent transcription factor,X-box-binding protein 1(Xbp1s).Xbp1s inhibited the transcription of miR-27 and ultimately reduced the production of miR-27b-3p.Therefore,our findings indicate that TGEV inhibits the expression of an anti-coronavirus micro RNA through the IRE1 pathway and suggest a novel way in which coronavirus regulates the host cell response to infection.

Boosting image-guiding radiation therapy through W_(18)O_(49) nanospheres and the second near-infrared light irradiation

More than 60%of cancer patients receive radiation therapy(RT)during their anticancer treatment.However,there is a huge challenge to improve the therapeutic efficacy of RT in less radioresponsive tumors and decrease damages dealt to the surrounding healthy tissues.Herein,we have reported the development of an efficacious RT treatment of relatively radio-resistant breast cancer using W_(18)O_(49)nanospheres and the second near-infrared(NIR)light irradiation.Featuring the X-ray attenuation ability and photothermal effect,together with ability to generate intracellular singlet oxygen and·OH,W_(18)O_(49)nanospheres can significantly increase radiation-induced DNA damage and decrease the mitochondrial membrane potential of cancer cells during RT,causing in nearby three-times improvement in inhibiting the proliferation of 4T1 cells.The in vivo evaluations verify that a rather effective therapeutic outcome is achieved by treatment of 4T1 tumor xenograft with NIR-enhanced RT using W_(18)O_(49)nanospheres.Moreover,the X-ray attenuation ability and the strong near-infrared absorption of W_(18)O_(49)nanospheres have enabled highly resolved in vivo computer tomography(CT)/photoacoustic(PA)imaging.This work presents an“all-in-one”synergistic platform to improve the therapeutic efficacy of RT in less radioresponsive tumors,therefore opening a new door for multimodal cancer therapy.

An activated excretion-retarded tumor imaging strategy towards metabolic organs

Intraoperative fluorescence-based tumor imaging plays a crucial role in performing the oncological safe tumor resection with the advantage of differentiating tumor from normal tissues.However,the application of these fluorescence contrast agents in renal cell carcinoma(RCC)and hepatocellular carcinoma(HCC)was dramatically hammered as a result of lacking active targeting and poor retention time in tumor,which limited the Signal to Noise Ratio(SNR)and narrowed the imaging window for complicated surgery.Herein,we reported an activated excretion-retarded tumor imaging(AERTI)strategy,which could be in situ activated with MMP-2 and self-assembled on the surface of tumor cells,thereby resulting in a promoted excretion-retarded effect with an extended tumor retention time and enhanced SNR.Briefly,the AERTI strategy could selectively recognize the Integrin α_(v)β_(3).Afterwards,the AERTI strategy would be activated and in situ assembled into nanofibrillar structure after specifically cleaved by MMP-2 upregulated in a variety of human tumors.We demonstrated that the AERTI strategy was successfully accumulated at the tumor sites in the 786-O and HepG2 xenograft models.More importantly,the modified modular design strategy obviously enhanced the SNR of AERTI strategy in the imaging of orthotopic RCC and HCC.Taken together,the results presented here undoubtedly confirmed the design and advantage of this AERTI strategy for the imaging of tumors in metabolic organs.