This paper aims to discuss the ideas and experience about the radiology residency training system of Canada with a presentation of its base accreditation standards for five aspects, competency goals for seven roles, four stages of training arrangement, and two types of final assessment questions. Although the Canada's radiology residency program differs from China's standardized resident and specialist training programs for radiology, there are still several points that are worth referencing, including emphasizing the training priority of competency goals, providing a specific basis for the stratification of training, offering clear guidance for the implementation of training content, and improving assessment methods to focus on competency goals. These points are of great value for improving the standardized radiology resident and specialist training programs in China, so as to provide a reference for the training of excellent radiologists in China.

BACKGROUND: Ischemic acute kidney injury (AKI) is a common syndrome associated with considerable mortality and healthcare costs. Up to now, the underlying pathogenesis of ischemic AKI remains incompletely understood, and specific strategies for early diagnosis and treatment of ischemic AKI are still lacking. Here, this study aimed to define the transcriptomic landscape of AKI patients through single-cell RNA sequencing (scRNA-seq) analysis in kidneys. METHODS: In this study, scRNA-seq technology was applied to kidneys from two ischemic AKI patients, and three human public scRNA-seq datasets were collected as controls. Differentially expressed genes (DEGs) and cell clusters of kidneys were determined. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as the ligand-receptor interaction between cells, were performed. We also validated several DEGs expression in kidneys from human ischemic AKI and ischemia/reperfusion (I/R) injury induced AKI mice through immunohistochemistry staining. RESULTS: 15 distinct cell clusters were determined in kidney from subjects of ischemic AKI and control. The injured proximal tubules (PT) displayed a proapoptotic and proinflammatory phenotype. PT cells of ischemic AKI had up-regulation of novel pro-apoptotic genes including USP47 , RASSF4 , EBAG9 , IER3 , SASH1 , SEPTIN7 , and NUB1 , which have not been reported in ischemic AKI previously. Several hub genes were validated in kidneys from human AKI and renal I/R injury mice, respectively. Furthermore, PT highly expressed DEGs enriched in endoplasmic reticulum stress, autophagy, and retinoic acid-inducible gene I (RIG-I) signaling. DEGs overexpressed in other tubular cells were primarily enriched in nucleotide-binding and oligomerization domain (NOD)-like receptor signaling, estrogen signaling, interleukin (IL)-12 signaling, and IL-17 signaling. Overexpressed genes in kidney-resident immune cells including macrophages, natural killer T (NKT) cells, monocytes, and dendritic cells were associated with leukocyte activation, chemotaxis, cell adhesion, and complement activation. In addition, the ligand-receptor interactions analysis revealed prominent communications between macrophages and monocytes with other cells in the process of ischemic AKI. CONCLUSION Together, this study reveals distinct cell-specific transcriptomic atlas of kidney in ischemic AKI patients, altered signaling pathways, and potential cell-cell crosstalk in the development of AKI. These data reveal new insights into the pathogenesis and potential therapeutic strategies in ischemic AKI.
Humans ; Mice ; Animals ; Transcriptome/genetics* ; Ligands ; Kidney/metabolism* ; Acute Kidney Injury/metabolism* ; Ischemia/metabolism* ; Reperfusion Injury/metabolism* ; Sequence Analysis, RNA ; Adaptor Proteins, Signal Transducing/metabolism* ; Tumor Suppressor Proteins/metabolism*

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

【Objective】 To evaluate and analyze the impact of COVID-19 epidemic on inventory of red blood cells (RBCs)in local and municipal blood stations in China, and to provide reference for the management of public health emergencies. 【Methods】 Relevant data from 2018 to 2021 were collected, and the differences in the volume of qualified RBCs, the usage efficiency of inventory RBCs, the average daily distribution of RBCs,the blood distribution rate of RBCs prepared by 400 mL whole blood, the difference in the average storage days of RBCs at the time of distribution, the average daily inventory of RBCs and the time of the average daily inventory of RBCs to maintain the distribution in 24 local and municipal blood stations in China during the COVID-19 epidemic and non-epidemic periods were retrospectively analyzed. 【Results】 Compared with non-epidemic periods, the volume of qualified RBCs [(117 525.979 ±52 203.175)U] and the average daily distribution of RBCs [( 156. 468 ± 70. 186) U ] increased significantly, but the usage efficiency of inventory RBCs decreased(97.24%±0.51%) significantly (P<0.05).There was no significant difference in the blood distribution rate of RBCs prepared by 400 mL whole blood(73.88%±20.30%), the average storage days of RBCs distribution(13.040 ±3.486), the average daily stock quantity of RBCs[(2 280.542 ±1 446.538) U ] and the time of the average daily inventory of RBCs to maintain the distribution[(15.062 ±7.453) d] (P>0.5). 【Conclusion】 During the COVID-19 epidemic, the inventory management of RBCs operated well, the overall inventory remained relatively stable, the stock composition and storage period showed no significant change.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective: Using two measuring tools to examine the prevalence and correlates of neurocognitive impairment (NCI) as well as characteristics of neurocognitive performance among people with HIV (PWH) on antiretroviral treatment (ART). Methods: A total of 2 250 treated PWH from the Comparative HIV and Aging Research in Taizhou (CHART) were recruited in Taizhou, Zhejiang province. The Chinese version of the Mini-mental State Examination (MMSE) and the International HIV Dementia Scale (IHDS) were used to evaluate their neurocognitive performance. Cluster analysis was conducted on the seven cognitive domains in the scale. Results: Among 2 250 treated PWH, 48.0% (1 080/2 250) were aged 45 to 89, 79.2% (1 782/2 250) were male, and 37.8% (852/2 250) had primary school education or below. The prevalence of neurocognitive impairment judged by MMSE and IHDS among HIV-infected people was 14.3% (321/2 250) and 31.8% (716/2 250), respectively. Aged 60 to 89 (aOR=2.63, 95%CI:1.52-4.56), depressive symptoms (aOR=5.58, 95%CI:4.20-7.40) and treatment with EFV (aOR=2.86, 95%CI:1.89-4.34) were main risk factors of NCI diagnosed by MMSE. Male (aOR=0.71, 95%CI:0.51-1.00), overweight (aOR=0.63, 95%CI:0.44-0.89), and high education level (aOR=0.11, 95%CI:0.05-0.25) were protective factors of NCI diagnosed by MMSE. Aged 60 to 89 (aOR=3.10, 95%CI:2.09-4.59), depressive symptoms (aOR=1.78, 95%CI:1.44-2.20) and treatment with EFV (aOR=1.79, 95%CI:1.41-2.29) were risk factors of NCI diagnosed by IHDS. Male (aOR=0.75, 95%CI:0.58-0.97), underweight (aOR=0.67, 95%CI:0.47-0.96), baseline CD4⁺ T lymphocyte (CD4) counts ≥350 cells/μl (aOR=0.69, 95%CI:0.53-0.91) and high education level (aOR=0.23, 95%CI:0.14-0.39) were protective factors of NCI diagnosed by IHDS. The neurocognitive performance of HIV-infected people can be divided into four main types. Among four types, age, gender, education level, alcohol drinking, depressive symptoms, waist-to-hip ratio, hypertension, diabetes, baseline CD4 counts and treatment with EFV were different statistically (all P<0.05). Conclusions: There are four main types of neurocognitive performance in treated PWH. The prevalence of NCI is high among this population, underscoring the need for tailored prevention and intervention.
Male ; Humans ; Female ; Anti-Retroviral Agents ; Educational Status ; CD4 Lymphocyte Count ; Protective Factors ; HIV Infections/drug therapy*

OBJECTIVE To study the protective effects o f valproic acid on cardiac and cerebral injury in rats subjected to severe scalding combined with seawater immersion injury with delayed fluid replacement. METHODS The rats were divided into scalding+delayed fluid replacement group （group S ），scalding+seawater immersion+delayed fluid replacement group （group SS ）， scalding+seawater immersion+valproic acid+delayed fluid replacement group （group SSV ）according to random number table ，with 60 rats in each group. All groups were subjected to 35％total body surface area third-degree full-thickness scalding with boiled water. Group SS and group SSV were immersed in artificial ；seawater（30 min）immediately after scalding ，and group SSV was subcutaneously injected with valproic acid 300 mg/kg immediately after out of water. Sodium lactate Ringer ’s 0314-2279277。E-mail：125467374@qq.com injection was injected intravenously within 30 minutes according to 1/2 Parkland formula at 2 h after scalding in each group for delayed fluid replacement. The death time of rats was recorded ，and the average survival time and 24 h survival rate of rats in each group were calculat ed. Mean arterial pressure （MAP），heart rate （HR），respiration rate （RR），rectal temperature （RT），arterial blood pH ，arterial partial pressure of oxygen （PaO2），arterial blood partial pressure of carbon dioxide （PaCO2），HCO3－，creatine kinase MB isoenzyme （CK-MB）and neuron specific enolase （NSE）were detected before scalding ，at 0，2，5 h after scalding. The pathological changes of cardiac and cerebral tissue were observed. RESULTS The 24 h survival rate of group SS （55％）was significantly lower than that of group S （90％）， while that of group SSV （75％）was increased significantly ，compared with group SS （P＜0.05）. Compared with group S ，the levels of MAP ，RT，HR，pH，PaO2 and HCO 3－ in group SS were significantly lowered ，while the levels of CK-MB and NSE were increased significantly at 0，2，5 h after scalding ；the levels of PaCO 2 were increased significantly at 2，5 h after scalding ， while the levels of RR were decreased significantly at 0，2 h after scalding （P＜0.05）. Compared with group SS ，the levels of MAP，RT，HR，pH，PaO2 and HCO 3－ in group SSV were significantly increased ，while the levels of PaCO 2，CK-MB and NSE were decreased significantly at 2，5 h after scalding ；the level of RR was increased significantly at 2 h after scalding （P＜0.05）. At 2，5 h after scalding ，cardiac and cerebral injury of rats in group SS were aggravated significantly than that in group S ；cardiac and cerebral injury of rats in group SSV were relieved significantly than that in group SS. CONCLUSIONS After severe scalding combined seawater immersion injury ，hypodermic injection of sodium valproate could protect cardiac and cerebral function of rats ， improve vital signs and blood gas index ，prolong survival time and improve survival rate in rats.

Real world study(RWS) refers to the process of collecting real world data related to the health of research subjects in the real world environment for pre-set clinical problems and obtaining the status of drug use and potential benefits/risks through analysis. The data are derived from the hospital information system(HIS), medical insurance system, disease registration system, adverse drug reaction monitoring system, etc. Human use experience of traditional Chinese medicine(TCM) is a new concept put forward by experts after summarizing the problems existing in clinical trials of new TCM drugs. The data come partially from the real world, and more importantly, such key elements as the formulated prescriptions of new TCM drugs, principles and methods, and clinical applications should be covered. RWS is mainly used for adverse drug reaction monitoring after marketing, benefit evaluation of listed drugs, decision-making of medical treatment and medical insurance, as well as supervision and approval of special medical devices and special drugs. It is complementary to randomized controlled clinical trials. Human use experience is suitable for the research and development of Chinese medicinal compound preparations and the expansion of functions and indications. There are no special provisions for clinical indications and target population. There exists a sequential relationship between the human use experience and clinical trials. Specifi-cally, the summarization of human use experience provides good support for the design and implementation of clinical trials, which is an important segment in the research and development of new TCM drugs. The correlation between real-world data and research results and their reliability should be ensured in RWS, and the unreality should be avoided. The key to summarizing the human use experience is to identify the clinical orientation, target population, course of treatment, usage and dosage of new TCM drugs, and it should be noted that human use experience does not only mean clinical experience. Experimental clinical trial(PCT), a type of study in the real world, has been commonly employed for the summary of human use experience. RWS and human use experience are different research designs targeting different clinical questions in the research and development of new TCM drugs, which can be flexibly selected depending on the actual situation.
Drugs, Chinese Herbal/adverse effects* ; Humans ; Medicine, Chinese Traditional ; Prescriptions ; Reproducibility of Results ; Research

BACKGROUND: Since 2019, a novel coronavirus named 2019 novel coronavirus (2019-nCoV) has emerged worldwide. Apart from fever and respiratory complications, acute kidney injury has been observed in a few patients with coronavirus disease 2019. Furthermore, according to recent findings, the virus has been detected in urine. Angiotensin-converting enzyme II (ACE2) has been proposed to serve as the receptor for the entry of 2019-nCoV, which is the same as that for the severe acute respiratory syndrome. This study aimed to investigate the possible cause of kidney damage and the potential route of 2019-nCoV infection in the urinary system. METHODS: We used both published kidney and bladder cell atlas data and new independent kidney single-cell RNA sequencing data generated in-house to evaluate ACE2 gene expression in all cell types in healthy kidneys and bladders. The Pearson correlation coefficients between ACE2 and all other genes were first generated. Then, genes with r values larger than 0.1 and P values smaller than 0.01 were deemed significant co-expression genes with ACE2. RESULTS: Our results showed the enriched expression of ACE2 in all subtypes of proximal tubule (PT) cells of the kidney. ACE2 expression was found in 5.12%, 5.80%, and 14.38% of the proximal convoluted tubule cells, PT cells, and proximal straight tubule cells, respectively, in three published kidney cell atlas datasets. In addition, ACE2 expression was also confirmed in 12.05%, 6.80%, and 10.20% of cells of the proximal convoluted tubule, PT, and proximal straight tubule, respectively, in our own two healthy kidney samples. For the analysis of public data from three bladder samples, ACE2 expression was low but detectable in bladder epithelial cells. Only 0.25% and 1.28% of intermediate cells and umbrella cells, respectively, had ACE2 expression. CONCLUSION This study has provided bioinformatics evidence of the potential route of 2019-nCoV infection in the urinary system.
Angiotensin-Converting Enzyme 2/metabolism* ; COVID-19 ; Gene Expression ; Humans ; Kidney/metabolism* ; SARS-CoV-2 ; Sequence Analysis, RNA ; Single-Cell Analysis ; Urinary Bladder/metabolism*

At present, the issues regarding multi-center clinical trials of new drugs of traditional Chinese medicine(TCM) remain: the lack of agreement on the content and scope of the ethical review among the ethics committee members of the center and the participating units results in repeated review, which leads to a time-consuming ethical review process. Moreover, the review capabilities of the ethics committees of various research centers are uneven, which is not necessarily beneficial to the protection of subjects' rights and safety. In view of the existing problems, to improve the efficiency of ethical review of multi-center clinical trials of new drugs of TCM and avoid repeated reviews, the TCM Clinical Evaluation Professional Committee of Chinese Pharmaceutical Association organized experts to formulate the "Consensus on collaborative ethical review of multi-center clinical trials of new drugs of TCM(version 1.0)"(hereinafter referred to as "Consensus"). The "Consensus" is formulated in accordance with the requirements of relevant documents such as but not limited to "the opinions on deepening the reform of the evaluation and approval system to encourage the innovation of pharmaceutical medical devices", "the regulations of ethical review of biomedical research involving human subjects". The "Consensus" covers the scope of application, formulation principles, conditions for the ethics committee of the center, sharing of ethical review resources, scope and procedure of collaborative review, rights and obligations, etc. The aims of the "Consensus" is to preliminarily explore and establish a scientific and operable ethical review procedure. Additionally, on the basis of fully protecting the rights and interests of the subjects, a collaborative ethical review agreement needs to be signed to clarify the ethical review responsibilities of all parties, to avoid repeated review, and to improve the efficiency and quality of ethical review in multi-center clinical trials of new drugs of TCM.
Biomedical Research ; Clinical Trials as Topic ; Consensus ; Drugs, Chinese Herbal ; Ethical Review ; Humans ; Medicine, Chinese Traditional ; Multicenter Studies as Topic ; Pharmaceutical Preparations