Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

School-age children are in a specific development stage corresponding to juvenility, when the white matter of the brain experiences ongoing maturation. Diffusion-weighted magnetic resonance imaging (DWI), especially diffusion tensor imaging (DTI), is extensively used to characterize the maturation by assessing white matter properties in vivo. In the analysis of DWI data, spatial normalization is crucial for conducting inter-subject analyses or linking the individual space with the reference space. Using tensor-based registration with an appropriate diffusion tensor template presents high accuracy regarding spatial normalization. However, there is a lack of a standardized diffusion tensor template dedicated to school-age children with ongoing brain development. Here, we established the school-age children diffusion tensor (SACT) template by optimizing tensor reorientation on high-quality DTI data from a large sample of cognitively normal participants aged 6-12 years. With an age-balanced design, the SACT template represented the entire age range well by showing high similarity to the age-specific templates. Compared with the tensor template of adults, the SACT template revealed significantly higher spatial normalization accuracy and inter-subject coherence upon evaluation of subjects in two different datasets of school-age children. A practical application regarding the age associations with the normalized DTI-derived data was conducted to further compare the SACT template and the adult template. Although similar spatial patterns were found, the SACT template showed significant effects on the distributions of the statistical results, which may be related to the performance of spatial normalization. Looking forward, the SACT template could contribute to future studies of white matter development in both healthy and clinical populations. The SACT template is publicly available now ( https://figshare.com/articles/dataset/SACT_template/14071283 ).

Objective To investigate the incidence of intraoperative hypothermia in elderly patients,and to analyze and discuss related influencing factors and targeted management strategies.Methods From February 2017 to February 2019,220 elderly patients admitted into our hospital for surgery were selected.According to whether or not they had intraoperative hypothermia,patients were divided into the hypothermia group and the non-hypothermia group.General information and surgical data were compared between the two groups.Measures for the prevention of intraoperative hypothermia were discussed.Results Of the 220 patients,103 had intraoperative hypothermia,and the incidence rate was 46.8％.The proportion of patients aged ≥70 years or with BMI ＜24 kg/m2 was higher in the hypothermia group than in the non-hypothermia group (all P ＜ 0.05).The proportion of patients with the anesthesia time ≥60 min or total intraoperative fluid intake ≥2000 ml was higher in the hypothermia group than in the non-hypothermia group(all P＜0.05).BMI ＜24 kg/m2 and total intraoperative fluid intake ≥ 2000 ml were the key risk factors for intraoperative hypothermia in elderly patients(all P＜0.05).Conclusions Intraoperative hypothermia is a common complication for elderly patients undergoing surgery.Intraoperative fluid intake and body mass are the key risk factors for intraoperative hypothermia.Targeted treatment measures based on the above related factors should be considered for elderly patients receiving surgery.

Objective To analyze the clinical features and validation of Brighton criteria in Guillain-Barré syndrome (GBS) patients from southern China.Methods The clinical data of hospitalized GBS patients from 69 hospitals of 14 provinces/cities in southern China,the area south of the Huaihe River,between 1 January 2013 and 30 September 2016,were collected and analyzed retrospectively,and patients were classified according to the Brighton criteria of case definition,ranging from a highest (defined as level one) to a lowest (level four) level of diagnostic certainty.Results A total of 1 358 GBS patients were collected,including 51 cases with cranial nerve variants,157 with Miler-Fisher syndrome and 1 150 with classic GBS characterized by flaccid weakness of limbs.Among 1 150 cases of classic GBS,49.57％ (570/1 150) patients had antecedent events,with respiratory infection predominated (71.23％,406/570);83.74％ (963/1 150) presented limb weakness at onset,99.21％ (1 124/1 133) reached the peak within four weeks,with a score of 3.15 ± 1.16 for Hughes Disability Scale;99.56％ (1 128/1 133)developed bilateral weakness and 95.39％ (1 097/1 150) manifested flexia or hyporeflexia;the cerebrospinal fluid showed albuminocytologic dissociation in 80.58％ (772/958) patients whose lumbar puncture was performed;demyelinating GBS accounted for 48.14％ (401/833) and axonal subtype 18.01％ (150/833) respectively in patients with findings of nerve conduction studies available.According to Brighton criteria,the patients were stratified as level one in 44.09％ (507/1 150),level two in 45.74％ (526/1 150),level three in 7.57％ (87/1 150) and level four in 2.61％ (30/1 150) of all the patients,and 69.55％ (507/729),28.67％ (209/729),0％ (0/729) and 1.78％ (13/729),respectively in the patients with complete data (n =729).Conclusions In southern China,demyelinating subtype of GBS is predominant,whereas the proportion of axonal subtype is remarkably lower than that in northern China.The Brighton criteria have a high sensitivity for the diagnosis of GBS in southern China,and examination of cerebrospinal fluid and electrodiagnostic studies are necessary for stratified diagnosis.

OBJECTIVE:To study the development and status quo of narcotics and psychotropic substances (NPS) in China since 1949,and to provide evidence for perfection of NPS control work in China. METHODS:The development and status quo of controlled substances control by China since 1949 were summarized and analyzed through retrieving and collecting literatures,re-ports and policies about NPS from domestic and foreign databases,news reports and related website. RESULTS & CONCLU-SIONS:Chinese narcotics and psychotropic substances control dated back to the release of Interim Regulations on Narcotics Con-trol in 1950 and Regulations on Narcotics Control,Drug Administration Law and other regulations have been issued. It had experi-enced the progress from no legal basis to having laws to follow and from executive-leading to legalization. Narcotics and psychotro-pic substances were gradually unified in systematic control,and the level of regulations rised from department rules to administra-tion regulation. At present,with Regulations on Narcotics and Psychotropic Drugs Control (2005) as regulatory basis and cata-logue of narcotics and psychotropic substances(2013)as object,China Food and Drug Administration are in charge of the national regulation,cooperating with health department,agricultural department,traffic department and other departments.

OBJECTIVE:To study the development and status quo of controlled drugs control in Britain,and to provide evi-dence for narcotics and psychotropic substances(NPS)control in China. METHODS:The development and status quo of NPS con-trol by Britain were summarized and studied through retrieving and collecting literatures,reports and policies about NPS from do-mestic and foreign databases,news reports and international website. RESULTS & CONCLUSIONS:British control for controlled drugs dated back to Pharmacy Act in 1868,and Britain was the first country to control drugs by legislations. A unique British sys-tem of narcotics control was established and improved after issued Rolleston Report and two pieces of Brain Report in Britain. Final-ly,the British system of narcotics control was established,which combined public health prevention with judicial redress. At pres-ent,controlled drugs are classified and controlled by Advisory Committee on Drug Abuse,Serious Organised Crime Agency and National Drug Abuse Treatment Agency subordinated to Ministry of Interior,based on Misuse of Drugs Act.

OBJECTIVE:To study the development and status quo of controlled substances control in the United States,and to provide evidence for narcotics and psychotropic substances (NPS) control in China. METHODS:The development and status quo of controlled substances control by the United States were summarized and studies through retrieving and collecting literatures,re-ports and policies about NPS from domestic and foreign databases,news reports and international website. RESULTS & CONCLU-SIONS:The United States'control for controlled substances dated back to Harrison Narcotics Tax Act in 1914,and the United States is the first nation to control narcotics addiction through the form of tax law after International Opium Convention is executed. Thereafter,the United States gradually extend the range by including cannabis,heroin and psychotropic substances into control range of Narcotics Drugs Import and Export Act,Heroin Act,Marijuana Tax Act,revising and developing comprehensive act Con-trolled Substances Act,and establishing comprehensive law enforcement agency Controlled Substances Enforcement Administration affiliated to Ministry of Justice by Nixon'sWar on Drugsplan.

OBJECTIVE:To study the development and status quo of international narcotics and psychotropic substances (NPS)control,and to provide evidence for NPS control in China. METHODS:The development and status quo of NPS control by international organization were summarized and studied through retrieving and collecting literatures,reports and policies about NPS from domestic and foreign databases,news reports and international website. RESULTS & CONCLUSIONS:International narcot-ics control dated back to opium trade with China in 19th century. International narcotics control system was established preliminarily by Shanghai conference and Haiya conference. The end of World War Ⅰ,the establishment of the League of Nations and the sign-ing of a number of international treaties promoted the development of internal control system. Through World War Ⅱ,the establish-ment of the United Nations and the change of international control organization,a number of international treaties were integrated into Single Convention on Narcotic Drugs in the early 1960s,which was used as the foundation of narcotics control system all round the world. In 1970s,the adoption of Convention on Psychotropic Substances meant psychotropic substances were included in the scope of internal control. In 1980s,the signing of United Nations Convention against Illicit Traffic in Narcotic Drugs and Psy-chotropic Substances marked the establishment of three conventions system of international NPS control. At present,internal NPS control is based on three conventions system and NPS list by Commission on Narcotic Drugs,International Narcotics Control Board and United Nations International Drug Control Program. The vast majority of countries are parties to that. International control orga-nizations and listed control have a great influence on NPS control all round the world.

OBJECTIVE:To make proposals to improve narcotics and psychotropic substances(NPS)control in China. METH-ODS:NPS control system of international organizations,the United States,Britain and China were compared in terms of concept, classification,regulatory basis and agency,etc. The suggestions and reference were put forward. RESULTS & CONCLUSIONS:NPS of international organizations,the United States,Britain and China are drug types included in relevant categories,besides ana-leptics,precursor chemicals and other drugs are included in control catalogue by the United States and Britain. NPS are divided in-toⅠ-Ⅳcategories by international organizations,Ⅰ-Ⅴcategories by the United States,A,B,C categories and temporary catego-ry by Britain,and narcotics,first and second class psychotropic substances by China. NPS control basis of the United States,Brit-ain and China are Controlled Substances Act,Misuse of Drugs Act and Regulations on Narcotics and Psychotropic Drugs Control, respectively;major regulation organizations are Controlled Substances Enforcement Administration,Advisory Committee on Drug Abuse subordinated to Ministry of Interior,Special Drug Section under China Food and Drug Administration,respectively;there al-so are differences in the functions of control organization and cooperative units. Considering about the problems of NPS control in China,it is suggested to improve laws and regulations system,establish independent system,extend abuse surveillance network and encourage chronic non-cancer pain therapy.

A male patient aged 23 years with chronic renal failure,who were treated with sequential living related donor kidney transplantation/nonmyeloablative syngeneic hematopoietic stem cell transplantation,were selected in April 2000 at the 153 Central Hospital of Chinese PLA.Donor is his mother.Nonmyeloablative syngeneic hematopoietic stem cells were transplanted after kidney transplantation.Microchimera in the recipient,rejection,infection and graft-versus-host reaction and dosage of immunodepressant were detected,and then compared with the control.Different nursing care plans were performed following different therapies.HLA-DR site,the same as the donor,could be detected in the recipient after 3 months,and present after 3 years.Immunodepressant dosage was half of that in subjects who did not receive hematopoietic stem cell transplantation.No rejection occurred during the 7 years follow-up.Microchimera or immunotolerance can be detected in the recipient following sequential living related donor kidney transplantation/nonmyeloablative syngeneic hematopoietic stem cell transplantation.