Persistent and maladaptive drug-related memories represent a key component in drug addiction. Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure (MRUP), a non-pharmacological strategy intertwining two distinct memory processes: reconsolidation and extinction-alternatively termed "the memory retrieval-extinction procedure". This procedure presents a promising approach to attenuate, if not erase, entrenched drug memories and prevent relapse. The present review delineates the applications, molecular underpinnings, and operational boundaries of MRUP in the context of various forms of substance dependence. Furthermore, we critically examine the methodological limitations of MRUP, postulating potential refinement to optimize its therapeutic efficacy. In addition, we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction. Overall, existing studies underscore the significant potential of MRUP, suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.
Humans ; Substance-Related Disorders/psychology* ; Memory Consolidation/physiology* ; Animals ; Extinction, Psychological/physiology*

Objective To evaluate the testing capabilities of laboratories,analyze existing issues,and improve testing quality,through carrying out the external quality assessment(EQA)of clinical laboratories for human papillomavirus(HPV)type 6 and 11 nucleic acid detection.Methods EQA plan was carried out twice a year.Each panel contains 4 positive samples,including one strong positive sample and one weak positive sample of HPV6 and HPV11,made from cervical secretions from patients with clinical manifestations of condyloma acuminata(CA)and positive for HPV6 or HPV11(from Shanghai First Maternity and Infant Hospital).One negative sample was cultured from the C-33A cell line(from Chinese Academy of Sciences).Samples were sent to participating laboratories by cold chain,and laboratories were required to detect test samples and upload their results within the specified time.Shanghai Center for Clinical Laboratory(SCCL)calculated the scores of each laboratory based on the return results.Results A total of 163 sample panels were sent out in the 6 rounds of EQA plan and 140 valid reports were received.The laboratory qualification rate was 96.43%(135/140)and the sample compliance rate was 97.86%(685/700).There were 13 false negative results and 2 false positive results,with weakly positive samples accounting for 76.92%(10/13)of the false negative results.Conclusion The detection accuracy of HPV6/11 nucleic acid in each laboratory was relatively high,and the detection ability of weak positive samples in individual laboratories may need to be improved.The laboratory could discover problems and improve its quality management by participating in EQA.

Background/Aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results: Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.

Background: The incidence density of metabolic dysfunction-associated fatty liver disease (MAFLD) and the effect of a healthy lifestyle on the risk of MAFLD remain unknown. We evaluated the prevalence and incidence density of MAFLD and investigated the association between healthy lifestyle and the risk of MAFLD. Methods: A cross-sectional analysis was conducted on 37,422 participants to explore the prevalence of MAFLD. A cohort analysis of 18,964 individuals was conducted to identify the incidence of MAFLD, as well as the association between healthy lifestyle and MAFLD. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) with adjustments for confounding factors. Results: The prevalence of MAFLD, non-alcoholic fatty liver disease, and their comorbidities were 30.38%, 28.09%, and 26.13%, respectively. After approximately 70 thousand person-years of follow-up, the incidence densities of the three conditions were 61.03, 55.49, and 51.64 per 1,000 person-years, respectively. Adherence to an overall healthy lifestyle was associated with a 19% decreased risk of MAFLD (HR, 0.81; 95% CI, 0.72 to 0.92), and the effects were modified by baseline age, sex, and body mass index (BMI). Subgroup analyses revealed that younger participants, men, and those with a lower BMI experienced more significant beneficial effects from healthy lifestyle. Conclusion Our results highlight the beneficial effect of adherence to a healthy lifestyle on the prevention of MAFLD. Health management for improving dietary intake, physical activity, and smoking and drinking habits are critical to improving MAFLD.

Tumor extracellular matrix (ECM) is the center component of tumor microenvironment (TME), ECM diversity constitutes the inherent heterogeneity of TME that contributes to tumor growth, dormancy, drug resistance, and metastasis. Discoidin domain receptor 1 is one of the ECM receptors that interact with multiple ECM ligands. It also regulates the occurrence and development of tumors. Accordingly, DDR1 plays an increasingly important role in the prevention, diagnosis, and treatment of cancer. In this review, we primarily summarize the research of ECM and its receptors with components, regulation, cell receptors, and signaling pathways in tumor progression.

In 2016, a national one million general population cohort project was set up in China for the first time in "Precision Medicine Research" Key Project, National Key Research and Development Program of China, which consists of general population cohorts in seven areas in China. As one of the seven major areas in China, northeastern China has unique climate and specific dietary patterns, and population aging is serious in this area. And the burden of chronic and non-communicable diseases ranks tops in China. Therefore, it is of great significance to establish a large general population cohort in northeastern China to explore the area specific exposure factors related to pathogenesis and prognosis of chronic and non-communicable diseases, develop new prevention strategies to reduce the burden of the diseases and improve the population health in northeastern China. In July 2018, the general population cohort study in northeastern China was launched, the study includes questionnaire survey, health examination and blood, urine and stool sample collection and detection in recruited participants. By now, the cohort has covered all age groups, and the baseline data of 115 414 persons have been collected. This paper summarizes the design and practice of the general population cohort study in northeastern China to provide reference for related research in China.

Objective:To investigate the quality of humanistic care for nursing students in Hebei province and to analyze its influencing factors.Methods:The humanistic care quality assessment scale of nursing students was designed and used as the research tool. A questionnaire survey was conducted among 2 693 nursing students from 11 medical colleges and universities in Hebei province and the results were analyzed. SPSS 21.0 was used for statistical analysis. Measurement data were expressed by (mean±standard deviation). The single factor analysis of variance and independent sample t-test were used for comparative study, and the multiple linear regression method was used to analyze the influencing factors. Results:The total Cronbach's coefficient of the scale was 0.966, and the Cronbach's coefficient of each dimension was 0.780-0.959, proving that the scale could be used. The data showed that the overall quality of humanistic care of nursing students in Hebei province was (119.70 ± 15.35), and the overall score rate was 85.50%. Among them, the comparison results of education background, grade, participation in volunteer activities, personality, the degree of concern of surrounding people, family atmosphere, and whether the teacher mentioned humanistic care were statistically significant ( P<0.05). Conclusion:The quality of humanistic care for nursing students in Hebei province is at a relatively high level. Colleges and universities can provide targeted education according to the current situation and influencing factors, create a good humanistic classroom atmosphere for nursing students, encourage nursing students to actively participate in humanistic practice, and improve the quality of humanistic care for nursing students.

OBJECTIVE: To analyze the clinical efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH), and preliminarily explore the role of an improved post-transplantation cyclophosphamide (PTCy) based conditioning regimen in PNH patients receiving transplantation. METHODS: Clinical related data of PNH sufferers receiving allo-HSCT in Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were collected, and hematopoietic reconstitution, chimerism, PNH cloning, graft-versus-host disease (GVHD), infection, and survival were analyzed. RESULTS: Totally five PNH patients receiving allo-HSCT were enrolled, including 1 case with classic PNH, 3 cases with aplastic anemia-PNH syndrome, 1 case with myelodysplastic syndrome, three of them (case 1-3) received the improved PTCy based conditioning regimen before HSCT. All sufferers engrafted successfully within 28 days, the median time of neutrophil and platelet engraftment was 11 days and 12 days, respectively, no patient occurred acute or chronic GVHD, after a median follow-up of 16 months, all recipients survived and completely eliminated PNH cloning. CONCLUSION Allo-HSCT can completely clear PNH cloning and restore hematopoietic function with controllable complications, and the improved PTCy based conditioning regimen is proved to be effective in PNH transplantation.
Anemia, Aplastic/therapy* ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Hemoglobinuria, Paroxysmal/therapy* ; Humans ; Transplantation Conditioning

Objective:To investigate the effects of metformin on the survival of patients with advanced non-small cell lung cancer (NSCLC).Methods:PubMed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang and other databases were searched from the beginning of database construction to February 2020, relevant literatures were screened and included, and the characteristics of the literatures were extracted. RevMan 5.3 software was used to analyze progression-free survival (PFS), overall survival (OS), hazard ratio(HR) and 95% CI; the heterogeneity and publication bias were also evaluated. Results:A total of 11 studies were enrolled, and metformin did not improve PFS in patients with advanced NSCLC ( HR = 0.80, 95% CI 0.58-1.09, P = 0.15). The subgroup analysis results of different treatment strategies showed that metformin combined with tyrosine kinase inhibitor (TKI) ( HR = 0.71, 95% CI 0.32-1.57, P = 0.39), chemoradiotherapy ( HR = 0.97, 95% CI 0.59-1.61, P = 0.92), and immune checkpoint inhibitor (ICI) ( HR = 0.64, 95% CI 0.35-1.16, P = 0.14) did not improve the PFS. Metformin improved OS in patients with advanced NSCLC ( HR = 0.84, 95% CI 0.75-0.93, P = 0.001). Metformin combined with TKI ( HR = 0.68, 95% CI 0.38- 1.22, P = 0.19) and ICI ( HR =0.80, 95% CI 0.39-1.63, P = 0.54) did not improve OS of patients, while metformin combined with chemoradiotherapy could improve OS ( HR = 0.85, 95% CI 0.78-0.93, P < 0.01). No evidence of publication bias was shown in the funnel plot analysis. Conclusions:Metformin can prolong OS time in patients with advanced NSCLC, especially in patients undergoing metformin combined with radiotherapy and chemotherapy, or concurrent chemoradiotherapy.

In the original publication the PDB numbers were not cited.