This paper reported a patient with early-onset Alzheimer's disease （AD） who had previously responded poorly to anti-dementia medications while showed improvement in cognitive functioning after treatment with occupational therapy and computerized cognitive remediation therapy （CCRT） for 50 minutes three times per week. This case report provided an in-depth evaluation of occupational therapy combined with CCRT for early-onset AD in an effort to inform cognitive rehabilitation of patients with AD. ［Funded by Chengdu Medical Scientific Research Project （number， 2023635）］

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objective:To explore the differences in clinical characteristics and treatment outcomes between patients with type A and type B alcohol dependence, and to find the independent risk factors of relapse.Methods:Alcohol-dependent male patients attending the Addiction Medicine Center of Beijing Huilongguan Hospital from January 2018 to December 2020 were selected for the study and divided into type A alcohol-dependent group ( n=77) and type B alcohol-dependent group ( n=87). All patients were given acute detoxification treatment and were followed up after treatment on relapse to drinking. Differences in demographic and clinical data were compared between the two groups, and differences in treatment outcomes between the two groups at different time points over 3 months were compared. Patients were divided into relapse group and non-relapse group according to whether they drank again after 3 months. Logistic regression model was established to screen the risk factors of relapse of alcohol-dependent patients by SPSS 25.0 software. Results:There was no significant difference between the two types of patients in years of education, marital status, smoking status and working status(all P>0.05), but the proportion of co-residents( χ2=5.69, P=0.017) and the proportion of positive family history of alcoholism were significant difference between the two type of patients( χ2=13.32, P<0.001). There were statistically significant differences between the two types of patients in the onset time( t=-7.28, P<0.001), the first drinking age( t=-2.36, P=0.020), the proportion of drinking in the morning( χ2=7.83, P=0.005), psychotic symptoms( χ2=4.31, P=0.038), convulsions after withdrawal( χ2=5.30, P=0.021), and alcohol use disorder identification test(AUDIT) score( t=4.30, P<0.001). At the 4th and 8th weekend of the follow-up, there were statistically significant differences in drinking frequency(0(0, 3), 0(0, 0), Z=-4.13, P<0.001; 3(0, 3), 0(0, 3), Z=-4.42, P<0.001) and relapse rate (40(45.98%), 9(11.69%), χ2=22.92, P<0.001; 61(70.11%), 24(31.17%), χ2=24.82, P<0.001) between the two types of alcohol dependence patients after drinking again. After 12-week follow-up, there were statistically significant differences between the two types of alcohol-dependent patients in the interval of first drinking(20(7, 30)d, 88(38, 90)d, Z=-7.83, P<0.001), the cumulative duration of abstinence(4(0, 8)weeks, 12(4, 12)weeks, Z=-5.13, P<0.001), the cumulative rate of abstinence(71(81.60%), 25(32.47%), χ2=40.62, P<0.001), the frequency of drinking after abstinence(3(3, 3), 0(0, 3), Z=-5.54, P<0.001), and the reduction of daily average alcohol consumption( t=3.36, P<0.001). Logistic regression model showed that type B alcohol dependence ( OR=3.121, P=0.03, 95% CI: 1.12-8.72) and AUDIT score ( OR=1.498, P<0.01, 95% CI: 1.29-1.74) were the risk factors for relapse of alcohol-dependent patients. Conclusions:Patients with type A and type B alcohol dependence have obvious differences in clinical characteristics and treatment outcomes, and type B alcohol dependence is independent risk factor for relapse to drinking in alcohol-dependent patients, which validate the rationality and necessity of alcohol dependence subtypes.

ObjectiveTo analyze the feasibility， reliability and validity of the disability assessment for dementia scale for the elderly. MethodsA total of 290 dementia patients from 17 survey sites in 13 districts and counties of Chengdu were enrolled by convenient sampling method， and they were assessed using demographic data inventory， Mini-Mental State Examination （MMSE）， Neuropsychiatric Inventory （NPI）， Physical Self-Maintenance Scale （PSMS） and disability assessment for dementia scale for the elderly. Cronbach's α coefficient， Spearman-Brown coefficient， Guttman split-half coefficient and test-retest reliability were used to evaluate the internal consistency of above scales. Criterion-related validity of the scale was analyzed based on MMSE， NPI and PSMS. ResultsA total of 276 patients （95.17%） completed valid questionnaires. The intraclass correlation coefficient of the total score and each dimension were between 0.828~0.976， the Spearman-Brown coefficient were between 0.790~0.917， the Guttman split-half coefficient were between 0.812~0.857， and the Cronbach’s α coefficient were between 0.737~0.886. The cognitive function dimension score was positively correlated with the MMSE score （r=0.948， P<0.01）， the mental behavior symptom dimension score was positively correlated with the NPI score （r=0.893， P<0.01）， and the daily living ability dimension score was positively correlated with the PSMS score （r=0.997， P<0.01）. The dimensions scores were positively correlated with the total score of the scale （r=0.634~0.841， P<0.05）. ConclusionDisability of dementia assessment scale has good feasibility， reliability and validity， which is a reliable tool to assess senile dementia and disability.

OBJECTIVE: To determine the composition and distribution of beta-thalassemia-associated genotypes in Liuzhou area of Guangxi, China. METHODS: From January to December 2017, 13 847 individuals who came for premarital examination, maternity examination or health check were recruited with informed consent. The subjects were analyzed by reverse dot blotting (RDB) for 17 common beta-thalassemia-associated variants among the Chinese population. Individuals with inconsistent results by blood test, electrophoresis, and RDB were subjected to Sanger sequencing to detect rare variants of the beta globin gene. RESULTS: In total 2098 individuals were found to harbor beta-thalassemia-associated variants, which included 2075 heterozygotes (98.90%), 12 compound heterozygotes (0.57%) and 11 homozygotes (0.52%). CD41-42 (48.43%) and CD17 (31.45%) were the most common variants. Three hundred and thirty eight-individuals were found to also carry heterozygous variants of the alpha globin gene, with the most common types being --SEA/aa, -a3.7/aa, aCSa/aa, -a4.2/aa. Through Sanger sequencing, rare genotypes such as beta-32/betaN, betaCD41-42/betaIVS-II-5 and betaCD30/betaN were detected. CONCLUSION Liuzhou area has a high incidence of beta-thalassemia, but with a complex variant spectrum and clinical phenotypes different from other regions. Genetic counseling and prenatal diagnosis for the carrier population is crucial for the reduction of the related birth defects. Our result may provide valuable information for the prevention and control of beta-thalassemia in this area.
China ; Female ; Genetic Counseling ; Genetic Variation ; Genotype ; Humans ; Mutation ; Pregnancy ; Prenatal Diagnosis ; alpha-Globins ; genetics ; beta-Globins ; genetics ; beta-Thalassemia ; diagnosis ; genetics

Objective:To investigate the clinical features, treatment and prognosis of anti-γ-aminobutyric acid type B receptor (GABA B R) encephalitis. Methods:Retrospective analysis of five patients of anti-GABA BR encephalitis from the Department of Neurology, the University of Hong Kong-Shenzhen Hospital from September 2017 to June 2019 was carried out. Clinical manifestations, auxiliary examination, and treatment were analyzed. The patients were followed up for 3.5-23.0 months to assess their prognosis. Results:Five cases of anti-GABA BR encephalitis (19-81 years old) presented acute onset, with refractory epilepsy as the main clinical manifestation. There were hyperintensive signals on T 2/fluid attenuated inversion recovery in four patients′ temporal lobe and hippocampus. Electroencephalogram showed slow wave or epileptic discharge; Lung mass was found in four patients, and all were small cell lung cancer. Five cases had poor response to first-line immunotherapy (intravenous use of pulse methylprednisolone, high dose immunoglobulin or plasma exchange), then three patients received second-line immunotherapy (rituximab, cyclophosphamide), two of whom with tumor also received tumor chemotherapy. Patients who received second-line treatment and tumor chemotherapy showed better outcome than those who only received first-line treatment. Conclusions:Anti-GABA BR encephalitis present with limbic encephalitis syndromes characterized by refractory epilepsy. For patients with poor response to first-line immunotherapy, initiating second-line immunotherapy as soon as possible can improve the prognosis significantly.

Objective: To investigate the value of combination of A²DS² score, procalcitonin (PCT) and C-reactive protein (CRP) predicting stroke-associated pneumonia (SAP) in patients with acute ischemic stroke. Methods: Patients with acute ischemic stroke admitted to the Department of Neurology, Suqian People's Hospital of Nanjing Drum Tower Hospital Group from March 2015 to March 2019 were enrolled retrospectively. Multivariate logistic regression analysis was used to determine the independent correlation of A²DS² scores as well as PCT and CRP levels with SAP. Receiver operating characteristic (ROC) curves were used to assess the individual and combined predictive values of A²DS² scores, PCT and CRP levels for SAP. Results: A total of 332 patients with acute ischemic stroke were enrolled, and 58 of them developed SAP (17.5%). After adjusting for age, smoking, and hyperlipidemia, the A²DS² score (odds ratio [OR] 1.613, 95% confidence interval [CI] 1.092-2.389), PCT (OR 8.047, 95% CI 3.012-16.138) and CRP (OR 1.409, 95% CI 1.064-2.672) were the independent predictors of SAP occurrence. ROC curve analysis showed that the area under the curve of A²DS² score, PCT and CRP alone, and the combination of the three for predicting SAP were 0.811, 0.825, 0.804 and 0.910, respectively. When the three are jointly used to predict SAP, the area under the curve is significantly higher than the individual prediction (all P<0.001). Conclusions The combination of A²DS² score, PCT and CRP can improve the ability to predict SAP.

Objective To construct human yippee-like 5(YPEL5) gene eukaryotic expression recombinant plasmid and to express in esophageal carcinoma EC9706 cells .Methods The cDNA from human normal tissue was taken as a template and amplified to YPEL5 gene coding sequence with 366 bp in length .Then this se-quence was inserted into the multiple cloning site areas of eukaryotic expression vector pCDH-CD513B for ob-taining the eukaryotic expression vector pCDH-CD513B-Flag-YPEL5 .After the bacterial colony PCR identifi-cation ,it was sent to the corporation for testing the sequence .The successfully constructed recombinant plas-mid was transfected into human esophageal carcinoma EC9706 cells .The expression of PEL5 gene in EC9706 cells was detected by QRT-PCR and Western Blot .Results The YPEL5 gene segment with 366 bp in length was successfully amplified .pCDH-CD513B-Flag-YPEL5 recombinant plasmid was obtained by double enzyme digestion ,connection ,conversion and screening .The gene sequencing identification showed that the inserted gene sequence in recombinant plasmid was consistent with that in the GenBank .After 2 d of transfecting into EC9706 cells ,the QRT-PCR and Western Blot revealed that YPEL5 gene expression was significantly up-reg-ulated .Conclusion The pCDH-CD513B-Flag-YPEL5 eukaryotic expression vector is successfully constructed and is expressed in esophageal squamous cancer cell line EC9706 ,thus which lays a foundation for studying its function in the progression of esophageal cancer .

Objective To evaluate the value of a new platelet function test PFA P2Y (PFA-200) in monitoring clopidogrel treatment for cardiovascular disease in elderly patients. Methods Fifty-six elderly patients receiving clopidogrel therapy in the Department of Cardiology of General Hospital of PLA from March to August in 2016 and 85 healthy volunteers were recruited for analysis. All the subjects underwent PFA P2Y, LTA (light transmittance aggregometry) and TEG (Thromboelastograph) tests, and Spearman correlation coefficients were used to test the associations between test results. The agreement among the 3 platelet function test methods was assessed using Cohen's kappa coefficient. Results Correlation coefficient (r) was-0.701 (P<0.001) between PFA P2Y and LTA, and 0.475 (P<0.001) between PFA P2Y and TEG. The agreement was 75%between PFA P2Y and LTA and 67.9%between PFA P2Y and TEG. Theκvalue was 0.434 (P=0.001) between PFA P2Y and LTA and 0.242 (P=0.046) between PFA P2Y and TEG. With ADP-induced maximum platelet aggregation rate of LTA>50%as the laboratory clopidogrel resistance, the cut-off value of PFA P2Y was 119 s (AUC=0.733) with a sensitivity of 75.6% and a specificity of 73.3%. Conclusion PFA P2Y has a moderate correlation and agreement with LTA, but has a poor correlation and agreement with TEG. PFA P2Y can be useful for assessing the effects of clopidogrel therapy and the association of the cut-off value (119 s) with the long-term clinical ischemic events needs be confirmed in further study.

Objective To evaluate the value of a new platelet function test PFA P2Y (PFA-200) in monitoring clopidogrel treatment for cardiovascular disease in elderly patients. Methods Fifty-six elderly patients receiving clopidogrel therapy in the Department of Cardiology of General Hospital of PLA from March to August in 2016 and 85 healthy volunteers were recruited for analysis. All the subjects underwent PFA P2Y, LTA (light transmittance aggregometry) and TEG (Thromboelastograph) tests, and Spearman correlation coefficients were used to test the associations between test results. The agreement among the 3 platelet function test methods was assessed using Cohen's kappa coefficient. Results Correlation coefficient (r) was-0.701 (P<0.001) between PFA P2Y and LTA, and 0.475 (P<0.001) between PFA P2Y and TEG. The agreement was 75%between PFA P2Y and LTA and 67.9%between PFA P2Y and TEG. Theκvalue was 0.434 (P=0.001) between PFA P2Y and LTA and 0.242 (P=0.046) between PFA P2Y and TEG. With ADP-induced maximum platelet aggregation rate of LTA>50%as the laboratory clopidogrel resistance, the cut-off value of PFA P2Y was 119 s (AUC=0.733) with a sensitivity of 75.6% and a specificity of 73.3%. Conclusion PFA P2Y has a moderate correlation and agreement with LTA, but has a poor correlation and agreement with TEG. PFA P2Y can be useful for assessing the effects of clopidogrel therapy and the association of the cut-off value (119 s) with the long-term clinical ischemic events needs be confirmed in further study.