Objective To explore the associations of the sub-components of central executive function ( inhibition, shifting and updating) with monoamine oxidase A ( MAOA ) and dopamine-β-hydroxylase ( DBH ).Methods The cognitive performance of the 719 healthy individuals,who were selected randomly from an university in Xi' an,was assessed by the world wide used paradigms of central executive function. Then, a populationbased study was performed to analysis the associations of central executive function with the 30-bp variable number tandem repeat and -C1021T in the promoters of MAOA and DBH ,respectively. Results The results indicated that the 30-bp variable number tandem repeat of MAOA was associated with the performance of inhibition and updating ( x2 = 4.82,4.50; P= 0. 03,0.03 ) in males. The reaction time of inhibition test was shorter in 3r genotype group ( (671.32 ±9.77 )ms) than that in 4r genotype group ( (706.61 ± 14.58 ) ms) ,and the indivudals with 3r genotype (47.85 ±0. 69) had more updating numbers than the indivudals with 4r (45.13 ± 1. 05). However, there was no significant association of the -C1021T and DBH with the components of excutive function (P＞0.05). Conclusion The present study suggests that the 30-bp variable number tandem repeat of MAOA contributs to the inhibition in males while -C1021T of DBH has no striking effects on the components of executive function in males and females.

Objective To explore the relationship between interleukin 1 receptor accessory protein-like 2 (IL1RAPL2) gene and cognitive abilities of children in Qin-Ba mountainous region. Methods Four tagged SNPs (rs5962434,rs5916817, rs3764765 and rs5962298 ) in IL1RAPL2 were selected, and then genotyped by PCR-SSCP method in a 320 children sample aged from six to fourteen years old. Results The results showed the rs5962434, rs5916817 ,rs3764765 and rs5962298 had no deviations from Hardy-Weinberg equilibrium (P＞0.05),and there were no significant statistical differences in the average psychometric scores of general cognitive ability(P=0.81,0.53,0.79,0.90) ,verbal comprehension (P=0.58,0.47,0.69,0.87 ) ,memory and concentration (P=0.69,0.35,0.76,0.90) among the compared genotype groups at each of the markers. Furthermore,the results also indicated that the four SNPs were not associated with perceptual organization in males and females respectively (P = 0.70,0.85,0.76,0.90,0.65,0.22,0.98,0.90 ). Conclusion The present work suggests that the human general cognitive ability, the three cognitive factors of C-WISC scale are not influenced manifestly by the genetic variations in IL1RAPL2.

Objective To investigate the correlation between subclinical hypothyroidism (SCH) and cerebral atherosclerosis burden in patients with large artery atherosclerotic stroke.Methods Consecutive inpatients with acute large artery atherosclerotic stroke were enrolled.SCH was defined as TSH 4.50-10.0 mU/L and serum thyroxine level was normal.Cerebral atherosclerosis burden score was used to evaluate the severity of cerebral atherosclerosis.The total score of 1 or 2 was defined as mild atherosclerosis,and >2 was defined as severe atherosclerosis.Univariate analysis and multivariate logistic regression analysis was used to evaluate the correlation between SCH and severe cerebral atherosclerosis.ResultsA total of 263 patients with large artery atherosclerotic stroke were enrolled,including SCH 62 (23.6%),mild atherosclerosis 119 (45.2%),and severe atherosclerosis 144 (54.8%).The age (63.6±10.9 years vs.60.5±11.4 years;t=2.274,P=0.024),homocysteine (17.10±6.20 μmol/L vs.15.63±5.17 μmol/L;t=2.058,P=0.041),National Institutes of Health Stroke Scale (NIHSS) score (8.0 [5.0-10.0]vs.6.0 [5.0-9.0];Z=2.059,P=0.039),as well as the proportions of patients with hypertension (72.9%vs.58.8%;χ2=5.812,P=0.016),smoking (38.2%vs.26.1%;χ2=4.366,P=0.037),and SCH (30.6%vs.15.1%;χ2=8.610,P=0.003) in the severe cerebral atherosclerosis group were significantly higher than those in the mild cerebral atherosclerosis group.Multivariate logistic regression analysis indicated that SCH was an independent risk factor for severe atherosclerosis in patients with large atherosclerotic stroke (odd ratio 3.345;95%confidence interval 1.692-6.612;P=0.001) after adjusting for age,sex,hypertension,smoking,homocysteine,and NIHSS score.ConclusionSCH is an independent risk factor for severe cerebral atherosclerosis in patients with large atherosclerotic stroke.

The mammalian liver has a very strong regeneration capacity after partial hepatectomy (PH). To further learn the genes participating in the liver regeneration (LR), 551 cDNAs selected from subtracted cDNA libraries of the regenerating rat liver were screened by microarray, and their expression profiles were studied by cluster and generalization analyses. Among them, 177 genes were identified unreported and up- or down-regulated more than twofold at one or more time points after PH, of which 62 genes were down-regulated to less than 0.5; 99 genes were up-regulated to 2-10 folds, and 16 genes were either up- or down-regulated at different time points during LR. By using BLAST and GENSCAN, these genes were located on responsible chromosomes with 131 genes on the long arms of the chromosomes. The cluster and generalization analyses showed that the gene expression profiles are similar in 2 and 4, 12 and 16, 96 and 144 h respectively after PH, suggesting that the actions of the genes expressed in the same profiles are similar, and those expressed in different profiles have less similarity. However, the types, characteristics and functions of the 177 genes remain to be further studied.
Animals ; Chromosome Mapping ; Expressed Sequence Tags ; Gene Expression Profiling ; Liver Regeneration ; genetics ; physiology ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Sequence Analysis, DNA ; Time Factors

Objective The aim of this study was to explore whether the down-regulation of tumor suppressor gene PRDM5 is one of the mechanisms of HPV16 virus infection leading to cervical cancer. Methods The expressions of PRDM5 protein and HPV16 E6/HPV18 E6 protein in cervical cancer tissues and normal cervical tissues were detected by immunohistochemistry. After transfected with HPV16 E6 shRNA plasmid,the expression of PRDM5 gene was detected in SiHa cells by RT-PCR and Western blot. Results The positive expression rate of HPV 16/18 E6 in cervical cancer tissues was significantly higher than that in normal cervical tissues. The expression level of PRDM5 protein in cervical cancer tissues was lower than that in normal cervical tissues. After HPV16 E6 shRNA3 was transfected into SiHa cells to interfere with the expression of HPV16 E6 gene,the expression of PRDM5 at mRNA and protein levels was up-regulated in SiHa cells. Conclusion PRDM5 may mediate the development of cervical cancer caused by HPV16 virus infection.

Purpose: Tamoxifen showed individual differences in efficacy under different CYP2D6*10 genotypes. Our study evaluated the prognosis of tamoxifen or toremifene in hormone receptor (HR)–positive breast cancer patients under different genotypes. Materials and Methods: CYP2D6*10 genotypes of HR-positive breast cancer patients were determined by Sanger sequencing, and all the patients were divided into tamoxifen group or toremifene group. Results: A total of 268 patients with HR-positive breast cancer were studied. The median follow-up time was 72.0 months (range, 5.0 to 88.0 months). Of these, 88 (32.9%), 114 (42.5%), and 66 (24.6%) patients had C/C, C/T, and T/T genotypes, respectively. Among patients who received tamoxifen (n=176), the 5-year disease-free survival (DFS) rate in patients with C/C and C/T genotype was better than that in patients with T/T genotype, and the difference was statistically significant (p < 0.001 and p=0.030, respectively). In patients receiving toremifene, CYP2D6*10 genotype was not significantly associated with DFS (p=0.325). Regardless of genotypes, the 5-year DFS rate was higher in patients treated with toremifene than in patients with tamoxifen (91.3% vs. 80.0%, p=0.011). Compared with tamoxifen, toremifene remained an independent prognostic marker of DFS in multivariate analysis (hazard ratio, 0.422; p=0.021). For all the 180 patients with CYP2D6*10 C/T and T/T genotypes, the 5-year DFS rate was significantly higher in the toremifene group than in the tamoxifen group (90.8% vs. 70.1%, p=0.003). Conclusion Toremifene may be an alternative adjuvant endocrine therapy for patients with CYP2D6*10 mutant genotypes.

【Objective】 To determine the best collection time period of plasma which can be used for human COVID-19 immunoglobulin for intravenous injection through SARS-CoV-2-IgG change and neutralizing antibody distribution against different virus strain in representative mixed plasma before and after Omicron strain infection by ELISA and pseudovirus neutralization test. 【Methods】 An ELISA method for quantitative detection of SARS-CoV-2-IgG was established and its linear range,accuracy and precision was verified. SARS-CoV-2-IgG potency was detected in 25 convalescent plasma which were collected 20-40 days after confirmed Omicron infection, two groups of mixed plasma samples WP1 and WP2 were prepared according to the SARS-CoV-2-IgG results, and pseudovirus neutralization experiments with different virus strain (prototype strain, BA. 1,BA.2, BA.4/5, BF.7, BQ.1.1) were carried out to determine the distribution of neutralizing antibodies against different virus strain. SARS-CoV-2-IgG potency of representative mixed plasma collected from 14 plasma stations subordinate to the company before and after Omicron strain infection was detected, including Omicron convalescent plasma (OP) collected from different plasma stations from December 2022 to May 2023 and normal pool plasma (VN) feed in March 2023 which collected from March 2022 to December 2022. According to the results, the difference and the change rule with time of SARS-CoV-2-IgG before and after Omicron strain infection were analyzed. 【Results】 The linearity of SARS-CoV-2-IgG ranged from 6.25 to 200 EIU/mL, the accuracy in-batch ranged from 81.793% to 106.985%, the precision in-batch ranged from 1. 100% to 13.000%, and the total error in-batch ranged from 2.988% to 22.679%. The accuracy between batches ranged from 90.788%to 96.893%, the precision between batches ranged from 4.870% to 6.272%, and the total error between batches ranged from 9.192% to 15.399%. The results of pseudovirus neutralizing antibody showed that the potency of different virus strain neutralizing antibodies were in the order of prototype strain>BA.2>BA.4/5>BF.7≈ BQ.1.1>BA.1 and the correlation between WP1 and WP2 was high (Pearson r=0. 931 1, P=0.002 3) which indicated that the potency distribution of neutralizing antibodies of different virus strain in Omicron convalescent plasma was basically stable. Compared with the mixed convalescent plasma sample G128 collected in June 2022, the potency of Omicron neutralizing antibodies of WP series were significantly higher, the ratio of BA.2 antibody to prototype antibody increased from 26.9% (before infection) to 82.6%-87.5% (after infection). The results of VN series before Omicron infection were < 100 EIU/mL, and the results of OP series after Omicron infection showed that the plasma collected from the beginning of December 2022 was the peak of antibody in the same month,and then dropped sharply, entering a short plateau in February-March 2023 (potency was about 40% of the peak value),and then dropped sharply again in April (potency was about 20% of the peak value). 【Conclusion】 The potency and proportion of neutralizing antibody against Omicron subtype in convalescent plasma after COVID-19 Omicron strain infection increased significantly. IgG antibody of plasma donors in different regions reached its peak in the month of infection, then continued to dropped sharply. The best collection period of plasma that can be used for human COVID-19 immunoglobulin for intravenous injection was 1 to 2 months after infection.

BACKGROUNDGallbladder carcinoma (GBC) has a high mortality rate, requiring synergistic anti-tumor management for effective treatment. The myxoma virus (MYXV) exhibits a modest clinical value through its oncolytic potential and narrow host tropism.

METHODSWe performed viral replication assays, cell viability assays, migration assays, and xenograft tumor models to demonstrate that bone marrow-derived stem cells (BMSCs) may enhance efficiency of intravenous MYXV delivery.

RESULTSWe examined the permissiveness of various GBC cell lines towards MYXV infection and found two supported single and multiple rounds of MYXV replication, leading to an oncolytic effect. Furthermore, we found that BMSCs exhibited tropism for GBC cells within a Matrigel migration system. BMSCs failed to affect the growth of GBC cells, in terms of tumor volume and survival time. Finally, we demonstrated in vivo that intravenous injection of MYXV-infected BMSCs significantly improves the oncolytic effect of MYXV alone, almost to the same extent as intratumoral injection of MYXV.

CONCLUSIONThis study indicates that BMSCs are a promising novel vehicle for MYXV to clinically address gallbladder tumors.

Animals ; Bone Marrow Cells ; cytology ; Cell Movement ; physiology ; Cell Survival ; physiology ; Female ; Gallbladder Neoplasms ; therapy ; virology ; Humans ; Immunohistochemistry ; Mice ; Myxoma virus ; pathogenicity ; Stem Cells ; cytology ; physiology ; Virus Replication ; physiology ; Xenograft Model Antitumor Assays

Cabozantinib, mainly targeting cMet and vascular endothelial growth factor receptor 2, is the second-line treatment for patients with advanced hepatocellular carcinoma (HCC). However, the lower response rate and resistance limit its enduring clinical benefit. In this study, we found that cMet-low HCC cells showed primary resistance to cMet inhibitors, and the combination of cabozantinib and mammalian target of rapamycin (mTOR) inhibitor, rapamycin, exhibited a synergistic inhibitory effect on the in vitro cell proliferation and in vivo tumor growth of these cells. Mechanically, the combination of rapamycin with cabozantinib resulted in the remarkable inhibition of AKT, extracellular signal-regulated protein kinases, mTOR, and common downstream signal molecules of receptor tyrosine kinases; decreased cyclin D1 expression; and induced cell cycle arrest. Meanwhile, rapamycin enhanced the inhibitory effects of cabozantinib on the migration and tubule formation of human umbilical vascular endothelial cells and human growth factor-induced invasion of cMet inhibitor-resistant HCC cells under hypoxia condition. These effects were further validated in xenograft models. In conclusion, our findings uncover a potential combination therapy of cabozantinib and rapamycin to combat cabozantinib-resistant HCC.
Anilides/pharmacology* ; Animals ; Carcinoma, Hepatocellular/drug therapy* ; Cell Line, Tumor ; Cell Proliferation ; Endothelial Cells/metabolism* ; Humans ; Liver Neoplasms/drug therapy* ; Pyridines/pharmacology* ; Sirolimus/pharmacology* ; Xenograft Model Antitumor Assays