OBJECTIVES: To investigate the mechanism by which transforming growth factor‑β (TGF‑β) regulates major histocompatibility complex class I (MHC-I) expression in hepatocellular carcinoma (HCC) cells and its role in immune evasion of HCC. METHODS: HCC cells treated with TGF‑β alone or in combination with SB-431542 (a TGF-β type I receptor inhibitor) were examined for changes in MHC-I expression using RT-qPCR and Western blotting. A RNA interference experiment was used to explore the role of miR-23a-3p/IRF1 signaling in TGF‑β‑mediated regulation of MHC-I. HCC cells with different treatments were co-cultured with human peripheral blood mononuclear cells (PBMCs), and the changes in HCC cell proliferation was assessed using CCK-8 and colony formation assays. T-cell cytotoxicity in the co-culture systems was assessed with lactate dehydrogenase (LDH) release and JC-1 mitochondrial membrane potential assays, and T-cell activation was evaluated by flow cytometric analysis of CD69 cells and ELISA for TNF-α secretion. RESULTS: TGF‑β treatment significantly suppressed MHC-I expression in HCC cells and reduced T-cell activation, leading to increased tumor cell proliferation and decreased HCC cell death in the co-culture systems. Mechanistically, TGF-β upregulated miR-23a-3p, which directly targeted IRF1 to inhibit MHC-I transcription. Overexpression of miR-23a-3p phenocopied TGF‑β‑induced suppression of IRF1 and MHC-I. CONCLUSIONS We reveal a novel immune escape mechanism of HCC, in which TGF‑β attenuates T cell-mediated antitumor immunity by suppressing MHC-I expression through the miR-23a-3p/IRF1 signaling axis.
Humans ; MicroRNAs/genetics* ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Interferon Regulatory Factor-1/metabolism* ; Transforming Growth Factor beta/metabolism* ; Signal Transduction ; Histocompatibility Antigens Class I/metabolism* ; Cell Line, Tumor ; Tumor Escape ; Coculture Techniques

Pulmonary hypertension (PH) is an extremely malignant pulmonary vascular disease of unknown etiology. ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine, thereby affecting RNA expression. However, the role of ADAR1 in PH development remains unclear. In the present study, we investigated the biological role and molecular mechanism of ADAR1 in PH pulmonary vascular remodeling. Overexpression of ADAR1 aggravated PH progression and promoted the proliferation of pulmonary artery smooth muscle cells (PASMCs). Conversely, inhibition of ADAR1 produced opposite effects. High-throughput whole transcriptome sequencing showed that ADAR1 was an important regulator of circRNAs in PH. CircCDK17 level was significantly lowered in the serum of PH patients. The effects of ADAR1 on cell cycle progression and proliferation were mediated by circCDK17. ADAR1 affects the stability of circCDK17 by mediating A-to-I modification at the A5 and A293 sites of circCDK17 to prevent it from m1A modification. We demonstrate for the first time that ADAR1 contributes to the PH development, at least partially, through m1A modification of circCDK17 and the subsequent PASMCs proliferation. Our study provides a novel therapeutic strategy for treatment of PH and the evidence for circCDK17 as a potential novel marker for the diagnosis of this disease.

【Objective】 To investigate the independent risk factors of urinary tract infection (UTI) in recipients under-going renal transplantation of donation after brain death (DBD), so as to provide a theoretical basis for the prevention and control of postoperative UTI. 【Methods】 A retrospective study was conducted for recipients who received renal transplantation of DBD in our hospital during Jan.2021 and Dec.2021. The recipients were divided into the infection group (n=26) and non-infection group (n=74) according to the incidence of UTI 3 months after operation. The risk factors of UTI were identified with univariate and multivariate analyses. 【Results】 The incidence of UTI was 26%. Univariate analysis showed that gender, postoperative urinary fistula, time of indwelling catheter and time of indwelling double J tube were the influencing factors of UTI (P<0.05). Forward stepwise regression analysis showed time of indwelling double J tube (OR=1.086,95%CI:1.003-1.177,P=0.042) and time of indwelling catheter(OR=4.687,95%CI:2.064-10.645, P<0.010) were the independent risk factors of UTI (P<0.05). 【Conclusion】 The time of indwelling catheter and time of indwelling double J tube are the independent factors of UTI after renal transplantation of DBD.

ObjectiveTo observe the effect of brain-computer interface (BCI) training based on motor imagery on hand function in hemiplegic patients with subacute stroke. MethodsFrom June, 2020 to December, 2021, 40 patients with hemiplegia in subacute stroke from Department of Rehabilitation Medicine, Fifth Affiliated Hospital of Zhengzhou University were divided into control group (n = 20) and experimental group (n = 20) using random number table. Both groups accepted medication and routine comprehensive rehabilitation, while the control group accepted hand rehabilitation robot training, and the experimental group accepted the robot training using motor imagery-based BCI, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), modified Barthel Index, modified Ashworth scale, and measured integrated electromyogram of the superficial finger flexors, finger extensors and short thumb extensors of the affected forearm during maximum isometric voluntary contraction with surface electromyography. ResultsTwo patients in the control group and one in the experimental group dropped off. All the indexes improved in both groups after treatment (t > 2.322, Z > 2.631, P < 0.05), and they were better in the experimental group than in the control group (t > 2.227, Z > 2.078, P < 0.05), except the FMA-UE score of wrist. ConclusionMotor imagery-based BCI training is more effective on hand function and activities of daily living in hemiplegic patients with subacute stroke.

ObjectiveTo conduct a visualized analysis of the research related to the use of brain-computer interface technology for stroke rehabilitation in the past ten years, and identify and predict the hot spots and hot trends in order to promote the further development of this field. MethodsThe Web of Science Core Collection database was searched for literature related to brain-computer interface technology for stroke rehabilitation from January, 2011 to October, 2022. CiteSpace 5.8.R3 was used to analyze the number of publications, countries, institutions, authors, keywords, co-citations, and grant support. Results and ConclusionA total of 592 papers were included, and the annual number of publications in this field of research showed a rapid growth trend, and the research enthusiasm continued to increase. The United States was in the leading position in this field, with the highest number of cooperative publications and the highest intermediary centrality; China had certain advantages in this field, but still needed to strengthen the exchange and cooperation with other countries/regions. Foreign institutions and authors had formed a network of close cooperative relationships, and formed a high-impact team represented by Niels Birbaumer, Cuntai Guan, Kai Keng Ang, etc.; there were poor cooperative relationships among domestic authors and institutions, and there were geographical restrictions and lack of high-impact academic groups. The keywords "motor imagery" and "recovery" formed ten major clusters and 15 prominent words with high variation rates, showing a trend of diversification in research directions. The study of the efficacy of upper limb motor rehabilitation and central mechanisms has been the hot topics in this field and will continue for some time in the future; the use of lower limb brain-computer interface systems for improving foot drop, gait and balance in stroke patients and the application of multimodal brain-computer interfaces will probably become a hot topic in the future. Finally, the use of brain-computer interface-guided neurofeedback training for cognitive and language rehabilitation in stroke also needs attention.

Establishment of vaginal immune defenses at the mucosal interface layer through gene vaccines promise to prevent infectious diseases among females. Mucosal barriers composed of a flowing mucus hydrogel and tightly conjugated epithelial cells (ECs), which represent the main technical difficulties for vaccine development, reside in the harsh, acidic human vaginal environment. Different from frequently employed viral vectors, two types of nonviral nanocarriers were designed to concurrently overcome the barriers and induce immune responses. Differing design concepts include the charge-reversal property (DRLS) to mimic a virus that uses any cells as factories, as well as the addition of a hyaluronic acid coating (HA/RLS) to directly target dendritic cells (DCs). With a suitable size and electrostatic neutrality, these two nanoparticles penetrate a mucus hydrogel with similar diffusivity. The DRLS system expressed a higher level of the carried human papillomavirus type 16 L1 gene compared to HA/RLS in vivo. Therefore it induced more robust mucosal, cellular, and humoral immune responses. Moreover, the DLRS applied to intravaginal immunization induced high IgA levels compared with intramuscularly injected DNA (naked), indicating timely protection against pathogens at the mucus layer. These findings also offer important approaches for the design and fabrication of nonviral gene vaccines in other mucosal systems.

Objective:To explore the relationship between marital status and mild cognitive impairment in older adults.Methods:This study is a cluster random sampling.From January to December 2020, a questionnaire survey was conducted among older adults aged 60 years and over in four cities of Hebei Province.Finally, 2690 older adults with mild cognitive impairment and normal cognitive function were enrolled.The older adults were divided into 2 groups according to their marital status: married and living with their spouses(group E1), divorced or living alone(group E2). The mini-mental state examination(MMSE)scores of older adults in the two groups were compared.Moreover, the cognitive differences of older adults between the two groups and the interaction of marital status, social activities and life events on cognitive outcomes were analyzed.Results:The married older adults with partners had better cognitive preservation( P<0.01). The more life events were more likely to cause cognitive impairment( P<0.01), and the interaction of marital status, social activities and life events had a significant impact on cognition( P<0.01). Older men who were married and lived with spouse had better cognition than older women who were married and lived with spouse( P<0.05 in Model 3). The cognition of widowed elderly women was better than those of widowed elderly men( P<0.1 in Model 1; P<0.1 in Model 2). Among elderly men, the cognition of those married and living with spouse was better than that those of widowed( P<0.01 in models 1 and 2, P<0.1 in model 3). Among elderly women, those married and living with spouse had better cognitive outcomes than those widowed( P<0.01 in Model 1, P<0.01 in Model 2). Conclusions:Marital companionship is a protective factor for the cognition of older adults, and there are gender differences in the impact of marital status on cognition in late life.

Objective:To explore the association between polymorphism of Histone Deacetylase 2 (HDAC2) gene and alcohol use disorder (AUD) in male people of Han nationality for seeking suitable single nucleotide loci(SNP), and provide reference for early diagnosis and intervention of alcohol use disorder(AUD).Methods:A total of 194 male AUD patients of Han nationality (case group) and 310 normal men of Han nationality (control group) were selected for the study. The genomic DNA of peripheral blood of the subjects in the two groups was extracted, and 13 SNP loci of HDAC2 gene were obtained from HapMap database. The subjects in the two groups were genotyped by Agena MassARRAY SNP genotyping method.SPSS 25.0 was used to statistically analyze the differences of genotype frequency and allele frequency between the two groups, and Haploview 4.2 software was used for linkage disequilibrium and haploid analysis. The multiple test correction was carried out by the replacement test with 50 000 replacement times.Results:The genotype frequency of the 3 SNP loci(rs9481408, rs6568819, rs9488289) of HDAC2 gene were statistically significant different between the case group and the control group (all P<0.05). Further analysis found that the three loci were significantly correlated with AUD in the recessive genetic model between case group and control group(T/T vs C/C-C/T: OR=1.78, 95% CI: 1.05-3.03, P=0.033; T/T vs C/C-C/T: OR=1.79, 95% CI: 1.05-3.03, P=0.032; G/G vs C/C-C/G: OR=1.85, 95% CI: 1.09-3.13, P=0.022). Seven SNP haplotypes were constructed and the association odds ratio of GATCTGCAATAA between the case group and control group was 2.44, and the difference was statistically significant ( P<0.05). Conclusion:The SNP loci rs9481408, rs6568819, rs9488289 in the HDAC2 gene and haplotype GATCTGCCAATAA are associate with AUD in male people of Han nationality. These results indicated that the HDAC2 gene is one of the susceptibility genes of AUD.

Objective:To explore the expressions of miRNAs related to accelerating senescence in serum of the patients with amnestic mild cognitive impairment (aMCI), and to clarify their effects in the pathogenesis of aMIC.Methods:The levels of miRNAs related to accelerating senescence (miR-132, miR-193b, miR-130b, miR-20a, miR-296, miR-329 and miR-206) were measured in the serum of the patients with aMCI (aMCI group,n=66) and healthy controls(control group,n=76) using quantitative real-time PCR(qRT-PCR).The genes targeted by the altered miRNAs were predicted by TargetScan 6.0.DAVID was used to analyze the function of miRNA target genes.The serum levels of brain derived neurotrophic factor (BDNF) and silent in formation regulator 1(SIRT1) were measured by enzyme-linked immunosorbent assay (ELISA) method.Results:The expression levels of miR-206 and miR-132 in serum of the patients in aMCI group were significantly higher than those in control group (P<0.05).BDNF and SIRT1 were both target genes of miR-206 and miR-132.The levels of BDNF (29.50 μg·L-1± 3.13 μg·L-1) and SIRT1 (1.86 μg·L-1± 0.25 μg·L-1) in serum of the patients in aMCI group were both obviously lower than those in control group (BDNF: 32.29 μg·L-1±3.66 μg·L-1;SIRT1: 2.10 μg·L-1± 0.29 μg·L-1, P<0.05).Conclusion:The expression levels of miR-206 and miR-132 in serum of the aMCI patients are significantly up-regulated.Both of them might be involved in the pathogenesis of aMCI through inhibiting the BDNF and SIRT1 expressions.

Objective To investigate the effect of Tangshan earthquake stress on the executive and memory func?tion in adults. Methods The objects were recruited from Tangshan Kailuan Mining Group. The exposed group included 251 subjects whose mothers exposed to the Tangshan earthquake during pregnancy in 1976. The control group included 341 subjects whose mothers was pregnant the year after the Tangshan earthquake. According to mother's pregnancy time relative to the earthquake exposed group was divided into 3 subgroups:the late pregnancy of earthquake exposed group, the second trimester of earthquake exposed group and the early pregnancy of earthquake exposed group. Wisconsin Card Sorting Test (WCST) was used to evaluate executive function, Brief Visuospatial Memory Test-Revised (BVMT-R) was used to evaluate memory function. Results The index of WCST were not different between two groups (P>0.05). Com?pared with control group, BVMT-R total scores were lower in earthquake exposed group [(25.54 ± 7.45) vs. (27.28 ± 7.10), P<0.01]. In the earthquake exposed group, pregnancy and sex had interaction effect on the nonpreservative errors (nRpe) of WCST (P<0.05). In the late pregnancy earthquake exposed group, male had higher nRpe than female (P<0.01). Preg?nancy time had main effect on offsprings' BVMT-R scores (P<0.05). The BVMT-R total scores were lower in late trimes?ter pregnancy and in second trimester pregnancy than in the early pregnancy (P<0.05). Conclusion The Tangshan earth?quake has potential effect on the memory function of the offsprings. The second trimester (4-to 6-month) and the third trimester (7-to 9-month) may be the sensitive pregnancy window of the stress during the pregnancy. The male offspring from late pregnancy of exposed earthquake have poorer executive function than female.