Objective To explore the pro-inflammation resolution and protective effects of reactive oxygen species (ROS)-responsive liposomes modified with a cardiac-targeted peptide and loaded with resolvin D1 (RvD1, C-LP-RvD1) on myocardial ischemia-reperfusion (MI/R) injury. Methods The C-LP-RvD1 nanoliposomes were constructed, characterized physically and chemically, and evaluated for in vitro release. Non-targeting peptide-modified drug-loaded liposomes (LP-RvD1) were served as controls. Apoptotic adult mouse cardiomyocytes (AMCMs) were used to verify in vitro targeted binding capacity of C-LP-RvD1. In MI/R mice models, the in vivo distribution and cardiac enrichment of C-LP-RvD1 were assessed. Levels of specialized pro-resolving mediator (SPM) and inflammatory factors in cardiac tissue homogenates and cell culture supernatants were measured using enzyme-linked immunosorbent assay (ELISA). Cardiac function and fibrosis remodeling were evaluated via echocardiography and Masson staining four weeks after treatment. Biosafety was evaluated in healthy mice injected by C-LP-RvD1. Results The C-LP-RvD1 exhibited good nanoscale uniformity and stability, with ROS-triggered accelerated release characteristics. In vitro experiments showed that C-LP-RvD1 had higher binding capacity to apoptotic AMCMs than LP-RvD1, with significantly higher SPM levels (P＜0.01) and lower inflammatory factor levels (P＜0.05). In vivo experiments indicated enhanced cardiac enrichment of C-LP-RvD1 in MI/R injured hearts, with higher local myocardial SPM levels and lower inflammatory factor levels compared to LP-RvD1 (P＜0.05). Four weeks after treatment, compared with LP-RvD1, the C-LP-RvD1 mice group showed improved cardiac function indicators and reduced ventricular fibrosis remodeling ratio (P＜0.05). Safety evaluation revealed no significant systemic inflammation, immunogenicity, or coagulation abnormalities in healthy mice, with liver and kidney function and major organ histology showing no notable damage. Conclusions C-LP-RvD1 improves effective delivery of RvD1 to MI/R injured hearts through injury-targeted enrichment and ROS-responsive release, promoting inflammation resolution and suppressing excessive inflammation, thereby improving cardiac function and reducing adverse remodeling, with favorable biosafety.

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

Objective To explore the impact of alcoholics anonymous (AA) online video conferences on relapse among alcohol dependent patients. Method Alcohol dependent patients who were hospitalized and discharged from the Mental Health Center of the First Hospital of Hebei Medical University from March 2020 to March 2022 were randomly divided into the AA group and the non AA group. The AA group underwent a 12-month remote AA treatment,participating in an AA online video conference once a week. The non-AA group did not receive any intervention. At baseline,the general condition of the subjects,such as alcohol consumption and addiction duration,as well as the severity of anxiety and depression symptoms,were evaluated. At 12 months after enrollment,clinicians communicated and assessed the subjects and their families via telephone or WeChat. The assessments included changes in anxiety and depression among the subjects,relapse into drinking,duration of abstinence after discharge,and other relevant factors. Result Eighty subjects were included,including 32 in the AA group and 48 in the non AA group. After intervention,the proportion of the AA group patients who resumed drinking was lower than that of the non AA group (68.8％ vs. 93.8％,P<0.01). The median duration of abstinence in the AA group was 7.5 (3.0,12.0) months,while the median duration of abstinence in the non AA group was 1.0 (0.3,5.0) months,with a significant difference (P<0.01). Multivariate logistic regression analysis showed that the risk of relapse in the non AA group was 14.85 times higher than that in the AA group (OR=14.85,95％CI:2.33-94.57). Conclusion Online videos for AA in quitting alcohol are convenient and easy to implement for alcohol dependent patients. This remote treatment can significantly prolong the duration of abstinence among alcohol dependent patients.

Objective To explore the impact of alcoholics anonymous (AA) online video conferences on relapse among alcohol dependent patients. Method Alcohol dependent patients who were hospitalized and discharged from the Mental Health Center of the First Hospital of Hebei Medical University from March 2020 to March 2022 were randomly divided into the AA group and the non AA group. The AA group underwent a 12-month remote AA treatment,participating in an AA online video conference once a week. The non-AA group did not receive any intervention. At baseline,the general condition of the subjects,such as alcohol consumption and addiction duration,as well as the severity of anxiety and depression symptoms,were evaluated. At 12 months after enrollment,clinicians communicated and assessed the subjects and their families via telephone or WeChat. The assessments included changes in anxiety and depression among the subjects,relapse into drinking,duration of abstinence after discharge,and other relevant factors. Result Eighty subjects were included,including 32 in the AA group and 48 in the non AA group. After intervention,the proportion of the AA group patients who resumed drinking was lower than that of the non AA group (68.8％ vs. 93.8％,P<0.01). The median duration of abstinence in the AA group was 7.5 (3.0,12.0) months,while the median duration of abstinence in the non AA group was 1.0 (0.3,5.0) months,with a significant difference (P<0.01). Multivariate logistic regression analysis showed that the risk of relapse in the non AA group was 14.85 times higher than that in the AA group (OR=14.85,95％CI:2.33-94.57). Conclusion Online videos for AA in quitting alcohol are convenient and easy to implement for alcohol dependent patients. This remote treatment can significantly prolong the duration of abstinence among alcohol dependent patients.

【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.

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 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.

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.