Objective:To explore the expression of long non-coding RNA(lncRNA)ZIM2-AS1 in hepatocellular carcinoma(HCC)and its clinical significance as well as diagnostic value using the data obtained from the Cancer Genome Atlas(TCGA).Meth-ods:The transcriptome sequencing(RNA-seq)data and clinical information of 374 HCC tissues and 50 paired paracancerous tissues were gathered from the TCGA database,then the expression trends of ZIM2-AS1 in HCC and its correlation with clinicopathological features,prognosis,immune cell infiltration,as well as diagnostic value was inspected by bioinformatics analysis using relevant R packages.The expression of ZIM2-AS1 in human normal liver cell line and HCC cell lines was examined by qRT-PCR.Results:The ex-pression of ZIM2-AS1 was highly expressed in HCC tissues(P<0.001),and its expression level was significantly correlated with age,gender,N stage,histologic grade and AFP level(P all<0.05).The overall survival(OS)and disease specific survival(DSS)of patients with high ZIM2-AS1 expression were significantly shorter than those of patients with low expression(P<0.05),and ZIM2-AS1 was an in-dependent risk factor affecting OS.Immune cell infiltration analysis showed that ZIM2-AS1 was closely related to the infiltration of Th2 cells,CD56brightNK cells,follicular helper T cells(Tfh),neutrophils and plasmacytoid dendritic cells(pDC)(|Spearman's r|>0.1,P<0.05)in HCC.ROC curve analysis revealed that the expression level of ZIM2-AS1 possesse potential diagnostic value in HCC,N0 stage,histologic grade G1 and G2,OS and DSS(AUC all>0.50).qRT-PCR results showed that the expression level of ZIM2-AS1 in HCC cell lines was significantly higher than that in human normal liver cells(P all<0.05).Conclusion:The elevated expression of lncRNA ZIM2-AS1 is an independent risk factor for poor prognosis of HCC patient and has potential application value as a biomarker for HCC diagnosis,prognosis as well as tumor immune microenvironment assessment.

Background: and Purpose A systematic review and meta-analysis was performed of the outcome of Coronavirus disease 2019 (COVID-19) infection in patients with multiple sclerosis (MS) who received disease-modifying therapies (DMTs). Methods: Relevant studies published before November 2022 in the PubMed, Cochrane Library, Chinese National Knowledge Infrastructure, and Web of Science databases were retrieved using the following search expression: (“multiple sclerosis” OR “MS”) AND (“DMT” OR “disease modifying therapies”) AND (“COVID-19”). Two authors independently screened the articles and extracted the data. Qualitative analyses and a meta-analysis constituted 22 of the 794 retrieved articles. Differences in the hospitalization and mortality rates were used as the main measures of efficacy, and the meta-analysis was performed using RevMan software. Results: 22 clinical trials were selected. The hospitalization rate was lower in the 3,216 patients who received DMTs than in the 774 patients who did not receive any treatment, with a moderate effect size of 0.43 (p<0.00001). The mortality rate was also lower among patients with MS treated using DMTs than in controls (odds ratio [OR]=0.19, 95% confidence interval [CI]=0.13–0.27, p<0.00001). The hospitalization rates for COVID-19 infection in patients with MS treated with anti-CD20 therapy also increased markedly (OR=3.32, 95% CI=2.63–4.20, p<0.00001). However, there was no significant difference between patients with MS who did and did not receive DMTs. Conclusions In summary, the application of DMTs was found to be valuable for patients with MS infected with COVID-19. However, more clinical studies are needed to determine the use of anti-CD20 drugs in patients with MS during the COVID-19 pandemic.

Clinical application of doxorubicin (DOX) is heavily hindered by DOX cardiotoxicity. Several theories were postulated for DOX cardiotoxicity including DNA damage and DNA damage response (DDR), although the mechanism(s) involved remains to be elucidated. This study evaluated the potential role of TBC domain family member 15 (TBC1D15) in DOX cardiotoxicity. Tamoxifen-induced cardiac-specific Tbc1d15 knockout (Tbc1d15^CKO) or Tbc1d15 knockin (Tbc1d15^CKI) male mice were challenged with a single dose of DOX prior to cardiac assessment 1 week or 4 weeks following DOX challenge. Adenoviruses encoding TBC1D15 or containing shRNA targeting Tbc1d15 were used for Tbc1d15 overexpression or knockdown in isolated primary mouse cardiomyocytes. Our results revealed that DOX evoked upregulation of TBC1D15 with compromised myocardial function and overt mortality, the effects of which were ameliorated and accentuated by Tbc1d15 deletion and Tbc1d15 overexpression, respectively. DOX overtly evoked apoptotic cell death, the effect of which was alleviated and exacerbated by Tbc1d15 knockout and overexpression, respectively. Meanwhile, DOX provoked mitochondrial membrane potential collapse, oxidative stress and DNA damage, the effects of which were mitigated and exacerbated by Tbc1d15 knockdown and overexpression, respectively. Further scrutiny revealed that TBC1D15 fostered cytosolic accumulation of the cardinal DDR element DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Liquid chromatography-tandem mass spectrometry and co-immunoprecipitation denoted an interaction between TBC1D15 and DNA-PKcs at the segment 594-624 of TBC1D15. Moreover, overexpression of TBC1D15 mutant (∆594-624, deletion of segment 594-624) failed to elicit accentuation of DOX-induced cytosolic retention of DNA-PKcs, DNA damage and cardiomyocyte apoptosis by TBC1D15 wild type. However, Tbc1d15 deletion ameliorated DOX-induced cardiomyocyte contractile anomalies, apoptosis, mitochondrial anomalies, DNA damage and cytosolic DNA-PKcs accumulation, which were canceled off by DNA-PKcs inhibition or ATM activation. Taken together, our findings denoted a pivotal role for TBC1D15 in DOX-induced DNA damage, mitochondrial injury, and apoptosis possibly through binding with DNA-PKcs and thus gate-keeping its cytosolic retention, a route to accentuation of cardiac contractile dysfunction in DOX-induced cardiotoxicity.

Objective:To explore any effects of combining virtual reality training with aromatherapy in caring for Alzheimer′s disease patients in a nursing home.Methods:Fifty nursing home residents with Alzheimer′s were divided at random into an observation group and a control group, each of 25. Both groups received routine rehabilitation, while the observation group was additionally given 45 minutes of virtual reality training combined with aromatherapy, 3 times a week for 6 months. Both groups′ cognition was then evaluated using the MMSE and an Alzheimer′s cognition assessment scale (ADAS-cog). Psycho-behavioral symptoms were quantified using the Alzheimer′s disease pathological behavior scale (BEHAVE-AD). Motor functioning was quantified using the timed up and go test (TUGT), the 30-second sit-to-stand test (30sCST), the 30-second arm curl test (30sACT) and the sit-and-reach test (CSRT). Ability in the activities of daily living (ADL) and life quality were quantified using the activity of daily living scale and of the quality of life scale for Alzheimer′s disease (QOL-AD) before and after the intervention.Results:After the intervention the average MMSE, ADAS-cog, BEHAVE-AD and ADL scores of both groups had improved significantly, with the average improvement in the observation group significantly greater than that in the control group. The TUGT, 30sCST, 30sACT and CSRT results of both groups were also significantly better, with those of the observation group again significantly superior, on average, to the control group′s results. The average QOL-AD score in the observation was significantly improved after the intervention, and was then significantly better than the control group′s average.Conclusions:Virtual reality training combined with aromatherapy can significantly improve the cognition, psycho-behavioral symptoms, activity in daily living, motor functioning and life quality of Alzheimer′s patients in a nursing home. It is worthy of promotion and application in nursing homes.

OBJECTIVE：To study the improvement ef fects of sanggenone C on lipid accumulation in human liver cancer HepG2 cells induced by free fatty acid （FFA）. METHODS ：HepG2 cells were divided into control group ，model group ， fenofibrate group （10 μmol/L），sangerone C low ，medium and high concentration groups （2，4，8 μmol/L）. Except for control group，other groups were treated with 1 mmol/L FFA to induce lipid accumulation model ，and administration groups were cultured with relevant medium containing drugs. The lipid accumulation was observed by oil red O staining ，and lipid level and triglyceride （TG） content were also determined. Real-time PCR and Western blot assay were adopted to detect the mRNA and protein expression of PPARα，CPT-1，SREBP-1c，FAS，SIRT1 and PGC- 1α in HepG2 cells. RESULTS ：Compared with control group ， the nucleus was atrophied significantly and the volume became smaller ，and the number of lipid droplets was significantly increased；the level of lipid ，TG content ，mRNA and protein expression of SREBP- 1c and FAS were significantly increased （P＜ 0.05 or P＜0.01），mRNA and protein expression of PPARα，CPT-1，SIRT1 and PGC- 1α were decreased significantly（P＜0.01）. Compared with model group ，no obvious nucleus atrophy and normal volume were observed in sangerone C groups ，and the number of lipid droplets was significantly reduced ；the levels of lipid ，TG content ，mRNA and protein expression of PPARα pathway related genes （except for SREBP- 1c protein in saggenone C low concentration group ）were significantly reversed （P＜ 0.05 or P＜0.01）. CONCLUSIONS ：Sangenone C can significantly improve the lipid accumulation of HepG 2 cells，and its mechanism may associated with regulating PPAR α signaling pathway，improving cell lipid oxidation ability and inhibiting lipid synthesis.

Objective:To explore the application value of non-invasive pressure-strain loop (PSL) in evaluating left ventricular systolic function of young strength athletes with different heart rates.Methods:Thirty-five young wrestlers were collected randomly and divided into 2 groups according to the heart rate: group 1 (heart rate of 40-59 beats/min, n=20) and group 2 (heart rate of 60-80 beats/min, n=15). Thirty healthy young males were selected as the control group at the same period. Non-invasive PSL was used to obtain left ventricular global longitudinal strain (GLS), longitudinal peak strain dispersion (PSD), global myocardial work index (GWI), global constructive myocardial work (GCW), global wasted myocardial work (GWW) and global myocardial work efficiency (GWE) in three groups, and the differences between them were measured. Results:Compared with the control group, GWE in the athlete group 1 and 2 reduced, PSD, GWW were increased, and GWI, GCW in the athlete group 1 were decreased, and all differences were statistically significant (all P<0.05). Compared with the athlete group 1, PSD, GWI, GCW, GWW in the athlete group 2 increased and GWE was reduced (all P<0.05). Conclusions:PSL can quantitatively evaluate the left ventricular myocardial work of young strength athletes with different heart rates, and then assess the effect of heart rates on the left ventricular systolic function of athletes.

Objective:To investigate the distribution characteristics and related factors of HBsAb in infants born to women with chronic hepatitis B virus (HBV) infection.Methods:A total of 605 infants born to women with chronic HBV infection who met the requirements for inclusion were selected as the subjects. Information about the mother′s previous HBV infection, biochemical indicators during pregnancy, pregnancy complications, information about delivery, and hepatitis B test result after birth were collected. HBsAg and HBsAb at the age of 1 year were determined, and HBsAg and HBsAb at the age of 7 months were retrospectively collected. The factors influencing HBsAb in infants were analyzed by ordered logistic regression.Results:In 605 infants, the infection rate was about 1%. Among them, 6 infants were positive for HBsAg and HBV DNA at 7 months and 1 year of age. Uninfected infants were divided into groups according to HBsAb titers. The result showed that there were significant differences in prothrombin activity (PTA) ( χ2=11.17, P=0.01), positive rate of HBeAg ( χ2=7.87, P=0.049) and HBsAg positive rate at birth ( χ2=10.52, P=0.02) among different groups. Multivariate ordered Logistic regression analysis showed that HBsAg negative at birth was an independent protective factor for HBsAb at 7 months of age ( OR=1.564, 95% CI 1.092-2.239, P=0.015). Logistic regression analysis of HBsAb at 1 year of age showed maternal gestational diabetes mellitus ( OR=1.578, 95% CI 1.126-2.210, P=0.008), infant enhanced immunization ( OR=81.207, 95% CI 31.202-211.352, P < 0.001) and antibody level at 7 months of age ( OR=42.123, 95% CI 22.824-77.739, P < 0.001) were independently associated with HBsAb at 1 year of age. Conclusions:HBsAg negative in venous blood at birth was an independent protective factor for HBsAb at 7 months of age, and enhanced immunization was an independent protective factor for HBsAb at 1 year of age.

Objective:To construct a prediction model for the prognosis of breast cancer patients with long non-coding RNA expression characteristics.Methods:To construct a long non-coding RNA(LncRNA) model for predicting the prognosis of breast cancer patients.Methods Analyzing LncRNA expression profiles and clinical characteristics of 1 081 breast cancer patients in the cancer genome atlas (TCGA) database.Performing differential expression analysis and univariate analysis on 112 paired breast cancer and normal breast tissues′ transcriptome sequencing data in the TCGA database, and screened for differentially expressed (DELncRNAs) that significantly correlated with the prognosis of BRCA (To reduce batch effects, sequencing data has been normalized using the DESeq function). One thousand eighty-one breast cancer patients were randomly divided into two groups: training set (541) and validation set (540). Performing Cox proportional hazard regression using DELncRNAs and establishing a multi-LncRNA prognosis model in the training set, followed by proportional hazards assumption test(PH assumption test). Patients were divided into high-risk and low-risk groups based on calculated risk score.Kaplan-Meier method was used for survival analysis, and 540 patients′ data were used for validation.To evaluate the prognostic value of the model in patients with squamous cell carcinoma of the lung and hepatocarcinoma in TCGA database.Gene Set Enrichment Analysis (GSEA) was used to analyze the specific mechanism of lncrna affecting the survival of patients.Results:There were 2815 differentially expressed genes screened by transcriptome sequencing, 91 of which were significantly related to the prognosis of breast cancer patients ( P<0.05). Based on the Cox regression analysis of 91 delncrna expression data from 541 breast cancer patients in training set, a Cox proportional risk regression model was constructed based on 5 LncRNA (training set AUC=0.746, validation set AUC=0.650): AC004551.1, MTOR-AS1, KCNAB1-AS2, FAM230G and LINC01283, and PH assumption test( P=0.388). K-M survival analysis showed that the survival time of high-risk group was significantly worse than that of low-risk group (median survival time: 7.049 and 12.21 years, HR 0.367, 95% CI0.228-0.597, P<0.001), and the survival time of high-risk group was significantly shorter than that of low-risk group (median survival time: 7.57 and 10.85 years, HR 0.412, 95% CI0.214-0.793, P<0.001). Similar prediction results were also obtained in other cancer species of TCGA: lung squamous cell carcinoma ( HR 0.604, 95% CI0.383-0.951, P=0.007) and liver cell carcinoma ( HR 0.551, 95% CI0.307-0.987, P=0.011). GSEA results suggested that the expression patterns of the above five LncRNA were related to the cell cycle regulation of tumor cells. Conclusion:The prognostic model constructed based on expression profile of AC004551.1, MTOR-AS1, KCNAB1-AS2, FAM230G and LINC01283 can be used to predict the prognosis of breast cancer patients, which is helpful to further guide clinical treatment.

Objective:To investigate the relationship between indicators of carotid atherosclerosis and onset of ischemic stroke in patients with non-valvular atrial fibrillation (NVAF).Methods:This is a case-control study, a total of 397 NVAF patients with newly diagnosed ischemic stroke (case group) and 3 038 NVAF patients without ischemic stroke (control group) from January 2015 to December 2017 were included in the study. Differences in general clinical features and carotid atherosclerosis indexes between the two groups were compared. Univariate and multivariate logistic regressions were used to analyze the correlation between carotid atherosclerosis indexes and ischemic stroke.Results:Proportions of patients with carotid intima thickening, carotid plaque, stable plaque, unstable plaque, and moderate to severe stenosis were higher in the ischemic stroke group than those in the control group (82.1% vs. 64.4%, 69.3% vs. 50.3%, 43.6% vs. 30.6%, 25.7% vs. 19.7%, and 7.3% vs. 4.0%, respectively, all P <0.05). After adjustment of age, gender, heart failure, hypertension, low density lipoprotein -cholesterol and drug use, multivariate analyses showed that subjects with carotid intima thickening, carotid plaque, stable plaque, unstable plaque, moderate to severe stenosis had 1.766, 2.111, 1.892, 2.256 and 1.824 times the risk for the development of ischemic stroke compared with the subjects without any carotid atherosclerosis indicators. Conclusion:Carotid atherosclerosis, especially with unstable carotid plaque, is associated with ischemic stroke in patients with NVAF.

OBJECTIVE：To study the protective effect of timosaponin BⅡ（TB-Ⅱ）on blood vessels and explore its possible mechanism. METHODS ：Using aquaculture water as blank control ，the effects of 100，200 and 400 μg/mL TB-Ⅱ treatment for 48 h on the situation of subintestinal veins （SIVs）in normal zebrafish embryos 24 h after fertilization （24 hpf）were investigated. PTK787（0.06 μg/mL），a tyrosine kinase inhibitor ，was used to induce the model of zebrafish intestinal vascular injury ；using combing with 0.1％ dimethyl sulfoxide but no PTK 787 as blank control ，combing with PTK 787 but no drug as model control ，the effects treatment of 100，200 and 400 μg/mL TB-Ⅱ for 48 h on the SIVs of zebrafish model with vascular injury were investigated. Relative expressions of fam-like tyrosine kinase 1（Flt-1），kinase insert domain containing receptor （Kdr），kinase insert domain containing receptor l （Kdr-l），vascular endothelial growth factor A （VEGF-A），tumor necrosis factor α（TNF-α）and interleukin 6 （IL-6）mRNA were detected by RT-PCR. RESULTS ：100 μg/mL TB-Ⅱ could significantly increase the sprouting vessel of normal zebrafish SIVs sprouting vessel number （P＜0.05），and 200 μg/mL TB-Ⅱ could significantly increase SIVs number of normal zebrafish （P＜0.05）. Compared with blank control ， SIVs treatment （P＜0.01），and the relative expressions of Flt-l ， Kdr，Kdr-l，VEGF-A，TNF-α and IL-6 mRNA were alse decreased significantly （P＜0.05 or P＜0.01）. After treated 化。E-mail：pn333@163.com with different concentrations of TB- Ⅱ ，SIVs number of vascular injury model zebrafish increase d to different extents ；relative expressions of Flt-l ，Kdr，Kdr-l，VEGF-A，TNF-α and IL-6 mRNA were increased to different extents. There was no significant difference in SIVs number and the expression of Flt-l ，TNF-α mRNA in zebrafish treated with 100 μg/mL TB-Ⅱ and the expression of TNF-α mRNA in zebrafish treated with 400 μg/mL TB-Ⅱ， but there was statistical significance in other indexes （P＜0.05 or P＜0.01）. CONCLUSIONS ：TB-Ⅱ has a certain function of promoting angiogenesis and repairing damaged blood vessels ，and its mechanism is related to the up-regulation of vascular endothelial growth factor receptor and pro-inflammatory cytokine expression.