Objective To investigate the effect of brain natriuretic peptide (BNP) on serum angiotensin-converting enzyme (ACE) 2 levels in acute heart failure patients with reduced ejection fraction (HFrEF). Methods A total of 106 patients with acute HFrEF were selected, and were divided randomly into control group and trial group. The control group was under routine treatment, while the trial group was under routine treatment combined with lyophiluzed recombinant human BNP for 24-hour. Cardiac functional parameters were measured by echocardiography both at the enrollment and the end of 7-day treatment. Serum levels of ACE2 and N-terminal pro-BNP (NT-proBNP) were determined using commercially available ELISA kits at the enrollment, the end of 24-hour treatment, and the end of 7-day treatment,respectively. Results A total of 103 patients with acute HFrEF were enrolled (control group=51, trial group=52). There were no significant differences in the use of drugs (e.g., aspirin) and serum biochemical indices (e.g. cardiac troponin I, creatinine) before treatment between these two groups. Compared to systolic blood pressure (SBP) at admission, SBP on the second day after treatment were significantly decreased in two groups (P<0.05). Compared to left ventricular ejection fraction (LVEF) at admission, LVEF values were significantly elevated on the seventh day after treatment in two groups ( P<0.05). There were no significant differences in SBP, diastolic blood pressure (DBP), and LVEF at admission between these two groups (P>0.05);there were also no significant differences in DBP on the second day after treatment, and LVEF on the seventh day after treatment (P>0.05), while SBP was significantly higher on the second day after treatment in control group than that of trial group (P < 0.05). Serum levels of NT-proBNP were decreased with the prolongation of time in two groups. Serum levels of ACE2 were decreased with the prolongation of time in control group, while were increased initially following decreased (which were still higher on the seventh day after treatment than that at admission) with the prolongation of time in trial group. Serum levels of NT-proBNP were higher after 2 days treatment or 7 days of treatment in control group than those of trial group, while serum levels of ACE2 were decreased after 2 days of treatment or 7 days of treatment in control group than those of trial group (P<0.05). Conclusion Patients with acute HFrEF may benefit from BNP by increasing serum ACE2 levels.

BACKGROUND:cAMP response element binding protein (CREB) is a key protein of memory, which is closely related to long-term memory. It wil provide a new way for the treatment of hypoxic ischemic brain damage (HIBD) to study the effects of dental pulp stem cel s transplantation on the long-term behavior and CREB protein via the lateral ventricle in neonatal HIBD rats. OBJECTIVE:To observe the changes in long-term behavior and CREB protein expression in neonatal HIBD rats after human dental pulp stem cel transplantation, thereby providing scientific evidence for clinical treatment of neonatal HIBD. METHODS:Thirty-six healthy 7-day-old Sprague-Dawley rats were randomly divided into normal, HIBD and cel transplantation group. The hypoxic ischemic brain damage models were established in the brain damage and cel transplantation groups. Twenty-four hours after HIBD, human dental pulp stem cel s were injected into the left lateral cerebral ventricle of rats in the cel transplantation group, total y 3×106 living cel s. Equal volume of normal saline was injected into the left lateral cerebral ventricle of rats in the normal control and HIBD groups. RESULTS AND CONCLUSION:The average time to seek water, the average escape latency and escape distance of the human dental pulp stem cel s group were significantly shorter than those of hypoxic ischemic brain injury group (P<0.01), but longer than those in the normal group (P<0.01). Nissl staining showed that the cel s in the hippocampal CA1 region in human dental pulp stem cel s group were more regular, the number of cel s was significantly higher than that of hypoxic ischemic brain injury group, but stil significantly less than that in the normal group (P<0.05). Immunohistochemical staining results showed that the number of CREB positive cel s in human dental pulp stem cel s group was significantly higher than those in HIBD group, but stil significantly less than those in the normal group (P<0.01). It is suggested that human dental pulp stem cel s transplantation could promote the expression of CREB protein in the hippocampal CA1 region, to improve the long-term learning and memory ability of hypoxic ischemic neonatal rats, and thus repair HIBD.

Bladder cancer (BC) is a common malignant tumor of the urinary system. Common white light cystoscopy is the most important method in the diagnosis and treatment of BC, but its ability to identify small tumors and residual tumors at surgical sites is limited, so it is urgent to develop new diagnosis and treatment techniques. With the rise of the concept of precision medicine, a group of targeted molecules that can specifically bind to BC at the cellular and molecular levels have been discovered in recent years, and the molecular image and targeted therapy based on them can significantly improve the diagnosis and treatment efficiency of BC, with a great potential for clinical application. Based on the latest progress and the research work of our research group, this paper comprehensively analyzes and systematically summarizes the application of targeted molecular carriers in the diagnosis and treatment of BC.

Objective: : The present study aimed to identify the function of ischemic stroke (IS) patients’ peripheral blood and its role in IS, explore the pathogenesis, and provide direction for clinical research progress by comprehensive bioinformatics analysis. Methods: : Two datasets, including GSE58294 and GSE22255, were downloaded from Gene Expression Omnibus database. GEO2R was utilized to obtain differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were performed using the database annotation, visualization and integrated discovery database. The protein-protein interaction (PPI) network of DEGs was constructed by search tool of searching interactive gene and visualized by Cytoscape software, and then the Hub gene was identified by degree analysis. The microRNA (miRNA) and miRNA target genes closely related to the onset of stroke were obtained through the miRNA gene regulatory network. Results: : In total, 36 DEGs, containing 27 up-regulated and nine down-regulated DEGs, were identified. GO functional analysis showed that these DEGs were involved in regulation of apoptotic process, cytoplasm, protein binding and other biological processes. KEGG enrichment analysis showed that these DEGs mediated signaling pathways, including HTLV-I infection and microRNAs in cancer. The results of PPI network and cytohubba showed that there was a relationship between DEGs, and five hub genes related to stroke were obtained : SOCS3, KRAS, PTGS2, EGR1, and DUSP1. Combined with the visualization of DEG-miRNAs, hsa-mir-16-5p, hsa-mir-181a-5p and hsa-mir-124-3p were predicted to be the key miRNAs in stroke, and three miRNAs were related to hub gene. Conclusion : Thirty-six DEGs, five Hub genes, and three miRNA were obtained from bioinformatics analysis of IS microarray data, which might provide potential targets for diagnosis and treatment of IS.

Objective:Bioinformatics method was used to screen out prognostic model constructed by the tumor microenvironment (TME)- related genes of adrenocortical carcinoma (ACC), and the prognostic model was verified to provide clinical guidances and related biomarkers for the diagnosis and treatment of ACC.Methods:Transcriptome and clinicopathological data of 79 ACC patients were collected from the Cancer Genome Atlas (TCGA) database. ESTIMATE algorithm was used to calculate immune score, stromal score (both reflect TME) and ESTIMATE score; VennDiagram was used to select differentially expressed genes among immune score, high and low stromal score groups (grouped by median value); Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genome (KEGG) database were used to perform functional enrichment analysis on selected genes and to explore the potential function and pathway of genes. Univariate Cox analysis, lasso regression analysis and multivariate Cox analysis were used to screen out genes related to ACC TME and to establish risk score (RS) model for ACC patients. The receiver operating characteristic (ROC) curve was used to evaluate the prognostic value of RS. The data sets GSE33371 and GSE19750 of Gene Expression Omnibus (GEO) were used as external validation sets to validate the prognostic model. The data of 79 ACC patients were extracted from the TCGA database, and the clinicopathological factors and the RS of the established prognostic model were included in the Cox regression analysis to obtain the prognostic factors of ACC patients.Results:According to the immune score and stromal score, 1 205 differentially expressed genes from intersection of both scores were screened out by using VennDiagram, including 833 up-regulated genes and 372 down-regulated genes. After continuing the regression analysis and screening of differentially expressed genes, the ACC prognostic model containing 9 TME-related genes (GREB1, POU4F1, HIC1, HOXC9, CACNB2, RAB27B, ZIC2, C3, CYP2D6) was finally constructed, that was, RS = GREB1×0.223 6+POU4F1×0.671 7+HIC1×0.167 5+HOXC9×0.211 3+CACNB2×0.156 0+RAB27B×0.956 5+ZIC2×0.582 7+C3×(-0.003 1)+CYP2D6×0.819 3. The area under the curve (AUC) of ROC for the 1, 3, and 5-year overall survival of 79 ACC patients predicted by the model in the TCGA database was 0.876, 0.919, 0.917, respectively. In the GEO validation set, the AUC of the 1, 3, and 5-year overall survival for 45 ACC patients predicted by the model was 0.689, 0.704, and 0.708, respectively, indicating that the model had a high prediction accuracy for survival results of ACC patients. Cox regression analysis on the data of 79 ACC patients in the TCGA database showed that the TME-related gene prognostic model RS was an independent factor influencing the prognosis of ACC patients ( HR = 1.011, 95% CI 1.005-1.016, P < 0.01). Conclusions:The established ACC TME-related gene prognostic model can be used to predict the prognosis of ACC patients. The model including 9 genes may become a new target for studying the pathogenesis and immunotherapy of ACC, and it is worthy of further research.

Objective:To explore the effect of sulforaphane (SFN) preconditioning on the cold myocardial ischemia-reperfusion injury (IRI) in the rats through PI3K/Akt signaling pathway.Methods:Sixty-four health male Sprague-Dawley (SD) rats were randomly divided into cold IRI group,SFN group,LY (LY294002) + cold IRI group,and LY+SFN group (n=16).The allogeneic heterotopic heart transplantation model was established by donor heart into recipient abdomen.The myocardium tissue was taken 24 h after reperfusion for the detection of histological changes using HE staining.The expression levels of Akt,p-Akt,Bax and Bcl-2 proteins were detected by immunohistochemistry and Western boltting methods.Results:The morphological results showed that the myocardium tissue damage was serious in cold IRI group and LY+cold IRI group,it was light in SFN group;the myocardium tissue damage of the rats in SFN+ LY group was ranged between cold IRI group and SFN group.Compared with IRI group,the expression levels of p-Akt protein and Bcl-2 protein in SFN group were increased (P＜0.05),and the expression level of Bax protein was decreased (P＜0.05).After treatment of blockage LY294002,compared with LY-+-cold IRI group,the expression level of p-Akt protein in LY-+-SFN group was not statistically significant (P＞0.05),the expression level of Bcl2 protein was increased (P＜0.05),the expression levels of Bax protein was decreased),and the ratio of Bcl-2/Bax was also increased (P＜0.05).Conclusion:SFN may attenuate cold IRI of heart transplantation through PI3K/Akt signaling pathway in the rats.

Objective:To investigate the association of abdominal fat distribution with glycolipid metabolism and diabetic complications in patients with T2DM.Methods:Totally 357 inpatients with T2DM were collected from the Endocrinology Department of our hospital. All patients received quantitative computed tomography to measure the visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and were divided into three groups depending on the tertile of VAT value: T1 group (VAT<162.0 cm 2), T2 group (162.0≤VAT<221.1 cm 2), T3 group (VAT≥221.1 cm 2). The incidences of diabetic kidney disease, diabetic retinopathy, diabetic peripheral neuropathy, peripheral atherosclerosis, and cardia-cerebrovascular disease were examined in all patients. Results:HbA 1C level in T1 group was higher than that in T3 group( P<0.05). High density lipoprotein-cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR) in T1 group were higher compared with those in T2 and T3 groups ( P<0.05). Male proportion, age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), 24h urinary albumin, diabetic kidney disease and peripheral atherosclerosis in T2 and T3 groups were higher than those in T1 group ( P<0.05). Fasting C- peptide (FCP) and modified homeostasis model assessment for insulin resistance (HOMA-IR) in T3 group were higher than those in T1 and T2 group ( P<0.01). VAT and SAT were positively correlated with BMI, FCP, and HOMA-IR (p<0.01). VAT was positively correlated with age, SBP, DBP, TG, 24h urinary albumin, diabetic kidney disease, peripheral atherosclerosis, and cardia-cerebrovascular disease ( P<0.05), while inversely correlated with HbA 1C, HDL-C, and eGFR ( P<0.05). SAT was positively correlated with total cholesterol and low density lipoprotein-cholesterol ( P<0.01), while negatively correlated with peripheral atherosclerosis ( P<0.01). Multivariate logistic regression analysis showed that VAT was still a risk factor for diabetic kidney disease after adjusted by age, BMI, SBP and fasting plasma glucose( P=0.013). Conclusion:VAT and SAT are associated with blood lipids and insulin resistance, while VAT seems to be a risk factor for diabetic kidney disease.

Objective: To explore the relationship between mobile phone dependence (MPD) and academic burden among junior middle school students in Guizhou Province, under the "double reduction" policy by using a multi level model, so as to provide a basis for preventing the occurrence of MPD. Methods: From December 2021 to January 2022, 7 868 students from grade 1 to grade 3 in 3 cities (prefecture) of Guizhou Province were selected by multi stage stratification random sampling method, and on site investigation was conducted by self compiled questionnaire and Self rating Questionnaire for Adolescent Problematic Mobile Phone Use(SQAPMPU). Using MLwiN 2.30 to fit a multi level model of the relationship between MPD and academic burden among junior middle school students. Results: The MPD detection rate of junior middle school students in Guizhou Province was 20.9%. The multi level model revealed that MPD of junior middle school students was clustered at the level of school and class ( χ 2= 1 565.32 , P <0.01), and high perceived academic pressure had a positive predictive effect on MPD among junior middle school students ( β =1.96). Homework duration ≥90 min/d at weekends had a negative predictive effect on MPD ( β =-0.55), while participation in off campus training on learning days had a positive predictive effect ( β =1.66)( P <0.05). Conclusion The MPD occurrence level is higher among junior middle school students in Guizhou Province. Perceived academic pressure, time spent on homework during weekends, off campus training and other academic burdens have an impact on MPD among junior middle school students, which should be a cause of concern for schools, families and social departments.

Objective:To summarize the clinical characteristics and factors that may affect the flare of patients with systemic lupus erythematosus (SLE).Methods:A total of 300 patients with SLE who were treated with standard treatment in the outpatient clinic of the department of rheumatology and immunology of the Second Affiliated Hospital of Air Force Military Medical University of PLA, were enrolled, and the patients were divided into 24 patients in the complete response group, 40 cases in the no response group, 192 cases in the treatment response group, and 44 cases in the low disease activity group according to the response to treatment. The differences in clinical characteristics and survival rates between the groups were compared and analyzed. Comparisons of count data were made using analysis of variance (ANOVA), comparisons of measurement data were made using the chi-square test or the Fisher′s ecact test, and survival rates were expressed as Kaplan-Meier curves. Cox regression analysis was adapted to explore risk factors for flare in these patients.Results:A total of 300 patients were followed. With a median follow-up time of 18 (1, 36) months, a total of 42 patients experienced flare. The clinical characteristics of the four groups were compared, and there were significant differences in age ( F=4.39, P=0.005), the presence of lupus nephritis ( χ2=12.66, P=0.005), hemoglobin level ( F=2.73, P=0.044), NLR level( F=3.88, P=0.010), cystatin C level( F=3.11, P=0.027), anti-RNP antibody ( χ2=12.04, P=0.007), anti-Sm antibody ( χ2=8.33, P=0.040), anti-SSB antibody ( P=0.014), anti-nucleosome antibody ( P=0.014), and anti-ribosomal P protein antibody ( χ2=11.83, P=0.008). There was no significant difference in survival between the four groups. Cox analysis showed that the combination of other autoimmune diseases [ HR(95%CI)=3.23(1.58, 6.57), P=0.001], anti-Sm antibody [ HR(95%CI)=2.15(1.04, 4.43), P=0.038], and anti-RNP antibody [ HR(95%CI)=2.54(1.13, 5.68), P=0.023] were risk factors for flare in patients with SLE who could reach the treatment target. Conclusion:Patients with SLE with different treatment responses have different clinical features, and all treatment can significantly improve the recurrence rate no matter what level of response to treatment. Patients concurrent with other autoimmune diseases, positive anti-Sm antibodies, and positive anti-RNP antibodies are at highrisk of flare.

Bladder cancer is one of the common malignant tumors of the urinary system, and the results of conventional diagnosis and treatment methods are not satisfactory at this stage.In recent years, photodynamic technology has been applied in the diagnosis and treatment of bladder cancer due to its rapid development, and its effect has been widely recognized in clinical practice. Photodynamic diagnosis (PDD) has shown value in the diagnosis of bladder cancer, and compared with white light cystoscopy (WLC), blue light cystoscopy (BLC) has higher sensitivity and specificity, and is better suitable for the diagnosis of minor lesions and hidden lesions such as CIS, but it is expensive and time-consuming.Non-invasive targeted photodynamic diagnostic techniques using urine as a sample are beginning to show potential; PDD-guided TURBT has better diagnostic sensitivity and surgical precision. Photodynamic therapy (PDT) is an ideal treatment modality for bladder cancer.New photosensitizers have been developed, and two-photon PDT technology, intermittent and rhythmic PDT technology have been applied, which can help to reduce the number of PDT operations and reduce additional trauma while improving the efficacy.Some scholars have tried to use nanotechnology to combine PDT with chemotherapy drugs to further improve the efficacy.Monoclonal antibodies, antibody fragments, protein scaffolds, peptides and small molecule targeted molecular tracers have different characteristics, and new combination therapy methods are being researched and developed, bringing new opportunities for bladder cancer treatment.