Clinical efficacy of intravesical gemcitabine combined with ubenimex in patients with non-muscle-invasive bladder carcinoma after transurethral resection of bladder tumor.

Objectives: To evaluate the clinical value of intravesical gemcitabine combined with immunotherapy in patients with non-muscle-invasive bladder carcinoma (NMIBC) after transurethral resection of bladder tumor (TURBT). Methods: Eighty patients with non-muscle-invasive urothelial carcinoma treated in Baoding No.1 Hospital from November 2016 to November 2019 were randomly divided into two groups, with 40 patients in each group. Both groups underwent TURBT. After surgery, the research group was treated with intravesical chemotherapy using gemcitabine combined with ubenimex, while the control group was given 40 mg pirarubicin by intravesical instillation. Postoperative condition was evaluated by cystoscopy every three months in both groups. The recurrence six months, one year and two years after treatment, the incidence of lower urinary tract symptoms such as dysuria, hematuria and frequent urination, general adverse drug reactions such as rashes, liver function damage and gastrointestinal reaction, as well as the changes in CD3+, CD4+, CD8+ and CD4+/CD8+ T lymphocyte subsets before and after treatment were comparatively analyzed between the two groups. Results: The recurrence rate showed no statistical significance between the two groups 6 months after treatment (p=0.17), but significant differences one year (p=0.04) and two years (p=0.03) after treatment, which were significantly lower in the research group than the control group. The incidence of adverse drug reactions was 22.5% in the research group and 7.5% in the control group, without significant difference (p=0.36). The incidence of lower urinary tract symptoms was 32.5% and 55%, respectively, in the research group and the control group. The incidence of lower urinary tract symptoms in the research group was significantly lower compared with the control group, with a statistically significant difference (p=0.04). After treatment, CD3+, CD4+ and CD4+/CD8+ levels in the research group increased significantly than those in the control group, with statistically significant differences (CD3+, p=0.01; CD4+, p=0.00; CD4+/CD8+, p=0.00). Conclusions: For NMIBC patients receiving bladder-preserving surgery, intravesical gemcitabine combined with immunotherapy can reduce the recurrence rate, relieve lower urinary tract symptoms, increase the tolerance of patients to intravesical chemotherapy and significantly improve the function of T lymphocytes, without obvious increase in adverse drug reactions. Therefore, it is safe and effective, and has certain clinical value.

[Inhibitory Effect of Kaempferol on Proliferation of KG1a Cells and Its Mechanism].

OBJECTIVE: To investigate the effect of kaempferol on proliferation of acute myeloid leukemia (AML) KG1a cells and its mechanism. METHODS: Human AML KG1a cells in logarithmic growth stage were taken and set at 25, 50, 75 and 100 µg/ml kaempferol group, another normal control group (complete medium without drug) and solvent control group (add dimethyl sulfoxide) were also set. After 24 and 48 hours of intervention, the cell proliferation rate was detected by CCK-8 assay. In addition, interleukin-6 (IL-6) combined with kaempferol group (Plus 20 µg/l IL-6 and 75 µg/ml kaempferol) was set up, 48 hours after culture, the cell cycle and apoptosis of KG1a cells were detected by flow cytometry, the mitochondrial membrane potential (MMP) of KG1a cells was detected by MMP detection kit (JC-1 method), and the expression of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway related proteins in KG1a cells were detected by Western blot. RESULTS: The cell proliferation rate of 25, 50, 75 and 100 µg/ml kaempferol group decreased significantly (P<0.05), and with the increase of kaempferol dose (r24 h=-0.990, r48 h= -0.999), the cell proliferation rate decreased gradually (P<0.05). The inhibitory effect of 75 µg/ml kaempferol on cell proliferation reached half of effective dose after 48 hours of intervention. Compared with normal control group, the G0/G1 phase cell proportion and apoptosis rate of cells in 25, 50 and 75 µg/ml kaempferol group increased, while the S phase cell proportion, MMP, phosphorylated JAK2 (p-JAK2)/JAK2 and phosphorylated STAT3 (p-STAT3)/STAT3 protein expression decreased in a dose-dependent manner (r=0.998, 0.994, -0.996, -0.981, -0.997, -0.930). Compared with 75 µg/ml kaempferol group, the G0/G1 phase cell proportion and apoptosis rate of cells in IL-6 combined with kaempferol group decreased, while the S phase cell proportion, MMP, p-JAK2/JAK2 and p-STAT3/STAT3 protein expression increased significantly (P<0.05). CONCLUSION: Kaempferol can inhibit KG1a cell proliferation and induce KG1a cell apoptosis, its mechanism may be related to the inhibition of JAK2/STAT3 signal pathway.

Identification of key proteins as potential biomarkers associated with post-infarction complications in diabetics.

Background: The ability of transcriptome analysis to identify dysregulated pathways and outcome-related genes following myocardial infarction in diabetic patients remains unknown. The present study was designed to detect possible biomarkers associated with the incidence of post-infarction complications in diabetes to assist thedevelopment of novel treatments for this condition.Methods: Two gene expression datasets, GSE12639 and GSE6880, were downloaded from the Gene Expression Omnibus (GEO) database, and then differentially expressed genes (DEGs) were identified between post-infarction diabetics and healthy samples from the left ventricular wall of rats. These DEGs were then arranged into a protein-protein interaction (PPI) network, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses were performed to explore the functional roles of these genes.Results: In total, 30 DEGs (14 upregulated and 16 downregulated) were shared between these two datasets, as identified through Venn diagram analyses. GO analyses revealed these DEGs to be significantly enriched in ovarian steroidogenesis, fatty acid elongation, biosynthesis of unsaturated fatty acids, synthesis and degradation of ketone bodies, and butanoate metabolism. The PPI network of the DEGs had 14 genes and 70 edges. We identified two key proteins, 3-hydroxymethylglutaryl-CoA synthase 2 (Hmgcs2) and Δ3, Δ2-Enoyl-CoA Delta Isomerase 1 (ECI1), and the upregulated gene Hmgcs2 with the highest score in the MCC method. We generated a co-expression network for the hub genes and obtained the top ten medications suggested for infarction with diabetes.Conclusion: Taken together, the findings of these bioinformatics analyses identified key hub genes associated with the development of myocardial infarction in diabetics. These hub genes and potential drugs may become novel biomarkers for prognosis and precision treatment in the future.

Measuring Sleep Stages and Screening for Obstructive Sleep Apnea with a Wearable Multi-Sensor System in Comparison to Polysomnography.

Objective: To assess the performance of a wearable multi-sensor system (SensEcho) in comparison to polysomnography (PSG) in measuring sleep stages and searching for obstructive sleep apnea (OSA). Methods: Participants underwent overnight simultaneous monitoring using SensEcho and PSG in a sleep laboratory. SensEcho analyzed the recordings spontaneously, and PSG was assessed as per standard guidelines. The degree of snoring was evaluated according to the guidelines for the diagnosis and treatment of OSA hypopnea syndrome (2011 revision). The Epworth Sleepiness Scale (ESS) was used to assess general daytime sleepiness. Results: This study included 103 Han Chinese, 91 of whom (age 39.02 ± 13.84 years, body mass index 27.28 ± 5.12 kg/m2, 61.54% male) completed the assessments. The measures of total sleep time (P = 0.198); total wake time (P = 0.182); shallow sleep (P = 0.297), deep sleep (P = 0.422), rapid eye movement sleep (P = 0.570), and awake (P = 0.336) proportions were similar between SensEcho and PSG. Using an apnea-hypopnea index (AHI) cutoff of ≥ 5 events/h, the SensEcho had 82.69% sensitivity and 89.74% specificity. Almost the same results were obtained at an AHI threshold of ≥ 15 events/h. Although the specificity increased to 94.67%, it decreased to 43.75% at an AHI cutoff of ≥ 30 events/h. Conclusion: This study demonstrated that SensEcho can be used to evaluate sleep status and screen for OSA. Nevertheless, improving the accuracy of its assessment of severe OSA and further testing its effectiveness in community and home environments is necessary.

[Correlation between Serum Homocysteine Level, MTHFR Gene Polymorphism and Patients with Hematological Diseases Complicated with Coronary Heart Disease].

OBJECTIVE: To observe the expression level of serum homocysteine (Hcy) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism in patients with hematological diseases complicated with coronary heart disease, and analyze the relationship between serum Hcy level, MTHFR gene polymorphism and coronary heart disease. METHODS: The medical records of 80 patients with coronary heart disease who completed treatment of hematological diseases during the period from March 2018 to March 2020 were selected as observation group. In addition, the medical records of 92 patients with hematological diseases who completed treatment in our hospital during the same period were selected as control group. Venous blood samples of the two groups were collected to detect serum Hcy level and MTHFR gene polymorphism. The serum Hcy levels of the two groups with different MTHFR genotypes were compared, and the effects of the above indicators on hematological diseases complicated with coronary heart disease were analyzed. RESULTS: The detection rates of MTHFR gene TT and TC in the observation group were higher than those in the control group, while the distribution frequency of MTHFR genotype CC was lower (P<0.05). The serum Hcy levels of the patients with MTHFR genotype TT and TC in the observation group was higher than the control group (P<0.05). Binary logistic regression analysis showed that MTHFR gene TC/CC genotype serum Hcy overexpression may be influencing factor which induced coronary heart disease in patients with hematological diseases (OR=2.107/OR=1.634, P<0.05). ROC curves showed that the AUC of serum Hcy level of MTHFR gene TC/CC genotype and hematological disease complicated with coronary heart disease were both > 0.8. When MTHFR gene TC reaching the optimal threshold of 22.165 µmol/L, the sensitivity was 0.950 and the specificity was 0.837, While MTHFR gene CC reached the optimal threshold of 19.630 µmol/L, the sensitivity was 0.938 and the specificity was 0.826, the best predictive value could be obtained. CONCLUSION: The changes of serum Hcy and MTHFR gene polymorphisms may be involved in the pathological process in patients with hematological diseases complicated with coronary heart disease. In the future, early detection of serum Hcy levels and MTHFR gene polymorphisms in patients with hematological diseases can be used to predict the risk of coronary heart disease.

Relationship of free thyroxine and triiodothyronine on recurrence in maintenance therapy for bipolar depression.

OBJECTIVE: To examine whether thyroid function in the normal range is associated with recurrence of depressive or mania in bipolar disorder patients. METHODS: 104 patients with bipolar disorder in maintenance therapy phase were assigned randomly to mood stabilizer combined with antidepressant group or mood stabilizer group. There were 52 patients in both groups respectively. Clinical symptoms were assessed at baseline, 3rd month, 6th month, 9th month, and 12th month using HAMD-17 and YMRS. Blood samples were analyzed for thyroid function. RESULTS: There was no statistically significant difference of recurrence rate of depressive episode and mania episode at the end of the 12-months between mood stabilizer combined with antidepressant group and mood stabilizer group. There was significant relation of baseline TT4 (P = 0.020, HR = 0.948), FT3 (P = 0.035, HR = 2.055), and FT4 (P = 0.047, OR=0.769) with the recurrence of depressive episode in mood stabilizer group. The area under curve (AUC) of TT4, FT3, FT4 were 0.685, 0.613, 0.544, respectively. There was significant relation of baseline FT3 (P = 0.044，HR = 4.493) with the recurrence of mania episode for mood stabilizer combined with antidepressants group. The AUC of FT3 was 0.806. CONCLUSION: Low level of TT4, FT4 and high level of FT3 within normal-range were related with the recurrence of depressive episode in the maintenance treatment with mood stabilizer of bipolar disorder. High level of FT3 within normal-range were related with recurrence of mania when mood stabilizer combined with antidepressants were used in the maintenance treatment of bipolar disorder.

The proportion and associated factors of anxiety in Chinese adolescents with depression during the COVID-19 outbreak.

BACKGROUND: Given the serious impact of the COVID-19 outbreak on the mental health of Chinese adolescents, this study aimed to examine the proportion of anxiety and its correlates among Chinese adolescents with depression during the pandemic. METHODS: This cross-sectional online survey was conducted from February 20th to February 27, 2020 in China. Symptoms of depression and anxiety were assessed by the 20-item Center for Epidemiological Studies-Depression (CES-D) and 7-item Generalized Anxiety Disorder (GAD-7), respectively. RESULTS: In this study, 3,498 adolescents with depression were identified. Of them, the proportion of anxiety was 45.1% (95% confidence interval [CI]=43.5%-46.8%). Multiple logistic regression analysis revealed that being concerned about graduation (OR=1.25, P=0.002, 95% CI=1.09-1.43), sleep duration <6hr/day (OR=1.80, P<0.001, 95% CI=1.38-2.34), study duration >8hr/day (OR=1.21, P=0.02, 95% CI=1.03-1.42), and quantity of homework higher than before (OR=1.68, P<0.001, 95% CI=1.40-2.02) were positively associated with anxiety; the number of confirmed COVID-19 cases at a provincial level of 100-999 (OR=0.70, P<0.001, 95% CI=0.59-0.83) and 1,000-9,999 (OR=0.69, P=0.001, 95% CI=0.55-0.87) were negatively related to anxiety in adolescents with depression. LIMITATIONS: Because this was a cross-sectional online study, the causality between variables and anxiety could not be examined among depressed adolescents. The use of self-reported scales may lead to an underestimation of the proportion of anxiety among adolescents with depression. CONCLUSIONS: The symptoms of anxiety were common in adolescents with depression during the COVID-19 outbreak. Timing screening and targeted interventions are necessary to mitigate the risks of mental illness of adolescents.