Cardiovascular diseases (CVDs) are a major cause of morbidity and mortality in the world. So far, there has been substantial progress toward understanding the pathophysiology and treatment of CVDs. There are multiple cell signaling cascades, some of which are beneficial or compensatory and others deleterious. The balance between these pathways determines the outcome as a diseased or non-diseased state. Protein phosphorylation, which is mediated by enzymes, called protein kinases, is a major mechanism for transducing external stimuli into intracellular signals. Electively targeting of signaling pathways using protein kinase inhibitors would have a potential advantage over receptor blockers. By now, there are types of protein kinase inhibitiors available for treating several diseases. The success of kinase inhibitors in cancer treatment has strongly supported application in the treatment of CVDs. Here, we will review several kinds of protein kinases as potential targets for CVDs and some difficulty in identifying a protein kinase as a putative therapeutic target for CVDs.

Objective There have been few research on the relationship between expression of HDAC4 and chemotherapy resistance in human lung adenocarcinoma.The present study aims to investigate the expression and clinical significance of HDAC4 in human lung adenocarcinoma tissues.Methods We selected 72 tissues in lung adenocarcinoma patients with docetaxel-resistant from January 2006 to December 2007 in Department of Oncology and Thoracic Surgery, Nanjing General Hospital of Nanjing Military Region, then evaluated the recent efficacy according to the RECIST criteria and divided the tissues into sensitive(n=32, included complete remission and partial remission) and insensitive(n=40, included stability and progress) groups.The expression of HDAC4 in tissues≥the HDAC4 optimal relative expression cut-off value(78.7) was high level HDAC4 group(n=35), otherwise it was low level HDAC4 group(n=37).QRT-PCR analysis was performed to detect the HDAC4 expression levels in sensitive group and insensitive group.Analyzed the progression free survival in high level HDAC4 group and low level HDAC4 group.Results The expression of HDAC4 was significantly higher in the insensitive group compared with the sensitive group [(1.42±0.30) vs (0.60±0.15), P<0.01].The median progression free survival was significantly shortened in the high level HDAC4 group compared with the low level HDAC4 group (10.2 months vs 5.8 months, P<0.05).ConclusionThe expression of HDAC4 increased in docetaxel-resistant lung adenocarcinoma patients, and it is expected to be a predictive indicator of the resistance of docetaxel.

AAV-ITR single strand DNA mini vector (AAV-ITR ssDNA mini vector) is a novel gene expression vector based on AAV-ITR. We have shown efficient gene expression of AAV-ITR ssDNA mini vector in HEK 293T. Here, we studied the efficacy of gene expression of AAV-ITR ssDNA mini vector in vivo. We injected the skeletal muscle of ICR mice separately with equal molars of AAV-ITR ssDNA mini vector, ITR mutated AAV-ITR single strand DNA mini vector (AAV-ITRmm ssDNA mutant vector), AAV-ITR dsDNA and pUC57-minivector-GFP, combined with TurboFect. Florescence microscope analysis of skeletal muscle section shows that AAV-ITR ssDNA mini vector had higher expression efficiency and longer expression period. We extracted DNA from the muscle three months after injection and quantified three vectors by Real-time PCR. RT-PCR analysis shows that there were highest copy numbers of AAV-ITR ssDNA mini vector existing in muscle. Stable existing of AAV- TR ssDNA mini vector in muscle could be the molecular basis of long term gene expression of the vector. The results suggest that AAV-ITR ssDNA mini vector might be a promising vector for gene therapy.
Animals ; DNA, Single-Stranded ; genetics ; Dependovirus ; genetics ; Gene Expression ; Genetic Therapy ; Genetic Vectors ; Mice ; Mice, Inbred ICR ; Muscle, Skeletal ; metabolism ; Real-Time Polymerase Chain Reaction

Cardiovascular diseases(CVDs) are a major cause of morbidity and mortality in the world.So far,there has been substantial progress toward understanding the pathophysiology and treatment of CVDs.There are multiple cell signaling cascades,some of which are beneficial or compensatory and others deleterious.The balance between these pathways determines the outcome as a diseased or non-diseased state.Protein phosphorylation,which is mediated by enzymes,called protein kinases,is a major mechanism for transducing external stimuli into intracellular signals.Electively targeting of signaling pathways using protein kinase inhibitors would have a potential advantage over receptor blockers.By now,there are types of protein kinase inhibitiors available for treating several diseases.The success of kinase inhibitors in cancer treatment has strongly supported application in the treatment of CVDs.Here,we will review several kinds of protein kinases as potential targets for CVDs and some difficulty in identifying a protein kinase as a putative therapeutic target for CVDs.

Objectives:To analyze the level and related factors of quality of life, caregiver burden in primary caregivers of adolescents with depression, and to explore the relationship between quality of life and caregiver burden. Methods: Totally 180 caregivers of adolescents with depression were investigated in the Second Xiangya Hospital of Central South University in Changsha, Hunan province. The Hamilton Depression Scale-17 (HAMD-17), Short Form 36 Health survey Questionnaire (SF-36) and Zarit Caregiver Burden Interview (ZBI) were used to assess depressive symptoms of patients, the quality of life and caregiver burden of primary caregivers of adolescents with depression. Results:The scores of SF-36 dimensions were lower in caregivers than in the national norm (P ＜ 0.01). The average score of ZBI was (32 ± 15), while 73.7％ caregiver's burden was in the low and moderate level. The SF-36 scores were lower in caregivers taking care of patients with longer course of disease and suicide history, with lower education level, with lower family income (P ＜0.05). The ZBI scores were higher in those taking care of the patients in hospital, with a long course of disease, with higher HAMD scores, and those with major events in the past 3 months, and being on-the-job, (P ＜0.05). The caregiver burden (personal burden and role burden) of caregivers was negatively related to the scores of quality of life (physical health and mental health) (r=-0.56——0.24, Ps ＜0.01). Conclusion: The quality of life of caregivers of adolescents with depression is severely impaired, and they have obvious caregiver burden. The caregivers with lower education level, lower family income, and being on-the-job, with major events in the past 3 months, and those taking care of patients with a long course of disease, suicide history, and higher HAMD score may have heavy burden and low quality of life. The caregiver burden of caregivers of adolescents with depression is negatively related to their quality of life.

Objective:To investigate the effect of self-help cognitive behavioral intervention on the recovery of patients with generalized anxiety disorder.Methods:A total of 123 patients with generalized anxiety disorder were recruited from a comprehensive hospital in Hunan province. The patients were randomly assigned into control group( n=62) and intervention group( n=61) according to random number table. The patients in the control group were received routine treatment alone, while the patients in the intervention group were received routine treatment and WeChat-based self-help cognitive behavioral therapy. The generalized anxiety disorder(GAD-7), self-rating depression scale(SDS), WHO quality of life scale(WHOQOL-BREF), Pittsburgh sleep quality index(PSQI) and medication adherence scale(MARS) were used to measure the anxiety, depression, quality of life, sleep quality and medication compliance at three time points: before intervention (T1), after intervention (T2) and during follow-up (T3). The SPSS 21.0 was used to analyze the data.Mean±standard deviation, frequency and constituent ratio were used to describe the data based on the type of data. Repeated measure ANOVA was used to compare the between-group variation, time effect and interaction effect of two groups at 3 time points. Results:The anxiety score of intervention group at T1, T2, T3 were (12.74± 2.02), (7.13± 1.48), (6.57±1.73) respectively, and the anxiety score of the control group were (12.08±2.11), (11.11±3.27), (10.11±3.33) respectively. Compared with the control group, the score of anxiety in the intervention group was significantly decreased at T2 and T3 ( P<0.05). Compared with control group, the sleep quality and quality of life of intervention group were significantly improved at T2, T3 ( P<0.05), and the medication compliance of the intervention group was significantly improved at T3 ( P<0.05). Conclusion:Self-help cognitive behavioral intervention can decrease anxiety significantly and improve the quality of life, sleep quality, and medication compliance in patients with generalized anxiety disorder.

Objective:To investigate the predictive value of neutrophil/lymphocyte ratio (NLR) on the discharge outcome in elderly patients with acute ischemic stroke (AIS) receiving intravenous thrombolysis (IVT).Methods:Elderly patients with AIS received IVT in the Department of Neurology, the Second Affiliated Hospital of Soochow University from August 2018 to August 2020 were retrospectively included. The modified Rankin Scale was used to evaluate discharge outcome, and the score >2 was defined as poor outcome. Symptomatic intracranial hemorrhage (sICH) was defined as any intracranial hemorrhage found on imaging examination accompanied by neurological deterioration, where the National Institutes of Health Stroke Scale (NIHSS) score increased by ≥4 from baseline or bleeding led to death. Multivariate logistic regression analysis was used to determine independent risk factors for sICH and poor discharge outcome. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of NLR for sICH and poor discharge outcome. Results:A total of 228 elderly patients with AIS receiving IVT were enrolled, including 118 males (51.8%), aged 73.64±8.16 years, with a baseline NIHSS score of 6.23±6.54. Ninety patients (39.5%) had poor outcome at discharge, and 16 (7.0%) developed sICH. Univariate analysis showed that the NLR in the poor outcome group was significantly higher than that in the good outcome group ( P<0.01). Multivariate logistic regression analysis showed that a higher NLR was an independent risk factor for poor discharge outcome (odds ratio [ OR] 1.245, 95% confidence interval [ CI] 1.044-1.484; P< 0.05) and sICH ( OR 1.124, 95% CI 1.010-1.251; P<0.05). ROC curve analysis showed that the area under the curve of NLR for predicting poor discharge outcome was 0.693 (95% CI 0.620-0.765; P<0.01). The optimal cutoff value was 4.345. Its corresponding sensitivity and specificity were 47.8% and 87.7%, respectively. The area under the curve of NLR for predicting sICH was 0.651 (95% CI 0.498-0.804; P<0.05). The optimal cutoff value was 3.515. Its corresponding sensitivity and specificity were 68.8% and 61.8%, respectively. Conclusions:A higher NLR is independently associated with sICH and poor discharge outcome in elderly patients with AIS receiving IVT, and have certain predictive value for sICH and poor discharge outcome.

【Objective】  To predict the active components and action targets of Wuyao (Linderae Radix) in the treatment of chronic pelvic inflammatory disease (CPID) based on network pharmacology, explore possible mechanisms of the treatment through animal experiments, and provide a scientific basis for clinical applications of Wuyao (Linderae Radix). 【Methods】  Possible active components and targets of Wuyao (Linderae Radix) in the treatment of CPID were obtained applying network pharmacology and molecular docking technology. CPID rat models were established using the mixed Escherichia coli, Staphylococcus aureus, and Ureaplasma urealyticum plus the performance of mechanical injury. Hematoxylineosin (HE) staining was applied to observe the pathological changes in the uterus, fallopian tube, and spleens of rat models. The contents of nitric oxide (NO), superoxide dismutase (SOD), and malondialdehyde (MDA) in the serum of rats were determined with the use of corresponding detection kits. Enzyme-linked immunosorbent assay (ELISA) test was used to measure the expression of interleukin (IL)-6 and IL-10 in the serum of rat models. Flow cytometry was used to determine the percentage of CD4+ and CD8a+ T cells as well as CD4+ CD25+ regulatory T cells (Tregs) in the spleen of rat models. 【Results】  A total of nine potential active components and four core therapeutic targets related to inflammatory response in Wuyao (Linderae Radix) were obtained. The animal experiments showed that Wuyao (Linderae Radix) markedly inhibited uterus swelling, regulated morphological changes in the fallopian tube and spleen,  effectively reduced inflammatory infiltration and injuries in the uterus and fallopian tube, and improved spleen functions in CPID rats. Moreover, Wuyao (Linderae Radix) markedly reduced the levels of NO, IL-6, and MDA, and increased the levels of IL-10 and SOD in the serum of rats. Wuyao (Linderae Radix) also elevated the percentage of CD4+T cells and the CD4+ T/CD8a+ T cell ratio, reduced the percentage of CD8a+ T cells, and raised the percentage of CD4+ CD25+ Tregs that had been abnormally decreased in rat models (P < 0.05). 【Conclusion】  Wuyao (Linderae Radix) could have therapeutic effects on CPID rats by relieving oxidative stress, mitigating inflammatory levels, and regulating the immuno-function of T cell subgroups to improve the pathological changes in CPID rats. It is a medicinal herb worth being further explored for its clinical values.