Structurally novel HDAC inhibitors based on the trans-β-arylacryl tetrahydroisoquinoline scaffold: the design, synthesis, and anti-cancer activity / 药学学报

In this study, a series of 18 histone deacetylases inhibitors (HDACis), derived from our in-house anti-cancer trans-β-arylacryl 1,2,3,4-tetrahydroisoquinoline-based scaffold, were designed, synthesized, and antitumor evaluated. HDAC1 inhibitory activity assay showed that compounds 13d-13f and 13m-13o demonstrated attractive enzymatic activity with IC50 at single-digit nanomolar or subnanomolar level.In addition, 13o exerted superior anti-proliferative activity (A549, IC50 = 0.89 μmol·L-1; HCT116, IC50 = 0.49 μmol·L-1) to that of vorinostat (SAHA).Besides,13e, with the most potent HDAC1 enzymatic activity (IC50 = 3.8 nmol·L-1), also displayed attractive cellular activity (A549, IC50 = 1.74 μmol·L-1; HCT116, IC50 = 2.43 μmol·L-1). The Western blot analysis illustrated that 13e treatment increased the acetylation of H3 and α-tubulin in a dose-dependent manner in A549 cells. In summary, 13e and 13o deserve further functional investigation.

Structural Equation Modeling of the Interaction between Mothers and Preschool-Age Children

Purpose@#This study aimed to identify the factors influencing the interaction between mothers and preschool-age children and construct a structural equation model based on the factors identified. @*Methods@#The data were collected from the mothers of children aged three to six years enrolled in kindergartens in Seoul, Gyeonggi, Chungbuk, and Jeonbuk. A total of 328 questionnaires were used for the analysis. Analysis was performed using SPSS 26.0 and AMOS 26.0 programs. @*Results@#The child’s self-regulation (β = .42, p < .001) had the most significant influence on the interaction between mothers and preschool children, followed by the mother’s parenting stress (β = - .23, p = .008), social support (β = .17, p < .001), and the child’s active temperament (β = .15, p < .001). The child’s gender, emotional temperament, social temperament, and mother’s education level had indirect influences. @*Conclusion@#These results suggest that interventions considering the child’s temperament, mother’s parenting stress, and social support are required to promote the interaction between preschool-age children and mothers.

Effect of Decomposed Zuoguiwan Recipes in Improving BMD of Ovariectomized Rats by Regulating OPG/RANKL Pathway Mediated by β2AR / 中国实验方剂学杂志

Objective:To investigate the mechanism of decomposed Zuoguiwan（ZGW） recipes in treating ovariectomized osteoporosis rats. Method:Forty Sprague-Dawley female rats were equally and randomly divided into Sham-operated group, ovariectomized model group, positive group, and low and high-dose ZGW groups. After 12 weeks of administration by gavage, the bone mineral density (BMD) of rats' distal femur was measured by micro-CT, the morphology of bone tissue were observed by hematoxylin-eosin staining (HE), β-cross-linked c-telopeptide of type Ι collagen (β-CTX) and bone-specific alkaline phosphatase (BALP) in serum were detected by enzyme-linked immunosorbent assay (ELISA), and the mRNA and protein expressions of β2AR, OPG and RANKL were evaluated by Western blot analysis and real-time quantitative polymerase chain reaction （PCR）. Result:Compared with Sham-operated group, BMD of rats in ovariectomized model group was decreased (P<0.01), morphology of bone tissue was destroyed, serum BALP was reduced, while β-CTX was boosted (P<0.01)，mRNA and protein expressions of OPG in tibia were reduced, while RANKL were increased, and mRNA and protein expressions of β2AR in the hypothalamus were decreased (P<0.05, P<0.01). Compared with ovariectomized model group, BMDs of rats in low and high-dose ZGW groups were increased (P<0.01), morphology of bone tissue was repaired, serum BALP and mRNA and protein expressions of OPG in tibia were up-regulated (P<0.05, P<0.01), whereas serum β-CTX and mRNA and protein expressions of β2AR in the hypothalamus and RANKL in tibia were down-regulated (P<0.05, P<0.01). Conclusion:Yang-nourishing components in decomposed Zuoguiwan recipes can improve BMD of ovariectomized rats by regulating OPG/RANKL pathway mediated by β2AR. "Seeking Yin in Yang" is a crucial mechanism of Zuoguiwan in treating ovariectomized osteoporosis in rats.

Practice on human genetic resources management using PDCA circle in new drug clinical research / 中华医学科研管理杂志

Objective:The paper aims to ensure the rational and legal utilization of genetic resources and maintain the national biosafety through the management of human genetic resources in clinical research carried out by medical institutions.Methods:Literature review and survey methods were adopted. Deming Circle, with focus on the four stages from planning, implementation, inspection, and countermeasures, was used to continuously improve the quality of human genetic resources management in the hospital.Results:The concept of hospital human genetic resources management was recognized and the management quality was significantly improved.Conclusions:The PDCA cycle management method is of positive significance to the management of human genetic resources in the clinical research of new drugs in medical institutions, and it is an effective way to improve the management level under current system.

Review of Zuoguiwan on Animal Models and Evaluation in Prevention and Treatment of Osteoporosis / 中国实验方剂学杂志

Zuoguiwan is a classic prescription for replenishing vital essence, tonifying kidney-Yin and nourishing the bone marrow. Zuoguiwan is one of the effective prescriptions for the prevention and treatment of osteoporosis (OP), which reflects the thought of Reinforcing Yang from Yin. The OP animal model simulates the pathological state and pathogenesis of OP in human, which is an important means to research the pathogenesis of OP and verify the effect of drugs. In this paper, two kinds of animal models and characteristics of Zuoguiwan in the prevention and treatment of osteoporosis were discussed in details. They are the primary osteoporosis animal models, including ovariectomized animal models and spontaneous elderly osteoporosis animal models, and the secondary osteoporosis models, including glucocorticoid-induced animal models, cyclophosphamide-induced animal models and subtotal nephrectomy animal models. The evaluation methods of Zuoguiwan in preventing and treating OP, including bone absorption markers and bone formation markers analyzed by enzyme-linked immunosorbent assay (ELISA), bone mineral density detected with dual-energy X-ray, the number of trabeculae, trabecular segregation, trabecular thickness, bone volume/tissue volume ratio and bone surface/volume ratio analyzed using micro-CT, bone pathological morphology observed by hematoxylin-eosin staining, bone biomechanical properties, such as the maximum load force based on biomechanical test. In order to provide scientific reference for the basic and clinical research of Zuoguiwan, the OP animal models and the pharmacodynamic effect of Zuoguiwan are evaluated comprehensively with five different and objective evaluation methods. However, the animal model of OP needs to be further optimized to highlight the pathogenesis and syndrome characteristics of Zuoguiwan in the treatment of OP.

Effect of Zuoguiwan on mRNA Expression of Orexin and Its Receptors in Hypothalamus of Ovariectomized Rats / 中国实验方剂学杂志

Objective: To observe the mRNA levels of Orexin and its receptors in the hypothalamus of ovariectomized osteoporosis rats, in order to explore the pathogenesis of postmenopausal osteoporosis(PMOP) and the mechanism Zuoguiwan. Method: An osteoporosis model induced by ovariectomy was established in rats. Totally 32 female Sprague-Dawley (SD) rats were randomly divided into sham-operated group, ovariectomized model group, 17β-estradiol treated positive group, and Zuoguiwan group, with 8 rates in each group. After 12 weeks of intragastric administration, the bone mineral density (BMD) and trabecular microstructural changes of femur were detected by micro-CT (μ-CT), and the morphological changes of bone tissue were observed by hematoxylin-eosin staining (HE) staining. The markers of bone turnover in serum osteocalcin (OCN), N-terminal propeptide of type Ⅰ procollagen (PINP), tartrate-resistant acid phosphatase (TRAP) were measured using enzyme-linked immunosorbent assay (ELISA). The mRNA expressions of orexin, orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R) were measured by Real-time PCR. Result: Compared with sham-operated group, the μ-CT showed that BMD, bone volume fraction(BV/TV), trabecular thickness(Tb. Th)and trabecular number(Tb. N)in ovariectomized model group were significantly decreased (PPN-terminal propeptide of type Ⅰ procollagen (PINP) levels decreased, whereas tartrate-resistant acid phosphatase (TRAP) content increased (PPPPPPPPPPConclusion: Decreased mRNA levels of Orexin and its receptors in the hypothalamus may be one of the mechanisms of PMOP. Zuoguiwan may correct the imbalance of bone metabolism, improve the trabecular microstructure and improve bone by up-regulating the mRNA expressions of Orexin and its receptors in the hypothalamus, density, so as to show a therapeutic effect on PMOP.

Effect of Zuoguiwan in Improving BMD and Trabecular Bone Microarchitecture in Ovariectomy-induced Osteoporosis Rats by Regulating RANKL/OPG Pathway Mediated by β2AR / 中国实验方剂学杂志

Objective: To investigate the mechanism of Zuoguiwan in treating ovariectomy-induced osteoporosis rats by receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) signaling pathway mediated by β2-adrenergic receptor (β2AR). Method: Forty Sprague-Dawley female rats were randomly divided into Sham-operated group (Sham) and four ovariectomized (OVX) subgroups. Rats in Sham and OVX groups were treated with 17β-estradiol (50 μg·kg-1·d-1), and low and high-dose ZGW (2.3,4.6 g·kg-1 lyophilized powder) for 3 months, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum markers of bone turnover. Micro-CT was used to evaluate and measure trabecular bone microarchitecture and bone mineral density (BMD) of the right distal femur. Western blot analysis and Real-time PCR were used to measure mRNA and protein expressions of β2AR, OPG and RANKL. Result: After 12 weeks of treatment with Zuoguiwan, the level of serum β-cross-linked c-telopeptide of type Ι collagen (β-CTX) (PPPβ2AR in the hypothalamus (PPConclusion: The mechanism of Zuoguiwan in alleviating BMD and trabecular bone microarchitecture in ovariectomy-induced osteoporosis rats might be related to the regulation of RANKL/OPG Pathway mediated by β2AR.

The Influence of Ego-identity, Parenting Efficacy and Stress Coping Style on Depression in Mothers of Toddlers

PURPOSE: This study was conducted to determine the influence of ego-identity, parenting efficacy, and stress coping style on depression in mothers of toddlers. METHODS: This was a cross-sectional, descriptive study. Data were collected from 164 mothers of toddlers, and analyzed using descriptive statistics, the t-test, analysis of variance, Pearson correlation coefficients, and multiple regression analysis using SPSS for Windows version 24.0. RESULTS: The factors influencing depression in mothers of toddlers included ego-identity, economic status, and perceived health status. These variables explained 60.0% of depression in mothers of toddlers. CONCLUSION: Lower ego-identity was associated with more intense depression. Therefore, healthcare providers should develop intervention programs that can improve ego-identity to decrease depression among mothers of toddlers.

Advance of exosomes in ischemic stroke / 中国病理生理杂志

Stroke is one of the major causes of death and disability in China and even worldwide.At present, treatment of stroke has been traditionally focused on reducing death of ischemic cells.However,clinical trials have shown that none of neuroprotective drugs tested achieve clinical benefit after acute stroke.Exosomes are 30~100 nm extracellular vesicles derived from cells with cell membrane structure.Many studies suggest exosomes play essential roles in intercellular communication by transferring their cargo between source and target cells in brain.Emerging data show that exsomes also make a contribution to brain recovery via regulating highly interactive process pathway after stroke.Here,we review these advances and highlight the potential therapeutic functions of exosomes in brain remodeling after stroke.

Effects of Perceived Daily Stress and Sense of Humor on Quality of Life among School-Age Children

PURPOSE: Quality of life is important to everyone including school-age children. Therefore this study was done to identify the effects perceived daily stress and sense of humor on quality of life for these children. METHODS: The study was a cross-sectional, descriptive study design with 371 participants from 5th and 6th grade children in 5 elementary schools. Data were analyzed using descriptive statistics, t-test, ANOVA, Pearson correlation coefficients, and multiple regression analysis with SPSS/WIN 24.0 program. RESULTS: Factors influencing quality of life in school-age children were daily stress, sense of humor, satisfaction with daily life, academic performance and home atmosphere. These variables explained 63.0% of quality of life in school-age children. CONCLUSION: Results showed that lower daily stress and higher sense of humor are associated with higher quality of life. Therefore, to improve quality of life in school-age children, healthcare providers should develop intervention programs considering these factors.

A probability model for analyzing speckles in intravascular ultrasound images to facilitate image segmentation / 南方医科大学学报

Ultrasonic image speckles result from the interference of the reflected signals by the scatters in the detected tissue. The physical characteristics of the speckles are closely correlated with the structures of the biological tissues, and the probability distribution of these speckles differs across different tissues. Based on the probability characteristics of intravascular ultrasound (IVUS) speckles, a Gamma mixture model and Gaussian mixture model are proposed to describe the calcified plaque, soft plaque and normal vascular regions on IVUS images. Using KS test, KL divergence and correlation coefficient analysis, we found that the probability distributions of the speckles generated by calcified plaques and normal blood vessels were better described by the Gaussian mixture model, while the speckles caused by soft plaques were described better by the Gamma mixture model. Based on this finding, we propose a probability mixture model combining neighborhood information for plaque segmentation on IVUS images. Compared with the existing probabilistic mixture model, the segmentation accuracy was greatly improved with a reduced noise.

Effects of CENP-W down-regulation on human glioma U87 cells / 中国病理生理杂志

AIM:To study the effect of centromere protein W ( CENP-W) down-regulation on human glioma U87 cells.METHODS:Small interfering RNA ( siRNA) was used to inhibit the expression of CENP-W in the U87 cells. The interference effect of siRNA was evaluated by RT-qPCR and Western blot .The proliferation of the cells was analyzed by MTT assay , BrdU staining and colony formation experiment .Transwell chamber assay was used to detect the invasion a-bility of the cells .The cell migration ability was measured by a scratch test .The changes of the cell cycle distribution and apoptosis were analyzed by flow cytometry .RESULTS:The results of MTT assay , colony formation experiment and BrdU staining showed that the cell proliferation and colony formation abilities in experimental group were significantly lower than those in control group and negative control group .The results of Transwell and scratch experiments showed that the migra-tion and invasion abilities in experimental group were weaker than those in blank control group and negative control group . The results of flow cytometry analysis showed that the cell cycle distribution in experimental group was arrested in G 0/G1 phase .The percentage of apoptotic cells in experimental group was higher than that in control group ( P<0.05 ) .CON-CLUSION:Down-regulation of CENP-W expression inhibits the proliferation , migration and invasion of human glioma cells and promotes the apoptosis of the cells , suggesting that CENP-W may be a potential target of gene therapy for human glioma.

Potent rapid antidepressant effects of effective fraction of GJ-PE and up-regulation of BDNF and TrkB / 中国药理学通报

Aim To identify whether the petroleum e-ther fraction of Gardenia jasminoides Ellis ( GJ-PE ) could effetive exhibit a rapid antidepressant effect and also to investigate the biological mechanism. Methods Tail suspension test ( TST ) , forced swimming test ( FST ) and novelty suppressed-feeding ( NSF ) were used to screen the rapid antidepressant potential of ef-fective fractions of GJ-PE in KM mice at 24 h post a single administration. Tail suspension test ( TST) was also used at 30 min and forced swimming test ( FST ) was used at 2 h to test the initial onset time of effective fractions of GJ-PE in KM mice. Western blot was per-formed to examine the expression of BDNF and p-eEF2 in hippocampus of KM mice at 2 h and 24 h. Results An acute administration of GJ-PE1 decreased the im-mobility time of KM mice in FST at 2 h and 24 h and decreased the latency time in NSF at 24 h. GJ-PE3 de-creased the latency time in NSF at 24 h. GJ-PE4 in-creased the unit food consumption in NSF at 24 h. At 2 h post a single GJ-PE1 treatment, the expression of BDNF was significantly up-regulated while the expres-sion of p-eEF2 was significantly down-regulated. At 24 h post a single GJ-PE1 treatment, the expression of BDNF was significantly down-regulated while p-eEF2 expression was significantly up-regulated. Conclusion GJ-PE1 has the most significant rapid antidepressant potential among the four fractions of GJ-PE. The effec-tive time of GJ-PE1 is 2 h after drug treatment. The mechanism of the rapid antidepressant effect of GJ-PE1 at 2 h is related to the up-regulation of BDNF and down-regulation of p-eEF2 . GJ-PE3 and GJ-PE4 also have some features of rapid antidepressants. GJ-PE2 doesn′t have the rapid antidepressant potential.

Prediction and prevention of stroke-associated pneumonia / 国际脑血管病杂志

Pneumonia is one of the most common medical complications after stroke.Stroke-associated pneumonia (SAP) can not only increase the length of hospital stay and medical cost of patients,but also an important risk factor for mortality and morbidity in patients with stroke.All these indicate that the importance of prediction and prevention of SAP.This article reviews the advances in research on the prediction and prevention of SAP.

Jiangtang decoction in combination with insulin in the treatmnet of type 1 diabetes mellitus in children / 国际中医中药杂志

Objective To investigate the efficacy of the combination ofJiangtang decoction and insulin in the treatment of type 1 diabetes mellitus in children.Methods A total of 43 children with type 1 diabetes mellitus were enrolled and randomly allocated to either a insulin group (control group) and a insulin plusJiangtang decoction group (treatment group) using the table of random digits, with 23 patients in the control group and 20 in the treatment group. The patients in the control group were treated with insulin, and those in the treatment group were administrated withJiangtangdecoction on the basis of the treatment in the control group for 2 months. Body mass index (BMI), fasting plasma glucose (FPG), postprandial blood glucose (PBG) and hemoglobin A1c (HbA1c) were measured.Results The levels of FPG, PBG and HbA1c were significantly decreased in the treatment group (twere 3.376, 54.493, and 2.798, respectively; allP<0.01), and the PBG level was significantly decreased in the control group (t=29.714,P=0.000). The levels of FPG, PBG and HbA1c in the treatment group were significantly lower than those in the control group (twere 2.715, 2.191 and 5.627, respectively;P<0.05 orP<0.01). There was no difference in BMI between the treatment group and the control group (t=0.159,P=0.874). The proportion of patients with HbA1c <7.5% in the treatment group (60.0%, 12/20) was higher than that in the control group (26.1%, 6/23;χ2=5.055,P=0.025).Conclusion Combination ofJiangtang decoction and insulin can decrease the level of FPG, PBG and HbAlc, and its therapeutic effect is superior to insulin alone for type 1 diabetes in children.

Effects of lentivirus-mediated RWDD3 silencing on proliferation and inva-sion of human glioma U251 cells / 中国病理生理杂志

AIM:To investigate the effect of RWDD3 gene silencing on the biological characteristics of human glioma U251 cells.METHODS: A lentiviral vector expressing RWDD3 shRNA was constructed and transfeeted into the U251 cells.The expression of RWDD3 at mRNA and protein levels was detected by real-time PCR and Western blot , re-spectively .The cell activity was determined by MTT assay .The colony formation ability was detected by the colony forma-tion assay .The cell proliferation ability was detected by BrdU incorporation assay .The cell invasion and migration were evaluated by Transwell assay .Flow cytometry was used to monitor the changes of cell cycle distribution and apoptosis .RE-SULTS:Recombinant lentivirus was successfully transfected into U 251 cells.Compared with the cells transfected with the scrambled shRNA and control cells, the cell activity, colony formation ability, and the invasive and migratory activities were inhibited, the cell cycle was arrested in G 0/G1 phase, and the apoptosis was increased in the U 251 cells transfected with RWDD3 shRNA ( P <0.05 ) .CONCLUSION: RWDD3 plays a vital role in proliferation and invasion of glioma cells.It may serve as a potential target of gene therapy for glioma .

Association between mitochondrial uncoupling protein 2 gene promoter -866G＞A polymorphism and ischemic stroke in diabetic patients / 中华内分泌代谢杂志

Objective To investigate the association of uncoupling protein 2 ( UCP-2 ) gene promoter -866G＞A polymorphism and ischemic stroke in diabetic patients.Methods A total of 844 type 2 diabetic patients including 404 cases with ischemic stroke and 440 cases without ischemic stroke were selected for the 4 year prospective study,Genomic DNA was extracted from the whole blood samples of subjects,UCP-2 gene promoter -866G ＞ A polymorphism was detected by TaqMan MGB probe method,and then the genotype and allele gene frequencies were compared.Results The risk of ischemic stroke in type 2 diabetic female patients with AA+GA genotypes of UCP-2 was higher than that with GG genotype (P＜0.05),but there was no difference among male patients with three genotypes.Conclusions UCP-2 gene promoter -866G ＞ A polymorphism increases the risk of ischemic stroke in Chinese diabetic women.

Analysis of the construction of drug clinical trial organization at The First Affiliated Hospital of Nanjing Medical University / 中华医学科研管理杂志

This study retrospectively reviewed the experimental clinical programs at The First Affiliated Hospital of Nanjing Medical University. Experience was summarized, and methods for improving clinical pharmaceutical research were discussed including recruiting talent people, managing resources and trail results, and establishing international cooperations.

Effects of iptakalim hydrochloride on H_2O_2 induced cytotoxicity in pheochromocytoma(PC12) cells / 中国临床药理学与治疗学

AIM: To investigate the protective effects and mechanisms of iptakalim hydrochloride(Ipt)on H_2O_2 induced neurotoxity. METHODS: Neurotoxity injury was induced by H_2O_2 in PC12 cells. The cell viability was tested by MTT assay. The glutamate released from PC12 cells was measured by HPLC combined with fluorescent detector analysis. Changes in the intracellular free Ca 2+ concentration ([Ca 2+ ]_i) were determined in fluo-3 AM loaded PC12 cells. RESULTS: Ipt (1, 10 and 100 ?mol?L -1 ) markedly mitigated H_2O_2-induced neurotoxity, 10 ?mol?L -1 Ipt inhibited the release of glutamate and the increase of [Ca 2+ ]_i induced by H_2O_2 .The protective effects was incompletely blocked by 5-HD which is a mitochondrial K_ ATP channels antagnist. CONCLUSION: Ipt provides neuroprotective effects on H_2O_2 induced cytoxixity in cultured PC12 cells and the protective effects may be partially related with mitochondrial KATP channels.