Aurora A Kinase Plays a Key Role in Mitosis Skip during Senescence Induced by Ionizing Radiation / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the fate and underlying mechanisms of G2 phase arrest in cancer cells elicited by ionizing radiation (IR).@*METHODS@#Human melanoma A375 and 92-1 cells were treated with X-rays radiation or Aurora A inhibitor MLN8237 (MLN) and/or p21 depletion by small interfering RNA (siRNA). Cell cycle distribution was determined using flow cytometry and a fluorescent ubiquitin-based cell cycle indicator (FUCCI) system combined with histone H3 phosphorylation at Ser10 (pS10 H3) detection. Senescence was assessed using senescence-associated-β-galactosidase (SA-β-Gal), Ki67, and γH2AX staining. Protein expression levels were determined using western blotting.@*RESULTS@#Tumor cells suffered severe DNA damage and underwent G2 arrest after IR treatment. The damaged cells did not successfully enter M phase nor were they stably blocked at G2 phase but underwent mitotic skipping and entered G1 phase as tetraploid cells, ultimately leading to senescence in G1. During this process, the p53/p21 pathway is hyperactivated. Accompanying p21 accumulation, Aurora A kinase levels declined sharply. MLN treatment confirmed that Aurora A kinase activity is essential for mitosis skipping and senescence induction.@*CONCLUSION@#Persistent p21 activation during IR-induced G2 phase blockade drives Aurora A kinase degradation, leading to senescence via mitotic skipping.

Arbutin isolated from Chinese yam inhibits LPS-induced NRK-52e cell apoptosis by ERp / 中国药理学通报

Aim To investigate the effect of arbutin on apoptosis of NRK-52e cells induced by LPS and the potential mechanism.Methods The model of NRK- 52e cells injury was constructed by LPS, and NRK-52e cells were divided into control, LPS ( 1 mg • L 1 ) , low dose arbutin (LPS, 1 mg • L 1 + arbutin, 5 (xmol • L_l ) , high dose arbutin ( LPS, 1 mg • L 1 + arbutin , 10 (xmol • L 1 ) and its corresponding inhibitor THC group ( 1 (xmol • L 1).The cell viability was detected ; the levels of ROS, apoptosis, Ca~' concentration and mitochondrial membrane potential ( MMP ) were detected by flow cytometry; the levels of key apoptosis proteins were detected by in cell western; the binding activity of arbutin with ER(3 was imitated by molecular docking technology, and verified by in cell western.Results Arbutin could effectively regulate the levels of ROS, Ca"+ , apoptosis proteins and ER(3 in NRK-52e cells induced by LPS and inhibit the de- cline of MMP, which is blocked by estrogen receptor inhibitor THC.In addition, arbutin has good binding activity with ERf}.Conclusion This study confirms that arbutin could inhibit LPS-induced apoptosis of NRK-52e cells through ER£.

MiR-663a Inhibits Radiation-Induced Epithelium-to-Mesenchymal Transition by Targeting TGF-β1 / 生物医学与环境科学（英文）

Objective@#miR-663a has been reported to be downregulated by X-ray irradiation and participates in radiation-induced bystander effect via TGF-β1. The goal of this study was to explore the role of miR-663a during radiation-induced Epithelium-to-mesenchymal transition (EMT).@*Methods@#TGF-β1 or IR was used to induce EMT. After miR-663a transfection, cell migration and cell morphological changes were detected and the expression levels of miR-663a, TGF-β1, and EMT-related factors were quantified.@*Results@#Enhancement of cell migration and promotion of mesenchymal changes induced by either TGF-β1 or radiation were suppressed by miR-663a. Furthermore, both X-ray and carbon ion irradiation resulted in the upregulation of TGF-β1 and downregulation of miR-663a, while the silencing of TGF-β1 by miR-663a reversed the EMT process after radiation.@*Conclusion@#Our findings demonstrate an EMT-suppressing effect by miR-663a via TGF-β1 in radiation-induced EMT.

Inhibition of Ciliogenesis Enhances the Cellular Sensitivity to Temozolomide and Ionizing Radiation in Human Glioblastoma Cells / 生物医学与环境科学（英文）

Objective@#To investigate the function of primary cilia in regulating the cellular response to temozolomide (TMZ) and ionizing radiation (IR) in glioblastoma (GBM).@*Methods@#GBM cells were treated with TMZ or X-ray/carbon ion. The primary cilia were examined by immunostaining with Arl13b and γ-tubulin, and the cellular resistance ability was measured by cell viability assay or survival fraction assay. Combining with cilia ablation by IFT88 depletion or chloral hydrate and induction by lithium chloride, the autophagy was measured by acridine orange staining assay. The DNA damage repair ability was estimated by the kinetic curve of γH2AX foci, and the DNA-dependent protein kinase (DNA-PK) activation was detected by immunostaining assay.@*Results@#Primary cilia were frequently preserved in GBM, and the induction of ciliogenesis decreased cell proliferation. TMZ and IR promoted ciliogenesis in dose- and time-dependent manners, and the suppression of ciliogenesis significantly enhanced the cellular sensitivity to TMZ and IR. The inhibition of ciliogenesis elevated the lethal effects of TMZ and IR via the impairment of autophagy and DNA damage repair. The interference of ciliogenesis reduced DNA-PK activation, and the knockdown of DNA-PK led to cilium formation and elongation.@*Conclusion@#Primary cilia play a vital role in regulating the cellular sensitivity to TMZ and IR in GBM cells through mediating autophagy and DNA damage repair.

Effects of Tingli Dazao Xiefei Decoction on the immune inflammation and intestinal flora in asthmatic rats / 药学学报

The study aims to explore the intervention mechanism of Tingli Dazao Xiefei Decoction on asthma from the perspective of immune inflammation and intestinal flora, providing a theoretical basis for guiding clinical medication. The ovalbumin (OVA) asthmatic rat model was established by intraperitoneal injection of OVA sensitization solution and aerosol challenge, and divided into control (CON), model (M), dexamethasone group (DEX, 0.075 mg·kg-1) and Tingli Dazao Xiefei Decoction (TLDZ, 3.5 g·kg-1). Firstly, the effects of Tingli Dazao Xiefei Decoction on asthma symptoms of rats, lung and trachea pathological changes of asthmatic rats were observed by inducing cough and asthma experiment, phenol red excretion, hematoxylin-eosin staining (H&E), Masson and periodic acid Schiff (PAS) staining; the levels of transforming growth factor β1 (TGF-β1), interleukin (IL) 6 and IL-10 in rat serum and the levels of interferon γ (IFN-γ), immunoglobulin E (IgE), IL-4, IL-17A and tumor necrosis factor α (TNF-α) in bronchoalveolar lavage fluid (BALF) were detected by ELISA; the mRNA levels of IL-5, IL-13 and IL-33 in the lung were determined by qRT-PCR; the levels of macrophages and neutrophils in the spleen and the levels of natural killer cell (NK), helper T cell (Thc), dendritic cell (DC), regulatory T cell (Treg) and T helper cell 17 (Th17) in the peripheral blood were measured by flow cytometry combined with immunohistochemistry; the intestinal flora of asthmatic rats were analyzed by 16S rDNA high-throughput sequencing. Pathology and inflammatory results showed that Tingli Dazao Xiefei Decoction could effectively alleviate the asthma symptoms in rats, improve the pathological changes of lung tissue, reduce the production of goblet cells and collagen fibers, and reduce the inflammatory response in asthmatic rats; the results of immune cells showed that Tingli Dazao Xiefei Decoction could effectively increase the levels of NK, Thc, DC and Treg cells and reduce the levels of macrophages, neutrophils and Th17 cells in asthmatic rats; the results of intestinal flora showed that Tingli Dazao Xiefei Decoction could increase the levels of Lactobacillus, Ruminococcus, Christensenellaceae, Bifidobacterium and Eubacterium]_xylanophilum-group, and decrease the levels of Firmicutes, Desulfovibrio, Mucispirillum and Romboutsia in asthmatic rats. Therefore, it is speculated that Tingli Dazao Xiefei Decoction can improve the symptom of asthmatic rats by regulating the immune inflammation and intestinal flora in the asthmatic rats. All animal experiments in this article were approved by the Ethics Committee of Henan University of Chinese Medicine.

Risk factors for gastric cancer: a large-scale, population-based case-control study / 中华医学杂志(英文版)

BACKGROUND@#Early detection of gastric cancer (GC) has been the topic of major efforts in China. This study aimed to explore the risk factors associated with GC and to provide evidence for the selection of a high-risk population of GC.@*METHODS@#Based on the cancer screening cohort of the National Cancer Screening Program in Urban China, GC patients diagnosed by endoscopy and pathological examinations constituted the case group, and controls were 1:3 matched by sex and age (±5 years) individually. The variables were selected by univariable analysis of factors such as body mass index (BMI), dietary habits, lifestyle, stomach disease history, and family history of GC; and multivariable logistic regression was used to analyze the influencing factors of GC and to calculate the odds ratio (OR) of related factors and its 95% confidence interval (CI).@*RESULTS@#A total of 215 GC cases and 645 matched healthy controls were included in the final analysis, with a median age of 61 years for the case and control groups. Overall analysis showed that high educational level (above primary school) (OR = 0.362, 95% CI = 0.219-0.599, P < 0.001), overweight/obesity (BMI ≥24 kg/m2; OR = 0.489, 95% CI = 0.329-0.726, P < 0.001), cigarette smoking (OR = 3.069, 95% CI = 1.700-5.540, P < 0.001), alcohol consumption (OR = 1.661, 95% CI = 1.028-2.683, P = 0.038), history of stomach disease (OR = 6.917, 95% CI = 4.594-10.416, P < 0.001), and family history of GC in first-degree relatives (OR = 4.291, 95% CI = 1.661-11.084, P = 0.003) were significantly correlated with the occurrence of GC. Subgroup analyses by age and gender indicated that GC risk was still increased in the presence of a history of stomach disease. A history of chronic gastritis, gastric ulcer, or gastric polyposis was positively associated with GC, with adjusted ORs of 4.155 (95% CI = 2.711-6.368), 1.839 (95% CI = 1.028-3.288), and 2.752 (95% CI = 1.197-6.326).@*CONCLUSIONS@#Subjects who smoke, drink, with history of stomach disease and family history of GC in first-degree relatives are the high-risk populations for GC. Therefore, attention should be paid to these subjects for GC screening.

Clinical features of children with Guillain-Barré syndrome and the significance of Brighton criteria / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features of children with Guillain-Barré syndrome (GBS) and the significance of Brighton criteria in childhood GBS.@*METHODS@#A retrospective analysis was performed on the medical data of 72 children with GBS. Brighton criteria were used for the grading of diagnostic certainty (level 1 as the highest level, and level 4 as the lowest level). A Spearman's rank correlation analysis was used to evaluate the correlation of auxiliary examinations with the level of diagnostic certainty of Brighton criteria.@*RESULTS@#A total of 72 children with GBS were enrolled, with a mean age of onset of (98±32) months. All children (100%, 72/72) had weakness of bilateral limbs and disappearance or reduction of tendon reflex, and limb weakness reached the highest level of severity within 4 weeks. Of all the 72 children, 68 (94%) had positive results of neural electrophysiological examination and 51 (71%) had positive results of cerebrospinal fluid (CSF) examination, and the positive rate of neural electrophysiological examination was significantly higher than that of CSF examination (@*CONCLUSIONS@#Most of the children with GBS meet Brighton criteria level 1, and the positive results of CSF examination and neural electrophysiological examination play an important role in improving the level of diagnostic certainty of Brighton criteria. Neural electrophysiological examination has a higher positive rate than CSF examination in the early stage of the disease.

Role and potential of adipose-derived stem cells in cranio-maxillofacial bone regeneration / 中国组织工程研究

BACKGROUND: The repair of cranio-maxillofacial bone defects is still facing severe challenges, and the introduction of the concept of bone regeneration points out a new direction for this problem. Adipose-derived stem cells are easy to access and have strong osteogenic differentiation capacity, which are considered as ideal seed cells for cranio-maxillofacial bone regeneration. OBJECTIVE: To review the influencing factors of osteogenic differentiation of adipose-derived stem cells as well as the research progress in cranio-maxillofacial bone regeneration, thus providing ideas for further study on adipose-derived stem cells in promoting cranio-maxillofacial bone regeneration. METHODS: A computer-based online search of PubMed, Wanfang, and CNKI databases was performed to retrieve papers published from January 2013 to February 2020 with the search terms of “adipose-derived stem cells, cranio-maxillofacial, oral tissue regeneration, periodontal tissue regeneration, bone regeneration, bone defects, osteogenesis” in English and Chinese. Finally, 88 papers were included for summary. RESULTS AND CONCLUSION: Adipose-derived stem cells can be induced to differentiate to osteoblasts and are easy to acquire in large quantities. It has a strong ability of expansion in vitro and has a broad application prospect in the field of cranio-maxillofacial bone regeneration. miRNAs/microRNAs play a role in the osteogenic differentiation of adipose-derived stem cells. The osteogenic differentiation ability of adipose-derived stem cells can be improved by the means of co-culture with other cells, combined with platelet-rich plasma or modified titanium and gene technology. Compared with conventional extracorporeal scaffolds, adipose-derived stem cells combined with injectable scaffolds have greater potential in osteogenesis. Some progress has been made in repairing cranio-maxillofacial bone defects with adipose-derived stem cells, but there is still a lack of sufficient evidence in large-scale clinical trials.

The relationship between inflammatory factors and the risk of breast cancer in Kailuan cohort / 中华疾病控制杂志

Objective To investigate whether elevated baseline levels of high sensitivity C-Reactive Protein (hsCRP) and neutrophil (NE) are associated with an increased risk of breast cancer in Kailuan female cohort. Methods Females from Kailuan cohort (2006-2007) were included in this study. Information on check-up, hsCRP and NE were collected at baseline for all subjects. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (95%CI) of association between baseline hsCRP and NE values and breast cancer risk. Results By December 31, 2015, a total of 18 866 participants were enrolled in this study. During the follow-up, 183 new cases of breast cancer were observed. All participants were divided into three groups according to the level of hsCRP (3 mg/L). The cumulative incidence of breast cancer were 829/105, 1 211/105 and 1 495/105 in these 3 groups, respectively ( 2=12.08， P=0.002). Compared with participants with lower hsCRP levels (3 mg/L) levels had significantly increased risk of breast cancer (HR=1.71,95%CI: 1.18-2.47, P=0.005), howerver, we didn’t find the statistically significant association between NE level (0.05). Conclusions Elevated levels of hsCRP at baseline might increase the risk of breast cancer in females.

Bone Loss Induced by Simulated Microgravity, Ionizing Radiation and/or Ultradian Rhythms in the Hindlimbs of Rats / 生物医学与环境科学（英文）

OBJECTIVE@#To better understand the pathological causes of bone loss in a space environment, including microgravity, ionizing radiation, and ultradian rhythms.@*METHODS@#Sprague Dawley (SD) rats were randomly divided into a baseline group, a control group, a hindlimb suspension group, a radiation group, a ultradian rhythms group and a combined-three-factor group. After four weeks of hindlimb suspension followed by X-ray exposure and/or ultradian rhythms, biomechanical properties, bone mineral density, histological analysis, microstructure parameters, and bone turnover markers were detected to evaluate bone loss in hindlimbs of rats.@*RESULTS@#Simulated microgravity or combined-three factors treatment led to a significant decrease in the biomechanical properties of bones, reduction in bone mineral density, and deterioration of trabecular parameters. Ionizing radiation exposure also showed adverse impact while ultradian rhythms had no significant effect on these outcomes. Decrease in the concentration of the turnover markers bone alkaline phosphatase (bALP), osteocalcin (OCN), and tartrate-resistant acid phosphatase-5b (TRAP-5b) in serum was in line with the changes in trabecular parameters.@*CONCLUSION@#Simulated microgravity is the main contributor of bone loss. Radiation also results in deleterious effects but ultradian rhythms has no significant effect. Combined-three factors treatment do not exacerbate bone loss when compared to simulated microgravity treatment alone.

Effects of rosuvastatin in homocysteine induced mouse vascular smooth muscle cell dedifferentiation and endoplasmic reticulum stress and its mechanisms / 中国应用生理学杂志

OBJECTIVE@#To investigate the effect of rosuvastatin on homocysteine (Hcy) induced mousevascular smooth muscle cells(VSMCs) dedifferentiation and endoplasmic reticulum stress(ERS).@*METHODS@#VSMCs were co-cultured with Hcy and different concentration of rosuvastatin (0.1, 1.0 and 10 μmol/L). Cytoskeleton remodeling, VSMCs phenotype markers (smooth muscle actin-α, calponin and osteopontin) and ERS marker mRNAs (Herpud1, XBP1s and GRP78) were detected at predicted time. Tunicamycin was used to induce, respectively 4-phenylbutyrate(4-PBA) inhibition, ERS in VSMCs and cellular migration, proliferation and expression of phenotype proteins were analyzed. Mammalian target of rapamycin(mTOR)-P70S6 kinase (P70S6K) signaling agonist phosphatidic acid and inhibitor rapamycin were used in Rsv treated VSMCs. And then mTOR signaling and ERS associated mRNAs were detected.@*RESULTS@#Compared with Hcy group, Hcy+ Rsv group (1.0 and 10 μmol/L) showed enhanced α-SMA and calponin expression (<0.01), suppressed ERS mRNA levels (<0.01) and promoted polarity of cytoskeleton. Compared with Hcy group, Hcy+Rsv group and Hcy+4-PBA group showed suppressed proliferation, migration and enhanced contractile protein expression (<0.01); while tunicamycin could reverse the effect of Rsv on Hcy treated cells. Furthermore, alleviated mTOR-P70S6K phosphorylation and ERS (<0.01)were observed in Hcy+Rsv group and Hcy+rapamycin group, compared with Hcy group; while phosphatidic acid inhibited the effect of Rsv on mTOR signaling activation and ERS mRNA levels (<0.01).@*CONCLUSIONS@#Rosuvastatin could inhibit Hcy induced VSMCs dedifferentiation suppressing ERS, which might be regulated by mTOR-P70S6K signaling.

Changes in electrocardiographic parameters in children with complete left bundle branch block early after transcatheter closure of ventricular septal defect / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To observe the changes in electrocardiographic parameters in children with complete left bundle branch block (CLBBB) after the transcatheter closure of simple ventricular septal defect (VSD).</p><p><b>METHODS</b>A total of 21 children with CLBBB early after transcatheter closure of perimembranous VSD were recruited. Another 21 children without any type of arrhythmia after transcatheter closure of perimembranous VSD were enrolled as the control group. The sex, age, and the size of occluder were matched between the two groups. The changes in the following indices were compared between the two groups: left ventricular voltage, QT interval, corrected QT interval (QTc), QT dispersion (QTd), corrected QT dispersion (QTcd), JT dispersion (JTd), and corrected JT dispersion (JTcd) on the electrocardiogram before transcatheter closure and at 1, 3, 5, 30 days after transcatheter closure.</p><p><b>RESULTS</b>Left ventricular voltage and JTcd changed with operation time in the CLBBB and control groups (P<0.05). There were interaction effects between time and grouping in the changes in left ventricular voltage and QTd (P<0.05). There was a significant difference in JTcd between the CLBBB and control groups (P<0.05). There was also a significant difference in left ventricular voltage between the CLBBB and control groups at 3 and 5 days after the transcatheter closure (P<0.05).</p><p><b>CONCLUSIONS</b>There are significant differences in electrocardiographic left ventricular voltage and JTcd between VSD children with and without CLBBB early after transcatheter closure. JTcd might be useful in predicting the development of CLBBB early after transcatheter closure of VSD.</p>

Inhibition of calpain on oxygen glucose deprivation-induced RGC-5 necroptosis / 华中科技大学学报（医学）（英德文版）

The purpose of this study was to investigate the effect of inhibition of calpain on retinal ganglion cell-5 (RGC-5) necroptosis following oxygen glucose deprivation (OGD). RGC-5 cells were cultured in Dulbecco's-modified essential medium and necroptosis was induced by 8-h OGD. PI staining and flow cytometry were performed to detect RGC-5 necrosis. The calpain expression was detected by Western blotting and immunofluorescence staining. The calpain activity was tested by activity detection kit. Flow cytometry was used to detect the effect of calpain on RGC-5 necroptosis following OGD with or without N-acetyl-leucyl-leucyl-norleucinal (ALLN) pre-treatment. Western blot was used to detect the protein level of truncated apoptosis inducing factor (tAIF) in RGC-5 cells following OGD. The results showed that there was an up-regulation of the calpain expression and activity following OGD. Upon adding ALLN, the calpain activity was inhibited and tAIF was reduced following OGD along with the decreased number of RGC-5 necroptosis. In conclusion, calpain was involved in OGD-induced RGC-5 necroptosis with the increased expression of its downstream molecule tAIF.

p21 is Responsible for Ionizing Radiation-induced Bypass of Mitosis / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To explore the role of p21 in ionizing radiation-induced changes in protein levels during the G2/M transition and long-term G2 arrest.</p><p><b>METHODS</b>Protein expression levels were assessed by western blot in the human uveal melanoma 92-1 cells after treatment with ionizing radiation. Depletion of p21 was carried out by employing the siRNA technique. Cell cycle distribution was determined by flow cytometry combined with histone H3 phosphorylation at Ser28, an M-phase marker. Senescence was assessed by senescence- associated-β-galactosidase (SA-β-gal) staining combined with Ki67 staining, a cell proliferation marker.</p><p><b>RESULTS</b>Accompanying increased p21, the protein levels of G2/M transition genes declined significantly in 92-1 cells irradiated with 5 Gy of X-rays. Furthermore, these irradiated cells were blocked at the G2 phase followed by cellular senescence. Depletion of p21 rescued radiation-induced G2 arrest as demonstrated by the upregulation of G2/M transition kinases, as well as the high expression of histone H3 phosphorylated at Ser28. Knockdown of p21 resulted in entry into mitosis of irradiated 92-1 cells. However, cells with serious DNA damage failed to undergo cytokinesis, leading to the accumulation of multinucleated cells.</p><p><b>CONCLUSION</b>Our results indicated that p21 was responsible for the downregulation of G2/M transition regulatory proteins and the bypass of mitosis induced by irradiation. Downregulation of p21 by siRNA resulted in G2-arrested cells entering into mitosis with serious DNA damage. This is the first report on elucidating the role of p21 in the bypass of mitosis.</p>

Correlation of the inner diameter parameters of the spermatic vein in different positions and states of the varicocele patient with the results of seminal examination / 中华男科学杂志

<p><b>Objective</b>To study the correlation of the inner diameter parameters of the spermatic vein in different positions and states of the varicocele (VC) patient with the results of seminal examination.</p><p><b>METHODS</b>A total of 149 VC patients underwent ultrasonography, routine semen examination, and sperm morphological analysis. The parameters obtained from ultrasonography included the bilateral testis volume in a supine position, the largest spermatic vein diameter in a supine position at rest (DSR), the largest spermatic vein diameter in a supine position following Valsalva manoeuvre (DSV), the largest spermatic vein diameter in an upright position at rest (DUR), and the largest spermatic vein diameter in an upright position following Valsalva manoeuvre (DUV). Then we calculated the parameters △DS=DSV－DSR, △DU=DUV－DUR, △DR=DUR－DSR, and △DV=DUV－DSV and analyzed the correlation of the above parameters with the results of semen examination using the ROC curve.</p><p><b>RESULTS</b>Based on the results of semen examination, 119 (79.87%) of the patients were allocated to the abnormal group and the other 30 (20.13%) to the normal group. Statistically significant differences were observed between the two groups in △DU (P=0.007), △DR (P=0.0001), and △DV (P=0.04), but not in DSR (P=0.35), DSV (P=0.34), DUR (P=0.06), DUV (P=0.12), and △DS (P=0.64), nor in the volume of the testis affected (P=0.323). The area under the ROC curve was 0.55 for DSR, 0.57 for DSV, 0.64 for DUR, 0.62 for DUV, 0.49 for △DS, 0.28 for △DU, 0.86 for △DR, and 0.69 for △DV. The corresponding cutoff values were 2.25, 2.51, 2.48, 2.63, 0.30, 0.23, 0.25, and 0.20, the corresponding sensitivities of semen detection were 50.42%, 65.55%, 60.50%, 60.50%, 49.90%, 29.41%, 79.83%, and 65.55%, and the corresponding specificities were 56.67%, 63.33%, 63.33%, 63.33%, 56.67%, 33.33%, 80%, and 63.33%, respectively.</p><p><b>CONCLUSIONS</b>The difference between the largest spermatic vein diameters in supine and upright positions at rest provides a high diagnostic accuracy for semen detection and helps to predict abnormality in seminal examination for VC patients.</p>

An evaluation on the clinical application of risk score method in predicting type 2 diabetes mellitus / 预防医学

Objective To evaluate the application value of the new chinese diabetes risk score in the clinical diagnosis of type 2 diabetes mellitus.Methods A total of 232 subjects who received physical examination at the outpatient department of endocrinology were selected.Medical history and demographic information were collected.Physical examination and 75 g oral glucose tolerance test (OGTT)were conducted.Fasting or 2 -h blood glucose,HbA1 c,serum triglyceride (TG), total cholesterol (TC)and low density lipoprotein cholesterol (LDL-C)were measured.Results The area under the receiver operating curve was 0. 788 (95%CI=0. 725 -0. 852),with 0. 832 (95%CI=0. 748 -0. 916)in males and 0. 754 (95%CI=0. 664-0. 844)in females.At the optimal cutoff value (25 scores)for detecting type 2 diabetes,the sensitivity was 88. 06%and the specificity was 37. 58%.The Diabetes Risk Score was positively related to the probability of type 2 diabetes.Conclusion The new chinese diabetes risk score could be a reliable screening tool to evaluate undiagnosed type 2 diabetes in the Chinese population.

Effects of Chinese yellow wine on rat vascular endothelial cells and atherosclerosis induced by TNF -α / 预防医学

Objective To determine similarities in effect of yellow wine as compared statin and the possibility that yellow wine inhibits TNF -α-induced NO production,eNOS activity,expression of eNOS and iNOS protein in cultured rat VECs.Methods Isolation,cultivation,purification and identification of vascular endothelial cells of rat thoracic aorta in vitro were conducted.The passages 3 or 4 of VECs were used in all studies.Then we divided cells into 9 groups according to assays before:control,TNF -α,TNF -α+rosuvastatin (10 umol/L),TNF -α+ethanol 0.5%,TNF -α+yellow wine 0.5%,TNF -α+ethanol 1.0%,TNF -α+yellow wine 1.0%,TNF -α+ethanol 1.5%,and TNF -α+yellow wine 1.5% and the cells were given the corresponding treatment.NO production of culture supernatant was determined by nitrate reduction method and eNOS activity of cells was measured by chemical colorimetric method after the corresponding treatment for 24 h.The expression of eNOS and iNOS protein were detected by western blotting after the corresponding treatment for 48 h.Results Compared with the TNF -αgroup,NO production,eNOS activity,and eNOS protein expression in the rosuvastatin,and yellow wine 1.0%,and 1.5% groups were significantly increased and expression of iNOS protein were significantly decreased.Compared with the rosuvastatin group,eNOS protein expression in yellow wine 0.5% and yellow wine 0.5% groups significantly decreased.The expression of iNOS protein were significantly increased. Compared with ethanol groups,eNOS protein expression in yellow wine 0.5% and yellow wine 0.5% groups significantly increased and expression of iNOS protein were significantly decreased.Conclusion Treatment with yellow wine increased NO production,eNOS activity,and eNOS protein expression,which decreases iNOS protein expression.We conclude that yellow wine has similar beneficial effects as rosuvastatin on the cardiovascular system.These effects may be attributed to their anti -atherosclerotic actions.

Exploring the active ingredient of Chinese yellow wine which could inhibit the Hcy induced proliferation and migration of vascular smooth muscle cells / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the active ingredients in the Chinese yellow wine could inhibit the proliferation and migration of rat vascular smooth muscle cells induced by homocysteine (Hcy).</p><p><b>METHODS</b>The primary culture and identification of rat vascular smooth muscle cells (VSMCs) was conducted, and the VSMCs in passage 4-7 were used in the following experiments. The VSMCs were divided into 7 groups: control, Hcy (1 mmol/L), Hcy + oligosaccharide, Hcy + polypeptides, Hcy + polyphenols, Hcy + alcohol, Hcy + Chinese yellow wine and were given the corresponding treatment. The proliferation of VSMCs was determined by MTT. Transwell chambers and would healing were employed to test the migratory ability of VSMCs. Wester blot and gelatin zymography were used to investigate the expressions and activities of metal matrix proteinase 2/9 (MMP-2/9) and tissue inhibitor of metalloproteinase 2 (TIMP-2) in VSMCs of each group.</p><p><b>RESULTS</b>Compared with control group, the proliferation, migration and the expression and activity of MMP-2/9 of VSMCs were significantly increased in the VSMCs of Hcy group (P < 0.01). Compared with Hcy group, the proliferation, migration and the expression and activity of MMP-2/9 of VSMCs were significantly decreases in the VSMCs of polypeptides group, polyphenols group and Chinese yellow wine group. However, the expression of TIMP-2 among each group had no significant difference.</p><p><b>CONCLUSION</b>Polypeptides and polyphenols in the Chinese yellow wine could inhibit the proliferation and migration of VSMCs induced by Hcy.</p>

Design, synthesis and PPAR agonist activities of novel L-tyrosine derivatives containing phenoxyacetyl moiety / 药学学报

The design, synthesis and bioevaluation of a series of novel L-tyrosine derivatives as peroxisome proliferator-activated receptor (PPAR) agonists are reported. Four intermediates and twenty L-tyrosine derivatives containing phenoxyacetyl moiety TM1 were synthesized starting from L-tyrosine via four step reactions including the esterification of carboxyl group, phenoxyacetylation of a-amino group, bromoalkylation of phenolic hydroxyl group and then nucleophilic substitution reaction with various heterocyclic amines in 21%-75% overall yield. Subsequently TM1 were hydrolyzed to give sixteen corresponding target compounds TM2 in 77%-99% yield. The chemical structures of the thirty-nine new compounds were identified using 1H NMR, 13C NMR techniques and thirty-five were confirmed by HR-MS techniques. Screening results in vitro showed that the PPAR relative activation activities of the target molecules are weak overall, while compound TM2i reaches 50.01%, which hints that the molecular structures of these obtained compounds need to be modified further.

Synthesis and PPAR activities of novel phenylacetic acid derivatives containing sulfonamide moiety / 药学学报

The discovery of high performance leading antidiabetic compounds containing sulfonamide and 4-aminophenylacetic acid moieties is reported. This was achieved by the synthesis of 6 intermediates and subsequently 20 target molecules using 4-aminophenylacetic acid as the starting materials, and through a few synthetic routes aided by multi-step reactions including sulfonylation of amino group, deacylation of amides and esterification of carboxyl group, as well as acylation of amino group. The chemical structures of the twenty-four new compounds were determined using 1H NMR, 13C NMR and HR-MS techniques. Screening in vitro of their peroxisome proliferator-activated receptor (PPAR) activation activities showed weak relative PPAR activation activities to most of the target molecules. However, 4 target molecules exhibit PPAR over 58%, and as high as 81.79% for TM2-i, presenting itself as potent leading compound for antidiabetic drugs. This research also confirms that it is probable to achieve esterification of carboxyl group and deacylation of fatty acid N-phenyl amides concurrently in SOCl2/alcohol solvent system. This provides new synthetic method for the selective reaction within molecules containing both carboxyl and N-aryl amido groups of fatty acids.