Immune suppressive signaling regulated by latent transforming growth factor beta binding protein 1 promotes metastasis in cervical cancer

Although metastasis is the major cause of death in cervical cancer, the mechanism of metastasis is still unclear. The mRNA expression and protein level of latent transforming growth factor beta binding protein 1 (LTBP1) were detected in tumor tissues and paracancerous tissues from in-house samples. Cell proliferation, cell cycle, migration, and in vivo metastasis were determined after LTBP1 was knocked down. Then, 13 drugs were screened, and the changes in cell apoptosis and proliferation and tumor metastasis were detected after drug treatment in shRNA cells. In our in-house samples, LTBP1 was lowly expressed in cervical cancer tissues. After LTBP1 knockdown, cell proliferation was increased, and the ability of in vitro migration and in vivo metastasis was enhanced. At the same time, the proportion of myeloid derived suppressor cells (MDSC) in situ increased, the proportion of T cells decreased, and transforming growth factor beta-1 (TGFβ1) signaling was activated. After carboplatin treatment, LTBP1 shRNA cell line apoptosis increased, metastasis in vivo was limited, and the proportion of MDSC in situ decreased. LTBP1 was lowly expressed in cervical cancer, and the inhibition of LTBP1 can improve the malignant degree of the tumor, and this process can be blocked by carboplatin.

Studies on the Anti-Proliferative Effects and Molecular Mechanism of a Novel Small Molecular BOC26P in Breast Cancer

Background To explore the pharmacodynamic evaluation and mechanism research of BOC26P against breastcancer, and to provide a basis for the treatment of breast cancer.Method MTT assay was used to detect the cytotoxicity of BOC26P against 4 breast cancer cell lines (MCF7/TAX, MDA-MB-231/PT, MDA-MB-231and MCF-7), and as well as the non-tumor cell lines MCF-10A, in variousdrug concentrations (from 0.004 to 1 μM). Western Blotting and Real-Time PCR assay were used to detect therelative protein and gene expression level after treatment with BOC26P in MCF-7/TAX. The effect of BOC26Pon Specific fluorescent P-gp substrate accumulation in MCF-7/TAX was analyzed by flow cytometry; Moleculardocking was used to analyze the binding capacity between BOC26P, Cyclosporine A, and Verapamil. FCM assaystaining with Annexin V-FITC/PI and Propidium iodide was used to measure the apoptosis and the cell cycleafter treatment with BOC26P in MCF-7/TAX, MDA-MB-231/PT, MDA-MB-231, and MCF-7; Detection ofmitochondrial membrane potential after treatment with BOC26P inMCF-7/TAX, MDA-MB-231/PT, MDA-MB231and MCF-7; Western Blotting and Real-Time PCR assay was used to detect the apoptosis relative proteinand gene expression level after treatment with BOC26P in MDA-MB-231, MCF-7, MDA-MB-231/PT, and MCF7/ADR.Results Cytotoxicity assay showed that BOC26P could effectively suppress 4 breast cancer cell lines (MCF7/TAX, MDA-MB-231/PT, MDA-MB-231, and MCF-7) with an IC50 value of under 0.5 μM. The IC50 value ofBOC26P on non-tumor cells MCF-10A was 32.29 μM. The binding ability of BOC26P to P-gp in breast cancercells was weak. There was no significant effect on the intracellular accumulation of Rhodamin 123(Rh123), Pgp binding specific fluorescence substrate, and multi-drug resistance protein P-gp expression in MCF-7/ADRand MDA-MB-231/PT tumor cells; BOC26P induced MCF-7/TAX, MDA-MB-231/PT, MDA-MB-231 and MCF-7cells cycle arrest at G2/M phase and lead to cell apoptosis. BOC26P induced significant activation of p53protein in MCF-7/ADR and MAD-MB-231/TAX cells. Under the same conditions, BOC26P promoted Baxexpression while inhibited Bcl-2 expression, and could significantly cause activation of Cleveland PARP andClevead Caspase3. The results demonstrated that BOC26P may induce apoptosis through the death receptorapoptosis pathway.Conclusion It is known that BOC26P has a significant proliferation inhibitory effect on breast cancer cellswithout serious side effects. BOC26P has the Potential to be developed into a clinical substitute drug for triple-

Prognostic Risk Model of Colorectal Cancer Constructed by Bioinformatics Method and Functional Study of The Gene CLCA1 & SPINK4

Background Colorectal cancer (CRC) is the most common malignant tumor of digestive system. The metastasesis the main cause of mortality in CRC patients, of whom the initial diagnosis is about 25%. In our study, weaimed to identify potential gene biomarkers based on RNA sequencing data to predict and improve CRCpatient survival.Method In this study, by screening differentially expressed genes of colon cancer related to liver metastasis, asurvival prognostic risk model was constructed by bioinformatics analysis. Here, we conducted our data mininganalysis for CRC by integrating the differentially expressed genes acquired from Gene Expression Omnibus(GEO) database by primary tumor versus liver metastasis (GSE81582，GSE41258，GSE49355，GSE68468)into The Cancer Genome Atlas (TCGA) database which includes 415 primary tumor and 132 liver metastasistissue. At the same time, we used transwell, RT-PCR and western to examine the effects of CLCA1 and SPINK4on the migration of colorectal cancer cells at the cell level.Results We identified intersections of 197 genes (117 up-regulated and 80 down-regulated) between GEO dataand TCGA data. Differentially expressed genes in TCGA-COAD by single factor cox analysis, lasso cycle trainingand multifactor cox analysis composed a survival prognosis prediction model consisted of 7 genes ORM1,CLCA1, C8B, SPINK4, ALDOB, GAMT, C8G. And results of transwell experiments showed that high expression ofCLCA1 and SPINK4 can inhibit the migration ability of colon cancer cells LOVO and SW620, meanwhile westernblotting showed that the high expression of both genes can upregulate the expression of epithelial phenotypicmarker E-cadherin, and Vimentin expression is down-regulated.Conclusion In this study, 197 differentially expressed genes were selected and a relatively robust survivalprognosis prediction model was constructed. The model consisted of seven genes: GAMT, C8G, ORM1, CLCA1,C8B, SPINK4, and ALDOB. At the same time, we found that CLCA1 and SPINK4 are closely related to survivalprognosis. The predictive model nomogram will enable patients with CRC to be more accurately managed intrials testing new drugs and in clinical practice.

Development of a LC-MS/MS Method for a New Ortho-aryl Chalcone Compound of OC26 and its Application to Bile

Background OC26 and its pro-drug BOC26P, both ortho-aryl chalcone compounds, showed a well-definedantitumor activity in various cancer cells especially in drug-resistant tumor cell lines.Aim The purpose of this study was to investigate the bile excretion characteristics of OC26 after OC26 and BOC26Padministered in rats respectively.Method An ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method wasdeveloped and validated for OC26 in rat bile. Liquid-liquid extraction with ethyl acetate method was use to pretreatthe bile samples. After that, a gradient mobile phase at a flow rate 0.5mL/min of acetonitrile and 2mM CH3COONH4with 0.1% aqueous ammonia solution (v/v) and the positive ion alternate mode separated and quantified OC26.Bile samples were collected from rats after intravenous injection (i.v) 12.5mg/kg of OC26 and BOC26P, respectively.Results For method validation, the method showed high extraction recovery. The assay showed a good linearitywith correlation coefficient >0.99 at the concentration ranges of 20-2000ng/mL. All data were within the requiredlimits. The bile excretion results showed that the excretion amount of OC26 was gradually stabilized after 2h. Theaccumulative excretion percentage of OC26 after i.v 12.5mg/kg BOC26P was significantly higher than that of OC26after i.v 12.5mg/kg OC26. Significant gender differences were also observed in bile excretion of OC26.Conclusion This method was selective, sensitive and reliable and successfully applied to the bile excretion of OC26.This study provided theoretical basis for OC26 further research.

Altered Mitochondrial Functions and Morphologies in Epithelial Cells Are Associated With Pathogenesis of Chronic Rhinosinusitis With Nasal Polyps

Purpose@#Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex inflammatory disease of the nasal and paranasal sinus mucosa. The disease is associated with mitochondrial dysfunction, structural changes in the mitochondria, and reactive oxygen species (ROS) generation. This study investigated whether there are functional and morphological changes in the mitochondria in the epithelial cells of nasal polyps (NPs) and Staphylococcus aureus enterotoxin B (SEB)-stimulated nasal epithelial cells. @*Methods@#In all, 30 patients with CRSwNP and 15 healthy subjects were enrolled. Mitochondrial ROS (mtROS) and changes in mitochondrial functions and structures were investigated in the uncinate tissue (UT) of healthy controls, the UT or NPs of CRSwNP patients, and human nasal epithelial cells with or without SEB stimulation. @*Results@#Oxidative phosphorylation complexes showed various responses following SEB stimulation in the nasal epithelial cells, and their expressions were significantly higher in the NPs of patients with CRSwNP than in the UT of controls. Generation of mtROS was increased following SEB exposure in nasal epithelial cells and was reduced by pretreatment with MitoTEMPO, which is used as an mtROS scavenger. In the tissues, mtROS was significantly increased in the NPs of CRSwNP patients compared to the UT of controls or CRSwNP patients. The expressions of fusion- and fission-related molecules were also significantly higher in SEB-exposed nasal epithelial cells than in non-exposed cells. In tissues, the expression of fission (fission mediator protein 1)- and fusion (membrane and mitofusin-1, and optic atrophy protein 1)-related molecules was significantly higher in the NPs of CRSwNP patients than in UT of controls or CRSwNP patients. Transmission electron microscopy revealed elongated mitochondria in SEB-exposed nasal epithelial cells and epithelial cells of NPs. @*Conclusions@#Production of mtROS, disrupted mitochondrial function, and structural changes in nasal epithelial cells might be involved in the pathogenesis of CRSwNP.

Effects of gross motor skills on physical activity in preschoolers aged 3-6 years / 中国学校卫生

Objective@#To investigate the effect of gross motor skills on physical activity of children aged 3-6 years, and to provide basis for children’s health behavior intervention.@*Methods@#A total of 332 young children in Shanghai Xiangyin kindergarten were selected as survey objects. The development of gross movements of young children was measured by TGMD-2. Caregivers reported children’s physical activity using the International Physical Activity Questionnaire (IPAQ-SF).@*Results@#The development level of gross movements of children aged 3-6 in Shanghai was relatively low(54.76±13.86). The physical activity of children was mainly light-intensity physical activity, and the daily moderate-to-vigorous intensity physical activity time was (58.62±52.73) minutes every day. Locomotor skills had the greatest effect on children’s VPA (β=0.19) and TPA(β=0.12), with a contribution rate of 3.3% and 1.1%, respectively; Object control skills has the greatest effect on children’s MVPA (β=0.17) and MPA (β=0.12) had the largest effect(P<0.05), with contribution rates of 2.5% and 1.2%, respectively. The relationship between gross motor skills and physical activity had nothing to do with gender and age.@*Conclusion@#Children’s gross motor skills in the 3-6 year-old population should be improved and may be an effective way to promote physical activity.

Altered Mitochondrial Functions and Morphologies in Epithelial Cells Are Associated With Pathogenesis of Chronic Rhinosinusitis With Nasal Polyps

Purpose@#Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex inflammatory disease of the nasal and paranasal sinus mucosa. The disease is associated with mitochondrial dysfunction, structural changes in the mitochondria, and reactive oxygen species (ROS) generation. This study investigated whether there are functional and morphological changes in the mitochondria in the epithelial cells of nasal polyps (NPs) and Staphylococcus aureus enterotoxin B (SEB)-stimulated nasal epithelial cells. @*Methods@#In all, 30 patients with CRSwNP and 15 healthy subjects were enrolled. Mitochondrial ROS (mtROS) and changes in mitochondrial functions and structures were investigated in the uncinate tissue (UT) of healthy controls, the UT or NPs of CRSwNP patients, and human nasal epithelial cells with or without SEB stimulation. @*Results@#Oxidative phosphorylation complexes showed various responses following SEB stimulation in the nasal epithelial cells, and their expressions were significantly higher in the NPs of patients with CRSwNP than in the UT of controls. Generation of mtROS was increased following SEB exposure in nasal epithelial cells and was reduced by pretreatment with MitoTEMPO, which is used as an mtROS scavenger. In the tissues, mtROS was significantly increased in the NPs of CRSwNP patients compared to the UT of controls or CRSwNP patients. The expressions of fusion- and fission-related molecules were also significantly higher in SEB-exposed nasal epithelial cells than in non-exposed cells. In tissues, the expression of fission (fission mediator protein 1)- and fusion (membrane and mitofusin-1, and optic atrophy protein 1)-related molecules was significantly higher in the NPs of CRSwNP patients than in UT of controls or CRSwNP patients. Transmission electron microscopy revealed elongated mitochondria in SEB-exposed nasal epithelial cells and epithelial cells of NPs. @*Conclusions@#Production of mtROS, disrupted mitochondrial function, and structural changes in nasal epithelial cells might be involved in the pathogenesis of CRSwNP.

Developing an UPLC-MSMS Method to Quantify a Novel Anticancer Chalcone BOC26P for Its Pharmacokinetic Study In vivo

Objective BOC26P is a potent anticancer candidate which inhibits microtubule polymerization and shows strongcytotoxic activity against numerous cancer cell lines and drug resistant cell lines. To support the pharmacokineticstudy of BOC26P, a rapid, selective and reproducible UPLC-MS/MS method was developed.Method Dexamethasone sodium phosphate (DSP) was used as an internal standard (IS). Following proteinprecipitation by using methanol-acetonitrile solution (1:1, v/v) with an internal standard DSP, the processedsamples were chromatographed on an UPLC X Bridge 71 TM C8 column (4.6 mm × 100 mm, 3.5 μm) with a mobilephase that consisted of acetonitrile and 2mmol/L ammonium acetate aqueous solution (containing 0.25%ammonia) with a gradient elution pumped at a flow rate of 0.4 mL/min. Mass spectrometric detection wasperformed in the positive electrospray ionization mode by multiple reaction monitoring (m/z 428.84→198.92 and472.90→434.93 for BOC26P and DSP, respectively). The quantification of BOC26P in rat plasma was fully verified.Results The linearity was established in the range of 50 to 2000 ng/mL(r2≥0.99). The recovery of BOC26P fromspiked plasma were ranged from 96.7% to 110.5%. This method showed acceptable accuracy (3.7% to 6.3%) andprecision (1.5% to 3.1%) both of intra- and inter-day.Conclusion The developed method was successfully applied for three intravenous dose (2, 5, 12.5 mg/kg BOC26P)pharmacokinetics in male and female rats

A case-control study on the risk factors of unintentional injuries among internal-migrant childrenLI Xin-yu, YANG Ya-ming, FEI Gao-qiang, ZHOU Yi-xi, GAO Liu-wei, / 中华疾病控制杂志

Objective To explore risk factors of unintentional injuries among internal-migrant children. Methods A 1 ∶〗1 matched case-control study was conducted between 332 internal-migrant children with unintentional injuries, based on the principle that same class, same gender and age was no more than two years old. The survey was based on the unified questionnaire. Epi Data 3.1 was used to establish database and SPSS 23.0 was used for univariate analysis and multi-conditional Logistic regression analysis. Results Multi-conditional Logistic regression analysis model indicated that caregiver put pressure on children before exam and the adjusted odd ratio (OR) was 2.086 and 95% confidence interval (CI) was 1.263-3.444, caregiver’s character was extravert type (OR=2.074, 95% CI:1.275-3.372) or middle type (OR=1.796, 95% CI: 1.158-2.784), caregiver’s educational background was illiteracy (OR=1.867, 95% CI: 1.280-2.722) or primary school (OR=2.458, 95% CI: 1.169-5.168), the neurotic behaviors of children (OR=1.466, 95% CI: 1.012-2.124) were risk factors of unintentional injuries among internal-migrant children. Conclusions The characteristics related to internal-migrant children’s caregiver and children’s neurotic behaviors are associated with the occurrence of unintentional injuries. Immediate and effective measures should be taken to ease the high injury prevalence and prevent the unintentional injuries among internal-migrant children.

Effect of Qiangjing Tablets on the MAPK signaling pathway in SD rats with asthenospermia / 中华男科学杂志

<p><b>Objective</b>To investigate the effects of Qiangjing Tablets (QJT) on sperm quality and the MAPK signaling pathway in the SD rat model of asthenospermia (AS).</p><p><b>METHODS</b>A total of 100 male SD rats were randomly divided into five groups of equal number, blank control, AS model control, high-dose QJT, medium-dose QJT, and low-dose QJT. All the rats were intragastrically administered ORN at 200 mg/kg/d for establishment of the AS model except those in the blank control group, which were given 1% CMC sodium solution at 1 ml/100 g by gavage. Meanwhile the animals of the high-, medium-, and low-dose QJT groups were gavaged with QJT at 6700, 3300 and 1700 mg/kg/d, respectively, qd 6 days a week for 20 days. Then the testis issue and the apoptosis of the testicular cells were observed under the electron microscope, the expression of vimentin in the testis was determined with the immunohistochemical SP method, that of ERK1/2 detected by Western blot, and the concentration of TGF-β1 in the semen measured by ELISA.</p><p><b>RESULTS</b>The AS model controls showed round nuclei of spermatocytes, homogeneously distributed chromatins, broken or lost mitochondria, and expanded rough endoplasmic reticulum in the testis tissue. In comparison, the rats of the high-, medium-, and low-dose QJT groups exhibited round nuclei of spermatocytes, homogeneously distributed chromatins, and well-structured mitochondria, rough endoplasmic reticulum and ribosome, which were all similar those of the blank controls. Compared with the blank controls, the AS model rats manifested significantly increased expressions of ERK1/2 (1.00 ± 0.00 vs 1.26 ± 0.10, P<0.01) and vimentin (0.16 ± 0.01 vs 0.17 ± 0.01, P<0.01) and apoptosis rate of cells in the testis tissue (［9.20 ± 3.07］ vs ［42.20 ± 9.17］ %, P<0.01), but decreased level of TGF-β1 in the semen (［627.67 ± 26.07］ vs ［566.73 ± 68.44］ ng/ml, P<0.05). In comparison with the model controls, the rats of the high- and medium- -dose QJT groups presented remarkably down-regulated expressions of ERK1/2 (1.26 ± 0.10 vs 1.14 ± 0.08, P<0.01; 1.26 ± 0.10 vs 1.18 ± 0.05, P<0.05) and vimentin (0.17 ± 0.01 vs 0.16 ± 0.01, P<0.01; 0.17 ± 0.01 vs 0.17 ± 0.09, P<0.05) and decreased rate of cell apoptosis (［42.20 ± 9.17］ vs ［21.60 ± 5.94］ %, P<0.01; ［42.20 ± 9.17］ vs ［33.95 ± 6.39］ %, P<0.05). The concentration of TGF-β1 in the semen was markedly lower in the high-dose QJT than in the AS model control group (［621.78 ± 30.80］ vs ［566.73 ± 68.44］ ng/ml, P < 0.05).</p><p><b>CONCLUSIONS</b>Qiangjing Tablets could improve semen quality in asthenospermia rats by acting against oxidative stress.</p>

Inhibitory effect of Qilan Capsules on the expressions of vasculogenic mimicry-related proteins in prostate cancer / 中华男科学杂志

<p><b>Objective</b>To investigate the effect of Qilan Capsules (QLC) on the expressions of the related proteins HIF-1α, VEGF-α, EphA2 and MMP-1 in the formation of vasculogenic mimicry (VM) in prostate cancer.</p><p><b>METHODS</b>Prostate cancer PC-3 cells were cultured, transfected with siRNA, and divided into eight groups, blank control, HIF-1α siRNA, VEGF-α siRNA, EphA2 siRNA, QLC intervention, QLC + HIF-1α siRNA, QLC + VEGF-α siRNA, and QLC + EphA2 siRNA. The expressions of the HIF-1α, VEGF-α and EphA2 proteins in the pathway of VEGF were determined by Western blot.</p><p><b>RESULTS</b>Compared with the blank control group, the expression of HIF-1α was evidently decreased in the HIF-lα siRNA and QLC + HIF-lα siRNA groups (0.624 7 ± 0.042 8 vs 0.032 8 ± 0.002 5 and 0.036 8 ± 0.018 1, P < 0.05), so were that of VEGF-α in the VEGF-α siRNA and QLC + VEGF-α siRNA groups (0.068 9 ± 0.005 1 vs 0.016 9 ± 0.000 7 and 0.010 9 ± 0.000 8, P < 0.05), that of EphA2 in the EphA2 siRNA and QLC + EphA2 siRNA groups though with no statistically significant difference (0.1684 ± 0.0126 vs 0.134 5 ± 0.028 6 and 0.165 4 ± 0.039 8, P > 0.05), and that of MMP-1 in the HIF-lα siRNA, VEGF-α siRNA and EphA2 siRNA groups (1.696 1 ± 0.152 7 vs 0.435 9 ± 0.036 9, 0.198 7 ± 0.009 0 and 0.0218 ± 0.000 7, P < 0.05).</p><p><b>CONCLUSIONS</b>Qilan Capsules can suppress VM formation in prostate cancer by inhibiting the expressions of HIF-1α, VEGF-α and MMP-1, which plays a role in the clinical treatment of prostate cancer by checking the growth and development of the blood supply system in the tumor tissue.</p>

Qilan Capsules plus androgen-deprivation therapy for Qi-deficiency blood-stasis type of prostate cancer after castration / 中华男科学杂志

Objective@#To observe the synergistic effect of Qilan Capsules in the treatment of the patient with Qi-deficiency blood-stasis type of prostate cancer receiving androgen-deprivation therapy after castration.@*METHODS@#This randomized controlled double-blind study included 246 cases of Qi-deficiency blood-stasis type of prostate cancer after castration, which were randomly divided into an experiment and a control group of equal number to be treated with Qilan Capsules + androgen-deprivation and placebo + androgen-deprivation, respectively. After 6 months of treatment, we compared the International Prostate Symptoms Scores (IPSS), TCM Symptoms Scores (TCMSS), maximal urine flow rate (Qmax), and the level of serum prostate-specific antigen (PSA) between the two groups of patients.@*RESULTS@#Statistically significant differences were observed between the experiment and control groups in the syndrome classification-based efficacy (87.7% vs 67.9%, P 0.05).@*CONCLUSIONS@#Qilan Capsules can significantly enhance the effect of androgen-deprivation therapy in the treatment of Qi-deficiency blood-stasis type of prostate cancer after castration though cannot obviously improve the PSA level.

A study on the association of AGTR1 promoter methylation and essential hypertension / 预防医学

Objective The purpose of this study was to investigate the association of AGTR1 promoter methylation with the risk of essential hypertension (EH),and to explore whether the methylation levels of AGTR1 were influenced by antihypertensive drug therapy.Methods In the current case-control study,with community population-based multi-stage sampling method,a total of 288 individuals including 96 controls,96 gender-and age-matched incidence essential hypertension(In-EH) patients and 96 gender-and age-matched prevalent essential hypertension(Pre-EH) patients were recruited from Han Chinese families in Ningbo City.The baseline data,blood samples and serum biochemical indexes of participants were obtained through questionnaire,conventional check-up and laboratory detection.Methylation levels of CpGdinucleotides in genepromoter of AGTR1 were measured using bisulfite pyrosequencing.Conditional logistic regression was used to adjust for confounding factors,and find the CpG sites which were sensitive to EH and drug.Results Body mass index,triglycerides,fasting blood glucose,high-density lipoprotein and uric acid among the three groups were significantly different (P ＜ 0.05).Conditional logistic regression showed that methylation of CpG1 was significantly lower in both In-EH and Pre-EH than in controls (Controls vs.In-EH):9.66 ± 5.45 vs.6.74 ± 4.32,OR =0.888,95 ％ CI:0.792-0.995;(Controls vs.Pre-EH):9.66 ± 5.45 vs.4.99 ± 3.97,OR =0.454,95 ％ CI:0.226-0.913.No significant result was observed between In-EH and Pre-EH (P ＞ 0.05).Conclusion Hypomethylation of CpG1 in AGTR1 gene is a risk factor for EH.However,no effect of antihyptensive drug therapy on the changes of DNA methylation levels in AGTR1 was found.

A study on the application of povidone - iodine diluent in intraoperative nursing of cervical cancer surgery / 预防医学

Objective To investigate the effect of povidone - iodine diluent on proliferation and apoptosis of cervical cancer cell HeLa and to provide the theoretical basis for its clinical application. Methods Human cervical cancer cell line HeLa in logarithmic growth phase were treated with different dilutions of povidone - iodine and the cells treated with physiological saline were set as the control group. The cells viability,morphological change,formation of apoptotic bodies,cell apoptosis and the apoptosis - related protein expression in HeLa cells were assessed by MTT assay,Hoechst33342 staining, AnnexinV / PI flow cytometry and Western blotting. Results Povidone - iodine diluent remarkably inhibited human cervical cancer cell line HeLa growth in a concentration - dependent manner. The inhibitory rates of HeLa cells were 25. 3% , 30. 8% ,33. 4% ,60. 3% ,71. 2% ,85. 3% ,89. 1% and 91. 2% when the concentration of povidone - iodine solution were 0. 001% ,0. 005% ,0. 01% ,0. 05% ,0. 1% ,0. 5% ,1% and 2% ,respectively. The nuclear chromatin of HeLa cells treated with povidone - iodine dilution was agglutinated and contracted,and the nucleus was fragile and appeared apoptotic body,with dense and dense stain or fragment dense staining. With the increase of the concentration of povidone -iodine dilution,the apoptotic rate of HeLa cells increased,so were Caspase - 8 ,Caspase - 3 and cleaved PARP. Conclusion Diluted povidone - iodine can strongly inhibit the proliferation of human cervical cancer cell line HeLa and the possible mechanism was the promotion of apoptosis.

Marsdeniae tenacissimae extract (MTE) suppresses cell proliferation by attenuating VEGF/VEGFR2 interactions and promotes apoptosis through regulating PKC pathway in human umbilical vein endothelial cells / 中国天然药物

Marsdeniae tenacissimae extract (MTE), commonly known as Xiao-Ai-Ping in China, is a traditional Chinese herb medicine capable of inhibiting proliferation and metastasis and boosting apoptosis in various cancer cells. However, little is known about the contribution of MTE towards tumor angiogenesis and the underlying mechanism. The present study aimed to evaluate the effects of MTE on the proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) and the molecular mechanism. 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium, inner salt (MTS) and PI-stained flow cytometry assays revealed that MTE dose-dependently reduced the proliferation of HUVECs by arresting cell cycle at S phase (P < 0.05). Annexin V-FITC/PI-stained flow cytometry confirmed that MTE (160 μL·L) enhanced the apoptosis of HUVECs significantly (P < 0.001). Real-time quantitative RT-PCR and Western blot analyses showed an increase in Bax expression and a sharply decline in Bcl-2 expression; caspase-3 was activated simultaneously in a dose-dependent manner (P < 0.05). Further study observed the dose-dependent down-regulation of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2), P2Y6 receptor (P2Y6R), and chemokine (C-C motif) ligand 2 (CCL-2), along with the activation of PKC Δ and up-regulation of p53 in a dose-dependent manner in MTE-treated selected cells (P < 0.05). Collectively, the results from the present study suggested that MTE suppressed the proliferation by attenuating CCL-2-mediated VEGF/VEGFR2 interactions and promoted the apoptosis through PKCΔ-induced p53-dependent mitochondrial pathway in HUVECs, supporting that MTE may be developed as a potent anti-cancer medicine.

The application of color Doppler flow imaging in the diagnosis and therapeutic effect evaluation of erectile dysfunction / 亚洲男科学杂志(英文版)

We aim to investigate the correlations between hemodynamic parameters, penile rigidity grading, and the therapeutic effects of phosphodiesterase type 5 inhibitors using color Doppler flow imaging after intracavernosal injection in patients with erectile dysfunction. This study involved 164 patients. After intracavernosal injection with a mixture of papaverine (60 mg), prostaglandin E 1 (10 mg), and lidocaine (2%, 0.5-1 ml), the penile vessels were assessed using color Doppler flow imaging. Penile rigidity was classified based on the Erection Hardness Score system as Grades 4, 3, 2 or 1 (corresponding to Schramek Grades V to II). Then, the patients were given oral sildenafil (50-100 mg) and scored according to the International Index of Erectile Function (IIEF-5) questionnaire. The number of patients with penile rigidities of Schramek Grades II to V was 14, 18, 21, and 111, respectively. The IIEF-5 score was positively correlated with the refilling index of the penile cavernosal artery (r = 0.79, P< 0.05), the peak systolic velocity (r = 0.45, P< 0.05), and penile rigidity (r = 0.75, P< 0.05), and was negatively correlated with the end diastolic velocity (r = -0.74, P< 0.05). For patients with erectile dysfunction, both the IIEF-5 score after sildenafil administration, which is correlated with penile rigidity, and the hemodynamic parameters detected using color Doppler flow imaging may predict the effects of phosphodiesterase type 5 inhibitor treatment and could provide a reasonable model for the targeted-treatment of erectile dysfunction.

Analgesic and Sedative Effect of Acupuncture Combined with Medicine on Patients Undergiong Cardiac Surgery / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe analgesic and sedative effect of acupuncture combined with medicine (ACM) on patients undergiong cardiac surgery.</p><p><b>METHODS</b>A total of 50 patients with cardiac surgery from January 2012 to October 2014 were randomly assigned to the conventional analgesia group (group A) and the ACM analgesia group (group B), 25 in each group. Patients in group A were subjected to analgesia and sedation by injecting dexmedetomidine, while patients in group B were subjected to analgesia and sedation by electro-acupuncture [EA, Shenting (GV24); Yintang (EX-HN3)] combined with injection of dexmedetomidine. Morphine hydrochloride injection was performed when analgesia and sedation effect was ineffective in the two groups. The indicators of patients at different time points in the two groups were observed, such as static and dynamic VAS scores, SAS scores, mean arterial pressure (MAP), heart rate (HR), oxygen saturation (SpO2). The injection dosage of dexmedetomidine and morphine hydrochloride, analgesia satisfaction rate, sedation satisfaction rate, the incidences of adverse reactions during treatment such as bradycardia and low blood pressure, mechanical ventilation time, ICU time, and hospitalization expense were observed and recorded in the two groups.</p><p><b>RESULTS</b>There was no statistical difference in static and dynamic VAS scores, SAS score, MAP, HR and SpO2 between the two groups at different time points (P > 0.05). The injection dosage of dexmedetomidine and morphine hydrochloride was significantly reduced in group B than in group A (P < 0.05). The analgesia satisfaction rate of patients in group B was much higher than that in group A (P < 0.05). The incidence of bradycardia also obviously decreased more in group B than in group A (P < 0.05). There was no statistical difference in patients' sedation satisfaction rate, incidences of low blood pressure, delirium, vomiting; mechanical ventilation time, ICU time, or hospitalization expense between the two groups (P > 0.05).</p><p><b>CONCLUSION</b>The analgesia method of ACM could reduce the dosage of traditional analgesic drugs and the occurrence of partial adverse reactions.</p>

Qilin Pills for obstructive azoospermia after ejaculatory duct reconstruction / 中华男科学杂志

<p><b>Objective</b>To observe the clinical effect of Qilin Pills in the treatment of severe oligozoospermia after microsurgical ejaculatory duct reconstruction for obstructive azoospermia.</p><p><b>METHODS</b>We retrospectively analyzed 75 cases of obstructive azoospermia treated by ejaculatory duct reconstruction followed by administration of Qilin Pills. The patients were divided into a Qilin group (n=42) and a control group (n=33) postoperatively, treated with Qilin Pills and placebo, respectively. After 3 months of medication, we compared the sperm quality between the two groups of patients.</p><p><b>RESULTS</b>After 3 months' treatment, all the patients experienced remarkable improvement in sperm quality (P<0.05). Compared with the controls, the patients in the Qilin group showed dramatic increases in sperm concentration, from (0.57±0.25) and (0.60±0.18) ×10⁶/ml before medication to (2.83±0.59) and (1.72 ±0.52) ×10⁶/ml after medication, significantly higher in the Qilin than in the control group (P<0.05). The percentage of grade a sperm was increased from (5.52±5.97) and (5.30±6.26)% to (11.56±9.96) and (10.27±6.52)%, that of grade a+b sperm from (9.68±8.63) and (8.64±10.10)% to (23.42 ±14.10) and (20.81±14.70)%, and that of morphologically normal sperm from (2.00±1.27) and (2.31±0.94)% to (3.54±2.47) and (3.47±1.33)%, respectively. No statistically significant differences were observed in sperm motility and normal sperm morphology between the two groups after treatment (P>0.05). The total effectiveness rate was higher in the Qilin group than in the controls (88.1% vs 72.7%), but with no significant difference between the two groups (P>0.05).</p><p><b>CONCLUSIONS</b>Qilin Pills are fairly effective in improving the quantity of sperm in obstructive azoospermia patients after ejaculatory duct reconstruction.</p>

Receptor expression and responsiveness of human peripheral blood mononuclear cells to a human cytomegalovirus encoded CC chemokine

Human cytomegalovirus is a ubiquitous pathogen that infects the majority of the world's population. After long period of time co-evolving with human being, this pathogen has developed several strategies to evade host immune surveillance. One of the major trick is encoding homologous to those of the host organism or stealing host cellular genes that have significant functions in immune system. To date, we have found several viral immune analogous which include G protein coupled receptor, class I major histocompatibility complex and chemokine. Chemokine is a small group of molecules which is defined by the presence of four cysteines in highly conserved region. The four kinds of chemokines (C, CC, CXC, and CX3C) are classified based on the arrangement of 1 or 2 N-terminal cysteine residues. UL128 protein is one of the analogous that encoded by human cytomegalovirus that has similar amino acid sequences to the human CC chemokine. It has been proved to be one of the essential particles that involved in human cytomegalovirus entry into epithelial/endothelial cells as well as macrophages. It is also the target of potent neutralizing antibodies in human cytomegalovirus-seropositive individuals. We had demonstrated the chemotactic trait of UL128 protein in our previous study. Recombinant UL128 in vitrohas the ability to attract monocytes to the infection region and enhances peripheral blood mononuclear cell proliferation by activating the MAPK/ERK signaling pathway. However, the way that this viral encoded chemokine interacting with peripheral blood mononuclear cells and the detailed mechanism that involving the virus entry into host cells keeps unknown. Here we performed in vitroinvestigation into the effects of UL128 protein on peripheral blood mononuclear cell's activation and receptor binding, which may help us further understand the immunomodulatory function of UL128 protein as well as human cytomegalovirus diffusion mechanism.

A study on the mechanism of Gal - 1 promote gastric cancer cell migration and invasion by up - regulating MMP - 9 / 预防医学

Objective To explore the possible mechanisms of Galectin - 1(Gal - 1)protein in promoting the invasion and migration of gastric cancer cells. Methods After treated with different concentrations(0,1,5 μg/ mL)of Gal - 1 protein, the Trans - well model was used to analyze the invasion and migration ability of gastric cancer. WB and gelatin zymography method were used to detect the MMP - 9 expression and active form change in gastric cancer cells after Gal - 1 stimulate, in order to explore the possible molecular mechanisms of Gal - 1 protein in promoting the invasion and migration of gastric cancer cells. Results In cell migration assay,the number of gastric cancer cells BGC - 823 treated with 1and 5 μg/ mL Gal - 1 stimulate were 117 ± 8. 19 and 167 ± 7. 55,higher than that treated with 0 μg/ mL(P < 0. 05). The number of gastric cancer cells 7 901 treated with 1and 5 μg/ mL Gal - 1 stimulate were 151 ± 5. 13 and 190. 3 ± 6. 8,higher than that treated with 0 μg/ mL(P < 0. 05). In cell invasion assay,the number of gastric cancer cells BGC - 823 treated with 1and 5μg/ mL Gal - 1 stimulate were 51 ± 3. 6 and 76. 7 ± 9. 07,higher than that treated with 0 μg/ mL(P < 0. 05). The number of gastric cancer cells 7 901 treated with 1and 5 μg/ mL Gal - 1 stimulate were 74. 0 ± 7. 21 and 105. 3 ± 11. 37,higher than that treated with 0 μg/ mL(P < 0. 05). The migration and invasion level were significantly increased in gastric cancer cells after Gal - 1 stimulate. The MMP - 9 expression level and active form change in gastric cancer cells were also increased after Gal - 1 stimulate. Conclusion Gal - 1cound significantly promote gastric cancer cell migration and invasion by up - regulated the MMP - 9 expression and active its enzyme activity.