Mechanism and experimental verification of "Polygoni Cuspidati Rhizoma et Radix-Ligustri Lucidi Fructus" combination in treatment of acute gouty arthritis based on network pharmacology / 中国中药杂志

Based on network pharmacology, the mechanism of Polygoni Cuspidati Rhizoma et Radix-Ligustri Lucidi Fructus(PL) combination against acute gouty arthritis(AGA) was explored and preliminarily verified by animal experiment. The chemical components and corresponding targets of PL were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The active components with oral bioavailability(OB)≥30% and drug-likeness(DL)≥0.18 were screened based on literature, and the related protein targets were collected. Then the protein targets were standardized with the help of UniProt database. The AGA-related targets were searched from GeneCards, NCBI, and DrugBank. The common targets of the disease and the medicinals were yielded by FunRich V3, and the protein-protein interaction(PPI) network was constructed to screen the key targets, followed by Gene Ontology(GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the key targets. Afterwards, some of the key targets were verified by sodium urate crystal-induced AGA mouse model. A total of 25 active components and 287 targets of PL, 811 targets of AGA, and 88 common targets were screened out. PPI network analysis showed that tumor necrosis factor(TNF), interleukin-6(IL-6), and interleukin-1β(IL-1β) may be the core targets of PL in the treatment of AGA. The key targets were mainly involved in 566 GO terms(P<0.05), including multiple biological processes such as inflammatory response and immune response. Moreover, they were related to 116 KEGG pathways and these pathways were involved in inflammation and immunity, mainly including NOD-like receptor signaling pathway and TNF signaling pathway. Animal experiment confirmed that PL can alleviate ankle swelling, improve abnormal gait, and down-regulate the protein expression of TNF-α, IL-6, and IL-1β in AGA mice, indicating that PL can treat AGA through TNF-α, IL-6, and IL-1β and the feasibility of network pharmacology to predict drug targets. This study preliminarily discussed the key targets and biological signaling pathways involved in the treatment of AGA with PL combination, which reflected the multi-pathway and multi-target action characteristics of Chinese medicine. Moreover, this study laid a scientific basis for research on the treatment of AGA with PL combination, as well as the mechanism of action.

Modified Wenjingtang Affects Caspase-8， MMP-9， N-cadherin and E-cadherin in Local Microenvironment of EM Rats with Kidney Deficiency and Blood Stasis / 中国实验方剂学杂志

Objective:To investigate the therapeutic effect and mechanism of modified Wenjingtang on endometriosis （EM） rats with kidney deficiency and blood stasis. Method:Healthy non-pregnant female Sprague-Dawley （SD） rats of SPF grade were randomly divided into the blank group and experimental group. After being modeled via soaking in ice water and subcutaneous injection of epinephrine hydrochloride， the ones in the experimental group were further divided into the sham operation group and EM model group， with the former only undergoing laparotomy and the latter further receiving autologous endometrial transplant for triggering EM. The successfully modeled rats with EM due to kidney deficiency and blood stasis were randomized into the positive drug （danazol， 63 mg·kg^-1） group and low- （5 g·kg^-1）， medium- （10 g·kg^-1）， and high-dose （20 g·kg^-1） modified Wenjingtang groups. The corresponding drugs were administered by gavage， once per day， for four weeks. Then the ectopic and eutopic endometrial tissues were stained with hematoxylin-eosin （HE） to observe the histopathological changes. The protein and mRNA expression levels of cysteinyl aspartate-specific proteinase-8 （Caspase-8）， matrix metalloproteinase-9 （MMP-9）， N-cadherin， and E-cadherin were detected by immunohistochemistry （IHC）， Western blotting， and real-time polymerase chain reaction （Real-time PCR）， respectively. Result:The IHC and Western blot revealed that the protein expression levels of MMP-9 and N-cadherin in eutopic and ectopic endometrial tissues of the model group were significantly increased as compared with those in the sham operation group （<italic>P</italic><0.01）， while the levels of Caspase-8 and E-cadherin was significantly decreased （<italic>P</italic><0.01）. Compared with the model group， the danazol and low-， medium-， and high-dose modified Wenjingtang groups exhibited obviously down-regulated MMP-9 and N-cadherin protein expression in eutopic and ectopic endometrial tissues （<italic>P</italic><0.05，<italic>P</italic><0.01）， but up-regulated Caspase-8 and E-cadherin （<italic>P</italic><0.05， <italic>P</italic><0.01）. Real-time PCR uncovered that the mRNA expression levels of MMP-9 and N-cadherin in eutopic and ectopic endometrial tissues of the model group were significantly elevated as compared with those in the sham operation group （<italic>P</italic><0.01）， whereas the levels of Caspase-8 and E-cadherin significantly declined （<italic>P</italic><0.01）. The comparison with the eutopic endometrial tissue in the model group showed that the mRNA expression levels of MMP-9 and N-cadherin in the danazol group and high- and medium-dose modified Wenjingtang groups were significantly down-regulated， while those of Caspase-8 and E-cadherin were significantly up-regulated （<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:Modified Wenjingtang alleviates the immunosuppression and blocks the angiogenesis in EM rats with kidney deficiency and blood stasis syndrome by regulating the expression of such cytokines as Caspase-8， MMP-9， N-cadherin， and E-cadherin， thus exerting the therapeutic effect against EM. The above-mentioned micro-indicators are potential markers reflecting the disease （EM）， syndrome （kidney deficiency and blood stasis）， and pathological mechanisms （immunosuppression and angiogenesis）.

Inhibition of Proliferation of Prostate Cancer Cell Line DU-145 in vitro and in vivo Using Salvia miltiorrhiza Bunge / 中国结合医学杂志

OBJECTIVE@#To investigate the antiproliferative activity of Salvia miltiorrhiza Bunge. (SM) on the castration-resistant prostate cancer (CRPC) cell line DU-145, in vitro and in vivo.@*METHODS@#Prostate cancer cell line (DU-145) and normal prostate cell line (RWPE-1) were treated with SM at different concentrations (3.125, 12.5, 25 and 50 μg/mL) to investigate the antiproliferative effects. DNA laddering analysis was performed to investigate the apoptosis of DU-145 cells. Molecular mechanism was investigated by Western blot analysis of p53, Bcl-2, prostate specific antigen (PSA), and androgen receptor (AR). Six-week-old male BALB/c nude mice were randomly divided into normal control group (n=101) and treated group (n=101) which administered 500 mg/kg SM for 2 weeks. Tumor volumes were measured.@*RESULTS@#Treatment with SM resulted in a dose-dependent decrease in cell number of DU-145 cells in comparison with RWPE-1. DNA laddering analysis indicated the apoptosis of DU-145 cells. Treatment with SM increased the expression of p53 and reduced the expression of Bcl-2 proteins. The levels of PSA were considerably reduced in SM-treated group compared to the controls, and a decrease in AR expression was observed when cells were treated with SM in the same pattern as a reduction in PSA. In the tumour xenograft study, SM given once a day for 2 weeks significantly inhibited tumour growth.@*CONCLUSION@#SM might contribute to the anticancer actions such as induction of apoptosis and inhibition of proliferation of prostate cancer cells.

Research Trends of Macrophage Polarization: A Bibliometric Analysis / 中华医学杂志(英文版)

Background@#Macrophage polarization is involved in the development of many diseases such as obesity, diabetes, and cancer. This study aimed to understand the trends and hotspots of macrophage polarization research.@*Methods@#We searched through the Web of Science Core Collection database to obtain original articles in this research domain. CiteSpace, HistCite, and VOSviewer software were used to facilitate the analysis and visualization of scientific productivity and emerging trends.@*Results@#The survey included 3064 articles, and the annual number of publications exhibited an exponential increase. These articles have received a total of 74,801 citations, and the number of annual citations grew from 68 to 18,074 in a decade. Research on macrophage polarization was performed in 76 countries, and the USA ranked first in terms of research output by contributing 1129 (36.8%) articles. The USA also had the highest H-index, total citations, and highly cited article number. PLOS One, Journal of Immunology, and Scientific Reports were the three journals that published the most articles. Interdisciplinary research areas involving macrophage polarization, such as biomaterials, cancer, and diabetes, were identified by journal citation analysis. The top 20 most productive institutions were located mainly in the USA, France, and China, and top authors originated mainly from the USA and Italy. Tumor biology, obesity, and infection were research hotspots and may be promising in the next few years.@*Conclusions@#This study provides a comprehensive analysis that delineates the scientific productivity, collaboration, and research hotspots of macrophage polarization research.

Clinical Application of Immediate Implant Placement of Zimmer Dental Implant System in the Mandibular Posterior Region / 中山大学学报(医学科学版)

[Objectives]To observe the clinical effects of the immediate implant placement of Zimmer dental implant sys-tem in the mandibular posterior region.[Methods]67 cases with a total of 89 mandible posterior teeth to deal with immediate implantion which selected to be treated with Zimmer dental implant system.76 teeth between implant and tooth socket bone wall were simultaneously filled with Bio-oss Collagen.The upper structure was repaired with PFM porcelain crown after the postoperative phase I of 3~6 months.All the patients were followed up for 6~24 months.[Results]During the clinical follow up,the implant survival rate was 100%. In 67 patients,89 implants was successfully loaded,with stable implants,good condition in synosteosis and without adverse subjective symptoms. All of the 67 patients had achieved good synosteosis and success loads clinically and radiologically.[Conclusion]A good osseointegration is obtained in the mandibular posterior re-gion with Zimmer dental implant system,Correctly dealing with Bio-oss Collagen between implant and tooth socket bone wall.At the same time,it can shorten the time of therapy,simplify the procedure,so that the clinical results are more satis-factory.

Determination of six constituents in Shiyifang Vinum by HPLC / 中成药

AIM To establish an HPLC method for the content determination of six constituents in Shiyifang Vinum (Notoginseng Radix et Rhizoma,Dipsaci Radix,Carthami Flos,etc.).METHODS The content determination of notoginsenoside R1,ginsenoside Rg1,ginsenoside Rb1 and asperosaponin Ⅵ was performed on a 30℃ thermostatic Inertsil(R) ODS-3 C18column (4.6 mm ×250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1％ phosphoric acid flowing at 1.0 mL/min in a gradient manner,and the detection wavelength was set at 203 nm.The content determination of brucine and strychnine was conducted on a 30 ℃ thermostatic Geminni(R) C18 110(A) column (4.6 mm × 250 mm,5 μm),with the mobile phase comprising of acetonitrile-mixed solution of 0.01 mol/L sodium heptanesulfonate and 0.02 mol/L potassium dihydrogen phosphate flowing at 1.0 mL/min in an isocratic elution manner,and the detection wavelength was set at 260 nm.RESULTS Six constituents showed good linear relationships within their own ranges (r ＞ 0.999 0),whose average recoveries were 98.52％-99.96％ with the RSDs of 2.0％-2.3％.CONCLUSION This simple,accurate and reproducible method can be used for the quality control of Shiyifang Vinum.

Preparation of Site-specific Smart Nanocomposites for Drug Delivery and Study on Light-Controlled Cytarabine Release Performance / 中国药学杂志

OBJECTIVE: To prepare smart & site-specific drug carrier for controlled release purpose and study the bio-compatibilities and release performance.METHODS: By using high pressure thermo-heat method in autoclave, superparamagnetic core was obtained and further coated by SiO2 and MCM-41, therefore the “core-shell” structure was formed. To make the carrier “smart” and thus responsive to stimuli which was light in this research, the tunnels of the molecular sieve were grafted with gating molecules, 4,5-diazafluoren-9-one (indicated in the paper as DAFO). For bio-compatibilities testing, MTT in-vitro experiment was conducted. Cytarabine was used as test drug to preliminarily evaluate the controlled release performance of the drug carrier in vitro.RESULTS: The Fe3O4 nano-particles synthesized via high-pressure hydro-thermo procedure exhibited superparamagnetic with mean diameter of 280 nm. After SiO2 & molecular sieve coating steps and ligand grafting steps, the particles grew to 540 nm. The sub-structure of the carrier was confirmed by scanning/transmission electron microscope(SEM & TEM) and nitrogen adsorption/desorption. Our “smart” carrier was able to be guided to the sites or organs with magnetic field and more importantly it was able to unload drug molecules under 510 nm light irritation that could flip the gating-molecule. Furthermore, the drug carrier illustrated bio-compatibility and showed obvious cytotoxicity.CONCLUSION: The novel nanocomposites developed in this study can be used as targeted drug carrier.

Synovial chondromatosis in the temporomandibular joint: analysis of 5 cases / 南方医科大学学报

Five patients with synovial chondromatosis in the temporomandibular joint were treated in our hospital between August, 2011 and August, 2014. All the patients underwent preoperative imaging examinations for clinical diagnosis and determining the involvement of the lesions. Surgeries were performed and the lesions were confirmed as synovial chondromatosis by pathological diagnosis. The clinical manifestations, imaging features, diagnosis and treatment results were analyzed. All the 5 patients had pain in the joint region, 3 had limited mouth opening, and 3 had swelling in the joint region. X-ray film showed widening of the joint space in all the 5 cases and radiographic findings showed space-occupying lesions in the intra-articular space. Open joint surgeries was performed and completed successfully in all the cases. The postoperative imaging showed no residual lesions in the surgical area. As a rare clinical entity, synovial chondromatosis in the temporomandibular joint was poorly documented without specific clinical manifestations. The diagnosis of synovial chondromatosis relies on imaging, arthroscopic and pathological findings. Corpus liberum is an important feature of the disease occurring frequently in the joint cavity. Surgical intervention is the primary choice for treatment of synovial chondromatosis in the temporomandibular joint, in which the corpus liberum and the affected synovial membrane shall be removed after joint incision.

Effect of macrophage inflammatory protein-1β on proliferation and apoptosis of human tongue squamous cell carcinoma CAL-27 cells in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To detect CCR5 protein expression in different human tongue squamous cell carcinoma cells and observe the effect of macrophage inflammatory protein-1β (MIP-1β) on the proliferation and apoptosis of CAL-27 cells.</p><p><b>METHODS</b>Western blotting and immunofluorescence staining were used to detect the expression of the CCR5, the receptor of MIP-1β, in 3 human tongue squamous cell carcinoma cells UM-1, CAL-27, and Tca-8113. CCK-8 assay was used to assess the proliferation of CAL-27 cells stimulated with 10, 20, and 40 ng/mL MIP-1β for 12, 24, or 48 h. The apoptosis of the cells stimulated with MIP-1β (10, 20, and 40 ng/mL) for 24 h was analyzed using flow cytometry with Annexin V/PI double staining.</p><p><b>RESULTS</b>CCR5 expression was detected both on the membrane and in the cytoplasm in all the 3 tongue squamous cell carcinoma cell lines. At the concentrations of 10, 20, and 40 ng/mL, MIP-1β stimulation for 12 and 24 h significantly promoted the proliferation of CAL-27 cells (P<0.05); MIP-1β stimulation for 48 h at the concentrations 10 and 20 ng/mL, but not at 40 ng/mL, promoted the proliferation of CAL-27 cells (P<0.05). MIP-1β stimulation at 40 ng/mL for 24 produced the most obvious apoptosis-inducing effect in CAL -27 cells (P<0.05), while MIP-1β at 10 or 20 ng/mL did not induce obvious apoptosis in the cells (P>0.05).</p><p><b>CONCLUSION</b>CCR5 is expressed in all the 3 human tongue squamous cell carcinoma cells. MIP-1β can promote the proliferation of CAL-27 cells but high concentrations of MIP-1β also induced cell apoptosis. Prolonged stimulation of the cells with a high concentration of MIP-1β shows attenuated effect in promoting cell proliferation probably as a result of cell apoptosis induced by MIP-1β.</p>

Risk Factors for the Rupture of Bifurcation Intracranial Aneurysms Using CT Angiography

PURPOSE: To investigate the clinical and morphological characteristics in relation to risk of bifurcation intracranial aneurysm rupture. MATERIALS AND METHODS: Data from 202 consecutive patients with 219 bifurcation aneurysms (129 ruptured and 90 unruptured) managed at the authors' facility between August 2011 and July 2014 were retrospectively reviewed. Based on their clinical records and CT angiographic findings, the ability of risk factors to predict aneurysm rupture was assessed using statistical methods. RESULTS: Age, hypertension, diabetes mellitus, and cerebral atherosclerosis were negatively correlated with aneurysm rupture. Aneurysms located in the middle cerebral artery, daughter artery ratio, lateral angle ratio (LA ratio), and neck width were negatively correlated with rupture. Aneurysms located in the anterior communicating artery, irregularity, with daughter sac, depth, width, maximum size, aspect ratio (AR), depth-to-width ratio, and bottleneck factor were significantly and positively correlated with rupture. Binary logistic regression model revealed that irregular shape [odds ratio (OR) 6.598] and AR (OR 3.507) strongly increased the risk of bifurcation aneurysm rupture, while age (OR 0.434), cerebral atherosclerosis (OR 0.125), neck width (OR 0.771), and LA ratio (OR 0.267) were negatively correlated with rupture (p<0.05). Receiver operating characteristic analysis revealed the threshold values of AR and LA ratio to be 1.18 and 1.50, respectively. CONCLUSION: Age (≥60 yr), cerebral atherosclerosis, and aneurysms with a larger neck width and larger LA ratio are protective factors against bifurcation aneurysm rupture. An aneurysm with an irregular shape and an increased AR reflect the greater likelihood of a rupture.

Preparation of lyophilized powder of oral Pueraria flavonoids nanosuspension and determination of dissolution rates of its four effective components / 中草药

Objective: To prepare the lyophilized powder of Pueraria flavonoids nanosuspension (PF-NS) and to determine the dissolution rates of its four effective components (3'-hydroxypuerarin, puerarin, daidzin, and daidzein). Methods: PF-NS was prepared by the high pressure homogenization (HPH) technology. The lyophilized formula contained mannitol as lyoprotectant. The dissolution rates of the four effective components from lyophilized powder of PF-NS as well as the physical mixture were determined, with artificial gastric juice (pH 1.2) as dissolvent. Results: The optimal lyophilized powder of PF-NS was loosed with the particle size of (479.7 ± 14.7) nm, polydisperse index of 0.524 ± 0.220, and Zeta potential of (29.68 ± 3.97) mV, respectively. The in vitro accumulated dissolution rate of lyophilized powder of PF-NS was higher than that of the physical mixture. Conclusion: The method employed to prepare the lyophilized powder in PF-NS is simple and feasible. The lyophilized powder of PF-NS could improve the in vitro dissolution rate notablely. It might be a novel vehicle potentially for nano-drug delivery system of PF.

Microbial transformation of ursolic acid by Penicillium adametzi / 中草药

Objective: To study the microbial transformation of ursolic acid by Penicillium adametzi. Methods: The biotransformed extract was obtained by co-culture of substrate (ursolic acid) and the transferring fungi in a liquid medium at certain conditions, and then the inocula were dealt in an ultrasonic bath and extracted with n-BuOH. The transformed extract was isolated by chromatography on macroporous resin column, silica gel column, and preparative HPLC. The structures of the isolated compounds were identified by spectral analyses, physical constants, and chemical evidences. Results: A microbial transformed product was isolated and identified as 3β, 21α-dihydroxyl-ursolic acid-28-O-β-D-glucopyranoside and it had the significant inhibitory effects against HepG2 cell with IC50 value of 19.72 μmol. Conclusion: The transformed product, 3β, 21α-dihydroxyl-ursolic acid-28-O-β-D-glucopyranoside, is a new compound with the stronger cytotoxic activity than that of substrate.

Genes associated with hypospadias: an update / 中华男科学杂志

Hypospadias is one of the most common congenital malformations, and its main clinical manifestation is the abnormal opening of the urethra. Etiologically, it can be attributed to many factors, mainly including genetic, hormonal, and environmental factors. Recently studies about its genetic etiologies have found a variety of hypospadias-associated genes from the aspects of epidemiology and polymorphism, mainly those involving the formation of the penis, the development of the testis, the anabolism of androgens, and so on. This review focuses on the progress in the studies on the genetic etiology of hypospadias.

Extracorporeal shock wave therapy for chronic pelvic pain syndrome: an update / 中华男科学杂志

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disease in males, which is characterized by persistent discomfort or pain in the pelvic region. As currently used drug therapies fail to produce satisfactory results, it is an urgent task to find new and effective methods for the treatment of CP/CPPS. In recent years, many reports are seen on the extracorporeal shock wave therapy (ESWT) for CP/CPPS. ESWT can significantly improve the symptoms of pelvic pain and urination disorders in CPPS patients, and its therapeutic effect is attributed to the improvement of angiogenesis and block of pain nerves.

Shang Ring circumcision versus conventional circumcision for redundant prepuce or phimosis: a meta analysis / 中华男科学杂志

<p><b>OBJECTIVE</b>To compare the effect and safety of Shang Ring circumcision with those of conventional circumcision in the treatment of redundant prepuce or phimosis.</p><p><b>METHODS</b>We retrieved the randomized controlled trials on Shang Ring circumcision and conventional circumcision for the treatment of redundant prepuce or phimosis published at home and abroad. Relevant data were selected according to the Cochrane Handbook for Systematic Reviews by two reviewers after quality evaluation of the included trials, and the statistical software RevMan 5.0 was used for meta analysis.</p><p><b>RESULTS</b>Totally 8 randomized controlled trials with 2277 cases were included in this study. Compared with conventional circumcision, Shang Ring circumcision showed a shorter operation time (SMD = -5.82, 95% CI [ -7.39, -4.24], P<0.00001), less intraoperative blood loss (SMD = -3.28, 95% CI [ -3.47, -3.09], P<0.00001), lower rate of infection (OR = 0.44, 95% CI [0.26, 0.72], P=0.001), lower rate of postoperative bleeding (OR =0.05, 95% CI [0.02, 0.12], P<0.00001), higher rate of satisfaction with the postoperative penile appearance (OR=12.72, 95% CI [1.30, 124.56], P=0.03), lower intraoperative pain score (SMD = -3.32, 95% CI [ -3.50, -3.14], P<0.00001), and lower 24-hour-postoperative pain score (SMD = -3.28, 95% CI [ - 3.47, - 3.00], P<0.00001), but longer wound healing time (OR=1.46, 95% CI [1.03, 1.90], P<0.00001).</p><p><b>CONCLUSION</b>In comparison with conventional circumcision, Shang Ring circumcision has the advantages of shorter operation time, fewer complications, mild pain, and higher rate of satisfaction with the postoperative penile appearance. However, more high-quality randomized controlled trials with large samples are required to lend further support to our findings.</p>

Involvement of the mitochondrion-dependent and the endoplasmic reticulum stress-signaling pathways in isoliquiritigenin-induced apoptosis of HeLa cell / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Isoliquiritigenin (ISL), a licorice chalconoid, is considered to be a bioactive agent with chemopreventive potential. This study investigates the mechanisms involved in ISL-induced apoptosis in human cervical carcinoma HeLa cells.</p><p><b>METHODS</b>Cell viability was evaluated using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Apoptosis was determined by flow cytometry using an Annexin V-FITC Apoptosis Detection Kit. The intracellular ROS levels were assessed using a 2, 7-dichlorofluorescein probe assay. The mitochondrial membrane potential was measured with the dual-emission potential-sensitive probe 5, 5', 6, 6'-tetra-chloro-1, 1', 3, 3'-tetraethyl-imidacarbocyanine iodide (JC-1). The degradation of poly-ADP-ribose polymerase (PARP) protein, the phosphorylation of PKR-like ER kinase (PERK), the phosphorylation of the α-subunit of eukaryotic initiation factor 2 (eIF2α), the expression of the 78 kD glucose-regulated protein (GRP 78), and the activation of caspase-12 were analyzed via western blot analysis.</p><p><b>RESULTS</b>ISL significantly inhibited the proliferation, the increase in ROS levels and apoptotic rates of HeLa cells in a concentration-dependent manner. Moreover, ISL induced mitochondrial dysfunction, caspase activation, and PARP cleavage, which displayed features of mitochondria dependent on apoptotic signals. Besides, exposure of HeLa cells to ISL triggered endoplasmic reticulum (ER) stress, as indicated by the increase in p-eIF2α and GRP78 expression, ER stress-dependent apoptosis is caused by the activation of ER-specific caspase-12.</p><p><b>CONCLUSION</b>The findings from our study suggest that ISL-induced oxidative stress causes HeLa cell apoptosis via the mitochondrion-dependent and the ER stress-triggered signaling pathways.</p>

Effect of carbon disulfide exposure during peri-implantation period on levels of calcitonin and progesterone in uterus of mice / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To evaluate the effect of carbon disulfide (CS2) exposure during the peri-implantation period on the levels of calcitonin (CT) and progesterone (P4) in the uterus of pregnant mice and to investigate the mechanism of embryo loss induced by CS2 exposure during the peri-implantation period.</p><p><b>METHODS</b>A total of 168 healthy pregnant Kunming mice were randomly assigned to receive an intraperitoneal injection of CS2 (631.4 mg/kg) or olive oil (control) on gestational day (GD) 3, GD4, GD5, or GD6. The experiment was completed at different end points (GD4, GD5, GD6, GD7, and GD9). The levels of CT and P4 in the uterus were measured by enzyme-linked immunosorbent assay at each end point.</p><p><b>RESULTS</b>The numbers of implanted embryos in GD3, GD4, GD5, and GD6 exposure groups significantly decreased by 42.85%, 63.74%, 60.45%, and 47.26%, respectively,compared with those in control group (P < 0.01). The GD3, GD4, GD5, and GD6 exposure groups had significantly decreased CT levels at each end point (P < 0.05), and the GD3, GD4, and GD5 exposure groups had significantly decreased P4 levels (P < 0.05). In the GD3, GD4, GD5, and GD6 exposure groups, the number of implanted embryos was positively related with the levels of CT and P4 expressed in the uterus (r = 0.670, P < 0.01; r = 0.632, P < 0.01); the expression level of CT was positively related with that of P4 in the uterus of pregnant mice (r = 0.325, P < 0.01).</p><p><b>CONCLUSION</b>Exposure to CS2 during the peri-implantation period can reduce the expression levels of CT and P4 in the uterus of pregnant mice, which might be one of the molecular mechanisms of embryo loss induced by CS2 exposure.</p>

DNA damage of splenic lymphocytes in pregnant mice exposed to carbon disulfide in implantation phase / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the DNA damage of splenic lymphocytes in pregnant mice exposed to carbon disulfide (CS2) in the implantation phase and to explore the mechanism of abnormal implantation induced by CS2 from the perspective of immune injury.</p><p><b>METHODS</b>Mice were exposed to CS2 at different doses or at different time points in the implantation phase to establish model 1 and model 2. For model 1, mice were assigned to four groups to receive a single intraperitoneal injection of low-dose CS2 (0.1 LD50, 157.8 mg/kg), middle-dose CS2 (0.2 LD50, 315.7 mg/kg), and high-dose CS2 (0.4 LD50, 631.4 mg/kg) as well as an equal volume of olive oil (control) on gestational day (GD) 4. For model 2, mice were assigned to four groups to receive a single intraperitoneal injection of CS2 (0.4 LD50, 631.4 mg/kg) or an equal volume of olive oil (control) on GD3, GD4, GD5, and GD6. At the end, single cell suspension of splenic lymphocytes was prepared. Cell viability was measured by trypan blue staining, and the DNA damage of splenic lymphocytes was evaluated by alkaline single cell gel electrophoresis assay.</p><p><b>RESULTS</b>The middle-dose and high-dose exposure groups showed significantly more DNA damage of splenic lymphocytes than the control group (P < 0.01); there was significant regression relationship between indicators of DNA damage and exposure doses (P < 0.01). The GD3, GD4, GD5, and GD 6 exposure groups showed significantly more DNA damage of splenic lymphocytes than the control group (P < 0.01), and the GD 4 exposure group had the most DNA damage.</p><p><b>CONCLUSION</b>Exposure to CS2 in the implantation phase can induce DNA damage of splenic lymphocytes in pregnant mice, and the DNA damage was aggravated with the increase in CS2 concentration. GD4 may be the sensitive time point for DNA damage of splenic lymphocytes induced by CS2 in pregnant mice.</p>

Effects of carbon disulfide exposure during peri-implantation on estrogen receptor-α expression in uterus and serum level of estrogen in pregnant mice / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To evaluate the effects of carbon disulfide (CS(2)) exposure during peri-implantation on the estrogen receptor-α (ER-α) expression in the uterus and serum level of estradiol (E(2)) in pregnant mice, and to explore the mechanism of embryotoxicity of CS(2).</p><p><b>METHODS</b>Healthy female mice were exposed to a single dose of CS(2) (631.4 mg/kg) or olive oil (solvent control) on gestational day (GD)3, GD4, GD5, or GD6. At different time points after exposure, the serum E(2) levels of the pregnant mice were measured by enzyme-linked immunosorbent assay, and the expression levels of ER-α in the uterus were measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot.</p><p><b>RESULTS</b>Compared with the control group, the GD3, GD4, GD5, and GD6 exposure groups showed significantly decreased serum E(2) levels on day 7 of gestation (P < 0.05); the GD3 and GD5 exposure groups showed significantly decreased serum E(2) levels on day 6 of gestation (P < 0.05). The expression level of ER-α in the GD 4 exposure group was 23.6% lower than that in the control group on day 5 of gestation, and the expression level of ER-α in the GD 5 exposure group was 72.9% lower than that in the control group on day 6 of gestation (P < 0.05); the GD 3 and GD 6 exposure groups showed lower expression levels of ER-α than the control group at any time point, but no significant difference was found (P > 0.05).</p><p><b>CONCLUSION</b>CS(2) exposure during peri-implantation can reduce the ER-α expression in the uterus and the serum level of E(2) in pregnant mice, which may be one of the mechanisms of embryotoxicity of CS(2).</p>

Effects of opioid analgesics on sperm motility in vitro / 中华男科学杂志

<p><b>OBJECTIVE</b>To observe the effects of short-term exposure to opioid analgesics on human sperm motility.</p><p><b>METHODS</b>Twenty normal semen samples were collected, each divided into 19 groups, one as the control and the others treated in vitro with six opioid analgesics at three different concentrations, respectively, and sperm motility was assessed by computer-assisted sperm analysis at 15 min, 2 h and 4 h.</p><p><b>RESULTS</b>Compared with the control group, fentanyl, alfentanil and sufentanil at 1 x 10(-5), 2 x 10(-3) and 0.05 mg/ml significantly decreased the percentage of grade a + b sperm at 15 min, 2 h and 4 h (P<0.05), and so did butorphanol at 2 x 10(-3) and 0.05 mg/ml (P<0.05) and dezocine at 0.05 and 0.5 mg/ml (P<0.05), but neither showed any remarkable effect at 1 x 10(-5) mg/ml at the three time points (P>0.05). Pentazocine effected no significant difference at 3 x 10(-5) and 0. 05 mg/ml (P>0.05) but a gradual increase in the percentage of grade a + b sperm at 0.5 mg/ml at the three time points (P<0.05). Butorphanol totally inhibited sperm motility at 0.05 mg/ml at 15 min and at 2 x 10(-3) mg/ml at 2 h, and so did dezocine at 0.05 and 0.5 mg/ml, but such inhibitory effect was not observed with fentanil, alfentanil and sulfentanil at 0.05 mg/ml. As for the sperm motility decreasing effect at 0.05 mg/ml at 15 min, sufentanil, butorphanol and dezocine exhibited significant differences (P<0.05) while fentanyl displayed none from alfentanil (P>0.05).</p><p><b>CONCLUSION</b>Given the same length of time of treatment, butorphanol and dezocine totally inhibit sperm motility at a high concentration, but make no significant change at a low concentration. While fentanyl, alfentanil and sufentanil can significantly decrease sperm motility at the same low concentration, and partially inhibit it at all concentrations. On the contrary, a high concentration of pentazocine can promote human sperm motility.</p>