Case Report: PD-L1-negative advanced bladder cancer effectively treated with anlotinib and tislelizumab: A report of two cases.

Second-line treatment for metastatic or locally advanced urothelial cancer (UC) is limited. Immunotherapy is approved as a second-line treatment for metastatic UC. Its use as a first-line agent is limited to patients who are ineligible for cisplatin-based treatments. The fibroblast growth factor receptor (FGFR) inhibitor, erdafitinib, can be applied as a third-line approach after the failure of these prior treatments in eligible patients. Therefore, it is especially important to combine limited drugs for second-line treatment of advanced or metastatic UC. Anlotinib is a multiple tyrosine kinase inhibitor agent with both anti-angiogenic and FGFR inhibitory effects. For two patients with advanced and metastatic UC, we combined anlotinib and tislelizumab therapy even though there is no indication of its use. We describe two patients with programmed death ligand-1 (PD-L1)-negative advanced bladder cancer, one with FGFR3 mutation and another with FGFR3 wild type. Both patients had progressed after first-line chemotherapy with gemcitabine and cisplatin. We selected anlotinib in combination with tislelizumab, a programmed death-1 (PD-1) immune checkpoint inhibitor, for second-line treatment. Responses were evaluated as partial remission in both cases, who achieved up to 12 months of progression-free survival with no significant adverse events. Two patients with PD-L1-negative UC underwent second-line therapy using tislelizumab in combination with anlotinib, and the efficacy was better than that of tislelizumab alone. These results suggest that anlotinib may act synergistically with tislelizumab in the treatment of UC.

PRDX1 Influences The Occurrence and Progression of Liver Cancer by Inhibiting Mitochondrial Apoptosis Pathway.

OBJECTIVE: The aim of this study is to elucidate the role of PRDX1 in hepatocellular carcinoma using hepatoma cells. MATERIALS AND METHODS: In this experimental study, we elucidated role of PRDX1, using hepatoma cell lines. RESULTS: PRDX1 was upregulated in different types of cancers, including lung adenocarcinoma, breast cancer and liver cancer reported by several studies. nevertheless, mechanism of inducing liver cell death by PRDX1 remains largely unknown. Here, we showed that PRDX1 expression is enhanced in different cell lines. Here, we used western blot, quantitative real time polymerase chain reaction (qRT-PCR) and different biochemical assays to explore the role of PRDX1. We observed that overexpression of PRDX1 significantly enhanced proliferation of hepatoma cell lines, while knock-down of this gene showed significant inhibitory effects. We found that knock-down of PRDX1 activated cleaved caspase-3, caspase-9 proteins and Poly [ADP-ribose] polymerase 1 (PARP-1), which further executed apoptotic process, leading to cell death. We found that PRDX1 knock-down significantly produced mitochondrial fragmentation. We showed that silencing PRDX1 led to the loss of B-cell lymphoma 2 (Bcl-2) and activated Bcl-2-like protein 11 (Bim) which further induced Bax activation. Bax further released cytochrome c from mitochondria and induced apoptotic proteins, suggesting a significant role of PRDX1 knock-down in apoptosis. Finally, we showed that knock-down of PRDX1 significantly activated expression of Dynein-related protein 1 (Drp1), fission 1 (Fis1) and dynamin-2 (Dyn2) suggesting a crucial role of PRDX1 in mitochondrial fragmentation and apoptosis conditions. This study highlighted an important role of PRDX1 in regulating proliferation of hepatoma cells and thus future studies are required to validate its effect on hepatcoytes. CONCLUSION: We propose that future works on PRDX1 inhibitors may act as a therapeutic candidate for treatment of liver cancer.

Circular RNA circNINL promotes breast cancer progression through activating ß-catenin signaling via miR-921/ADAM9 axis.

We investigated the expression and functions of circular RNA (circRNA) circNINL and miR-921 in breast cancer (BC) in this study. We found that the expression of circNINL increased while the expression of miR-921 decreased in BC tissues and cell lines, and their anomalous expressions were associated with malignant features and poor prognostic of BC. Then, we demonstrated that circNINL could interact with miR-921 and facilitate BC cells malignant process including proliferation acceleration, migration enhancement and apoptosis evasion via sponging miR-921 in vitro. Further investigations revealed that circNINL/miR-921 axis could mediate the expression of ADAM9 which was a direct target of miR-921. In addition, we exhibited that ADAM9 may activate ß-catenin signaling by interacting with E-cadherin. We presented the vital roles of circNINL/miR-921/ADAM9/ß-catenin signaling in the progression of BC.

Artesunate Suppresses the Proliferation and Development of Estrogen Receptor-α-Positive Endometrial Cancer in HAND2-Dependent Pathway.

Endometrial cancer (EC) is a common leading cause of cancer-related death in women, which is associated with the increased level of estrogen in the body. Artesunate (ART), an active compound derived from Artemisia annua L., exerted antitumor properties in several cancer types. However, the role of artesunate and the molecular basis on EC remains unclear. Here, we aimed to explore the effects and mechanisms of artesunate. Our results identified that estrogen receptor-α (ER-α) was a key factor for the type I EC (ER-α-positive), which might suppress the downstream LKB1/AMPK/mTOR pathway. Besides, we found ART significantly inhibited tumor proliferation in a dose-dependent manner. Mechanistic studies identified that ART led to tumor cell apoptosis and cell cycle arrest by downregulating the ER-α expression and activating the LKB1/AMPK/mTOR pathway. In addition, we found ART could increase the expression of heart and neural crest derivatives expressed 2 (HAND2) in the ER-α-positive EC cells, which could interact with ER-α. Through the gain-and loss-function experiments, we showed that over expression of HAND2 repressed the proliferation and migration of ER-α-positive EC cells via inhibition of ER-α expression. HAND2 knockdown increased ER-α expression and alleviated the antitumor effect of ART in vitro and in vivo. Overall, our study first showed that ART could be an effective antitumor agent through modulating ER-α-mediated LKB1/AMPK/mTOR pathway in the HAND2 dependent manner. Our findings provide an effective therapeutic agent for ER-α-positive EC treatment.

A case control study of risk factors and neonatal outcomes of preterm birth.

OBJECTIVE: The aim is to examine risk factors and neonatal outcomes of preterm birth and to provide basis in preventing preterm birth. MATERIALS AND METHODS: we carried out our study on 1328 term controls and 1328 preterm birth cases. By using multivariable logistic regression procedures we estimated odds ratio (OR) of potential preterm birth risk factors. T-test and chi-square test were used to estimate differences between groups. RESULTS: Maternal age, prior history of pregnancy and abortion, prenatal care, complications of pregnancy (includes hypertension, intrahepatic cholestasis of pregnancy (ICP), fetal growth restriction (FGR), premature rupture of the membranes (PROM), placenta previa, abnormal presentation, abnormal S/D ratio et al.) were significantly associated with preterm birth. Several factors emerged as being statistically significant risk factors for preterm birth, such as prior history of pregnancy, hypertension, ICP, FGR, PROM, placenta previa and abnormal presentation. The time of prenatal care was shown to be a protective factor. Additionally, we observed evidence suggested that male babies are known to have a significant higher risk of preterm birth than female babies. CONCLUSION: Prior history of pregnancy, hypertension, ICP, FGR, PROM, placenta previa and abnormal presentation were covariates identified in this study as risk factors for preterm birth. Preterm birth is an important reason of neonatal poor prognosis and death.

High Serum Tumor Necrosis Factor-Alpha Levels in Women with Polycystic Ovary Syndrome: A Meta-Analysis.

The objective of the study is to assess the TNF-α levels in PCOS patients and healthy controls. A comprehensive electronic search in Medline, Embase, and the Cochrane Library database was conducted up to July 2016. Random-effects model was used to estimate the standardized mean differences (SMDs) with 95% confidence intervals (CIs). Twenty-nine studies with a total of 1960 participants (1046 PCOS patients and 914 controls) were included in this meta-analysis. The TNF-α levels in PCOS patients were significantly higher than those in controls (random-effects, SMD = 0.60, 95% CI = 0.28-0.92, P<0.001). With regard to the subgroup analyses stratified by ethnicity, study quality, methods, and BMI, significantly high TNF-α levels were found in patients with PCOS in almost all of these subgroups. In the subgroup stratified by HOMA-IR ratio and T ratio, significant differences were only observed in the subgroups with HOMA-IR ratio of >1.72(SMD = 0.967, 95% CI = 0.103-1.831, P = 0.028, I2 = 93.5%) and T ratio>2.10 (SMD = 1.420, 95% CI = 0.429-2.411, P = 0.005, I2 = 96.1%). By meta-regression it was suggested that ethnicity might contribute little to the heterogeneity between the included studies. Through cumulative meta-analysis and sensitivity analysis it was supposed that the higher TNF-α levels of PCOS patients compared to healthy controls was stable and reliable. This meta-analysis suggests that the circulating TNF-α levels in women with PCOS are significantly higher than those in healthy controls. It may be involved in promoting insulin resistance and androgen excess of PCOS.

Perioperative and long-term outcomes of laparoscopy and laparotomy for endometrial carcinoma.

OBJECTIVE: To compare the efficacy and the clinical value of laparoscopic surgery and traditional abdominal surgery for the treatment of endometrial carcinoma. Meanwhile, assessing the value of preoperative MRI in the depth of myometrial invasion of endometrial carcinoma. METHODS: we retrospectively analyzed 32 patients with endometrial carcinoma who underwent laparoscopic surgery in Department of Obstetrics and Gynecology in the Subei People's Hospital from September 2008 to March 2015, comparing data using the same surgeons' traditional laparotomy cases during the same period. Data collected includes patient demography, intraoperative and postoperative clinical parameters and follow-up data. RESULT: All laparoscopic and laparotomy surgery were successful. laparoscopic surgery was better than traditional surgery with less blood loss, more early postoperative anal exhaust time, less postoperative hospital stay, and no seriously complications, there were significant differences (all P<0.05). The average operative time, in the laparoscopy group, was a little longer than the laparotomy group with no statistical significance (P>0.05). There were no differences in the two groups in terms of the number of excised lymph nodes and the recurrence and mortality rate (P>0.05). The sensitivity and specificity of the MRI imaging in assessment of deep myometrial invasion of endometrial carcinoma were 89.3% and 96.2%, respectively. CONCLUSION: Compared to conventional approaches, laparoscopic surgery showed favorable short-term outcomes with comparable survival. People with endometrial cancer can, therefore, be as safely managed using laparoscopy as laparotomy. MRI is of high value in assessing deep myometrial invasion in patients with endometrial carcinoma.

Magnetic resonance imaging for detection of depth of myometrial invasion and cervical invasion in patients with endometrial carcinoma.

AIMS: The aim of this study was to evaluate clinical significance of depth of myometrial invasion and cervical invasion by magnetic resonance imaging (MRI) in patients with endometrial carcinoma. METHODS: Between September 2011 and October 2014 on 98 patients who were diagnosed with and treated for endometrial carcinoma at Subei People's Hospital in China included in this study. Main outcome measure was the correlation between the depth of myometrial invasion and cervical invasion by preoperative MRI, transvaginal sonography, hysteroscopy with directed biopsy study and the subsequent histopathological findings following examination of the hysterectomy specimen. RESULTS: The mean age was 54.6 years old and the most common histological subtype was the endometrioid type of endometrial adenocarcinoma (87.8%). In the evaluation of deep myometrial invasion (>50%), sensitivity, specificity, positive and negative predictive value and positive and negative likelihood ratios of MRI were 70.00%, 94.87%, 77.78%, 92.50%, 13.65, 0.316, respectively. For cervical invasion, these values were 72.73%, 98.85%, 88.89%, 96.63%, 63.27, 0.30, respectively. CONCLUSION: MRI is the superior diagnostic method to detect the myometrial invasion and cervical invasion.

Injection of MTX for the treatment of cesarean scar pregnancy: comparison between different methods.

The aim of this study was to analyze clinical treatment and outcome of injection MTX for Cesarean scar pregnancy (CSP). We use retrospective study to compare the time in CSP of blood chorionic gonadotropin (ß-HCG) and progesterone drooped to the normal, blood flow resistance and hospitalization days. 34 patients diagnosed with CSP were reviewed in our department from 2000 to 2013, including clinical characteristics, early diagnosis, treatment methods and treatment outcome. All patients were divided into B ultrasound-guided gestational MTX inject group (Group one), local intramuscular treatment group (Group two) and uterine artery perfusion MTX group (Group three). All cases had responded well to treatment. Except three cases of local intramuscular serum ß-HCG decreased slowly MTX 10 mg intramuscular again, the average serum ß-HCG decline of 65% the 4th day after treatment. In intramuscular group, the average length of stay is 19 ± 2.1 days. Serum ß-HCG, progesterone recovery time were 20 to 89 days, an average of 54.5 days. B ultrasound-guided group hospital stay were 15 ± 3.1 days, serum ß-HCG, progesterone recovery time were 18 to 71 days, an average of 44.5 days. In Uterine artery embolization group, the average length of stay is 16 ± 2.4 days, serum ß-HCG, progesterone recovery time were 20 to 70 days, an average of 45 days. Statistical data results using T-test and chi-square test analysis. Three groups of ß-HCG, progesterone decreased to normal days the difference was statistically significant (P < 0.05), but uterine artery embolization group and ultrasound-guided group B showed no significant difference (P > 0.05). B ultrasound-guided gestational injection of MTX and uterine artery embolization perfusion MTX are the better ways to treat uterine scar pregnancy.

Clinical efficiency investigation of laparoscopic uterine artery occlusion combined with myomectomy for uterine fibroids.

To investigate the effectiveness of laparoscopic uterine artery occlusion combined with myomectomy for uterine fibroids. From August 2008 to August 2009, forty-eight women with uterine fibroids desiring to preserve their uteri underwent laparoscopic myomectomy. Among them, 18 women received laparoscopic uterine artery occlusion before uterine myomectomy while the others received laparoscopic myomectomy only. All of the 48 cases with uterine fibroids underwent laparoscopic myomectomy successfully, and no patient developed Intraoperative or postoperative complications. The average operation time was (105.6±27.6) min, and the average surgical blood loss was (87.52±18.35) ml. Blocking uterine artery before laparoscopic myomectomy is valuable and feasible for the management of women with symptomatic fibroids. Adopting this method can obtain pleasing therapeutic effect. The method can reduce blood loss thus make the surgical field clean and clear, and it can reduce the operating time and recurrence rate. It can also reduce electro-coagulation on the surgical surface and therefore cause less tissue necrosis and lower incidence of complications.

Clinical observation of laparoscopic radical hysterectomy for cervical cancer.

To evaluate safety, feasibility and the improvement of surgical method of laparoscopic extensive hysterectomy and pelvic lymph node dissection in patients with early-stage cervical cancer. Clinical data were prospectively collected from patients with IA2-IIA cervical cancer who underwent laparoscopic extensive hysterectomy (n1=22) and laparotomy (n2=23) in Department of Obstetrics and Gynecology in the Subei People's Hospital from June 2010 to August 2013. The successful rates in two groups of operation were 100%. Blood loss, postoperative hospital stay, complication rate, postoperative recovery of gastrointestinal tract and bladder function of the laparoscopy group of the laparoscopic group were all better than those of the laparotomy group, and there were significant differences (all P < 0.05). But in the laparoscopy group, the operative time was longer than the laparotomy group with statistical significance (P < 0.05). There was no statistically significant difference in the number of excised lymph nodes and the duration time of postoperative urinary catheterization between the two groups (P > 0.05). Laparoscopic extensive hysterectomy and pelvic lymph node dissection can fully meet the requirement of laparotomy. It has the properties of minor trauma and rapid recovery. The clinical efficacy is superior to laparotomy surgery. The results indicated laparoscopic is an ideal method for the treatment of early cervical cancer.

Clinical analysis of endometrial cancer patients with obesity, diabetes, and hypertension.

The purpose of our study was to study the postoperation outcome and incidence of deep vein thrombosis (DVT) in endometrial cancer (EC) patients with or without hypertension, diabetes, and obesity. This analysis included 219 patients with endometrial carcinoma who were treated between 2002 and 2012 at the Department of Obstetrics and Gynecology, Yangzhou University Hospital. Patients were divided into five groups based on the comorbidities. Group 1 EC & Diabetes, Group 2 EC & Hypertension, Group 3 EC & Obesity, Group 4 EC Combined two, Group 5 no combined. Then the five groups were analyzed in postoperation outcomes and DVT incidence using one-way analysis of variance or Pearson χ(2) tests. we found that there was no significant difference in pelvic lymph node metastasis (P=0.102), aortic lymph node metastasis (P=0.221), and operative time (P=0.503). But there was significant difference in blood loss (P<0.01), hospital stay (P<0.01). No significant difference (P>0.05) in treatment outcome between surgical operation, surgical operation+ radiotherapy and radiotherapy. Deep vein thrombosis and pulmonary embolism have some significantly (P<0.01) (P<0.01), respectively. Compared to patients who simply suffer from endometrial cancer, diabetes make patients easy bleeding in surgery and increase hospitalization time in corresponding. VTE is a common complication of EC surgery with comorbidities, such as diabetes and hypertension, and it's a remarkable proportion of events occurring late after surgery.

Impact of Part D low-income subsidies on medication patterns for Medicare beneficiaries with diabetes.

BACKGROUND: It is not known whether low-income subsidies (LIS) under Medicare Part D help beneficiaries overcome impediments to medication use associated with poor socioeconomic status and high disease burden. OBJECTIVES: To compare Medicare beneficiaries with LIS and Medicaid (duals), LIS without dual eligibility, and non-LIS recipients on use of medications recommended in diabetes treatment. RESEARCH DESIGN: Fixed-effect comparisons among beneficiaries in the same Part D plans in 2006-2007. SUBJECTS: Nationally representative sample of enrollees in Part D prescription drug plans. A total of 109,292 beneficiaries were in 204 prescription drug plans; 47.5% non-LIS, 44.4% duals, and 8.1% nondual LIS recipients. MEASURES: Medications included antidiabetic agents, renin-angiotensin-aldosterone system inhibitors, and antihyperlipidemics. Drug use was measured by exposure, duration of therapy, and medication possession ratio. RESULTS: The LIS dual cohort had significantly higher comorbidity compared with non-LIS comparisons, LIS nonduals were significantly more likely to take medications in all 3 drug classes compared with non-LIS recipients, but differences were small (between 2% and 4%; P<0.05). Non-LIS recipients and duals had equivalent exposure to any antidiabetic drug and antihyperlipidemics, but duals were 3% less likely to receive renin-angiotensin-aldosterone system inhibitors compared with non-LIS recipients (P<0.05). Small differences in adjusted values for duration of therapy and medication possession ratio among the 3 cohorts were also observed, none of which were clinically meaningful. CONCLUSIONS: Similarities in medication utilization among Part D enrollees with and without LIS coverage supports the program objective of providing enhanced access to needed medications for diverse groups of Medicare beneficiaries.

Effect of exposure to evidence-based pharmacotherapy on outcomes after acute myocardial infarction in older adults.

OBJECTIVES: To assess the effect of exposure to evidence-based medication after hospital discharge for Medicare beneficiaries with acute myocardial infarction (AMI). DESIGN: A discrete-time hazard model was used to estimate time to outcome associated with exposure to four drug classes (angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin-II receptor blockers (ARBs), beta-blockers (BBs), statins, and clopidogrel) used for post-AMI secondary prevention of cardiovascular events and mortality. SETTING: Medicare administrative data for a 5% random sample of beneficiaries. PARTICIPANTS: Medicare beneficiaries (N = 9,538) hospitalized for an AMI between April 1, 2006, and December 31, 2007, who survived for at least 30 days after discharge. The cohort was followed until death or December 31, 2008. MEASUREMENTS: Time-varying exposure was measured as proportion of days covered (PDC) for each quarter during the follow-up period. PDC was classified into five categories (0-0.2, 0.2-0.4, 0.4-0.6, 0.6-0.8, 0.8-1.0). Outcomes were mortality and a composite outcome of death or post-AMI hospitalization. RESULTS: Over a median follow-up of 18 months, mean PDC rates ranged from 0.37 (clopidogrel) to 0.50 (statins). When comparing the highest versus lowest categories of exposure, the hazard of the composite outcome was significantly lower for all drug classes except BBs (statins, adjusted hazard ratio (aHR) = 0.71, ACEIs/ARBs, aHR = 0.81, clopidogrel, aHR = 0.85, BBs, aHR = 0.93). All four drug classes were significantly associated with reductions in mortality; the magnitude of effect for the mortality outcome was largest for statins and smallest for BBs. Age modified the effect of statins on mortality. CONCLUSION: Use of evidence-based medications for secondary prevention after AMI is suboptimal in the Medicare population, and low exposure rates are associated with significantly higher risk for subsequent hospitalization and death.

Impact of silencing MMP9 gene on the biological behaviors of trophoblasts.

This study examined the effect of MMP9 gene on the biological behaviors of trophoblasts and explore the relation between MMP9 gene and the "superficial implantation of placenta". In vitro cultured trophoblasts (TEV-1 cells) were transfected with synthesized double-stranded MMP9 RNA (siRNA) by using lipofectamine2000™ technique and the expressions of MMP9 mRNA and protein and the growth and invasiveness of the TEV-1 cells were determined. Our results showed that siRNA transfection could significantly inhibit the expression of MMP9 gene in the TEV-1 cells and the growth and invasiveness of the TEV-1 cells transfected RNA was significantly reduced (P<0.01). We are led to conclude that silencing of MMP9 gene with siRNA can inhibit the growth and invasiveness of trophoblasts and increasing the expression of MMP9 might help prevent and treat preeclampsia.

Medication use and adherence among elderly Medicare beneficiaries with diabetes enrolled in Part D and retiree health plans.

BACKGROUND: Employer-based retiree drug benefits have long been viewed as the gold standard of drug coverage for elderly Medicare beneficiaries. The question for policy makers is whether beneficiaries enrolled in Part D plans exhibit drug utilization patterns comparable with those seen in retiree plans. OBJECTIVE: To compare utilization patterns for antidiabetic agents, renin-angiotensin-aldosterone system inhibitors, and antihyperlipidemics by elderly Medicare beneficiaries with diabetes enrolled in Medicare prescription drug plans (PDPs) and retiree health plans (RHPs). METHODS: A random 5% sample (N=45,613) of elderly diabetic patients with continuous 2006 PDP enrollment was selected from Medicare files and compared with a similar sample of elderly RHP enrollees from MarketScan (N=211,919) on any use, duration of therapy, and medication possession ratio for each drug class. Adjusted comparisons were made on samples (N=16,859 each) using propensity score matching. RESULTS: Drug utilization and adherence rates were high in both groups. In propensity score adjusted comparisons, prevalence rates for PDP enrollees were within 2.2% of the level of RHP enrollees for antidiabetic agents and renin-angiotensin-aldosterone system inhibitors, but differed sharply for antihyperlipidemics (61% vs. 69%; P<0.0001). There were no clinically meaningful differences between PDP and RHP enrollees in duration of therapy or medication possession ratio for any drug class. CONCLUSION: When otherwise similar Medicare beneficiaries with diabetes have drug coverage, the source of benefits has little effect on use and adherence with most (but not all) drugs recommended in diabetes guidelines.

Hypoxia induces FGF2 production by vascular endothelial cells and alters MMP9 and TIMP1 expression in extravillous trophoblasts and their invasiveness in a cocultured model.

The role of fibroblast growth factor 2 (FGF2) secretion by vascular endothelial cells during trophoblast invasion was assessed. The human extravillous trophoblast cell line, TEV-1, and umbilical vein endothelial cell line, HUVE-12, were cocultured under normal and hypoxic conditions. FGF2 expression in HUVE-12 cells and matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase 1 (TIMP1) expression in TEV-1 cells were analyzed using quantitative RT-PCR and Western blot analyses. TEV-1 cell invasion was also examined. FGF2 expression in the HUVE-12 cells cocultured with TEV-1 cells was significantly increased under hypoxic conditions. In the TEV-1 cells cocultured with HUVE-12, hypoxia reduced MMP9 expression and increased TIMP1 expression; it also reduced cell invasion by 43%. However, the expression of MMP9 and TIMP1 and ratio of MMP9/TIMP1 were increased when the TEV-1 cells were cultured alone under hypoxic conditions. These findings suggest that FGF2 release by stressed endothelial cells of uterine spiral arteries play roles in decreasing MMP9 and increasing TIMP1 production in extravillous trophoblasts (EVT) in response to stress, resulting in reduced EVT invasion and possibly shallow implantation of the placenta.

Impact of Silencing MMP9 Gene on the Biological Behaviors of Trophoblasts / 华中科技大学学报（医学）（英德文版）

This study examined the effect of MMP9 gene on the biological behaviors of trophoblasts and explore the relation between MMP9 gene and the "superficial implantation of placenta".In vitro cultured trophoblasts (TEV-1 cells) were transfected with synthesized double-stranded MMP9 RNA (siRNA) by using lipofectamine2000TM technique and the expressions of MMP9 mRNA and protein and the growth and invasiveness of the TEV-1 cells were determined.Our results showed that siRNA transfection could significantly inhibit the expression of MMP9 gene in the TEV-1 cells and the growth and invasiveness of the TEV-1 cells transfected RNA was significantly reduced (P＜0.01).We are led to conclude that silencing of MMP9 gene with siRNA can inhibit the growth and invasiveness of trophoblasts and increasing the expression of MMP9 might help prevent and treat preeclampsia.

Three-dimensional contrast-enhanced multidetector CT for anatomic, dynamic, and perfusion characterization of abnormal myocardium to guide ventricular tachycardia ablations.

BACKGROUND: Advances in contrast-enhanced multidetector CT enable detailed characterization of the left ventricular myocardium. Myocardial scar and border zone (BZ), as the target of ventricular tachycardia ablations, displays abnormal anatomic, dynamic, and perfusion characteristics during first-pass CT. This study assessed how contrast-enhanced CT can predict voltage-defined scar and BZ and integrate its scar reconstructions into clinical mapping systems to guide ventricular tachycardia ablations. METHODS AND RESULTS: Eleven patients with ischemic cardiomyopathy underwent contrast-enhanced CT before ventricular tachycardia ablation. Segmental anatomic (end-systolic and end-diastolic wall thickness), dynamic (wall thickening, wall motion), and perfusion (hypoenhancement) characteristics were evaluated. Receiver operating characteristic curves assessed the ability of CT to determine voltage-defined scar and BZ segments. Three-dimensional epi- and endocardial surfaces and scar borders were reconstructed, coregistered, and compared to voltages using a 17-segment model. Abnormal anatomic, dynamic, and perfusion data correlated well with abnormal (<1.5 mV) endocardial voltages (r=0.77). Three-dimensional reconstruction integrated into the clinical mapping system (registration accuracy, 3.31±0.52 mm) allowed prediction of homogenous abnormal voltage (<1.5 mV) in 81.7% of analyzed segments and correctly displayed transmural extent and intramural scar location. CT hypoperfusion correlated best with scar and BZ areas and encompassed curative ablations in 82% cases. CONCLUSIONS: Anatomic, dynamic, and perfusion imaging using contrast-enhanced CT allows characterization of left ventricular anatomy and 3D scar and BZ substrate. Integration of reconstructed 3D data sets into clinical mapping systems supplements information of voltage mapping and may enable new image approaches for substrate-guided ventricular tachycardia ablation.

[Effects of sanqi qiancao recipe on hemorheological parameters of rabbits with copper intrauterine device].

OBJECTIVE: To explore the mechanism of Sanqi Qiancao Recipe (SQR) in treating metrorrhagia caused by copper intrauterine device (IUD) in rabbits and to provide experimental evidence for preventing and treating this disease. METHODS: Fifty-six rabbits were randomly divided into seven groups, which were normal control group, sham-operation group, untreated group, indomethacin-treated group, low-dose SQR-treated group, medium-dose SQR-treated group and high-dose SQR-treated group. Copper IUD insertion was operated in rabbits of the last five groups. Rabbits in the last four groups were treated orally with indomethacin and low-, medium- and high-dose SQR respectively for a week. Rabbits in the untreated group, normal control group and sham-operation group were given distilled water orally. Hematocrit, blood viscosity at low, medium and high shear rate, plasma viscosity and blood sedimentation were examined after treatment. RESULTS: The hematocrit, blood viscosity at low, medium and high shear rate and plasma viscosity were higher in the untreated group than those in the normal control group with significant differences (P<0.01) while those indexes in low-, medium- and high-dose SQR-treated groups were significantly lower than those in the untreated group (P<0.05 or P<0.01). CONCLUSION: SQR can lead to a decrease in blood viscosity and improve the blood flow, which may be one of the mechanisms of SQR in treating metrorrhagia after copper IUD insertion.