Fentanyl Promoted the Growth of Placenta Trophoblast Cells through Regulating the METTL14 Mediated CCL5 Levels.

Gestational diabetes mellitus (GDM) is an important cause of the increase in incidence rate and mortality of pregnant women and perinatal infants. This study aimed to analyze the role of fentanyl, a µ-opioid agonist, in the GDM progression. The high glucose (HG) treatment HTR8/SVneo cells was used as a GDM model in vitro. The cell viability was assessed with cell counting kit-8 assay. The apoptosis rate was analyzed with flow cytometry and the transwell assay was conducted to test the cell migration and invasion. RT-quantitative PCR (qPCR) assay was performed to determine the relative expressions of related genes. The N6-Methyladenosine (m6A) levels were analyzed with MeRIP analysis. The tumor necrosis factor-α (TNF-α), interleukin 1ß (IL-1ß), and IL-10 levels of the cells were analyzed with commercial kits. The results showed that fentanyl increased the cell viability, migration and invasion, and IL-10 levels, and declined the apoptosis rate, TNF-α and IL-1ß levels of the HG stimulated HTR8/SVneo cells. The chemokine ligand 5 (CCL5) was over expressed in GDM tissues and HG stimulated HTR8/SVneo cells, which was depleted after fentanyl treatment. Over expressed CCL5 neutralized the fentanyl roles in the HG stimulated HTR8/SVneo cells. The methyltransferase-like protein 14 (METTL14) levels was decreased in HG stimulated HTR8/SVneo cells, which was up-regulated after fentanyl treatment. Additionally, METTL14 silenced prominently decreased the m6A and mRNA levels, along with the mRNA stability of CCL5. In conclusion, fentanyl promoted the growth and inhibited the apoptosis of the HG stimulated HTR8/SVneo cells through regulating the METTL14 mediated CCL5 levels.

Successful laparoscopic resection of fallopian tube abscess caused by Escherichia coli in a 12-year-old adolescent virgin:a case report and review of the literature.

BACKGROUND: Upstream infection with vaginal flora can develop into tubal endothelial damage and tubal edema, which can lead to tubal obstruction and fallopian tube abscess if left untreated. Fallopian tube abscess in adolescent virgins is very rare, it may lead to long-term or even lifelong complications once it occurred. CASE PRESENTATION: A 12-year-old adolescent virgin with no history of sexual intercourse and previous physical fitness who presented with lower abdominal pain with nausea and vomiting for 22 h, body temperature up to 39.2 °C. Laparoscopic surgery revealed an abscess in the left fallopian tube, the left fallopian tube was surgically removed, successfully treated, and the pus was cultured for escherichia coli. CONCLUSION: It is important to consider possibility of tubal infection in young.

Safe abortion: A retrospective study of negative pressure suction in abortion under the monitoring of ultrasound.

OBJECTIVE: To observe the effectiveness of ultrasound monitoring during negative pressure suction for abortion. METHODS: This retrospective study analyzed patients with abortion who underwent negative pressure suction, excluding 23 cases with incomplete information and missing interviews, leaving a total of 200 patients included in the study. They were divided into an ultrasound group (n = 100) and a non-ultrasound group (n = 100) based on whether ultrasound monitoring was used. The ultrasound group was applied negative pressure suction under ultrasound monitoring, and the non-ultrasound group was applied traditional negative pressure suction. The operative time and complications were assessed after the treatment. RESULTS: The operative time in the ultrasound group was 3.19 ± 0.62 min and in the non-ultrasound group was 6.35 ± 1.20 min, revealing a significantly shorter operative time in the ultrasound group than in the non-ultrasound group (P < 0.05). There was one case of uterine residual in the ultrasound group. There were eight cases with uterine residuals, four cases with intrauterine adhesions, one case with missed aspiration, and one case with perforation of the uterus in the non-ultrasound group. The complication rate in the ultrasound group was less than that in the non-ultrasound group (P < 0.05). CONCLUSION: Ultrasound-monitored negative pressure suction has obvious advantages over ordinary negative pressure suction in that it can shorten operation time, reduce operative complications, and ensure a safe and effective abortion.

Clinical analysis on the influencing factors related to preterm twin pregnancy.

OBJECTIVE: The aim of this study was to explore the influencing factors of preterm twin pregnancy. METHODS: In total, 602 twin-pregnant women delivered from February 2016 to February 2020 were analyzed retrospectively. According to whether the pregnant women were preterm or not, they were divided into preterm group (n=363) and term group (n=239). Baseline information, such as maternal age, address, and education level of the pregnant women, were collected. The clinical information of pregnant women, such as chorionic, preeclampsia, gestational diabetes, premature rupture of membranes, abnormal fetal position, and fetal weight, were analyzed. Logistic regression analysis was used to analyze the risk factors. p-value <0.05 was considered statistically significant. RESULTS: In the preterm group, monochorionic diamniotic comorbidities were significantly higher compared with the control group (p<0.05). Higher risks of preterm group have lower education (p<0.05). Multiple logistic regression analysis demonstrated that education, preeclampsia, and premature rupture of membranes were risk factors for preterm twin pregnancy. CONCLUSIONS: Preterm birth in twin pregnancy is associated with many risk factors, such as education, preeclampsia, and premature rupture of membranes. Pregnancy supervision and prenatal guidance for twin pregnancy should be strengthened. Furthermore, early detection and diagnosis of comorbidities can improve maternal and neonatal outcomes.

Efficacy of atosiban combined with ritodrine in the treatment of threatened preterm labor and related risk factors of different pregnancy outcomes.

OBJECTIVE: To investigate the efficacy of atosiban combined with ritodrine in threatened preterm labor (TPL) treatment and analysis of related risk factors of different pregnancy outcomes. METHODS: A retrospective study was conducted on the clinical data of 127 patients with TPL who were hospitalized in the Children's Hospital of Shanxi and Women's Health Center of Shanxi from January 2020 to November 2021. There from, 58 patients treated with ritodrine were seen as the control group (CG), and 69 treated with atosiban and ritodrine were regarded as the joint group (JG). The inhibition rate after treatment was compared, and the changes of tissue inhibitor of metalloproteinase-1 (TIMP-1), nitric oxide (NO), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in the amniotic fluid before and after treatment were assessed. The pregnancy outcomes of patients were recorded, and the risk factors of adverse pregnancy outcomes were analyzed. The full-term delivery rate, cesarean section rate and neonatal Apgar score >7 were compared, and their adverse reactions were evaluated. RESULTS: Compared with the JG, the improvement of uterine contraction in the CG was obviously lower, and so was the inhibition rate (P<0.05). The rates of full-term delivery and neonatal Apgar score >7 in the CG were lower than those in the JG, while that of cesarean section was higher (P<0.01). After treatment, the TIMP-1 level in the amniotic fluid in the CG was markedly lower (P<0.001), while the NO, IL-6 and PGE2 levels were higher (P<0.001) as compared with the joint group. The total incidence of adverse reactions in the JG was lower than that in the CG (P<0.05). Logistics regression analysis revealed that age<26 and use of Atosiban combined with Ritodrine are protective factors for pregnancy outcomes, while BMI≥20 before pregnancy is a risk factor for adverse pregnancy. CONCLUSION: Atosiban combined with ritodrine can improve the condition of TPL patients, enhance the treatment efficacy, and reduce the occurrence of adverse pregnancy outcomes.

Pamiparib Monotherapy for Patients with Germline BRCA1/2-Mutated Ovarian Cancer Previously Treated with at Least Two Lines of Chemotherapy: A Multicenter, Open-Label, Phase II Study.

PURPOSE: Phase I results of this phase I/II study showed that pamiparib 60 mg twice a day had antitumor activity and an acceptable safety profile in Chinese patients with advanced cancer, including epithelial ovarian cancer. PATIENTS AND METHODS: This open-label phase II study was conducted in China and enrolled adult (≥18 years) patients with platinum-sensitive ovarian cancer (PSOC; disease progression occurring ≥6 months after last platinum treatment) or platinum-resistant ovarian cancer (PROC; disease progression occurring <6 months after last platinum treatment). Eligible patients had known or suspected deleterious germline BRCA mutation (gBRCAmut) and had previously received ≥2 lines of therapy. Pamiparib 60 mg orally twice a day was administered until disease progression, toxicity, or patient withdrawal. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC) per RECIST version 1.1. RESULTS: In the total patient population (N = 113; PSOC, n = 90; PROC, n = 23), median age was 54 years (range, 34-79) and 25.6% of patients received ≥4 prior systemic chemotherapy lines. Median study follow-up was 12.2 months (range, 0.2-21.5). Eighty-two patients with PSOC and 19 patients with PROC were evaluable for efficacy. In patients with PSOC, 8 achieved a complete response (CR) and 45 achieved a partial response (PR); ORR was 64.6% [95% confidence interval (CI), 53.3-74.9]. In patients with PROC, 6 achieved a PR; ORR was 31.6% (95% CI, 12.6-56.6). Frequently reported grade ≥3 adverse events were hematologic toxicities, including anemia and decreased neutrophil count. CONCLUSIONS: Pamiparib 60 mg twice a day showed antitumor activity with durable responses in patients with PSOC or PROC with gBRCAmut, and had a manageable safety profile.

Clinical analysis on the influencing factors related to preterm twin pregnancy

SUMMARY OBJECTIVE: The aim of this study was to explore the influencing factors of preterm twin pregnancy. METHODS: In total, 602 twin-pregnant women delivered from February 2016 to February 2020 were analyzed retrospectively. According to whether the pregnant women were preterm or not, they were divided into preterm group (n=363) and term group (n=239). Baseline information, such as maternal age, address, and education level of the pregnant women, were collected. The clinical information of pregnant women, such as chorionic, preeclampsia, gestational diabetes, premature rupture of membranes, abnormal fetal position, and fetal weight, were analyzed. Logistic regression analysis was used to analyze the risk factors. p-value <0.05 was considered statistically significant. RESULTS: In the preterm group, monochorionic diamniotic comorbidities were significantly higher compared with the control group (p<0.05). Higher risks of preterm group have lower education (p<0.05). Multiple logistic regression analysis demonstrated that education, preeclampsia, and premature rupture of membranes were risk factors for preterm twin pregnancy. CONCLUSIONS: Preterm birth in twin pregnancy is associated with many risk factors, such as education, preeclampsia, and premature rupture of membranes. Pregnancy supervision and prenatal guidance for twin pregnancy should be strengthened. Furthermore, early detection and diagnosis of comorbidities can improve maternal and neonatal outcomes.

Comparison of the Efficacy and Safety of PARP Inhibitors as a Monotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis.

BACKGROUND: The present COVID-19 pandemic has tended toward normality. To provide convenient, safe, and effective home treatment programs for patients with recurrent ovarian cancer (ROC), the clinical efficacy and safety of poly (ADP-ribose) polymerase inhibitor (PARPi) (including olaparib, niraparib, and rucaparib) monotherapy as a maintenance treatment for platinum-sensitive ROC were systematically evaluated. METHODS: Numerous electronic databases were systematically searched for randomized controlled trials (RCTs) of PARPi maintenance treatment for ROC that were published before June 2021. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was grade 3-4 adverse effects (AEs). After data extraction and the quality evaluation of the included studies, Bayesian network meta-analysis (NMA) was performed using R software. The ability of each treatment was ranked using the surface under the cumulative ranking (SUCRA) curve. RESULTS: The analysis included five studies and 1390 patients. The NMA results demonstrated that compared with the placebo, olaparib and niraparib exhibited significant benefits in the gBRCA-mutated population, and respectively reduced the risk of death by 31% (HR = 0.69, 95% CI: 0.53-0.90) and 34% (HR = 0.66, 95% CI: 0.44-0.99). Olaparib, niraparib, and rucaparib were all found to be very effective in prolonging PFS in patients with ROC. All three PARPi treatments increased the number of grade 3-4 AEs in patients with ROC as compared with the placebo. CONCLUSIONS: Overall, olaparib and niraparib maintenance treatment can significantly prolong the OS of patients with gBRCA mutations. Furthermore, the three investigated PARPi monotherapy maintenance treatments can prolong PFS regardless of BRCA mutation status. Although the incidence of AEs in the treatment groups was found to be significantly higher than that in the placebo group, the patients in the treatment group tolerated the treatment. Home oral PARPi treatment can balance tumor treatment and pandemic prevention and control, and is the most convenient, safe, and effective home treatment method available against the background of the current COVID-19 pandemic. SYSTEMATIC REVIEW REGISTRATION: https://inplasy.com/inplasy-2021-6-0033/.

Apatinib Plus Gefitinib as First-Line Treatment in Advanced EGFR-Mutant NSCLC: The Phase III ACTIVE Study (CTONG1706).

INTRODUCTION: Blocking vascular endothelial growth factor pathway can enhance the efficacy of EGFR tyrosine kinase inhibitors in EGFR-mutant NSCLC. ACTIVE is the first phase 3 study conducted in the People's Republic of China evaluating apatinib, a vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor, plus gefitinib as first-line therapy in EGFR-mutant NSCLC. METHODS: Treatment-naive patients with stage IIIB or IV nonsquamous NSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, and EGFR exon 19 deletion or exon 21 L858R mutation were randomized 1:1 to receive oral gefitinib (250 mg/d), plus apatinib (500 mg/d; apatinib [A] + gefitinib [G] group), or placebo (placebo [P] + gefitinib [G] group). Stratification factors were mutation type, sex, and performance status. The primary end point was progression-free survival (PFS) by blinded independent radiology review committee (IRRC). Secondary end points were investigator-assessed PFS, overall survival, quality of life (QoL), safety, etc. Next-generation sequencing was used to explore efficacy predictors and acquired resistance. RESULTS: A total of 313 patients were assigned to the A + G (n = 157) or P + G group (n = 156). Median IRRC PFS in the A + G group was 13.7 months versus 10.2 months in the P + G group (hazard ratio 0.71, p = 0.0189). Investigator- and IRRC-assessed PFS were similar. Overall survival was immature. The most common treatment-emergent adverse events greater than or equal to grade 3 were hypertension (46.5%) and proteinuria (17.8%) in the A + G group and increased alanine aminotransferase (10.4%) and aspartate aminotransferase (3.2%) in the P + G group. QoL in the two groups had no statistical differences. Post hoc analysis revealed PFS benefits tended to favor the A + G group in patients with TP53 exon 8 mutation. CONCLUSIONS: Apatinib + gefitinib as first-line therapy had superior PFS in advanced EGFR-mutant NSCLC versus placebo + gefitinib. Combination therapy brought more adverse events but did not interfere QoL. TRIAL REGISTRATION: NCT02824458.

[Fetal malnutrition assessment program].

OBJECTIVE: To study the application of ponderal index (PI), body mass index (BMI), mid-arm circumference/head circumference (MAC/HC), and Clinical Assessment of Nutritional Status (CANS) score in assessing the nutritional status of neonates at birth, and to find a simple and reliable scheme for the assessment of fetal nutritional status. METHODS: PI, BMI, MAC/HC, and CANS were used to assess the nutritional status of full-term infants and preterm infants shortly after birth. The assessment results of these methods were analyzed. RESULTS: Among the 678 full-term infants, 61, 102, 47, and 131 were diagnosed with malnutrition by PI, BMI, MAC/HC, and CANS respectively. Among the 140 preterm infants, 30, 87, 9, and 112 were diagnosed with malnutrition by PI, BMI, MAC/HC, and CANS respectively. The combination of BMI and CANS had a detection rate of 99.3% in full-term infants and 100% in preterm infants. Compared with the single method, the combination significantly improved the detection rate of malnutrition (P < 0.05), while there was no significant difference between the combination of BMI+CANS and the combination of PI+BMI+CANS (P > 0.05). CONCLUSIONS: The combination of BMI+CANS can reduce the rate of missed diagnosis of fetal malnutrition. It is therefore a simple and reliable method for the assessment of fetal malnutrition.

Poor Sleep Quality Is Associated with a Higher Risk of Pulmonary tuberculosis in Patients with a Type 2 Diabetes Mellitus Course for More than 5 Years.

A case-control study was conducted in Shandong from January to December 2017 to explore the relationship between sleep quality and the risk of active pulmonary tuberculosis (PTB). Seventy-nine patients with type 2 diabetes mellitus coincident with newly diagnosed pulmonary tuberculosis (DM-PTB) and 169 age, sex, and DM course frequency-matched controls (DM alone) were enrolled. Univariate and multivariable unconditional logistic regression analyses were conducted. We further conducted subgroup analyses to explore the relationship between sleep quality and PTB risk, including DM course (≤5 and ＞5 years), age, sex, and the presence of overweight or obesity (body mass index (BMI) ＞ 24 kg/m2). Multivariate logistic regression demonstrated that poor sleep quality had a borderline negative association with the odds of PTB (P ＝ 0.065). Subgroup multivariate analyses showed that poor sleep quality increased the risk of PTB to more than 3 times among patients with a DM course ＞ 5 years (odds ratio 3.31, 95% confidence interval: 1.08-10.13; P ＝ 0.036) after adjusting for potential confounding factors including residential area, educational level, BMI, history of contact with tuberculosis patients, smoking, alcohol consumption, physical exercise, immune status, and frequency of blood glucose monitoring. In conclusion, poor sleep quality is an independent risk factor of PTB among DM patients with a course of ＞ 5 years, which indicates significant epidemiological implications for PTB control.

VEGF-A/Neuropilin 1 Pathway Confers Cancer Stemness via Activating Wnt/ß-Catenin Axis in Breast Cancer Cells.

BACKGROUND/AIMS: Targeting cancer stem cells (CSCs) is emerging as a promising method for cancer treatment. We previously indicated that knockdown of Neuropilin 1(NRP-1) could inhibit breast cancer cell proliferation. Here, we continue exploring the roles and mechanisms of VEGF-A/NRP-1 axis in breast CSCs formation. METHODS: qRT-PCR was used to detect the levels of VEGF-A and NRP-1 in breast cancer sphere cells and wild-type cells. Mammospheres formation, flow cytometry, soft agar colony and tumor formation assays were performed to evaluate the effects of VEGF-A/NRP-1 on breast cancer stemness. Further HUVECs tube formation, cell invasion assays were carried out to detect the effects of VEGF-A/NRP-1 on breast cancer spheres-induced angiogenesis. Finally, Annexin V/PI apoptosis and CCK8 assays were used to detect the effects of VEGF-A/NRP-1 on chemoresistance. RESULTS: Overexpression of VEGF-A or NRP-1 conferred CSCs-related traits in MCF-7 cells, while knockdown of VEGF-A or NRP-1 reduced CSCs-related traits in MDA-MB-231 cells in vitro and in vivo. Notably, VEGF-A acted in a NRP-1 dependent way. Mechanistically, the VEGF-A/NRP-1 axis conferred CSCs phenotype via activating Wnt/ß-catenin pathway. CONCLUSION: our results suggest that VEGF-A/NRP-1 axis could confer CSCs-related traits and chemoresistance.

Thalidomide for Control Delayed Vomiting in Cancer Patients Receiving Chemotherapy.

OBJECTIVE: To explore the efficacy and safety of thalidomide for the treatment of delayed vomiting, induced by chemotherapy in cancer patients. STUDY DESIGN: Randomized, double-blind controlled study. PLACE AND DURATION OF STUDY: The Oncology Department of Affiliated Hospital of Xuzhou Medical University, Jiangsu Xuzhou, China, from January 2012 to January 2014. METHODOLOGY: A total of 78 cancer patients, who had delayed vomiting observed from 24 hours to 1 week after chemotherapy, were included in the study. Patients were divided in a treatment group (40 patients, 51.28%) and a control group (38 patients, 48.71%). The treatment group received thalidomide at an oral dose of 100 mg per night; 50 mg was added daily up to a dose of 200 mg per night, if the curative effect was suboptimal and the medicine was tolerated. Both the treatment and the control groups received a drip of 10 mg azasetron 30 minutes before chemotherapy. The control group only proportions of antiemetic effects and adverse reactions were compared using the c2 test. Antiemetic effects and adverse reactions were assessed from Odds Ratios (OR) with 95% Confidence Intervals(95% CI). RESULTS: The effective control rate of delayed vomiting in the treatment group was significantly higher than that in the control group (c2=5.174, p=0.023). No significant difference was found between the two groups in other adverse effects of chemotherapy. Karnofsky scores or the overall self-evaluation of the patients (p>0.05). CONCLUSION: Thalidomide can effectively control the delayed vomiting of cancer patients receiving chemotherapy and the adverse reactions of the agent can be tolerated.

Robot-assisted versus conventional laparoscopic surgery in the treatment of advanced stage endometriosis: a meta-analysis.

OBJECTIVE: To evaluate the safety and efficacy of robot-assisted laparoscopy (RAL) versus conventional laparoscopy (CL) in the treatment of advanced stage endometriosis. MATERIALS AND METHODS: Utilizing electronic databases (PubMed, Embase, and Elsevier), a systematic literature review was performed between 2008 and 2015 to compare the RAL surgery with CL surgery (CLS) in the treatment of advanced stage endometriosis. According to meta-analysis criteria, two comparative clinical trials were selected. Outcome measures including length of operation, blood loss, operative complications, and the length of hospitalization, were estimated by the RevMan 5.1 software. RESULTS: In the meta-analysis, there were no significant differences in blood loss, complication, and hospital stay between RAL and CL surgeries in the treatment of advanced stage endometriosis. However, RAL surgery required a higher mean operating time than CL surgery (WMD: 73.85, 95% CI: 56.77-90.94; p < 0 .00001). Comparative studies demonstrated that RAL displayed no outstanding advantages. CONCLUSIONS: As a new minimally invasive method, RAL technology is safe and efficient alternative to CL in the treatment of advanced stage endometriosis. The latent benefits of RAL technology for the treatment of advanced stage endometriosis remain uncertain.

Menopausal Symptoms and Sleep Quality During Menopausal Transition and Postmenopause.

BACKGROUND: Menopausal symptoms and sleep difficulty were physiological processes that were affected by genetic and other factors. This study was to investigate the prevalence of menopausal symptoms and sleep quality in menopausal transition (MT) and postmenopause (PM) women in Taiyuan, Shanxi. METHODS: A community-based survey of women's menopausal symptoms and sleep quality was conducted between July 2012 and May 2013 at six municipal districts of Taiyuan, Shanxi. A sample of 2429 women aged 40-59 years was divided into four groups: early MT, late MT, early PM, and late PM. Sleep quality in the past 2 weeks before the interview was recorded. The data were analyzed using SPSS 16.0. RESULTS: The prevalence of menopausal symptoms was 49.8%. Mild, moderate, and severe symptoms were observed in 28.9%, 18.5%, and 2.5% of participants, respectively. The highest prevalence of menopausal symptoms occurred in the early postmenopausal stage; the subsequences were the late postmenopausal stage and the early MT stage. Interestingly, among the 13 items of modified Kupperman index, the five most common symptoms were fatigue, arthralgia and myalgia, decreased libido, insomnia, and nervousness. Meanwhile, 55% perimenopausal women had poor sleep. CONCLUSIONS: Menopausal symptoms are common but mild among women in Taiyuan, Shanxi during MT and PM. In these stages, the prevalence of poor sleep is high.

Effects of RNA interference-mediated NRP-1 silencing on the proliferation and apoptosis of breast cancer cells.

Lentiviral expression vectors carrying human NRP-1 short hairpin RNA (shRNA) were constructed and selected to present highly efficient NRP-1/shRNA interference sequences, in order to investigate the effects of RNA interference (RNAi)-mediated NRP-1 silencing on the biological activities of breast cancer cells. Three pairs of human NRP-1 targeted specific interference sequences and one pair of non-specific control sequences were designed, synthesized and subcloned into pLB lentiviral vectors, which were further identified by polymerase chain reaction (PCR) and sequencing. Recombinant and lentiviral packaging plasmids were co-transfected into 293FT cell lines in order to produce lentiviral particles and to infect breast cancer cells with high NRP-1 expression. Flow cytometry was used to sort green fluorescent protein-positive cells. Fluorescence quantitative-reverse transcription-PCR and western blot analysis were employed to identify the interference silencing sequence with the most efficient silencing profile. A cell counting kit-8 assay and an Annexin V-propidium iodide method in combination with flow cytometry were used to examine the effects of RNA interference-mediated NRP-1 gene silencing on cell proliferation, apoptosis and sensitivity to chemotherapy. The recombinant lentiviral plasmid pLB-NRP-1/shRNA was constructed successfully, as confirmed by PCR and sequencing. After the infection of recombinant lentiviral plasmids, the expression profiles of NRP-1 mRNA, and proteins of MCF-7 and SK-BR-3 cell-specific interference group (pLB-NRP-1/shRNA3) were significantly lower than that of the control group (P<0.05). Compared with the control group, the MCF-7 and SK-BR-3 cell-specific interference group (pLB-NRP-1/shRNA3) showed lower optical density values and higher apoptotic rates at 48, 72 and 96 h; these differences were statistically significant (P<0.05). EPI administration resulted in increased apoptosis in the MCF-7 and SK-BR-3 cell-specific interference groups compared with the control group (P<0.05). Lentiviral vectors encoding the human NRP-1 gene were constructed successfully and highly efficient NRP-1/shRNA interference sequences were selected. Furthermore, RNA interference (RNAi)-mediated NRP-1 silencing may induce proliferation suppression, apoptosis promotion, as well as enhanced sensitivity to chemotherapeutic agents.

Antiemetic role of thalidomide in a rat model of cisplatin-induced emesis.

The efficacy of thalidomide to attenuate cisplatin-induced emesis was evaluated in a rat model. Four groups were utilized: control group (peritoneal injection and gastric lavage with normal saline), cisplatin group (peritoneal injection of cisplatin at 10 mg/kg and gastric lavage with normal saline), thalidomide group (cisplatin as above and gastric lavage with thalidomide at 10 mg/kg), and granisetron group (positive control for antiemetic effects; cisplatin given as above and gastric lavage done with granisetron at 0.5 mg/kg). The cisplatin-induced kaolin consumption (pica behavior) was used as a model of emesis in patients. The animals' kaolin and food intakes were measured. Further, medulla and gastric tissues were obtained 5 and 33 h after peritoneal injections to quantify the levels of Substance P and Neurokinin-1 receptor (NK-1R). The cisplatin-induced kaolin consumption was significantly (p < 0.05 vs. cisplatin group) attenuated by thalidomide 72 h after the injection. The levels of Substance P in the medulla and gastric tissue were increased 5 h after the injection in both cisplatin and thalidomide groups, however, returned faster to normal levels in the thalidomide group (p < 0.05 vs. cisplatin group). Further, levels of NK-1R in the cisplatin, thalidomide, and granisetron group were significantly increased at both 5 and 33 h (p < 0.05 vs. control group), with no obvious difference among these three groups. In conclusion, thalidomide attenuates animal equivalent of cisplatin-induced emesis, and this beneficial effect is associated with decreased levels of Substance P levels in the medulla and gastric tissue.

Overcoming paclitaxel resistance in lung cancer cells via dual inhibition of stathmin and Bcl-2.

Lung cancer is the leading cause of death from malignancy in people and over 85% of these patients eventually die from disseminated disease. Paclitaxel (TAX) is widely used as an antimicrotubule agent for the treatment of lung cancer. Unfortunately, the resistance to this antimicrotubule agent occurs frequently. Stathmin (STMN1) is a ubiquitous microtubule destabilizing protein linked to cancer and cell health and its expression level often correlates with cancer stage progression and prognosis for survival. Overexpression of the antiapoptotic protein Bcl-2 has been shown to prolong drug-induced growth arrest, potentially inducing resistance. In this study, we used a short hairpin RNA (shRNA) approach to evaluate the effect of STMN1 and Bcl-2 downregulation in the sensitivity to TAX in lung cancer cells. We achieved significant downregulation of STMN1 and Bcl-2 mRNA and protein expression by a combination of double shRNA treatment strategy. Our experimental data showed that inhibition of STMN1 and Bcl-2 expression with RNA interference can sensitize lung cancer cells to TAX. These findings suggest a novel approach to improve the efficacy of certain antimicrotubule agents against lung cancer by regulating the function of STMN1 and Bcl-2.

Fasting plasma glucose at 24-28 weeks to screen for gestational diabetes mellitus: new evidence from China.

OBJECTIVE: To evaluate the usefulness of a fasting plasma glucose (FPG) at 24-28 weeks' gestation to screen for gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: The medical records and results of a 75-g 2-h oral glucose tolerance test (OGTT) of 24,854 pregnant women without known pre-GDM attending prenatal clinics in 15 hospitals in China were examined. RESULTS: FPG cutoff value of 5.1 mmol/L identified 3,149 (12.1%) pregnant women with GDM. FPG cutoff value of 4.4 mmol/L ruled out GDM in 15,369 (38.2%) women. With use of this cutoff point, 12.2% of patients with mild GDM will be missed. The positive predictive value is 0.322, and the negative predictive value is 0.928. CONCLUSIONS: FPG at 24-28 weeks' gestation could be used as a screening test to identify GDM patients in low-resource regions. Women with an FPG between ≥4.4 and ≤5.0 mmol/L would require a 75-g OGTT to diagnose GDM. This would help to avoid approximately one-half (50.3%) of the formal 75-g OGTTs in China.

The assessment of environmental pollution along the coast of Beibu Gulf, northern South China Sea: an integrated biomarker approach in the clam Meretrix meretrix.

The clam Meretrix meretrix was used as a biomonitor to implement an environmental monitoring program along the coast of Beibu Gulf in October 2011. This program not only analyzed biomarkers including acetylcholinesterase, glutathione peroxidase, glutathione S-transferase, catalase and superoxide dismutase activities, total glutathione content and lipid peroxidation level in M. meretrix but also adopted a multi-biomarker approach - integrated biomarker response (IBR) to assess the environmental quality in this ecosystem. In addition, the metal (Hg, As, Cu, Pb, Zn, Cd and Cr) and polychlorinated biphenyls (PCBs) content in the surface sediment at the study area were also measured. The results showed that IBR index was able to distinguish a space trend between sampling sites with different degrees of anthropogenic environmental stress. Integrated contamination degree were displayed in the form of star plots and compared to IBR plots. There was a visual consistency between the pollution level and IBR variation. Based on the results, it was proved that the IBR method coupled with chemical analysis was quite useful for the assessment of environmental pollution in the coastal system.