Identification of FCER1G as a key gene in multiple myeloma based on weighted gene co-expression network analysis.

PURPOSE: Although the prognosis of multiple myeloma (MM) has remarkably improved with the emerge of novel agents, it remains incurable and relapses inevitably. The molecular mechanisms of MM have not been well-studied. Herein, this study aimed to identify key genes in MM. MATERIALS AND METHODS: The GSE39754 dataset was used to screen differentially expressed genes (DEGs) and construct a co-expression network. Hub nodes were identified in the protein and protein interaction (PPI) network. Datasets GSE13591 and GSE2658 were used to validate hub genes. Moreover, function and gene set enrichment analyses were performed to elucidate the molecular pathogenesis of MM. RESULTS: In this study, 11 genes were found to be hub genes in the co-expression network, among which four genes (CD68, FCER1G, PLAUR and LCP2) were also identified as hub nodes. In the test dataset GSE13591, CD68 and FCER1G were significantly downregulated in MM. Besides, the areas under the curve (AUCs) of CD68 and FCER1G were greater than 0.8 in both the training dataset and the test dataset. Our results also confirmed that FCER1G highly expressed patients had remarkably longer survival times in MM. Function and pathway enrichment analyses suggested that hub genes were associated with epithelial mesenchymal transition, TNF-α signaling via NF-κB and inflammatory response. GSEA in our study indicated that FCER1G participated in NK cell mediated cytotoxicity and the NOD-like receptor signaling pathway. CONCLUSION: Our study identified FCER1G as a key gene in MM, providing a novel biomarker and potential molecular mechanisms of MM for further studies.

Clinical study on multi-focused laser in the treatment of vulvar lichen sclerosus.

Objective: To investigate the clinical effect of Multi-focused (MF) laser in the treatment of vulvar lichen sclerosus (VLS). Methods: In this single-center, randomized controlled trial, we compared the effect of fractionated MF laser with other treatments on patients with biopsy-proven VLS. Patients with VLS were enrolled in this study and randomly divided into three groups. Patients in the experimental group were treated with a CO2 laser, control group 1 was treated with radiofrequency, and control group 2 was treated topically with glucocorticoids and soaking with Chinese patent medicine. The pruritus degree, skin elasticity, skin color, lesion scope, and total score were compared before treatment, at one month after treatment, and three months after treatment. Results: One month after treatment, the pruritus degree, skin elasticity, skin color, lesion scope, and total score decreased in the experimental group, and the differences were statistically significant (P < 0.05). In control group 1, the differences in pruritus degree, skin color, and total score were statistically significant (P < 0.05), but the differences in skin elasticity and lesion scope were not statistically significant (P > 0.05). In control group 2, the differences in pruritus degree and total score were statistically significant (P < 0.05), but the differences in skin elasticity, skin color, and lesion scope were not statistically significant (P > 0.05). At one month after the end of treatment, the differences in pruritus degree, skin elasticity, skin color, lesion scope, and total score among the three groups were not statistically significant. At three months after the end of treatment, the differences in the scores of the five indicators were statistically significant. Conclusion: For the three treatment methods for VLS, topical corticosteroids + traditional Chinese medicine can quickly relieve itching symptoms in patients, but it cannot significantly improve skin elasticity, skin color, and lesion scope, and VLS easily relapses after treatment. Radiofrequency can improve itching symptoms and skin color but has poor effects on the change of skin elasticity and lesion scope. Multi-focused laser treatment can alleviate the degree of pruritus, improve skin color and elasticity, and narrow the lesion scope, and VLS will not relapse within three months after treatment.

High nerve density in breast cancer is associated with poor patient outcome.

Active crosstalk between the nervous system and breast cancer cells has been experimentally demonstrated in vitro and in animal models. However, low frequencies of peripheral nerve presence in human breast cancers reported in previous studies (~30% of cases) potentially negate a major role of the nervous system in breast cancer development and progression. This study aimed to clarify the incidence of nerves within human breast cancers and to delineate associations with clinicopathological features. Immunohistochemical staining was conducted in formalin-fixed paraffin-embedded breast cancer tissue sections using antibodies against the pan-neuronal markers protein gene product 9.5 and growth-associated protein 43, and the sympathetic nerve-specific marker tyrosine hydroxylase. Nerve trunks and isolated nerve fibers were quantitated. The chi-squared test was used to determine the associations between nerve counts and clinicopathological parameters. The log-rank test was used to compare differences in patient progression-free survival (PFS) and overall survival (OS). The overall frequency of peripheral nerves in breast cancers was 85%, a markedly higher proportion than reported previously. Of note, most nerves present in breast cancers were of the sympathetic origin. While high density of nerve trunks or isolated nerve fibers was associated with poor PFS and OS of patients, high nerve trunk density appeared also to predict poor patient PFS independently of lymph node metastasis. Innervation of breast cancers is a common event correlated with poor patient outcomes. These findings support the notion that the nervous system plays an active role in breast cancer pathogenesis.

GAS6-mediated dialogue between decidual stromal cells and macrophages is essential for early pregnancy maintenance by inducing M2-like polarization and cell proliferation of decidual macrophages.

Maternal immunotolerance towards the semi-allogeneic foetus is critical for normal pregnancy (NP). As a secretory protein, growth arrest-specific factor 6 (GAS6) promotes cancer progression by inducing the conversion of tumour-associated macrophages to an immunosuppressive M2-like phenotype. However, little is known about whether GAS6 regulates decidual macrophages (dMφs) in the early maternal-foetal interface. In this study, first-trimester decidual tissues were obtained from normal pregnant women undergoing elective terminations and patients with miscarriages. The expression of GAS6 and its receptors (AXL, TYRO3 and MERTK) in decidua and GAS6 secretion by decidual stromal cells (DSCs) was measured. Then, we investigated the effect of recombinant human GAS6 (rhGAS6) on dMφs isolated from NP and THP-1 cells, and revealed the underlying mechanism. Both the expression of GAS6 in DSCs and MERTK in dMφs, in addition to GAS6 secretion by DSCs, was found to be significantly decreased in miscarriage patients compared to that in NPs. Additionally, we observed that rhGAS6 polarized dMφs and THP-1 cells towards an M2-like phenotype, as evidenced by the up-regulated CD163 expression. Moreover, rhGAS6 enhanced the clearance of toxic cell-free haemoglobin by dMφs by up-regulating CD163 expression, and rhGAS6 also boosted cell proliferation of dMφs and THP-1 cells. Finally, we demonstrated that rhGAS6 stimulated CD163 expression and cell proliferation by activating the PI3K/Akt signalling pathway. Collectively, these findings suggest that GAS6-mediated dialogue between DSCs and dMφs is crucial for the establishment and maintenance of maternal-foetal immunotolerance, and decreased GAS6 secretion by DSCs may lead to the occurrence of miscarriage in the first trimester.

[Effect of rFLC and dFLC on Clinical Prognosis of Patients with Newly Diagnosed Multiple Myelome and Best Cutoff Value].

OBJECTIVE: To investigate the influence of rFLC and dFLC on clinical prognosis and best cutoff value in patients with newly diagnosed multiple myelome(MM). METHODS: Clinical data of 240 patients with newly diagnosed MM treated in Western Theater General Hospital of People's Liberation Army from January 2010 to June 2016 were collected and retroanalyzed. All patients were divided into different groups according to the interquartile spacing levels of rFLC and dFLC, the median OS and PFS of patients in different groups were compared. The influencing factors of prognosis in newly diagnosed MM patients were analyzed by univariate and multivariate methods, the influence of different cutoff values of rFLC and dFLC on clinical prognosis were evaluated. RESULTS: The median progression-free survival time of female patients with M-protein IgA type and I stage for ISS stage were significantly longer than those of male, other M-protein types and other ISS stage（P<0.05）. The median OS of patients without hypercalcemia was significantly higher than that of patients with hypercalcemia（P<0.05）. The median progression-free survival(PFS) time of patients with dFLC <110.95 mg/L was significantly longer than that of patients with dFLC=110.95-2 781.44 mg/L and >2 781.44 mg/L（P<0.05）. The median overall survival time of patients with dFLC ＜110.95 mg/L and ＞2 781.44 mg/L was significantly longer than that of patients with dFLC=110.95-2 781.44 mg/L（P<0.05）. The median overall survival time of patients with rFLC <14.71 mg/L was significantly longer than that of patients with rFLC >14.71-367.96 mg/L and >367.96 mg/L（P<0.05）. Univariate analysis of Cox regression model indicated that dFLC at all levels showed higher influence on the OS and PFS of patients as compared with rFLC（P<0.05）. Multivariate analysis of Cox regression model showed that rFLC and dFLC expression level were the independent prognostic factors of patients（P<0.05）. The most significant influence value on clinical prognosis of patients were observed when rFLC level ≤14.71 or dFLC level ≤110.95 mg/L（P<0.05）. The median OS of patients with rFLC level ≤14.71 was significantly higher than that of other groups（P<0.05）. There was significant difference in median PFS between patients with rFLC ≤14.71 and ≥367.96 mg/L（P<0.05）. The median OS and PFS of patients with dFLC ≤110.95 mg/L were significantly longer than those in other two groups（P<0.05）. CONCLUSION: The levels of rFLC and dFLC closely relate to clinical prognosis of patients with new diagnosed MM; the risk of recurrence or death is lowest in patients with rFLC level ≤14.71 mg/L or dFLC level ≤110.95 mg/L, which can be used as the ideal cutoff value for prognosis evaluation.

[Influencing Factors on Prognosis of Adult Patients with Chronic Primary ITP Treated with Rituximab and Predictive Value of Platelet Count].

OBJECTIVE: To investigate the influencing factors on prognosis of adult patients with chronic primary immune thrombocytopeuia (ITP) after rituximab treatment and predictive value of platelet (Plt) count. METHODS: Clinical data of 52 adult patients with chronic primary ITP treated with rituximab from January 2012 to December 2016 were retrospectively analyzed, including 32 patients for failed in treatment as group A and 20 patients for succeeded in treatment as group B. The independent risk factors influencing the clinical efficacy of rituximab were analyzed. The influence of CD41+ megakaryocyte count in bone marrow diagnosed for first time on the response rate of patients with 1-year followed-up were observed, and the Plt count were calculated to predict the clinical efficacy index and the best cut-off point. RESULTS: The CD41+ megakaryocyte count in bone marrow for first time treatment in group B were significantly higher than that in group A (P＜0.05). Multivariate Logistic regression analysis showed that the number of CD41+ megakaryocytes in bone marrow＜150 at first diagnosis was the independent risk factor influencing the clinical efficacy of rituximab (OR=5.40，95%CI：1.82-15.66，P=0.00). The response rate of 1-year followed-up in patients with CD41+ megakaryocyte count ≥150 at first diagnosis was significantly higher than that of CD41+ megakaryocyte count ＜150 (P＜0.05). The Plt count level in group B was significantly lower than that in group A at the 3rd, 14th, 21th, 30th, 60th, 90th, 180th, 270th and 360th days after first treatment with rituximab (P＜0.05). ROC curve analysis showed that the best cut-off point for Plt count was 50×109/L and AUC was 0.68 at the 14th day after first treatment with rituximab (95%CI: 0.57-0.78, P=0.00). The predictive sensitivity and specificity of clinical efficacy in adult patients with chronic primary ITP treated with rituximab were separately 48.73% and 87.58%, and the AUC in 30th and 60th day after rituximab treatment were separately 0.74 (95%CI: 0.64-0.87, P=0.00), 0.93 (95%CI：0.82-0.98，P=0.00). CONCLUSION: Adult patients with chronic primary ITP may possess long-term remission after rituximab treatment, but the prognosis is poor for patients with bone marrow megakaryocyte count ＜150. The Plt counts in 14th, 30th and 60th days after rituximab treatment can effectively predict the long-term clinical efficacy and guide the formulation of treatment plans.

A Six-Epithelial-Mesenchymal Transition Gene Signature May Predict Metastasis of Triple-Negative Breast Cancer.

PURPOSE: Pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) is associated with favourable outcomes of patients with triple-negative breast cancer (TNBC). However, a proportion of TNBC patients with the residual disease do not relapse and achieve long-term survival. The aim of this study was to identify biomarkers that predict clinical outcomes in these patients. PATIENTS AND METHODS: A retrospective series of 10 TNBC patients who displayed non-pCR to NACT were included in the discovery cohort. Total RNA from pre-NACT core biopsies and paired surgical specimens were subjected to the Affymetrix Human Transcriptome Array. Gene set enrichment analysis (GSEA) was used to identify signal pathways and gene signatures associated with metastasis. The Cox proportional hazard model and Kaplan-Meier survival curves were employed to assess the prognostic value of the identified signature in two independent TNBC datasets included in Gene Expression Omnibus (GEO). RESULTS: The epithelial-mesenchymal transition (EMT) pathway was markedly more enriched in pre- (NES = 1.92; p.adjust = 0.019) and post-NACT samples (NES = 2.02; p.adjust = 0.010) from patients who developed metastasis after NACT. A subset of 6 EMT genes including LUM, SFRP4, COL6A3, MMP2, CXCL12, and HTRA1 were expressed constantly at higher levels in samples from patients who progressed to metastatic disease. The potential of the 6-EMT gene signature to predict TNBC metastasis after NACT was validated with a GEO dataset (HR=0.36, p=0.0008, 95% CI: 0.200-0.658). Moreover, the signature appeared of predictive value in another GEO dataset of TNBC patients who received surgery followed by adjuvant chemotherapy (HR = 0.46, 95% CI: 0.225-0.937). CONCLUSION: Expression analysis of the 6-EMT gene signature at diagnosis may be of predictive value for metastasis in TNCB patients who did not achieve pCR to NACT and for patients treated with surgery in combination with adjuvant therapy.

OnclncRNA-626 promotes malignancy of gastric cancer via inactivated the p53 pathway through interacting with SRSF1.

Gastric cancer (GC) is a serious health problem worldwide. The potential involvement of long noncoding RNAs in GC progression remains largely unexplored. Here, we identified a novel long noncoding RNA referred to as onclncRNA-626 (oncogenic lncRNA RP11-626H12.3), which was highly upregulated in GC tissues. The high expression levels of onclncRNA-626 in GC patients predicted poor prognoses. Functional assays indicated that onclncRNA-626 could promote the proliferation and metastasis of GC cells in vitro and in vivo. In exploring the molecular mechanisms guiding these functions, we found that onclncRNA-626 specifically interacted with serine- and arginine-rich splicing factor 1 (SRSF1) and increased its stability. SRSF1 was upregulated in GC tissues and correlated with onclncRNA-626 expression and patient survival. Furthermore, RNA-seq data revealed that onclncRNA-626 affected multiple signaling pathways, including the p53 signaling pathway. Rescue experiments showed that onclncRNA-626 probably performed its biological function through SRSF1 mediation of the p53 pathway. Together, our findings demonstrate that onclncRNA-626 promotes GC progression by binding SRSF1; further, this lncRNA is a potential prognostic biomarker for GC patients.

[IMSI versus ICSI for male factor infertility: A meta-analysis].

OBJECTIVE: To evaluate the efficacy and safety of intracytoplasmic morphologically selected sperm injection (IMSI) versus intracytoplasmic sperm injection (ICSI) in in vitro fertilization (IVF) for couples with male factor infertility. METHODS: Using the Cochrane system evaluation method, we searched MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov, and SinoMed and manually searched the reference lists of the included studies and relevant reviews for randomized controlled trials (RCT) comparing ICSI and IMSI published from 1992 to July 2017. We performed a meta-analysis on the included literature with the RevMan 5.3 software and subgroup analyses due to the prominent clinical heterogeneity of the patients. RESULTS: Of the 280 articles retrieved, 8 RCTs were included, involving 1 741 IVF cycles (842 cycles of IMSI versus 899 cycles of ICSI). There was no evidence for any significant difference between IMSI and ICSI in the live birth rate in the subgroup of infertility induced by pure male factors (RR = 1.31, 95% CI: 0.68－2.51; very low quality evidence from 1 RCT with 77 cycles) but an association of IMSI with an increased clinical pregnancy rate (RR = 1.46, 95% CI: 1.02－2.07; low quality evidence from 4 RCTs with 813 cycles), nor was there any evidence for that in the live birth rate (RR = 0.88, 95% CI: 0.60－1.31; low quality evidence from 1 RCT with 255 cycles) or clinical pregnancy rate (RR = 1.03, 95% CI: 0.86－1.23; moderate quality evidence from 3 RCTs with 851 cycles) in the subgroup of infertility caused by accompanying male factors. CONCLUSIONS: The evidence is of low quality for the association of IMSI with an increased rate of clinical pregnancy and is not sufficient to support the routine use of IMSI in IVF for male factor infertility.

Comparison of Mitoxantrone in Combination with Intermediate-dose Cytarabine versus High-dose Cytarabine as Consolidation Therapies for Young Non-APL Acute Myeloid Leukemia Patients with Favorable and Intermediate Cytogenetics.

In this study, we compared the efficacy of mitoxantrone in combination with intermediate-dose cytarabine (HAM) with that of high-dose cytarabine alone (HiDAC) as consolidation regimens in non-acute promyelocytic leukemia (APL) acute myeloid leukemia patients with favorable and intermediate cytogenetics. A total of 62 patients from Shenzhen People's Hospital were enrolled in this study. All patients enrolled received standard induction chemotherapy and achieved the first complete remission (CR1). In these patients, 24 received HiDAC and 38 received HAM as consolidation. The median relapse free survival (RFS) and overall survival (OS) were similar between these two consolidation regimens. Even in subgroup analysis according to risk stratification, the combination regimen conferred no benefit in longterm outcome in patients with favorable or intermediate cytogenetics. However, in patients receiving HAM regimen, the lowest neutrophil count was lower, neutropenic period longer, neutropenic fever rate higher, and more platelet transfusion support was required. HAM group also tended to have higher rate of sepsis than HiDAC group. According to our results, we suggest that combination treatment with mitoxantrone and intermediate-dose cytarabine has limited value as compared to HiDAC, even in young non-APL AML patients with favorable and intermediate cytogenetics.

Assisted Hatching in Couples with Advanced Maternal Age: A Systematic Review and Meta-analysis.

This systematic review aimed to evaluate the efficacy and safety of assisted hatching (AH) performed in couples with advanced maternal age. We searched for randomized controlled trials (RCTs) in electronic databases, including MEDLINE, EMBASE and CENTRAL (from inception to January 2018); in addition, we hand-searched the reference lists of included studies and similar reviews. We included RCTs comparing AH versus no treatment (control). The meta-analysis was performed by RevMan 5.3 software. The search retrieved 943 records and 8 RCTs were included, comprising 870 cycles (n=440 for AH, and n=430 for control). There was no significant difference in the rates of live birth (RR 0.88, 95% CI 0.65 to 1.18, 3 RCTs, n=427, I2=0%), clinical pregnancy (RR 1.00, 95% CI 0.83 to 1.19, 8 RCTs, n=870, I2=22%), implantation (RR 1.07, 95% CI 0.83 to 1.39, 4 RCTs, n=1359, I2=0%), miscarriage (RR 1.13, 95% CI 0.66 to 1.94, 2 RCTs, n=116, I2=0%) and multiple pregnancy (RR 0.89, 95% CI 0.31 to 2.52, 1 RCT, n=97, I2=not applicable) between the treatment group and control group. No reasonable conclusions could be drawn regarding reproductive outcomes after AH in patients with advanced maternal age due to the small sample pooled in meta-analyses. Studies of high methodological quality and with adequate power are necessary to further investigate the value of AH in assisted conception of those patients.

Proportion of Uterine Malignant Tumors in Patients with Laparoscopic Myomectomy: A National Multicenter Study in China.

BACKGROUND: The Food and Drug Administration recently announced that the use of morcellation may cause fibroids or pelvic dissemination and metastasis of uterine sarcoma; therefore, the use of morcellation is limited in the USA. A large sample study is necessary to assess the proportion of uterine malignant tumors found in patients with laparoscopic myomectomy. METHODS: A national multicenter study was performed in China. From 2002 to 2014, 33,723 cases were retrospectively selected. We calculated the prevalence and recorded the clinical characteristics of the patients with malignancy after morcellation application. A total of 62 cases were finally pathologically confirmed as malignant postoperatively. Additionally, the medical records of the 62 patients were analyzed in details. RESULTS: The proportion of postoperative malignancy after morcellation application was 0.18% (62/33,723) for patients who underwent laparoscopic myomectomy. Nearly 62.9% (39/62) of patients had demonstrated blood flow signals in the uterine fibroids before surgery. And, 23 (37.1%) patients showed rapid growth at the final preoperative ultrasound. With respect to the pathological types, 38 (61.3%) patients had detectable endometrial stromal sarcoma, 13 (21.0%) had detectable uterine leiomyosarcoma, only 3 (3.2%) had detectable carcinosarcoma, and 5 (8.1%) patients with leiomyoma had an undetermined malignant potential. CONCLUSIONS: The proportion of malignancy is low after using morcellation in patients who undergo laparoscopic myomectomy. Patients with fast-growing uterine fibroids and abnormal ultrasonic tumor blood flow should be considered for malignant potential, and morcellation should be avoided.

The effects of hyaluronic acid vaginal gel on the vaginal epithelium of ovariectomized rats.

OBJECTIVE: Hyaluronic acid is one of the best materials of water retention which can be used in vaginal atrophy. This study is to evaluate the role and mechanism of the hyaluronic acid vaginal gel (Hyalofemme) in the vaginal epithelium of ovariectomized rats. MATERIALS AND METHODS: Sixty SD rats were randomly divided into control group (Sham ovariectomy, Sham-OVX), tendency group (ovariectomy, OVX), and experiment group (ovariectomy+Hyalofemme, OVX+Hyalofemme). The hyaluronic acid vaginal gel was administered local vaginal therapy to the experiment group with cytologicaly confirmed vaginal atrophy. The doses were adjusted by animal weight according to human dosage. After daily treatment for 14 days, VEGF and P-AKT activations were detected by Western blot in the experiment group. RESULTS: The hyaluronic acid vaginal gel proved to be very effective in the cytological reversal of vaginal atrophy but did not increase uterine weight. Vaginal microecosystem indicators were negative in the control group and the experiment group. By contrast, the indicators were positive in the tendency group. CONCLUSION: Hyaluronic acid vaginal gel is effective in the reversal of vaginal atrophy and is beneficial for improving vaginal microecosystem in the postmenopausal rat model. The hyaluronic acid vaginal gel can also improve the repair capacity of the vaginal epithelium.

Provincial maternal mortality surveillance systems in China.

BACKGROUND: Provincial maternal mortality surveillance systems (PMMSS) have been set up in nearly all the provinces in China to monitor local maternal mortality and provide the evidence for maternal health interventions suited to local conditions. However, till now little is known outside of China about the characteristics of PMMSS. METHODS: A systematic review of the literature contained in PubMed and China Academic Journal Network Publishing database was carried out. The current situation on PMMSS was described. Provincial disparities on PMMR in six provinces were analyzed by Poisson regression analysis. RESULTS: A total of 35 studies met the inclusion criteria, of which 31 were published in Chinese. PMMSS were set up and adjusted by the provincial government based on their own financial resources and demand. Provinces from remote region had the highest risk of maternal mortality, followed by provinces from inland region and coast region. CONCLUSIONS: PMMSS may be the most reliable data source for measuring provincial level MMR in each province. Great provincial disparities on PMMSS and PMMR do exist within the country; more emphasis should be placed on improving PMMSS and reducing PMMR particularly in the provinces with high maternal death burden.

[Effects of NF-kappaB inhibitor on cisplatin-induced apoptosis in cervical cancer].

OBJECTIVE: To observe whether cisplatin-induced apoptosis were increased when SiHa cells were preincubated with nuclear factor-kappa B (NF-kappaB) inhibitors [aspirin, sulindac, curcumin or pyrrolidine dithiocarbamate (PDTC)]. METHODS: SiHa cells were preincubated 2 hours with aspirin, sulindac, curcumin and PDTC respectively, then a further incubation were done with cisplatin, and Western blot analysis were applied to detect P65 level of nuclear extraction. MTT assay was done to detect relative cell viability. TUNEL was applied to detect apoptosis rates. Flow cytometryies with PI staining were also used to detect apoptosis as well as cell cycle. RESULTS: When SiHa cells were pretreated with aspirin, sulindac, curcumin or PDTC, Western blot showed that the expression of P65 was inhibited upon cisplatin stimulus (P < 0.05). MTT assay demonstrated that a preincubation with NF-kappaB inhibitor could signifianctly increase cisplatin-induced chemosensitivity (P < 0.05). When cells pretreated with aspirin, sulindac, curcumin, or PDTC, TUNEL and flow cytometries assay showed that the apoptotic rates were all increased after 24 hours cisplatin stimulus (P < 0.05). Results of flow cytometries were also showed that a pretreation with aspirin, sulindac, curcumin, or PDTC could significantly increase cisplatin-induced apoptosis. CONCLUSION: Aspirin, sulindac, curcumin and PDTC could all inhibit cisplatin induced NF-kappaB activiation, which could increase cispaltin-induced chemosensativity by augments of apoptosis.

[Expression of long non-coding RNA HOTAIR mRNA in ovarian cancer].

OBJECTIVE: To investigate the long non-coding RNA HOTAIR (long non-coding HOX antisense intergenic RNA) by examining HOTAIR expression levels in ovarian cancer tissue and normal ovarian tissue. METHODS: The mRNA of long non-coding RNA HOTAIR expressions were detected by real-time fluorescence quantitative PCR in ovarian cancer (44) and normal ovary tissues (14). RESULTS: The expression of HOTAIR in ovarian cancer tissue was higher than that in normal ovarian tissue (1.26 +/- 0.27 vs. 0.14 +/- 0.09, P < 0.05). The expression was statistically higher in poorly differentiated ovarian cancer than poorly-moderately, moderately-well, and well-differentiated ones (1.65 +/- 0.41 vs. 0.39 +/- 0.14, P < 0.05). CONCLUSION: RNA HOTAIR expressions were higher in ovarian cancer; it may play a role in ovarian cancer, and become a biomarker for malignant degree of ovarian cancer and may provide a novel therapeutic target for ovarian cancer.

Energy controllable steep pulse (ECSP) treatment suppresses tumor growth in rats implanted with Walker 256 carcinosarcoma cells through apoptosis and an antitumor immune response.

Electrochemotherapy has been widely used for the treatment of solid tumors, although the underlying mechanism remains unclear. We aimed to investigate the effects of energy controllable steep pulse (ECSP) on the regulation of tumor growth and apoptosis in rats implanted with Walker 256 carcinosarcoma cells. A rat tumor model was established by injection of Walker 256 carcinosarcoma cells into the inguinal area. H&E staining, transmission electron microscopy, and the TUNEL assay were used to detect apoptosis. Concanavalin A-induced lymphocyte transformation and MTT assays were used to assess lymphocyte proliferation. ELISA was used to determine serum cytokine levels. After 2 weeks of ECSP treatment, tumor growth in rats was effectively suppressed, while tumor cell apoptosis was significantly induced compared to the control tumor group. Moreover, ECSP treatment enhanced proliferation and activation of lymphocytes and natural killer (NK) cells. Serum IL-2 and IFN-gamma levels were significantly decreased, and IL-4 and 1-10 levels dramatically increased in rats with control tumors compared to rats without tumors and lacking treatment (p < 0.05). In contrast, ECSP treatment increased IL-2 and IFN-gamma levels, but reduced IL-4 and IL-10 levels to normal values. Moreover, ECSP also increased TNF-alpha production, possibly from peritoneal microphages. Our current study demonstrates that ECSP treatment is able to effectively reduce tumors in rats via induction of apoptosis and activation of the rat antitumor immune response. These data provide insightful information for the future application of ECSP-based electrochemotherapy in clinical trials against solid tumors.

Wogonin potentiates cisplatin-induced cancer cell apoptosis through accumulation of intracellular reactive oxygen species.

Chemoresistance to cisplatin is a major limitation of cisplatin-based chemotherapy in the clinic. The combination of cisplatin with other agents has been recognized as a promising strategy to overcome cisplatin resistance. Previous studies have shown that wogonin (5,7-dihydroxy-8-methoxyflavone), a flavonoid isolated from the root of the medicinal herb Scutellaria baicalensis Georgi, sensitizes cancer cells to chemotheraputics such as etoposide, adriamycin, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and TNF. However, the effect of wogonin on cisplatin-induced cytotoxicity has not been previously reported. In this study, the non-small cell lung cancer cell line A549 and the cervical cancer cell line HeLa were treated with wogonin or cisplatin individually or in combination. It was found for the first time that wogonin is able to sensitize cisplatin-induced apoptosis in both A549 cells and HeLa cells as indicated by the potentiation of activation of caspase-3, and cleavage of the caspase-3 substrate PARP in wogonin and cisplatin co-treated cells. Importantly, wogonin robustly induced H2O2 accumulation in these cells, which substantially contributes to the sensitization of cisplatin cytotoxicity by wogonin, as two reactive oxygen species scavengers, butylated hydroxyanisole (BHA) and N-acetyl-L-cysteine (NAC), significantly suppressed the potentiated cytotoxicity caused by wogonin and cisplatin co-treatment. The results from this study provide important new evidence supporting the potential use of wogonin as a cisplatin sensitizer for cancer therapy.

[Prospective multi-center study in "Xiehe" pelvic floor reconstruction surgery for severe pelvic organ prolapse].

OBJECTIVE: To evaluate clinical efficiency and quality-of-life outcomes in treatment of severe pelvic organ prolapse by the "Xiehe" pelvic floor reconstruction surgery. METHODS: From Jun. 2006 to Dec. 2008, 277 severe pelvic organ prolapse patients with stage III to IV from 8 hospitals in China were enrolled in this prospective study. Pelvic organ prolapse quantitative examination (POP-Q) and anatomic improvement in these patients after surgery were analyzed in this interim study. Comparisons of pelvic floor impact questionnaire-short form 7 (PFIQ-7) and pelvic floor distress inventory-short form 20 (PFDI-20) in these patients before and after surgery was used to evaluate quality of life. Comparison of pelvic organ prolapse-urinary incontinence sexual questionnaire (PISQ) in these patients before and after surgery was used to evaluate quality of sexual life. RESULTS: With a median follow-up of 14.0 months (6 - 28 months), twenty-three patients showed recurrent prolapse (8.3%, 23/277), and anatomical success (< stage 2 in the treated compartment) was 91.7% (254/277). In this series, mesh exposure or erosion rate was 6.9% (19/277). The postoperative de novo stress incontinence rate was 6.5% (18/277). The scores for PFIQ-7 and PFDI-20, and its subscales were significantly improved, the scores of before treatment were lower than those after treatment (P < 0.01). And there was no significant difference in the average score of PISQ before and after the surgery (76.6 ± 15.4 versus 75.5 ± 14.5 versus 73.6 ± 12.6, P > 0.05), but the rate of de novo dyspareunia was 11% (9/80). CONCLUSIONS: "Xiehe" pelvic floor reconstruction surgery was safe and efficacy in treatment of pelvic organ prolapse. It could improve quality of life remarkably with less cost when compared with the traditional total pelvic floor reconstruction surgery.

High expressions of bcl-2 and survivin, and decreased apoptosis in uterine cervical carcinosarcoma compared to cervical squamous cell carcinoma.

PURPOSES: Uterine cervical carcinosarcoma (CS) is very rare. To date, only 40 cases have been reported. It seems to have a more aggressive clinical behavior than does cervical squamous cell carcinoma (SCC). The purposes of our study were to characterize the clinicopathologic characteristics and human papillomavirus (HPV) status of the rare tumor and to analyze the molecular features in cervical CS that may account for its aggressive behavior. METHODS: Three patients were diagnosed with uterine cervical CS at West China Second Hospital of Sichuan University between 1995 and 2009. Data were retrospectively analyzed from available charts and pathological reports. Twelve patients with FIGO stage Ib-IIa cervical SCC were enrolled as the controls, and the expression profiling of p53, Ki-67, bcl-2, survivin and apoptosis index between cervical CS and SCC was compared. Immunohistochemical and apoptosis results were scored separately for the carcinomatous and sarcomatous components. RESULTS: All three patients were shown to be negative for HPV infection by Hybribio HPV genoarray assay. Expression of p53 was observed in one patient in both carcinomatous and sarcomatous components in a similar proportion; in contrast, the Ki67, bcl-2 and survivin expressions were higher in carcinomatous components than in sarcomatous components in all three cases. Compared to cervical SCC, stronger immunostaining for bcl-2, survivin and lower apoptosis was observed in cervical CS. CONCLUSIONS: Cervical CS is a peculiar tumor with many different clinicopathologic characteristics from cervical SCC. Dysregulation of apoptosis may confer tumor cells of cervical CS with survival and growth advantages, and thereby facilitate the aggressive behavior of cervical CS.