Development and internal validation of a multivariable prediction model for 6-year risk of stroke: a cohort study in middle-aged and elderly Chinese population.

OBJECTIVE: To develop and internally validate a prediction model for 6-year risk of stroke and its primary subtypes in middle-aged and elderly Chinese population. DESIGN: This is a retrospective cohort study from a prospectively collected database. PARTICIPANTS: We included a total 3124 adults aged 45-80 years, free of stroke or myocardial infarction at baseline in the 2009-2015 cohort of China Health and Nutrition Survey. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome of the prediction model was stroke. Investigated predictors were: age, gender, body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), hypertension (HBP), drinking status, smoking status, diabetes and site. Stepwise multiple Cox regression was applied to identify independent predictors. A nomogram was constructed to predict 6-year risk of stroke based on the multiple analysis results. Bootstraps with 1000 resamples were applied to both C-index and calibration curve. RESULT: The overall incidence of overall stroke was 2.98%. Age, gender, HBP and TC were found as significant risk predictors for overall stroke; age, gender, HBP and LDL-C were found as significant risk predictors for ischaemic stroke; age, gender, HBP, BMI and HDL-C were found as significant risk predictors for haemorrhagic stroke. The nomogram was constructed using significant variables included in the model, with a C-index of 0.74 (95% CI: 0.72 to 0.76), 0.74 (95% CI: 0.71 to 0.77), and 0.81 (95% CI: 0.78 to 0.84) for overall stroke, ischaemic stroke, and haemorrhagic stroke model, respectively. The calibration curves demonstrated the good agreements between predicted and observed 6-year risk probability. CONCLUSION: Our nomogram could be convenient, easy to use and effective prognoses for predicting 6-year risk of stroke in middle-aged and elderly Chinese population.

Linc00161 regulated the drug resistance of ovarian cancer by sponging microRNA-128 and modulating MAPK1.

This study aimed to investigate the regulatory mechanism of linc00161/miR-128/MAPK1 axis on drug resistance of ovarian cancer. Methods: the differentially expressed lncRNAs were screened based on microarray analysis. The expression of linc00161, miR-128 and MAPK1 in ovarian cancer-resistant tissues and cells was tested qRT-PCR, whereas MAPK1 protein expression was examined via western blot in the ovarian cancer resistant cells. The targeted relationship between miR-128 and linc00161 as well as the relationship between miR-128 and MAPK1 were testified by Dual luciferase gene reporter assay. The influence of miR-128 and MAPK1 on the proliferation of ovarian cancer-resistant cells was demonstrated by CCK-8 and colony formation assay. The effect of linc00161 on ovarian cancer was demonstrated by xenograft tumor model in vivo. Results: Linc00161 was highly expressed in ovarian cancer-resistant tissues and SKOV3/DDP cells while the miR-128 displayed a lower expression. Overexpression of linc00161 increased the colony formation ratio in SKOV3 cells, whereas sh-linc00161 reduced colony formation ratio in SKOV3/DDP cells. MAPK1 was highly expressed in ovarian cancer-resistant tissues and cells and could be regulated by linc00161 and miR-128. The proliferation ability of SKOV3 cell was enhanced after transfected with miR-128 inhibitor, whereas that of SKOV3/DDP cells was attenuated by miR-128 mimics. In addition, the colony formation ratio of SKOV3 cells co-transfected with DDP + MAPK1 + sh-linc00161 decreased. The colony formation ratio of SKOV3/DDP cells also declined after transfected with DDP+ MAPK1. Linc00161 regulated the drug resistance of ovarian cancer via modulating microRNA-128/MAPK1. In vivo, sh-linc00161 inhibited the tumor growth.

Expression profile of circulating microRNAs as a promising fingerprint for cervical cancer diagnosis and monitoring.

Sensitive and specific biomarkers for the early detection of cervical cancer are urgently required to reduce the high morbidity and mortality of this disease. We previously demonstrated that circulating microRNAs (miRNAs) are correlated with certain types of human cancer. The aim of this study was to investigate the altered profile of serum miRNAs in cervical cancer patients in order to predict cervical cancer at a relative early stage. Serum samples were collected from 213 cervical cancer patients and 158 age- and ethnicity-matched controls. An initial screening of miRNA expression was performed by Solexa sequencing. Differential expression was validated using the stem-loop miRNA quantitative polymerase chain reaction (qPCR) assay in individual samples and the samples were arranged by two-phase selection and validation. The Solexa sequencing results revealed 12 markedly upregulated serum miRNAs in cervical cancer patients compared with controls. The reverse transcription-qPCR analysis identified a profile of 5 serum miRNAs (miR-21, -29a, -25, -200a and -486-5p) as a cervical cancer biomarker. The receiver operating characteristic curves indicated that a panel of 5 miRNAs constitutes a more sensitive and specific diagnostic test compared with any single miRNA-based assay, the squamous cell carcinoma antigen or the carbohydrate antigen 125. More importantly, miR-29a and miR-200a may indicate tumor histological grade and progression stage. Therefore, a 5-miRNA signature identified from genome-wide serum miRNA expression profiling may serve as a fingerprint for cervical cancer diagnosis.

Congenital Atresia of Uterine Isthmus: Successful Diagnosis and End-To-End Anastomosis.

BACKGROUND: Müllerian duct anomalies are rare and occasionally diagnosed in adolescents with primary amenorrhea, abdominal pain, and sexual difficulties. They are present in a variety of forms and sometimes difficult to appropriately classify. The management of malformations remains controversial. CASE: A 15-year-old girl with primary amenorrhea and cyclic lower abdominal pain was found on laparoscopic examination to have an asymmetric ball-shaped uterus with isthmus stenosis suspended in the pelvis. The junction between the lower segment of uterus and the cervix was very thin and stenotic with scar-like tissue changes. Combined with pathologic evaluation, it was finally diagnosed as congenital atresia of uterine isthmus. Thus, an end-to-end anastomosis was performed instead of surgical resection. SUMMARY AND CONCLUSION: Müllerian duct anomalies in a variety of forms can be difficult to diagnosis correctly and treat appropriately. Preservation of reproductive ability is the first objective of all treatments.

Activation of G-protein coupled estrogen receptor inhibits the proliferation of cervical cancer cells via sustained activation of ERK1/2.

Cervical cancer is one of the most common gynaecological women cancer and suggested to be modulated by estrogenic signals. G protein-coupled receptor (GPER), a seven-transmembrane G protein-coupled receptor, has been reported to regulate the cell proliferation of various cancers. But there is no study investigating the effects of GPER on the progression of cervical cancer. In the present study, we revealed for the first time that GPER was also highly expressed in various human cervical cancer cells. Activation of GPER via its specific agonist G-1 induced G2/M cell cycle arrest and down regulation of cyclin B via a time dependent manner. Furthermore, G-1 treatment induced sustained activation of extracellular-signal-regulated kinases (ERK)1/2 via epidermal growth factor receptor (EGFR) signals. Both inhibitors of ERK1/2 and EGFR significantly abolished G-1-induced suppression of cell proliferation and down regulation of cyclin B. Generally, our study revealed that GPER is highly expressed in human cervical cancer cells and its activation inhibits cell proliferation via EGFR/ERK1/2 signals. It suggested that G-1 can be considered as a potential new pharmacological tool to reduce the growth of cervical cancer.

Nearly Normal Congenital Cervical Fragmentation: A Hard-To-Diagnose and Successful End-To-End Anastomosis.

BACKGROUND: Congenital cervical fragmentation is a very rare genital tract malformation that usually presents in adolescence with primary amenorrhea and cyclic, monthly, lower abdominal pain. We report a nearly normal case of congenital cervical fragmentation and successful end-to-end anastomosis. CASE: A 15-year-old girl presented with primary amenorrhea with cyclic, monthly lower abdominal pain lasting for 15 months without any abnormal imaging findings (pelvic CT scan, ultrasonography, and hysteroscopy). Misdiagnosis and appendectomy was performed at the time of the initial lower abdominal pain. Diagnostic combined hysteroscopy and laparoscopy were performed in our hospital, and cervical fragmentation was diagnosed. A converted laparotomy end-to-end anastomosis was performed successfully, and regular menstruation was restored after the operation. SUMMARY AND CONCLUSION: The malformation of nearly normal congenital cervical fragmentation is existent and hard to diagnose. As long as the patient has persistent primary amenorrhea with cyclic, monthly lower abdominal pain, even if no abnormal findings on imaging, obstructive malformation of the reproductive duct should be the primary suspicion. Diagnosis and treatment should occur as early as possible to preserve the patient's fertility. End-to-end anastomosis is the best method for this type of patient.

Identification of four serum microRNAs from a genome-wide serum microRNA expression profile as potential non-invasive biomarkers for endometrioid endometrial cancer.

Serum microRNAs (miRNAs), with their remarkable stability and unique concentration profiles in patients with various diseases, are promising non-invasive biomarkers for tumor detection. The present study investigated the altered profiles of serum microRNAs in patients with endometrioid endometrial cancer (EEC) in order to predict the malignancy of the disease at a relatively early stage. TaqMan® low-density arrays (TDLAs) were used to perform an analysis in the initial screening phase using serum samples pooled from seven EEC patients and 20 controls. The differential expression was validated using a hydrolysis probe-based stem-loop quantitative reverse transcription polymerase chain reaction (qRT-PCR) in samples taken from 26 EEC patients and 22 age- and gender-matched healthy controls. The data obtained from the TLDAs demonstrated that 22 serum miRNAs were markedly upregulated in the EEC patients compared with the controls. The qRT-PCR analysis further identified a profile of four serum miRNAs (miR-222, miR-223, miR-186 and miR-204) as a fingerprint for EEC detection. The area under the receiver operating characteristic (ROC) curve of this four-serum miRNA signature was 0.927, which was markedly higher than that of carbohydrate antigen 125 (CA-125; 0.673). The four-miRNA signature identified by genome-wide serum miRNA expression profiling analysis provides a novel, non-invasive approach for EEC diagnosis.

Insulin-like growth factors in endometrioid adenocarcinoma: correlation with clinico-pathological features and estrogen receptor expression.

BACKGROUND: Endometrial carcinoma is a common malignancy of female genital tract. Insulin-like growth factor is known to elicit estrogen-induced mitogenic activity and anti-apoptotic effect in endometrial tissues. METHODS: The retrospective study investigated the expression of insulin-like growth factors, estrogen receptors and their associations in endometrioid adenocarcinoma (EAC) from 80 EAC patients in immunohistochemistry, and 58 EAC patients and 42 control patients in quantitative RT-PCR. The Pearson correlation analysis was used to analyze their correlations with clinic-pathological parameters. RESULTS: Our results showed that insulin-like growth factor-1 and insulin-like growth factor-2 mRNA levels were higher in tumor tissues and tumor-adjacent tissues than those in control cells, and were inversely correlated with the malignancy of the tumor with a positive correlation with ERα and ERß expression. Insulin-like growth factor-1R protein expression was correlated with clinical stage, and insulin-like growth factor-2R protein expression was inversely correlated with histological grade. CONCLUSIONS: Insulin-like growth factor system plays an important role in estrogen-induced endometrial carcinogenesis, and overexpression of insulin-like growth factor-1R in the advanced endometrioid adenocarcinoma is not estrogen-dependent.

[Inhibiting effect of letrozole combined with curcumin on xenografted endometrial carcinoma growth in nude mice].

BACKGROUND AND OBJECTIVE: Letrozole is an aromatase inhibitor that is used in the treatment of estrogen-sensitive tumors such as endometrial carcinoma, however, its therapeutic effect is still to be further improved. It is reported that curcumin has antitumor capability and can enhance the sensitivity of tumor cells to anticancer agents. This study was to investigate the inhibitory effect of letrozole combination with curcumin on the implanted endometrial tumor growth. METHODS: Nude mice were implanted with endometrial carcinoma RL-952 cells. All tumor-bearing mice were randomly divided into 5 groups: control(without treatment), Let(1) (letrozole, 1 microg/d), Let(10) (letrozole, 10 microg/d), Cur [ curcumin, 300 mg/kg.d)], and Let + Cur group [10microg/d letrozole + 50mg/ (kg.d) curcumin]. The tumor growth was monitored. Tumor cells apoptosis was detected in both control and treated groups. The expressions of bcl-2 mRNA and bcl-2 protein were detected using RT-PCR and Western blot, respectively. RESULTS: Fifty mice were successfully implanted with the endometrial tumor. Treatment with letrozole markedly inhibited tumor growth; the inhibitory effect was further enhanced by the combination of letrozole and curcumin. The inhibitory rates in Let (1), Let (10), the Cur, and the Let + Cur groups were 15.95%, 22.49%, 21.57%, and 35.89%, respectively. Treatment with curcumin inhibited the expression of bcl-2 in tumor cells at the mRNA and protein levels. The apoptosis rates in the control group and the four experimental groups mentioned above were 16.97%, 32.90%, 35.80%, 34.16%, and 47.24%, respectively. Tumor cells apoptosis were observed in mice treated with either letrozole or curcumin; however, combination of letrozole and curcumin further enhanced the inhibitory rate in tumor growth. CONCLUSIONS: Treatment with letrozole or curcumin could inhibit the xenografted endometrial tumor growth by inducing apoptosis in tumor cells. Combination of letrozole and curcumin further enhanced the inhibitory effect of tumor growth.

Uterus-like mass in the left broad ligament misdiagnosed as a malformation of the uterus: a case report of a rare condition and review of the literature.

OBJECTIVE: To describe a rare extrauterine mass of an unknown origin that was composed of smooth muscle with a central cavity lined by endometrium, which resembled a uterus. DESIGN: Case report. SETTING: Academic teaching hospital. PATIENT(S): A 17-year-old girl with severe dysmenorrhea was found to have a uterus-like mass composed of smooth muscle and lined by endometrium in the left broad ligament. INTERVENTION(S): Abdominal surgery. RESULT(S): The mass was successfully removed surgically, and her dysmenorrhea resolved. Histopathological examination revealed that the uterus-like mass was composed of smooth muscle with a cavity lined by endometrial glands and stroma. CONCLUSION(S): The histogenesis of a uterus-like mass is theorized to be a Müllerian system anomaly, metaplastic change, and/or heterotopia. We believe metaplasia is the most likely cause in this case. Alhough rare, it should be considered in the differential diagnosis of dysmenorrhea of uncertain etiology.

Aromatase inhibitor letrozole in synergy with curcumin in the inhibition of xenografted endometrial carcinoma growth.

OBJECTIVE: Endometrial carcinoma is a malignant tumor in the uterus. Its current treatment is not satisfactory. The present study aimed to promote the inhibitory effect on the implanted endometrial tumor growth. METHODS: Nude mice were implanted with endometrial carcinoma. Some tumor-laden mice were treated with aromatase inhibitor letrozole and/or curcumin. The tumor growth was monitored. Tumor cell apoptosis was detected in both control and treated groups. RESULTS: Fifty mice were successfully implanted with the endometrial tumor. Treatment with letrozole markedly inhibited the tumor growth; the inhibitor effect was further strengthened by combination with letrozole and curcumin. The results also showed that letrozole enhanced the expression of Bax and cytochrome c release and suppressed the expression of estrogen receptor in tumor cells. Treatment with curcumin inhibited the expression of Bcl-2 in tumor cells at the mRNA and protein levels. Tumor cell apoptosis was observed in mice treated with either letrozole or curcumin; however, combination of letrozole and curcumin further enhanced the inhibitory rate in tumor growth. CONCLUSIONS: Treatment with either letrozole or curcumin could inhibit the xenografted endometrial tumor growth via inducing apoptosis in tumor cells. Combination of letrozole and curcumin further strengthened the inhibitory effect on tumor growth.

[Angiogenesis and micrometastases of regional lymph node in ovarian cancer].

BACKGROUND & OBJECTIVE: In many investigation it was demonstrated that intratumor microvessel density (IMD) is the best factor for no tumor survival for patients with ovarian cancer. Occult axillary node micrometastases as the prognostic factor for the patients with breast cancer was proved, but currently no literature of the pelvic lymph node micrometastases in ovarian cancer is provided. This study try to detect the microvessel density of tumor tissues and micrometastases of regional lymph nodes in ovarian cancer and to investigate the relationship between these two factors and their prognostic significance. METHODS: The sections of ovarian cancer from 39 patients were stained immunohistochemically for cytokeratin(CK) and factor VIII-related antigen (F8-RA). Microvessels on the section were counted by computerized morphometry (40 fields). Sections of 212 regional lymph nodes from 39 patients were stained also with HE and CK. RESULTS: (1)We found 7 lymph node metastases with HE staining in 39 patients and 12 micrometastases with CK staining.(2) Average value of intratumor microvessel density (IMD) in the HE positive group was 48.86+/-16.60 and was obviously higher than that in the HE negative group (29.16+/-10.02,P< 0.01). The average IMD was 41.67+/-21.69 in the CK positive group and was also obviously higher than that in the CK negative group (28.70+/-10.77,P< 0.05). We found 8(50%) micrometastases in 16 patients with higher IMD (> or = 30/40 x fields) and only 4(17.4%) micrometastases in 23 patients with lower IMD (< 30/40 x fields), the difference was significant (P< 0.05). (3)IMD (P=0.03) and regional lymph node micrometastases(P=0.04) were the most significant factors to the survival time through Cox proportional hezard model analysis,the IMD (P=0.0008) and clinical stage (P=0.03) were also the most important factors to predict recurrence. CONCLUSION: The study suggests the CK immunohistochemical staining could detect the micrometastases in the HE negative lymph node in patients with epithelial ovarian cancer. The IMD is closely related to the micrometastases and these two factors have prognostic significance in ovarian cancer. The IMD and micrometastases could act as independent prognosis factors of patients with ovarian cancer.