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Secreted protein acidic and rich in cysteines-like 1 (SPARCL1) is implicated in tumor progression and considered as a tumor suppressor. Aim of the study is to investigate the role of SPARCL1 in the regulation of tumor biology. SPARCL1 expression in human cervical cells was determined through western blot and RT-PCR. The effects of SPARCL1 overexpression on cell proliferation, migration and invasion were evaluated through CCK8 assay, colony formation assay, Wound healing assay and Transwell assay, respectively. The gain function of Secreted phosphor protein 1 (SPP1) was also evaluated in these cell functions. We observed that SPARCL1 expression at protein levels and transcription levels was lower in HeLa cells than that in Ect1/E6E7 cells. When SPARCL1 was overexpressed in HeLa cells, cell proliferation, migration and invasion were greatly repressed. Additionally, SPARCL1 overexpression markedly downregulated SPP1 expression at transcription levels. Mechanistical study revealed that SPP1 overexpression could greatly counteract the effects of SPARCL1 overexpression on the aforementioned cell processes and inhibit the phosphorylation of focal adhesion kinase (FAK) and extracellular regulated protein kinases (ERK). Our findings indicated that HeLa cells overexpressing SPARCL1 showed weaker abilities of proliferation, migration and invasion, and its effects could be neutralized by SPP1 overexpression possibly via FAK/ERK pathway. The relationship of SPARCL1 and SPP1 could help us to further understand the pathogenesis of cervical cancer and SPARCL1/SPP1 could be beneficial therapeutic targets in cervical cancer.

BACKGROUND Malignant obstructive jaundice (MOJ) leads to hyperbilirubinemia and systemic pathophysiological changes. The main clinical treatments for MOJ include radical pancreatoduodenectomy, palliative surgical treatment, and minimally invasive treatment, which can relieve biliary obstruction, drain bile, reduce jaundice, and improve liver function. In rat models, hepatic exposure to endotoxin resulted in rapid increases in biliary and plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) levels, and our previous study revealed that Lp-PLA2 activity was strongly associated with liver damage. The present study aimed to clarify the serum Lp-PLA2 activity changes and evaluate the associations between Lp-PLA2 activity and laboratory parameters in MOJ patients preoperatively and postoperatively. METHODS Twenty-one patients with MOJ were enrolled in this prospective study. Lp-PLA2 activity and other laboratory parameters were analyzed using a Hitachi 7600 automatic biochemical analyzer. Spearman correlation coefficients, percent differences, and dynamic difference plots were used to evaluate the changes in preoperative and postoperative Lp-PLA2 activity and the associations of Lp-PLA2 activity with other laboratory parameters. RESULTS The postoperative Lp-PLA2 activity at 1 day [646 (range, 175-1,025) U/L], 1 week [419 (range, 144-949) U/L], and day of hospital discharge [347 (range, 165-698) U/L] differed significantly from the preoperative baseline activity (636 (range, 172-1,664) U/L; P

Objective: To analyze the correlation between placenta related disease of pregnant women with antecedent hysteroscopic adhesiolysis due to intrauterine adhesions (IUA). Materials and methods: This is a single center, non-randomized, open-label, retrospective cohort Study. 74 patients who had adhesiolysis and hormone therapy for IUA and progressed into the third trimester were group A and 296 without IUA were group B. The main outcome measure is the incidence of placenta related disease including placenta accreta spectrum, placenta previa, placental abruption, intrauterine growth restriction (IUGR), and pregnancy-induced hypertension (PIH). The second outcome is the perinatal, and intrapartum complications. Results: Patients in group A had a higher frequency of prior pregnancy times (2.51 ± 1.56 vs.1.84 ± 1.06, p = 0.001) and lower frequency of prior delivery times (0.20 ± 0.41 vs. 1.30 ± 0.51, p

Background Platinum resistance is an important cause of clinical recurrence and death for ovarian cancer. This study tries to systematically explore the molecular mechanisms for platinum resistance in ovarian cancer and identify regulatory genes and pathways via text mining and other methods. Methods Genes in abstracts of associated literatures were identified. Gene ontology and protein-protein interaction (PPI) network analysis were performed. Then co-occurrence between genes and ovarian cancer subtypes were carried out followed by cluster analysis. Results Genes with highest frequencies are mostly involved in DNA repair, apoptosis, metal transport and drug detoxification, which are closely related to platinum resistance. Gene ontology analysis confirms this result. Some proteins such as TP53, HSP90, ESR1, AKT1, BRCA1, EGFR and CTNNB1 work as hub nodes in PPI network. According to cluster analysis, specific genes were highlighted in each subtype of ovarian cancer, indicating that various subtypes may have different resistance mechanisms respectively. Conclusions Platinum resistance in ovarian cancer involves complicated signaling pathways and different subtypes may have specific mechanisms. Text mining, combined with other bio-information methods, is an effective way for systematic analysis.

Study Objective This study aims to evaluate the efficacy of the combination of bipolar radiofrequency impedance-controlled endometrial ablation (NovaSure; Hologic Inc., Bedford, MA) and levonorgestrel intrauterine system (LNG-IUS; Mirena; Schering AG, Berlin, Germany) placement in comparison with NovaSure endometrial ablation alone in patients with abnormal uterine bleeding (AUB). Design A propensity score matching study. Setting Beijing Tiantan Hospital, Capital Medical University, Beijing, China. Patients A retrospective study was conducted on 246 patients with AUB who underwent NovaSure endometrial ablation with (NovaSure+LNG-IUS group) or without (NovaSure group) LNG-IUS between January 2013 and August 2016. To overcome selection bias, propensity score matching was used to establish a 1:1 match between these 2 groups. Accordingly, 41 patients were included in each group. Intervention NovaSure endometrial ablation, immediately followed by LNG-IUS insertion in the NovaSure+LNG-IUS group, and NovaSure endometrial ablation alone in the control group. Measurements and Main Results Follow-up assessments performed at postablation months 6, 12, and 24 revealed the following: The rate of amenorrhea (78.05% vs 46.34%, 85.37% vs 53.65%, and 87.80% vs 58.54%, respectively; p Conclusion For women with AUB, the combination of NovaSure endometrial ablation and LNG-IUS is more effective than NovaSure alone in achieving amenorrhea, alleviating dysmenorrhea and reducing reinterventions.

Background: The outcomes of ovarian cancer patients are very poor, therefore it is necessary to find prognostic biomarkers and explore the potential underlying molecular mechanisms of ovarian cancer. Methods: In this study, a gene expression microarray data set covering 562 ovarian serous cystadenocarcinomas and 12,042 genes was downloaded from The Cancer Genome Atlas (TCGA) database. For each candidate gene, samples were allocated into a “high group” or a “low group” according to the expression level. The overall survival (OS) rates were compared between the two groups. Then, a univariate analysis and a multivariate Cox proportional hazards test were carried out to examine the associations between genes and multiple clinicopathological parameters. Results: Among all candidate genes, PI3 (peptidase inhibitor 3, often called elafin) and HLA-DOB (major histocompatibility complex, class II, DO beta) were identified as hub genes. PI3 (P=7.99e-7) and HLA-DOB (P=7.52e-6) showed significant associations with OS, especially in patients with stage III or IV disease. Both PI3 (HR =1.84, P=3.77e-7) and HLA-DOB (HR =0.68, P=0.001134) were identified as independent predictors of ovarian cancer patients OS. In addition, IRF1 (interferon regulatory factor 1) (P=1.16e-15) and SPI1 (Spi-1 proto-oncogene) (P=2.03e-6) were identified as the most significant transcription factors. Conclusions: Our data indicate that PI3 and HLA-DOB are potential biomarkers that could be used to predict the prognosis of ovarian cancer patients, and may play important roles in ovarian cancer progression. Further experimental and clinical studies with larger sample sizes are needed to confirm these findings.

Pulmonary hypertension (PH) is a frequent complication in patients with pulmonary fibrosis (PF), whereas the mechanism was not well-understood. This study aimed to explore the influence of immune cell infiltration on PH status based on the genomic expression profiles. Microarray data of GSE24988 were downloaded from the GEO database, including 116 lung tissue samples derived from PF patients with various PH status. Proportion of infiltrated immune cells was evaluated using CIBERSORT, a gene expression-based de-convolution algorithm. A random forest classifier was constructed and out of bag (OOB) cross-validation was carried out for PH prediction. The proportions of immune infiltration cells varied differently in PH samples except T regulatory cells (p-value = 0). Compared with non-PH samples, increased number of naive B cells and plasma cells were identified in PH samples, whereas activated dendritic cells and M2 macrophages were relatively lower (p < 0.05). In the random forest model, these four types of immune cells obtained a higher variable importance score than other cells, including mean decreased accuracy and mean decreased gini evaluation. We ran the OOB cross-validation in each sample of datasets (training set and testing set) and obtained 79 and 69% accuracy, respectively. Abnormal proportions of four types of immune cells were identified in PH samples compared with non-PH samples, suggesting their involvement in PH development. In summary, the immune cell infiltration in PF patients is associated with the PH status of patients, which deserves further investigation in the future.

Study Objective To evaluate the feasibility, effectiveness, and reproductive outcome of hysteroscopic management using the Hysteroscopy Endo Operative system (HEOS) in patients with diffuse uterine leiomyomatosis (DUL). Design Retrospective study (Canadian Task Force classification III). Setting Beijing Tiantan Hospital, Capital Medical University, Beijing, China. Patients Eight women of reproductive age suffering from menorrhagia and anemia or infertility diagnosed with DUL by ultrasonography and hysteroscopy. Interventions Hysteroscopic surgery using cold graspers combined with electric loop by the HEOS was performed to excise submucous myomas (including types 0, I, and II), leaving other intramural myomas in place. The fenestration method is used in electrical hysteroscopic myomectomy. Postoperative endometrial repair and synechiae, menstrual improvement, conception, and pregnancy were recorded. Measurements and Main Results Two patients underwent a single hysteroscopic myomectomy, whereas 6 patients underwent 2 to 3 myomectomies. No complications were observed. The mean follow-up period was 39.13 ± 17.01 months (range, 21–67). The endometrium recovered 2 to 3 months after the initial surgery, and 100% improvement in menstruation was observed. Two patients had mild synechia after the first hysteroscopic surgery. Seven patients conceived spontaneously (postoperative pregnancy rate, 87.5%), 6 of whom had a full-term pregnancy. One patient suffered a miscarriage in the second trimester (live birth rate, 75%). Conclusion Hysteroscopic surgery using cold graspers combined with electric loop by the HEOS is a feasible and effective for treatment of DUL because it preserves the uterus and yields favorable reproductive outcomes. The cold surgery and fenestration method minimizes electrical and thermal damage to the endometrium surrounding the myoma, consequently reducing surgical risks.

OBJECTIVE To evaluate the safety and efficacy of a modified vaginal closure in older women with severe pelvic organ prolapse (POP) with respect to symptoms, quality of life, postoperative satisfaction, regret rate, and complications METHODS:: From March, 2014 to December, 2016, in all, 32 women were enrolled in the study. All the participants underwent a modified vaginal closure. Records were reviewed to collect demographic characteristics and perioperative parameters. The Pelvic Floor Distress Inventory-short form 20 (PFDI-20) and the Short Form 36 Health Survey Profile (SF-36) were used to evaluate pelvic symptoms and self-perceived quality of life, respectively, 6 months postoperatively and at the latest follow-up. The Patient Global Impression of Change (PGI-C) was used to estimate the satisfaction. The satisfaction and regret rates were assessed at the latest follow-up. RESULTS After an average follow-up period of 23 months (range 8-41 months), none of the 32 women experienced recurrence of prolapse that required reoperation. During follow-up, significant improvements were observed in the Pelvic Organ Prolapse Distress Inventory (POPDI-6), Urinary Distress Inventory (UDI-6), and SF-36 results (P

The aim of the study was to evaluate the performance of a folate receptor-mediated tumor detection (FRD) assay for detection of cervical high-grade lesions.A total of 1504 patients with abnormal cytology and/or positive human papillomavirus (HPV) testing during primary screening from November 2014 to August 2015 were enrolled. The patients were recruited from the Peking University People's Hospital and 12 other hospitals. Folate receptor-mediated tumor detection was applied in all the patients before colposcopy to compare the detection rate, sensitivity, specificity, positive predictive value, negative predictive value, and coincidence rate with HPV and cytology tests according to the pathologic diagnosis.In the total of 1504 patients, 503 patients were negative for intraepithelial lesion or malignancy, 440 patients were cervical intraepithelial neoplasia (CIN) 1, 254 patients were CIN 2, 257 patients were CIN 3, 46 patients were squamous cell carcinoma, and 4 patients were adenocarcinoma in situ. The sensitivity of FRD was 77.72%, which was less than cytology (80.39%) and HPV testing (95.54%). The specificity of FRD was 60.02%, which was greater than cytology (30.12%) and HPV testing (14.95%). The coincidence rate of FRD to the pathologic diagnosis (66.62%) was also significantly greater than atypical squamous cells of undetermined significance cytology and above (48.87%) and HPV testing (45.01%, p.0001). The detection rate of FRD for all grades of lesions increased with the severity of lesions.Folate receptor-mediated tumor detection has a slightly lower sensitivity and a higher specificity than cytology and HPV testing for detection of CIN 2+. Simplicity of FRD requires less professional skill. Folate receptor-mediated tumor detection could be a candidate test for cervical cancer screening especially in low- and middle-income countries. However, FRD still needs more clinical trial data to demonstrate its ability in general screening population.

• BackgroundThe septate uterus is the most common uterine malformation. The uterus septum increases the possibility of adverse pregnancy outcomes which can be improved by hysteroscopic metroplasty (trans-cervical resection of septate, TCRS). Various methods are used to prevent postoperative intrauterine adhesion in clinical practice. However, there is insufficient evidence to support or oppose the use of any of them. This study will be a multi-center, open labeled, prospective, randomized, controlled study. We will examine whether it is necessary to use the anti-adhesion barrier or a certain dose estrogen to prevent intrauterine adhesion after TCRS and further improve the fertility outcome.• MethodsA total of 243 patients with septate uterus who meet the inclusion criteria will be randomly assigned into three groups with 1:1:1 allocation ratio. Group A will be the control group without any application of anti-adhesion method after TCRS; the participants in group B will be inserted an intrauterine balloon stent after TCRS for one week; the participants in group C will take estradiol valerate (2mg, bid) for 2 months after the surgery. A second-look hysteroscopy will be carried out after two menstrual cycles after the surgery to evaluate the intrauterine condition. Pregnancy outcomes, particularly the live birth rate, will be followed for at least one year.• DiscussionThis study will be the first well-powered clinical trial to assess the effectiveness of the anti-adhesion barrier or a certain dose of estrogen to prevent intrauterine adhesion after TCRS and further improve the fertility outcome. Our findings will guide the clinical care of patients after TCRS.Trial registration: ChiCTR, ChiCTR2000032061. Registered on Apr 19, 2020, http://www.chictr.org.cn/showproj.aspx?proj=52499

Since December 2019, the outbreak of novel coronavirus disease 2019 became a major epidemic threat in China and later spread worldwide. During the coronavirus disease 2019 outbreak in mainland China, the Chinese Obstetricians and Gynecologists Association distributed guidelines regarding the care of gynecologic patients. These guidelines were developed by the Department of Obstetrics and Gynecology at the Peking Union Medical College Hospital and represent an effort to integrate infection control strategy and promote professionalism in medical practice. The guidelines represent collaboration with experts from 31 provinces and autonomous regions of mainland China over 2 weeks' time. With the implementation of these guidelines, no nosocomial infections of coronavirus disease 2019 have been identified at the Peking Union Medical College Hospital. We think these guidelines might be helpful to departments of obstetrics and gynecology internationally during these unprecedented times. In our guidelines, we describe basic infection precaution principles, an epidemiologic screening tool, prioritization of surgical procedures, and operating room requirements. Using these principles, we then review the management of gynecologic patients during the coronavirus disease 2019 epidemic in the outpatient and operative and nonoperative inpatient settings and in clinical trials.

The severity and complexity evaluation of coronary artery disease in patients with coronary heart disease (CHD) require objective and accurate prognosis indexes. We assessed the relationship between lncRNA-Ang362 and prognosis of CHD patients after percutaneous coronary intervention (PCI). Clinical follow-up data of CHD patients were prospectively collected. LncRNA-Ang362 levels were detected by real-time quantitative polymerase chain reaction. Survival rate was calculated by the Kaplan–Meier method, and risk ratios and 95% confidence intervals were computed using univariate and multivariate COX proportional hazard models. Finally, 434 patients were included in the follow-up cohort. The median follow-up time was 24.8 months (6.7–40). The incidence of adverse cardiovascular events was 13.6%. The high expression group significantly tended to be smoker and higher body mass index, low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, creatinine, and uric acid levels compared with the low expression group. According to the SYNTAX grade, the high-risk and medium-risk groups had significantly higher lncRNA expression levels than the low-risk group. The univariate COX regression analysis indicated that high lncRAN-Ang362 expression significantly increased the risk of adverse cardiovascular events in CHD patients after PCI (hazard risk (HR) = 3.19, 95% confidence interval (CI): 1.29–7.92). Multivariate analysis found high lncRNA-Ang362 expression was independently related to worse prognosis in CHD patients after PCI (HR = 2.83, 95%CI: 1.34–6.02). Plasma lncRNA-Ang362 may be a prognosis factor in CHD patients after PCI. The patients with higher lncRNA-Ang362 expression usually have poor prognosis.

Reperfusion after myocardial ischemia can induce cardiomyocyte death, known as myocardial reperfusion injury. The pathophysiology of the process of reperfusion suggests the confluence multiple pathways. Recent studies have focused on the inflammatory response, which is considered to be the main mechanism during the process of myocardial ischemia-reperfusion injury and can cause cardiomyocyte apoptosis. Peroxisome proliferator-activated receptors gamma activated by endogenous ligands and exogenous ligand can decrease the inflammatory response in cardiomyocytes. Thiazolidinediones are synthetic, high-affinity, selective ligands for peroxisome proliferator-activated receptors gamma, and can inhibit the inflammatory response, decrease myocardial infarct size, and protect cardiac function. However, thiazolidinediones, including rosiglitazone and pioglitazone, can also contribute to adverse cardiovascular events such as congestive heart failure. Therefore, there are some limitations to the use of thiazolidinediones. Most endogenous ligands were of low affinity until hexadecyl azelaoyl phosphatidylcholine was identified as a high-affinity ligand and agonist for peroxisome proliferator-activated receptors gamma. Hexadecyl azelaoyl phosphatidylcholine binds recombinant peroxisome proliferator-activated receptors with an affinity (Kd(app) ≈40 nM) which is equivalent to rosiglitazone. Therefore, hexadecyl azelaoyl phosphatidylcholine is a specific peroxisome proliferator-activated receptors gamma agonist. Given these findings, we hypothesized that the use of hexadecyl azelaoyl phosphatidylcholine can activate the peroxisome proliferator-activated receptors gamma signal pathways and prevent the inflammatory response process of myocardial ischemia-reperfusion injury, with reduced cardiomyocyte apoptosis and death.

Background/Aims: Co-stimulating molecule B7-H4 regulates T cell-mediated immune responses, participates in tumor immune escape, and promotes the proliferation and metastasis of pancreatic cancer cells. However, the specific mechanisms are unclear. MicroRNAs (miRNAs) participated in the pathogenesis and progression of cancer. Methods: In this study, a microarray technique was used to screen B7-H4-related differentially expressed miRNAs in a pancreatic cancer cell line find those associated with pancreatic cancer. Using a miRCURYTM LNA Array approach, we compared the miRNA expression profiles of L3.6p1 pancreatic cancer cells transfected with B7-H4 siRNA for 72 h with those transfected with non-target siRNAs. Results: B7-H4 siRNA significantly up-regulated 57 miRNAs and down-regulated 14 miRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis of predicted miRNA targets showed that these genes were mainly involved in protein binding, pathways in cancer, mitogen-activated protein kinase (MAPK) signaling pathway, and phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling pathway. Conclusions: This is the first description of target genes of B7-H4, showing that miRNAs participate in the B7-H4 mediated regulation of oncogenicity and pathogenesis of pancreatic cancer. These results may help us better understand the role of B7-H4 in the progression of pancreatic cancer and its possible mechanisms. We also provide novel biomarkers for potential treatments of pancreatic cancer.

With the rapid expansion of maritime traffic, increases in air emissions from shipping have exacerbated numerous environmental issues, including air pollution and climate change. However, the effects of such emissions on marine biogeochemistry remain poorly understood. Here, we collected ship-emitted particles (SEPs) from the stack of a heavy-oil-powered vessel using an onboard emission test system and investigated the impact of SEPs on phytoplankton growth over the northwest Pacific Ocean (NWPO). In SEP microcosm experiments conducted in oceanic zones with different trophic statuses, the phytoplankton response, as indicated by chlorophyll a (Chl a), has been shown to increase with the proportion of SEP-derived nitrogen (N) relative to N stocks (PSN) in baseline seawater, suggesting that SEPs generally promote phytoplankton growth via N fertilisation. Simulations using an air quality model combined with a ship emission inventory further showed that oxidised N (NOx) emissions from shipping contributed ~43% of the atmospheric N deposition flux in the NWPO. Air emissions from shipping (e.g. NOx and sulphur dioxide) also indirectly enhanced the deposition of reduced N that existed in the atmosphere, constituting ~15% of the atmospheric N deposition flux. These results suggest that the impact of airborne ship emissions on atmospheric N deposition is comparable to that of land-based emissions in the NWPO. Based on the ship-induced PSN in surface seawater calculated by modeling results and World Ocean Atlas 2013 nutrient dataset, and the well-established quantitative relationship between Chl a and PSN obtained from microcosm experiments, we found a noticeable change in surface Chl a concentrations due to N deposition derived from marine traffic in the NWPO, particularly in the coastal waters of the Yellow Sea and open oceans. This work attempts to establish a direct link between marine productivity and air emissions from shipping.

// Ya Zhao 1, 2, * , Li-Min Feng 1, * , Li-Juan Liu 1 , Xian Zhang 1 , Rui-Zhi Zhao 1 1 Department of Chinese Medicine Property Team, Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China 2 The Postdoctoral Research Station, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China * These authors have contributed equally to this work Correspondence to: Rui-Zhi Zhao, email: 13610241754@163.com Keywords: clerosterol, transporter, Pgp, Mrp, Oct Received: August 04, 2016 Accepted: January 24, 2017 Published: February 09, 2017 ABSTRACT Vinegar-baked Radix Bupleuri (VBRB) is reportedly used to treat liver cancer when combined with traditional chemotherapy and data show that this combination may modify drug transport. We isolated clerosterol from VBRB and studied its effect on drug transporters in normal or transporter-overexpressing cells. Transporter activity was assayed using cellular substrate concentration and transporter expression with Western blot and RT-qPCR. Clerosterol decreased cisplatin uptake in BRL cells mainly through increasing Mrp2 gene expression. Clerosterol also decreased the uptake of colchicine in HEK 293 cells by increasing both Pgp and Mrp1 activity; in detail, it could increase Pgp protein but had marginal effects on Mrp1 protein and gene expression. Further study showed clerosterol increased OCT2 activity in HEK293-Pgp cells by increasing OCT2 protein and mRNA. Clerosterol could suppress Pgp overexpression but not by regulating protein and gene expression. And clerosterol had marginal effects on Mrp2 and Mrp1 activity in Mrp2- and Mrp1-overexpressing HEK293 cells. Thus, Clerosterol may be an active constituent of VBRB and may work against cancer multidrug resistance by inhibiting Pgp activity.

Background Epilepsy during pregnancy and puerperium is infrequent, and it can induce severe complications and poor prognosis. Pregnancy in women with epilepsy (WWE) is usually uneventful. Previous studies have mainly focused on the effects of different treatments on prognosis. However, few articles have addressed if different epilepsy types were associated with a higher incidence of seizure breakthrough/recurrence and pregnancy outcomes. Methods In the present study, based on a unique sample with a low incidence of epilepsy, we evaluated the main clinical characteristics of epilepsy patients. Results Mean age of pregnant WWE was 29.95±4.65 (range, 21-42) years. Pregnancies were at a mean gestational age of 33.80±9.14 (range, 7-41) weeks, and 88.24% (52/61) of WWE were in their third trimester. There was 9.84% (6/61) of pregnant WWE underwent abortion or induced labor in midpregnancy to ensure maternal safety. There was 75.41% (46/61) of pregnant WWE using antiepileptic drugs (AEDs), of which 52.46% (32/61) were taking a single AED and 22.95% (14/61) were using multiple AEDs. There was 47.54% (29/61) of WWE experiencing seizures during their pregnancy. We found that the type of epilepsy did not affect seizures during pregnancy or the prognosis. However, more pregnant WWE with hypertensive disorder had seizures compared with pregnant WWE without hypertensive disorder. Conclusions The study highlighted a novel direction for effectively improving seizures during pregnancy and the prognosis of pregnancy-associated epilepsy.

BACKGROUND Reference intervals (RIs) of Apo E levels are an important parameter for the clinical evaluation of patient health, and the RIs of serum Apo E could be variable in different population. We plan to establish RIs of apolipoprotein E (Apo E) according to the CLSI EP28-A3 guideline in healthy Chinese Han adults. METHODS Serum Apo E values of 1,206 healthy adults (from 19 to 87 years old) were measured by immunoturbidimetry. The relationship between Apo E and age was analyzed by using Spearman's correlation. The differences between the gender and age groups were compared using Mann-Whitney U test/Kruskal-Wallis H test. We calculated recommended nonparametric Q2.5 and Q97.5 percentile intervals and the 90% confidence intervals (CI) of lower and upper limits to define the age- and gender- related RIs. RESULTS The level of Apo E was higher in females than males. Apo E was significantly associated with aging in adult females (r = 0.108, p < 0.05), but not in males (p = 0.518). The RIs of Apo E for females were 0.0268 - 0.0619, 0.0247 - 0.0603, and 0.0269 - 0.0658 g/L for 18 - 29, 30 - 59, and ≥ 60 years old, respectively, that for males was 0.0242 - 0.0579 g/L. CONCLUSIONS Our results established the age- and gender-specific RIs of serum Apo E in healthy Chinese Han adults in our laboratory.

To describe the fertility outcomes after hysteroscopic adhesiolysis combined with preoperative hormone treatment in women with intrauterine adhesion (IUA). This study is a retrospective cohort study. A total of 230 patients with IUA underwent hysteroscopic adhesiolysis combined with hormone treatment from Jan 2012 to Jun 2018. 148 patients who received preoperative estrogen treatment were enrolled into group A and 82 patients without preoperative estrogen treatment were enrolled into group B. All the patients underwent hysteroscopic adhesiolysis and received postoperative estrogen therapy, intrauterine indwelling device. Second or third look was performed after 2–3 months. 90.87% (209/230) patients complete the study. The AFS scores at baseline were higher in the group A than group B. After the preoperative E2 treatment, group A achieved the comparable AFS score to group B before the surgery. The cumulative fertility rate in group A was comparable in group B, both in the ITT analysis (49.32% vs. 52.44%, p = 0.651) and the PP analysis (54.07% vs.58.10%, p = 0.575).The mean conception time was also similar in group A and group B (8.30 ± 6.47 vs. 8.54 ± 5.68 months, p = 0.837). Besides, the surgery times in group A were less than group B. There was no difference in the rate of adverse events between two groups. Hysteroscopic adhesiolysis combined with preoperative oestrogen could reduce the preoperative AFS scores and the times of surgery which yield a similar conception rate in women with less severe intrauterine adhesions.

OBJECTIVE To evaluate the efficacy of folate receptor-mediated tumor detection (FRD) for identifying high-grade intraepithelial squamous lesions (HSIL) in the triage of women who are positive for human papillomavirus (HPV), and those with cytology findings of atypical squamous cells of undetermined significance (ASCUS). METHOD A secondary analysis of prospectively collected data from 1504 women who had abnormal results during primary cervical cancer screening at 13 hospitals in Beijing, China, between November 2014 and August 2015. The detection accuracy of FRD was evaluated among HPV-positive women and women with ASCUS referred for colposcopy examination. RESULTS Among 1338 women with HPV, the percentage coincidence with pathology findings was higher for FRD (66.7%) than for cytology of ASCUS or higher (51.5%). The rate of colposcopy referral for cytology and FRD as a triage tool was 969 (72.4%) and 736 (55.0%), respectively. Thus, 233 (17.4%) fewer women would be referred for colposcopy by FRD. Among 476 women with cytology of ASCUS, the percentage coincidence with pathology findings was higher for FRD (63.4%) than for HPV (35.9%). CONCLUSION FRD was found to be a promising triage tool for women who are HPV-positive and those with cytology findings of ASCUS.

Previous studies investigate the relationship between peroxisome proliferator-activated receptor γ-2 (PPAR) gene Pro12Ala polymorphisms and risk of hypertension. However, the number of available studies was extremely limited. We updated this evidence and gave more significant results. We performed comprehensive computer-based searches in the PubMed, Web of Science, Embase, Google Scholar, the Cochrane library, Wanfang database, China National Knowledge Infrastructure, and China Biological Medicine Database. All studies that reported the association between the PPARγ2Pro12Ala polymorphisms and hypertension were identified. Twenty-one studies were finally included in the present study. In the domain model, the PPARγ1Pro12Ala polymorphism was not associated with hypertension (odds ratio (OR) = 0.85, 95% confidence interval (CI): 0.71–1.03, P=0.108). The significant relationship was found in the recessive model (OR = 0.67, 95% CI: 0.53–0.85), in the additive model (OR = 0.61, 95% CI: 0.48–0.77), and in the allele genetic model (OR = 0.81, 95% CI: 0.66–0.99). Subgroup analysis indicated that the PPARγ1Pro12Ala polymorphism from the all gene models was also not related to the risk of hypertension in Caucasians. In Asians, however, the results (P=0.002; I2 = 57.6%) suggested a significant relationship between PPARγ1Pro12Ala and hypertension in the domain model (OR = 0.80, 95% CI: 0.65–0.99), in the recessive model (OR = 0.57, 95% CI: 0.44–0.75), in the additive model (OR = 0.51, 95% CI: 0.39–0.66), and in the allele model (OR = 0.75, 95% CI: 0.60–0.94). The PPARγ1Pro12Ala polymorphism could affect the risk of primary hypertension amongst Asians. The A allele gene was a protective genotype for primary hypertension. The PPARγ1Pro12Ala polymorphism was not associated with hypertension amongst Caucasians.

Epilepsy in pregnancy can lead to substantial maternal and neonatal morbidity and mortality. Early intervention in pregnant women with epilepsy (WWE), accurate assessment of the severity of their condition, and effective treatment are required to improve maternal and neonatal prognosis. Many obstetricians lack experience in monitoring and treating pregnant WWE.The aim of this study was to describe the demographic and clinical characteristics of pregnant WWE and examine maternal and neonatal outcomes.Medical records of 75 pregnant women with a history of epilepsy who delivered at Beijing Tiantan Hospital, China between January 2006 and December 2019 were retrospectively reviewed. Pregnant women with a history of epilepsy were matched 1:2 with a control group of 150 pregnant women without epilepsy who delivered at Beijing Tiantan Hospital during the same time period. Information including type and frequency of epilepsy and seizures, maternal complications, medication, delivery mode, newborn weight, and newborn Apgar score were recorded. In subgroup analyses, pregnant WWE were stratified according to presence or absence of seizures during pregnancy and generalized seizure vs. nongeneralized seizure.The incidence of anemia, hypertensive disorder of pregnancy, premature rupture of membranes (PROM), cesarean section, and postpartum hemorrhage was significantly higher (p 0.05), and mean newborn weight and newborn Apgar score were significantly lower (p 0.05) in pregnant WWE compared with pregnant women without epilepsy. The incidence of premature delivery was significantly higher (p 0.05), and mean newborn weight was significantly lower (p 0.05) in pregnant WWE with seizures vs. without seizures. Mean newborn weight was significantly lower (p = 0.01) in pregnant WWE with nongeneralized seizures vs. generalized seizures.Pregnant WWE are at high risk of anemia, gestational hypertension, PROM, cesarean section, postpartum hemorrhage, and low newborn weight and Apgar score. Women with epilepsy who experience seizures during pregnancy are at high risk of preterm birth and having low birth weight infants. Pregnant WWE who experience nongeneralized seizures are at high risk of having low birth weight infants. These data emphasize the need to routinely monitor fetal weight on ultrasound and offer appropriate intervention. These findings highlight the need for healthcare providers to take a multidisciplinary approach to the management of pregnant WWE.Pregnant WWE are at high risk of obstetric complications. Women with epilepsy who experience seizures during pregnancy are at high risk of preterm birth and having low birth weight infants. Pregnant WWE who experience nongeneralized seizures are at high risk of having low birth weight infants. These data highlight the need for healthcare providers to take a multidisciplinary approach to the management of pregnant WWE.

Background Metabolic risk factors including obesity, insulin resistance, dyslipidemia, metabolic syndrome (MS), and diabetes are associated with nonalcoholic fatty liver disease (NAFLD). γ-Glutamyl transpeptidase (GGT) and high-density lipoprotein cholesterol (HDL-C) are associated with insulin resistance, dyslipidemia, oxidative stress, and obesity. We investigated the associations between GGT/HDL-C ratio and prevalence of NAFLD in a Chinese population. Methods The study included 1,813 NAFLD (526 females, 1,287 males) and 4,513 non-NAFLD (3,077 females, 1,436 males) participants. The diagnosis of NAFLD was based on ultrasonography. Results Participants with NAFLD had higher GGT/HDL-C ratio, BMI, WC, TG, TC, and HOMA-IR, but lower HDL-C than participants without NAFLD. GGT/HDL-C ratio was significantly associated with prevalence of NAFLD. Specifically, for each 1 unit increase in GGT/HDL-C ratio, the prevalence of NAFLD will increase by 0.3%. As GGT/HDL-C ratio quartiles increased, prevalence of NAFLD/MS in Q4 (highest GGT/HDL-C ratio quartile) was 6.362/3.968 times higher than that in Q1 (lowest GGT/HDL-C ratio quartile). The AUC [0.799 (0.788-0.810)] for GGT/HDL-C ratio was significantly higher than those for GGT and HDL-C alone. Conclusions The present results suggest that GGT/HDL-C ratio can be used as a predictive factor for prevalence of NAFLD after adjustment for confounding variables.

OBJECTIVES The levels of tumor markers in pancreatic neuroendocrine carcinoma (PNEC) are unknown, and imaging findings of PNEC and pancreatic ductal adenocarcinoma (PDAC) have overlaps. In this study, we show the tumor markers in PNEC and evaluate their values for distinguishing PNEC from PDAC. METHODS Thirty-three cases of PDAC and 21 cases of PNEC were retrospectively evaluated. The demographic information and clinical data were reviewed. RESULTS Pancreatic neuroendocrine carcinoma was usually misdiagnosed (57.1%) as PDAC based on imaging findings. Abnormal carbohydrate antigen (CA) 19-9, carcinoembryonic antigen (CEA), and α-fetoprotein (AFP) were observed in 19.0% to 28.6% of PNECs. Abnormal CA 19-9 and CA 125 levels were more common in PDAC than in PNEC (P < 0.05). Higher level of AFP was more common in PNEC than in PDAC (33.3% vs 3.0%, P < 0.05). The cutoff value of CA 19-9 for detecting PNEC was calculated as 38.5 U/mL or less with 0.788 sensitivity and 0.800 specificity. Carbohydrate antigen 19-9 (odds ratio [OR], 22.9; 95% confidence interval [CI], 2.94-179.3), AFP (OR, 0.08; 95% CI, 0.012-0.564), and CA 125 (OR, 17.4; 95% CI, 1.13-267.3) were predictors in differentiating PDAC from PNEC. CONCLUSIONS Carbohydrate antigen 19-9, AFP, and CA 125 have potential for distinguishing hypovascularized PNEC from PDAC.

The manifestations of pulmonary cryptococcosis with multiple nodules or masses on computed tomography (CT) are diverse and difficult to differentiate from those of lung cancer and pulmonary tuberculosis. The present study compared the multislice spiral CT signs with pathological results and used the pathological results to explain the CT signs with the aim of improving the accuracy of the diagnosis of this disease. A retrospective analysis of 20 patients with primary pulmonary cryptococcosis with multiple nodules or masses was performed. Based on the CT signs, eight patients had been misdiagnosed with lung cancer accompanied by intrapulmonary metastasis andthree patients had been misdiagnosed with tuberculosis. The major CT manifestations were a cluster of nodules or masses located within 2 cm below the pleura and distributed along the bronchi. A total of nine patients had primary lesions with diameters of 1.1–2.0 cm and 12 patients had satellite lesions with diameters of 0.1–1.0 cm. Regarding treatment, 5 patients underwent surgical monotherapy, 12 patients underwent antifungal monotherapy and three patients received surgery in combination with antifungal therapy. HE staining indicated that Cryptococcus neoformans was engulfed by macrophages, which were surrounded by massive infiltrating lymphocytes and a large amount of fibrous tissue, which formed multinucleated macrophages or granulomas. Periodic acid-Schiff staining was positive and acid fast staining was negative. In conclusion, comparison of CT signs with the pathological manifestation of pulmonary cryptococcosis with multiple nodules or masses indicated that the pathological results may explain certain imaging signs. Combination of CT and pathological examination may provide a deeper understanding of this disease and improve the accuracy of its diagnosis.

BACKGROUND Reperfusion injury is one of the leading causes of myocardial cell death and heart failure. This study was performed to identify new candidate lipid biomarkers for the purpose of optimizing the diagnosis of myocardial ischemia reperfusion (I/R) injury, assessing the severity of myocardial I/R injury and trying to find the novel mechanism related to lipids. MATERIAL AND METHODS Forty patients who were diagnosed with ST-segment elevation myocardial infarction (STEMI) were randomly selected for this study. Serum samples from all the patients with STEMI were collected at 3 time periods: after STEMI diagnosis but prior to reperfusion (T0); and then at 2 hours (T2) and 24 hours (T24) after the end of the percutaneous coronary intervention procedure. Plasma lipidomics profiling analysis was performed to identify the lipid metabolic signatures of myocardial I/R injury using lipidomics. RESULTS Sixteen types of potential lipid biomarkers at different time periods (T0, T2, T24) were identified by using lipidomics technology. The T0 time periods exhibited 16 differentially metabolized lipid peaks in the patients after STEMI diagnosis but prior to reperfusion. With the increase of reperfusion times, the contents of these 16 lipid biomarkers decreased gradually, but there was a 1.5- to 2-fold increase of those 16 lipid biomarkers contents at T2 compared with T24. CONCLUSIONS Lipidomics analysis demonstrated differential change before and after reperfusion, suggesting a potential role of some of these lipids as biomarkers for optimizing the diagnosis of myocardial I/R, as well as for therapeutic targets against myocardial I/R injury.

Background Accurate determination of screening coagulation tests and factors VIII and IX activities (FVIII:C and FIX:C) in fresh plasma is very important for diagnosing abnormalities in the intrinsic or extrinsic coagulation pathways and factor deficiencies. If thawed samples cannot be detected for all required items at the same time, or need to be re-tested or re-stored, the thawed samples need to be re-frozen. We planned to perform in-house validation studies on freeze-thawed samples for screening coagulation tests, FVIII:C and FIX:C. Methods Mean percent changes, numbers of samples with > 10% changes, and difference plots were evaluated to determine clinically relevant differences between results for fresh and freeze-thawed samples. The statistical significance of differences between repeated-measure multiple groups and baseline values were evaluated by repeated-measures analysis of variance. Results The acceptable freeze-thaw cycles for activated partial thromboplastin time, fibrinogen, prothrombin time/international normalized ratio, thrombin time, and FIX:C were three times at -20°C/-80°C, while the acceptable freeze-thaw cycles for FVIII:C were three times at -80°C and once at -20°C. Conclusions The freeze-thaw results on stabilities were affected by time and temperature, with lower temperature and fewer times associated with more stable activity.

Vinegar-baked Radix Bupleuri (VBRB) is clinically used to enhance the pharmacological activity of drugs used to treat liver diseases. Our previous study demonstrated that this effect is dependent on increased drug accumulation in the liver; however, the underlying mechanism remains unclear. We hypothesize that VBRB mediated its effects by altering drug transporters. Thus, the present study was designed to determine the effects of VBRB's main components, saikosaponin A, C, and D, on drug transporters. Transporter activity was determined by measuring the intracellular concentration of transporter substrates. Protein and mRNA levels were measured by Western blot and qPCR, respectively. Colchicine was used as the substrate for P-glycoprotein (Pgp) and multidrug resistance protein (MRP) 1, cisplatin was used as the substrate for Mrp2 and organic cation transporters 2 (Oct2), and verapamil and MK571 were used as inhibitors of Pgp and MRP1, respectively. Saikosaponin A, C, and D differentially affected transporter activity. All of the saikosaponins inhibited Pgp activity in Pgp over-expressing HEK293 cells and increased substrate uptake of OCT2 in OCT2 over-expressing HEK293. Saikosaponin C and D inhibited MRP2 activity in HEK293 cells and BRL 3A cell with high MRP2 expression; saikosaponin A increased colchicine accumulation in GSH-stimulated HEK293 cells, but decreased colchicine uptake in HEK293 cells. Saikosaponin D inhibited MRP1 activity in GSH-stimulated HEK293 cells, but marginally affected the uptake of colchicine in HEK293 cells. In conclusion, saikosaponins play a role in VBRB's induced liver targeting effect through affecting drug transporters with a transporter expression amount depending manner.

We analyzed the scats of Amur tigers and Amur leopards, and examined their annual and seasonal food habits in Northeast China to comprehend their coexistence. Wild boar had the highest annual and seasonal consumption frequencies by the tigers, while both roe deer and sika deer were mostly preyed by the leopards annually. The three species appeared to be the key preys in terms of high proportion of consumed biomass by the two felids. Our data also revealed numerous mid-sized carnivores and small mammals included in the two felids’ food list. We used the relative abundance and biomass density estimation in prey density estimation to calculate the prey preferences of tigers and leopards, and both methods confirmed that Amur tigers strongly preferred wild boar. However, preference estimations of Amur leopards were not consistant, or even opposite to one another from the two methods. The results of the study suggested that prey preference of predators is largely determined by body size of the prey species. Variation in diet composition of the two felids suggests that resource partitioning may contribute to their coexistence.

Objectives Inflammation-based prognostic markers (neutrophil–lymphocyte ratio (NLR), prognostic nutritional index (PNI), red cell distribution width (RDW) and lymphocyte–monocyte ratio (LMR)) are associated with overall survival in some diseases. This study assessed their prognostic value in mortality and severity in acute pancreatitis (AP). Design A retrospective cohort study. Setting Patients with AP were recruited from the emergency department at our hospital. Participants A total of 359 patients with AP (31 non-survivors) were enrolled. Primary and secondary outcome measures Mortality and severity of AP were the primary and secondary outcome measures, respectively. Biochemistry and haematology results of the first test after admission were collected. Independent relationships between severe AP (SAP) and markers were assessed using multivariate logistic regression models. Mortality prediction ability was evaluated using receiver operating characteristic (ROC) curves. Overall survival was evaluated using the Kaplan-Meier method, with differences compared using the log-rank test. Independent relationships between mortality and each predictor were estimated using the Cox proportional hazard models. Results Compared with survivors of AP, non-survivors had higher RDW (p

Preanalytical quality control of blood samples is critical for tests of coagulation function and coagulation factor activity. Preanalytical storage time and temperature are the main variables. We investigated the effects of preanalytical frozen storage time and temperature on activated partial thromboplastin time (APTT), fibrinogen (Fbg), prothrombin time (PT)/international normalized ratio (INR), thrombin time (TT), factor VIII activity (FVIII:C), and factor IX activity (FIX:C) in frozen plasma. Samples (n = 144) were randomly and equally divided into four groups (storage at −80 °C or −20 °C) and analysed by CS5100 or CA7000 coagulation analysers. Baseline values and results after storage for 15 days, 1 month, 3 months, 6 months, and 1 year were measured after thawing. Mean percent changes and scatter plots were used to determine clinically relevant differences. The stabilities of coagulation tests and coagulation factor activities measured by the CS5100 system were consistent with those measured by the CA7000 system. At −80 °C, assessment samples of PT/INR, Fbg, and TT can be safely stored for 1 year, APTT for 6 months, and FVIII:C and FIX:C for 1 month. At −20 °C, samples of Fbg and TT can be stored for 1 year, PT/INR and FIX:C for 1 month, and APTT and FVIII:C for 15 days.

Aims: Vinegar-baked Radix Bupleuri (VBRB) potentiates the activity of anticancer drugs in the liver by increasing their hepatic distribution. However, this phenomenon may be associated with drug transporters. We investigated the effect of saikosaponin b2 (SSb2; the main component of VBRB) on the activity and expression of different drug transporters in both normal cells and those that overexpress the transporter. Main methods: The activities of transporters were analyzed by concentration of their cellular substrates. Concentrations of colchicine (substrate of Pgp and MRP1) and cisplatin (substrate of OCT2 and MRP2) were determined by high-performance liquid chromatography (HPLC). The concentration of rhodamine B was determined by flow cytometry. The expression of transporter gene and protein were determined by qRT-PCR and Western blotting analysis. Key findings: SSb2 increased colchicine efflux in HEK293 cells by primarily increasing Mrp1 activity, independent of gene and protein expression. SSb2 enhanced Mrp2 function and increased cisplatin efflux in BRL3A cells by upregulating Mrp2 gene expression, with a marginal effect on Pgp in normal cells. SSb2 increased OCT2 activity in OCT2-HEK293 cells by increasing the expression of OCT2 protein and mRNA; however, SSb2 inhibited MRP2 activity in MRP2-HEK293 cells by decreasing MRP2 protein expression, and decreased Pgp and MRP1 activity in Pgp- and MRP1-HEK293 cells. Significance: SSb2 might potentially be the key active component of VBRB that enhances the hepatotargeting of anticancer drugs through the inhibition of multidrug resistance-associated drug transporters (Pgp, MRP1, and MRP2) in an environment-dependent manner.

Background Depression is common in the aftermath of myocardial infarction (MI) and may not only lead to impaired long-term quality of life, but also cause increased mortality among patients with MI. The reported prevalence of depression among patients with MI varied considerably across studies, for which a pooled prevalence was obtained in the only 1 meta-analysis conducted in March 2004. Subsequently, numerous relevant studies have been published, indicating the need for an update on the pooled prevalence. Therefore, this study was aimed at updating the pooled prevalence of depression among patients with MI. Methods A comprehensive literature search in 3 electronic databases, PubMed, Embase, and PsycINFO, was performed in April 2018. The heterogeneity across studies was examined by the Cochran's Q test and quantified by the I statistic. If significant heterogeneity was observed, meta-regression analyses and subgroup analyses were performed to identify the source of heterogeneity. Publication bias was assessed by a funnel plot and verified by the Egger's and Begg's tests. Results Nineteen eligible studies conducted in 10 countries were included, which consisted of 12,315 patients with MI, among whom 3818 were identified with depression. High heterogeneity was observed across the eligible studies (I = 98.4%), with the reported prevalence of depression ranging from 9.17% to 65.88%. The pooled prevalence of depression among patients with MI was 28.70% (95% CI: 22.39-35.46%) by a random effects model. Subgroup analyses showed that the pooled prevalence differed significantly by region, tool used to identify depression, study quality, sex, race, anterior MI, and diabetes status (P .05). Conclusions Given the high pooled prevalence of depression found in this study and the association between depression and adverse health outcomes among patients with MI, more psychological resources including early assessment and effective treatment of depression should be allocated to patients with MI.

Objective A liver biopsy is the ‘reference standard’ for diagnosing and staging liver fibrosis but with many disadvantages. Therefore, developing a non-invasive index for predicting fibrosis is very valuable. We developed and validated a novel non-invasive index for predicting significant fibrosis in patients with chronic hepatitis B infection. Design A retrospective cohort study. Setting Chronic hepatitis B virus-infected patients were recruited in the Department of Infectious Disease in the First Affiliated Hospital of Zhejiang University. Participants A total of 506 patients were enrolled, and patients were randomly divided into estimation (n=253) and validation (n=253) cohorts. Primary and secondary outcome measures Chronic hepatitis B virus-infected patients were studied retrospectively using routine parameters. A novel index was developed from an estimation cohort and validated in another cohort. Liver histology was assessed for fibrosis according to the Xi9an Meeting Scoring System. The novel index using α-fetal protein (AFP) and activated partial thromboplastin time (APTT; denoted AA index) was compared with 10 other indices using receiving operating characteristics curves. Multivariate forward stepwise regression analysis revealed that AFP and APTT were significantly associated with the Xi9an Meeting Scoring System, and were used to calculate the AA index (log index=−9.164+0.114×AFP+0.236×APTT). Results The AA index predicted significant fibrosis with an area under the curve of 0.822, exhibited a significantly higher area compared with the other 10 indices in the estimation cohort, and was validated in the validation cohort. Conclusions The AA index can be used to predict significant fibrosis, and may decrease the need for liver biopsy in patients with chronic hepatitis B infection.

Objective Infection with hepatitis B virus (HBV) remains a major cause of liver cirrhosis (LC) in China. Recent reports suggest that the lymphocyte-to-monocyte ratio (LMR) is a potential biomarker for predicting clinical outcomes. In our study, we investigated if LMR can be used as a prognostic marker of mortality in patients with HBV-related LC. Design A retrospective cohort study. Setting HBV-infected patients with LC and patients with chronic hepatitis B infection (CHB) from the Department of Infectious Disease were enrolled and 240 healthy individuals were recruited from the healthcare centre at the First Affiliated Hospital of Zhejiang University. Participants 479 HBV-infected patients with LC, 134 patients with CHB and 240 healthy individuals were enrolled. Primary and secondary outcome measures The receiver operating characteristic (ROC) curve and multivariable logistic regression analysis after adjusting for total protein, albumin, total bilirubin and the model for end-stage liver disease (MELD) score were used to evaluate the power of LMR for predicting 1 year mortality in patients with LC. Results The LMR was statistically lower in patients with LC. The MELD score and mortality were statistically higher in patients with LC compared with the CHB and control groups. The area under the ROC curve, cut-off values, sensitivity and specificity of LMR for predicting mortality LC in the training cohort were 0.817 (95% CI 0.746 to 0.888; p

Ovarian cancer is the most lethal cause of death among gynecological malignancies. Despite advancements in surgery and chemotherapy treatment strategies, the prognosis of ovarian cancer patients remains poor; a majority of patients relapse and eventually succumb to this disease. Therefore, novel therapeutic approaches to improve patient outcome are urgently needed. The hedgehog signaling pathway is vital for embryonic development and tissue homeostasis, and its deregulation is implicated in cancer cell growth, survival, differentiation, and metastasis. The critical role of hedgehog signaling in multiple biologic processes raises concerns about its potential therapeutic use in cancer. Consequently, many studies are focusing on hedgehog signaling as an attractive target in cancer treatment. In this review, we present an overview of the hedgehog pathway and its pathological aberrations in ovarian cancer. We also discuss inhibitors of the hedgehog signaling pathway that are currently being investigated in the laboratory and in early clinical trials; as well as the clinical challenges these inhibitors face.

Moyamoya disease (MMD) is a rare chronic occlusive cerebrovascular disease, with some non-typical symptoms including ischaemic stroke, transient ischaemic attack (TIA), intracranial haemorrhage, se...