Search

BACKGROUND Currently, there is a lack of sepsis screening tools that can be widely used worldwide. Pulmonary sepsis can be of sufficient concern to physicians due to their noticeable symptoms, which usually rely less on screening tools. AIM To investigate the efficiency of the international normalized ratio (INR) for the early rapid recognition of adult nonpulmonary infectious sepsis. METHODS This is a prospective observational study. A total of 108 sepsis patients and 106 nonsepsis patients were enrolled according to relevant inclusion and exclusion criteria. Commonly used clinical indicators, such as white blood cell, neutrophil count, lymphocyte count, neutrophil-lymphocyte count ratio (NLCR), platelets (PLT), prothrombin time, INR, activated partial thromboplastin time, and quick Sequential “Sepsis-related” Organ Failure Assessment (qSOFA) scores were recorded within 24 h after admission. The diagnostic performances of these clinical indicators were analyzed and compared through multivariate logistic regression analysis, Spearman correlation, and receiver operating characteristic curve analysis. RESULTS The INR value of the sepsis group was significantly higher than that of the nonsepsis group. INR has superior diagnostic efficacy for sepsis, with an area under the curve value of 0.918, when those preexisting diseases which significantly affect coagulation function were excluded. The diagnostic efficacy of the INR was more significant than that of NLCR, PLT, and qSOFA (P < 0.05). Moreover, INR levels of 1.17, 1.20, and 1.22 could be used to categorize the relative risk of nonpulmonary infections sepsis into three categories: low, medium and high risk, respectively. CONCLUSION The INR is a promising and easily available biomarker for diagnosis, and it can be used as one of the indicators for early screening of adult nonpulmonary infectious sepsis. When its value is higher than the optimal cutoff value (1.22), high vigilance is required for adult nonpulmonary infectious sepsis.

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder with evidence of polygenetic components, and obesity may be a risk factor for hyperandrogenism. Previous studies have shown that LHCGR is enriched in the ovary and LHCGR deficiency causes infertility without typical PCOS phenotypes. ALMS1 is implicated in obesity and hyperandrogenism, the common phenotypes among PCOS patients. Through whole-exome sequencing of 22 PCOS families and targeted candidate gene sequencing of additional 65 sporadic PCOS patients, we identified potential causative mutations in LHCGR and ALMS1 in a sibling-pair PCOS family and three sporadic PCOS patients. The expression of LHCGRL638P in granulosa-like tumor cell line (KGN) cells promoted cyclic adenosine monophosphate production and granulosa cell proliferation, indicating that LHCGRL638P is an activating mutation. LhcgrL642P/L642P mice showed an irregular estrous cycle, reduced follicles with dynamic folliculogenesis, and increased testosterone (T), estradiol (E2), and dehydroepiandrosterone. Lhcgr+/L642PAlms1+/PB mice displayed increased T and E2 but decreased late secondary and preovulatory follicles. We showed that activating mutation of LHCGR likely plays important roles in the pathophysiology of PCOS involving abnormal reproductive physiology, whereas ALMS1 deficiency may promote anovulatory infertility via elevated androgens, suggesting that the disturbed LHCGR and ALMS1 cooperatively induce PCOS phenotypes, characterized as anovulation and hyperandrogenemia frequently observed in PCOS patients with obesity.

Background This study aimed to validate the feasibility of deformable image registration (DIR) in assessing the cumulative dose distributions in combined external beam radiotherapy (EBRT) and intracavitary brachytherapy (ICBT) for cervical cancer. Methods This retrospective study included 23 patients with stage IIB disease treated with combined EBRT to the whole pelvis (50.4 Gy in 28 fractions) using an intensity-modulated radiotherapy technique with 6-MV X-ray, followed by three-dimensional (3D) ICBT (28 Gy in 4 fractions). Tumor gross target volume at diagnosis (GTV-Tinit), tumor gross target volume before brachytherapy, high-risk clinical target volume (HR-CTV), intermediate-risk clinical target volume (IR-CTV), and parametrium and organs at risk were recontoured on computed tomography images of EBRT and ICBT, respectively. The dose-volume parameters were also determined. The DIR results were reviewed using MIM Maestro (Reg Review) and modified by function (Reg Refine). To evaluate the accuracy of DIR, DIR-based cumulative dose-volume histogram (DVH) parameters and simple DVH parameter addition were compared using Wilcoxon rank-sum tests. Results The cumulative dose distributions of EBRT and four ICBT sessions were successfully illustrated using DIR. The mean tumor diameters were 68.35 cm3 at diagnosis and 29.63 cm3 at ICBT initiation. The mean tumor regression was 56.6%. The median minimum dose covering 90% (D90) of HR-CTV, GTV-Tinit, IR-CTV, and parametrium were 69.58±4.94, 68.81±7.98, 59.28±3.78, and 60.97±1.1 Gyα/β=10, respectively, for DIR and 69.11±5.68, 68.49±8.62, 58.89±3.59, and 61±1.49 Gyα/β=10, respectively, with conventional simple DVH parameter addition.No statistically significant differences in dosimetric parameters were observed between the two methods. Conclusions Although there were limitations in the DIR accuracy, DIR-based dose accumulation was significantly beneficial in visually showing the cumulative dose distribution in the target area to clinicians in combined radiotherapy for cervical cancer in routine clinical practice.

To evaluate the effect of adjuvant chemotherapy on improving the prognosis of patients with stage I triple-negative breast cancer (TNBC). TNBC patients diagnosed in the SEER 18 database from 2010 to 2015 were included. Kaplan–Meier plots and log-rank tests were used to compare the differences in breast cancer-specific survival (BCSS) and overall survival (OS) between subgroups of variables. A Cox proportional hazard model was used to determine the prognostic factors affecting BCSS and OS. A total of 9256 patients were enrolled in this study. Among these patients, 380 died from breast cancer, and 703 died from all causes. Patients who received chemotherapy had significantly better BCSS and OS than those who did not receive chemotherapy for stage T1cN0M0 (BCSS, hazard ratio (HR) = 0.68, 95% confidence interval (CI) 0.51–0.90; OS, HR = 0.54, 95% CI 0.44–0.67) and stage IB (BCSS, HR = 0.39, 95% CI 0.16–0.95; OS, HR = 0.41, 95% CI 0.19–0.87) disease. Patients who received chemotherapy did not have significantly better BCSS or OS than those who did not receive chemotherapy for stage T1aN0M0 or T1bN0M0 disease. The patients who received chemotherapy in the poorly differentiated and undifferentiated groups had better BCSS (HR = 0.68, 95% CI 0.52–0.88) and OS (HR = 0.54, 95% CI 0.44–0.66) than the patients who did not receive chemotherapy. According to current clinical guidelines, patients with stage T1bN0M0 TNBC are probably overtreated. The prognosis of these patients with stage T1aN0M0 or T1bN0M0 disease is good enough that adjuvant chemotherapy cannot improve it further.

Life-threatening electrolyte imbalance is not uncommon in preemies. Differential diagnosis is important for immediate treatment. The syndrome of pseudohypoaldosteronism (PHA) is characterized by increased aldosterone secretion associated with clinical signs of hypoaldosteronism reflecting mineralocorticoid resistance. There are type I, type II, and secondary type of PHA. Most secondary PHA reported in the pediatric population result from urinary infection and obstructive uropathy and extremely rarely from gastrointestinal fluid loss. Seven preemies accepted jejunostomy or ileostomy, and they suffered from high output stoma. Electrolyte imbalance with bodyweight loss or cardiac event was noted. We found a high level of aldosterone and renin and diagnosed them with secondary PHA due to excessive gastrointestinal losses. After stomal reversal, aldosterone and renin level became normalized, and electrolyte was corrected. This study reports the finding of secondary pseudohyperaldosteronism (hyponatremia, hyperkalemia, and metabolic acidosis) in a series of cases with intestinal resection and ostomy of different causes. Early stomal reversal was recommended.

Purpose To evaluate the accuracy of 18F-FDG-PET/CT for the detection of recurrent and/or metastatic diseases in differentiated thyroid cancer (DTC) patients with thyroglobulin elevation and negative iodine scintigraphy. Whether PET/CT with TSH stimulation (sPET/CT) had better diagnostic performance than PET/CT without TSH stimulation (nsPET/CT) in this scenario was also evaluated. Methods PubMed and Embase databases were searched for eligible studies from January 2001 to December 2018. Only studies with clearly stated reference standard (histopathology confirmation and/or clinical/imaging follow-up) were included. Publication bias was assessed by Deeks funnel plot. The pooled sensitivity, specificity, diagnostic odds ratio (DOR) and the area under the summary receiver-operating characteristics curve (AUC) for PET/CT was determined by random-effect analysis, respectively. sPET/CT and nsPET/CT were compared pairwise for all diagnostic estimate indexes using Z-test. Results We included 17 studies with 1195 patients in this meta-analysis. The pooled sensitivity, specificity, DOR and AUC for PET/CT on patient-based data were 0.86 (95% CI: 0.79–0.91), 0.84 (95% CI: 0.72–0.91), 31.00 (95% CI: 12.00–80.00) and 0.91 (95% CI: 0.88–0.93), respectively. There was high heterogeneity (I 2 = 80% for sensitivity, I 2 = 82% for specificity) and possible publication bias (P = 0.01). Z test did not detect statistically significant difference between sPET/CT and nsPET/CT for all the diagnostic estimate indexes (all P > 0.05). Conclusions On patient-based analysis, 18F-FDG-PET/CT has high diagnostic accuracy for the detection of recurrent and/or metastatic diseases in DTC patients with thyroglobulin elevation and negative iodine scintigraphy, but existing studies were limited by high heterogeneity and possible publication bias. The diagnostic performance of sPET/CT may be not superior to nsPET/CT.

Negative 99mTc-pertechnetate uptake of the thyroid bed indicates the absence or a small volume of remnant thyroid tissue (RTT) after total thyroidectomy (TT). The aim of this study is to evaluate the predictive value of negative 99mTc-pertechnetate scintigraphy for excellent response (ER) to radioactive iodine therapy (RIT) in low- to intermediate-risk differentiated thyroid cancer (DTC) patients. One-hundred and eighty-nine low- to intermediate-risk DTC patients who underwent TT, RIT with a single dose of 30 mCi and suppressive therapy with thyroid-stimulating hormone (TSH) from July 2015 to February 2016 in our hospital were retrospectively evaluated. 99mTc-pertechnetate thyroid scintigraphy was performed just before RIT and images were reported dichotomously as negative or positive. The response of patients was assessed for 23.2 ± 3.8 months after RIT and dichotomized as excellent response (ER) or non-excellent response (NER). 99mTc-pertechnetate uptake, age at diagnosis, gender, multifocality, T stage, N stage, preablative stimulated thyroglobulin (ps-Tg), and TSH were explored as potential predictors for ER. 80.68% (71/88) of patients with negative 99mTc-pertechnetate uptake achieved ER. When patients were evaluated according to different ps-Tg levels, we found that 94.83% (55/58) of patients with ps-Tg < 1 ng/ml and negative 99mTc-pertechnetate uptake achieved ER. Multivariate Cox regression analysis revealed that ps-Tg (P = 0.0001) and 99mTc-pertechnetate uptake (P = 0.0473) were independent predictors for ER. In addition to ps-Tg, negative 99mTc-pertechnetate uptake is also a significant independent predictor for an excellent response in low- to intermediate-risk patients. It may be possible to omit RIT in patients with ps-Tg < 1 ng/ml and concurrent negative 99mTc-pertechnetate uptake.

Background Our previous studies have reported the down-regulation of EGFL8 correlates to the development and prognosis of colorectal and gastric cancer. The present study is carried out to explore the expression pattern and role of EGFL8 in hepatocellular carcinoma (HCC). Methods and materials EGFL8 expression in 102 cases of HCC tissues matched with adjacent non-tumorous liver tissues, a normal liver cell line and three liver cancer cell lines with different metastatic capacity was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot. Moreover, the clinicopathological features and prognosis of HCC patients were correlated with expression of EGFL8. Subsequently, the gain-and loss-of-function experiments were carried out to investigate the biological function of EGFL8 in HCC. We also used N-[N-(3,5-Difluorophenacetyl-L-alanyl)]-(S)- phenylglycine t-butyl ester (DAPT), an inhibitor for Notch signaling pathway, in these experiments to verify the involvement of Notch signaling pathway in the effects of EGFL8. Additionally, a mouse model was established to investigate the effect of EGFL8 on metastasis of HCC cells. The expression of Notch signaling pathway in HCC cells and xenograft mouse tumors were detected by Western blot and immunohistochemistory. Results The expression of EGFL8 was significantly decreased in HCC tissues and cell lines and EGFL8 down-regulation correlated to multiple nodules, vein invasion, high TNM stage and poor prognosis of HCC. Interestingly, the expression levels of EGFL8 in three liver cancer cell lines were negatively associated with their metastatic capacity. In vitro and in vivo experiments indicated that EGFL8 obviously suppressed metastasis and invasion of HCC cells but slightly promoted apoptosis. Meanwhile, the expression of Notch signaling pathway was obviously suppressed in EGFL8 overexpressed HCCLM3 cells and xenograft mouse tumors generated from these cells but markedly elevated in EGFL8 depleted Hep3B cells. Furthermore, the up-regulated expression of Notch signaling pathway and effects induced by EGFL8 knockdown in Hep3B cells could be counteracted by DAPT treatment. Conclusion The down-regulation of EGFL8 was correlated to progression and poor prognosis of HCC and regulates HCC cell migration, invasion and apoptosis through activating the Notch signaling pathway, suggesting EGFL8 as a novel therapeutic target and a potential prognostic marker for HCC.

Rosanortriterpenes A–B (RTA and RTB), two nortriterpenoids, are characteristic constituents in the fruits of Rosa laevigata var. leiocapus. However, pharmacological studies on these compounds are still scarce. In the present study, we aim to investigate the anti-inflammatory mechanisms associated with the effects of RTA–B in RAW264.7 macrophages and LO2 cells by detecting cell viabilities, nitric oxide (NO) production, tumour necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) production. Simultaneously, the anti-inflammatory action mechanisms of these two compounds were illustrated through western blot assay. Besides, the antihepatic fibrosis activities of these compounds have also been explored. The results demonstrated that RTA and RTB inhibited the production of NO, TNF-α, and IL-6 and suppressed liver fibrosis. RTA and RTB treatment also greatly inhibited the activation of NF-kappaB (NF-κB) pathway. Our study confirmed the promising anti-inflammatory and anti-liver fibrosis actions of RTA–B, suggesting that they might be developed as alternative and promising drugs for the treatment of hepatic inflammatory and fibrotic diseases.

Summary Purpose The inhibition of Mus81, a critical DNA repair gene, is recently related to the chemosensitivity of several human cancer cells such as hepatocellular carcinoma (HCC) cells. However, the role of Mus81 knockdown in chemotherapy response of colon cancer cells remains largely unknown. Methods and materials The effects of Mus81 knockdown by lentivirus-mediated short hairpin RNA in sensitivity of HCT116 and LS180 colon cancer cell lines to four therapeutic drugs, including cisplatin (CDDP), were evaluated by MTT assay as well as a mouse model. Apoptosis and cell cycle distribution of HCT116 cell line was detected by flow cytometric analysis. Western blot was also employed to determine the expression of CHK1 pathway and apoptosis-related proteins in HCT116 cells and the xenograft mouse tumors. Results Mus81 knockdown could significantly improve the chemosensitivity of colon cancer cells in vitro and in vivo , especially to CDDP. Mus81 knockdown also induced S phase arrest and elevated apoptosis in CDDP treated HCT116 cells through activating CHK1/CDC25A/CDK2 and CHK1/p53/Bax pathways, while these effects could be counteracted by CHK1 inhibition. Conclusion Mus81 knockdown improves the chemosensitivity of colon cancer cells by inducing S phase arrest and promoting apoptosis through activating CHK1 pathway.

// Huan-Huan Wang 1, * , Lei Deng 2, * , Qing-Lian Wen 3, * , Chun-Ze Zhang 4, * , Nicholas G. Zaorsky 5 , Bai-Lin Zhang 1 , Jie Chen 1 , Xian-Liang Zeng 1 , Yao-Li Cui 6 , Yang-Yang Shi 7 , Hai-Ling Hou 1 , Wei Wang 1 , Bo Jiang 1 , Jun Wang 1 , Qing-Song Pang 1 , Lu-Jun Zhao 1 , Zhi-Yong Yuan 1 , Ping Wang 1 and Mao-Bin Meng 1 1 Department of Radiation Oncology and CyberKnife Center, Tianjin’s Clinical Research Center for Cancer and Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China 2 Department of Thoracic Cancer, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China School of Medicine, Sichuan University, Chengdu 610041, China 3 Department of Oncology, Affiliated Hospital of Southwest Medical University, Luzhou 646000, China 4 Department of Surgery, Nankai University Tianjin People’s Hospital, Tianjin People’s Hospital, Tianjin 300121, China 5 Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA 6 Department of Lymphoma, Tianjin’s Clinical Research Center for Cancer and Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China 7 Stanford University School of Medicine, Stanford, CA 94305, USA * These authors have contributed equally to this work Correspondence to: Mao-Bin Meng, email: doctormm991@hotmail.com Keywords: non-small cell lung cancer, postoperative radiotherapy, postoperative chemotherapy, multimodality therapy, overall survival Received: December 10, 2016 Accepted: April 24, 2017 Published: May 23, 2017 ABSTRACT Aims: The aim of this study was to evaluate the ideal timing of PORT in the management of completely resected (R0) Stage IIIA-N2 NSCLC. Patients and Methods: Between January 2008 and December 2015, patients with known histologies of pathologic Stage IIIA-N2 NSCLC who underwent R0 resection and received PORT concurrent with or prior to two sequential cycles of chemotherapy (“early PORT”) or with PORT administered after two cycles of chemotherapy (“late PORT”) at multiple hospitals. The primary endpoint was OS; secondary end points included pattern of the first failure, LRRFS, and DMFS. Kaplan–Meier OS, LRRFS, and DMFS curves were compared with the log-rank test. Cox regression analysis was used to determine prognosticators for OS, LRRFS, and DMFS. Results: Of 112 included patients, 41 (36.6%) and 71 (63.4%) patients received early PORT and late PORT, respectively. The median OS, LRRFS, and DMFS were longer for those who received early PORT than for those who received late PORT at the median follow-up of 29.6 months (all p < 0.05). Uni- and multi-variate analyses showed that number of POCT cycles and the combination schedule of PORT and POCT were independent prognostic factors for OS, LRRFS, and DMFS. Conclusions: Early PORT is associated with improved outcomes in pathologic Stage IIIA-N2 R0 NSCLC patients.

AimIt has been shown that G-protein-coupled receptor kinase 2 (GRK2) negatively regulates the insulin-like growth factor 1 receptor (IGF1R) signalling pathway in hepatocellular carcinoma (HCC). The aim of this study was to evaluate the clinicopathological and prognostic significance of GRK2 and IGF1R in HCC.MethodsExpression of GRK2 and IGF1R was first detected by tissue microarray-based immunohistochemistry in 156 patients with HCC. Staining results, termed the H-score, were then correlated with clinicopathological variables and patient survival. Finally, the prognostic value of GRK2 and IGF1R was validated in the publically available TCGA (The Cancer Genome Atlas) RNA-sequencing database.ResultsThe H-score of GRK2 staining (which was significantly lower in tumour than non-tumour tissue) was negatively associated with that of IGF1R with a reverse trend. No clinicopathological significance of the proteins was found except for a relationship between tumoral IGF1R expression and tumour–node–metastasis stage. In univariate analysis, high IGF1R expression predicted poor overall and disease-free survival, whereas GRK2 was not prognostic. In multivariate analysis, IGF1R was significant for overall survival. Furthermore, IGF1R was also of prognostic value in the TCGA database.ConclusionsOur data indicate that GRK2 and IGF1R show a negative correlation in HCC. IGF1R could be a potential marker of poor prognosis for this malignancy.

Sepsis is a life-threatening disease that affects 30 million people worldwide each year. Despite the rapid advances in medical technology and organ support systems, it is still difficult to reduce the mortality rate. Early and rapid diagnosis is crucial to improve the treatment outcome. The aim of this study was to investigate the prediction efficiency of lymphopenia and other clinical markers, such as white blood cell (WBC), neutrophil count (N#), procalcitonin (PCT), and arterial lactic acid (Lac) in the diagnosis and prognosis assessment for adult patients with nonviral infection-related sepsis. A total of 77 sepsis- and 23 non-sepsis adult patients were enrolled in this study from September 2016 to September 2018. Daily lymphocyte count (Lym) of the patients was calculated until discharge or death. The diagnostic performance of the Lym and other biomarkers were compared using the area under the receiver operating characteristic curve (ROC) value. The level of Lym was decreased significantly in the sepsis group. Lym had a high diagnostic performance for sepsis, with an area under the curve (AUC) value of 0.971 (95% CI = 0.916–0.994). The diagnostic efficacy of Lym was more significant than WBC, N#, and PCT (P 3 days indicates a higher 28-day mortality rate.

Long noncoding RNAs (lncRNAs) have been confirmed to be aberrantly expressed in various diseases including tumors. Recently, a new tumor-related lncRNA, lncRNA TRPM2 antisense RNA (TRPM2-AS), was shown to be involved in many tumors, such as lung cancer and breast cancer. However, the expression and role of TRPM2-AS in the development of gastric cancer (GC) have not been elucidated. In the current study, we provided evidence that the expression levels of TRPM2-AS were increased in both GC tissues and cell lines. We also showed that overexpression of TRPM2-AS was modulated by ELK1, a transcription factor. The results of clinical assays showed that higher expressions of TRPM2-AS were significantly related with invasion depth, TNM stage, lymphatic metastasis, and shorter overall survival. Further clinical assays using multivariate analysis suggested that TRPM2-AS expression was an independent prognostic factor in patients with GC. Functional experiments illustrated that depression of TRPM2-AS suppressed proliferation, migration, and invasion in GC cells. In terms of mechanism, we found that TRPM2-AS directly inhibited miR-195, which targeted the 3'-untranslated region of high-mobility group AT-hook 1 (HMGA1) messenger RNA. Overall, these findings revealed that ELK1-induced overexpression of TRPM2-AS promoted the development and progression of GC in part through miR-195/HMGA1 signaling axis, and established its candidacy as a new cancer biomarker for GC patients.

Diarrhea can occur at an early or advanced stage of acquired immunodeficiency syndrome (AIDS) as a usual symptom in people with human immunodeficiency virus (HIV) infection. While it is usually not fatal, it can influence patients' quality of life seriously. It has shown to be efficacious and improves people's immune status to a certain extent to treat HIV/AIDS-related diarrhea on the basis of syndrome differentiation and treatment or Chinese herbs plus conventional treatment. Therefore, it may have a good application potential. Here, we outline a protocol for the systematic review of this health-care intervention, with the aim to evaluate the beneficial effects and safety of Traditional Chinese Medicine (TCM) for patients who suffer from HIV/AIDS-associated diarrhea. Randomized controlled trials that compare Chinese herbs with placebo or other effective treatments will be searched and included, in spite of publication status or language. The primary outcomes include diarrhea frequency and fecal character. The databases we will search as follows: China Science and Technology Journal Database (VIP), Chinese Biomedical Literature Database (SinoMed), Wanfang Data, China National Knowledge Infrastructure, PubMed and the CENTRAL in Cochrane Library. Two authors will respectively conduct the screening of trials, data extraction, and use the Cochrane risk of bias tool to assess the methodological quality. We will analyze the data and perform a meta-analysis if possible. We intend to identify potential therapeutic modalities that may be of benefit to inform clinical practice by supplying existing evidence of the helpful effects and safety of TCM to treat patients suffering from HIV/AIDS-associated diarrhea.

Background: Neutrophil to lymphocyte ratio (NLR) in peripheral blood is established to correlate with the morbidity and mortality of heart disease patients. We aimed to define the severity of inflammation (NLR) by observing the association of NLR with cardiac functions or myocardial damage parameters in patients with acute myocardial infarction. Methods: Data from 715 patients who underwent percutaneous coronary intervention (PCI) within 72 hours of incidence in 2016 were analysed retrospectively. Results: The NLR ranges from 0.50 to 46 (medium ± SD, 2.76 ± 2.96) in 715 patients. NLR positively correlated with myocardial damage (NLR vs. CK-mB: p 2.76 compared to those of NLR 4. The correlation was diminished between NLR and CK-mB at NLR > 2.76 or at NLR > 4, but that of NLR and EF or FS was maintained in NLR > 2.76 and at NLR > 4. EF and FS were comparable between NLR > 2.76 and NLR > 4. But myocardial damage parameters increased significantly at NLR > 4 compared to those of NLR > 2.76. Conclusion: NLR is a strong predictor of myocardial damage in acute myocardial patients. High NLR are associated with myocardial dysfunction in all the patients. Severe inflammation (NLR) can predict the consequence of the heart in patients with coronary syndrome. Keywords: Neutrophil, Lymphocyte, Acute myocardial infarction, Myocardial damage, Dysfunction

Prophylactic central neck dissection (pCND) is controversial in papillary thyroid carcinoma (PTC) without clinical positive lymph nodes. The aim of this study was to investigate the effect of radioactive iodine (RAI) therapy on the clinical outcome in clinically node-negative (cN0) PTC patients treated with total thyroidectomy (TT) alone or in combination with pCND.One-hundred and sixty-seven cN0 PTC patients who underwent TT alone (TT) or in combination with pCND (TT+pCND) in our hospital from January 2014 to August 2015 were evaluated retrospectively. Adjuvant RAI therapy was recommended depending on tumor diameter, multifocality, extrathyroidal extension, the presence of positive lymph nodes, and adverse histopathologic features. Serological and imaging data were collected with a mean follow-up of 29.9±5.2 months after RAI administration. Suppressed and stimulated thyroglobulin, thyroglobulin antibody, diagnostic whole-body scintigraphy, and other imaging examinations were used to assess clinical outcome, which was defined as excellent response, indeterminate response, biochemical incomplete response, and structural incomplete response.TT was performed in 62 (37.1%) and TT+pCND in 105 (62.9%). The rate of permanent hypoparathyroidism was significantly higher in TT+pCND than that of TT alone (14.2 vs. 3.2%, P=0.0316). Because of the detection of central neck lymph node metastases by pCND, 42 (40%) patients developed higher recurrence risk stratification (from low to intermediate) and 12 (11.4%) patients were upstaged in TNM staging. RAI therapy was performed for 46 (74.2%) patients in the TT group and 87 (82.9%) in the TT+pCND group. The mean dose for patients receiving RAI in the TT+pCND group was significantly higher than that in the TT group (113.9±23.1 vs. 93.9±18.1, P0.0001). No significant difference in response to RAI therapy was found between the TT group and the TT+pCND group (P=0.9474).Although the addition of pCND to TT, with a concomitant higher frequency of permanent hypoparathyroidism, upstages 40% of patients, thereby changing the dose of RAI therapy, the clinical response to RAI therapy for TT+pCND is not superior to TT alone in cN0 PTC patients.

We have reported that SIAH1 is down-regulated and associated with apoptosis and invasion in human breast cancer. However, the molecular mechanisms leading to SIAH1 down-regulation remain to be elucidated. Here, we demonstrated that miR-107 directly down-regulates SIAH1 expression in human breast cancer cells. Over- expression of miR-107 reduced SIAH1 expression, promoted human breast cancer cell proliferation, colony formation, migration and invasion, and inhibited apoptosis. On the contrary, silencing of miR-107 increased SIAH1 expression and inhibited the tumor growth of MDA-MB-231 cells, a kind of triple-negative breast cancer (TNBC) cells, in vitro and in vivo. Our results reveal that miR-107 is an upstream regulator for SIAH1 down-regulation in human breast cancer cells and miR-107 provides a potential effective target for the treatment of TNBC.

Excessive triple CGG repeats in the FMR1 gene have been widely associated with premature ovarian failure. The number of AGG interruptions and length of uninterrupted CGG repeats have been correlated with repeat instability on transmission. In this study, FMR1 CGG repeats and AGG interruption status were determined by triplet-primed PCR in 117 premature ovarian failure patients and 82 matched controls. A possible relationship between CGG repeats or AGG interruption and serum FSH concentrations in patients and controls was evaluated. One patient had a premutation allele (73 repeats) (1/117), while no such mutations were observed in controls (0/82). Other patients and all controls had CGG repeats in the normal range. There was no significant difference in the incidence of intermediate mutations of CGG repeats between patients and controls and no relationship between CGG repeats with serum FSH concentrations. Interestingly, more individuals with premature ovarian failure carried no AGG interruptions than the controls (4.27% versus 1.83%) but statistical significance was not reached. This small case–control study failed to find associations between CGG repeat sizes or AGG interruptions in FMR1 and premature ovarian failure in Chinese women. Further study with large sample size is warranted.

BACKGROUND Although there is increasing recognition of the role of somatic mutations in genetic disorders, the prevalence of somatic mutations in neurodevelopmental disease and the optimal techniques to detect somatic mosaicism have not been systematically evaluated. METHODS Using a customized panel of known and candidate genes associated with brain malformations, we applied targeted high-coverage sequencing (depth, = 200x) to leukocyte-derived DNA samples from 158 persons with brain malformations, including the double-cortex syndrome (subcortical band heterotopia, 30 persons), polymicrogyria with megalencephaly (20), periventricular nodular heterotopia (61), and pachygyria (47). We validated candidate mutations with the use of Sanger sequencing and, for variants present at unequal read depths, subcloning followed by colony sequencing. RESULTS Validated, causal mutations were found in 27 persons (17%; range, 10 to 30% for each phenotype). Mutations were somatic in 8 of the 27 (30%), predominantly in persons with the double-cortex syndrome (in whom we found mutations in DCX and LIS1), persons with periventricular nodular heterotopia (FLNA), and persons with pachygyria (TUBB2B). Of the somatic mutations we detected, 5 (63%) were undetectable with the use of traditional Sanger sequencing but were validated through subcloning and subsequent sequencing of the subcloned DNA. We found potentially causal mutations in the candidate genes DYNC1H1, KIF5C, and other kinesin genes in persons with pachygyria. CONCLUSIONS Targeted sequencing was found to be useful for detecting somatic mutations in patients with brain malformations. High-coverage sequencing panels provide an important complement to whole-exome and whole-genome sequencing in the evaluation of somatic mutations in neuropsychiatric disease. (Funded by the National Institute of Neurological Disorders and Stroke and others.)

Objective To evaluate the role of copy number abnormalities detectable by chromosomal microarray (CMA) testing in patients with epilepsy at a tertiary care center.

// Huan-Huan Wang 1, * , Chun-Ze Zhang 2, * , Bai-Lin Zhang 1 , Jie Chen 1 , Xian-Liang Zeng 1 , Lei Deng 3 , Mao-Bin Meng 1 1 Department of Radiation Oncology, Tianjin’s Clinical Research Center for Cancer and Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China 2 Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, China 3 Department of Thoracic Cancer and Huaxi Student Society of Oncology Research, West China Hospital, West China School of Medicine, Sichuan University, Sichuan Province 610041, China * These authors contributed equally to this work Correspondence to: Mao-Bin Meng, email: mmeng@tmu.edu.cn Keywords: non-small cell lung cancer, radiotherapy, sublobar resection, overall survival, pattern of failure Received: October 04, 2016 Accepted: December 12, 2016 Published: December 17, 2016 ABSTRACT Background and Aim: A matched-pair comparison was performed to compare the efficacy and safety of sublobar resection versus radiotherapy for high-risk elderly patients with Stage I non-small cell lung cancer (NSCLC). Patients and Methods: We searched the Cochrane Library, MEDLINE, CENTRAL, EMBASE and manual searches. The meta-analysis was performed to compare overall survival, pattern of failure, and toxicity among the homogeneous studies. Subdivided analyses were also performed. Results: Sixteen studies containing 11540 patients were included in the meta-analysis. Among these studies, 9 were propensity-score matched (PSM) cohort studies, and 7 were cohort studies. Sublobar resection, compared with radiotherapy (either conventional fraction radiation therapy or stereotactic body radiation therapy), significantly improved the overall survival regardless in both PSM and non-PSM analyses (all p 0.05). Conclusions: Sublobar resection was associated with improved outcomes in high-risk elderly patients with Stage I NSCLC, which supports the need to compare both treatments in large prospective, randomized, controlled clinical trials.

A combination of oligonucleotide and single-nucleotide polymorphism probes on the same array platform can detect copy-number abnormalities and copy-neutral aberrations such as uniparental disomy and long stretches of homozygosity. The single-nucleotide polymorphism probe density in commercially available platforms varies widely, which may affect the detection of copy-neutral abnormalities. We evaluated the ability of array platforms with low (Oxford Gene Technology CytoSure ISCA uniparental disomy), mid-range (Agilent custom array), and high (Affymetrix CytoScan HD) single-nucleotide polymorphism probe density to detect copy-number variation, mosaicism, uniparental isodisomy, and absence of heterozygosity in 50 clinical samples. All platforms reliably detected copy-number variation, mosaicism, and uniparental isodisomy; however, absence-of-heterozygosity detection varied significantly. The low-density array called absence-of-heterozygosity regions not confirmed by the other platforms and also overestimated the length of true absence-of-heterozygosity regions. Furthermore, the low- and mid-density platforms failed to detect some small absence-of-heterozygosity regions that were identified by the high-density platform. Variation in single-nucleotide polymorphism density can lead to major discrepancies in the detection of and confidence in copy-neutral abnormalities. Although suitable for uniparental disomy detection, copy-number plus single-nucleotide polymorphism arrays with 30,000 or fewer unique single-nucleotide polymorphism probes miscall absence-of-heterozygosity regions due to identity by descent. Genet Med 15 9, 706–712.

OBJECTIVES: The aim of this study is to compare thoracoscopic mobilization of the oesophagus in the lateral decubitus position and the semiprone position and to identify potential differences between the two techniques. METHODS: A retrospective review of a prospectively maintained oesophagectomy database identified 150 patients undergoing combined thoracoscopic and laparoscopic oesophagectomy (TLO). Of these, 90 cases underwent thoracoscopic oesophageal mobilization in the left lateral decubitus position. The remaining 60 cases underwent thoracoscopic oesophageal mobilization in the semiprone position. RESULTS: There were no differences in the clinicopathological factors and tumour characteristics between the two groups. There was no significant difference in the blood loss, operation time, the incidence of conversion, length of hospital stay or in the number of retrieved mediastinal and abdominal nodes between the two groups. There was no significant difference with regard to the incidence of respiratory complications, anastomotic leaks, vocal cord palsy, chylothorax, delayed gastric emptying, arrhythmia and intestinal obstruction between the two groups. CONCLUSIONS: The semiprone and lateral decubitus positions each have their inherent advantages and disadvantages. Our initial experience confirmed that while the semiprone position is associated with superior surgical ergonomics and better exposure of the posterior mediastinum, there is no convincing evidence that semiprone thoracoscopic oesophagectomy is superior to the left lateral decubitus positioning with respect to the major surgical outcomes and oncological clearance.

Increasing evidence that mutation of planar cell polarity (PCP) genes contributes to human cranial neural tube defect (NTD) susceptibility prompted us to hypothesize that rare variants of genes in the core apical-basal polarity (ABP) pathway are risk factors for cranial NTDs. In this study, we screened for rare genomic variation of PARD3 in 138 cranial NTD cases and 274 controls. Overall, the rare deleterious variants of PARD3 were significantly associated with increased risk for cranial NTDs (11/138 vs.7/274, P

SUMMARY Malignant migrating partial seizures in infancy (MMPEI) is an early onset epileptic encephalopathy with few known etiologies. We sought to identify a novel cause of MMPEI in a child with MMPEI whose healthy parents were consanguineous. We used array comparative genomic hybridization (CGH) to identify copy number variants genome-wide and long-range polymerase chain reaction to further delineate the breakpoints of a deletion found by CGH. The proband had an inherited homozygous deletion of chromosome 20p13, disrupting the promoter region and first three coding exons of the gene PLCB1. Additional MMPEI cases were screened for similar deletions or mutations in PLCB1 but did not harbor mutations. Our results suggest that loss of PLCb1 function is one cause of MMPEI, consistent with prior studies in a Plcb1 knockout mouse model that develops early onset epilepsy. We provide novel insight into the molecular mechanisms underlying MMPEI and further implicate PLCB1 as a candidate gene for severe childhood epilepsies. This work highlights the importance of pursuing genetic etiologies for severe early onset epilepsy syndromes.

OBJECTIVES: The aim of this study was to assess the experience of a high-volume centre with thoracolaparoscopy radical oesophagectomy and to evaluate the feasibility, tumour clearance, the learning curve and reproducibility of this technique. METHODS: Eighty patients with thoracic oesophageal cancer who underwent thoracolaparoscopic oesophagectomy (TLE) were enrolled in this study. Two attending surgeons (Mingqiang Kang and Ruobai Lin) independently performed the procedure as operating surgeons. The 60 patients who had surgery performed on them by the senior attending surgeon, Mingqiang Kang, were divided into three groups of 20 patients: groups A, B and C. The results from the three groups were compared in order to detect any changes in the success of TLE as a way of monitoring the development of the surgeon’s technical skill. Another 20 patients had surgery performed on them by the new attending surgeon, Ruobai Lin, and were classified into the fourth group, D. The results from Group D were compared with those of the other three groups to evaluate the reproducibility of our technique. RESULTS: There was no significant difference between the four groups with respect to age, gender, location of tumour or staging. The duration of both the thoracoscopic and laparoscopic procedures was significantly longer in Group A. The amount of estimated blood loss was significantly more in Group A than in the other groups. The number of lymph nodes dissected was similar in Groups A and D, whereas that of retrieved nodes was larger in Groups B and C. There was no significant difference in the incidence of respiratory complications, recurrent nerve palsy, anastomotic leaks, arrhythmia, chylothorax and delayed gastric emptying among the four groups. CONCLUSIONS: When TLE procedures are started in units with a large volume of oesophageal resections, and when there is support from colleagues within the unit, transition from open to TLE can be achieved safely, with a satisfactory oncological outcome. A plateau of TLE skill was reached after 40 cases had been performed. If mini-fellowship training with supervision from senior surgeons is used, it is possible for a new attending surgeon to attain the requisite basic skill to perform TLE in a relatively short period of time.

BACKGROUND: Classic galactosemia is an autosomal recessive disorder due to galactose-1-phosphate uridyltransferase (GALT) deficiency. Newborn screening and early treatment do not completely prevent tremor, speech deficits, and diminished IQ in both sexes and premature ovarian insufficiency (POI) in women. Data on how individuals with galactosemia fare as adults will improve our ability to predict disease progression.METHODS: Thirty-three adults (mean age = 32.6 ± 11.7 years; range = 18-59) with classic galactosemia, confirmed by genotype and undetectable GALT enzyme activity, were evaluated. Analyses assessed associations among age, genotype, clinical features and laboratory measures.RESULTS: The sample included 17 men and 16 women. Subjects exhibited cataracts (21%), low bone density (24%), tremor (46%), ataxia (15%), dysarthria (24%), and apraxia of speech (9%). Subjects reported depression (39%) and anxiety (67%). Mean full scale IQ was 88 ± 20, (range = 55-122). All subjects followed a dairy-free diet and 75-80% reported low intake of calcium and vitamin D. Mean height, weight and body mass were within established norms. All female subjects had been diagnosed with POI. One woman and two men had had children. Logistic regression analyses revealed no associations between age, genotype or gender with IQ, tremor, ataxia, dysarthria, apraxia of speech or anxiety. Each 10- year increment of age was associated with a twofold increase in odds of depression.CONCLUSIONS: Taken together, these data do not support the hypothesis that galactosemia is a progressive neurodegenerative disease. However, greater attention to depression, anxiety, and social relationships may relieve the impact of this disorder in adults.

Distal partial trisomies involving the region 1q32 have been associated with dysmorphic features and developmental delay [1-11]. To further define the critical region for developmental delay and to investigate the genotype-phenotype association of 1q trisomy syndrome, we report two patients with much smaller (3 Mb and 3.5 Mb in size) trisomic regions on 1q32.1. The two micro-duplications largely overlap and both patients exhibited cognitive and motor delays. Case 1 is a 5-year-old boy with global developmental delay, behavioral problems, pervasive developmental disorder not otherwise specified (PDD-NOS), staring spells, headaches, and paresthesias. Case 2 is a 14-year-old girl with seizures, cognitive and motor difficulties, and minor dysmorphic features. These two cases suggest that 1q32.1 region on distal arm of 1q and genes involved are critical to cognitive and motor development in a gene dosage sensitive manner and that other neurological features are variable within this syndrome.

In the present study, the antimicrobial activity of glycyrrhetinic acid (GA) against Staphylococcus aureus, and its influence on the production of S. aureus alpha-haemolysin (Hla) were investigated, along with the in vivo activity of GA against S. aureus-induced pneumonia. GA could not inhibit the growth of S. aureus, but the secretion of Hla by S. aureus was significantly inhibited by low concentrations of GA in a dose-dependent manner. Furthermore, in vivo data show that GA provides protection against staphylococcal pneumonia in a murine model system.

Background Ventricular septal defects (VSDs) constitute the most prevalent congenital heart disease (CHD), occurs either in isolation (isolated VSD) or in combination with other cardiac defects (complex VSD). Copy number variation (CNV) has been highlighted as a possible contributing factor to the etiology of many congenital diseases. However, little is known concerning the involvement of CNVs in either isolated or complex VSDs. Methods We analyzed 154 unrelated Chinese individuals with VSD by chromosomal microarray analysis. The subjects were recruited from four hospitals across China. Each case underwent clinical assessment to define the type of VSD, either isolated or complex VSD. CNVs detected were categorized into syndrom related CNVs, recurrent CNVs and rare CNVs. Genes encompassed by the CNVs were analyzed using enrichment and pathway analysis. Results Among 154 probands, we identified 29 rare CNVs in 26 VSD patients (16.9 %, 26/154) and 8 syndrome-related CNVs in 8 VSD patients (5.2 %, 8/154). 12 of the detected 29 rare CNVs (41.3 %) were recurrently reported in DECIPHER or ISCA database as associated with either VSD or general heart disease. Fifteen genes (5 %, 15/285) within CNVs were associated with a broad spectrum of complicated CHD. Among these15 genes, 7 genes were in “abnormal interventricular septum morphology” derived from the MGI (mouse genome informatics) database, and nine genes were associated with cardiovascular system development (GO:0072538).We also found that these VSD-related candidate genes are enriched in chromatin binding and transcription regulation, which are the biological processes underlying heart development. Conclusions Our study demonstrates the potential clinical diagnostic utility of genomic imbalance profiling in VSD patients. Additionally, gene enrichment and pathway analysis helped us to implicate VSD related candidate genes. Electronic supplementary material The online version of this article (doi:10.1186/s12920-015-0163-4) contains supplementary material, which is available to authorized users.

We examined parenting stress and mental health status in parents of autistic children and assessed factors associated with such stress. Participants were parents of 188 autistic children diagnosed with DSM-IV criteria and parents of 144 normally developing children. Parents of autistic children reported higher levels of stress, depression, and anxiety than parents of normally developing children. Mothers of autistic children had a higher risk of depression and anxiety than that did parents of normally developing children. Mothers compared to fathers of autistic children were more vulnerable to depression. Age, behavior problems of autistic children, and mothers' anxiety were significantly associated with parenting stress.

The aim of this study was to study the role of interleukin-1 receptor-associated kinase 4 (IRAK-4) in the formation of endotoxin tolerance (ET) in liver ischemia/reperfusion (I/R) injury.Animals were randomly divided into 3 groups: control group, I/R group, and ET group. Liver morphological changes were observed using optical microscopy with hematoxylin eosin (HE) staining. Alanine aminotransferase (ALT) was quantified to measure liver functional injury. The messenger RNA (mRNA) and protein expressions of IRAK-4 in Kupffer cells (KCs) isolated from recipients were detected using real-time polymerase chain reaction (PCR) and Western blot, respectively. The activities of NF-κB and the supernatant levels of tumor necrosis factor-alpha (TNF-α), IL-10 were assayed using enzyme-linked immunosorbent assay (ELISA).Endotoxin preconditioning improved hepatic tissue injury as indicated by morphological analysis, whereas serum ALT levels were significantly decreased at various times (P.05); concurrently, the expression of IRAK-4 and TNF-α in KCs was down-regulated (P.05) and the secretion of IL-10 was enhanced (P.05); NF-κB DNA-binding activity of KCs was also significantly inhibited by endotoxin preconditioning (P.05).Endotoxin preconditioning attenuated the liver I/R injury caused by transplantation. The expression of IRAK-4 in KCs may play an important role in the formation of ET.

Recurrent genomic imbalances at 16p11.2 are genetic risk factors of variable penetrance for developmental delay and autism. Recently, 16p11.2 (chr16:29.5 Mb–30.1 Mb) deletion has also been detected in individuals with early-onset severe obesity. The penetrance of 16p11.2 deletion as a genetic risk factor for obesity is unknown. We evaluated the growth and body mass characteristics of 28 individuals with 16p11.2 (chr16:29.5 Mb–30.1 Mb) deletion originally ascertained for their developmental disorders by reviewing their medical records. We found that nine individuals could be classified as obese and six as overweight. These individuals generally had early feeding and growth difficulties, and started to gain excessive weight around 5–6 years of age. Thirteen out of the 18 deletion carriers aged 5 years and older (72%) were overweight or obese, whereas only two of 10 deletion carriers (20%) younger than five were overweight or obese. Males exhibited more severe obesity than females. Thus, the obesity phenotype of 16p11.2 deletion carriers is of juvenile onset, exhibited an age- and gender-dependent penetrance. 16p11.2 deletion appears to predispose individuals to juvenile onset obesity and in this case are similar to the well-described Prader–Willi syndrome (PWS). Early detection of this deletion will provide opportunity to prevent obesity.

The molecular testing options available for the diagnosis of genetic disorders are numerous and include a variety of different assay platforms. The consultative input of molecular pathologists and cytogeneticists, working closely with the ordering clinicians, is often important for definitive diagnosis. Herein, we describe two patients who had long histories of unexplained signs and symptoms with a high clinical suspicion of an underlying genetic etiology. Initial molecular testing in both cases was negative, but the application of high-resolution array comparative genomic hybridization technology lead to definitive diagnosis in both cases. We summarize the clinical findings and molecular testing in each case, discuss the differential diagnoses, and review the clinical and pathological findings of Mowat-Wilson syndrome. This report highlights the importance for those involved in molecular testing to know the nature of the underlying genetic abnormalities associated with the suspected diagnosis, to recognize the limitations of each testing platform, and to persistently pursue repeat testing using high-resolution technologies when indicated. This concept is applicable to both germline and somatic molecular genetic testing.

The 16p11.2 deletion is a recurrent genomic event and a significant risk factor for autism spectrum disorders (ASD). This genomic disorder also exhibits extensive phenotypic variability and diverse clinical phenotypes. The full extent of phenotypic heterogeneity associated with the 16p11.2 deletion disorder and the factors that modify the clinical phenotypes are currently unknown. Multiplex families with deletion offer unique opportunities for exploring the degree of heterogeneity and implicating modifiers. Here we reported the clinical and genomic characteristics of three 16p11.2 deletion carriers in a Chinese family. The father carries a de novo 16p11.2 deletion, and it was transmitted to the proband and sib. The proband presented with ASD, intellectual disability, learning difficulty, congenital malformations such as atrial septal defect, scoliosis. His dysmorphic features included myopia and strabismus, flat and broad nasal bridge, etc. While the father shared same neurodevelopmental problems as the proband, the younger brother did not show many of the proband's phenotypes. The possible unmasked mutation of TBX6 and MVP gene in this deleted region and the differential distribution of other genomic CNVs were explored to explain the phenotypic heterogeneity in these carriers. This report demonstrated the different developmental trajectory and discordant phenotypes among family members with the same 16p11.2 deletion, thus further illustrated the phenotypic complexity and heterogeneity of the 16p11.2 deletion. © 2010 Wiley-Liss, Inc.

ObjectiveTo explore the mechanism of Xiaotan Sanjie Recipe (XtSjR, Recipe for dissolving phlegm to eliminate stagnation) in inhibiting proliferation of gastric cancer cells.MethodsThe nude mouse human gastric cancer MKN-45 in situ transplantation tumor model was established by use of OB glue, and 40 model mice were randomized into 5 groups, model group, low-dose XtSjR group, middle-dose XtSjR group, high-dose XtSjR group, and 5-Fu group, 8 rats in each group. Human gastric cancer MKN-45 telomerase reverse transcriptase (hTERT) protein and mRNA expressions were assayed by immunohistochemical method and real-time fluorescence quantitative RT-PCR, and influences of XtSjR on the expressions of hTERT protein and mRNA were investigated in the nude mouse human gastric cancer MKN-45 in situ tumor transplantation model.Results1) There were significant differences in the mean tumor weight between the low-, middle-, high-dose XtSjR groups and the model group (all P

Interplay between integrins and extracellular matrix is suggested to play an important role in malignant progression and tumor differentiation. The aim of the study was to determine the combined expression of integrin β3 and tenascin-c (TN-c) in breast cancer and examine whether integrin β3 and TN-c can activate urokinase-type plasminogen activator (uPA) through p38 mitogen-activated protein kinase (p38 MAPK). We detected the expression of integrin β3, TN-c, p-p38, and uPA in 80 cases of breast invasive ductal carcinoma by immunohistochemistry. In addition, we blocked integrin β3 and TN-c in the MDA-MB-231 breast cancer cells and detected the expression of p-p38 and uPA by Western blot. Integrin β3, TN-c, p-p38, and uPA showed high levels of expression in breast invasive ductal carcinoma. The expression of integrin β3, TN-c, and uPA was correlated with lymph node metastasis and TNM stage in breast cancer. Furthermore, correlations were noted between any two of the three proteins. The expression of p-p38 and uPA decreased in MDA-MB-231 cells after the addition of integrin β3 antibody and TN-c antibody. The expression of uPA decreased after addition of SB203580. Our results demonstrate that inhibition of the expression of integrin β3 and TN-c could decrease the expression of uPA through p38 MAPK in breast cancer, suggesting that the interaction between integrin β3 and TN-c serves an important role in breast cancer.

To describe cognitive and behavioral features of patients with chromosome 16p11.2 deletion syndrome, a recently identified and common genetic cause of neurodevelopmental disability, especially autism spectrum disorder (ASD).Twenty-one patients with 16p11.2 deletion were evaluated by medical record review. A subset of 11 patients consented to detailed cognitive, behavioral, and autism diagnostic assessment.Patients with 16p11.2 deletion had varying levels of intellectual disability, variable adaptive skills, and a high incidence of language delay. Attention issues were not as frequent as had been reported in previous clinical reports. Atypical language, reduced social skills, and maladaptive behaviors were common, as was diagnosis of ASD. Based on medical record review, 7 of 21 patients (33%) had an ASD diagnosis. Among patients receiving detailed phenotyping, 3 of 11 (27%) met full criteria (met cutoff scores on both Autism Diagnostic Observation Schedule and Autism Diagnostic Interview) for an ASD diagnosis, whereas 6 other patients (55%) met criteria for ASD on either the Autism Diagnostic Observation Schedule or the Autism Diagnostic Interview, but not both measures.Rates of ASD were similar to previous reports that are based on medical record reviews, but formal assessment revealed that a majority of patients with 16p11.2 deletion demonstrate features of ASD beyond simple language impairment. All patients with 16p11.2 deletion should receive formal neurodevelopmental evaluation including measures to specifically assess cognitive, adaptive, language, and psychiatric/behavioral issues. Clinical evaluation of this patient population should always include assessment by Autism Diagnostic Interview and Autism Diagnostic Observation Schedule to detect behaviors related to ASD and possible ASD diagnosis.

Li Dong Wang and colleagues report a genome wide association study for esophageal squamous cell carcinoma in the Chinese population. They identify two risk loci at PLCE1 and C20orf54.

BACKGROUND: Neural tube defects are severe, common birth defects that result from failure of neural tube closure. They are considered to be a multifactorial disorder, and our knowledge of causal mechanisms remains limited. We hypothesized that abnormal DNA methylation occurs in NTD-affected fetuses. The correlations of global DNA methylation levels with complexity of NTDs and known risk factors of NTDs, MTHFR genotype and fever, were analyzed. METHODS: A hospital-based case-control study was performed. Epidemiologic data, pathologic diagnosis, and methylenetetrahydrofolate reductase (MTHFR) genotype analysis were completed. Array comparative genomic hybridization was used to exclude cytogenetic abnormalities. Global DNA methylation statuses were determined for both brain and skin tissue. RESULTS: Sixty-five NTD-affected fetuses and 65 normal controls matched for gestational and maternal ages were collected. In brain tissue, global DNA methylation levels were significantly decreased in cases compared with controls (4.12 vs. 4.99%; p < 0.001). DNA hypomethylation (

Sonic Hedgehog (Shh) plays an essential role in vertebrate organogenesis as well as the development of some cancers, including breast cancer. The aim of the present study was to characterize more precisely its role in breast carcinogenesis and elucidate its regulation mechanisms. The expression of Shh was investigated in 97 breast carcinomas and 22 paired non-tumorous tissues (distant from the primary tumor) by immunohistochemistry and in four breast cell lines by Western blotting. We also analyzed the methylation status of the Shh gene with methylation-specific PCR and assessed whether nuclear factor-kappa B (NF-kappaB) and Gli1 were expressed in breast tissues by immunohistochemistry. Our results showed that Shh protein expression in breast carcinomas was significant higher than that in normal breast tissues (P < 0.01). The up-regulation of Shh in breast carcinomas was correlated significantly with early clinical stage (P < 0.05). In addition, we found a substantial increase in Shh expression at both the mRNA and protein levels in several human breast carcinoma cell lines. The expression level of nuclear Gli1 was positively associated with the expression level of Shh in breast tissues (P < 0.001). Promoter region hypomethylation (43/61, 70.5%) was frequently observed in breast carcinomas and significantly associated with Shh up-regulation (P < 0.05). The DNA methyltransferase inhibitor 5-azacytidine (5-Aza) reduced the methylation of Shh promoter and increased the expression of Shh protein in MDA-MB-435 and MCF-10A cells. Furthermore, most of the breast carcinoma cases with Shh up-regulation had increased expression of NF-kappaB (35/49, 71.4%; P < 0.001). Taken together, these observations suggest that Shh overexpression is a critical event in breast carcinogenesis, and Shh promoter hypomethylation and NF-kappaB up-regulation are responsible for the up-regulation of Shh.

Seven in absentia homolog1 (SIAH1) was reported as a tumor suppressor and played an important role in regulating cell apoptosis. However, its effects on the breast carcinogenesis remain unclear. In this study, our aims were to examine the relationship between SIAH1 and Bcl-2-interacting mediator of cell death (Bim) and to explore the effects of SIAH1 on the breast carcinogenesis. Immunohistochemical analysis in 231 cases of breast tissues showed that the expression of SIAH1 and Bim were significantly decreased in the breast carcinogenesis. Moreover, SIAH1 expression was significantly correlated with Bim. Both SIAH1 and Bim expression were significantly higher in well to moderately differentiated and in early-stage breast cancer. Reverse transcription (RT)-polymerase chain reaction (PCR) and Western blot analysis in paired breast cancer tissues and breast cell lines found that the expression of SIAH1 was lower in the breast cancer tissues and cell lines. SIAH1 inducing apoptosis of the breast cancer cells was dependent on Bim. However, SIAH1 inhibiting invasion of the breast cancer cells was independent of Bim. The increase of the function of SIAH1 to upregulate the expression of Bim may play an important role in the progression of breast cancer. Restoration of the function of SIAH1 may be a new therapeutic target of human breast cancer. © 2010 Wiley-Liss, Inc.

Seven in absentia homolog 1 (SIAH1), a homologue of Drosophila seven in absentia (Sina), has emerged as a tumor suppressor and plays an important role in regulating cell apoptosis. To investigate the role and possible mechanism of SIAH1 in breast cancer cells, we up-regulated the expression of SIAH1 using pcDNA3-myc-SIAH1 and knocked down SIAH1 using SIAH1 siRNA. We found that the overexpression of SIAH1 induced cell apoptosis by up-regulating the level of Bim through the activation of the JNK signaling pathway, and the suppression of SIAH1 expression increased cell invasion via the activation of the ERK signaling pathway in breast cancer cells. All these results indicate that the JNK and ERK signaling pathways may play an important role in the SIAH1-dependent biological behavior of breast cancer, and it may be a good molecular therapeutic target to increase the expression level of SIAH1 through promoting cell apoptosis and inhibiting cell invasion in human breast cancer.