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Background Mounting evidence shows that microRNA-34a (miR-34a) is involved in cancer prognosis. Therefore, we summarize the predictive role of miR-34a for survival in patients with gastrointestinal cancers (GICs). Methods All eligible studies were found by searching PubMed, Web of Science and EMBASE, and survival results were extracted. Then, the hazard ratio (HR) with the corresponding 95% confidence interval (CI) was calculated to evaluate the prognostic role of miR-34a in GICs. The association between miR-34a expression and clinicopathological characteristics was estimated by odds ratios (ORs) and 95% CIs. Results A total of 20 studies were included in this meta-analysis. For overall survival (OS), lower miR-34a expression could probably predict poorer outcome in GICs, with a pooled HR of 1.86 (95% CI: 1.52–2.28, P P Conclusion This meta-analysis revealed that lower miR-34a expression is significantly connected with worse OS and DFS/PFS/RFS in GIC patients. In addition, the miR-34a expression level is relatively lower in patients with lymph node metastasis than in patients without lymph node metastasis, and decreased miR-34a expression levels are linked to poor tumour differentiation and late TNM stage. MiR-34a may become a new factor for the prognosis prediction and progression of GICs.

Epidemiological studies on the association of sulfur dioxide (SO2) with neural tube defects (NTDs) are lacking. The purpose of this study was to assess the aforementioned association through a population-based case–control study. This study involved 1457 NTDs cases and 7950 randomly selected healthy infants born in 14 cities in Liaoning province between 2010 and 2015. Ambient SO2 levels were acquired from 75 monitoring stations. The exposure assessment was based on the mean concentration of all stations in mother’s residential city. We used logistic regression models to assess the associations. In multivariable models adjusted for the confounding variables selected based on the 10 percent change-in-estimate method, we found that maternal SO2 exposure was positively associated with an increased risk of NTDs during the first month after conception (per 10 μg/m3 increase: adjusted odds ratio [aOR] = 1.02, 95% confidence interval [CI]: 1.00–1.04; highest versus lowest quartile: aOR = 2.55, 95% CI: 1.97–3.31) and the second month after conception (per 10 μg/m3 increase: aOR = 1.02, 95% CI: 1.00–1.04; highest versus lowest quartile: aOR=2.31, 95% CI: 1.77–3.00). For other exposure windows, positive associations also emerged in high- versus low-exposure analyses, except for the third month before conception; however, we could not further confirm significant findings from the continuous exposure analyses. Our study provides a new evidence that SO2 exposure may increase the risk of NTDs.

BackgroundCurrent literature describes limited and controversial evidence on the associations between maternal preconception and first trimester exposure to particulate matter with a diameter ≤10 µm (PM10) and the risk of oral cleft (OC).MethodsWe conducted a case–control study involving 3086 OC cases and 7950 controls, registered in the Maternal and Child Health Certificate Registry in Liaoning Province between 2010 and 2015. PM10 concentrations were obtained from the Environment Protection Bureau. The exposure windows included the 3 months before pregnancy, the first trimester and the individual months. Unconditional logistic regression model was performed to estimate the OR and 95% CI for the association between PM10 exposure and the risk of OC, cleft lip only (CLO), cleft palate only (CPO), and cleft lip and palate (CLP).ResultsMaternal PM10 exposure was positively associated with an increased risk for OC during the 3 months preconception (per 10 µg/m3 increment: OR=1.04, 95% CI 1.01 to 1.07; highest vs lowest quartile: OR=1.23, 95% CI 1.04 to 1.45) and the first trimester (per 10 µg/m3 increment: OR=1.05, 95% CI 1.02 to 1.08; highest vs lowest quartile: OR=1.37, 95% CI 1.15 to 1.64). Analyses based on individual months presented similar positive associations, particularly in the second month of pregnancy (OR=1.77, 95% CI 1.51 to 2.09) for highest versus lowest quartile. In the subtype analysis, stronger associations were observed for CLO, whereas there was negligible evidence for CPO and CLP. Sensitivity analyses using propensity score matching generated similar findings.ConclusionsOur study provides evidence that PM10 exposure during the 3 months preconception and the first trimester increases the risk of OC.

Background/Aims Pancreatic ductal adenocarcinoma (PDAC) is associated with high mortality, even after surgical resection. The existing predictive models for survival have limitations. This study aimed to develop better nomograms for predicting overall survival (OS) and cancer‐specific survival (CSS) in PDAC patients after surgery. Methods A total of 6323 PDAC patients were retrospectively recruited from the Surveillance, Epidemiology, and End Results (SEER) database and randomly allocated into training, validation, and test cohorts. Multivariate Cox regression analysis was conducted to identify significant independent factors for OS and CSS, which were used for construction of nomograms. The performance was evaluated, validated, and compared with that of the 8th edition AJCC staging system. Results Ten independent factors were significantly correlated with OS and CSS. The 1‐, 3‐, and 5‐year OS rates were 40%, 20%, and 15%, and 1‐, 3‐, and 5‐year CSS rates were 45%, 24%, and 19%, respectively. The nomograms were calibrated well, with c‐indexes of 0.640 for OS and 0.643 for CSS, respectively. Notably, relative to the 8th edition AJCC staging system, the nomograms were able to stratify each AJCC stage into three prognostic subgroups for more robust risk stratification. Furthermore, the nomograms achieved significant clinical validity, exhibiting wide threshold probabilities and high net benefit. Performance assessment also showed high predictive accuracy and reliability. Conclusions The predictive ability and reliability of the established nomograms have been validated, and therefore, these nomograms hold potential as novel approaches to predicting survival and assessing survival risks for PDAC patients after surgery., In the present study, we constructed and validated nomograms for predicting the 1‐, 3‐, and 5‐year OS and CSS rates after surgical resection of PDAC. The nomograms established in the present study showed good performance for the prediction of OS and CSS, which was superior to that of the existing, conventional AJCC staging system with an improved net benefit. Therefore, these nomograms hold promise as novel prognosis models for improving the prediction of individualized postoperative survival and improving the care of PDAC patients following surgical resection.

Limited studies have focused on the impact of ambient air pollution on spina bifida. A population-based case-control study was conducted in Liaoning Province, China to assess the associations between maternal PM10 exposures in various exposure windows and spina bifida risk. Data on spina bifida cases born between 2010 and 2015 were available from the Maternal and Child Health Certificate Registry of Liaoning Province. Controls were a random sample of healthy livebirths without any birth defects delivered in the selected five cities during 2010–2015. Ambient air monitoring data for PM10 were obtained from 75 monitoring stations in Liaoning Province. The multivariable logistic regression models were established to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI). We further performed sensitivity analyses by using three propensity score methods. A total of 749 spina bifida cases and 7,950 controls were included. After adjusting for potential confounders, spina bifida was associated with a 10 μg/m3 increment in PM10 during the first trimester of pregnancy (adjusted OR = 1.06, 95% CI: 1.00–1.12) and the 3 months before pregnancy (adjusted OR = 1.12, 95% CI: 1.06–1.19). The adjusted ORs in the final model for the highest vs. the lowest quartile were 1.51 (95% CI: 1.04–2.19) for PM10 during the first trimester of pregnancy and 2.01 (95% CI: 1.43–2.81) for PM10 during the 3 months before pregnancy. Positive associations were found between PM10 exposures during the single month exposure windows and spina bifida. Sensitivity analyses based on two propensity score methods largely reported similar positive associations. Our findings support the evidence that maternal PM10 exposure increases the risk of spina bifida in offspring. Further, validation with a prospective design and a more accurate exposure assessment is warranted.

The mitochondria DNA (mtDNA) editing tool, zinc finger nucleases (ZFNs), transcription activator-like effector nuclease (TALENs), and clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9) system, is a promising approach for the treatment of mtDNA diseases by eliminating mutant mitochondrial genomes. However, there have been no reports of repairing the mutant mtDNA with homologous recombination strategy to date. Here, we show a mito-CRISPR/Cas9 system that mito-Cas9 protein can specifically target mtDNA and reduce mtDNA copy number in both human cells and zebrafish. An exogenous single-stranded DNA with short homologous arm was knocked into the targeting loci accurately, and this mutagenesis could be steadily transmitted to F1 generation of zebrafish. Moreover, we found some major factors involved in nuclear DNA repair were upregulated significantly by the mito-CRISPR/Cas9 system. Taken together, our data suggested that the mito-CRISPR/Cas9 system could be a us...

Pancreatic cancer (PC) represents a relatively rare but severe malignancy worldwide. Accumulated studies have emphasized the potential of long noncoding RNA (lncRNA) as therapeutic strategies for several human cancers. Thus, we aimed to investigate whether a novel non-coding RNA regulatory circuitry involved in PC. Aberrantly expressed lncRNAs and mRNAs were screened out of microarray database. Following the determination of RNA expression, PANC-1 and BxPC-3 PC cells were adopted, after which the expression of miR-330-5p, PAX8 and LINC00958 were subsequently altered. RNA crosstalk was validated by dual-luciferase reporter gene assay. In order to detect whether LINC00958 could act as ceRNA to competitively sponge miR-330-5p and regulate PAX8, subcellular location of LINC00958 and interaction between LINC00958 and miR-330-5p were measured by FISH and RNA pull down respectively. The epithelial mesenchymal transition (EMT) process, cell invasion, and tumor growth were determined in vitro and in vivo. LINC00958 and PAX8 were up-regulated, while miR-330-5p was down-regulated during PC. LINC00958 mainly expressed in the cytoplasm and LINC00958 competitively sponged miR-330-5p. Upregulated miR-330-5p or downregulated PAX8 inhibited the EMT process as well as the invasion and metastasis ability of the PC cells. Moreover, the results indicated that miR-330-5p negatively targeted PAX8, and LINC00958 ultimately showcasing its ability to bind to miR-330-5p through its interaction with AGO2. Therefore, silencing of LINC00958 may bind to miR-330-5p to inhibit PAX8 in a competitive fashion, thereby preventing the progression of PC.

Purpose Primary hepatic angiosarcoma is a very rare and highly malignant tumor with poor prognosis. It is difficult to diagnose because of the lack of typical clinical features, and the treatment protocols for PHA are also not clear. Therefore, this study wants to find out the clinical characteristics and surgical treatments of primary hepatic angiosarcoma. Methods Among 8990 patients diagnosed with primary malignant tumor of the liver from January 2000 to December 2019 in our hospital, only four patients were diagnosed with primary hepatic angiosarcoma. The demographics, clinical manifestation, past history, serology test results, MRI features, pathology, treatment modality and prognosis of four patients were collected and analyzed. Results Three of four patients had no clinical symptoms, while one patient's symptom was abdominal pain. The levels of tumor markers of all four patients were within the normal reference range and serological tests were negative for hepatitis B and C virus. The MRI imaging findings of all four patients were mixed mass with highly disordered vascular characteristics. All four patients were misdiagnosed preoperatively. One patient who underwent hepatic lobectomy was still alive for about 18 months after surgery. One patient who underwent hepatic lobectomy has survived for only 6 months due to severe pneumonia. The other two patients who received transarterial chemoembolization survived 16 months and 11 months respectively. Conclusion The clinical symptoms of primary hepatic angiosarcoma are not typical, and primary hepatic angiosarcoma is easily misdiagnosed. The typical imaging manifestations are structural disorder and heterogeneous tumor. Hepatic lobectomy and transarterial chemoembolization may be important surgical treatments to improve the prognosis of patients.

Background/AimsPancreatic ductal adenocarcinoma (PDAC) can occur in different parts of the pancreas. This study aimed to identify clinicopathological characteristics independently correlated with the prognosis of PDAC of the pancreatic head/uncinate (PHC) or body-tail (PBTC), and to develop novel nomograms for predicting cancer-specific survival (CSS) according to different primary cancer locations.Methods1160 PDAC patients were retrospectively enrolled and assigned to training and test sets with each set divided into PHC and PBTC groups. Comparative analysis of clinicopathologic characteristics, survival analysis, and multivariate analysis were performed. Independent factors were identified and used for constructing nomograms. The performance of the nomograms was validated in the test set.ResultsPrimary tumor location was an independent risk factor for prognosis of PDAC after surgery. Specially, gender, fasting blood glucose, and preoperative cancer antigen 19-9 were significantly associated with prognosis of PHC, whereas age, body mass index, and lymph nodes were significantly correlated with the prognosis of PBTC. A significant difference in prognosis was found between PHC and PBTC in stage Ia and stage III. Three nomograms were established for predicting the prognosis for PDAC, PHC, and PBTC. Notably, these nomograms were calibrated modestly (c-indexes of 0.690 for PDAC, 0.669 for PHC, and 0.704 for PBTC), presented better accuracy and reliability than the 8th AJCC staging system, and achieved clinical validity.ConclusionsPHC and PBTC share the differential clinical-pathological characteristics and survival. The nomograms show good performance for predicting prognosis in PHC and PBTC. Therefore, these nomograms hold potential as novel approaches for predicting survival of PHC and PBTC patients after surgery.

Airway stenosis is a common problem in the neonatal intensive care unit (NICU) and pediatric intensive care unit (PICU). A tissue-engineered trachea is a new therapeutic method and a research hotspot. Successful vascularization is the key to the application of a tissue-engineered trachea. However, successful vascularization studies lack a complete description. In this study, it was assumed that rabbit bone marrow mesenchymal stem cells were obtained and induced by ascorbic acid to detect the tissue structure, ultrastructure, and gene expression of the extracellular matrix. A vascular endothelial cell culture medium was added in vitro to induce the vascularization of the stem cell sheet (SCS), and the immunohistochemistry and gene expression of vascular endothelial cell markers were detected. At the same time, vascular growth-related factors were added and detected during SCS construction. After the SCS and decellularized tracheal (DT) were constructed, a tetrandrine allograft was performed to observe its vascularization potential. We established the architecture and identified rabbit bone marrow mesenchymal stem cell membranes by 14 days of ascorbic acid, studied the role of a vascularized membrane in inducing bone marrow mesenchymal stem cells by in vitro ascorbic acid, and assessed the role of combining the stem cell membranes and noncellular tracheal scaffolds in vivo. Fourteen experiments confirmed that cell membranes promote angiogenesis at gene level. The results of 21-day in vitro experiments showed that the composite tissue-engineered trachea had strong angiogenesis. In vivo experiments show that a composite tissue-engineered trachea has strong potential for angiogenesis. It promotes the understanding of diseases of airway stenosis and tissue-engineered tracheal regeneration in newborns and small infants.

Background T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease with a high risk of induction failure and poor outcomes, with relapse due to drug resistance. Recent studies show that bromodomains and extra-terminal (BET) protein inhibitors are promising anti-cancer agents. ARV-825, comprising a BET inhibitor conjugated with cereblon ligand, was recently developed to attenuate the growth of multiple tumors in vitro and in vivo. However, the functional and molecular mechanisms of ARV-825 in T-ALL remain unclear. This study aimed to investigate the therapeutic efficacy and potential mechanism of ARV-825 in T-ALL. Methods Expression of the BRD4 were determined in pediatric T-ALL samples and differential gene expression after ARV-825 treatment was explored by RNA-seq and quantitative reverse transcription-polymerase chain reaction. T-ALL cell viability was measured by CCK8 assay after ARV-825 administration. Cell cycle was analyzed by propidium iodide (PI) staining and apoptosis was assessed by Annexin V/PI staining. BRD4, BRD3 and BRD2 proteins were detected by western blot in cells treated with ARV-825. The effect of ARV-825 on T-ALL cells was analyzed in vivo. The functional and molecular pathways involved in ARV-825 treatment of T-ALL were verified by western blot and chromatin immunoprecipitation (ChIP). Results BRD4 expression was higher in pediatric T-ALL samples compared with T-cells from healthy donors. High BRD4 expression indicated a poor outcome. ARV-825 suppressed cell proliferation in vitro by arresting the cell cycle and inducing apoptosis, with elevated poly-ADP ribose polymerase and cleaved caspase 3. BRD4, BRD3, and BRD2 were degraded in line with reduced cereblon expression in T-ALL cells. ARV-825 had a lower IC50 in T-ALL cells compared with JQ1, dBET1 and OTX015. ARV-825 perturbed the H3K27Ac-Myc pathway and reduced c-Myc protein levels in T-ALL cells according to RNA-seq and ChIP. In the T-ALL xenograft model, ARV-825 significantly reduced tumor growth and led to the dysregulation of Ki67 and cleaved caspase 3. Moreover, ARV-825 inhibited cell proliferation by depleting BET and c-Myc proteins in vitro and in vivo. Conclusions BRD4 indicates a poor prognosis in T-ALL. The BRD4 degrader ARV-825 can effectively suppress the proliferation and promote apoptosis of T-ALL cells via BET protein depletion and c-Myc inhibition, thus providing a new strategy for the treatment of T-ALL.

Percutaneous ethanol injection is a well-known ablation therapy for hepatocellular carcinoma and is well-tolerated, inexpensive, and effective with few adverse events. In this study, another type of ethanol injection was introduced in the present study. Sixty two patients with hepatocellular carcinoma received 133 percutaneous peritumor ethanol injection treatments and the 15-year follow-up outcomes were analyzed through a collected database. The technical efficiency was 89.5% (119/133 treatments) after the first percutaneous peritumor ethanol injection procedure. However, after the second repeated percutaneous peritumor ethanol injection procedure, technical efficiency increased to 98.5% (131/133 treatments). The 1 year, 3 years, 5 years, 10 years, and 15 years rates of tumor recurrence were 12.9%, 50.0%, 59.7%, 74.2%, and 74.2%, respectively. Multivariate analysis demonstrated that diabetes, Child–Pugh class B, and tumor size greater than 2 cm were significantly related to tumor recurrence. The 1 year, 3 years, 5 years, 10 years, and 15 years rates of overall survival were 98.4%, 83.6%, 61.3%, 19.4%, and 0%, respectively. Multivariate analysis demonstrated that Child–Pugh class B, tumor size greater than 2 cm, and multiple tumors were significantly related to overall survival. Compared with other ablation methods (including peritumor ethanol injection), percutaneous peritumor ethanol injection can avoid tumor ruptures, reduce tumor proliferation and metastasis, and is suitable for the treatment of small tumors. In addition, when combined with other treatment methods, percutaneous peritumor ethanol injection can form a tumor metastatic isolation zone in advance and improve the comprehensive treatment effect.

Systemic inflammation and interactions with host-tumor are currently identified as a hallmark of cancer. The purpose of this study was to assess the prognostic value of preoperative modified Glasgow Prognostic Score (mGPS), systemic inflammation score (SIS) and "lymphocyte C-reactive protein score" (LCS) in gastric cancer (GC) patients.358 GC patients were enrolled in this retrospective study. Kaplan-Meier method, multivariate Cox regression analysis, time-dependent receiver operating characteristics analysis (ROC), concordance index (C-index), and Akaike information criterion (AIC) were applied for assessments of the prognostic values.Preoperative increased mGPS, SIS and LCS were all significantly linked with unfavorable overall survival using the Kaplan-Meier method (P 0.001). Multivariate analysis proved that SIS was the only independent indicator among these three scoring systems. At the 4th-month point postoperatively, the time-dependent ROC curves of SIS and LCS crossed the curve of mGPS and were consistently superior to that of mGPS thereafter. The model incorporating SIS had higher C-index and smaller AIC than did the model without SIS or the models with mGPS or LCS.Preoperative SIS exceeded both the mGPS and LCS and was the most clinically promising and feasible prognostic scoring system for GC patients.

Chronic inflammatory arthritis (CIA) severely impacts quality of life in over 100 million people in China. In 2011, the European League Against Rheumatism (EULAR) developed recommendations for the role of nurses in the management of CIA. However, it remains unknown whether these recommendations could be fully implemented in China. Therefore, we aimed to solve the problem in this study. We conducted a nationwide cross-sectional study among 485 nurses in rheumatology and immunology departments based on an online questionnaire. The agreement of the recommendations by the subjects and the feasibility of the recommendations they believe were assessed by visual analogue scale (VAS). Our results showed that over 80% of the subjects agreed with each recommendation (VAS 5–10), and over 80% of the subjects considered the recommendations feasible (VAS 5–10). This study indicates that the EULAR recommendations can also be well implemented in China.

Background There is no epidemiological evidence on the effects of maternal exposure to ambient particulate matter 10 μm or less in diameter (PM10) and anencephaly risk in offspring. Methods We conducted a population-based case-control study in Liaoning Province, China. The case group consisted of 663 cases with anencephaly and the control group consisted of 7950 healthy infants from the Maternal and Child Health Certificate Registry of Liaoning Province that were born between 2010 and 2015. Daily PM10 concentrations were obtained from 77 monitoring stations located within the study area. A multivariable logistic regression model was established to calculate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results Maternal PM10 exposure was significantly associated with an increased risk of anencephaly at three months before conception (highest versus lowest tertile: OR = 1.74, 95% CI: 1.29–2.34; per 10 μg/m3 increment: OR = 1.13, 95% CI: 1.06–1.20) and three months after conception (highest versus lowest tertile: OR = 1.93, 95% CI: 1.44–2.60; per 10 μg/m3 increment: OR = 1.01, 95% CI: 0.95–1.08). The evaluation of shorter exposure windows revealed similar associations for PM10 exposure from the third month before pregnancy to the third month after pregnancy. Conclusions Maternal PM10 exposure is positively associated with anencephaly risk during the critical period of neural system development.

The aim of this study was to assess the prevalence and trends of congenital hydrocephalus (CH) using a large population-based sample with cases retrieved from the Liaoning Birth Defects Registry, which included 14 cities, over a 10-year period. CH prevalence, percent change, average change, and contribution rates of each city were calculated. Statistical analysis was performed using a Poisson regression model. There was a total of 3008 CH cases among 3,248,954 live births during the observational period (9.26 cases/10,000 live births). On average, the prevalence of CH had significantly decreased by 11.84% each year (P < 0.01). The three leading cities with the highest prevalence of CH were Chaoyang (13.73/10,000), Huludao (13.18/10,000), and Fuxin (12.71/10,000), while Yingkou (6.06/10,000), Dalian (6.27/10,000), and Anshan (6.56/10,000) had the lowest prevalence. Notably, significantly decreasing trends were observed in 10 (71.4%) of these 14 cities. In addition, the cities of Fushun, Shenyang, and Dalian had contributed to more than one-third of the decreasing trend in Liaoning province. In conclusion, this study provides evidence of the decreasing prevalence of CH over a 10-year period (2006–2015) in Liaoning province. Preventative efforts should be strengthened to further reduce the risk of CH in these high prevalence areas.

Nitrogen oxide (NOx) is produced during combustion at high temperature, which is a major constituent of air pollutants. Recent studies suggested inconsistent results on the association between NOx exposure and cardiovascular-related malformations. We aimed to assess aforementioned association in pregnant women in the first trimester and cardiovascular-related malformations of infants. A systematic literature review identified studies for observational studies about NOx exposure and cardiovascular-related malformation in PubMed. Random-effect models were used to estimate summary odds ratio (SOR) and 95% confidence intervals (CIs) for aforementioned association. Finally, nine studies met the inclusion criteria. Overall, the SOR of cardiovascular-related malformation per 10 ppb increment in NOx and NO2 concentration was 1.01 (95% CI: 0.98–1.04; I2 = 38.6%, P=0.09) and 0.99 (95% CI: 0.95–1.04; I2 = 37.8%, P=0.13), respectively. Stratifying by study design, geographic locations, and confounded adjustments, the majority of strata showed negative results, which were consistent with the main findings. However, we found that exposure to NOx and NO2 in the first trimester increased the risk of coarctation of the aorta (COA) malformation by 13% and 19%, respectively. Our study provided limited evidence regarding the association between NOx exposure in the first trimester and cardiovascular-related malformations in infants.

The prognosis of patients with intrahepatic cholangiocarcinoma (ICC) is undefined among the different macroscopic types. This study evaluated the viability of the American Joint Committee on Cancer (AJCC) 8th edition staging classification for different macroscopic types. Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we enrolled a total of 2,679 eligible patients with an estimated 199 periductal infiltrating type of ICC (ICC-PI) patients and 2,480 mass-forming type of ICC (ICC-MF) patients. After conducting a multivariate Cox analysis, we found that the AJCC 8th edition staging system was suitable for ICC-MF patients but not for ICC-PI patients according to cancer-specific survival (CSS) and overall survival (OS). The main reason was the similar hazard ratio (HR) between the ICC-PI patients with stage I and stage II disease according to CSS (HR:0.969, P = 0.949) and OS (HR:0.832, P = 0.703). Moreover, we found that ICC-PI patients in AJCC stage I had a similar HR as ICC-MF patients in AJCC stage II according to CSS (HR: 1.208, P = 0.475) and OS (HR:1.206, P = 0.456). Therefore, we suggested that ICC-PI patients may be defined as T2, which is classified as stage II disease. This suggestion for the AJCC 8th edition staging system would be more suitable for different macroscopic types of ICC but requires further verification in prospective clinical trials.

Background Cross-border malaria transmission in China is a major component of Chinese imported malaria cases. Such cases mostly are travellers returning from malaria endemic countries in Africa. By investigating malaria infectious status among Chinese worker in Africa, this study analysed the malaria risk factors, in order to establish infectious forecast model. Methods Chinese returnees data from Africa were collected at Guangzhou Baiyun International Airport, Guangzhou, China between August 2015 and March 2016 and were included in the cross-sectional and retrospective survey. Results A total of 1492 respondents were included in the study with the majority consisting of junior middle school educated male. Most of them are manual and technical workers hired by companies, with average of 37.04 years of age. Overall malaria incidence rate of the population was 8.98% (134/1492), and there were no significant differences regarding age, gender, occupation, or team. Forecast model was developed on the basis of malaria risk factors including working country, local ecological environment type, work duration and intensity of mosquito bite prevention. Conclusions The survey suggested that malaria incidence was high among Chinese travellers who had worked in Africa countries of heavy malaria burden. Further research on the frequency and severity of clinical episodes among Chinese travellers having worked in Africa is needed.

// Ting-Ting Gong 1 , Qi-Jun Wu 2 , Yan-Ling Chen 3 , Cheng-Zhi Jiang 4 , Da Li 1 , Jing Li 5 , Li-Li Li 6 , Chen Zhou 7 and Yan-Hong Huang 5 1 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China 2 Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China 3 Liaoning Women and Children’s Health Hospital, Shenyang, China 4 School of Environmental and Chemical Engineering, Shenyang Ligong University, Shenyang, China 5 Department of Science and Education, Shenyang Women and Children Health Care Centre, Shenyang, China 6 Department of Children’s Health Prevention, Shenyang Women and Children Health Care Centre, Shenyang, China 7 Department of Information Statistics, Shenyang Women and Children Health Care Centre, Shenyang, China Correspondence to: Qi-Jun Wu, email: wuqj@sj-hospital.org Keywords: anencephaly, Liaoning province, prevalence, time trend Received: November 04, 2016 Accepted: February 22, 2017 Published: April 26, 2017 ABSTRACT The goal of this study was to assess the prevalence and trends of anencephaly on the basis of a large population-based cases identified by the Liaoning Birth Defects Registry, which included 14 cities over a 10-year period. Anencephaly prevalence, percent change, average changeand the contribution rates of each city were calculated. Statistical analysis was undertaken on the basis of a Poisson regression model. A total of 1600 anencephaly cases were collected during the observational period (4.92/10,000 live births). On average, the prevalence decreased 10.15% each year; this overall time trend was statistically significant (P

// Gen Ba 1 , Qi-Jun Wu 2 , Yan-Ling Chen 3 , Yan-Hong Huang 4 , Ting-Ting Gong 5 1 Department of Orthopaedics, Shengjing Hospital of China Medical University, Shenyang, China 2 Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China 3 Liaoning Women and Children’s Health Hospital, Shenyang, China 4 Department of Science and Education, Shenyang Women and Children Health Care Centre, Shenyang, China 5 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China Correspondence to: Qi-Jun Wu, email: wuqj@sj-hospital.org Keywords: Liaoning Province, prevalence, spina bifida, time trend Received: October 04, 2016 Accepted: January 08, 2017 Published: January 27, 2017 ABSTRACT The present study sought to assess the time trends of spina bifida on the basis of cases identified by the Liaoning Birth Defects Registry in 14 cities from 2006 to 2015. We calculated the prevalence of spina bifida, percent and average change of time trends, and contribution rates of each city. Poisson regression model was used to find the line of best fit for spina bifida prevalence by year, with year as a continuous independent variable. From 2006 to 2015, a total of 2,029 spina bifida cases were identified from 3,248,954 live births (6.25/10,000 live births). We observed statistically significant decreasing trend of overall time trend (11.57% each year). Chaoyang, Fuxin, and Huludao were the top three leading cities, with 14.30/10,000 live births, 9.70/10,000 live births, and 9.20/10,000 live births, respectively. Inversely, the bottom three cities with lowest prevalence were Anshan (2.64/10,000 live births), Dandong (3.43/10,000 live births), and Dalian (3.45/10,000 live births). Of note, we observed significant decreasing trends in over half of these cities ( n = 8). In addition, the decreasing trend of overall time trend could be mainly attributed to cities of Shenyang, Fushun, and Jinzhou which accounted for nearly one third. In summary, our study suggested a decreasing time trend of spina bifida during the past decade in the Liaoning province. The findings of this study provide evidence that the nationwide folic acid supplement program has been an effective strategy to prevent spina bifida.

Background The number of studies on air pollution with birth defects as the primary outcome has increased dramatically over the past two decades, but the potential role of specific air pollutants in congenital limb anomalies remains unclear. Objectives To evaluate associations between preconception and first-trimester PM10 exposure and polydactyly and syndactyly in a population-based case-control study. Methods Polydactyly cases (n = 2605), syndactyly cases (n = 595), and controls without any birth defects (n = 7950) born between 2010 and 2015 were selected from the Maternal and Child Health Certificate Registry of Liaoning Province. The monthly mean PM10 concentrations were obtained from 75 air monitoring stations, and the exposure assessment was based on the mean concentration of all stations in mother's residential city. A multivariable logistic regression model was constructed to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results PM10 exposure was positively associated with the risks of polydactyly (preconception: aORT3 vs. T1 = 1.95, 95% CI 1.56–2.45, aOR = 1.06, 95% CI 1.01–1.10 [per 10-μg/m3 increment]; first-trimester: aORT3 vs. T1 = 2.51, 95% CI 2.00–3.15) and syndactyly (preconception: aORT3 vs. T1 = 2.86, 95% CI 1.98–4.13, aOR = 1.11, 95% CI 1.03–1.20 [per 10-μg/m3 increment]; first-trimester: aORT3 vs. T1 = 3.10, 95% CI 2.11–4.56). Analyses based on single month exposure windows basically showed similar positive associations. Additionally, these findings were robust in sensitivity analyses and broadly consistent across subgroups. Conclusion Our study suggest that preconception and first-trimester PM10 exposures are related to increased risks of polydactyly and syndactyly.

Background The potential association between maternal exposure to ambient PM10 and offspring neural tube defects (NTDs) is a contentious issue. This study aims to evaluate the aforementioned association at a provincial level in China. Methods A total of 2736 cases and 7950 randomly selected healthy infants included in the Maternal and Child Health Certificate Registry of Liaoning Province and delivered between 2010 and 2015 were recruited. Daily PM10 concentrations were obtained from all available monitoring stations located within the study area. A multivariable logistic regression model was established to calculate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results PM10 exposure was significantly associated with the risk of NTDs during the three months preconception (per 10 μg/m3 increment: OR = 1.10, 95% CI 1.07–1.14; per standard deviation [27 μg/m3] increment: OR = 1.29, 95% CI 1.18–1.41; highest tertile: OR = 1.61, 95% CI 1.37–1.91) and the first trimester (highest tertile: OR = 1.57, 95% CI: 1.31–1.87). When focusing on shorter exposure windows, similar associations were observed for PM10 exposure from the third month before pregnancy to the third month after pregnancy. Sensitivity analyses using propensity score matching yielded consistent findings. Conclusions Maternal exposure to PM10 is positively associated with NTDs during the critical period of fetal neural tube development. However, due to the limitation of the exposure assessment as well as potential residual confounding, further research is warranted to confirm our findings.

Breast cancer is one of the most common cancers in women around the world. In Taiwan, the number of women suffering from breast cancer is increasing year by year. Furthermore, the incidence rate and mortality rate of breast cancer in women were ranked first and fourth, respectively, but its free screening rate had the lowest proportion of mammography examination usage. That statistic is due to the breasts being a very private part of the body and women being unlikely to get the screening done due to social perceptions and poor awareness of the disease. Therefore, the ideal timing for getting early treatment is often missed. This study was initiated to collect the perceptions of the general public about breast cancer screening by way of the comments and replies to any query or experience sharing left on different social media websites (PTT, Mobile01, and Facebook). Using the text mining technique to catch important features and connect them to different personalities of people, the identification model can be established by CART (Classification and Regression Tree) machine learning. The model will then be applied to explore the lifestyles and personalities of those people concerned about breast cancer screening so that different prevention and management policies can be proposed to meet their different needs. The study experiment example was based on gender identification to proceed with the model simulation and forecast accuracy.

Background: Chronic inflammatory arthritis(CIA) is considered the leading cause of disability that places severe limits on daily activity and quality of life for over 100 million Chinese. Nurse-led CIA management reveals tremendous benefits for CIA patients. European League Against Rheumatism(EULAR) developed the recommendations for the role of the nurse in the management of CIA in 2011, however, whether or not the recommendations could be fully implemented in China is unknown. Objectives: The aim was to test the EULAR recommendations among registered Chinese rheumatology nurses in terms of its agreement level, practicality, and adverse conditions to the implementation. Methods: We conducted an anonymous online questionnaire among registered clinical nurses in the department of rheumatology and immunology nationwide based on convenience sampling. The agreement and feasibility of the recommendations were assessed by visual analogue scale(VAS 0=total disagreement/completely infeasible, VAS 1–4=partial disagreement/partially infeasible, VAS 5–9=partial agreement/partially feasible, VAS 10=complete agreement/completely feasible). The respondents needed to select the reasons they agreed or disagreed and if they thought the recommendations were feasible or not. Results: 485 subjects were included, and 438 valid questionnaires were retrieved(valid recovery rate=90.3%). The subjects were from 49 national medical centers with the average age of 31.65±6.65. The average years of working experience were 6.41±5.438. With each and every piece of the recommendation, approximately 50% of the subjects completely agreed(VAS 10), about 40% partially agreed(VAS 5–9), under 10%(VAS 1–4) partially disagreed and around 1%(VAS 0) totally disagreed(shown in figure 1A). As for the feasibility, around 30% of the subjects thought the recommendations were fully feasible(VAS 10), about 50% considered partially feasible (VAS 5–9), 10% partially infeasible(VAS 1–4), and less than 1% totally infeasible(shown in figure 1B). Factors made the subjects disapprove of the recommendations include busy clinical loading(39.98%), lack of professional knowledge and nursing skills(25.7%), patients did not accept the extended role of nurses(17.35%). In the meantime, lack of working time(16.33%), shortage of professional nurses(12.74%), lack of training and education(10.59%), lack of professional knowledge(9.22%), attitude of patients toward nurses(8.28%), and lack of financial support(7.53%) were the reasons that made subjects think the recommendations infeasible in China. Figure 1 the agreement and feasibility analysis of the EULAR recommendations in China Conclusions: The role and tasks of nurses should be clearly described in the framework in China. Professional training and educational nursing programs at both basic and advanced levels need to be well developed with the aim of providing better care and bringing added value to patients at a lower cost. Acknowledgements: The authors are grateful to 49 national medical centers that participated in this study. Disclosure of Interest: None declared

Gallbladder cancer is an invasive cancer with a discouraging prognosis, and early detection and active intervention are of great value. To establish a more accurate and effective survival model to predict the prognosis of patients with non-metastatic gallbladder after surgical resection. A retrospective analysis was conducted in non-metastatic gallbladder cancer patients who were registered in the surveillance, epidemiology and end results database from 2010 to 2014. Univariate analysis and multivariate analysis were performed for the related factors that might affect the gallbladder cancer-specific survival. A prognostic gallbladder cancer-specific survival model was established using the nomogram tool. The discrimination test was measured by the c-index, and the conformance test was performed by a calibration curve. In all, 1422 patients with non-metastatic gallbladder cancer were identified. The prognostic factors include age, gender, lymph node dissection, postoperative chemotherapy, tumor size, histological grading, pT stage and pN stage. The gallbladder cancer-specific survival model was established based on the prognostic factors. The model’s c-index was 0.775, and the 7th AJCC staging c-index was 0.649. The calibration curves showed a good correlation between prediction and actual survival. This study established the gallbladder cancer-specific survival model successfully. Compared with the 7th AJCC stage, this model refined the contribution of the pT stage, pN stage and other related factors and was demonstrated to be more accurate and reliable. More importantly, this model may allow clinicians to screen patients with a poor prognosis for closer follow-up or adjuvant treatment.

The present study aimed to examine the functional and molecular effects of miR‑128 in epilepsy, in order to investigate its potential protective mechanisms. Firstly, miR‑128 expression in rats with lithium chloride‑induced epilepsy was demonstrated to be increased compared with the control rats. Subsequently, results from an in vitro epilepsy model demonstrated that overexpression of miR‑128 promoted nerve cell apoptosis, increased the protein expression of tumor protein p53, BCL2 associated X (Bax) and Cytochrome c, and enhanced caspase‑3/9 activity, whereas it suppressed the protein expression of sirtuin 1 (SIRT1). In addition, these alterations may be reversed by the downregulation of miR‑128. Furthermore, treatment with CAY10602, a SIRT1 agonist, reduced the effects of miR‑128 on nerve cells in vitro. Treatment with pifithrin‑β hydrobromide, a p53 inhibitor, was additionally able to mitigate the effects of miR‑128 in vitro. In conclusion, the present findings indicated that anti‑miR‑128 may exert neuroprotective effects in epilepsy, through the SIRT1/p53/Bax/Cytochrome c/caspase signaling pathway.

BACKGROUND Laparoscopic common bile duct exploration (LCBDE) has been verified to be a comparatively effective treatment approach for uncomplicated choledocholithiasis, and it has been previously proposed that the primary duct closure (PDC) technique, in which the bile duct can directly be sutured in only 1 step compared with the T-tube drainage (TTD), can be deemed a choice after LCBDE; however, the conventional TTD performance is controversial in the minimally invasive surgery era. On the basis of the above-mentioned point, this meta-analysis was conducted to assess the different effects between TTD and PDC after LCBDE. MATERIALS AND METHODS In PubMed, EMBASE, and the Cochrane Library, literature search was conducted to screen out randomized controlled trials (RCTs) to compare PDC with TTD. The analyzed outcome variables included overall morbidity, biliary-specific morbidity (retained stones, biliary leak, biliary peritonitis), other morbidities, operating time, postoperative hospital stay, reintervention (surgery, endoscopy/radiology), and median hospital expenses. RESULTS In this meta-analysis, there are 4 RCTs qualifying for inclusion, including 396 patients in all (222 in PDC and 214 in TTD). With respect to postoperative overall morbidity (P

Myostatin (Mstn) is a negative regulator of muscle development in vertebrates. Although its function in muscle growth has been well studied in mammals and fish, it remains unclear whether or how mstn functions in the immune system. In this study, mstna−/- and mstnb−/- homozygous zebrafish were firstly generated using CRISPR/Cas9 (Clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9). Deletion of mstnb but not mstna enhanced growth performance. Although survival rates under normal conditions were slightly decreased in both strains, mortality after dexamethasone-induced stress was increased by ∼30%. Furthermore, transcriptional levels of several critical immune-related genes were decreased, and the ability to withstand exposure to pathogenic E. tarda was decreased, compared with that of controls. In mstnb−/- but not mstna−/- zebrafish, expression of NF-κB subunits and several pro-inflammatory cytokines failed to respond to E. tarda exposure except nfkb1, c-rel and tnfα. Taken together, these results indicate that mstnb but not mstna plays a key role in zebrafish muscle growth. While each paralogue contributes to the response to bacterial insult, mstnb affects the immune system through activation of the NF-κB pathway, and mstna is likely to act upstream of NF-κB at some as yet unidentified target.

Vasculogenic mimicry (VM) is a process by which aggressive tumor cells generate non-endothelial cell-lined channels in malignant tumors including hepatocellular carcinoma (HCC). It has provided new insights into tumor behavior and has surfaced as a potential target for drug therapy. The molecular events underlying the process of VM formation are still poorly understood. In this study, we attempted to elucidate the relationship between Notch4 and VM formation in HCC. An effective siRNA lentiviral vector targeting Notch4 was constructed and transfected into Bel7402, a HCC cell line. VM networks were observed with a microscope in a 3 dimensional cell culture system. Cell migration and invasion were evaluated using wound healing and transwell assays. Matrix metalloproteinases (MMPs) activity was detected by gelatin zymography. Furthermore, the role of Notch4 inhibition in Bel7402 cells in vivo was examined in subcutaneous xenograft tumor model of mice. The results showed that downregulation of Notch4 destroyed VM network formation and inhibited migration and invasion of tumor cells in vitro (P

Background Enterovirus 71 (EV-A71) shows a potential of rapid death, but the natural history of the infection is poorly known. This study aimed to examine the natural history of EV-A71 infection. Methods This was a prospective longitudinal observational study performed between January 1st and October 31st, 2012, at three hospitals in Guangdong, China. Subjects with positive EV-A71 RNA laboratory test results were included. Disease progression was documented with MRI, autopsies, and follow-up. Symptoms/signs with potential association with risk of death were analyzed. Results Among the 288 patients, neurologic symptoms and signs were observed (emotional movement disorders, dyskinesia, involuntary movements, autonomic dysfunction, and disturbance of consciousness). Some of them occurred as initial symptoms. Myoclonic jerks/tremors were observed among >50% of the patients; nearly 40% of patients presented fatigue and 25% were with vomiting. Twenty-eight patients (9.7%) presented poor peripheral perfusion within 53.4 ± 26.1 h; 23 patients (8.0%) presented pulmonary edema and/or hemorrhage within 62.9 ± 28.6 h. Seventeen (5.9%) patients were in a coma. Seven (2.4%) patients died within 62.9 ± 28.6 h. Seventy-seven survivors underwent head and spinal cord MRI and 37.7% (29/77) showed abnormalities. Two fatal cases showed neuronal necrosis, softening, perivascular cuffing, colloid, and neuronophagia phenomenon in the brainstem. Conclusions Patients with EV-A71 infection showed high complexity of symptoms and onset timing. Death risk may be indicated by autokinetic eyeball, eyeball ataxia, severe coma, respiratory rhythm abnormality, absent pharyngeal reflex, ultrahyperpyrexia, excessive tachycardia, pulmonary edema and/or hemorrhage, and refractory shock and ataxic respiration. Early assessment of these symptoms/signs is important for proper management. Electronic supplementary material The online version of this article (doi:10.1186/s12879-017-2228-9) contains supplementary material, which is available to authorized users.

This study aims to investigate the roles of lncRNA ANRIL in epithelial-mesenchymal transition (EMT) by regulating the ATM-E2F1 signaling pathway in pancreatic cancer (PC). PC rat models were established and ANRIL overexpression and interference plasmids were transfected. The expression of ANRIL, EMT markers (E-cadherin, N-cadherin and Vimentin) and ATM-E2F1 signaling pathway-related proteins (ATM, E2F1, INK4A, INK4B and ARF) were detected. Small molecule drugs were applied to activate and inhibit the ATM-E2F1 signaling pathway. Transwell assay and the scratch test were adopted to detect cell invasion and migration abilities. ANRIL expression in the PC cells was higher than in normal pancreatic duct epithelial cells. In the PC rat models and PC cells, ANRIL interference promoted the expressions of INK4B, INK4A, ARF and E-cadherin, while reduced N-cadherin and Vimentin expression. Over-expressed ANRIL decreased the expression of INK4B, INK4A, ARF and E-cadherin, but raised N-cadherin and Vimentin expressions. By inhibiting the ATM-E2F1 signaling pathway in PC cells, E-cadherin expression increased but N-cadherin and Vimentin expressions decreased. After ANRIL was silenced or the ATM-E2F1 signaling pathway inhibited, PC cell migration and invasion abilities were decreased. In conclusion, over-expression of lncRNA ANRIL can promote EMT of PC cells by activating the ATM-E2F1 signaling pathway.

To evaluate time trends of exomphalos prevalence using a large population-based study with cases identified by the Liaoning Birth Defects Registry including 14 cities over the course of a 10-year period. Exomphalos prevalence, percent change, annual percent change (APC), and contribution rates of each city were calculated. Additionally, epidemiological characteristics of this malformation were described. We observed 516 cases of exomphalos among 3,248,954 live births. Birth prevalence of exomphalos was 1.59 per 10,000 live births with non-significant change during the observational period (APC = −1.19%, P = 0.48). However, significantly decreasing trends were noticed in three cities: Fushun (APC = −9.15%, P = 0.03), Benxi (APC = −11.49%, P = 0.05), and Yingkou (APC = −16.47%, P = 0.04), contributing 62.77% of the decreasing trend of overall prevalence. The mean maternal age, gestational age, and birth weight was 28.4 years (standard deviation [SD], 6.1 years), 25.6 weeks (SD, 8.6 weeks), and 1236.2 gram (SD, 1164.4 gram). For time of diagnosis, 79.8% (n = 412) cases were diagnosed during pregnancy. In summary, the prevalence of exomphalos in Liaoning province did not change remarkably during 2006 to 2015. Future studies are warranted to investigate the risk factors and create prevention strategies for this disease.

Antibiotics as emerging environmental contaminants, are widely used in both human and veterinary medicines. A solid-state nanopore sensing method is reported in this article to detect Tetracycline, which is based on Tet-off and Tet-on systems. rtTA (reverse tetracycline-controlled trans-activator) and TRE (Tetracycline Responsive Element) could bind each other under the action of Tetracycline to form one complex. When the complex passes through nanopores with 8 ~ 9 nanometers in diameter, we could detect the concentrations of Tet from 2 ng/mL to 2000 ng/mL. According to the Logistic model, we could define three growth zones of Tetracycline for rtTA and TRE. The slow growth zone is 0–39.5 ng/mL. The rapid growth zone is 39.5−529.7 ng/mL. The saturated zone is > 529.7 ng/mL. Compared to the previous methods, the nanopore sensor could detect and quantify these different kinds of molecule at the single-molecule level.

To identify trends in the prevalence of gastroschisis on the basis of a large population-based observation study with cases identified by the Liaoning Birth Defects Registry including 14 cities over the course of a 10-year period. Data were obtained from the aforementioned registry which was maintained by the Liaoning Women and Children’s Health Hospital, a comprehensive care institution as well as being responsible for the women’s and children’s health care guidance in this province. Gastroschisis prevalence, percent change, annual percent change (APC), and contribution rates of each city were calculated. We observed 747 cases of gastroschisis among 3,248,954 live births, for a prevalence of 2.30 per 10,000 births. The gastroschisis prevalence significantly decreased by 12.63% per year in Liaoning Province. Although the decreasing trends were observed in all these 14 cities, significant results were only observed in Shenyang (APC = −16.31%), Tieling (APC = −20.23%), and Chaoyang (APC = −13.50%). Notably, Tieling, Shenyang, and Yingkou were the three major cities which contributed almost 37.17% of the decreasing trend of gastroschisis in Liaoning Province. In conclusion, our findings demonstrate that the prevalence of gastroschisis has been decreasing during the recent decade among 14 cities in Liaoning Province.

Hypoxia-inducible factor-1 (HIF-1) plays a central role in tumor progression by regulating genes involved in proliferation, glycolysis, angiogenesis, and metastasis. To improve our understanding of HIF-1 regulation by kinome, we screened a kinase-specific small interference RNA library using a hypoxia-response element (HRE) luciferase reporter assay under hypoxic conditions. This screen determined that depletion of cellular SMG-1 kinase most significantly modified cellular HIF-1 activity in hypoxia. SMG-1 is the newest and least studied member of the phosphoinositide 3-kinase-related kinase family, which consists of ATM, ATR, DNA-PKcs, mTOR, and SMG-1. We individually depleted members of the phosphoinositide 3-kinase-related kinase family, and only SMG-1 deficiency significantly augmented HIF-1 activity in hypoxia. We subsequently discovered that SMG-1 kinase activity was activated by hypoxia, and depletion of SMG-1 up-regulated MAPK activity under low oxygen. Suppressing cellular MAPK by silencing ERK1/2 or by treatment with U0126, a MAPK inhibitor, partially blocked the escalation of HIF-1 activity resulting from SMG-1 deficiency in hypoxic cells. Increased expression of SMG-1 but not kinase-dead SMG-1 effectively inhibited the activity of HIF-1alpha. In addition, cellular SMG-1 deficiency increased secretion of the HIF-1alpha-regulated angiogenic factor, vascular epidermal growth factor, and survival factor, carbonic anhydrase IX (CA9), as well as promoted the hypoxic cell motility. Taken together, we discovered that SMG-1 negatively regulated HIF-1alpha activity in hypoxia, in part through blocking MAPK activation.

Intrahepatic cholangiocarcinoma (ICC) was differentiated from hepatocellular carcinoma, as defined in the American Joint Committee on Cancer (AJCC) 6th edition staging manual, using the revised staging system described in the AJCC 7th edition staging manual. This study was conducted to analyze the application of the AJCC 6th and 7th edition staging classifications and to evaluate a modified staging classification to potentially reduce the limitations associated with the different AJCC staging systems. We compared the prognostic value of cancer staging using data from the Surveillance, Epidemiology, and End Results database (N = 2124). The Kaplan–Meier method and Cox regression models were used to analyze survival. The Harrell concordance index (C-index) was used to analyze the discriminative abilities of cancer staging. Patients with stages I and II disease were found to have similar prognoses according to the 6th edition staging system. Using the 7th edition staging system, a low proportion of patients had stage III disease (5.0%), and the hazard ratio (HR) for stage III disease was comparable to that of stage IV disease (stage III and IV, 2.653 and 2.694). We modified the AJCC staging classification by adopting the 7th edition T, N, and M definitions and the 6th edition staging definitions. Consequently, the proportion of patients with stage III disease increased (22.8%). The HR for stage IV disease was higher than that for stage III disease (stage III and IV, 2.425 and 2.956). Meanwhile, the C-index of the modified AJCC staging system was 0.721 (95% CI: 0.696–0.745), which was significantly higher than the AJCC 7th edition staging system (0.694, P

The incidence rate of intrahepatic cholangiocarcinoma is rising, and treatment options are limited. Therefore, new biological markers of intrahepatic cholangiocarcinoma are needed. Immunohistochemistry and enzyme-linked immunosorbent assay were applied to analyze the expressions of CD97, CD55, and soluble CD97 in 71 patients with intrahepatic cholangiocarcinoma and 10 patients with hepatolithiasis. CD97 and CD55 were not expressed in hepatolithiatic tissues, but positive expression was observed in 76.1% (54/71) and 70.4% (50/71) of intrahepatic cholangiocarcinoma patients. The univariate analyses indicated that the positive expressions of CD97 and CD55 were related to short intrahepatic cholangiocarcinoma survival of patients (both p = 0.001). Furthermore, CD97 and CD55 expressions and biliary soluble CD97 levels were significantly associated with histological grade (p = 0.004, 0.002, and 0.012, respectively), lymph node metastases (p = 0.020, 0.038, and 0.001, respectively), and venous invasion (p = 0.003, 0.002, and 0.001, respectively). The multivariate analyses indicated that lymph node metastases (hazard ratio: 2.407, p = 0.003), positive CD55 expression (hazard ratio: 4.096, p = 0.003), and biliary soluble CD97 levels (hazard ratio: 2.434, p = 0.002) were independent risk factors for the intrahepatic cholangiocarcinoma survival. The receiver operating characteristic (ROC) curve analysis indicated that when the cutoff values of biliary soluble CD97 were 1.15 U/mL, the diagnostic value for predicting lymph node metastasis had a sensitivity of 87.5% and a specificity of 51.3%. For intrahepatic cholangiocarcinoma patient death within 60 months at a cutoff value of 0.940 U/mL, the diagnostic value sensitivity was 89.3% and the specificity was 93.3%. Biliary soluble CD97 may be a new biological marker for early diagnosis, prediction of lymph node metastasis and poor prognosis, and discovery of a therapeutic target.

International audience; Prp43p is a RNA helicase required for pre-mRNA splicing and for the synthesis of large and small ribosomal subunits. The molecular functions and modes of regulation of Prp43p during ribosome biogenesis remain unknown. We demonstrate that the G-patch protein Pfa1p, a component of pre-40S pre-ribosomal particles, directly interacts with Prp43p. We also show that lack of Gno1p, another G-patch protein associated with Prp43p, specifically reduces Pfa1p accumulation, whereas it increases the levels of the pre-40S pre-ribosomal particle component Ltv1p. Moreover, cells lacking Pfa1p and depleted for Ltv1p show strong 20S pre-rRNA accumulation in the cytoplasm and reduced levels of 18S rRNA. Finally, we demonstrate that Pfa1p stimulates the ATPase and helicase activities of Prp43p. Truncated Pfa1p variants unable to fully stimulate the activity of Prp43p fail to complement the 20S pre-rRNA processing defect of Deltapfa1 cells depleted for Ltv1p. Our results strongly suggest that stimulation of ATPase/helicase activities of Prp43p by Pfa1p is required for efficient 20S pre-rRNA-to-18S rRNA conversion.