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Objectives: The significance of self-esteem in the relationship between physical activity and Internet addiction among college students cannot be over, as it lays a solid foundation for the prevention and control of Internet addiction. Methods: A total of 950 college students were surveyed using the Physical Activity Rating Scale (PARS-3), Rosenberg Self-Esteem Scale (SES), and Chinese Internet Addiction Scale (CIAS-R) through a cluster random sampling method. Descriptive statistics, independent sample t-test, partial correlation analysis, mediation effect, moderation effect, and Bootstrap testing were conducted on the collected data to analyze and interpret the results. Results: (1) Significant gender differences were found in the amount of physical activity and the degree of Internet addiction among college students(P&& lt;0.001); (2) Physical activity was significantly and positively correlated with self-esteem (r = 0.26, P < 0.001), but significantly and negatively correlated with Internet addiction (r=-0.23, P < 0.001); Meanwhile, self-esteem and Internet addiction were significantly and negatively related to self-esteem (r=-0.22, P < 0.001). (3) Mediating effect analyses showed that self-esteem played a partial mediating role in physical activity and Internet addiction among college students, accounting for a portion of 78.95%. (4) A moderating effect of gender on the relationship between physical activity and Internet addiction was discovered. Conclusion: The physical activity level of male students is significantly higher than that of female students, while the degree of internet addiction among female students is notably higher than that of male students. Physical activity can not only directly improve the issue of internet addiction among college students, but also indirectly improve it through self-esteem, with gender playing a moderating role in this process. This conclusion has practical reference significance for preventing and controlling internet addiction among college students, and provides evidence support for using physical activity as a reference solution in clinical applications. Additionally, it suggests that gender should be taken into account when preventing and intervening in internet addiction among college students, and different strategies and methods should be adopted for male and female students. Male students should be encouraged to participate more in physical activities, gradually increasing the frequency, duration, and intensity of their participation, in order to divert their attention and enhance their sense of achievement in sports, thereby reducing their use of mobile phones. For female students, on the other hand, it is important to strengthen real-life communication, change the form of sports participation, engage in group, collaborative, and different situational sports activities, and enhance their focus and attention in sports, in order to reduce their internet dependency, better guide them to use the internet reasonably, and enable them to achieve emotional release through sports. [ABSTRACT FROM AUTHOR]

Background: Genetic variations in key DNA repair genes may influence DNA repair capacity, DNA damage and breast carcinogenesis. The current study aimed to estimate the association of APEX1 and OGG1 polymorphisms with the risk of breast cancer development. Methods: A total of 518 patients with histopathologically confirmed breast cancer and 921 region- and age-matched cancer-free controls were genotyped for the APEX1 polymorphisms rs3136817 and rs1130409 and the OGG1 polymorphisms rs1052133 and rs2072668 using a QuantStudio™ 12 K Flex Real-Time PCR System. Results: The rs3136817 heterozygous TC genotype along with the rs3136817 dominant model (TC + CC) was strongly associated with breast cancer susceptibility (odds ratio [OR] = 0.670, 95% confidence interval [95% CI]: 0.513 - 0.873, P = 0.003; OR = 0.682, 95% CI: 0.526 - 0.883, P = 0.004, respectively). No significant associations were observed among rs1130409, rs1052133, rs2072668 and breast cancer risk. Furthermore, an allele combination analysis revealed that APEX1 haplotypes containing C-T (alleles rs3136817 and rs1130409) conferred a significantly lower risk (corrected P < 0.001). Conclusion: This research is the latest report showing that an APEX1 rs3136817 heterozygous genotype may have a positive influence on DNA repair capacity in patients with breast cancer and thus may have a potential protective effect for Chinese Han women. [ABSTRACT FROM AUTHOR]

Background: The protistan pathogens Cryptosporidium and Giardia can cause significant intestinal diseases in animals and humans. Cattle, particularly calves, carrying these protists can be significant reservoirs for human infections and disease. However, little is known about the genetic make-up of Cryptosporidium and Giardia populations in cattle and other ruminants in some regions of China. Results: In the present study, PCR-based tools were used to genetically characterise these protists in faecal samples from a total of 339 pre- and post-weaned calves from four distinct locations in Hubei Province using markers in the large (LSU) or small (SSU) subunits of nuclear ribosomal RNA genes. Cryptosporidium andersoni, C. bovis, C. ryanae and Giardia duodenalis assemblage E were detected in 0.6%, 10.9%, 4.1% and 22.6% of calves, respectively. Conclusions: This study is the first to report the prevalence of Cryptosporidium and Giardia in pre- and post-weaned calves in Hubei Province, and encourages large-scale molecular studies of animals and humans, in an effort to better understand the epidemiology of these enteric pathogens in China. [ABSTRACT FROM AUTHOR]

Background: Proton stress and aluminum (Al) toxicity are major constraints limiting crop growth and yields on acid soils (pH < 5). In Arabidopsis, STOP1 is a master transcription factor that controls the expression of a set of well-characterized Al tolerance genes and unknown processes involved in low pH resistance. As a result, loss-of-function stop1 mutants are extremely sensitive to low pH and Al stresses. Results: Here, we report on screens of an ethyl-methane sulphonate (EMS)-mutagenized stop1 population and isolation of nine strong stop1 suppressor mutants, i.e., the tolerant to proton stress (tps) mutants, with significantly enhanced root growth at low pH (4.3). Genetic analyses indicated these dominant and partial gain-of-function mutants are caused by mutations in single nuclear genes outside the STOP1 locus. Physiological characterization of the responses of these tps mutants to excess levels of Al and other metal ions further classified them into five groups. Three tps mutants also displayed enhanced resistance to Al stress, indicating that these tps mutations partially rescue the hypersensitive phenotypes of stop1 to both low pH stress and Al stress. The other six tps mutants showed enhanced resistance only to low pH stress but not to Al stress. We carried out further physiologic and mapping-by-sequencing analyses for two tps mutants with enhanced resistance to both low pH and Al stresses and identified the genomic regions and candidate loci in chromosomes 1 and 2 that harbor these two TPS genes. Conclusion: We have identified and characterized nine strong stop1 suppressor mutants. Candidate loci for two tps mutations that partially rescue the hypersensitive phenotypes of stop1 to low pH and Al stresses were identified by mapping-by-sequencing approaches. Further studies could provide insights into the structure and function of TPSs and the regulatory networks underlying the STOP1-mediated processes that lead to resistance to low pH and Al stresses in Arabidopsis. [ABSTRACT FROM AUTHOR]

Background: A targeted drug nanoparticle (NP) delivery system has shown potential as a possible cancer treatment. Given its merits, such as its selective distribution at tumor sites and its controllable drug release, drug-loaded NPs can be effectively delivered to selected organs and targeted cells, thus enhancing its antitumor efficiency and reducing its toxicity. Methods: We reported that hyaluronic acid (HA)-coated chitosan NPs promoted the drug delivery of 5-fluorouracil (5-Fu) into tumor cells that highly expressed CD44. Results: Our new findings suggested that HA-coated chitosan NPs enhanced drug accumulation by effectively transporting NPs into CD44-overexpressed tumor cells, and they also resulted in mitochondrial damage induced by the production of reactive oxygen species (ROS). Compared to free drug and uncoated NPs, HA-coated chitosan NPs exhibited stronger inhibition rates and induced obvious apoptosis in CD44-overexpressed A549 cells. Conclusions: Biocompatible and biodegradable HA-coated chitosan NPs were developed to encapsulate a chemotherapeutic drug (5-Fu) to enhance drug accumulation in tumor cells and to improve the agent's antitumor efficiency by offering targeted drug delivery via CD44. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNAs (lncRNAs) are known to play important roles in different cell contexts, including cancers. However, little is known about lncRNAs in cholangiocarcinoma (CCA), a cholangiocyte malignancy with poor prognosis, associated with chronic inflammation and damage to the biliary epithelium. The aim of the study is to identify if any lncRNA might associate with inflammation or oxidative stress in CCA and regulate the disease progression. Methods: In this study, RNA-seqs datasets were used to identify aberrantly expressed lncRNAs. Small interfering RNA and overexpressed plasmids were used to modulate the expression of lncRNAs, and luciferase target assay RNA immunoprecipitation (RIP) was performed to explore the mechanism of miRNA-lncRNA sponging. Results: We firstly analyzed five available RNA-seqs datasets to investigate aberrantly expressed lncRNAs which might associate with inflammation or oxidative stress. We identified that two lncRNAs, H19 and HULC, were differentially expressed among all the samples under the treatment of hypoxic or inflammatory factors, and they were shown to be stimulated by short-term oxidative stress responses to H2O2 and glucose oxidase in CCA cell lines. Further studies revealed that these two lncRNAs promoted cholangiocyte migration and invasion via the inflammation pathway. H19 and HULC functioned as competing endogenous RNAs (ceRNAs) by sponging let-7a/let-7b and miR-372/miR-373, respectively, which activate pivotal inflammation cytokine IL-6 and chemokine receptor CXCR4. Conclusions: Our study revealed that H19 and HULC, up-regulated by oxidative stress, regulate CCA cell migration and invasion by targeting IL-6 and CXCR4 via ceRNA patterns of sponging let-7a/let-7b and miR-372/miR-373, respectively. The results suggest that these lncRNAs might be the chief culprits of CCA pathogenesis and progression. The study provides new insight into the mechanism linking lncRNA function with CCA and may serve as novel targets for the development of new countermeasures of CCA. [ABSTRACT FROM AUTHOR]

Background: Studies examining the association between alcohol intake and the risk of pancreatic cancer have given inconsistent results. The purpose of this study was to summarize and examine the evidence regarding the association between alcohol intake and pancreatic cancer risk based on results from prospective cohort studies.Methods: We searched electronic databases consisting of PubMed, Ovid, Embase, and the Cochrane Library identifying studies published up to Aug 2015. Only prospective studies that reported effect estimates with 95% confidence intervals (CIs) for the risk of pancreatic cancer, examining different alcohol intake categories compared with a low alcohol intake category were included. Results of individual studies were pooled using a random-effects model.Results: We included 19 prospective studies (21 cohorts) reporting data from 4,211,129 individuals. Low-to-moderate alcohol intake had little or no effect on the risk of pancreatic cancer. High alcohol intake was associated with an increased risk of pancreatic cancer (risk ratio [RR], 1.15; 95% CI: 1.06-1.25). Pooled analysis also showed that high liquor intake was associated with an increased risk of pancreatic cancer (RR, 1.43; 95% CI: 1.17-1.74). Subgroup analyses suggested that high alcohol intake was associated with an increased risk of pancreatic cancer in North America, when the duration of follow-up was greater than 10 years, in studies scored as high quality, and in studies with adjustments for smoking status, body mass index, diabetes mellitus, and energy intake..Conclusions: Low-to-moderate alcohol intake was not significantly associated with the risk of pancreatic cancer, whereas high alcohol intake was associated with an increased risk of pancreatic cancer. Furthermore, liquor intake in particular was associated with an increased risk of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background: Hemorrhagic fever with renal syndrome (HFRS) is highly endemic in mainland China, where human cases account for 90 % of the total global cases. Yiyuan County is one of the most serious affected areas in China. Therefore, there is an urgent need for monitoring and predicting HFRS incidence in Yiyuan to make the control of HFRS more effective.Methods: The study was based on the reported cases of HFRS from the National Notifiable Disease Surveillance System. The demographic and spatial distributions of HFRS in Yiyuan were established. Then we fit autoregressive integrated moving average (ARIMA) models and predict the HFRS epidemic trend.Results: There were 362 cases reported in Yiyuan during the 10-year study period. The human infections in the fall and winter reflected a seasonal characteristic pattern of Hantaan virus (HTNV) transmission. The best model was ARIMA (2, 1, 1) × (0, 1, 1)12 (AIC value 516.86) with a high validity.Conclusion: The ARIMA model fits the fluctuations in HFRS frequency and it can be used for future forecasting when applied to HFRS prevention and control. [ABSTRACT FROM AUTHOR]

Background: Cryptosporidium spp. have been extensively reported to cause significant diarrheal disease in humans and domestic animals. On the contrary, little information is available on the prevalence and characterization of Cryptosporidium in wild animals in China, especially in giant pandas. The aim of the present study was to detect Cryptosporidium infections and identify Cryptosporidium species at the molecular level in both captive and wild giant pandas in Sichuan province, China. Findings: Using a PCR approach, we amplified and sequenced the 18S rRNA gene from 322 giant pandas fecal samples (122 from 122 captive individuals and 200 collected from four habitats) in Sichuan province, China. The Cryptosporidium species/genotypes were identified via a BLAST comparison against published Cryptosporidium sequences available in GenBank followed by phylogenetic analysis. The results revealed that both captive and wild giant pandas were infected with a single Cryptosporidium species, C. andersoni, at a prevalence of 15.6 % (19/122) and 0.5 % (1/200) in captive and wild giant pandas, respectively. Conclusions: The present study revealed the existence of C. andersoni in both captive and wild giant panda fecal samples for the first time, and also provided useful fundamental data for further research on the molecular epidemiology and control of Cryptosporidium infection in giant pandas. [ABSTRACT FROM AUTHOR]

Background: In cervical cancer patients with intermediate-risk factors, the optimal adjuvant therapy is still controversial. We undertook a randomized trial (ClinicalTrials.gov Identifier: NCT01418859) to compare the efficacy and toxicity of concurrent chemoradiotherapy with topotecan and cisplatin with radiotherapy alone in intermediate-risk cervical cancer patients. Methods: Eligible patients were randomly assigned to one of three treatment arms including arm A (radiotherapy only,RT), arm B(concurrent chemoradiotherapy only, CCRT), and arm C (concurrent chemoradiotherapy with following consolidation chemotherapy, CCRT+CT). All eligible patients completed external RT (IMRT or 3D-CRT), receiving 45-50Gy /25f uniformly to the pelvis. Concurrent chemotherapy regimen was topotecan 0.75 mg/m2 for days 1, 2 and 3, followed by cisplatin 25 mg/m² for days 1, 2 and 3. Three cycles of consolidation chemotherapy regimen was topotecan 1.5 mg/m² for days 1 and 2, and 0.75 mg/m² for day 3; followed by cisplatin 25 mg/m² for days 1, 2 and 3, repeated every 21 days. Adverse events of each group were investigated and compared. Results: Thirty-nine patients enrolled onto the remaining regimens: 14 to RT, 15 to CCRT and 10 to CCRT + CT. Six patients (15.4%) did not complete the protocol treatment. Hematologic toxicity was more frequent and more severe in the CCRT and CCRT+CT arms compared with the RT arm. The incidence of grade 3-4 neutropenia was significantly different statistically between the RT, CCRT and CCRT + RT groups (15.4%, 46.7% and 100%, respectively; P = 0.002). Specially, three patients in CCRT + CT arm of all six patients who did not complete the protocol treatment discontinued planned therapy because of persistent grade 4 neutropenia. However, there were no significant differences in grade 3-4 non-hematologic toxicities between the three groups(all P> 0.05). Recurrence-free survival and overall survival of each group were not analyzed on account of a median follow-up of only 16 months. Conclusions: Concurrent chemoradiotherapy with topotecan and cisplatin showed severe hematologic toxicity in intermediate-risk cervical cancer patients after radical hysterectomy. Thus, the study was closed ahead of schedule. Trial registration: ClinicalTrials.gov Identifier: NCT01418859. [ABSTRACT FROM AUTHOR]

Background: Cryptosporidium spp. have been extensively reported to cause significant diarrheal disease in humans and domestic animals. On the contrary, little information is available on the prevalence and characterization of Cryptosporidium in wild animals in China, especially in giant pandas. The aim of the present study was to detect Cryptosporidium infections and identify Cryptosporidium species at the molecular level in both captive and wild giant pandas in Sichuan province, China. Findings: Using a PCR approach, we amplified and sequenced the 18S rRNA gene from 322 giant pandas fecal samples (122 from 122 captive individuals and 200 collected from four habitats) in Sichuan province, China. The Cryptosporidium species/genotypes were identified via a BLAST comparison against published Cryptosporidium sequences available in GenBank followed by phylogenetic analysis. The results revealed that both captive and wild giant pandas were infected with a single Cryptosporidium species, C. andersoni, at a prevalence of 15.6 % (19/122) and 0.5 % (1/200) in captive and wild giant pandas, respectively. Conclusions: The present study revealed the existence of C. andersoni in both captive and wild giant panda fecal samples for the first time, and also provided useful fundamental data for further research on the molecular epidemiology and control of Cryptosporidium infection in giant pandas. [ABSTRACT FROM AUTHOR]

Background: Metabolic profile was initially designed as a presymptomatic diagnostic aid based on statistical analyses of blood metabolites to provide an early warning of certain types of metabolic disorder. However, there is little metabolic profile data available about Korean Hanwoo cows. Therefore, this study aimed to determine the reference intervals of metabolic profile for Korean Hanwoo cows. Methods: Healthy animals (2,205) were selected and divided into early (day 1 to 95), middle (day 96 to 190) and late (day 191 to 285) period according to their gestating period. Metabolic profile including total protein (TP), albumin (Alb), urea (UREA), glucose (Glu), total cholesterol (T-Cho), long-chain fatty acid (LCFA), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), creatinine (Crea), calcium (Ca), inorganic phosphorous (iP) and magnesium (Mg) were analyzed using a TBA-40FR automatic biochemical analyzer. The data of Korean Hanwoo cows were then compared to those of the Japanese Wagyu cows. Results: Most of the data of the Korean Hanwoo cows were relatively higher than those of Japanese Wagyu cows, with the exception of Glu and GGT. This may indicate that the nutritional level of feed for the Korean Hanwoo cows was higher than that of the Japanese Wagyu cows because of the different feeding system. In particular, relatively higher levels of UREA and LCFA were observed in the Korean Hanwoo cows, and this may also contribute to the low reproduction efficiency. Conclusions: These findings may provide some theoretical basis for understanding the reproductive and feeding situation of Korean Hanwoo cows. [ABSTRACT FROM AUTHOR]

Background: Metabolic profile was initially designed as a presymptomatic diagnostic aid based on statistical analyses of blood metabolites to provide an early warning of certain types of metabolic disorder. However, there is little metabolic profile data available about Korean Hanwoo cows. Therefore, this study aimed to determine the reference intervals of metabolic profile for Korean Hanwoo cows. Methods: Healthy animals (2,205) were selected and divided into early (day 1 to 95), middle (day 96 to 190) and late (day 191 to 285) period according to their gestating period. Metabolic profile including total protein (TP), albumin (Alb), urea (UREA), glucose (Glu), total cholesterol (T-Cho), long-chain fatty acid (LCFA), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), creatinine (Crea), calcium (Ca), inorganic phosphorous (iP) and magnesium (Mg) were analyzed using a TBA-40FR automatic biochemical analyzer. The data of Korean Hanwoo cows were then compared to those of the Japanese Wagyu cows. Results: Most of the data of the Korean Hanwoo cows were relatively higher than those of Japanese Wagyu cows, with the exception of Glu and GGT. This may indicate that the nutritional level of feed for the Korean Hanwoo cows was higher than that of the Japanese Wagyu cows because of the different feeding system. In particular, relatively higher levels of UREA and LCFA were observed in the Korean Hanwoo cows, and this may also contribute to the low reproduction efficiency. Conclusions: These findings may provide some theoretical basis for understanding the reproductive and feeding situation of Korean Hanwoo cows [ABSTRACT FROM AUTHOR]

Since the discovery of circulating microRNAs (miRNAs) in body fluids, an increasing number of studies have focused on their potential as non-invasive biomarkers and as therapeutic targets or tools for many diseases, particularly for cancers. Because of their stability, miRNAs are easily detectable in body fluids. Extracellular miRNAs have potential as biomarkers for the prediction and prognosis of cancer. Moreover, they also enable communication between cells within the tumor microenvironment, thereby influencing tumorigenesis. In this review, we summarize the progresses made over the past decade regarding circulating miRNAs, from the development of detection methods to their clinical application as biomarkers and therapeutic tools for cancer. We also discuss the advantages and limitations of different detection methods and the pathways of circulating miRNAs in cell-cell communication, in addition to their clinical pharmacokinetics and toxicity in human organs. Finally, we highlight the potential of circulating miRNAs in clinical applications for cancer. [ABSTRACT FROM AUTHOR]

Background Goserelin plus aromatase inhibitors (AI) have already been used in male advanced breast cancer, but the cases that fulvestrantin male breast cancer are rare. Case presentation Here we report a case of long-term (3 years) response to Goserelin plus continuing endocrine treatments given for a male advanced breast cancer. The patient prolongs his life with high life quality, and has more time with his family. Conclusion Goserelin plus endocrine treatments may benefit male breast cancer. [ABSTRACT FROM AUTHOR]

Introduction: Avascular necrosis of femoral head (ANFH) is a progressive disease that often leads to hip joint dysfunction and even disability in young patients. Although the standard treatment, which is core decompression, has the advantage of minimal invasion, the efficacy is variable. Recent studies have shown that implantation of bone marrow containing osteogenic precursors into necrotic lesion of ANFH may be promising for the treatment of ANFH. Methods: A prospective, double-blinded, randomized controlled trial was conducted to examine the effect of bone-marrow buffy coat (BBC) grafting combined with core decompression for the treatment of ANFH. Forty-five patients (53 hips) with Ficat stage I to III ANFH were recruited. The hips were allocated to the control group (core decompression + autologous bone graft) or treatment group (core decompression + autologous bone graft with BBC). Both patients and assessors were blinded to the treatment options. The clinical symptoms and disease progression were assessed as the primary and secondary outcomes. Results: At the final follow-up (24 months), there was a significant relief in pain (P <0.05) and clinical joint symptoms as measured by the Lequesne index (P <0.05) and Western Ontario and McMaster Universities Arthritis Index (P <0.05) in the treatment group. In addition, 33.3% of the hips in the control group have deteriorated to the next stage after 24 months post-procedure, whereas only 8% in the treatment group had further deterioration (P <0.05). More importantly, the non-progression rates for stage I/II hips were 100% in the treatment group and 66.7% in the control group. Conclusion: Implantation of the autologous BBC grafting combined with core decompression is effective to prevent further progression for the early stages of ANFH. [ABSTRACT FROM AUTHOR]

Background The stem cell-associated intermediate filament nestin has recently been linked with neoplastic transformation, but the specific mechanism by which nestin positive tumor cells leads to malignant invasion and metastasis behaviors of esophageal squamous cell carcinoma (ESCC) remains unclear. Methods To obtain insight into the biological role of nestin in ESCC, we explored the association of the nestin phenotype with malignant proliferation and apoptosis in esophageal squamous cancer cells. Nestin expression was determined in ESCC specimens and cell lines, and correlated with clinicopathological properties, including clinical prognosis and proliferative markers. The association of the nestin phenotype with apoptotic indicators was also analyzed. Results Nestin was expressed in ESCC specimens and cell lines. ESCC patients with nestin-positive tumors had significantly shorter median survival and progression-free survival times than those with nestin-negative tumors. Positive staining for the proliferation markers Ki67 and PCNA (proliferating cell nuclear antigen) was detected in 56.9% and 60.2% of ESCC specimens, respectively, and was strongly correlated with the nestin phenotype. Notably, expression of cyclin dependent kinase-5 (CDK5) and P35 was detected in 53.8% and 48.4% of ESCC specimens, respectively, and was strongly associated with the nestin phenotype. Conclusion Our data demonstrated nestin expression in ESCC specimens and cell lines, and revealed a strong association of the nestin phenotype with poor prognosis in ESCC patients. Furthermore, we showed that nestin positive ESCC cells played an important role in the malignant proliferation and apoptosis. [ABSTRACT FROM AUTHOR]

Background Gastric carcinoma (GC) is a common and lethal malignancy, and epithelial-mesenchymal transition (EMT) is believed to contribute to invasive and metastatic tumor growth. Aquaporin 3 (AQP3) is overexpressed in human GC tissues, while human epidermal growth factor (EGF) and hepatocyte growth factor, which can induce EMT, are able to up-regulate AQP3 expression, subsequently promoting GC cell migration and proliferation. The purpose of this study was to investigate the effects of AQP3 on EMT in human GC. Methods AQP3 and EMT-related proteins were detected by immunohistochemistry in human GC specimens and their clinical significance evaluated. AQP3 knockdown was attempted using small interfering RNAs, while EGF was used to up-regulate AQP3 expression. Western blotting, real-time quantitative polymerase chain reaction assays and immunofluorescence were used to evaluate changes in expression of AQP3 and EMT-related proteins in the SGC7901 and MGC803 human GC cell lines. Results AQP3 up-expression was associated with EMT-related proteins in human GC specimens, which correlated with poor prognosis for GC. AQP3 modulated GC cell proliferation, migration and invasion in vitro, and induced E-cadherin repression. AQP3 also up-regulated the expression of vimentin and fibronectin in vitro. The PI3K/AKT/SNAIL signaling pathway was likely involved in the induction of EMT by AQP3 in GC. Conclusions AQP3 promotes EMT in human cases of GC, allowing us to understand the mechanisms of AQP3 in GC progression, thus providing a potential strategy for its treatment. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to detect the serum microRNAs (miRNAs) that are differentially expressed in cervical squamous cell carcinoma (SCC) patients and negative controls, with a focus on the miRNA profiles of the patients before and after surgery. The aim of the study is to evaluate the potential of these miRNAs as novel markers for the posttherapeutic monitoring of cervical SCC patients. Results A total of 765 serum miRNAs from 10 cervical SCC patients before surgery, 10 cervical SCC patients after surgery, and 10 negative controls were profiled using a TaqMan MicroRNA Array. A set of selected differentially expressed miRNAs were further analyzed in the patients at different perioperative periods, including preoperative, 1 week postoperative, and one month postoperative. The results showed that several serum miRNAs were differentially expressed in the cervical SCC patients compared with the negative controls, including miR- 646, miR-141" and miR-542-3p. More importantly, we found that levels of specific serum miRNAs were deregulated in the pre- and postoperative stages, and these miRNAs could be useful for post-therapeutic monitoring of disease progression. Finally, we depicted a regulatory network of differentially expressed serum miRNAs, and many possible target genes were predicted in the estrogen-mediated signal pathways, supporting the hypothesis that cervical SCC is a hormone-associated gynecological disease. Conclusions Our study demonstrated that the circulating miRNAs miR-646, miR-141" and miR-542-3p could potentially serve as non-invasive biomarkers for cervical SCC. The levels of these specific miRNAs might be useful for the post-therapeutic monitoring of disease progression. This is the first report showing that circulating miRNAs could serve as biomarkers for the therapeutic intervention of cervical SCC. [ABSTRACT FROM AUTHOR]

Background The goal of this study was to compare treatment outcomes for Federation of Gynecology and Obstetrics (FIGO) stage IIB cervical carcinoma patients receiving radical surgery followed by adjuvant postoperative radiotherapy versus radical radiotherapy. Methods Medical records of FIGO stage IIB cervical cancer patients treated between July 2008 and December 2011 were retrospectively reviewed. A total of 148 patients underwent radical hysterectomy with pelvic lymph node dissection followed by adjuvant radiotherapy (surgery-based group). These patients were compared with 290 patients that received radical radiotherapy alone (RT-based group). Recurrence rates, progression-free survival (PFS), overall survival (OS), local control rates, and treatment-related complications were compared for these two groups. Results Similar rates of recurrence (16.89% vs. 12.41%, p = 0.200), PFS (log-rank, p = 0.211), OS (log-rank, p = 0.347), and local control rates (log-rank, p = 0.668) were observed for the surgery-based group and the RT-based group, respectively. Moreover, the incidence of acute grade 3-4 gastrointestinal reactions and late grade 3-4 lower limb lymphedema were significantly higher for the surgery-based group versus the RT-based group. Cox multivariate analyses found no significant difference in survival outcome between the two groups, and tumor diameter and histopathology were identified as significant prognostic factors for OS. Conclusions Radical radiotherapy was associated with fewer treatment-related complications and achieved comparable survival outcomes for patients with FIGO stage IIB cervical cancer compared to radical hysterectomy followed by postoperative radiotherapy. [ABSTRACT FROM AUTHOR]

Background Microglia/macrophages are known to play important roles in initiating brain inflammation after spontaneous intracerebral hemorrhage (ICH). T cell immunoglobulin and mucin domain-3 (Tim-3) have been proven to play a critical part in several inflammatory diseases through regulation of both adaptive and innate immune responses. Tim-3 can be expressed by microglia/macrophages and regulates their function in the innate immune response. However, the effect of Tim-3 on inflammatory responses following ICH is unclear. Methods In this study, we investigated Tim-3 expression, the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and brain water content in peri-hematomal brain tissue at 12 hours and at 1, 3, 5, and 7 days post-ICH in wild type (WT) ICH and Tim-3-/- ICH mice. The numbers of Tim-3 positive cells,astrocytes, neutrophils and microglia/macrophages were detected using immunofluorescence staining. Cytokines were measured by ELISA. Double immunoflurorescence labeling was performed to identify the cellular source of Tim-3 expression. Mouse neurological deficit scores were assessed through animal behavior. Results Expression of Tim-3 increased early in mouse peri-hematomal brain tissue after autologous blood injection, peaked at day 1, and was positively correlated with the concentrations of TNF-α, IL-1β, and brain water content. Tim-3 was predominantly expressed in microglia/macrophages. Compared with WT mice, Tim-3-/- mice had reduced ICH-induced brain inflammation with decreased TNF-α and IL-1β, cerebral edema and neurological deficit scores. Moreover, Tim-3 inhibited activation of microglia/macrophages. The number of activated microglia/macrophages in Tim-3-/- ICH mice was much lower than that in WT ICH mice. Conclusions Our findings demonstrate that Tim-3 plays an important role in brain inflammation after ICH, and may be a potential treatment target. [ABSTRACT FROM AUTHOR]

Background Astragalus memebranaceus is a traditional Chinese herbal medicine used in treatment of common cold, diarrhea, fatigue, anorexia and cardiac diseases. Recently, there are growing evidences that Astragalus extract may be a potential anti-tumorigenic agent. Some research showed that the total saponins obtained from Astragalus membranaceus possess significant antitumorigenic activity. Gastric cancer is one of the most frequent cancers in the world, almost two-thirds of gastric cancer cases and deaths occur in less developed regions. But the effect of Astragalus membranaceus on proliferation, invasion and apoptosis of gastric cancer BGC-823 cells remains unclear. Methods Astragalus saponins were extracted. Cells proliferation was determined by CCK-8 assay. Cell cycle and apoptosis were detected by the flow cytometry. Boyden chamber was used to evaluate the invasion and metastasis capabilities of BGC-823 cells. Tumor growth was assessed by subcutaneous inoculation of cells into BALB/c nude mice. Results The results demonstrated that total Astragalus saponins could inhibit human gastric cancer cell growth both in vitro and in vivo, in additional, Astragalus saponins deceased the invasion ability and induced the apoptosis of gastric cancer BGC-823 cells. Conclusions Total Astragalus saponins inhibited human gastric cancer cell growth, decreased the invasion ability and induced the apoptosis. This suggested the possibility of further developing Astragalus as an alternative treatment option, or perhaps using it as adjuvant chemotherapeutic agent in gastric cancer therapy. [ABSTRACT FROM AUTHOR]

CXC chemokine receptor 4 was found to be expressed by many different types of human cancers and its expression has been correlated with tumor aggressiveness, poor prognosis and resistance to chemotherapy. However the effect of CXCR4 on the esophageal carcinoma cells remains unclear, the present study explored the effects of CXCR4 siRNA on proliferation and invasion of esophageal carcinoma KYSE-150 and TE-13 cells. Two siRNA sequence targeting CXCR4 gene were constructed and then were transfected into KYSE-150 and TE-13 cells by Lipofectamine™2000. Changes of CXCR4 mRNA and protein were analyzed by qRT-PCR and Western blot. Effect of CXCR4 siRNA on KYSE-150 and TE-13 cells proliferation was determined by MTT. Transwell invasion assay was used to evaluate the invasion and metastasis of KYSE-150 and TE-13 cells. Tumor growth was assessed by subcutaneous inoculation of cells into BALB/c nude mice. qRT-PCR and Western blot demonstrate that the expression level of CXCR4 gene were obviously decreased in KYSE-150 and TE-13 cells transfected with CXCR4 targeting siRNA expression vectors. The average amount of cells transfected with CXCR4 siRNA penetrating Matrigel was significantly decreased (p<0.05). Injection of CXCR4 siRNA transfected cells inhibited tumor growth in a xenograft model compared with blank and negative control groups (p <0.05). CXCR4 silenced by siRNA could suppress the proliferation, invasion and metastasis of esophageal carcinoma cell lines KYSE-150 and TE-13 in vitro and in vivo. The results provide a theoretical and experimental basis for the gene therapy of ESCC using RNAi technology based on CXCR4 target site. [ABSTRACT FROM AUTHOR]

Background: Elevated serum cholesterol level is generally considered to be a risk factor for the development of cardiovascular diseases which seriously threaten human health. The cholesterol-lowering effects of lactic acid bacteria have recently become an area of great interest and controversy for many researchers. In this study, we investigated the effects of two NS lactobacillus strains, Lactobacillus plantarum NS5 and Lactobacillus delbrueckii subsp. bulgaricus NS12, on lipid metabolism of rats fed a high cholesterol diet. Methods: Thirty-two SD rats were assigned to four groups and fed either a normal or a high-cholesterol diet. The NS lactobacillus treated groups received the high-cholesterol diet supplemented with Lactobacillus plantarum NS5 or Lactobacillus delbrueckii subsp. bulgaricus NS12 in drinking water. The rats were sacrificed after a 6-week feeding period. Body weights, visceral organ and fat weights, serum and liver cholesterol and lipid levels, intestinal microbiota and liver mRNA expression levels related to cholesterol metabolism were analyzed. Liver lipid deposition and adipocyte size were evaluated histologically. Results: Compared with rats fed a high cholesterol diet, serum total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B and free fatty acids levels were decreased and apolipoprotein A-I level was increased in NS5 or NS12 strain treated rats, and with no significant change in high-density lipoprotein cholesterol level. Liver cholesterol and triglyceride levels were also significantly decreased in NS lactobacillus strains treated groups. Meanwhile, the NS lactobacillus strains obviously alleviated hepatic injuries, decreased liver lipid deposition and reduced adipocyte size of high cholesterol diet fed rats. NS lactobacillus strains restored the changes in intestinal microbiota compositions, such as the increase in Bacteroides and the decrease in Clostridium. NS lactobacillus strains also regulated the mRNA expression levels of liver enzymes related to cholesterol metabolism, including the down regulation of acyl-CoA: cholesterol acyltransferase (ACAT) and the upregulation of cholesterol 7α-hydroxylase (CYP7A1). Conclusion: This study suggested that the two NS lactobacillus strains may affect lipid metabolism and have cholesterol-lowering effects in rats fed a high cholesterol diet. [ABSTRACT FROM AUTHOR]

Background: Fragile X syndrome (FXS) is a common form of inherited intellectual disability caused by an expansion of CGG repeats located in the 5' untranslated region (UTR) of the FMR1 gene, which leads to hypermethylation and silencing of this locus. Although a dramatic increase in DNA methylation of the FMR1 full mutation allele is well documented, the extent to which these changes affect DNA methylation throughout the rest of the genome has gone unexplored. Methods: Here we examined genome-wide methylation in both peripheral blood (N = 62) and induced pluripotent stem cells (iPSCs; N = 10) from FXS individuals and controls. Results: We not only found the expected significant DNA methylation differences in the FMR1 promoter and 50 UTR, we also saw that these changes inverse in the FMR1 gene body. Importantly, we found no other differentially methylated loci throughout the remainder of the genome, indicating the aberrant methylation of FMR1 in FXS is locus-specific. Conclusions: This study provides a comprehensive methylation profile of FXS and helps refine our understanding of the mechanisms behind FMR1 silencing. [ABSTRACT FROM AUTHOR]

Human and animals studies support the idea that there is a gender-related co-morbidity of pain-related and inflammatory gastrointestinal (GI) diseases with psychological disorders. This co-morbidity is the evidence for the existence of GI-brain axis which consists of immune (cytokines), neural (vagus nerve) and neuroendocrine (HPA axis) pathways. Psychological stress causes disturbances in GI physiology, such as altered GI barrier function, changes in motility and secretion, development of visceral hypersensitivity, and dysfunction of inflammatory responses. Whether GI inflammation would exert impact on psychological behavior is not well established. We examined the effect of experimental gastritis on anxiety- and depression-like behaviors in male and female Sprague-Dawley rats, and evaluated potential mechanisms of action. Gastritis was induced by adding 0.1% (w/v) iodoacetamide (IAA) to the sterile drinking water for 7 days. Sucrose preference test assessed the depression-like behavior, open field test and elevated plus maze evaluated the anxietylike behavior. IAA treatment induced gastric inflammation in rats of either gender. No behavioral abnormality or dysfunction of GI-brain axis was observed in male rats with IAAinduced gastritis. Anxiety- and depression-like behaviors were apparent and the HPA axis was hyperactive in female rats with IAA-induced gastritis. Our results show that gastric inflammation leads to anxiety- and depression-like behaviors in female but not male rats via the neuroendocrine (HPA axis) pathway, suggesting that the GI inflammation can impair normal brain function and induce changes in psychological behavior in a gender-related manner through the GI-to-brain signaling. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) remains a major public health burden in many developing countries. China alone accounted for an estimated 12% of all incident TB cases worldwide in 2010. Several studies showed that the spatial distribution of TB was nonrandom and clustered. Thus, a spatial analysis was conducted with the aim to explore the spatial epidemiology of TB in Linyi City, which can provide guidance for formulating regional prevention and control strategies. Methods: The study was based on the reported cases of TB, between 2005 and 2010. 35,308 TB cases were geo-coded at the town level (n = 180). The spatial empirical Bayes smoothing, spatial autocorrelation and space-time scan statistic were used in this analysis. Results: Spatial distribution of TB in Linyi City from 2005 to 2010 was mapped at town level in the aspects of crude incidence, excess hazard and spatial smoothed incidence. The spatial distribution of TB was nonrandom and clustered with the significant Moran's I for each year. Local Gi* detected five significant spatial clusters for high incidence of TB. The space-time analysis identified one most likely cluster and nine secondary clusters for high incidence of TB. Conclusions: There is evidence for the existence of statistically significant TB clusters in Linyi City, China. The result of this study may assist health departments to develop a better preventive strategy and increase the public health intervention's effectiveness. [ABSTRACT FROM AUTHOR]

Background: Streptomyces species are widely distributed in natural habitats, such as soils, lakes, plants and some extreme environments. Replication loci of several Streptomyces theta-type plasmids have been reported, but are not characterized in details. Conjugation loci of some Streptomyces rolling-circle-type plasmids are identified and mechanism of conjugal transferring are described. Results: We report the detection of a widely distributed Streptomyces strain Y27 and its indigenous plasmid pWTY27 from fourteen plants and four soil samples cross China by both culturing and nonculturing methods. The complete nucleotide sequence of pWTY27 consisted of 14,288 bp. A basic locus for plasmid replication comprised repAB genes and an adjacent iteron sequence, to a long inverted-repeat (ca. 105 bp) of which the RepA protein bound specifically in vitro, suggesting that RepA may recognize a second structure (e.g. a long stem-loop) of the iteron DNA. A plasmid containing the locus propagated in linear mode when the telomeres of a linear plasmid were attached, indicating a bi-directional replication mode for pWTY27. As for rolling-circle plasmids, a single traA gene and a clt sequence (covering 16 bp within traA and its adjacent 159 bp) on pWTY27 were required for plasmid transfer. TraA recognized and bound specifically to the two regions of the clt sequence, one containing all the four DC1 of 7 bp (TGACACC) and one DC2 (CCCGCCC) and most of IC1, and another covering two DC2 and part of IC1, suggesting formation of a high-ordered DNA-protein complex. Conclusions: This work (i) isolates a widespread Streptomyces strain Y27 and sequences its indigenous theta-type plasmid pWTY27; (ii) identifies the replication and conjugation loci of pWTY27 and; (iii) characterizes the binding sequences of the RepA and TraA proteins. [ABSTRACT FROM AUTHOR]

Background: Expression of the stem cell marker octamer 4 (Oct-4) in various neoplasms has been previously reported, but very little is currently known about the potential function of Oct-4 in this setting. The purpose of this study was to assess the prognostic value of Oct-4 expression after surgery in primary non-small cell lung cancer (NSCLC) and investigate its possible molecular mechanism. Methods: We measured Oct-4 expression in 113 NSCLC tissue samples and three cell lines by immunohistochemical staining and RT-PCR. The association of Oct-4 expression with demographic characteristics, proliferative marker Ki67, microvessel density (MVD), and expression of vascular endothelial growth factor (VEGF) were assessed. Results: Oct-4 expression was detected in 90.3% of samples and was positively correlated with poor differentiation and adenocarcinoma histology, and Oct-4 mRNA was found in each cell lines detected. Overexpression of Oct-4 had a strong association with cells proliferation in all cases, MVD-negative, and VEGF-negative subsets. A Kaplan-Meier analysis showed that overexpression of Oct-4 was associated with shorter overall survival in all cases, adenocarcinoma, squamous cell carcinoma, MVD-negative, and VEGF-negative subsets. A multivariate analysis demonstrated that Oct-4 level in tumor tissue was an independent prognostic factor for overall survival in all cases, MVD-negative, and VEGF-negative subsets. Conclusion: Our findings suggest that, even in the context of vulnerable MVD status and VEGF expression, overexpression of Oct-4 in tumor tissue represents a prognostic factor in primary NSCLC patients. Oct-4 may maintain NSCLC cells in a poorly differentiated state through a mechanism that depends on promoting cell proliferation. [ABSTRACT FROM AUTHOR]

Background: Embryonic stem (ES) cells have attracted significant attention from researchers around the world because of their ability to undergo indefinite self-renewal and produce derivatives from the three cell lineages, which has enormous value in research and clinical applications. Until now, many ES cell lines of different mammals have been established and studied. In addition, recently, AS-ES1 cells derived from Apodemus sylvaticus were established and identified by our laboratory as a new mammalian ES cell line. Hence further research, in the application of AS-ES1 cells, is warranted. Results: Herein we report the generation of multiple mesodermal AS-ES1 lineages via embryoid body (EB) formation by the hanging drop method and the addition of particular reagents and factors for induction at the stage of EB attachment. The AS-ES1 cells generated separately in vitro included: adipocytes, osteoblasts, chondrocytes and cardiomyocytes. Histochemical staining, immunofluorescent staining and RT-PCR were carried out to confirm the formation of multiple mesodermal lineage cells. Conclusions: The appropriate reagents and culture milieu used in mesodermal differentiation of mouse ES cells also guide the differentiation of in vitro AS-ES1 cells into distinct mesoderm-derived cells. This study provides a better understanding of the characteristics of AS-ES1 cells, a new species ES cell line and promotes the use of Apodemus ES cells as a complement to mouse ES cells in future studies. [ABSTRACT FROM AUTHOR]

Background: Cigarette smoking is an important risk factor for pulmonary arterial hypertension (PAH) in chronic obstructive pulmonary disease (COPD). Chymase has been shown to function in the enzymatic production of angiotensin II (AngII) and the activation of transforming growth factor (TGF)-β1 in the cardiovascular system. The aim of this study was to determine the potential role of chymase in cigarette smoke-induced pulmonary artery remodeling and PAH. Methods: Hamsters were exposed to cigarette smoke; after 4 months, lung morphology and tissue biochemical changes were examined using immunohistochemistry, Western blotting, radioimmunoassay and reversetranscription polymerase chain reaction. Results: Our results show that chronic cigarette smoke exposure significantly induced elevation of right ventricular systolic pressures (RVSP) and medial hypertrophy of pulmonary arterioles in hamsters, concurrent with an increase of chymase activity and synthesis in the lung. Elevated Ang II levels and enhanced TGF-β1/Smad signaling activation were also observed in smoke-exposed lungs. Chymase inhibition with chymostatin reduced the cigarette smoke-induced increase in chymase activity and Ang II concentration in the lung, and attenuated the RVSP elevation and the remodeling of pulmonary arterioles. Chymostatin did not affect angiotensin converting enzyme (ACE) activity in hamster lungs. Conclusions: These results suggest that chronic cigarette smoke exposure can increase chymase activity and expression in hamster lungs. The capability of activated chymase to induce Ang II formation and TGF-β1 signaling may be part of the mechanism for smoking-induced pulmonary vascular remodeling. Thus, our study implies that blockade of chymase might provide benefits to PAH smokers. [ABSTRACT FROM AUTHOR]

Background: Spectral processing and post-experimental data analysis are the major tasks in NMR-based metabonomics studies. While there are commercial and free licensed software tools available to assist these tasks, researchers usually have to use multiple software packages for their studies because software packages generally focus on specific tasks. It would be beneficial to have a highly integrated platform, in which these tasks can be completed within one package. Moreover, with open source architecture, newly proposed algorithms or methods for spectral processing and data analysis can be implemented much more easily and accessed freely by the public. Results: In this paper, we report an open source software tool, Automics, which is specifically designed for NMR-based metabonomics studies. Automics is a highly integrated platform that provides functions covering almost all the stages of NMR-based metabonomics studies. Automics provides high throughput automatic modules with most recently proposed algorithms and powerful manual modules for 1D NMR spectral processing. In addition to spectral processing functions, powerful features for data organization, data pre-processing, and data analysis have been implemented. Nine statistical methods can be applied to analyses including: feature selection (Fisher's criterion), data reduction (PCA, LDA, ULDA), unsupervised clustering (K-Mean) and supervised regression and classification (PLS/PLS-DA, KNN, SIMCA, SVM). Moreover, Automics has a user-friendly graphical interface for visualizing NMR spectra and data analysis results. The functional ability of Automics is demonstrated with an analysis of a type 2 diabetes metabolic profile. Conclusion: Automics facilitates high throughput 1D NMR spectral processing and high dimensional data analysis for NMR-based metabonomics applications. Using Automics, users can complete spectral processing and data analysis within one software package in most cases. Moreover, with its open source architecture, interested researchers can further develop and extend this software based on the existing infrastructure. [ABSTRACT FROM AUTHOR]

Background: Human glucose 6-phosphate dehydrogenase (G6PD), active in both dimer and tetramer forms, is the key entry enzyme in the pentose phosphate pathway (PPP), providing NADPH for biosynthesis and various other purposes, including protection against oxidative stress in erythrocytes. Accordingly haemolytic disease is a major consequence of G6PD deficiency mutations in man, and many severe disease phenotypes are attributed to G6PD folding problems. Therefore, a robust refolding method with high recovery yield and reproducibility is of particular importance to study those clinical mutant enzymes as well as to shed light generally on the refolding process of large multi-domain proteins. Results: The effects of different chemical and physical variables on the refolding of human recombinant G6PD have been extensively investigated. L-Arg, NADP+ and DTT are all major positive influences on refolding, and temperature, protein concentration, salt types and other additives also have significant impacts. With the method described here, ~70% enzyme activity could be regained, with good reproducibility, after denaturation with Gdn-HCl, by rapid dilution of the protein, and the refolded enzyme displays kinetic and CD properties indistinguishable from those of the native protein. Refolding under these conditions is relatively slow, taking about 7 days to complete at room temperature even in the presence of cyclophilin A, a peptidylprolyl isomerase reported to increase refolding rates. The refolded protein intermediates shift from dominant monomer to dimer during this process, the gradual emergence of dimer correlating well with the regain of enzyme activity. Conclusion: L-Arg is the key player in the refolding of human G6PD, preventing the aggregation of folding intermediate, and NADP+ is essential for the folding intermediate to adopt native structure. The refolding protocol can be applied to produce high recovery yield of folded protein with unaltered properties, paving the way for future studies on clinical G6PD mutants with folding defects and providing a useful model system to study the folding process of oligomeric proteins. [ABSTRACT FROM AUTHOR]

Background: Although intrapartum analgesia has been in use since Victorian times, there have been few attempts to study its usage from routinely collected data. This population based epidemiological study aimed to analyse retrospective data on the distribution of different types of labour analgesia used by women in the Grampian region of Scotland between 1986 and 2001 in order to examine time trends and associations. Methods: Data records on all deliveries occurring in the years 1986 to 2001 were extracted from the Aberdeen Maternity and Neonatal Databank. The rates of the use of epidural, opioid and Entonox or no analgesia for pain relief in labour in each year were calculated. Maternal, pregnancy, labour and delivery characteristics were compared among the users of three different analgesics by univariate and multivariate analyses. Results: A total of 81,418 deliveries were analysed. Of these, 12,659 (15.5%) women had epidural, 33,819 (41.5%) had used opioids and 26,974(33.1%) received either Entonox or no analgesia at all. The women who received epidural analgesia were younger, shorter and heavier and had larger babies (OR = 1.05, 95% CI 1.01, 1.08). Three quarters of them were primigravidae and had longer periods of gestation. They were also more likely to have suffered pregnancy related complications (OR = 2.11, 95% CI 1.8, 2.4). Labour was more likely to have been induced (OR = 2.8, 95% CI 2.6, 2.9) and to have lasted longer in this group of women. Women in this group were 5 times more likely to have an instrumental delivery (95% CI 4.9, 5.1) and 7 times more likely to have a Caesarean section (95% CI 5.7, 9.3). Conclusion: Non epidural analgesia was found to be the most popular choice for pain relief in labour in the Grampian region between 1986 and 2001, although an increase in the uptake of epidural services is starting to occur. The type of labour analgesia used is associated with the epidemiological characteristics of the women's pregnancy, labour and delivery. [ABSTRACT FROM AUTHOR]

Background: Elevated blood pressure in middle age is a major risk factor for subsequent cardiovascular complications. An important longitudinal characteristic of blood pressure is the "tracking phenomenon". Tracking is defined as the persistence of the rank of a person's blood pressure level in a group over a long period of time. In this analysis, we used the Framingham data to investigate whether there are some genes responsible for this phenomenon. Results: Both two-point and multipoint linkage analyses were applied to family members with complete data only and to all family data with missing values imputed by a Gaussian model. The results of two-point linkage analysis indicated that two loci for linkage with the intercept were on chromosomes 10 and 13, and two loci for linkage with both slope and intercept were on chromosomes 1 and 3. Multipoint linkage analysis indicated only one region, 200-240 cM on chromosome 1, to be linked with both intercept and slope. For the intercept of SBP, the highest LOD (4.43) was found at 214 cM when missing data were imputed, and the highest LOD (2.81) was at 231 cM for the complete case data. For the slope of SBP, the highest multipoint LODs were 3.63 at 227 cM and 2.02 at 234 cM for the complete case data and imputation data, respectively. Conclusion: One or more genes in the range of 200-240 cM on chromosome 1 may be related to the tracking phenomenon of SBP. [ABSTRACT FROM AUTHOR]

The article presents a retraction note for the article "Astragalus saponins affect proliferation, invasion and apoptosis of gastric cancer BGC-823 cells" published in the previous issue of the journal is presented.

Background: The alphaherpesvirus virion host shutoff (vhs) gene, UL41, can induce degradation of host mRNAs and shut off host protein synthesis. The roles of vhs in HSV-1 and HSV-2 have been studied extensively in previous studies, however, relatively little is known about the vhs protein of PRV. Methods: A novel method combining CRISPR/Cas9 and Gibson assembly was developed to generate UL41 null PRV variant. The properties of UL41 null PRV in vitro and in vivo were further characterized. And the vhs activity of UL41 protein of PRV variant was evaluated by luciferase assay, Western-blot and RT-qPCR. Results: Gibson assembly based on homologous recombination can accomplish one-step insertion of viral DNA fragments into donor plasmids efficiently (> 80%). Cas9/gRNA further largely enhanced the efficiency of homologous recombination. Using this method we were able to rapidly generate the UL41 null and revertant viruses of PRV variant. Compared to wild type (JS-2012), the UL41 null virus showed significantly smaller plaques and lower titers in Vero cells and impaired lethality and neuroinvasion in mice. Further the UL41 protein from different PRV strains exhibited unequal vhs activity in vitro, which of JS-2012 showed significantly weaker vhs activity than that of European-American strains. In addition UL41 null virus can also significantly decrease the expression of host genes during the early period of infection, which suggests other viral factors may be also involved in host shutoff. Conclusions: CRISPR/Cas9 combined with Gibson assembly efficiently generated UL41 null PRV. Compared to wild type, UL41 null PRV showed impaired both replication capability in vitro and neuroinvasion in vivo. Further UL41 protein of PRV variant showed significantly weaker vhs activity than that of PRV SC (European-American-like strain), suggesting the deficiency of vhs activity by the PRV variant UL41 protein. [ABSTRACT FROM AUTHOR]

An abstract of the article "C-Terminal Part of Alpha-Synuclein Mediates its Activity in Promoting Proliferation of Dopaminergic Cells," by Juanjuan Yin, Tao Wang, Junyan Han, Chen Zhang, Qiulan Ma, Xin Li, Furong Cheng, Yaohua Li, Guangwei Liu, Piu Chan, and colleagues, is presented.

Background: Recently, total pelvic floor reconstruction (TR) has been the treatment of choice for improving urinary incontinence (UI) after radical prostatectomy (RP). However, the superiority of TR with respect to urinary continence recovery following RP remains controversial. This study identified the effect of TR versus nonTR of the pelvic floor on short-term and long-term continence rates after RP. Methods: A literature search was performed in November 2017 using the PubMed, Embase, and Web of Science databases. Only comparative research or clinical studies reporting urinary continence outcomes was included in the meta-analysis, and the quality of evidence was evaluated using the 2011 Level of Evidence for therapy research. Results: We analyzed ten studies reporting urinary continence rates after RP at one or more postoperative time points (1, 2, 4, 12, 24, and 52 weeks). TR was associated with significantly better urinary continence outcomes at 1 week (OR 2. 76, 95% CI 1.58-4.84, P < 0.001), 2 weeks (OR 2.57, 95% CI 1.74-3.80, P < 0.001), 4 weeks (OR 2.61, 95% CI 1.56-4.38, P < 0.001), 12 weeks (OR 4.33, 95% CI 2.01-9.33, P < 0.001), 24 weeks (OR 3.83, 95% CI 1.54-9.55, P = 0.004), 52 weeks (OR 4. 10, 95% CI 1.80-9.38, P < 0.001) after RP. There was no difference in the rate of complications between the two arms (OR 0.54, 95% CI 0.19-1.54, P = 0.25). Conclusions: Compared with nonTR, TR is significantly and positively associated with a return to continence but not with complication rate in men following RP, suggesting that TR may be useful for decreasing the urinary incontinence rate after surgery. [ABSTRACT FROM AUTHOR]

Background: Infection with the hepatitis B virus (HBV) is closely associated with the development of hepatocellular carcinoma (HCC). The osmoregulatory transcription factor nuclear factor of activated T-cells 5 (NFAT5) has been shown to play an important role in the development of many types of human cancers. The role of NFAT5 in HBV-associated HCC has never previously been investigated. Methods: We compared expression profiles of NFAT5, DARS2 and miR-30e-5p in HCC samples, adjacent nontumor tissues and different hepatoma cell lines by quantitative real-time polymerase chain reaction and /or Western blot. Clinical data of HCC patients for up to 80 months were analyzed. The regulatory mechanisms upstream and convergent downstream pathways of NFAT5 in HBV-associated HCC were investigated by ChIP-seq, MSP, luciferase report assay and bioinformation anaylsis. Results: We first found that higher levels of NFAT5 expression predict a good prognosis, suggesting that NFAT5 is a potential tumor-suppressing gene, and verified that NFAT5 promotes hepatoma cell apoptosis and inhibits cell growth in vitro. Second, our results showed that HBV could suppress NFAT5 expression by inducing hypermethylation of the AP1-binding site in the NFAT5 promoter in hepatoma cells. In addition, HBV also inhibited NFAT5 through miR-30e-5p targeted MAP4K4, and miR-30e-5p in turn inhibited HBV replication. Finally, we demonstrated that NFAT5 suppressed DARS2 by directly binding to its promoter. DARS2 was identified as an HCC oncogene that promotes HCC cell cycle progression and inhibits HCC cell apoptosis. Conclusion: HBV suppresses NFAT5 through the miR-30e-5p/mitogen-activated protein kinase (MAPK) signaling pathway upstream of NFAT5 and inhibits the NFAT5 to enhance HCC tumorigenesis via the downstream target genes of DARS2. [ABSTRACT FROM AUTHOR]

Background: Degradation of pectin in lignocellulosic materials is one of the key steps for biofuel production. Biological hydrolysis of pectin, i.e., degradation by pectinolytic microbes and enzymes, is an attractive paradigm because of its obvious advantages, such as environmentally friendly procedures, low in energy demand for lignin removal, and the possibility to be integrated in consolidated process. In this study, a metagenomics sequence-guided strategy coupled with enrichment culture technique was used to facilitate targeted discovery of pectinolytic microbes and enzymes. An apple pomace-adapted compost (APAC) habitat was constructed to boost the enrichment of pectinolytic microorganisms. Results: Analyses of 16S rDNA high-throughput sequencing revealed that microbial communities changed dramatically during composting with some bacterial populations being greatly enriched. Metagenomics data showed that apple pomace-adapted compost microbial community (APACMC) was dominated by Proteobacteria and Bacteroidetes. Functional analysis and carbohydrate-active enzyme profiles confirmed that APACMC had been successfully enriched for the targeted functions. Among the 1756 putative genes encoding pectinolytic enzymes, 129 were predicted as novel (with an identity <30% to any CAZy database entry) and only 1.92% were more than 75% identical with proteins in NCBI environmental database, demonstrating that they have not been observed in previous metagenome projects. Phylogenetic analysis showed that APACMC harbored a broad range of pectinolytic bacteria and many of them were previously unrecognized. Conclusions: The immensely diverse pectinolytic microbes and enzymes found in our study will expand the arsenal of proficient degraders and enzymes for lignocellulosic biofuel production. Our study provides a powerful approach for targeted mining microbes and enzymes in numerous industries. [ABSTRACT FROM AUTHOR]

Background: This study was initiated to investigate the difference in HER2 status between tumor tissue and circulating tumor cells (CTCs), as well as the predictive value of CTC HER2 status for predicting the outcomes of anti-HER2 therapy in histologically HER2-positive metastatic breast cancer (MBC) patients.Methods: HER2 expression on CTCs was detected using a CellSearch system within 7 days before a new line of anti-HER2 therapy was begun. According to the criterion proposed in our previous report, patients were defined as CTC HER2-positive or -negative. After close follow-up, the correlation between CTC HER2 status and the outcome of the treatment was evaluated by statistical analysis.Results: CTCs were detected in 57.4 % (58/101) of the patients. Notably, 62.1 % (36/58) of these patients had an inconsistent HER2 status between their tissue and CTCs. The discordant rate may correlate with the time interval between histological and CTC HER2 testing and is more likely to occur in the subgroup of patients with an interval of > 1 year than in those with an interval < 1 year (70.7 % vs. 41.2 %, P = 0.043). For PFS, positive HER2 status on CTCs was shown to be a valuable predictor, both in univariate (HR = 0.321, 95%CI, 0.156-0.62, P = 0.0011) and multivariate (HR = 0.383, 95%CI, 0.166-0.831, P = 0.019) Cox regression analysis. Meanwhile, Kaplan-Meier survival curves revealed that the median PFS of CTC HER2-positive patients was significantly longer than CTC HER2-negative ones (8.5 vs. 3.5 months, P < 0.001).Conclusions: HER2 status on CTCs was different from that of tumor tissues and predicted a different outcome of the patients' anti-HER2 therapy. This difference may be correlated with the time interval between tissue and CTC HER2 testing, indicating the necessity of real-time HER2 analysis for histologically HER2-positive MBC patients. [ABSTRACT FROM AUTHOR]

An abstract of the article "Oxidative DNA Damage Triggers ProNGF-Mediated Apoptosis in the Striatum of 6-OHDA-Treated Rats," by Tao Wang, Pingping Zuo and Piu Chan is presented.

Background: Studies have indicated that interleukin 23 (IL-23) plays an important role in many inflammatory- and autoimmune-related diseases. However, there is little knowledge about IL-23 in lumbar disc herniation (LDH). Thus, in this study, we aimed to find out whether IL-23 is expressed in intervertebral discs (IVDs) and what roles it may play. Methods: Human IVD tissues were collected from 29 LDH patients and 8 vertebral fracture patients (normal control, NC group). According to the integrity of annulus fibrosus, LDH patients were divided into two groups: R group (ruptured group, n = 16) and NR group (non-ruptured group, n = 13). Morphological changes of IVDs were assessed by hematoxylin and eosin (HE staining), and expression of IL-23 in IVD tissues was detected by immunohistochemical staining. Besides gene expression of IL-23, IL-17, IL-6, IL-1 β, and TNF-α was also evaluated by reverse transcription polymerase chain reaction (RT-PCR). Results: The results showed that the R group was more degenerated than the other two groups and NC group showed the least degenerated performance; stronger positive IL-23 expression was observed in herniated IVDs, especially in the R group. Meanwhile, higher gene expression of IL-23, IL-17, IL-6, IL-1 β, and TNF-α was found in the tissues from LDH patients and a positive correlation between IL-17 and IL-23 gene expression was also observed. Conclusions: Taken all above results together, it may be deduced that higher expression of IL-23 may contribute to the deterioration of IVDs through the IL-23/IL-17 pathway. [ABSTRACT FROM AUTHOR]

The Chinese medicine herb pair Flos Lonicerae japonicae (FLJ) and Forsythiae fructus (FF), is a representative heat-clearing (qing re) and detoxifying (jie du) combination that exhibits many pharmacological activities, including antibacterial, antiviral, antitumor, anti-inflammatory, and antioxidant effects. Extensive phytochemical studies have identified a series of bioactive compounds, such as chlorogenic acid from FLJ and forsythoside A from FF. This article provides a comprehensive review on the chemical and pharmacological principles of the traditional functions of FLJ-FF, and sheds light on further developments of this herb pair. [ABSTRACT FROM AUTHOR]

Background: In biological systems, metabolomics can not only contribute to the discovery of metabolic signatures for disease diagnosis, but is very helpful to illustrate the underlying molecular disease-causing mechanism. Therefore, identification of disease-related metabolites is of great significance for comprehensively understanding the pathogenesis of diseases and improving clinical medicine. Results: In the paper, we propose a disease and literature driven metabolism prediction model (DLMPM) to identify the potential associations between metabolites and diseases based on latent factor model. We build the disease glossary with disease terms from different databases and an association matrix based on the mapping between diseases and metabolites. The similarity of diseases and metabolites is used to complete the association matrix. Finally, we predict potential associations between metabolites and diseases based on the matrix decomposition method. In total, 1,406 direct associations between diseases and metabolites are found. There are 119,206 unknown associations between diseases and metabolites predicted with a coverage rate of 80.88%. Subsequently, we extract training sets and testing sets based on data increment from the database of disease-related metabolites and assess the performance of DLMPM on 19 diseases. As a result, DLMPM is proven to be successful in predicting potential metabolic signatures for human diseases with an average AUC value of 82.33%. Conclusion: In this paper, a computational model is proposed for exploring metabolite-disease pairs and has good performance in predicting potential metabolites related to diseases through adequate validation. The results show that DLMPM has a better performance in prioritizing candidate diseases-related metabolites compared with the previous methods and would be helpful for researchers to reveal more information about human diseases. [ABSTRACT FROM AUTHOR]

Background: mi-663 is associated with many important biologic processes, such as the evolution, development, viral infection, inflammatory response, and carcinogenesis among vertebrates. However, the molecular function and mechanism of mi-663 in pancreatic cancer growth and invasion is still unclear. Methods: Western blot and real-time PCR were used to study the expression level of eEF1A2 protein and mi-663 in pancreatic cancer tissues and cell lines. The Pearson X2 test was used to determine the correlation between mi-663 expression and clinicopathologic features of patients. Patients' survival was analyzed using the Kaplan-Meier method, using the log-rank test for comparison. The biological function of mi-663 was examined by measuring cell growth, cell invasion and apoptosis analysis in vitro and in vivo. mi-663 target gene and signaling pathway was identified by luciferase activity assay and western blot. Results: We found that, in pancreatic cancer, eEF1A2 was significantly upregulated but mi-663 was significantly downregulated. Further results showed that the expression level of eEF1A2 and mi-663 was strongly associated with TNM stage and node metastasis status of the patients. mi-663 and eEF1A2 were inversely correlated with each other, and the changes in the expression levels of each can also predict the survival of patients with pancreatic cancer. We identified mi-663 as a tumor attenuate molecular that attenuated the proliferation and invasion of pancreatic cancer cells both in vitro and in vivo. Finally, we confirmed that the expression of eEF1A2 can partially restore the pro-apoptotic and anti-invasion functions of mi-663. Conclusions: mi-663 attenuated the proliferation and invasion of pancreatic cells both in vitro and in vivo by directly targeting eEF1A2. mi-663 and eEF1A2 might be potential targets for the treatment of pancreatic cancer in the future. [ABSTRACT FROM AUTHOR]

Objective: This study aims to determine if the involvement of tensile stress affects the expressions of inflammatory cytokines interleukin-17(IL-17), interleukin-1β (IL-1β), and inducible nitric oxide synthase (iNOS) at intervertebral discs in vivo. Material and method: Sixty-four female Sprague–Dawley rats were randomly divided into four groups: sham, tail-suspended (TS), tail-suspended with needle puncture (TSNP), and single-needle puncture (SNP) groups. A tail-suspension device provides low magnitude of tensile stress (2.45 Newton (N)), and aseptic needle puncture on the tail disc induces inflammatory response. After 4 weeks, the treated discs were harvested for histologic analysis, quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA). Result: Pathological examination demonstrated that compared to the sham group, the morphologies of nucleus pulposus (NP) and anulus fibrosus (AF) in TS, SNP, and TSNP groups displayed degenerative changes in varying degrees. Results from RT-qPCR showed that IL-17 and iNOS mRNA expression levels were significantly higher in both TSNP and SNP groups than those in the sham groups. Expression of IL-17 and iNOS are not significantly different between the sham and TS groups (P > 0.05). Compared with the SNP group, the mRNA expression of IL-17 and iNOS in the TSNP groups were markedly decreased (P < 0.05). The regulation of IL-1β and IL-17 detected by ELISA was coincident with the qRT-PCR results. Conclusion: The results from this study suggested that relatively low magnitude tensile stress might play an essential role in the anti-inflammatory process and the relief of low-back pain (LBP). [ABSTRACT FROM AUTHOR]

Background Proximal humeral fractures are common lesions of the elderly, but there are no established treatment guidelines. A surgical treatment for comminuted and displaced fractures of the proximal humerus was developed and is still evolving. The aim of this study was to perform a quantitative review to evaluate the risk of avascular necrosis (AVN) in patients with proximal humeral fractures who were treated by operative fixation compared with conservative treatment. Methods We searched the PubMed, MEDLINE, Springer, Elsevier Science Direct, Cochrane Library, Google Scholar, China National Knowledge Infrastructure (in Chinese), and Wanfang database (in Chinese) up to December 2013 to identify studies related to operative fixation and AVN in patients with proximal humeral fractures. Results Seven studies with a total of 291 patients (142 operative fixation cases and 149 conservative treatment cases) with proximal humeral fractures were considered in the meta-analysis. The overall meta-analysis showed no significant difference in the incidence of AVN between the two groups [odds ratio (OR) 1.42, 95% confidence interval (CI) 0.33-6.11, p = 0.64]. The subgroup meta-analysis by study design (retrospective/prospective), sample size (≤40/>40), and ethnicity (European/Asian) demonstrated similar results. However, the subgroup analysis by specific operative approach (plate fixation/tension band wiring fixation/others) indicated that plate fixation was associated with a higher rate of AVN than conservative treatment (OR 0.20, 95% CI 0.05-0.76, p = 0.019). Conclusions Plate fixation was associated with a higher risk of AVN development than conservative treatment in patients with proximal humeral fractures. [ABSTRACT FROM AUTHOR]

Background: Asthma is a chronic disease that is characterized by airway hyperresponsiveness and airway remodeling. The underlying mechanisms that mediate the pathological processes are not fully understood. Abl is a non-receptor protein tyrosine kinase that has a role in the regulation of smooth muscle contraction and smooth muscle cell proliferation in vitro. The role of Abl in airway hyperresponsiveness and airway remodeling in vivo is largely unknown. Methods: To evaluate the role of Abl in asthma pathology, we assessed the expression of Abl in airway tissues from the ovalbumin sensitized and challenged mouse model, and human asthmatic airway smooth muscle cells. In addition, we generated conditional knockout mice in which Abl expression in smooth muscle was disrupted, and then evaluated the effects of Abl conditional knockout on airway resistance, smooth muscle mass, cell proliferation, IL-13 and CCL2 in the mouse model of asthma. Furthermore, we determined the effects of the Abl pharmacological inhibitors imatinib and GNF-5 on these processes in the animal model of asthma. Results: The expression of Abl was upregulated in airway tissues of the animal model of asthma and in airway smooth muscle cells of patients with severe asthma. Conditional knockout of Abl attenuated airway resistance, smooth muscle mass and staining of proliferating cell nuclear antigen in the airway of mice sensitized and challenged with ovalbumin. Interestingly, conditional knockout of Abl did not affect the levels of IL-13 and CCL2 in bronchoalveolar lavage fluid of animals treated with ovalbumin. However, treatment with imatinib and GNF-5 inhibited the ovalbumin-induced increase in IL-13 and CCL2 as well as airway resistance and smooth muscle growth in animals. Conclusions: These results suggest that the altered expression of Abl in airway smooth muscle may play a critical role in the development of airway hyperresponsiveness and airway remodeling in asthma. Our findings support the concept that Abl may be a novel target for the development of new therapy to treat asthma. [ABSTRACT FROM AUTHOR]