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Background The incidence of bronchopulmonary dysplasia (BPD), a chronic lung disease of newborns, has been paradoxically rising despite medical advances. Histone deacetylase 3 (Hdac3) has been reported to be a crucial regulator in alveologenesis. Hence, this study aims to investigate the mechanism of Hdac3 in the abnormal pulmonary angiogenesis and alveolarization of BPD. Methods A hyperoxia-induced BPD model of was developed in newborn mice, and primary lung fibroblasts were isolated from adult mice. Hdac3 was knocked out in vivo and knocked down in vitro, while microRNA (miR)-17 was downregulated in vivo and in vitro to clarify their roles in abnormal pulmonary angiogenesis and alveolarization. Mechanistic investigations were performed on the interplay of Hdac3, miR-17-92 cluster, enhancer of zeste homolog 1 (EZH1), p65 and placental growth factor (Pgf). Results Hdac3 was involved in abnormal alveolarization and angiogenesis in BPD mice. Further, the expression of the miR-17-92 cluster in BPD mice was downregulated by Hdac3. miR-17 was found to target EZH1, and Hdac3 rescued the inhibited EZH1 expression by miR-17 in lung fibroblasts. Additionally, EZH1 augmented Pgf expression by recruiting p65 thus enhancing the progression of BPD. Hdac3 augmented the recruitment of p65 in the Pgf promoter region through the miR-17/EZH1 axis, thus enhancing the transcription and expression of Pgf, which elicited abnormal angiogenesis and alveolarization of BPD mice. Conclusions Altogether, the present study revealed that Hdac3 activated the EZH1-p65-Pgf axis through inhibiting miR-17 in the miR-17-92 cluster, leading to accelerated abnormal pulmonary angiogenesis and alveolarization of BPD mice.

Background::In recent years, visual quality has been extensively investigated in various conditions. In this community-based population study, we analyzed the effects of aging, refraction, and Lens Opacification Classification System III (LOCSIII) score on retinal imaging quality in healthy Chinese adults.Methods::This cross-sectional study was conducted on sub-group subjects from The Handan Eye Study between October 2012 and January 2013. Healthy subjects over 30-years-old with logarithm of the minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA) less than 0 were included. Retinal image quality was measured by optical quality analysis system (OQAS) and recorded as modulation transfer function cutoff frequency (MTF cutoff), OQAS value (OV) 100%, OV20%, OV9%, Strehl ratio (SR), and objective scatter index (OSI). The correlation between age, spherical equivalent refraction (SE), LOCSIII score, and optical quality parameters were investigated by multivariate analysis. Results::Among 1108 verified subjects, 690 subjects (1380 eyes) met the inclusion criteria. Their age ranged from 30 to 76 years, SE ranged from -4.75 to 2.75 D. They were divided into five age groups (30-39, 40-49, 50-59, 60-69, and ≥70 years) for further analysis. After multivariate analysis by mixed-effect linear model, SR ( t = -3.03, P = 0.002), OV20% ( t = -2.39, P = 0.017), and OV9% ( t = -3.16, P = 0.001) significantly decreased with the increasing age, whereas logMAR BCVA ( t = 4.42, P < 0.001) and OSI ( t = 4.46, P < 0.001) significantly increased with age. As SE increased, SR ( t = 2.74, P = 0.01), OV20% ( t = 2.31, P = 0.02), and OV9% ( t = 2.79, P = 0.005) significantly elevated, and OSI ( t = -3.38, P < 0.001) significantly decreased. With the increase in cortical opacity score, all optical quality parameters except for SR significantly decreased, including MTF cutoff ( t = -2.78, P = 0.01), OV100% ( t = -2.78, P = 0.005), OV20% ( t = -2.60, P = 0.009), and OV9% ( t = -2.05, P = 0.04). As posterior sub capsular opacity score increased, MTF cutoff ( t = -2.40, P = 0.02) and OV100% ( t = -2.40, P = 0.01) significantly decreased, while OSI ( t = 7.56, P < 0.001) significantly increased. Conclusions::In healthy Chinese adult population, optical quality-related parameters significantly decrease with the increasing age, and OSI significantly increases with age. In normal BCVA subjects, optical quality is significantly impacted by cortical and posterior sub capsular opacity rather than by nuclear opacity.

To evaluate intravitreal conbercept injection for treatment of macular oedema secondary to central retinal vein occlusion (CRVO) in Chinese patients during 1-year follow-up in the real-world setting. Twenty-seven eyes of 27 patients with macular oedema associated with CRVO were retrospectively reviewed. The eyes received monthly intravitreal conbercept injection (0.5 mg in 50 µl) for 3 months. From then on, the patients were followed up every month and received injection pro re nata (PRN) up to 12 months. The primary outcome measurements included changes of best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to month 3 and month 12. Other outcome measurements included proportion of patients gaining ≥15 letters in BCVA at month 3 and 12, the mean number of injections and safety concerns. The mean BCVA gain from baseline was 12.7 ± 7.6 letters at month 3 and 14.8 ± 9.6 letters at month 12. The mean CRT reduction from baseline was 374.5 ± 280.7 μm at month 3 and 428.2 ± 241.3 μm at month 12. The proportion of patients who gained ≥15 letters in BCVA was 45.1% at month 3 and 52.9% at month 12. The mean number of injections was 7.6 ± 1.5. No severe local and systemic complications occurred following injection. Intravitreal conbercept injection by three monthly loading doses followed by PRN treatment regimen was safe and efficacious for patients with macular oedema secondary to CRVO through 1-year follow-up.

Background: As a noninvasive respiratory support mode, high-flow nasal cannula (HFNC) is widely used in preterm infants at neonatal care units. HFNC is often used as an alternative to nasal continuous positive airway pressure (NCPAP) for initial or post-extubation respiratory support. The purpose of this meta-analysis is to evaluate and compare the efficacy and safety of HFNC and NCPAP for respiratory support in preterm infants. Methods: We searched PubMed, Web of Science, Embase, Cochrane Library, Clinicaltrials.gov, Controlled-trials.com, Google Scholar, VIP, and Wang Fang for articles from their inception to December 2018. All published randomized controlled trials (RCTs) evaluating and comparing the effects of HFNC and NCPAP therapy for primary respiratory support in newborns were included. All meta-analyses were performed using Review Manager 5.3. Results: In total, 21 RCTs involving 2886 preterm infants were included. The results of the meta-analysis revealed the following: (1) for primary respiratory support, the rates of treatment failure at trial entry were similar between HFNC and CPAP (relative risk 1.03, 95% confidence interval 0.79–1.33), and HFNC had reduced nasal trauma (p < .00001); and (2) for respiratory support after extubation, CPAP was associated with a lower likelihood of treatment failure than HFNC (relative risk 1.23, 95% confidence interval 1.01–1.50). The incidences of nasal trauma and pneumothorax in the HFNC group were significantly lower than that in the CPAP group (p < .0001 and p = .03). Serious adverse events did not significantly differ. Conclusions: HFNC had effects similar to those of CPAP regarding the failure of initial respiratory support in premature infants and was associated with reduced nasal trauma compared to CPAP. Following extubation, CPAP had fewer treatment failures than HFNC, but CPAP had a significantly increased rate of nasal trauma and pneumothorax. Further studies are needed to clarify the potential benefits of HFNC as primary respiratory support in extremely low birth weight or extremely preterm infants.

Background Metastasis remains the biggest obstacle for breast cancer treatment. Therefore, identification of specific biomarker of metastasis is very necessary. The RNA binding protein 3 (RBMS3) acts as a tumor suppressor in various cancers. Whereas, its role and underlying molecular mechanism in breast cancer is far from elucidated. Methods Quantitative real-time PCR and western blots were carried out to determine the expression of RBMS3 in breast cancer cells and tissues. Transwell and in vivo metastasis assay were conducted to investigate the effects of RBMS3 on migration, invasion and metastasis of breast cancer cells. Transcriptome sequencing was applied to screen out the differential gene expression affected by RBMS3. RNA immunoprecipitation assay combined with luciferase reporter assay were performed to explore the direct correlation between RBMS3 and Twist1 mRNA. Results RBMS3 was downregulated in breast cancer and ectopic expression of RBMS3 contributed to inhibition of cell migration, invasion in vitro and lung metastasis in vivo. Furthermore, RBMS3 negatively regulated Twsit1 expression via directly binding to 3′-UTR of Twist1 mRNA, and thereby decreased Twist1-induced expression of matrix metalloproteinase 2 (MMP2). Additionally, Twist1-induced cell migration, invasion and lung metastasis could be reversed by the upregulation of RBMS3. Conclusions In summary, our study revealed a novel mechanism of the RBMS3/Twsit1/MMP2 axis in the regulation of invasion and metastasis of breast cancer, which may become a potential molecular marker for breast cancer treatment.

Background: The transforming growth factor-β (TGF-β) pathway plays a vital role in driving cancer cell epithelial–mesenchymal transition (EMT). Zonula occludens-1 (ZO-1), which is downregulated in response to TGF-β, is able to control endothelial cell–cell tension, cell migration, and barrier formation. However, the molecular mechanism of how TGF-β regulates ZO-1 expression remains unclear. Methods: Breast cancer cells were treated with TGF-β to induce an EMT progress. Chromatin immunoprecipitation and dual-luciferase reporter assay were performed to investigate direct relationship between Snail and RNA binding motif protein 38 (RBM38). The RNA immunoprecipitation combined with RNA electrophoretic mobility shift assay and dual-luciferase reporter assay were conducted to testify direct relationship between RBM38 and ZO-1. The ZO-1 siRNA was transfected to breast cancer cells that overexpress RBM38 and the control, followed by transwell and Matrigel invasion assays to examine cell migratory and invasive ability. Results: Transforming growth factor-β induced a remarkable downregulation of RBM38 in breast cancer that was directly regulated by transcription repressor Snail targeting the E-box elements in promoter region of RBM38 gene. Additionally, RBM38 positively regulated ZO-1 transcript via directly binding to AU/U-rich elements in its mRNA 3′-UTR. Moreover, by magnifying RBM38 expression, cell migration and invasion mediated by knockdown of ZO-1 in breast cancer were reversed. Conclusions: All the results clarified a linear regulation relationship among Snail, RBM38, and ZO-1, implicating RBM38 as a pivotal mediator in TGF-β-induced EMT in breast cancer.

Background Evidence-based practice (EBP) education or training are considered fundamental to building and strengthening an EBP culture, as well as to encouraging evidence-based academic and clinical practice in the nursing community. However, few valid and reliable instruments are available for the assessment of EBP teaching and learning in clinical nurses in China. Translation, reliability, and validity testing of the English Evidence-Based Practice Profile Questionnaire (EBP2Q), which has strong psychometric properties, may encourage evaluation and promote the implementation of EBP in Mainland China. Methods Based on established guidelines for the development of questionnaires, the English EBP2Q was translated and cross-culturally adapted. The Chinese version of the EBP2Q (EBP2Q-C) was validated using a sample of 543 nurses. Structural validity was evaluated through exploratory factor analysis and confirmatory factor analysis, and the questionnaire was tested for convergent and criterion validity. The internal consistency and test-retest reliability were also evaluated. Results The content validity index demonstrated good content validity (≥0.98). An eight-factor structure was obtained in the exploratory factor analysis, and verified by a three-order factor model from the confirmatory factor analysis (χ2/df = 2.001; RMSEA = 0.065; SRMR = 0.077; and CFI = 0.884). The Spearman’s rank correlation analysis of the EBP2Q-C with the Evidence-Based Practice Questionnaire showed moderate correlations for Practice (0.58) and Confidence (0.68) and a low correlation for Sympathy (0.32). Criterion validity was demonstrated by significant differences in terms of nurses’ highest education, present position, EBP training, involvement in research programs, and level of understanding of English. Both the overall Cronbach’s α and the Cronbach’s α for the domains exceeded 0.70. The intraclass correlation coefficients for the domains ranged between 0.75 and 0.96, indicating satisfactory repeatability. Conclusions Except for the convergent validity of the Sympathy domain, the EBP2Q-C provided evidence of validity and reliability. Therefore, it can be applied in EBP education or training assessment in Mainland China.

Objective: This study aims to evaluate the value of the ultrasound-related scoring system on pregnant patients receiving assisted reproductive technology (IVF/ICSI) and early pregnancy outcome. Materials and methods: This prospective study included 208 pregnant women receiving assisted reproductive technology (IVF/ICSI). The following ultrasound parameters were measured: gestational sac size, the proportion of the embryo and gestational sac (embryo/gestational sac), yolk sac size, and fetal cardiac activity. The above data were assigned according to the ongoing pregnancy rate (up to 14 weeks), and the score increased parallel to the pregnancy rate. All patients were grouped according to their scores. Results: Patients with a score of 4–5 had a low ongoing pregnancy rate of 14.29%, while patients with a score of 6–7 had an ongoing pregnancy rate of 55.56%. Surprisingly, patients with a score of 8–9 had an ongoing pregnancy rate of 97.22%. In addition, it was found that the ongoing pregnancy rate was 100% (36/36) in patients with a score of 9. Conversely, there was no ongoing pregnancy in patients with a score of 4. Conclusion: First, this scoring system is strongly associated with an ongoing pregnancy of over 14 weeks. Second, some reassurance can be given to patients with favorable ultrasound parameters, regardless of maternal age or previous pregnancy loss. Third, it would be meaningless to continue the pregnancy in patients with a score of 4, according to the scoring system. Fourth, patients without cardiac activity and embryos at days 33–35 after embryo transfer should discontinue the pregnancy, while patients with embryos should proceed with the pregnancy. Keywords: Gestational sac, Embryo/gestational sac, Yolk sac, Fetal cardiac activity, Ongoing pregnancy

Background Noninvasive high-frequency oscillatory ventilation (nHFOV), a relatively new modality, is gaining popularity despite scarce evidence. This meta-analysis was designed to evaluate the efficacy and safety of nHFOV as respiratory support in premature infants. Methods We searched MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL from inception of the database to January 2019. All published randomized controlled trials (RCTs) evaluating the effect of nHFOV therapy with nasal continuous positive airway pressure (nCPAP) or biphasic nCPAP (BP-CPAP) in newborns for respiratory support were included. All meta-analyses were performed using Review Manager 5.3. Results A total of 8 RCTs involving 463 patients were included. The meta-analysis estimated a lower risk of intubation (relative risk = 0.50, 95% confidence interval of 0.36 to 0.70) and more effective clearance of carbon dioxide (weighted mean difference = − 4.61, 95% confidence interval of − 7.94 to − 1.28) in the nHFOV group than in the nCPAP/BP-CPAP group. Conclusions Our meta-analysis of RCTs suggests that nHFOV, as respiratory support in preterm infants, significantly remove carbon dioxide and reduce the risk of intubation compared with nCPAP/BP-CPAP. The appropriate parameter settings for different types of noninvasive high-frequency ventilators, the effect of nHFOV in extremely preterm infants, and the long-term safety of nHFOV need to be assessed in large trials.

// Peipei Lou 1, * , Chunlian Li 1, * , Liang Shi 1, * , Tian-Song Xia 1 , Wenbin Zhou 1 , Jing Wu 1 , Xujie Zhou 1 , Xiaoxia Li 1 , Ying Wang 1 , Ji-Fu Wei 2 , Qiang Ding 1 1 Jiangsu Breast Disease Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing City, Jiangsu Province, 210000, China 2 Research Division of Clinical Pharmacology, The First Affiliated Hospital with Nanjing Medical University, Nanjing City, Jiangsu Province, 210000, China * These authors have contributed equally to this work Correspondence to: Ji-Fu Wei, email: weijifu@hotmail.com Qiang Ding, email: dingqiang@njmu.edu.cn Keywords: progesterone receptor, RNPC1, mRNA stability, breast cancer, proliferation Received: January 04, 2016 Accepted: July 26, 2016 Published: September 14, 2016 ABSTRACT Progesterone receptor (PR) could activate transcriptional process involved in normal mammary gland proliferation and breast cancer development. Moreover, PR expression is an important marker of luminal breast cancer, which is associated with good prognosis and indicates better responding to endocrine therapies. The regulation of PR expression was studied mainly on its post-translational levels. In this study, we found PR was positively regulated by RNA-binding region-containing protein 1 (RNPC1), a RNA-binding protein, in PR positive breast cancer. Overexpression of RNPC1 increased, whereas knockdown of RNPC1 decreased, the level of PR protein and transcripts. Additionally, we demonstrated that RNPC1 could bind to PR mRNA via AU-rich elements (AREs) within PR 3′-untranslated region (3′-UTR) and then enhance PR mRNA stability. Moreover, we proved that progesterone-dependent PR functions which could induce breast cancer proliferation were enhanced by RNPC1, both in vitro and in vivo . Conclusively, we revealed a novel mechanism by which PR could be regulated by RNPC1 via stabilizing its mRNA.

To investigate the influence of daily activities on myopic refractive change and myopic onset in Chinese urban students. The Beijing Myopia Progression Study was a 3-year cohort study. Cycloplegic refraction and a daily activity questionnaire were assessed at baseline and at follow-up examinations. Refractive change was defined as the difference in cycloplegic spherical equivalent (SE) between the final follow-up and baseline. 386 students were initially enrolled in the baseline study. At the final follow-up, 222 students (57.5 %) with completed refractive error and daily activity data were analyzed. These students spent 0.32 ± 2.33 h/day more on near work (p = 0.04), and 0.21 ± 1.31 h/day less on outdoor leisure (p = 0.02), than they did at baseline. In the multivariate analysis, the younger among the secondary students (β = 0.06, p

A total of 70% of breast cancers express the estrogen receptor (ER)α; therefore, targeting the ER may be an effective endocrine therapy with which to inhibit breast cancer growth. Tamoxifen is the most common‑used clinically used drug for the treatment of advanced or metastatic ER‑positive (ER+) breast cancer. However, a substantial proportion of patients become resistant to endocrine therapies. To overcome this limitation, in this stud, we sought to maximize the benefits associated with tamoxifen therapy via drug combination strategies. We demonstrated that rapamycin, an FDA‑approved mammalian target of rapamycin (mTOR) inhibitor, enhanced the effects of endocrine therapy with tamoxifen, and the concentration of tamoxifen required for ER+ breast cancer cell growth inhibition was substantially reduced. Moreover, treatment with rapamycin plus tamoxifen significantly inhibited tumor growth in vivo. In addition, this synergistic effect may be mediated by the induction of p73. We revealed a novel mechanism in which p73 increases ERα expression by directly binding to the promoter region of the ERα gene. Taken together, the findings of this study indicate that combination therapy with rapamycin and tamoxifen underlying p73‑mediated ERα expression may provide new insight into the drug combination for the treatment of ER+ breast cancer.

We investigated the effects of perioperative blood transfusion in the prognosis of hereditary and sporadic colon cancer. There are 1075 colon cancer patients, including 936 sporadic colon cancer and 139 with hereditary colon cancer undergoing surgery at our hospital. All patients underwent 10 years of follow-up. In the sporadic group, mortality, local recurrence rate and distant metastases rate of transfused patients were significantly higher than non-transfused patients. The 10-year survival rates were significantly lower in patients receiving blood transfusions compared to non-transfused patients. In the hereditary group, mortality was higher in transfused patients compared to non-transfused patients.

The fungus Nodulisporium sp. (No. 65-12-7-1), which can produce a rare class of steroids (4-methyl-progesteroids) in rice solid medium, was subjected to a one strain-many compounds (OSMAC) approach. It was found to produce ten new 4-methyl-progesteroid derivatives named nodulisporisteroids C-L (1-10) in potato-dextrose-broth (PDB) medium, which showed that the fungus was a prolific producer of 4-methyl-progesteroids. The structures of 1-10 were elucidated by spectroscopic and X-ray crystallographic analysis. Their cytotoxic activities against five human cancer cell lines had been evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method.

The goal of the present study is to explore the physiological effects of injected human immunoglobulin on patients with severe bronchiolitis before and after treatment. 86 young children with severe bronchiolitis were randomly divided into the observation group (43 cases) and the treatment group (43 cases). On the basis of conventional therapy, the children in the treatment group were given human immunoglobulin (400 mg/kg, 1–3 times) via intravenous injection. 60 healthy young children, as determined by a physical examination given at the Zhumadian Central Hospital, were enrolled as the control group. The T lymphocytes, cytokines, IgA, IgG, and IgM immunoglobulins in the peripheral blood of all 3 groups were measured. The clinical efficacy of the immunoglobulins to mitigate the effects of bronchiolitis and the amount of time for the reduction of symptoms to occur were observed. The serum Ca, Fe, and Zn levels of children with severe bronchiolitis were significantly lower than those of the healthy control group (p < 0.05). As such, the CD8, IgA, IgG, IgM and IFN-γ levels were also significantly lower in the children with severe bronchiolitis than in the children in the healthy control group (p < 0.05). Furthermore, the CD4, IgE, IL-4, and IL-4/IFN-γ levels and CD4/CD8 ratio were dramatically higher than in the healthy control group (p < 0.05). Serum levels of the aforementioned indicators either increased or decreased after IVIG treatment. The amount of time required for coughing, wheezing, and pulmonary rales to seize, and the duration of illness for the children with the severe bronchiolitis children was significantly shorter for those in the treatment group than for those in the observation group. Human immunoglobulin via intravenous injection showed active therapeutical effects on trace elements, T lymphocytes, and cytokines in patients with severe bronchiolitis.

To explore the preventive effect of aspirin on the cardiovascular complications in prostate cancer after endocrinotherapy.A total of 92 patients with prostate cancer were divided into observation group (n=44) and control group (n=48). The control group was treated with medical castration plus anti-androgenic drugs. Based on the above treatment, the observation group was added aspirin. The follow-up duration was 2 years. The changes of partial prothrombin time (PT), activated partial thromboplastin time (APTT), platelet aggregation rate (PAG), prostate-specific antigen (PSA) and serum testosterone (T) before and after treatment as well as incidence of cardiovascular disease were observed.The 2-year survival rates of patients without cardiovascular disease in observation group and control group were 95.45% (42/44) and 72.92% (35/48), respectively, and significant difference was presented between two groups by comparison to the survival rates (χ2=8.5453, p=0.0035). There was no statistical significance between two groups as well as before and after treatment regarding PT (p0.05). After treatment, APTT went down and PAG was gradually on the rise in control group, while PAG down and APTT on the rise increasingly in observation group. Significant differences were presented between two groups as well as before and after treatment (p0.01). Both PSA and T levels were decreased significantly in two groups after treatment (p0.01), but there was no statistical significant between two groups (p0.05).Application of endocrinotherapy in prostate cancer can easily lead to occurrence of cardiovascular disease, but cardiovascular complications can be prevented by aspirin, without affecting the effect of endocrinotherapy.

Eight new viridins, nodulisporiviridins A-H (1-8), were isolated from the extract of an endolichenic fungal strain Nodulisporium sp. (No. 65-17-2-1) that was fermented with potato-dextrose broth. The structures were determined using spectroscopic and X-ray crystallographic analysis. Nodulisporiviridins A-D (1-4) are unique viridins with an opened ring A. The Aβ42 aggregation inhibitory activities of 1-8 were evaluated using a thioflavin T (ThT) assay with epigallocatechin gallate (EGCG) as the positive control (EGCG IC50 of 0.5 μM). Nodulisporiviridin G (7) displayed potent inhibitory activity with an IC50 value of 1.2 μM, and the preliminary trend of activity of these viridins as Aβ42 aggregation inhibitors was proposed. The short-term memory assay on an Aβ transgenic drosophila model of Alzheimer's disease showed that all eight compounds improved the short-term memory capacity, with potencies close to that of the positive control (memantine).

Galiellalactone analogs (1-4) (including two new compounds), together with their possible precursors (5-9, named pregaliellalactone B-F), were obtained from the solid cultures of an endophytic fungus Sarcosomataceae NO.45-1-8-1. Their chemical structures were elucidated by analyses of HR ESI-TOF MS, 1D-, 2D-NMR, CD spectra and single crystal X-ray diffraction methods. Compounds 5-9, the possible precursors of galiellalactbne analogs, were found to exist as enantiomers for the first time. The cytotoxicity of these compounds against six tumor cell lines was examined and preliminary structure-activity relationship (SAR) was also discussed. (C) 2015 Elsevier B.V. All rights reserved.

Background PTEN (phosphatase and tensin homolog gene on chromosome 10), a well-characterized tumor suppressor, is a key regulator of the phosphatidylinositol-3-kinase (PI3K)/AKT pathway involved in cell survival, metastasis and cell renewal. PTEN expression is closely related to the phenotype, prognosis and drug selection in breast cancer. It is mainly regulated by transcriptional and post-transcriptional modifications. RNA binding motif protein 38 (RBM38), an RNA-binding protein (RBP) and a target of P53 family, plays a crucial role in the regulation of cellular processing, especially in post-transcription regulation and gene transcription. In this study, we investigated a new post-transcription regulation mechanism of PTEN expression by RBM38 in breast cancer. Methods Immunohistochemistry, lentivirus transfections, Western blotting analysis, qRT-PCR and ELISA were used to conduct the relation between RBM38 and PTEN. RNA immunoprecipitation, RNA electrophoretic mobility shift and dual-luciferase reporter assays were employed to identify the direct binding sites of RBM38 with PTEN transcript. Colony formation assay was conducted to confirm the function of PTEN in RBM38-induced growth suppression. Results PTEN expression was positively associated with the expression of RBM38 in breast cancer tissues and breast cancer cells. Moreover, RBM38 stabilized PTEN transcript to enhance PTEN expression via binding to multiple AU/U- rich elements (AREs) in 3′-untranslated region (3′-UTR) of PTEN transcript. Additionally, specific inhibitors of PTEN activity and small interfering (siRNA) of PTEN expression inhibited RBM38-mediated suppression of proliferation, which implied that RBM38 acted as a tumor suppressor partly by enhancing PTEN expression. Conclusion The present study revealed a new PTEN regulating mechanism that PTEN was positively regulated by RBM38 via stabilizing its transcript stability, which in turn alleviated RBM38-mediated growth suppression. Electronic supplementary material The online version of this article (10.1186/s13046-017-0620-3) contains supplementary material, which is available to authorized users.

Purpose To identify disease-causing gene mutations in 21 northern Chinese families with congenital cataracts. Methods Medical record collection and ophthalmologic examinations were conducted for 21 families with congenital cataracts. A volume of 5 ml of peripheral blood was drawn from each participant for genomic DNA isolation. Thirty-four known candidate genes for congenital cataracts were analyzed in the probands of 21 families with targeted next-generation sequencing (NGS). Bioinformatics analysis of the sequence variants was performed through computational predictive programs. Sanger sequencing was used to perform the cosegregation analysis. Genotyping and haplotype analyses were performed in two patients with a p.V44M mutation in the GJA8 gene. Results Twelve disease-causing mutations were detected in 13 of the 21 patients, and the mutation detection rate was 61.9%. The 12 gene mutations included one nonsense, one splice site, seven missense, and three insert and deletion (INDELs) mutations. Four mutations were novel. Of the 13 patients with pathogenic gene mutations, five (38.5%) were affected by mutations in lens crystallin genes, three (23%) were affected by mutations in connexin genes, three (23%) were affected by mutations in transcription factor genes, one (7.7%) was affected by a mutation in a transmembrane transporter gene, and one (7.7%) was affected by a mutation in a chromatin-modifying protein gene. Two families carried the p.V44M mutation in the GJA8 gene. Haplotype analysis revealed a chromosome region of 475 kb containing the mutation in the GJA8 gene was harbored by two families. Conclusions Compared with traditional Sanger sequencing, targeted NGS for genetic testing of congenital cataracts markedly increases the mutation detection rate and is cost-effective. The p.V44M mutation in the GJA8 gene was the most common mutation and was due to a founder effect within the Chinese cohort studied. The results of this study expand the gene mutation spectrum of congenital cataracts.

Cell proliferation, apoptosis, autophagy, oxidative stress and metabolic dysregulation are the basis of many diseases. Forkhead box transcription factor O1 (FOXO1) changes in response to cellular stimulation and maintains tissue homeostasis during the above-mentioned physiological and pathological processes. Substantial evidences indicate that FOXO1's function depends on the modulation of downstream targets such as apoptosis- and autophagy-associated genes, anti-oxidative stress enzymes, cell cycle arrest genes, and metabolic and immune regulators. In addition, oxidative stress, high glucose and other stimulations induce the regulation of FOXO1 activity via PI3k-Akt, JNK, CBP, Sirtuins, ubiquitin E3 ligases, etc., which mediate multiple signalling pathways. Subsequent post-transcriptional modifications, including phosphorylation, ubiquitination, acetylation, deacetylation, arginine methylation and O-GlcNAcylation, activate or inhibit FOXO1. The regulation of FOXO1 and its role might provide a significant avenue for the prevention and treatment of diseases. However, the subtle mechanisms of the post-transcriptional modifications and the effect of FOXO1 remain elusive and even conflicting in the development of many diseases. The determination of these questions potentially has implications for further research regarding FOXO1 signalling and the identification of targeted drugs.

This study evaluates patients with congenital aniridia and cataract who underwent phacoemulsification, capsular tension ring placement, and foldable intraocular lens implantation. In this prospective case series, 10 patients (17 eyes) underwent cataract surgery via a 3.2 mm clear corneal incision. A continuous circular capsulorhexis with

Background RNA-binding protein 38 (RBM38) is a member of the RNA recognition motif (RRM) family of RNA-binding proteins (RBPs). RBM38 often exerts its function by forming regulatory loops with relevant genes. c-Myc is an oncogenic transcription factor that is upregulated in one-third of breast cancers and involved in many cellular processes in this malignancy. In our previous study, RBM38 was identified as a tumor suppressor in breast cancer. In the present study, we investigated the mechanisms underlying the regulation of this tumor suppressor. Methods Lentivirus transfections, Western blotting analysis, qRT-PCR and immunohistochemistry were employed to study the expression of c-Myc and RBM38. Chromatin immunoprecipitation and dual-luciferase reporter assays were performed to investigate the direct relationship between c-Myc protein and the RBM38 gene. RNA immunoprecipitation combined with dual-luciferase reporter assays was conducted to confirm the direct relationship between the RBM38 protein and the c-Myc transcript. Results Knockdown of c-Myc increased RBM38 expression by binding directly to specific DNA sequences (5′-CACGTG-3′), known as the E-box motif, in the promoter region of RBM38 gene. Additionally, RBM38 destabilized the c-Myc transcript by directly targeting AU-rich elements (AREs) in the 3′-untranslated region (3′-UTR) of c-Myc mRNA to suppress c-Myc expression. Moreover, specific inhibitors of c-Myc transcriptional activity inhibited RBM38-induced suppression of growth, implying that RBM38 acts as a tumor suppressor via a mechanism that depends, at least partially, on the reduction of c-Myc expression in breast cancer. Conclusions RBM38 and c-Myc form a unique mutually antagonistic RBM38-c-Myc loop in breast cancer. Electronic supplementary material The online version of this article (doi:10.1186/s13046-017-0521-5) contains supplementary material, which is available to authorized users.

The aim of this study is to investigate the remission rate of rheumatoid arthritis (RA) in China and identify its potential determinants. A multi-center cross-sectional study was conducted from July 2009 to January 2012. Data were collected by face-to-face interviews of the rheumatology outpatients in 28 tertiary hospitals in China. The remission rates were calculated in 486 RA patients according to different definitions of remission: the Disease Activity Score in 28 joints (DAS28), the Simplified Disease Activity Index (SDAI), the Clinical Disease Activity Index (CDAI), and the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definition. Potential determinants of RA remission were assessed by univariate and multivariate analyses. The remission rates of RA from this multi-center cohort were 8.6 % (DAS28), 8.4 % (SDAI), 8.2 % (CDAI), and 6.8 % (Boolean), respectively. Favorable factors associated with remission were: low Health Assessment Questionnaire (HAQ) score, absence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP), and treatment of methotrexate (MTX) and hydroxychloroquine (HCQ). Younger age was also predictive for the DAS28 and the Boolean remission. Multivariate analyses revealed a low HAQ score, the absence of anti-CCP, and the treatment with HCQ as independent determinants of remission. The clinical remission rate of RA patients was low in China. A low HAQ score, the absence of anti-CCP, and HCQ were significant independent determinants for RA remission.

Two new 4-methyl-progesteroids, nodulisporisteriod A (1) and nodulisporisteriod B (2), were isolated from the extract of an endolichenic fungal strain Nodulisporium sp. (No. 65-17-2-1), along with two related metabolites, demethoxyviridin (3) and inoterpene B (4). Their structures were determined by detailed spectroscopic analyses, X-ray crystallographic analysis and comparison of the NMR data with those of the closely related compounds previously reported. Nodulisporisteriod A (1) and nodulisporisteriod B (2) possess new carbon skeletons, which are the first cases of fission at C-3,4 in 4-methyl-progesteroids. A hypothetical biosynthetic pathway for 1 and 2 was proposed. Moreover, the Aβ42 aggregation inhibitory activities of 1-4 were evaluated using standard thioflavin T (ThT) fluorescence assay with epigallocatechin gallate (EGCG) as positive control. Demethoxyviridin (3) displayed anti-Aβ42 aggregation activity with IC50 value of 13.4μM.

Objective To evaluate visual outcomes and complications after phacoemulsification in eyes with cataract and previous radial keratotomy (RK) cuts using different sizes of clear corneal incisions. Methods The study was a retrospective study. Thirty eyes with cataract and previous RK underwent phacoemulsification and intraocular lens (IOL) implantation. Among them 7 eyes had 8 RK cuts, 13 eyes had 12 RK cuts, and 10 eyes had 16 RK cuts. Phacoemulsification and IOL implantation were performed through a 2.0–3.2 mm clear corneal incision by a single surgeon. In the 8 RK cuts group, 3.2 mm clear corneal incisions were used in 4 eyes, and 3.0 mm clear corneal incisions were used in 3 eyes. In the 12 RK cuts group, 3.2 mm clear corneal incisions were used in 6 eyes, and 2.2 mm clear corneal incisions were used in 7 eyes. In the 16 RK cuts group, 3.2 mm clear corneal incisions were used in 5 eyes, and 2.0 mm clear corneal incisions were used in 5 eyes. Patients were followed up 1 day, 1 week, 1 month, 3 months, 6 months, 1 year, 2 years, and 3 years postoperatively and were examined for the dehiscence of RK cuts during or after the surgery, post-operative best-corrected visual acuity (BCVA), corneal astigmatism, corneal endothelial cell density and complications. Results Successful phacoemulsification with IOL implantation was performed in all eyes. No wound dehiscence was noted in any eyes with 8 or 12 RK cuts. Wound dehiscence was noted in 2 eyes with 16 RK cuts. The dehiscence of RK cuts was closed successfully by injecting an air bubble with or without viscoelastic agent into the anterior chamber at the end of surgery. During the follow-up, the cuts were well apposed in all eyes, and no new dehiscence of RK cuts was noted. At the last follow-up, mean BCVA (0.2 ± 0.18 logMAR) was better than preoperative BCVA(0.45±0.19 logMAR) (P < 0.001). There was no significant difference between the long-term preoperative and postoperative mean corneal astigmatism (P = 0.3). However, there was a significant reduction in postoperative corneal endothelial cell density (1866.5±773.9 / mm2 vs 2421.7±655.7 / mm2) (P < 0.001). Conclusions Phacoemulsification and IOL implantation with clear corneal incisions in eyes with previous RK were associated with good surgical outcomes. Wound dehiscence was not specificaly related to the size of clear corneal incision during phacoemulsification in these eyes.

Anti-cyclic citrullinated peptide (anti-CCP) antibodies have proved to be a specific marker for the diagnosis of rheumatoid arthritis (RA). However, the antibodies can also be detected in other rheumatic diseases, especially systemic lupus erythematosus (SLE). Recent studies have shown anti-CCP antibodies are associated with erosive arthritis in SLE patients. Since erosive arthritis is not common in SLE and many patients with non-erosive arthritis also have anti-CCP antibodies, the clinical significance of anti-CCP antibodies in SLE needs to be further studied.To investigate the prevalence and clinical significance of anti-CCP antibodies in Chinese SLE patients.Serum samples from 138 SLE patients were examined for anti-CCP with the second generation anti-CCP detection kit. The associations of anti-CCP with clinical and laboratory features, especially arthritis, in such SLE patients were analyzed.The prevalence of anti-CCP was 13.8% (19/138) in Chinese SLE patients. Seventy of 138 SLE patients had experienced arthritis, of whom 14 patients were anti-CCP+. Significantly, anti-CCP antibodies were more frequently found in SLE patients with arthritis than without arthritis (20% vs 7.4%, P0.05). A statistical correlation between anti-CCP and rheumatoid factor (RF) was found in SLE patients with arthritis (r=0.36, P=0.002). The frequency of arthritis was significantly higher in SLE patients with anti-CCP than without (73.7% vs 47.1%,P0.05). Eight out of 138 SLE patients showed joint erosions on radiographs. When compared with anti-CCP- patients, erosive arthritis occurred more often in anti-CCP+ patients (35.7% vs 5.4%, P0.001). Interestingly, two patients without anti-CCP and RF who had erosive arthritis were anti-RA33 antibodies positive. All of 8 SLE patients with erosive arthritis in our study fulfilled 1987 ACR criteria for RA. With regard to other clinical and laboratory features, there were no differences between SLE patients with arthritis and without or between anti-CCP+ patients and anti-CCP- patients.Anti-CCP antibodies have a frequency of 13.8% in Chinese SLE patients and its presence is closely associated with the onset of arthritis and bone erosion.

Posttraumatic stress disorder (PTSD) is a severely debilitating anxiety disorder. Over 80% of patients with PTSD also exhibit other psychiatric condition, such as bipolar disorder (BP) or major depression (MDD). Previously, it has been found that p11 mRNA expression was significantly changed in post mortem cortex of patients with PTSD and depression. We hypothesize that p11 mRNA levels in the peripheral blood cells will be a potential biomarker for PTSD with heterogeneity in terms of type of trauma, time since trauma and duration of illness. We examined the peripheral blood mononuclear cell (PBMC) P11 mRNA of patients with PTSD (n=13), major depressive disorder (MDD, n=16), bipolar disorder (BP, n=24), and schizophrenia (SCZ, n=12) or controls (n=14) using quantitative real-time PCR and the circulating levels of cortisol in blood plasma and saliva of PTSD using radioimmunoassay kit CORT-CT2. The Hamilton Rating Scale for Depression (HAMD) and Anxiety (HARS), the Chinese version of the Davidson Trauma Scale-Frequency (CDTS-F) and the Chinese version of the Davidson Trauma Scale-Severity (CDTS-S), and Impact of Event Scale-Revised (IES-R) were administered. We found that patients with PTSD had lower levels of p11 mRNA than control subjects, while those with MDD, BP and SCZ had significantly higher p11 levels than the controls. P11 mRNA levels were positively correlated with the scores of HAMD (r=0.62, p

We had reported that neural stem cells from human fetal striatum (hsNSCs) expressed neural stem cell markers, and were capable of differentiation into neurons, astrocytes, and oligodendrocytes in vitro. To examine multipotency of hsNSCs, some experiments of transgerm layer differentiation in vitro were carried out. Our data indicated that hsNSCs could also generate osteocytes, adipocytes, and hepatocyte-like cells in vitro. Meanwhile, we injected hsNSCs into murine blastocysts at embryonic day 3.5 of gestation. Microinjection of hsNSCs led to the generation of chimeric embryos. Embryos at embryonic day 3.5 of gestation were shown to contribute to the hsNSC-derived cells by PCR-southern blot of 17alphamod, a special method to discover human cells from animals. Analysis of the donor distribution in different tissues showed that donor-derived cells seeded to various tissues. The cellular nature of the human donor cells in chimeric tissues is, however, currently unknown, and further work will be done to identify what differentiated phenotypes have developed from the human cells.

Background The aim of this study was to investigate associations of 3 common polymorphisms in the VEGF gene, −2578C>A, −634C>G, and 936C>T, with risk of tetralogy of Fallot (TOF) in Chinese Han children. Material/Methods From January 2010 to June 2013, a total of 400 pediatric subjects were recruited, including 160 cases with TOF (TOF group) and 240 healthy controls (control group). The genotypes of 3 common VEGF polymorphisms, −2578C>A, −634C>G, and 936C>T, were analyzed by polymerase chain reaction restriction fragment length polymorphism. All data were analyzed with SPSS 18.0 software. Results No significant differences were observed in body mass index or sex between TOF patients and controls (both P>0.05), but significant differences in age and family history of TOF were observed between the 2 groups (both PA of VEGF was correlated with a significantly increased risk of TOF, and TOF risk in A allele carrier was 1.54-fold higher than that of C allele carrier (OR=1.54, 95%CI=1.14–2.09, P=0.005); the statistical significance was still present after Bonferroni correction (Pc=0.045). GG genotype in −634C>G of VEGF gene was also associated with an increased risk of TOF, and TOF risk in patients with G allele was 1.62-fold higher compared to patients with C allele (OR=1.62, 95%CI=1.19–2.21, P=0.002); the statistical significance was still present after Bonferroni correction (Pc=0.018). Interestingly, T allele in VEGF 936C>T polymorphism is associated with a decreased TOF risk (OR=0.65, 95%CI=0.49–0.87, P=0.003, the statistical significance was still present after Bonferroni correction (Pc=0.027). The result of logistic regression analysis revealed that −2578C>A, −634C>G, and 936C>T genotypes are independently related to the prevalence of TOF (all PA and −634C>G, may be associated with an increased TOF risk, while 936C>T polymorphism may be associated with decreased TOF risk.

We reported a case of pulmonary capillary hemangiomatosis (PCH) and introduced its diagnosis, differential diagnosis, pathogenesis and development of treatment based on the review of Dana Point 2008 Classification of Pulmonary Hypertensiona and current literatures. A 43-year-old female presented progressive dyspnea, elevated pulmonary arterial pressures and CT pulmonary angiography (CTPA) imaging of main pulmonary arterial enlargement and wide spread ill-defined centrilobular nodules of ground-glass opacity. Her histologic features were proliferation of capillary channels within alveolar walls as well as muscularization of arterioles and medial hypertrophy of muscular pulmonary arteries. The treatment with diuretics and warfarin was used promptly, but unfortunately was ineffective. The patient died three months after diagnosis. PCH is a very rare vascular disease with poor prognosis. The diagnosis of PCH rests on the integration of clinical and radiographic information with pathologic features, however pathology is the most reliable means. Because clinical symptoms, imaging and histological features of pulmonary veno-occlusive disease (PVOD) and PCH broadly overlap, differential diagnosis should be made carefully. Among the various pathologic features proliferation of capillaries within alveolar walls is the key point for diagnosing PCH, which is also the most critical criteria for differentiating PCH from PVOD. So far the only definitive treatment for PCH is lung transplantation, without which the patient will die several months after diagnosis.

To identify the functions and mechanisms of prostaglandin E2 (PGE2)-induced bone marrow-derived progenitor cells (BMPCs) maturation and its involved angiogenesis.BMPCs harvested by flushing through the femoral and tibial bones and cultured. This population of cells was identified by immunofluorescence staining. From which, 1 μmol/L PGE2 was taken, and quantitative-PCR (Q-PCR) and Western blot were used to detect the expressions of endothelial markers and Kruppel like factor 2 (KLF2) in BMPCs. In vitro tube formation assay was performed to demonstrate the capacity of angiogenesis. Furthermore, PGE2 and its receptors EP2 and EP4 agonists were used to elucidate the regulation of PGE2 to KLF2.C-kit, von Willebrand factor (vWF) and vascular endothelial cadherin expressed in BMPCs. Treatment with PGE2 (1 μmol/L) significantly increased the differentiation of BMPCs. The mRNA levels of endothelial markers platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) and endothelial nitric oxide synthase (eNOS), were significantly upregulated in about 2 folds by PGE2 detected with Q-PCR assay. Matrigel tube formation assay also demonstrated PGE2 enhanced the ability of angiogenesis in BMPCs. In addition, the expression of KLF2 increased in more than 2 folds with PGE2 treatment compared with the control. Such effect of PGE2 could be blocked by EP4 blocking peptide.Promoting the differentiation of BMPCs, PGE2 reinforced their angiogenesis by binding to the receptor of EP4 in a KLF2-dependent manner.

Stachybisbins A (1) and B (2), two new meroterpenoids with unprecedented seco-bisabosqual skeleton, together with three biogenetically related metabolites (3-5), were isolated from a wetland fungal strain of Stachybotrys bisbyi. The structures of the new compounds were determined by spectroscopic analyses, modified Mosher's method, and quantum chemical CD method. The cytotoxic activities of all compounds were tested against HL-60, SMMC-7721, A-549, MCF-7, and SW480 human cancer cell lines. (C) 2015 Elsevier B.V. All rights reserved.

Objective To investigate the impacts of perioperative blood transfusion on the immune function and prognosis in colorectal cancer (CC) patients. Methods A retrospective analysis was conducted in 1404 CC patients, including 1223 sporadic colorectal cancer (SCC) patients and 181 hereditary colorectal cancer (HCC) patients. Among them, 701 SCC and 102 HCC patients received perioperative blood transfusion. The amount of T lymphocyte subsets and natural killer (NK) cells was measured. All patients received a 10-year follow-up and relapse, metastasis and curative conditions were recorded. Results In SCC group, mortality, local recurrence and distant metastasis rate of transfused patients were significantly higher than non-transfused patients (all P 0.05). In HCC group, mortality was apparently higher in transfused patients than non-transfused patients ( P = 0.002). SCC patients transfused with ≥3 U of blood had significantly higher mortality than patients transfused with P = 0.006). The amount of T lymphocyte subsets and NK cells showed statistical differences before and after perioperative blood transfusion in SCC and HCC patients (all P 0.05). Also, there existed statistical differences in CD4+/CD8+ ratio among SCC patients before and after the perioperative blood transfusion ( P 0.05). CC patients who received perioperative blood transfusion had markedly lower 10-year survival rates as compared with those who did not receive (both P 0.05). SCC patients transfused with ≥3 U of blood had remarkably lower survival rates compared with SCC patients transfused with P = 0.002). Conclusions Perioperative blood transfusion could impact immune function, increased postoperative mortality, local recurrence rate and distant metastasis rate in CC patients; and survival rate of CC patients is negatively related to blood transfusion volume.

The purpose of this study was to examine effects of osthole on postmenopausal osteoporosis using ovariectomized (OVX) rats. All of the rats were divided into sham and OVX groups. At 2 weeks post-operation, the sham-operated rats received solvent vehicle (97% corn oil and 3% ethanol, 1.0 ml/kg, subcutaneously); the OVX rats were divided into three groups which were treated with solvent vehicle (same the sham rats, 1.0 ml/kg, subcutaneously), 17beta-estradiol (30 microg/kg, subcutaneously) or osthole (9.0 mg/kg, orally) 5 d/week for 4 weeks, respectively. In OVX rats, the increases of body weight, spleen and thymus weight were significantly decreased and the atrophy of uterus was preserved by 17beta-estradiol treatment, but not by osthole. Treatment with either 17beta-estradiol or osthole significantly protected cancellous bone loss owing to estrogen deficiency and significantly increased the maximal load in the femoral neck of OVX rats. In addition, the increases of serum osteocalcin (OC) and urinary deoxypyridinoline (DPD) levels caused by ovariectomy were all significantly suppressed by 17beta-estradiol. However, only urinary DPD was significantly reduced by osthole and no change was found in serum OC. Our results demonstrate that osthole may be just as effective as 17beta-estradiol in suppressing bone loss due to ovariectomy but osthole perhaps does not work through the estrogen pathway.

This study was aimed to investigate the effects of the intermediate-conductance Ca(2+)-activated K(+) (IKCa1) channels on the proliferation, migration, invasion ability and monoclonal immunoglobulin (IgE) secretion of multiple myeloma (MM) cells. Trypan blue exclusion was used to evaluate the impact of clotrimazole (CLO, an inhibitor of the KCa1) on the survival ability of MM cell line U266; transwell chamber and matrigel experiments were used to evaluate the impact of CLO on the ability of the migration and invasion of U266 cells; the influence of CLO on IgE secretion in U266 cells was detected by ELISA. The results showed that small dose of CLO ( ≤ 1.0 µmol/L) could not inhibit the viability of U266 cells. The Transwell and Matrigel invading tests displayed that the cell number moving into lower chamber of transwell decreased after U266 cells treated with small dose of CLO ( ≤ 1.0 µmol/L). After treating the cells with 1.00 µmol/L CLO for 24 h and 48 h, the concentration of IgE in cell supernatant was (4.98 ± 0.39) and (4.38 ± 0.32) ng/ml, while those in control group were (15.41 ± 1.88) and (19.73 ± 2.01) ng/ml, respectively, suggesting significant difference between them(P0.05). It is concluded that CLO can decrease the ability of migration and monoclonal immunoglobulin secretion of multiple myeloma cells by blocking the IKCa1, thus this study provides a new think for the targeted therapy of MM.

OBJECTIVE: This meta-analysis was performed to evaluate the role of toll-like receptor 4 (TLR-4) in colorectal carcinogenesis. METHODS: The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched from inception through November 1st, 2013 without language restrictions. Odds ratios (ORs) or standardized mean differences (SMD) with their 95% confidence intervals (CI) were calculated. RESULTS: Fourteen case-control studies met the inclusion criteria for this meta-analysis. A total of 1,209 colorectal cancer (CRC) cases and 1,218 healthy controls were involved in this meta-analysis. Two common polymorphisms (299 A>G and 399 C>T) in the TLR-4 gene, TLR-4 mRNA and protein expression were assessed. Our meta-analysis results revealed that the TLR-4 399 C>T polymorphism might increase the risk of CRC (allele model: OR = 1.77, 95%CI = 1.32 ∼ 2.36, PG polymorphism and CRC risk (all P>0.05). A subgroup analysis by ethnicity suggested that TLR-4 genetic polymorphisms were associated with an increased risk of CRC among Asians (allele model: OR = 1.50, 95%CI = 1.19 ∼ 1.88, P = 0.001; dominant model: OR = 1.49, 95%CI = 1.16 ∼ 1.92, P = 0.002; respectively), but not among Caucasians and Africans (all P>0.05). Furthermore, our results showed that TLR-4 mRNA and protein levels in CRC patients were higher than those in healthy controls (TLR-4 mRNA: SMD = 2.51, 95%CI = 0.98 ∼ 4.05, P = 0.001; TLR-4 protein: OR = 4.75, 95%CI = 1.16 ∼ 19.36, P = 0.030; respectively). CONCLUSION: Our findings provide empirical evidence that TLR-4 may play an important role in colorectal carcinogenesis. Thus, TLR-4 is a promising potential biomarker for the early diagnosis of CRC.

To compare the total thyroidectomy or subtotal resection and gland lobe and isthmus lobectomy as initial treatment to TNM stage I and II differentiated thyroid cancer. The difference between recurrence rate and surgical complications were analysed.The literatures published between 1972-2012 were searched in Pubmed, Medline, Wanfang database, Chinese Biomedical Literature Database, Chinese scientific Journals database and China National Knowledge Infrastructure. According to the inclusion and deletion criteria, 17 articles were included to compare the postoperative recurrence and complications in randomized controlled or case-control studies, involving 13 articles in recurrence rate and 11 articles in complications.RevMan5.0 software package was used to perform meta-analysis.Thirteen articles involved with the recurrence rate, the total case number was 3511. Among these cases, 414 recurred, overall recurrence rate was 11.59%, of which, 150 recurred cases in total or subtotal resection group (experimental group), the recurrence rate was 6.51%; 264 recurred cases in gland lobe lobectomy plus isthmus group (control group), the recurrence rate was 21.83%. Comparing the two groups, the odds ratio (OR) and their 95% confidence interval (95%CI) was 0.26 [0.21,0.33], Z value was 11.33, P0.01, which showed that the recurrence rate in experimental group was significantly lower than that in control group.Eleven articles involved with the complications, the total case number was 2388, 166 cases had postoperative complications. The complication rate was 6.95%, of which, 109 cases in experimental group, the complication rate was 8.52%; 57 cases in control group, the complication rate was 5.15%. Compared with the two groups, OR values and their 95%CI was 3.63 [2.47, 5.33], Z was 6.58, P0.01, the experimental group had significantly higher incidence of complications.For I and II differentiated thyroid cancer, total thyroidectomy or subtotal resection may reduce the chance of recurrence, but the postoperative complications is higher; while gland lobe and isthmus lobectomy has lower postoperative complications, but may increase the risk of relapse.

Cytoglobosins H (1) and I (2), together with seven known cytochalasan alkaloids (3–9), were isolated from the deep-sea-derived fungus Chaetomium globosum. The structures of new compounds 1 and 2 were elucidated by extensive 1D and 2D NMR and mass spectroscopic data. All the compounds were evaluated for their antiproliferative activities against MDA-MB-231 human breast cancer cells, LNCaP human prostate cancer cells, and B16F10 mouse melanoma cells. Compound 6 showed significant antiproliferative activity against LNCaP and B16F10 cell lines with IC50 values of 0.62 and 2.78 μM, respectively. Further testing confirmed that compound 6 inhibited the growth of LNCaP cells by inducing apoptosis.

Objective: To evaluate the serious response during tilt-table test (TTT) and its prophylactic management. Method: Seventy-six elderly patients were tested at a tilt angle of 70 degrees for a maximum of 45 min and then subjected to isoproterenol-provocative tilt testing. ECG and blood pressure were monitored during the test and patients were kept at normal saline condition through a peripheral intravenous duct. Results: Fifty-one of 76 patients were defined as positive including 23 having serious response; 6 of the 23 patients had arteriosclerosis involving internal carotid arteries and 7 cases had bradycardia, two of which were associated with II°-I A-V block and the others with chronic atrial fibrillation. The serious response consisted of cardiac arrest for more than 5 s (6 cases), or serious bradycardia for more than 1 min (7 cases) or serious hypotension for more than 1 min (10 cases). Those with serious response were managed by returning to supine position, thus driving up legs and intravenous atropine, CPR (2 cases with cardiac arrest) and needing oxygen supplementation (11 cases). Only 2 hypotension patients recovered gradually by 10 min after emergency management, while others recovered rapidly with no complications. Conclusion: Although non-invasive, TTT may result in serious response, especially in elderly. Therefore proper patient selection, control of isoproterenol infusion and close observation of vital signs are decisive for a safe consequence.

The interaction between stressful life events and leukocyte telomere length is associated with PTSD

Chaetoglobosin Y (1), was isolated from the endolichenic fungal strain Chaetomium globosum (No. 64-5-8-2), along with related six known cytochalasans, chaetoglobosin Fex (2), chaetoglobosin E (3), isochaetoglobosin D (4), chaetoglobosin G (5), cytoglobosin B (6), and cytoglobosin C (7). Their structures were determined by detailed spectroscopic analyses and comparison with those of the closely related compounds previously reported. The cytotoxicity to HCT-116 cell line of 2-7 was evaluated in vitro with doxorubicin as positive control.

To study the epidemic characteristics of human rhinovirus (HRV) in children with acute respiratory infections in Gansu Province. 286 throat swabs were collected from children with acute respiratory in fections in Gansu Province during 2011. Multiplex reverse transcription-PCR (multiplex RT-PCR) assay was used to screen those specimens for detection of common respiratory tract pathogens. For HRV-positive samples, nested reverse transcription polymerase chain reaction (nested RT-PCR) was performed to amplify VP1 and VP4/VP2 gene fragments of HRV. The VP4/VP2 and VP1 regions of HRV-positive samples were sequenced and performed genotype analysis. Of 286 specimens fested, 27 were positive for HRV by multiplex RT-PCR and nested RT-PCR, of which 16 children were made (16/185), 8.64%) and 11 female (11/101,10.89%). The positive rate was 9.44% (27/286). The mean age of HRV-positive children was 3 years in this study, children less than one year old had the highest proportion 44.4% (12/ 27, 44.4%). The highest HRV positive rate fell on May, 2011 (6/27, 22.2%). Common cold accounted for the highest proportion, 12.24% (12/98) followed by pneumonia, 8.50% (13/153). The remaining 2 cases were bronchitis. Sequence analysis showed HRV A was the predominant genotype in Gansu Province in 2011, accounting for 84.62% (22/26) of positive cases, followed by HRV C (11.54%, 3/26) and only one HRV B was detected (3.85%, 1/26). HRV could be detected throughout the year in Gansu Province and primarily infected children under one year old. The group A was the epidemic genotype of HRV and move than one genotype existed in Gansu Province during 2011.

To detect the expression of Robo1 in lung cancer tissues, adjacent non-cancerous tissues as well as lung cancer brain metastasis, and explore the correlation of Robo1 expression to lung cancer brain metastasis.SP (streptavidin-peroxidase) staining method was used to examine the Robo1 expression in specimens from 80 cases of NSCLC, 52 cases of adjacent non-cancerous tissues and 72 cases of lung cancer with single brain metastasis (without metastasis in other organs). The Robo1 expression was further examined in 17 self control cases with lung cancer tissues and their brain metastasis tissues. The results were assessed by Kaplan-Meier analysis and log-rank test.The positive expression rate of Robo1 among adjacent non-cancerous tissues, lung cancers tissues and the lung cancer brain metastasis tissues were 1.9% (1/52), 13.8% (11/80) and 40.3% (29/72), respectively, and significant differences were detected among them (P0.05). During the 17 self control cases, the positive expression rate of Robo1 in lung cancer tissue and their brain metastasis tissues were 17.6% and 64.7%, respectively, with a significant difference between them (P0.01). Among the 72 cases of lung cancer brain metastasis, the median survival time of cases with positive Robo1 expression was 10 months, significantly shorter than that of cases with negative expression of Robo1 (17 months, P0.05).The positive expression rate of Robo1 was increased in sequence from the lowest in adjacent non-cancerous tissues, intermediate in the lung cancer tissues to highest in the lung cancer brain metastasis tissues. The expression of Robo1 in lung cancer brain metastasis is negatively correlated with the prognosis of patients with lung cancer brain metastasis. Robo1 may promote the genesis and progression of lung cancer and lung cancer brain metastasis as a cancer-promoting oncogene.

Two new naphthaline glucosides, 2-hydroxy-3-methoxy-8-methyl-1-O-β-d-glucopyranosylnaphthaline (1) and 1-hydroxy-3-methoxy-8-methyl-2-O-β-d-glucopyranosylnaphthaline (2), together with one new isocoumarin glucoside, 3-(3,3-dichloro-2-hydroxylpropyl)-6-methoxy-8-O-β-d-glucopyranosyl-1H-isochromen-1-one (3), were isolated from a cold-adapted fungal strain Mucor sp. (No. XJ07027-5). Their structures were characterized by detailed analyses of IR, MS, 1D- and 2D-NMR spectra. Among them, 2 showed moderate cytotoxic activity against five tumor cells (A-549, HL-60, MCF-7, SMMC-7721, and SW480).

Five new xanthoquinodins, A4-A6 (1-3), B4 (4), and B5 (5), were isolated from the crude extract of the endolichenic fungal strain Chaetomium elatum (No. 63-10-3-1), along with three known xanthoquinodins, A1-A3 (6-8). Their structures were determined by detailed spectroscopic analysis and comparison of the NMR data with those of the closely related compounds previously reported. The absolute configuration of 1 was established by X-ray crystallographic analysis and ECD calculation. The cytotoxic activity of all compounds was tested against HL-60, SMMC-7721, A-549, MCF-7, and SW480 human cancer cell lines.

Brain-derived neurotrophic factor (BDNF), which regulates neuronal survival, growth, differentiation and synapse formation, broadly regulates the stress response.1 A common single-nucleotide polymorphism in the BDNF gene (Val66Met) influences hippocampal volume,2 memory3 and appears related to susceptibility to a variety of neuropsychiatric disorders, including posttraumatic stress disorder (PTSD).1 Therefore, we hypothesized that BDNF may be an important mediator of the abnormal stress response contributing to PTSD. We analyzed genetic variation in 461 and the plasma levels of BDNF in 68 US. Army Special Operations soldiers deployed during the Iraq and Afghanistan wars. A probable-PTSD diagnosis was made if subjects endorsed Diagnostic and Statistical Manual of Mental Disorders-IV PTSD criteria (at least one re-experiencing, three avoidance and two hyper-arousal symptoms) and had a total PTSD check list (PCL) score of 50 or above (see Supplementary Methods). We found that 42 (9%) participants met criteria for probable-PTSD, while the remaining 419 (91%) subjects did not. In those with probable-PTSD, the frequency of Met/Met was nearly threefold higher than in the controls. The allelic frequency of Met was twofold higher in individuals with probable-PTSD than in controls (Supplementary Information). BDNF levels in plasma of the subjects with PTSD were significantly higher than those in the non-PTSD controls. These results agree with evidence suggesting that BDNF is involved in the development of PTSD.1 Met carriers have a smaller hippocampus volume, relative to controls2 and perform more poorly than controls (Val/Val) on memory tasks.4 Veterans with psychotic PTSD carry more Met alleles than non-psychotic veterans with PTSD or veterans without PTSD,5 even though a case–control genetic association study showed no relationship between BDNF gene Val66Met and PTSD diagnosis.6

The technology of tongue near-infrared reflectance spectra was used for human serum total protein (TP) content of noninvasive testing for the first time. Reflectance spectrum on the tongue tips of 58 volunteers was collected, and the biochemical values of serum total protein were recorded at the same time. The samples were separated into two parts: training set and prediction set. Two prediction models were established using PCA combined with BP neural network and PLS. Using PCA-BP model to predict the prediction set, the average relative error is 7.35%, RMSEP was 6.3771 g x L(-1), and the correlation coefficient was 0.9021. Using PLS model to predict the prediction set, the average relative error is 4.77%, RMSEP was 0.1304 g x L(-1), and the correlation coefficient was 0.9718. It was approved that reflectance spectra of tongue can be used to predict TP accurately and noninvasively.

The aim of this study was to perform a meta-analysis to evaluated the association between interleukin-1β (IL-1β) C(3953/4)T polymorphism and chronic periodontitis (CP). Systematic searches of electronic databases and hand searching of references were performed, including PubMed, Embase and Web of Science. The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated. Publication bias was tested by Begg’s funnel plot and Egger’s regression test. Sensitivity analysis was conducted by limiting the meta-analysis studies conforming to Hardy–Weinberg equilibrium (HWE) or high quality (score ⩾ 7). Data analyses were carried out by Stata 11.0. There were significant associations between IL-1β C(3953/4)T polymorphism and CP (for T allele vs. C allele: OR = 1.30, 95%CI = 1.05–1.60, p = 0.02; for T/T vs. C/C: OR = 1.66, 95%CI = 1.12–2.45, p = 0.01; for C/T + T/T vs. C/C: OR = 1.28, 95%CI = 0.99–1.65; and for T/T vs. C/T + C/C: OR = 1.62, 95%CI = 1.15–2.29, p = 0.006). When stratified by ethnicity, statistically significantly elevated risk was found for Caucasians, but not for Asians. When stratified by study design, evidences of significant association was observed between IL-1β C(3953/4)T polymorphism and CP in both population-based studies and hospital-based studies. This meta-analysis indicates that there is strong evidence for association between IL-1β C(3953/4)T polymorphism and CP.