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To evaluate whether the results of the health-related quality of life (HRQOL) is associated with the various clinical aspects of intermittent exotropia in children. The HRQOL of children and their parents was evaluated prospectively using the Intermittent Exotropia Questionnaire (IXTQ). The deviation angle, stereo function, sensory fusion, and strabismus control were measured. Two hundred and sixty six children with intermittent exotropia (aged 5–17 years) were included in the study. Child HRQOL was significantly correlated with clinical severity; lower IXTQ scores were associated with a larger deviation (p

Background: miR-142-3p has proved to be involved in tumorigenesis and the development of renal cell carcinoma. The present study aimed to explore the prognostic value of miR-142-3p. Methods: Total RNA was extracted from renal cell carcinoma specimens and the expression level of miR-142-3p was measured. Pearson Chi-square test, Kaplan–Meier analysis, as well as univariate and multivariate regression analysis were performed to determine the correlation between miR-142-3p and the prognosis of renal cell carcinoma patients. Receiver operating characteristic curves were constructed to evaluate the predictive efficiency of miR-142-3p for the prognosis of renal cell carcinoma patients. Data from The Cancer Genome Atlas (TCGA) were utilized to validate our findings. Results: Our results demonstrated that upregulation of miR-142-3p was correlated with shorter overall survival (P=0.002) and was, in the meantime, an independent prognostic factor for renal cell carcinoma patients (P=0.002). The receiver operating characteristic curve combining miR-142-3p expression with tumor stage showed an area under the curve of 0.633 (95% confidence interval 0.563, 0.702). The result of TCGA data was consistent with our findings. Conclusions: Our results suggest miR-142-3p expression is correlated with poor prognosis of renal cell carcinoma patients and may serve as a prognostic biomarker in the future.

Hepatocellular carcinoma (HCC) is one of the most frequently occurring cancer worldwide and the fifth most common malignancy. The Hippo pathway has been found to play a critical role in cancer development. YAP, a transcriptional coactivator, is the major downstream effector of the Hippo signaling pathway. Hypocrellin A (HA), a natural perylenequinone light-sensitive compound, is usually used for the therapy of eukoplakia of the vulva and keloids in China. Oleanolic acid (OA), a pentacyclic triterpene compound, is prevalent in the treatment of human liver diseases such as viral hepatitis. In this study, we aimed to explore the mechanism by which HA modulates the Hippo/YAP signaling pathway in HCC cells and the anticancer effect of HA combined with OA. Treatment with HA resulted in a decrease in cell viability and migration in HCC cells. Furthermore, we found that HA decreased the YAP and TEAD protein levels of the Hippo pathway. Next we demonstrated that HA could potentiate OA's effect on HCC cells. Our results indicated that HA could inhibit the growth of HCC cells in darkness through Hippo-YAP signaling and HA combined with OA had a better effect than HA or OA alone.Thus, our results provide an alternative combinational inhibitor to combat hepatocellular carcinoma diseases.

PurposeRecently, Eyetronix Flicker Glass (EFG) has been introduced as a novel treatment for amblyopia. It alternatively deprives the visual input of each eye rapidly (e.g., 7 Hz). However, whether it is comparable with standard patching therapy is unclear. In this randomized clinical trial, we evaluate the efficacy of an EFG therapy as treatment for amblyopia in children and compare it to the patching therapy.MethodsWe tested 31 children (aged 4–13 years) with amblyopia. They were assigned into one of the two treatment groups and were treated for 12 weeks. The first group was treated with EFG for 1 h/day (Flicker Group) and the latter with a standard patch (Patching Group) for 2 h/day. We designated changes from baseline in best-corrected visual acuity (BCVA) of the amblyopic eye as our primary outcome. Changes from baseline in other visual outcomes, such as contrast sensitivity, stereopsis, and fusional vergence range were measured as secondary outcome.ResultsBCVA improved significantly at 12 weeks relative to baseline in both the Flicker (0.13 ± 0.11 logMAR; mean ± SD) and Patching Groups (0.21 ± 0.14 logMAR). However, the improvements were not significantly different between groups (p = 0.13). Contrast sensitivity also significantly improved at 3 and 12 cycles/degree between baseline and 12 weeks in both groups (p’s < 0.05). However, stereopsis and fusion range did not improve significantly in both groups.ConclusionAn EFG therapy and patching improved BCVA similarly for children with amblyopia at 12 weeks. Both therapies improved the contrast sensitivity at 3 and 12 cycles per degree (cpd); however, only patching improved the contrast sensitivity at 6 cpd. Both therapies did not benefit binocular visual functions (stereopsis and fusional vergence range). We believe that EFG can be an additional choice for therapy.Clinical Trial Registrationchictr.org number: ChiCTR2000034436.

Screening of CRC continues to show poor compliance of endoscopy examination. The detection of mSEPT9 in peripheral blood is among the safe and simple early screening methods for CRC. The issue of how to elucidate whether detection of mSEPT9 in peripheral blood can effectively improve compliance of endoscopy and increase the early diagnosis rate of CRC and the relationship between levels of mSEPT9 in the peripheral blood and clinical stage, pathological classification, and expression of characteristic molecules in CRC remains unsolved. A total of 7759 individuals participated in the study that was performed using a questionnaire for screening of high-risk CRC. The endoscopic detection compliance of individuals with high-risk CRC who underwent the fecal occult blood test (FOBT) or mSEPT9 test was compared based on the results of the questionnaire. Additionally, correlation of mSEPT9 levels in the peripheral blood with clinicopathological features, mutation status of TP53, mismatch repair deficiency (dMMR), and KRAS/NRAS/BRAF/PIK3CA genotype was analyzed, and association of biomarkers with cancer-specific survival (CSS) and time to recurrence (TTR) was compared. We also detected levels of mSEPT9 in the peripheral blood of patients with CRC 7 days after surgery and compared the prognostic value of mSEPT9 with CEA. Results of our study showed that the mSEPT9 test could improve compliance of endoscopy and indicated a higher percentage of patients with positive mSEPT9 willing to undergo endoscopy detection than in those with positive FOBT. The specificity and sensitivity of mSEPT9 were better than that of FOBT for the detection of CRC. mSEPT9 was associated with the TNM stage, dMMR, and mutations in TP53, BRAF, and PIK3CA. A Ct value of mSEPT9 ≤ 37.5 was significantly related to poor CSS. mSEPT9 could affect association of dMMR and BRAF and PIK3CA mutations with CSS in a specific stage of CRC. The positive rate of mSEPT9 after surgery was found to correlate with poor TTR, and sensitivity was higher than CEA. The combination of mSEPT9 with CEA had a better prognostic value than that of mSEPT9 alone. The level of mSEPT9 was related to dMMR, mutations in TP53, BRAF, and PIK3CA, and was an effective biomarker for the prognosis of patients with CRC.

Background The Rapid Assessment of Hearing Loss (RAHL) survey protocol aims to measure the prevalence and causes of hearing loss in a low cost and rapid manner, to inform planning of ear and hearing services. This paper reports on the first field-test of the RAHL in Gao’an County, Jiangxi Province, China. This study aimed to 1) To report on the feasibility of RAHL; 2) report on the estimated prevalence and causes of hearing loss in Gao’an. Methods A cross-sectional population-based survey was conducted in September–October 2018. Forty-seven clusters in Gao’an County were selected using probability-proportionate-to-size sampling. Within clusters, compact segment sampling was conducted to select 30 people aged 50+. A questionnaire was completed covering sociodemographics, hearing health, and risk factors. Automated pure-tone audiometry was completed for all participants, using smartphone-based audiometry (hearTest), at 0.5, 1, 2, 4 kHz (kHz). All participants had their ears examined by an Ear Nose and Throat (ENT) doctor, using otoscopy, and probable causes of hearing loss assigned. Prevalence estimates were age and sex standardised to the Jiangxi population. Feasibility of a cluster size of 30 was examined by assessing the response rate, and the proportion of clusters completed in 1 day. Results 1344 of 1421 eligible participants completed the survey (94.6%). 100% of clusters were completed in 1 day. The survey was completed in 4.5 weeks. The prevalence of moderate or greater hearing loss (pure-tone average of 0.5, 1, 2, 4 kHz of > = 41dBHL in the better ear) was 16.3% (95% CI = 14.3, 18.5) and for any level of hearing loss (pure-tone average of > = 26dBHL in the better ear) the prevalence was 53.2% (95% CI = 49.2, 57.1). The majority of hearing loss was due to acquired sensorineural causes (91.7% left; 92.1% right). Overall 54.0% of the population aged 50+ (108,000 people) are in need of diagnostic audiology services, 3.4% were in need of wax removal (7000 people), and 4.8% were in need of surgical services (9500 people). Hearing aid coverage was 0.4%. Conclusion The RAHL survey protocol is feasible, demonstrated through the number of people examined per day, and the high response rate. The survey was completed in a much shorter period than previous all-age surveys in China. Some remaining challenges included assignment of causes of probable sensorineural loss. The data obtained from this survey can be used to scale-up hearing services in Gao’an.

Background MicroRNA(miRNA) plays a key regulatory role in various stages of tumorigenesis, including cell growth, cell cycle control, apoptosis avoidance, tissue invasion, and metastasis. Several microRNAs are involved in the development of renal cell carcinoma (RCC) and the malignant transformation process. However, the effects of miR-663a on RCC have rarely been reported. Methods In the present study, the expression of miR-663a was examined in RCC using matched normal kidney tissues and four cell lines (786-O, Caki-1, ACHN and HK-2). MicroRNA mimics were transiently transfected into RCC cells and the effects of over expression on proliferation, migration, invasion, and apoptosis was observed. In addition, the relationship between miR-663a expression in 42 formalin-fixed paraffin-embedded (FFPE) clear cell renal carcinoma (ccRCC) samples and clinical pathological variables and overall survival was investigated. We evaluated the prognostic value of miR-663a expression in ccRCC by experimental results. Results The results showed that the expression of miR-663a was up-regulated in RCC cells and tissues and miR-663a was associated with proliferation, migration, invasion, and apoptosis of RCC. Cox proportional hazard regression analysis showed that a high expression of miR-663a patients had a significantly shorter overall survival in univariate and multivariate analysis. Kaplan-Meier survival curves showed that a high expression of miR-663a patients had a significantly shorter overall survival. Conclusions These results indicate that miR-663a can be used as an independent marker for the poor prognosis of ccRCC, and may also play an important role as a tumor oncogene in the occurrence and development of RCC.

Background Bladder cancer, the ninth-most-common malignancy worldwide with an estimated 356,000 new cases and 145,000 deaths annually, has a propensity to relapse, requiring lifelong monitoring after diagnosis. 75% patients diagnosed with BC are non-muscle invasive BC and over 50% of them experience recurrences within 6–12 years of initial diagnosis. miRNA are small, noncoding RNA and shown to be oncogenes or anti-oncogenes in bladder cancer, contributing to numerous BC cell processes, including cell proliferation, differentiation, migration and apoptosis. Methods RT-qPCR were performed to detect the expression of miR-187-5p in tissues and cell lines, After which, clinicopathological variables and the prognostic value of altered miR-187-5p expression in BC was analyzed with the 48 formalin-fixed paraffin-embedded BC samples. Moreover, Cell functional assays (wound healing assay, CCK-8 assay, transwell assay and flow cytometry assay) were performed to explore the relationship between miR-187-5p expression and cell proliferation, migration, invasion and apoptosis in BC. Results Up-regulation of miR-187-5p was observed in BC tissues and BC cell lines. Cox proportional hazard regression analysis demonstrated that the patients with low expression of miR-187-5p experience lower risks of recurrence in the univariate and multivariate analysis. The Kaplan-Meier recurrence-free curves suggested that the patients with low expression of miR-187-5p experience lower risks of recurrence. Up-regulation of miR-187-5p promotes cell proliferation and mobility and inhibits the apoptosis of 5637 and UM-UC-3 cell, while down-regulation of miR-187-5p reverses these effects. Conclusions The results of our study demonstrated that oncogene miR-187-5p is associated with cellular proliferation, migration, invasion, apoptosis and an increased risk of recurrence in bladder cancer.

A neuromodulatory role for dopamine has been reported for magnocellular neuroendocrine cells in the mammalian hypothalamus. We examined its potential role as a local intercellular messenger in the neuroendocrine Dahlgren cell population of the caudal neurosecretory system (CNSS) of the euryhaline flounder Paralichthys olivaceus . In vitro application of dopamine (DA) caused an increase in electrical activity (firing frequency, recorded extracellularly) of Dahlgren cells, recruitment of previously silent cells, together with a greater proportion of cells showing phasic (irregular) activity. The dopamine precursor, levodopa (L-DOPA), also increased firing frequency, cell recruitment and enhanced bursting and tonic activity. The effect of dopamine was blocked by the D1, D5 receptor antagonist SCH23390, but not by the D2, D3, D4 receptor antagonist amisulpride. Transcriptome sequencing revealed that all DA receptors (D1, D2, D3, D4, and D5) were present in the flounder CNSS. However, quantitative RT-PCR revealed that D5 receptor mRNA expression was significantly increased in the CNSS following dopamine superfusion. These findings suggest that dopamine may modulate CNSS activity in vivo , and therefore neurosecretory output, through D5 receptors.

Background Chemotherapy resistance remains a major challenge in cancer treatment. COX-2 (cyclooxygenase 2) is involved in drug resistance and poor prognosis of many neoplastic diseases or cancers. However, investigations identifying new modulators of COX-2 pathway and searching for new chemicals targeting these valid resistant biomarkers are still greatly needed. Methods HCT15, HCT-116, HT-29, COLO205, FHC, IMCE, SW480 cell lines were used to detect the expression of YAP and COX-2. Site-directed mutagenesis, luciferase reporter analysis and ChIP assay were used to test whether YAP activated COX-2 transcription through interaction with TEAD binding sites in the promoter of COX-2. Cell line models exhibiting overexpression or knockdown of some genes were generated using transfection agents. Coimmunoprecipitation was used to detect protein mutual interaction. mRNA and protein levels were measured by qRT-PCR and western blot respectively. Results Here, we reported that both YAP and COX-2 were overexpressed in colorectal cancer cells. YAP increased COX-2 expression at the level of transcription requiring intact TEAD binding sites in the COX-2 promoter. YAP conferred drug resistance through COX-2 and its related effectors such as MCL, MDR, Survivin. GCCSysm-4 (G-4), a YAP and COX-2 inhibitor, effectively inhibited both YAP and COX-2 activation, induced apoptosis and decreased viability in Taxol-resistant cells. Inhibition of YAP and COX-2 acted synergistically and more efficiently reduced the resistance of CRC cells than either of them alone. Conclusions Our data provide new mechanisms that YAP is a new upstream regulator of COX-2 pathway and plays an important role in conferring resistance in CRC cells. G-4, targeting YAP-COX-2, may be a novel valuable strategy to combat resistance in CRC. Electronic supplementary material The online version of this article (10.1186/s13046-017-0612-3) contains supplementary material, which is available to authorized users.

Many inconsistent findings are reported on the correlation between circulating betatrophin and insulin resistance in the different population. The aim of this analysis was to explore the correlation between the level of betatrophin and insulin resistance in the general population. The databases of PubMed, EMBASE, and the Cochrane Library (inception to October 26, 2016) were searched without language restrictions for publications that reported studies on associations between betatrophin and insulin resistance in adults. Subgroup analyses were performed to investigate potential sources of heterogeneity. The pooled effect size was calculated using a random-effects model. Twenty-five studies were included in this meta-analysis. Meta-analysis showed that betatrophin was positively and significantly correlated with insulin resistance (r=0.16, 95% CI: 0.08–0.25). When all participants were divided into DM, GDM, and Non-DM groups, this association was also significant in T2DM, GDM, and Non-DM participants (T2DM: r=0.09, 95% CI: 0.01–0.17; I 2=45.1%; GDM: r=0.39, 95% CI: 0.24–0.55; I 2=0.0%; non-DM: r=0.15, 95% CI: 0.04–0.26; I 2=89.3%), and it was obvious that heterogeneity existed in Non-DM group (I 2=89.3%, p

Background Cryptosporidium spp. and Giardia duodenalis are major intestinal pathogens that can cause diarrheal diseases in humans, especially children. Enterocytozoon bieneusi is another parasite which can cause gastrointestinal tract disorders, with diarrhea being the main clinical symptom. However, few genetic studies of these parasites in pediatric inpatients in China have been published. Methods To assess the genetic characteristics and epidemiological status of these parasites, a total of 2284 fecal samples were collected from children in the pediatric departments of three hospitals in Zhengzhou, central China, and screened for these protozoans with PCR, based on the small subunit ribosomal RNA (SSU rRNA) genes of Cryptosporidium spp. and G. duodenalis and the internal transcribed spacer (ITS) of E. bieneusi. Results Six (0.26%), 14 (0.61%), and 27 (1.18%) of the samples were positive for Cryptosporidium spp., G. duodenalis and E. bieneusi, respectively. Of the 12 successfully sequenced G. duodenalis isolates, four were identified as assemblage A and eight as assemblage B. In subtype and multilocus genotype (MLG) analyses, C. parvum IIdA19G1 (n = 4) and two novel G. duodenalis MLGs belonging to subassemblage AII (n = 3) and BIV (n = 5) were successfully identified. The E. bieneusi isolates included genotypes D (n = 17), J (n = 2), PigEBITS7 (n = 1), BEB6 (n = 1), and CM8 (n = 1). This is the first report of C. parvum subtype IIdA19G1 in HIV-negative children and E. bieneusi genotype CM8 in humans. Conclusions The dominance of zoonotic C. parvum subtype IIdA19G1 indicates that this parasite is turning into zoonotic origin from human-to-human transmission. The phylogenetic analysis also revealed the zoonotic origins and anthroponotic transmission potential of G. duodenalis and E. bieneusi, suggesting more efforts must be made to minimize the threat these pathogens pose to public health.

Background Cocoon abdomen is a relatively rare abdominal disease characterized by the total or partial encasement of the small intestinal by a dense fibro-collagenous membrane. Case presentation We reported an unusual case of idiopathic cocoon abdomen with congenital colon malrotation. Laparotomy and sac release were performed on the patient. The patient was no recurrence 6 months after operation. A literature review was also performed. Conclusion Preoperative diagnosis of abdominal cocoon is difficult. A careful history, physical examination and appropriate radiology may be helpful in making a definitive diagnosis. If conservative treatment can’t relieve symptoms effectively, surgery is currently considered to be important in the management of this disease.

Background Upregulation of staphylococcal nuclease domain-containing protein 1 (SND1) is a common phenomenon in different human malignant tissues. However, little information is available on the underlying mechanisms through which SND1 affects glioma cell proliferation and invasion. Methods SND1, Ras homolog family member A (RhoA), and marker of proliferation Ki-67 (MKI67) were analyzed in 187 gliomas by immunostaining. The correlation between those markers and patients' prognoses was assessed using the Kaplan-Meier estimator. Gene Ontology, chromatin immunoprecipitation, electrophoretic mobility shift assay, and chromosome conformation capture were applied to identify SND1-activated target genes. We also used MTT, colony formation, transwell and orthotopic implantation assays to investigate SND1 function in glioma cell proliferative and invasive activity. Results We identified SND1 and RhoA as independent predictors of poor prognosis in glioma patients. SND1 knockdown significantly suppressed the proliferation and invasion of glioma cells. Mechanistically, we discovered that SND1 facilitated malignant glioma phenotypes by epigenetically inducing chromatin topological interaction, which activated downstream RhoA transcription. RhoA sequentially regulated expression of CCND1, CCNE1, CDK4, and CDKN1B and accelerated G1/S phase transition in glioma cell proliferation. Conclusions Our findings identify SND1 as a novel chromatin architectural modifier and promising prognostic indicator for glioma classification and treatment.

γ-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervous system. We investigated its potential role as a neurotransmitter in the neuroendocrine Dahlgren cell population of the caudal neurosecretory system (CNSS) of the flounder Paralichthys olivaceus. The application of GABA in vitro resulted in a decrease in electrical activity of Dahlgren cells, followed by an increase of the number of silent cells, together with a decreased firing frequency of all three activity patterns (tonic, phasic, bursting). GABAA receptor agonist etomidate decreased Dahlgren cell firing activity, in a similar way to GABA. The response to GABA was blocked by the GABAA receptor antagonist bicuculline. GABAA receptor gamma2 subunit (Gabrg2) and chloride channel (Clcn2) mRNA expression were significantly upregulated in the CNSS after GABA superfusion. These data suggest that GABA may modulate CNSS activity in vivo mediated by GABAA receptors.

Accurate prediction of the environmental fate of Pb depends on the understanding of Pb coordination to mineral surfaces. Here, the proton and Pb adsorption and speciation on hematite nanocrystals with different exposed crystallographic facets were investigated. High-resolution transmission electron microscopy images revealed that hematite nanoplates (HNP) were of 75.3 ± 9.5% (001) facets and 24.6 ± 9.3% (012) facets, while hematite nanocubes (HNC) were of 76.0 ± 11.1% (012) facets and 24.0 ± 3.2% (110) facets. Our modeling results revealed that the proton affinity constant (log KH) of ≡FeOH−0.5 and ≡Fe3O−0.5 was 7.8 and 10.8 on hematite (012) facets, and changed to 7.7 and 11.7 on (110) facets, respectively. Owing to the different atomic arrangements, (012) facets not only have higher adsorption performance for Pb, but also present a greater dependence on pH than (110) facets. Additionally, our modeling further indicated that (012) facets bind Pb via both bidentate and tridentate complexes, while (110) facets bind Pb only through bidentate complexes at pH 3.0–6.5. These results facilitate a more detailed understanding of the complex species of Pb on hematite surface while also provide new insight into the reactivity mechanism of individual hematite facets.

Background Several studies have evaluated the effects of oolong tea extracts on obesity. However, only few studies focused on the anti-obesity effect of specific components of oolong tea. Objective This study investigated the specific anti-obesity capabilities of oolong tea polysaccharide (TPS) and tea polyphenols (TPP) in high-fat diet-induced Sprague-Dawley rats. Methods Oolong tea water extract, TPS, TPP, and polysaccharide mixed with polyphenol (TPSM) given at doses of 400 or 800 mg/kg were administered to rats fed with high-fat diet for 6 weeks to explore the anti-obesity effects of the treatments. Results TPS and TPP were responsible for the suppressive effect on body fat accumulation. TPSM exhibited the highest effect on body weight reduction, and TPS and TPP effectively reduced serum leptin levels and significantly improved blood lipid and antioxidant levels. Moreover, microarray analysis of hepatic and adipose gene expression profiles revealed that TPP and TPS inhibited obesity through effects on the pathways of fatty acid biosynthesis, steroid hormone biosynthesis, unsaturated fatty acid biosynthesis, fatty acid elongation, glycerolipid metabolism, and glycerophospholipid metabolism. Conclusions TPSM might be a potential therapy for the treatment of obesity.

Objective The present study aims to determine the association of microRNA-106b-5p (miR-106b-5p) expression with the clinicopathological features and prognosis of renal cell carcinoma (RCC). Patents and methods The formalin-fixed paraffin-embedded(FFPE) Tumor tissues were collected from 284 RCC patients. The expression of miR-106b-5p was examined by Reverse Transcription Real-time Quantitative Polymerase Chain Reaction (RT-qPCR), followed by correlation analysis with clinicopathological features and prognosis. Patient survival analysis was determined by the Kaplan-Meier method using the log-rank test was used for patient survival analysis, and the univariate and multivariate analysis was determined by a Cox’s regression model. Results Kaplan-Meier analysis indicated that patients with high miR-106b-5p expression showed a significantly shorter overall survival, compared with patients with low miR-106b-5p expression (p = 0.001). Univariate and multivariate analysis considered miR-106b-5p expression as an independent risk factor for predicting the prognosis of RCC patients. No significant evident showed that the expression level of miR-106b was related to gender, age, tumor size or tumor stage. Also, the results above were verified by analyzing the data of 506 cases from The Cancer Genome Atlas database (TCGA). Conclusions The results pointed out that the high expression of miR-106b-5p serves as an independent factor for predicting the worse prognosis of RCC patients.

Background Bladder cancer is the most common urogenital tumor with substantial morbidity, high recurrence rate and mortality. miRNAs, a class of endogenous noncoding RNA, were found to involve in the genesis, maintenance and metastasis of cancer. Genomic profiling revealed that miR-302b is down-regulated in bladder cancer while its functions in bladder cancer remain to be ascertained. Methods Cell functional assays including wound healing assay, CCK-8 assay, Transwell assay and flow cytometry assay were performed to clarify the functions of miR-302b expression in cell proliferation, migration, invasion and apoptosis in BC. Furthermore, RT-qPCR was performed to study the expression of miR-302b in bladder cancer tissues and the prognostic value of altered miR-302b expression with 48 formalin-fixed paraffin-embedded bladder urothelial carcinoma samples. Results The results of RT-qPCR demonstrated that expression level of miR-302b was significantly reduced in bladder cancer tissues and cell lines. The cells after transfected with miR-302b mimic showed lower mobility, lower proliferation and increased apoptosis, while opposite results were obtained after inhibiting the expression of miR-302b. The prognosis analysis demonstrated that the patients with low expression of miR-302b experienced high risks of recurrence. Conclusions The results of our study demonstrate that miR-302b regulates cell functions and acts as a potential biomarker to predict recurrence in bladder cancer.

The aim of the present study was to investigate the role of microRNA (miR)‑222‑3p in renal cell carcinoma (RCC). The expression level of miR‑222‑3p was detected in RCC tissues and cell lines (ACHN, 786‑O, Caki‑1 and 769‑P) and was identified to be significantly upregulated compared with the level in adjacent normal renal tissues and HK‑2 cells. Further in vitro experiments demonstrated that the over-expression of miR‑222‑3p promoted the migration and invasion, and attenuated the apoptosis of 786‑O cells, whereas the knockdown of miR‑222‑3p suppressed the migration and invasion and induced the apoptosis of 786‑O cells. Similar results were observed in the ACHN cell line in terms of migration, invasion and apoptosis. Furthermore, the expression level of miR‑222‑3p was measured in 42 RCC formaldehyde‑fixed paraffin‑embedded samples, and the association between the expression of miR‑222‑3p and the pathological characteristics and overall survival rate of patients with RCC was analyzed. The results demonstrated that patients with a higher expression of miR‑222‑3p had a significantly lower overall survival rate, compared with those with a lower expression of miR‑222‑3p [hazard ratio (HR)=5.120; P=0.036]. Multivariate analysis identified that patients with a higher expression of miR‑222‑3p retained the statistically significant decrease in overall survival rate compared with patients with a lower expression of miR‑222‑3p (HR=5.636; P=0.030). Furthermore, Kaplan‑Meier survival curves indicated that patients with higher miR‑222‑3p had significantly lower overall survival rates compared with patients with lower miR‑222‑3p (P=0.020). Taken together, these results suggested that miR‑222‑3p serves as an onco‑miR in RCC and may be a potential prognostic biomarker and therapeutic target in patients with RCC.

Aims In adult population, the renal cell carcinoma (RCC) is one of the most common urological malignancies. It is meaningful to research for the molecular markers which are involved in the occurrence and development of RCC. Therefore, we concentrate on illuminating the role of microRNA-154-5p in progression of RCC and explore its prognostic values. Main methods The real-time quantitative polymerase chain reaction (RT-qPCR) was applied to determine expression level of miR-154-5p in tissues. Afterwards, the transfected cell lines ACHN and 786-O were used for the CCK-8 assay, MTT assay, wound healing assay, transwell assay and flow cytometric assay to explore the role of miR-154-5p in regulating cellular function. In addition, formalin-fixed paraffin-embedded (FFPE) renal cancer samples were used for detecting the relationship between expression level of miR-154-5p and clinical information. Furthermore, univariate and multivariate Cox proportional-hazards regression analyses, and the Kaplan-Meier survival curves were performed to evaluate the prognostic value of miR-154-5p in RCC. Key findings The RT-qPCR indicated that miR-154-5p is up-regulated in RCC pathologic specimens and cell lines. Results of study also demonstrated that upregulation of miR-154-5p reduced cell apoptosis and promoted cell proliferation, viability, migration as well as invasion in RCC cells. The prognosis analyses indicated that the expression level of miR-154-5p is associated with the prognosis of renal cancer, and the overall survival of patients with low expression is longer. Significance The present study revealed that the oncogene miR-154-5p regulates cellular function and acts as a molecular marker with poor prognosis in renal cell carcinoma.

MiR-216a-5p has been acknowledged as an oncogene and is known to be involved in the progression and metastasis of numerous cancer subtypes. However, the potential role of miR-216a-5p in renal cell carcinoma (RCC) remains to be elucidated. In the present study, reverse transcription-quantitative polymerase chain reaction was performed to detect the expression levels of miR-216a-5p in RCC tissues. Cell counting kit-8, MTT, wound scratch, Transwell and flow cytometric assays were performed to establish the biological functions of miR-216a-5p in RCC. Functional experiments demonstrated that the expression of miR-216a-5p was upregulated in RCC (P

MicroRNAs (miRs) are involved in diverse physiological and developmental processes at the post-transcriptional level in cells. Previous studies have demonstrated that miR-136-5p is involved in certain types of cancer. However, the function of miR-136-5p in renal cell carcinoma (RCC) remains to be fully elucidated. In present study, miR-136-5p expression levels were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and MTT assays, CCK-8 assays, Transwell assays, wound healing assays and flow cytometry were performed to investigate the function of miR-136-5p in RCC. RT-qPCR revealed that the expression of miR-136 was significantly lower in RCC tissues and cells compared with adjacent non-tumor tissues and cells in vitro. miR-136-5pwas also demonstrated to be associated with RCC cell proliferation, viability, migration, invasion and apoptosis. miR-136-5p may therefore function as a tumor suppressor in RCC. Further studies are required to elucidate the molecular mechanisms and signaling pathways underlying these functions of miR-136-5p, to investigate the potential function of miR-136-5p as a biomarker for the early detection and prognosis of RCC, and its potential as a therapeutic target for the treatment of RCC.

Renal cell carcinoma (RCC) is the third most common urological malignancy in the USA and represents 2‑3% of all adult malignancies. Furthermore, the incidence of RCC has been progressively increasing over recent years. Although the morbidity of treatment has decreased with the use of multidisciplinary synthetic therapy, the prognosis of terminal cancer remains poor, with a 5‑year survival rate of 5‑10%. MicroRNAs (miRs) have been correlated with the regulation of 30‑60% of the protein-coding genes and act as oncogenes or anti‑oncogenes in RCC. Considering this research, miRNAs are likely to be the biomarkers for tumor diagnosis, prognosis and the targets for RCC management. In the present study, 42 formalin‑fixed paraffin‑embedded RCC samples were used. The expression of miR‑572 and the role of miR‑572 in RCC cell proliferation, migration and apoptosis was determined by performing reverse transcription‑quantitative polymerase chain reaction analysis, wound scratch assays, cell proliferation assays, Transwell assays and flow cytometry assays, respectively. Further experiments were conducted to clarify the correlation between miR‑572 expression and clinicopathological variables or overall survival. Furthermore, the expression levels of miR‑572 were evaluated for the prognosis value of patients with RCC. Upregulation of miR‑572 was observed in RCC tissues and RCC cell lines. miR‑572 promoted 786‑O and ACHN cell proliferation and mobility and inhibited early apoptosis. In Cox proportional hazard regression analyses, results of the univariate and multivariate analysis indicated that the patients with low miR‑572 expression had a significantly longer overall survival compared with the patients with high miR‑572 expression (univariate analysis, P=0.037; multivariate analysis, P=0.034). Results of the Kaplan‑Meier survival curves revealed that the patients with downregulated miR‑572 have a significantly longer overall survival compared with the patients with highly expressed miR‑572 (P=0.019). To conclude, the results of the present study suggest that tumor oncogene miR‑572 is a potential biomarker for the diagnosis, treatment and prognosis for RCC.

A neuromodulatory role for glutamate has been reported for magnocellular neuroendocrine cells in mammalian hypothalamus. We examined the potential role of glutamate as a local intercellular messenger in the neuroendocrine Dahlgren cell population of the caudal neurosecretory system (CNSS) in the euryhaline flounder Paralichthys olivaceus. In pharmacological experiments in vitro, glutamate (Glu) caused an increase in electrical activity of Dahlgren cells, recruitment of previously silent cells, together with a greater proportion of cells showing phasic (irregular) activity. The glutamate substrate, glutamine (Gln), led to increased firing frequency, cell recruitment and enhanced bursting activity. The glutamate effect was not blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801, or the GluR1/GluR3 (AMPA) receptor antagonist IEm1795-2HBr, but was blocked by the broad-spectrum α-amino-3-hydroxy- 5- methyl-4-isoxazo-lepropionic acid (AMPA) receptor antagonist ZK200775. Our transcriptome sequencing study revealed three AMPA receptor (GluR1, GluR2 and GluR3) in the olive flounder CNSS. Quantitative RT-PCR revealed that GluR2 receptor mRNA expression was significant increased following dose-dependent superfusion with glutamate in the CNSS. GluR1 and GluR3 receptor mRNA expression were decreased following superfusion with glutamate. L-type Ca2+ channel mRNA expression had a significant dose-dependent decrease following superfusion with glutamate, compared to the control. In the salinity challenge experiment, acute transfer from SW to FW, GluR2 receptor mRNA expression was significantly higher than the control at 2 h. These findings suggest that GluR2 is one of the mechanisms which can medicate glutamate action within the CNSS, enhancing electrical activity and hence secretory output.

COX-2 and YAP are shown to be highly associated with hepatocellular carcinoma (HCC) and frequently upregulated during tumor formation. However, despite their importance, whether there is a mutual interaction between COX-2 and YAP and how they regulate each other are not clear. In this paper, we showed that COX-2 overexpression in HCC cell lines resulted in increased levels of YAP mRNA, protein, and its target genes. COX-2 promoted proliferation of HCC cell lines, and knockdown of YAP antagonized this effect. In addition, our results indicated that EP2 and Wnt/β-Catenin mediate the transcriptional induction of YAP by COX-2. On the other hand, YAP increased COX-2 expression at the level of transcription requiring intact TEAD binding sites in the COX-2 promoter. Collectively, these findings indicated that COX-2 is not only a stimulus of YAP but also a target of Hippo-YAP pathway, thus forming a positive feedback circuit, COX-2-PGE2-EP2-Gαs-β-catenin-YAP-COX-2. In a further study, we showed that inhibition of YAP and COX-2 acted synergistically and more efficiently reduced the growth of HCC cells and tumor formation than either of them alone, suggesting that dual governing of YAP and COX-2 may lead to the discovery of promising therapeutic strategies for HCC patients via blocking this positive feedback loop.

SUMMARYTo investigate the prevalence ofCyclospora cayetanensisin a longitudinal study and to conduct a population genetic analysis, fecal specimens from 6579 patients were collected during the cyclosporiasis – prevalent seasons in two urban areas of central China in 2011–2015. The overall incidence ofC. cayetanensisinfection was 1·2% (76/6579): 1·6% (50/3173) in Zhengzhou and 0·8% (26/3406) in Kaifeng (P< 0·05), with infections in all age groups (P> 0·05). All the isolates clustered in theC. cayetanensisclade based on the small subunit ribosomal RNA gene sequence phylogenetic analysis. There were 45 specimens positive for all the fiveC. cayetanensismicrosatellite loci, and formed 29 multilocus genotypes (MLGs). The phylogenetic relationships of 54 distinct MLGs (including 25 known reference MLGs), based on the concatenated multilocus sequences, formed three main clusters. A population structure analysis showed that the 79 isolates (including 34 known reference isolates) ofC. cayetanensisproduced three distinct subpopulations based on allelic profile data. In conclusion, we determined the frequency ofC. cayetanensisinfection in humans in Henan Province. The clonal population structure of the humanC. cayetanensis isolates showed linkage disequilibrium and three distinct subpopulations.

Supplemental Digital Content is available in the text, Background: The aim of this study was to describe the design, methods, and baseline characteristics of children enrolled in the Personalized Addition lenses Clinical Trial (PACT). PACT aims to test the myopia control efficacy of progressive addition lenses (PALs) with personalized addition values compared with standard (+2.00 D) addition PALs and single vision lenses (SVLs). Methods: PACT is a randomized, controlled, double-masked clinical trial. Two hundred eleven myopic Chinese children (7–12 years) were enrolled and randomized into 1 of the 3 following groups: personalized addition PALs; +2.00 addition PALs; and SVLs. Personalized addition values were determined based on the highest addition that satisfied Sheard criterion. Axial length and other biometric data were also recorded. Results: At baseline, no differences were found between the right and left eyes for any of the main parameters. The enrolled children were 9.7 ± 1.1 years’ old with cycloplegic autorefraction (right eye [OD]: −2.36 ± 0.64 D), near phoria (1.0 ± 5.0 prism diopter esophoria), lag of accommodation (1.40 ± 0.50 D) and axial length (OD: 24.58 ± 0.74 mm). The personalized addition values ranged from +0.75 to +3.00 (average ± SD: 2.19 ± 0.73 D). Conclusion: PACT is a clinical trial evaluating whether myopia progression in children can be slowed by wearing personalized addition PALs compared with fixed addition PALs and SVLs as measured by cycloplegic autorefraction and axial length. Baseline data were comparable with those of previous myopia control studies in children. Subjects will be followed up every 6 months for 2 years.

Interocular suppression was quantified by the interocular luminance difference that was needed when the two eyes were balanced in discriminating a black–white stripe formed butterfly stimulus, which was dichoptically presented through polarized glasses. Stronger interocular suppression was found in amblyopes than that in controls at both the near (33 cm, 0.95 ± 1.00 vs. 0.14 ± 0.18, p

Purpose. To evaluate the distribution pattern and changes of strabismus surgery in children based on the data collected from a local eye hospital in the south of China between 2006 and 2011. Methods. A retrospective analysis of all strabismus surgeries in children ( Result. A total of 2,219 strabismus surgeries were performed during the study period, with concomitant exotropia (44% of all surgeries) more than esotropia (27%, χ2=42.7, p<0.001). Total number of surgeries increased from 250 in 2006 to 508 in 2011, with a significant increase in concomitant exotropia: 38% of all surgeries in 2006 increased to 47% in 2011 (χ2=29.4, p<0.001). The increase of intermittent exotropia was approximately 26% of all increments of strabismus surgery between 2006 and 2011. Conclusion. Surgery for childhood exotropia was more frequent than esotropia in China. The proportion of exotropia progressively increased, while the proportion of esotropia decreased during these years. Intermittent exotropia was the main increment of strabismus surgery. Further population-based studies are needed to confirm the proportion of surgery and whether the incidence of strabismus surgery increased in China.

Background: To evaluate the longitudinal impact on health-related quality of life (HRQOL) during amblyopia treatment for school-aged children from children’s perspective. Methods: School-aged children prescribed amblyopia treatment for the first time were recruited into the current study. Using a questionnaire, subjects’ HRQOL was assessed before patching treatment, and at 8 weeks and 16 weeks after the commencement of patching treatment. Evaluation of visual function and psychosocial aspect was included in the questionnaire. Visual acuity and demographic data of the subjects were recorded. Results: Forty-four children, aged 7–12 years, with anisometropic amblyopia were included in the study. Visual acuity in the amblyopic eye improved 1.90 (0.41–3.74) and 3.98 (2.22–5.11) lines at follow-up weeks 8 and 16, respectively. Both the total score and subscales of the questionnaire were reduced at the first follow-up and recovered at the second follow-up. Scores at week 16 were higher than those before treatment in the psychosocial aspect (p = 0.003), and lower in the visual function aspect (p p = 0.207). Visual acuity in the amblyopic eye and psychosocial expectations for treatment were the most important factors that influenced HRQOL during treatment. Conclusions: From the children’s perspective, the impacts on visual function and psychosocial aspect were significant in the first two months of treatment, and could be adapted during therapy for school-aged children. More attention should be paid to negative effects of treatment on daily life and study at the stage of amblyopia treatment for school-aged children. Meanwhile, necessary precautions should be taken to help reduce the impacts.

Insulin regulates development, metabolism, and lifespan via a conserved PI3K/Akt pathway that promotes cytoplasmic sequestration of FoxO transcription factors. The regulation of nuclear FoxO is poorly understood. In the nematode Caenorhabditis elegans, insulin-like signaling functions in larvae to inhibit dauer arrest and acts during adulthood to regulate lifespan. In a screen for genes that modulate C. elegans insulin-like signaling, we identified eak-3, which encodes a novel protein that is specifically expressed in the two endocrine XXX cells. The dauer arrest phenotype of eak-3 mutants is fully suppressed by mutations in daf-16/FoxO, which encodes the major target of C. elegans insulin-like signaling, and daf-12, which encodes a nuclear receptor regulated by steroid hormones known as dafachronic acids. eak-3 mutation does not affect DAF-16/FoxO subcellular localization but enhances expression of the direct DAF-16/FoxO target sod-3 in a daf-16/FoxO- and daf-12-dependent manner. eak-3 mutants have normal lifespans, suggesting that EAK-3 decouples insulin-like regulation of development and longevity. We propose that EAK-3 activity in the XXX cells promotes the synthesis and/or secretion of a hormone that acts in parallel to AKT-1 to inhibit the expression of DAF-16/FoxO target genes. Similar hormonal pathways may regulate FoxO target gene expression in mammals.

Akt/protein kinase B (PKB) functions in conserved signaling cascades that regulate growth and metabolism. In humans, Akt/PKB is dysregulated in diabetes and cancer; in Caenorhabditis elegans, Akt/PKB functions in an insulin-like signaling pathway to regulate larval development. To identify molecules that modulate C. elegans Akt/PKB signaling, we performed a genetic screen for enhancers of the akt-1 mutant phenotype (eak). We report the analysis of three eak genes. eak-6 and eak-5/sdf-9 encode protein tyrosine phosphatase homologs; eak-4 encodes a novel protein with an N-myristoylation signal. All three genes are expressed primarily in the two endocrine XXX cells, and their predicted gene products localize to the plasma membrane. Genetic evidence indicates that these proteins function in parallel to AKT-1 to inhibit the FoxO transcription factor DAF-16. These results define two membrane-associated protein tyrosine phosphatase homologs that may potentiate C. elegans Akt/PKB signaling by cell autonomous and cell nonautonomous mechanisms. Similar molecules may modulate Akt/PKB signaling in human endocrine tissues., Synopsis Insulin and insulin-like growth factor (IGF) signaling regulates critical physiological processes in a wide variety of multicellular organisms. In humans, dysregulation of IGF signaling underlies the pathogenesis of cancer and diabetes. In the nematode Caenorhabditis elegans, the DAF-2 insulin-like pathway regulates development, metabolism, and longevity. All known components of DAF-2 insulin-like signaling are structurally and functionally conserved in mammals, suggesting that insights gained from studying this pathway in C. elegans may shed light on pathogenetic mechanisms underlying cancer and diabetes. In this study, the authors describe a genetic screen designed to identify novel components of DAF-2 insulin-like signaling in C. elegans. They have characterized three genes that may encode parts of a novel multimolecular membrane-associated complex that potentiates DAF-2 insulin-like signaling in two neuroendocrine cells, the XXX cells. Two of these genes encode proteins similar to mammalian protein tyrosine phosphatases. These results suggest that protein tyrosine phosphatase–like molecules may transduce IGF signals in mammalian endocrine cells and highlight the role of endocrine circuits in the pathogenesis of cancer and diabetes.

Summary Background miRNAs are an abundant class of small, endogenous regulatory RNAs. Although it is now appreciated that miRNAs are involved in a broad range of biological processes, relatively little is known about the actual mechanism by which miRNAs downregulate target gene expression. An exploration of which protein cofactors are necessary for a miRNA to downregulate a target gene should reveal more fully the molecular mechanisms by which miRNAs are processed, trafficked, and regulate their target genes. Results A weak allele of the C. elegans miRNA gene let-7 was used as a sensitized genetic background for a whole-genome RNAi screen to detect miRNA pathway genes, and 213 candidate miRNA pathway genes were identified. About 2/3 of the 61 candidates with the strongest phenotype were validated through genetic tests examining the dependence of the let-7 phenotype on target genes known to function in the let-7 pathway. Biochemical tests for let-7 miRNA production place the function of nearly all of these new miRNA pathway genes downstream of let-7 expression and processing. By monitoring the downregulation of the protein product of the lin-14 mRNA, which is the target of the lin-4 miRNA, we have identified 19 general miRNA pathway genes. Conclusions The 213 candidate miRNA pathway genes identified could act at steps that produce and traffic miRNAs or in downstream steps that detect miRNA::mRNA duplexes to regulate mRNA translation. The 19 validated general miRNA pathway genes are good candidates for genes that may define protein cofactors for sorting or targeting miRNA::mRNA duplexes, or for recognizing the miRNA base-paired to the target mRNA to downregulate translation.