The role of human umbilical cord mesenchymal stem cells-derived exosomal microRNA-431-5p in survival and prognosis of colorectal cancer patients.

We aim to discuss the role of miR-431-5p in colorectal cancer (CRC) progression via regulating peroxiredoxin 1 (PRDX1). miR-431-5p and PRDX1 expression were detected in CRC tissues and cells, and the relationship between miR-431-5p expression and prognosis of CRC patients was analyzed. Exosomes were extracted from human umbilical cord mesenchymal stem cells (hUCMSCs) and co-cultured with LoVo cells. MTT assay, flow cytometry and Transwell assay were implemented to test cell viability, apoptosis and invasion and migration ability, respectively. The tumor growth was determined as well, and the binding relation between miR-431-5p and PRDX1 was confirmed. miR-431-5p was downregulated and PRDX1 was upregulated in CRC, and miR-431-5p downregulation was associated with poor prognosis. hUCMSC-Exos suppressed the malignant behaviors of LoVo cells, and overexpression of miR-431-5p further aggravated the inhibitory effect of hUCMSC-Exos on LoVo cells. hUCMSC-Exos inhibited PRDX1 expression via miR-431-5p. PRDX1 was targeted by miR-431-5p. miR-431-5p serves as a prognostic biomarker in CRC, and hUCMSC-Exos transfer of miR-431-5p decelerates CRC cell growth by inhibiting PRDX1.

Analysis on spatial development mode of eco-sports tourism in Grand Canal landscape environment culture belt.

The development mode of sports tourism is based on the ecological environment. In order to reduce the negative impact of sports tourism on the environment, the development of ecological sports tourism based on the perspective of ecology is the top priority for the healthy and sustainable development of sports tourism. On the basis of summarizing and analyzing the previous research results, this paper expounds the elements and value of ecological sports culture tourism resources, introduces the ecological sports tourism complex model of landscape environmental culture belt, and expounds the cultural connotation characteristics of ecological sports tourism environment. Environmental science is mainly reflected in the promotion of the benign cycle of natural ecological environment, the protection of living things, the protection of water bodies and the treatment of water pollution, and the good protection of atmospheric environment, geology, and geomorphology. Based on the development of ecological sports tourism space with landscape environment culture belt, this paper introduces the resource development system of Beijing-Hangzhou Canal ecological sports culture tourism, constructs the landscape space development mode of ecological sports tourism, and analyzes the landscape space structure of ecological sports tourism. Based on landscape culture with the basis of sports tourism resources, analyzes the influence factors of sports tourism spatial structure from the direction of the depth and breadth of two dimensions expand sports events and the ecological sports cultural tourism, the depth of the fusion depth aspects emphatically at sporting events, and the ecological sports cultural tourism into the connotation of mining, breadth aspect focuses on the formats of the extension of rich and associated industries. To study the important carrier of promoting the development of ecological sports culture resources and sports industry in the Canal, to plan the layout and establish the sports culture tourism industry base reasonably, and to form the sports culture tourism industry ecosphere. The results show that the scale and speed of the development of sports tourism not only depend on the attractive sports tourism resources but also highly depend on the level of economic and social development in the region. The supply of sports tourism must take the demand of sports tourism market as the guide, combine sports activities with tourism activities in an ecological and organic way, develop various sports items to meet the needs of tourists, and realize the ecological, economic, and social benefits of ecological sports tourism. The research results of this paper provide reference for the further development of eco-sports tourism in landscape environment and culture belt.

A cross-sectional survey based on blood VOCs, hematological parameters and urine indicators in a population in Jilin, Northeast China.

The objective of this study was to examine whether long-term exposure to low-dose volatile organic compounds (VOCs) will have an effect on the health of non-occupational population. A total of 499 non-occupational participants aged more than 18 that live around Jilin Petrochemical Industrial Zone were chosen by stratified cluster random sampling. Their blood VOCs' levels, hematological parameters and urine indicators together with detailed questionnaire data were used to find possible relationships using binary logistic regression analysis. The detection rate of benzene in the blood was high in the non-occupational population around the industrial area, and it even reached 82.3% in males but no significant difference was recorded between male and female population. In addition, trichloroethane (male: 33.2% V female: 21.7%; p = 0.002), carbon tetrachloride (males: 20.3% V females: 7.5%; p < 0.001) and trichlorethylene (male: 34.9% V female: 24.7%; p = 0.004) all showed significant differences in gender, and without exception, the prevalence of males was higher in these three VOCs than of females. The changes in red blood cell (RBC), hematocrit (HCT) and basophils are correlated with carbon tetrachloride, trichloroethylene and chloroform, respectively. And RBC, HCT and basophils are statistically significant in male compared with female of the study population. The increase in trichlorethylene was associated with an increase of 1.723% (95% CI 1.058-2.806) in HCT. The increase in carbon tetrachloride showed a more significant correlation with an increase of 2.638% in RBC count (95% CI 1.169-5.953). And trichloromethane led to a 1.922% (95% CI 1.051-3.513) increase in basophils. The changes in urinary WBC, urine ketone (KET) and urinary bilirubin (BIL) showed significant correlation with benzene, carbon tetrachloride and dibromochloromethane, respectively. The correlation in females is more significant than in males. The increase of benzene in the female population increased urinary leukocyte count by 2.902% (95% CI 1.275-6.601). The effect of carbon tetrachloride on KET was particularly pronounced, resulting in an increase of 7.000% (95% CI 1.608-30.465). Simultaneously, an increase in dibromochloromethane caused an increase of 4.256% (95% CI 1.373-13.192) in BIL. The changes in RBC, HCT and basophils can only serve as an auxiliary indicator for disease diagnosis, so they have no significant clinical significance. However, the alteration of urinary WBC, KET and BIL has great clinical significances, and it is suggested that the monitoring of the above indicators from low-dose long-term exposure be strengthen in this area.

The biological roles and clinical implications of microRNAs in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) accounts for about 3% of tumors in adults as well as 85% of all primary renal carcinoma. And it is the third most predominant urological carcinoma, but it has the maximum mortality rate. Early diagnosis and proper follow-up of ccRCC patients may improve the prognosis of the illness. Thus, it is imperative to understand the new biomarkers of ccRCC and study new method for the modern therapy of this deadly disease. Furthermore, a large number of microRNAs (miRNAs), small non-coding RNAs, have been relevant to tumor type, stage, or survival and miRNAs might be progressed as the markers of diagnosis or prognosis in ccRCC. A growing body of data also advised the rationality of regarding miRNAs as therapeutic targets for ccRCC treatment. In this review, we tried to summarize biogenesis of miRNAs and their expression profiles, biological roles, and clinical implications in ccRCC.

The miR-193a-3p regulated PSEN1 gene suppresses the multi-chemoresistance of bladder cancer.

Chemoresistance prevents the curative cancer therapy, our understanding of which remains inadequate. Among the differentially expressed genes between the chemosensitive (5637) and chemoresistant (H-bc) bladder cancer cell lines, the expression level of the PSEN1 gene (presenilin 1), a key component of the γ-secretase, is negatively correlated with chemoresistance. A small interfering RNA mediated repression of the PSEN1 gene suppresses cell apoptosis and de-sensitizes 5637 cells, while overexpression of the presenilin 1 sensitizes H-bc cells to the drug-triggered cell death. As a direct target of microRNA-193a-3p that promotes the multi-chemoresistance of the bladder cancer cell, PSEN1 acts as an important executor for the microRNA-193a-3p's positive impact on the multi-chemoresistance of bladder cancer, probably via its activating effect on DNA damage response pathway. In addition to the mechanistic insights, the key players in this microRNA-193a-3p/PSEN1 axis are likely the diagnostic and/or therapeutic targets for an effective chemotherapy of bladder cancer.

Cryptolepine derivative-6h inhibits liver fibrosis in TGF-ß1-induced HSC-T6 cells by targeting the Shh pathway.

Liver fibrosis is a worldwide problem with a significant morbidity and mortality. Cryptolepis sanguinolenta (family Periplocaceae) is widely used in West African countries for the treatment of malaria, as well as for some other diseases. However, the role of C. sanguinolenta in hepatic fibrosis is still unknown. It has been reported that Methyl-CpG binding protein 2 (MeCP2) had a high expression in liver fibrosis and played a central role in its pathobiology. Interestingly, we found that a cryptolepine derivative (HZ-6h) could inhibit liver fibrosis by reducing MeCP2 expression, as evidenced by the dramatic downregulation of α-smooth muscle actin (α-SMA) and type I collagen alpha-1 (Col1α1) in protein levels in vitro. Meanwhile, we also found that HZ-6h could reduce the cell viability and promote apoptosis of hepatic stellate cells (HSCs) treated with transforming growth factor beta 1(TGF-ß1). Then, we investigated the potential molecular mechanisms and found that HZ-6h blocked Shh signaling in HSC-T6 cells, resulting in the decreased protein expression of Patched-1 (PTCH-1), Sonic hedgehog (Shh), and glioma-associated oncogene homolog 1 (GLI1). In short, these results indicate that HZ-6h inhibits liver fibrosis by downregulating MeCP2 through the Shh pathway in TGF-ß1-induced HSC-T6 cells.

Loss of miR-638 in vitro promotes cell invasion and a mesenchymal-like transition by influencing SOX2 expression in colorectal carcinoma cells.

BACKGROUND: Colorectal carcinoma (CRC) is a major cause of cancer mortality. The aberrant expression of several microRNAs is associated with CRC progression; however, the molecular mechanisms underlying this phenomenon are unclear. METHODS: miR-638 and SRY-box 2 (SOX2) expression levels were detected in 36 tumor samples and their adjacent, non-tumor tissues from patients with CRC, as well as in 4 CRC cell lines, using real-time quantitative RT-PCR (qRT-PCR). SOX2 expression levels were detected in 90 tumor samples and their adjacent tissue using immunohistochemistry. Luciferase reporter and Western blot assays were used to validate SOX2 as a target gene of miR-638. The regulation of SOX2 expression by miR-638 was assessed using qRT-PCR and Western blot assays, and the effects of exogenous miR-638 and SOX2 on cell invasion and migration were evaluated in vitro using the HCT-116 and SW1116 CRC cell lines. RESULTS: We found that miR-638 expression was differentially impaired in CRC specimens and dependent on tumor grade. The inhibition of miR-638 by an antagomiR promoted cell invasion and a mesenchymal-like transition (lamellipodium stretching increased and cell-cell contacts decreased, which was accompanied by the suppression of the epithelial cell marker ZO-1/E-cadherin and the upregulation of the mesenchymal cell marker vimentin). A reporter assay revealed that miR-638 repressed the luciferase activity of a reporter gene coupled to the 3'-untranslated region of SOX2. miR-638 overexpression downregulated SOX2 expression, and miR-638 inhibition upregulated SOX2 expression. Moreover, miR-638 expression levels were correlated inversely with SOX2 mRNA levels in human CRC tissues. The RNAi-mediated knockdown of SOX2 phenocopied the invasion-inhibiting effect of miR-638; furthermore, SOX2 overexpression blocked the miR-638-induced CRC cell transition to epithelial-like cells. CONCLUSIONS: These results demonstrate that the loss of miR-638 promotes invasion and a mesenchymal-like transition by directly targeting SOX2 in vitro. These findings define miR-638 as a new, invasion-associated tumor suppressor of CRC.

miR-193a-3p regulates the multi-drug resistance of bladder cancer by targeting the LOXL4 gene and the oxidative stress pathway.

BACKGROUND: Chemoresistance is a major obstacle to the curative cancer chemotherapy and presents one of the most formidable challenges in both research and management of cancer. RESULTS: From the detailed studies of a multi-chemosensitive (5637) versus a chemoresistant (H-bc) bladder cancer cell lines, we showed that miR-193a-3p [GenBank: NR_029710.1] promotes the multi-chemoresistance of bladder cancer cells. We further demonstrated that lysyl oxidase-like 4 (LOXL4) gene [GenBank: NM_032211.6] is a direct target of miR-193a-3p and executes the former's impact on bladder cancer chemoresistance. The Oxidative Stress pathway activity is drastically affected by a forced reversal of miR-193a-3p or LOXL4 levels in cell and may act at the downstream of LOXL4 gene to relay the miR-193a-3p's impact on the multi-chemoresistance in both cultured cells and the tumor xenografts in nude mice. CONCLUSIONS: In addition to a new mechanistic insight, our results provide a set of the essential genes in this newly identified miR-193a-3p/LOXL4/Oxidative Stress axis as the diagnostic targets for a guided anti-bladder cancer chemotherapy.

DNA methylation-regulated miR-193a-3p dictates resistance of hepatocellular carcinoma to 5-fluorouracil via repression of SRSF2 expression.

Chemoresistance prevents effective cancer therapy and is rarely predictable prior to treatment, particularly for hepatocellular carcinoma (HCC). Following the chemoresistance profiling of eight HCC cell lines to each of nine chemotherapeutics, two cell lines (QGY-7703 as a sensitive and SMMC-7721 as a resistant cell line to 5-fluorouracil (5-FU) treatment) were systematically studied for mechanistic insights underpinning HCC 5-FU chemoresistance. Genomic profiling at both DNA methylation and microRNA (miR) levels and subsequent mechanistic studies illustrate a new mechanism for how DNA methylation-regulated miR-193a-3p dictates the 5-FU resistance of HCC cells via repression of serine/arginine-rich splicing factor 2 (SRSF2) expression. In turn, SRSF2 preferentially up-regulates the proapoptotic splicing form of caspase 2 (CASP2L) and sensitizes HCC cells to 5-FU. Forced changes of miR-193a-3p level reverse all of the phenotypic features examined, including cell proliferation, cell cycle progression, and 5-FU sensitivity, in cell culture and in nude mice. Importantly, the siRNA-mediated repression of SRSF2 phenocopies all of the miR-193a-3p mimic-triggered changes in QGY-7703. This newly identified miR-193a-3p-SRSF2 axis highlights a new set of companion diagnostics required for optimal 5-FU therapy of HCC, which involve assaying both the DNA methylation state of the miR-193a gene and the expression of miR-193a-3p and SRSF2 and the relative level of the proapoptotic versus antiapoptotic splicing forms of caspase 2 in clinical samples.

MicroRNA 34c gene down-regulation via DNA methylation promotes self-renewal and epithelial-mesenchymal transition in breast tumor-initiating cells.

Tumor-initiating cells (T-ICs), a subpopulation of cancer cells with stem cell-like properties, are related to tumor relapse and metastasis. Our previous studies identified a distinct profile of microRNA (miRNA) expression in breast T-ICs (BT-ICs), and the dysregulated miRNAs contribute to the self-renewal and tumorigenesis of these cells. However, the underlying mechanisms for miRNA dysregulation in BT-ICs remain obscure. In the present study, we demonstrated that the expression and function of miR-34c were reduced in the BT-ICs of MCF-7 and SK-3rd cells, a breast cancer cell line enriched for BT-ICs. Ectopic expression of miR-34c reduced the self-renewal of BT-ICs, inhibited epithelial-mesenchymal transition, and suppressed migration of the tumor cells via silencing target gene Notch4. Furthermore, we identified a single hypermethylated CpG site in the promoter region of miR-34c gene that contributed to transcriptional repression of miR-34c in BT-ICs by reducing DNA binding activities of Sp1. Therefore, miR-34c reduction in BT-ICs induced by a single hypermethylated CpG site in the promoter region promotes self-renewal and epithelial-mesenchymal transition of BT-ICs.

The DNA methylome of human peripheral blood mononuclear cells.

DNA methylation plays an important role in biological processes in human health and disease. Recent technological advances allow unbiased whole-genome DNA methylation (methylome) analysis to be carried out on human cells. Using whole-genome bisulfite sequencing at 24.7-fold coverage (12.3-fold per strand), we report a comprehensive (92.62%) methylome and analysis of the unique sequences in human peripheral blood mononuclear cells (PBMC) from the same Asian individual whose genome was deciphered in the YH project. PBMC constitute an important source for clinical blood tests world-wide. We found that 68.4% of CpG sites and <0.2% of non-CpG sites were methylated, demonstrating that non-CpG cytosine methylation is minor in human PBMC. Analysis of the PBMC methylome revealed a rich epigenomic landscape for 20 distinct genomic features, including regulatory, protein-coding, non-coding, RNA-coding, and repeat sequences. Integration of our methylome data with the YH genome sequence enabled a first comprehensive assessment of allele-specific methylation (ASM) between the two haploid methylomes of any individual and allowed the identification of 599 haploid differentially methylated regions (hDMRs) covering 287 genes. Of these, 76 genes had hDMRs within 2 kb of their transcriptional start sites of which >80% displayed allele-specific expression (ASE). These data demonstrate that ASM is a recurrent phenomenon and is highly correlated with ASE in human PBMCs. Together with recently reported similar studies, our study provides a comprehensive resource for future epigenomic research and confirms new sequencing technology as a paradigm for large-scale epigenomics studies.

Baseline urine pH is related to effective urine alkalization by short-term alkaline water supplementation: data from a self-controlled study in healthy Chinese volunteers following a systematic review and meta-analysis of literature.

Background: The outcomes of urine alkalization with alkaline water supplementation vary greatly across studies and therefore remain inconclusive, probably arising from differences in study design, ethnic group, and source of alkaline water, which needs further clarification. With a systematic review of literature, followed by an empirical observation among healthy Chinese volunteers, we aimed to investigate the outcomes of urine alkalization with alkaline water vs. daily drinking water, and whether these outcomes are intersected by certain factors such as gender and body mass index (BMI). Methods: We conducted a literature search of related studies on alkaline water supplementation and urine pH using the PubMed, Embase, Medline and Cochrane Library databases. The publication bias was assessed with inverted funnel plotting. Chi-square-based Q-test and I2-statistic test were used to examine the data heterogeneity. The studies were evaluated for quality using the Cochrane risk of bias tool or Newcastle-Ottawa Scale (NOS). The meta-analysis was followed by a study in healthy volunteers. As per protocol, all subjects remained on regular drinking water for one week and were switched to alkaline water for the next week. Urine pH was measured thrice daily and averaged. The mean urine pH values in the first and second weeks were compared for all subjects. Alkalization gains in urine pH (AGU-pH) was computed to determine the outcome of alkaline water supplementation in relation to baseline urine pH. Results: Our systematic review of literature yielded limited data about the effect of alkaline water on urine pH. Despite an increase in urine pH after supplementation of alkaline water as indicated by the random-effect model, a high heterogeneity across the included studies (I2=94%, P<0.001) precluded a robust determination. In our volunteer study, alkaline water led to elevation of urine pH from baseline in 84.9% of all subjects or by BMI stratification. Effective urine alkalization was noted in males but not in females. Subjects who presented effective urine alkalization had significantly lower baseline urine pH compared with those who did not (5.94±0.27 vs. 6.22±0.22, P=0.0016). The negative correlation between AGU-pH and baseline urine pH (r=-0.236, P=0.044) and receiver operating curve (ROC) analysis suggested that subjects with more "acidic" urine, particularly those with a baseline urine pH ≤6.0 (maximum Youden index =1.548, cut-off =5.977), could show more pronounced outcome of urine alkalization from oral alkaline water. Conclusions: Our meta-analysis and human subjects study revealed that alkaline water supplementation may be useful for urine alkalization, particularly in individuals with a lower urine pH. The outcomes seem not significantly pronounced in females, although more efforts warranted for validation. Short-term use of alkaline water is well-tolerated and not associated with over-alkalization of the urine.

Transvaginal approach for rectovaginal fistula: experience from a single institution.

Transvaginal (TV) repair, featuring its feasibility, effectiveness, safety, and technically less demandingness, is one of the surgical approaches for management of rectovaginal fistula (RVF). However, there are limited numbers of publications available on the transvaginal approach for RVF repair. To this end, the purpose of this study is to evaluate the preliminary outcomes of the transvaginal approach performed by the team, and to further assess its feasibility, safety and effectiveness in the management of RVF. A retrospective analysis was conducted at a single institution. Patients with RVF who had undergone three transvaginal surgical techniques, i.e. transvaginal fistulectomy and stratified suture, transvaginal flip and ligation fistula tract and transvaginal fistula stapled closure were included. Besides, the demographics, operative data, postoperative complications and follow-up outcomes of the patients were collected prospectively. A total of 49 female patients (mean age, 35.76 ± 13.97 years) underwent transvaginal approach, 42 of which were followed up with a median follow-up of 26 months (range 3-82 months), and 29 had closure of the fistula (successful closure rate of 59.1%). The successful closure rates were only significantly different between previous repair times (p = 0.031), and several minor complications including postoperative pain (n = 3), constipation (n = 1), and lower urinary tract infection (n = 1) were observed. Symptomatic improvement was reported in all patients with failed closure. Transvaginal approach for RVF repair is effective, safe, and feasible, and is therefore considered an alternative to transrectal advancement flap for low and mid-level traumatic RVF with normal sphincter function. With the advantage of better surgical access, transvaginal approach is recognized as the initial choice for the surgical repair of RVF.

Minimally invasive endoscopic repair of rectovaginal fistula.

BACKGROUND: Surgical techniques for repair of rectovaginal fistula (RVF) have been continually developed, but the ideal procedure remains unclear. Endoscopic repair is a novel and minimally invasive technique for RVF repair with increasing reporting. AIM: To review the current applications and preliminary outcomes of this technique for RVF repair, aiming to give surgeons an alternative in clinical practice. METHODS: Available articles were searched according to the search strategy. And the sample size, fistula etiology, fistula type, endoscopic repair approaches, operative time and hospital stay, follow-up period, complication and life quality assessment were selected for recording and further analysis. RESULTS: A total of 11 articles were eventually identified, involving 71 patients with RVFs who had undergone endoscopic repair. The principal causes of RVFs were surgery (n = 51, 71.8%), followed by obstetrics (n = 7, 9.8%), inflammatory bowel disease (n = 5, 7.0%), congenital (n = 3, 4.2%), trauma (n = 2, 2.8%), radiation (n = 1, 1.4%), and in two patients, the cause was unclear. Most fistulas were in a mid or low position. Several endoscopic repair methods were included, namely transanal endoscopic microsurgery, endoscopic clipping, and endoscopic stenting. Most patients underwent > 1-year follow-up, and the success rate was 40%-93%, and all cases reported successful closure. Few complications were mentioned, while postoperative quality of life assessment was only mentioned in one study. CONCLUSION: In conclusion, endoscopic repair of RVF is novel, minimally invasive and promising with acceptable preliminary effectiveness. Given its unique advantages, endoscopic repair can be an alternative technique for surgeons.

Deep learning for real-time auxiliary diagnosis of pancreatic cancer in endoscopic ultrasonography.

In recent year, many deep learning have been playing an important role in the detection of cancers. This study aimed to real-timely differentiate a pancreatic cancer (PC) or a non-pancreatic cancer (NPC) lesion via endoscopic ultrasonography (EUS) image. A total of 1213 EUS images from 157 patients (99 male, 58 female) with pancreatic disease were used for training, validation and test groups. Before model training, regions of interest (ROIs) were manually drawn to mark the PC and NPC lesions using Labelimage software. Yolov5m was used as the algorithm model to automatically distinguish the presence of pancreatic lesion. After training the model based on EUS images using YOLOv5, the parameters achieved convergence within 300 rounds (GIoU Loss: 0.01532, Objectness Loss: 0.01247, precision: 0.713 and recall: 0.825). For the validation group, the mAP0.5 was 0.831, and mAP@.5:.95 was 0.512. In addition, the receiver operating characteristic (ROC) curve analysis showed this model seemed to have a trend of more AUC of 0.85 (0.665 to 0.956) than the area under the curve (AUC) of 0.838 (0.65 to 0.949) generated by physicians using EUS detection without puncture, although pairwise comparison of ROC curves showed that the AUC between the two groups was not significant (z= 0.15, p = 0.8804). This study suggested that the YOLOv5m would generate attractive results and allow for the real-time decision support for distinction of a PC or a NPC lesion.

Impact of air pollution on human activities: Evidence from nine million mobile phone users.

To measure the effects of air pollution on human activities, this study applies statistical/econometric modeling to hourly data of 9 million mobile phone users from six cities in China's Zhejiang Province from December 18 to 21, 2013. Under a change in air quality from "Good" (Air Quality Index, or AQI, between 51 and 100) to "Heavily Polluted" (AQI between 201 to 300), the following effects are demonstrated. (i) Consistent with the literature, for every one million people, 1, 482 fewer individuals are observed at parks, 95% confidence interval or CI (-2, 229, -735), which represents a 15% decrease. (ii) The number of individuals at shopping malls has no statistically significant change. (iii) Home is the most important location under worsening air quality, and for every one million people, 63, 088 more individuals are observed at home, 95% CI (47, 815, 78, 361), which represents a 19% increase. (iv) Individuals are on average 633 meters closer to their home, 95% CI (529, 737); as a benchmark, the median distance from home ranges from 300 to 1900 meters across the cities in our sample. These effects are not due to weather or government regulations. We also provided provisional evidence that individuals engage in inter-temporal activity substitutions within a day, which leads to mitigated (but not nullified) effects of air pollution on daily activities.

The Effect of Residential Environment on Respiratory Diseases and Pulmonary Function in Children from a Community in Jilin Province of China.

PURPOSE: Respiratory disease is a major and increasingly global epidemic that has a great impact on humans, especially children. The purpose of this study was to identify environmental risk factors for respiratory diseases and pulmonary function in children. PATIENTS AND METHODS: A population-based, cross-sectional survey of respiratory diseases and environmental risk factors was conducted in Jilin Province, China. Complete questionnaire information was available for 2419 children, while adequate pulmonary function data were available for a subgroup of 627 children. RESULTS: Our study found that environmental risk factors for respiratory health in children were mainly concentrated indoors. After adjusting for demographic factors, insecticide exposure and passive smoking were risk factors for respiratory disease and industrial pollutant sources, insecticide exposure and the use of a fume exhauster may be independent risk factors for recurrent respiratory infections. The main fuel for cooking in the winter and passive smoking were the main influencing factors of pulmonary function indicators. CONCLUSION: The primary risk factors differ in different respiratory diseases. Passive smoking remains a critical adverse factor for respiratory illness and pulmonary function in children, and it is important to reduce children's exposure to passive smoking to increase pulmonary health. Insecticide exposure may be a neglected environmental risk factor, and further investigations are still needed to explore the relationship and mechanisms between insecticide exposure and children's respiratory health.

[Correlation of the methylation status of CpG islands in the promoter region of 10 genes with the 5-Fu chemosensitivity in 3 breast cancer cell lines].

OBJECTIVE: To explore the relationship between the methylation status of CpG islands in the promoter region of 10 genes in breast cancer cells and their sensitivity to 5-fluouracil (5-Fu), and to identify the genes responsible for the 5-Fu resistance in breast cancer. METHODS: Three cell lines (differently resistant to chemotherapy) were used in this study: Bcap-37 (IC(50): 289.77 microg/ml), T47D (IC(50): 134.16 microg/ml) and ZR-75-30 (IC(50): 4.20 microg/ml). The methylation profile of 10 genes (BAG1, C11ORF31, CBR1, CBR4, GJA1, FOXL2, IGFBP6, P4HA1, SRI and TYMS) in the 3 breast cancer cell lines was determined by methylation specific PCR. The steady-state mRNAs of ABCC8, CHFR and IGFBP6 genes were quantified by real-time RT PCR analysis. RESULTS: Among the 10 genes, only genes IGFBP6 and FOXL2 displayed differential DNA methylation pattern between the 5-Fu-resistant and 5-Fu-sensitive cell lines. The mRNA expression level of genes PRSS21, LOX, IGFBP6, ABCC8 and CHFR was quantified by real-time RT-PCR analysis. Except for CHFR, the expression level of the other 4 genes was correlated with the methylation status of CpG islands, namely, a lower expression level with methylation status and a higher level with demethylation status. CONCLUSION: The results of the present study have demonstrated that there are 8 genes with differential methylation status in chemosensitive and chemoresistant breast cancer cell lines, i.e. two genes more than the six genes we reported previously. Our findings provide both mechanistic insights for the drug resistance of breast cancer and the basis for further studies on potential application of the DNA methylation in this set of genes for prediction of chemosensitivity of breast cancer.

Autophagy as a Vital Therapy Target for Renal Cell Carcinoma.

Autophagy is a process that degrades and recycles superfluous organelles or damaged cellular contents. It has been found to have dual functions in renal cell carcinoma (RCC). Many autophagy-related proteins are regarded as prognostic markers of RCC. Researchers have attempted to explore synthetic and phytochemical drugs for RCC therapy that target autophagy. In this review, we highlight the importance of autophagy in RCC and potential treatments related to autophagy.

Hepatoprotective and Anti-Oxidative Effects of Total Flavonoids From Qu Zhi Qiao (Fruit of Citrus Paradisi cv.Changshanhuyou) on Nonalcoholic Steatohepatitis In Vivo and In Vitro Through Nrf2-ARE Signaling Pathway.

Nonalcoholic steatohepatitis (NASH) is a liver disease defined as the dynamic condition of hepatocellular injury during the progress of nonalcoholic fatty liver disease (NAFLD). Total flavonoids from the dry and immature fruits of Citrus Paradisi cv.Changshanhuyou (accepted species name: Citrus × aurantium L) (Qu Zhi Qiao, QZQ) are purified and named TFCH. This study was purposed to investigate and analyze the effect of TFCH on NASH model through Nuclear factor erythroid 2-related factor 2 (Nrf2)- antioxidant response elements pathway in vivo and in vitro. In vivo study was performed using male C57BL/6 mice fed with high fat diet 16 weeks for NASH model. After 7-week modeling, mice in TFCH-treated group were daily treated with intragastric administration of TFCH at 25 mg/kg, 50 mg/kg, 200 mg/kg, respectively, for successive 8 weeks. Histopathological and immunohistochemical analyses were conducted for evaluating severity of NASH-mice model and the effect of TFCH treatment. In vitro experiment was performed by using human LX-2 cells and cultured with Free fatty acid (FFA) (Oleic acid: palmitic: l: 0.5 mmol/L) for 24 h and then treated with TFCH at different concentrations (0, 25, 50, 100, 200 mg/ml) for 6 h,12 h, and 24 h. Anti-apoptosis effect of TFCH on LX-2 cells cultured with FFA was revealed by the CCK-8 assay. Lipid parameters and oxidative stress markers were measured in vivo and in vitro, results showed that TFCH dose-dependently and greatly increased the antioxidant ability and reduced the oxidative damage in NASH model. The protein expression of Nrf2 and the downstream target genes in mice liver and human LX-2 cells were tested by Western blot analysis to investigate the possible molecular mechanisms of TFCH. Our results indicated that TFCH up-regulated protein expression of these genes and have the significant influence in activating the Nrf2-ARE signaling pathway. This study shows Nrf2-ARE signaling pathway may provide novel therapeutic opportunities for NASH therapy in the future.