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.

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.

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.

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.

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.

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.

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.

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.

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.

Small Intestine Protection of Mica Against Non-Steroidal Anti-Inflammatory Drugs-Injury Through ERK1/2 Signal Pathway in Rats.

Objective: The impact of non-steroidal anti-inflammatory drugs (NSAIDs) to damage the small intestine has been well known. Mica, one kind of natural clay, has been widely marketed in China for the treatment of gastric diseases. However, the role and mechanism of mica in small intestinal injure is still unknown. The study was designed to declare the effects of mica on intestinal injury induced by diclofenac in rats. Methods: Rats were randomly divided into control, model, PAR-2 agonist group (SLIGRL-NH2group), control peptide group (LRGILS-NH2 group), and ERK blocker group (eight mice per group). Morphological changes of mucous membrane of small intestine were observed, and the expression of tryptase, PAR-2, and p-ERK1/2 was measured by immunohistochemistry and western blot. PAR-2 mRNA was tested by qRT-PCR. Rats were also randomly divided into control, model, and mica group (eight mice per group). Morphological changes of mucous membrane were observed. The expression of tryptase, PAR-2, and p-ERK1/2 was measured by immunohistochemistry. Results: The expression of trypsin, PAR-2, and p-ERK1/2 was increased in model group compared with control. The expression of PAR-2 and p-ERK1/2 was increased in SLIGRL-NH2 group compared with model, but not LRGILS-NH2 group. The expression of PAR-2 was down-regulated in ERK blocker group compared with SLIGRL-NH2 group. Macroscopically visible lesions of mucous membrane were positively correlated with the expression of PAR-2 and p-ERK1/2. Furthermore, we also found that mica could inhibit small intestinal injure, as evidenced by the improvement of macroscopic damage. Tryptase, PAR-2, and p-ERK1/2 expression was down-regulated in mica group compared with model group. Conclusion: Mica inhibit small intestinal injury induced by NSAIDs via ERK signaling pathway.

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.

NLRC5 mediates cell proliferation, migration, and invasion by regulating the Wnt/ß-catenin signalling pathway in clear cell renal cell carcinoma.

NLRC5, a newly discovered member of the NLR family, has been reported to regulate immune responses and promote cell proliferation, migration, and invasion in hepatocellular carcinoma. However, to date, the potential regulatory roles and molecular mechanisms by which NLRC5 affects the development and progression of clear cell renal cell carcinoma (ccRCC) remain largely unknown. In this study, human clinical data from The Cancer Genome Atlas database revealed that increased NLRC5 expression was associated with advanced stage and poor prognosis in ccRCC patients. Moreover, experimental results showed that NLRC5 is aberrantly overexpressed in human ccRCC tissues and cell lines. Depletion of NLRC5 attenuated ccRCC cell proliferation, migration, and invasion and suppressed ccRCC growth in a nude mouse model. By contrast, overexpression of NLRC5 promoted the proliferation, migration, and invasion of ccRCC cells in vitro. Additionally, NLRC5 expression is not only positively correlated with ß-catenin but also coordinates the activation of the downstream Wnt/ß-catenin signalling pathway. Together, our data suggest that NLRC5 may be a potential therapeutic target for ccRCC therapy.

Molecular mechanisms of the action of Arctigenin in cancer.

Since antediluvian times, the scientific community has realized that natural compounds exhibit enormous potential for the treatment of terrible diseases, such as cancer. Despite a variety of effective bioactive molecules, effective therapies still need to be developed to treat cancer. Hence, it is necessary to study the interactions of natural molecules with their cellular targets. Arctigenin (ATG), a natural lignan compound extracted from Arctium lappa, inhibits the growth of various cancer cells, such as those of the stomach, lungs, liver, and colon, as well as leukocytes, and regulates numerous intracellular activities, such as antioxidative, anti-inflammatory, and anticancer activities. The intention of this paper is to summarize and generally analyse the molecular pathways that are involved in the anticancer effects of ATG. In addition, the interactions of ATG with other drugs are also highlighted in this paper.

Emerging roles of hsa_circ_0005075 targeting miR-431 in the progress of HCC.

Circular RNAs (circRNAs) are non-coding RNAs that play key roles in the pathogenesis of diseases and are associated with human hepatocellular carcinoma (HCC). Previous reports have shown the circRNA hsa_circ_0005075 is highly expressed in HCC tissues, but its function is unknown. In this study, we confirmed circ_0005075 is significantly increased in HCC tissues and cell lines. This overexpression was associated with increased numbers of proliferative, migrated and invasive SMMC-7721 cells. In addition, hsa_circ_0005075 inhibited the transcription activity of miR-431 measured by dual-luciferase reporter assays. In contrast, silencing hsa_circ_0005075 decreased cell number. Finally, effects after hsa_circ_0005075 silencing were rescued by co-transfection with miR-431 inhibitor. These results suggest hsa_circ_0005075 promotes HCC via miR-431 regulation.

Short-term effects of fine particulate matter on non-accidental and circulatory diseases mortality: A time series study among the elder in Changchun.

BACKGROUND AND OBJECTIVES: Fine particulate matter (PM2.5, particulate matter with an aerodynamic diameter less than or equal to 2.5 µm) has multiple adverse effects on human health, especially on the respiratory and circulatory system. The purpose of this study was to evaluate the short-term effect of PM2.5 on the mortality risk of non-accidental and circulatory diseases, and to explore the potential effect modification by sex, education and death location. METHODS: We collected daily mortality counts of Changchun (China) residents, daily meteorology and air pollution data, from January 1, 2014, to January 1, 2017. We focused on the elderly (≥65 years old) population who died from non-accidental causes and circulatory diseases, and stratified them by sex, education, and death location. A generalized additive Poisson regression model (GAM) was used to analyse the impact of air pollutants on mortality. We fit single pollutant models to examine PM2.5 effects with different lag structures of single-day (distributed lag:lag0-lag3) and multi-day (moving average lag: lag01-lag03). To test the sensitivity of the model, a multi-pollutant model was established when the PM2.5 effect was strongest. RESULTS: In the single pollutant models, an increment of PM2.5 by 10 µg/m3 at lag0-3 was associated with a 0.385% (95% CI: 0.069% to 0.702%) increase in daily non-accidental mortality and a 0.442% (95% CI: 0.038% to 0.848%) increase in daily circulatory disease mortality. NO2 (lag1) and O3 (lag0, lag1, lag2, lag01,lag02, lag03) were associated with daily non-accidental death and NO2 (lag1, lag3, lag03) and O3 (lag0, lag1, lag01,lag02, lag03) were associated with daily circulatory disease mortality. In the co-pollutant models, the risk estimates for PM2.5 changed slightly. The excess mortality risk of non-accidental and circulatory diseases was higher for women, people with low education, and died outside hospital. CONCLUSIONS: We found that short-term exposure to PM2.5 increased the mortality risk of non-accidental and circulatory diseases among the elderly in Changchun. Women, people with low education and died outside hospital are more susceptible to PM2.5. NO2 and O3 were also associated with an increase in mortality from non-accidental and circulatory diseases and the O3 is a high effect.

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.

Therapeutic potential of cysteine-rich protein 61 in rheumatoid arthritis.

Cysteine-rich protein 61 (Cyr61)/CCN1, a product of an immediate early gene, can directly accommodate cell adhesion and migratory processes whilst simultaneously regulating the production of other cytokines and chemokines through paracrine and autocrine feedback loops. This intricate functionality of Cyr61 indicate its important role in targeting components of the infectious or chronic inflammatory disease processes including rheumatoid arthritis (RA). Recent work has focused on the role of Cyr61 in RA. For example, Cyr61 induced proIL-1ß production in FLS via the AKT-dependent NF-κB signaling pathway. Moreover, Cyr61-siRNA decreased the levels of matrix metalloproteinase (MMP)-3 and MMP-13, and induced apoptosis in RA-FLS cells. These results indicated that Cyr61 may represent a novel target for the treatment of RA. In this article we will introduce the molecular properties of Cyr61, discuss the function of Cyr61, and the therapeutic potential of modulating the Cyr61 in RA.

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.