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Prior reports have examined the relationship between obstructive sleep apnea (OSA) and the mortality rate of lung cancer. However, the findings remain controversial. The present meta-analysis was performed to assess the relationship between OSA and increased risk of mortality in patients with lung cancer. PubMed, Web of Science, and Embase were systematically searched for the correlative studies. Data were analyzed and pooled to evaluate odds ratios (ORs) of lung cancer mortality related to OSA. From 249 identified studies, 3 met inclusion criteria and were analyzed, including 67 patients with lung cancer and comorbid OSA and 45 patients with lung cancer and no OSA. The meta-analysis indicated that OSA was not significantly correlated with mortality rate in lung cancer (OR = 2.005, 95% CI = 0.703 to 5.715, z = 1.30, p = 0.193). There was no significant publication bias according to Begg’s tests (p = 0.296) and Egger’s tests (p = 0.097). This meta-analysis suggests that OSA is not significantly correlated with the mortality rate in lung cancer.

Introduction Angiogenesis is a key factor in promoting tumor growth, invasion and metastasis. In this study we aimed to investigate the prognostic value of angiogenesis-related genes (ARGs) in gastric cancer (GC). Methods mRNA sequencing data with clinical information of GC were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The differentially expressed ARGs between normal and tumor tissues were analyzed by limma package, and then prognosis‑associated genes were screened using Cox regression analysis. Nine angiogenesis genes were identified as crucially related to the overall survival (OS) of patients through least absolute shrinkage and selection operator (LASSO) regression. The prognostic model and corresponding nomograms were establish based on 9 ARGs and verified in in both TCGA and GEO GC cohorts respectively. Results Eighty-five differentially expressed ARGs and their enriched pathways were confirmed. Significant enrichment analysis revealed that ARGs-related signaling pathway genes were highly related to tumor angiogenesis development. Kaplan–Meier analysis revealed that patients in the high-risk group had worse OS rates compared with the low-risk group in training cohort and validation cohort. In addition, RS had a good prognostic effect on GC patients with different clinical features, especially those with advanced GC. Besides, the calibration curves verified fine concordance between the nomogram prediction model and actual observation. Conclusions We developed a nine gene signature related to the angiogenesis that can predict overall survival for GC. It’s assumed to be a valuable prognosis model with high efficiency, providing new perspectives in targeted therapy.

The role of hepatitis E virus (HEV) in developing hepatocellular carcinoma (HCC) is unclear. Our study aimed to investigate the role of HE infection in HCC development and the effect of hepatitis B virus (HBV) and HEV coinfection on HCC risk. A hospital-based case-control study was conducted. A total of 474 eligible HCC cases and 586 control patients were successfully recruited. The fasting venous blood was collected from the patients at the first visited to hospital and HBV infection and HEV infection were examined within 5 days. Crude and adjusted odd ratios (ORs) with 95% confidence interval (95% CI) were estimated by using logistic regression model. HBV infection (OR: 63.10, 95% CI: 42.02-97.26) rather than HEV infection (OR: 1.08, 95% CI: 0.721-1.65) was associated with an increased risk of HCC after adjustment for confounders. The association between HBV infection and HCC risk was more remarkable in male (OR: 72.61, 95% CI: 45.10-121.38) than in female (OR: 61.89, 95% CI: 25.74-169.26). In comparison with patients who infected with neither HEV nor HBV, those who infected with only HBV (OR: 69.62, 95% CI: 40.90-123.52) and who coinfected with HEV and HBV (OR: 67.48, 95% CI:37.23-128.19) were significantly associated with an increased risk after adjustment for potential confounders. The results showed that HBV infection rather than HEV infection was associated with an increased risk of HCC, and the HEV infection may alleviate the promoting impact of HBV on HCC development.

Background Distant metastasis (DM) is relatively rare in superficial gastric cancer (SGC), especially in patients without lymph node metastasis. This study aimed to explore the main clinical risk factors for DM in patients with superficial gastric cancer‐no lymph node metastasis (SGC‐NLNM) and the prognostic factors for patients with DM. Methods Records of patients with SGC‐NLNM between 2004 and 2015 were collected from the public Surveillance, Epidemiology, and End Results (SEER) database. Both univariate and multivariate logistic regressions were performed to analyze the clinical risk factors for DM. The Kaplan–Meier method and Cox regression model were used to identify prognostic factors for patients with DM. A nomogram was built based on multivariate logistic regression and evaluated by the C‐index, the calibration, and the area under the receiver operating characteristic curve (AUC). Results We developed and validated a nomogram to predict DM in patients with SGC‐NLNM, showing that race, age, primary site, depth, size, and grade were independent risk factors. The built nomogram had a good discriminatory performance, with a C‐index of 0.836 (95% confidence interval [CI]: 0.813–0.859). Calibration plots showed that the predicted DM probability was identical to the actual observations in both the training and validation sets. AUC was 0.846 (95% CI: 0.820–0.871) and 0.801 (95% CI: 0.751–0.850) in the training and validation sets, respectively. The results of the survival analysis revealed that surgery (hazard ratio [HR] = 0.249; 95% CI, 0.125–0.495), chemotherapy (HR = 0.473; 95% CI, 0.353–0.633), and grade (HR = 1.374; 95% CI, 1.018–1.854) were independent prognostic factors associated with cancer‐specific survival (CSS), but radiotherapy was not (log‐rank test, p = 0.676). Conclusions We constructed a sensitive and discriminative nomogram to identify high‐risk patients with SGC‐NLNM who may harbor dissemination at initial diagnosis. The tumor size and primary site were the largest contributors to DM prediction. Compared with radiotherapy, aggressive surgery, and chemotherapy may be better options for patients with DM., We identified the main clinical risk factors for distant metastasis (DM) in superficial gastric cancer‐no lymph node metastasis patients and the prognostic factors for the metastatic patients. Besides, a clinical tool was built for the DM prediction.

N-6-Methyladenosine (m

A series of novel rhein-piperazine-dithiocarbamate hybrids 3 were efficiently synthesized from rhein through a catalyst-free and one-pot, three-step sequence involving chlorination and N-acylation followed by dithiocarbamate formation. Hybrids 3 were evaluated for their in vitro cytotoxic potency by MTT assay against several human cancer and non-cancer cells. Five of the hybrids were more cytotoxic to human lung cancer cell line A549 than the parent rhein and the reference, cytarabine (CAR). Structure-activity relationship (SAR) analysis indicated that cytotoxicity was significantly enhanced when ester groups were incorporated into the hybrids (3h-j). In particular, hybrid 3h (IC

The objective of this study was to investigate the cumulative fraction of response (CFR) of various tigecycline dosing regimens in patients with hepatic or renal impairment.Monte Carlo simulations were performed using pharmacokinetic parameters and microbiological data to evaluate various tigecycline regimens in patients with hepatic or renal impairment.For HAP and cIAI, the regimen of 25 mg q12h achieved CFR values of90% in Child-Pugh C patients against Gram-positive bacteria and partial Gram-negative bacteria (It is necessary to optimize tigecycline dosage regimens in patients with hepatic or renal impairment in order to maximise clinical response and minimise the probability of exposure-related toxicity.

Based on previous researches of HoxC6, this study aims to investigate the expression levels of isoforms HoxC6-1 and HoxC6-2 and to explore their roles in gastric carcinogenesis as well as the possible molecular mechanism. We investigated expression levels of HoxC6, HoxC6-1, and HoxC6-2 in gastric cancer tissues, coupled with relevant data in TCGA dataset. In vitro, HoxC6, HoxC6-1, and HoxC6-2 knockdown by small interference RNA was carried for evaluating the changes of malignant biological behaviors of gastric cancer cells, such as proliferation, migration, invasion, apoptosis, and cell cycle alternation. Metastasis-related nucleotide lncRNA HOTAIR was selected by bioinformatics, and verification was carried out by in vitro researches. Data suggested HoxC6-1 and HoxC6-2 were considerably over-expressed with different folds in gastric cancerous tissues. Decreased expression of HoxC6-2 was detected in well-differentiated type of gastric cancer. In vitro, the conclusion that HoxC6 functions as a tumor oncogene illuminated by previous studies was verified again. Additionally, down-regulating of HoxC6-2 significantly inhibited SGC-7901 and BGC-823 cells from proliferation, migration, invasion, apoptosis, while quite slight results or none statistically significant results were observed when HoxC6-1 was knockdown. Besides, over-expression of HOTAIR, which is relevant with HoxC6 during gastric carcinogenesis, was detected in gastric cancerous tissues. Restored expression of HoxC6 partially reversed the decreased migration caused by down-regulating HOTAIR in gastric cancer cells. HoxC6 acts as an oncogene in gastric carcinogenesis and might be a promising therapeutic target. Isoform HoxC6-2 plays a primary carcinogenic role in gastric carcinogenesis. HOTAIR, over-expressed in gastric cancer, might regulate HoxC6 on the protein level in promoting migration of gastric cells.

Gastric cancer (GC) patients with metastasis had limited treatment options and dismal outcome. We have previously reported the aberrant expression of Zic family member 1 (Zic1) in GC. However, the functional roles and underlying mechanism of Zic1 in GC metastasis remain unknown. Here, we demonstrate that lower expression of Zic1 was correlated with more lymph node metastasis and poor outcome of GC patients. Ectopic expression of Zic1 suppressed both lung metastasis and peritoneal tumor dissemination of GC in mice. The metastatic suppressing ability of Zic1 was mediated by regulating the process of cell invasion, adhesion and epithelial-mesenchymal transition (EMT). Mechanistically, Zic1 could downregulate Wnt targets including c-Myc and Cyclin D1 by inhibiting LEF transcriptional activity in GC cells. Notably, Zic1 was inversely related to the expression of Cyclin D1 in GC tissues tested. In addition, Zic1 could physically interact with β-catenin/transcription factor 4 (TCF4) and disrupt their complex formation, while not affecting β-catenin nuclear localization. Collectively, our study indicated that Zic1 suppressed GC metastasis through attenuating Wnt/β-catenin signaling and the EMT process. Our work may provide novel therapeutic strategies for the metastasis of GC.

Objective The prevalence of inflammatory bowel disease (IBD) has been increasing worldwide, and the risk of infection has increased due to the use of immunosuppressive and biologic medications. Some of these infections can be prevented with vaccinations. The aim of this study was to evaluate the vaccination practices of Chinese gastroenterologists for patients with IBD. Methods Questionnaires based on quick response codes were sent using email and the WeChat platform to gastroenterologists at 20 hospitals in China. The vaccination practices of the gastroenterologists, including vaccinating for hepatitis B, hepatitis A, and varicella, were assessed. Results Of the 468 gastroenterologists who received the questionnaire, 307 (65.6%) completed it. Of the gastroenterologists who were most concerned about hepatitis B; 83.4% always or frequently asked about an infection history, 53.7% took an immunization history, and 73.6% tested patients for hepatitis B infection. However, few gastroenterologists did so for hepatitis A or varicella. The proportion of patients who were asked about an infection and immunization history and tested for varicella infection was 16.0%, 15.0%, and 9.4%, respectively. Only a few gastroenterologists recommended vaccination for patients without an infection before IBD medical treatment (26.7% for hepatitis A, 45.6% for hepatitis B, and 28% for varicella vaccination). Conclusion Vaccination practices for patients with IBD used by Chinese gastroenterologists vary greatly, suggesting that education about immunization is needed.

AimAnnual T1 stage papillary thyroid carcinoma (PTC) incidence rates continue to rise, yet the optimal treatment for this cancer type remains controversial. Central lymph node metastasis (CLNM) is a critical determinant in the context of treatment decision-making. While several prior studies have evaluated patients with clinica l T1a(cT1a) stage PTC, there have been fewer analyses of clinical T1b(cT1b) disease to date. The present study was thus formulated to explore predictors of CLNM in patients with cT1a and cT1b stage PTC.MethodsA retrospective analysis of data including clinicopathological characteristics and BRAFV600E mutation status was conducted for 452 PTC patients undergoing surgical treatment. Logistic univariate and multivariate analyses were performed to identify risk factors associated with CLNM in particular patients’ characteristics and the accuracy of the established logistic regression models was evaluated using the R software platform.ResultsRespective CLNM incidence rates in cT1a and cT1b disease were 39.39% and 67.21%. Factors associated with a higher risk of CLNM among PTC(cT1a) patients included male sex, young age, tumor size, contact with capsule, and multifocality as determined through comparisons of the area under the curve for logistic regression models. Whereas male sex and age were associated with CLNM risk in PTC(cT1b) patients in univariate and multivariate analyses, age was the only risk factor associated with CLNM incidence among women with PTC(cT1b).ConclusionPredictors of CLNM differ between PTC patients with cT1a and cT1b stage disease, and a comprehensive assessment of these risk factors should thus be conducted when designing individualized treatment regimens for PTC patients.

Colorectal cancer (CRC) is among the leading cause of cancer-related morbidity and mortality worldwide. Aerobic glycolysis, as a metabolic hallmark of cancer, plays an important role in CRC progression. Enolase 3 (ENO3) is a glycolytic enzyme that catalyzes 2-phosphoglycerate into phosphoenolpyruvate, while its role in CRC is still unknown.Bioinformatics analysis was performed to examine the expression changes and roles of ENO3 in CRC patients from public databases. Then, ENO3 expression was validated in CRC tissues using Quantitative real-time PCR (qRT-PCR), immunohistochemical (IHC) analysis, and western blot. Overexpression and silencing models were constructed using plasmid and lentivirus transfection. Cell viability, proliferation, and migration in vitro were applied to evaluate the protumoral effects of ENO3 on CRC. RNA sequencing and GO enrichment analysis of differentially expressed genes (DEGs) were performed to explore the underlying molecular mechanisms of ENO3 in CRC progression. The ATP and lactate production level were detected to assess cell glycolysis.ENO3 was significantly up-regulated in CRC. High ENO3 expression was positively correlated with poor prognosis and higher clinical stages of CRC patients. ROC curve demonstrated the diagnostic value of ENO3 for CRC with the AUC of 0.802. Gain- and loss-of function experiments demonstrated that ENO3 significantly enhanced the proliferation and migration ability of CRC cells in vitro. After ENO3 knockdown, RNA sequencing screened out a list of DEGs which were enriched in the regulation of the glycolytic process. The detection of lactate production and ATP level verified the role of ENO3 in the glycolytic process.Our findings illustrate that ENO3 could promote the progression of CRC by the enhancement of cell glycolysis, indicating the potential value of ENO3 as a novel biomarker and therapeutic target for CRC.

Objective. Develop a set of knee joint martial arts injury monitoring models based on deep learning, train and evaluate the model’s effectiveness. Methods. This paper mainly collects knee MRI images of 1546 patients with knee joint martial arts injuries from 2015 to 2020. Through manual annotation, the data set is divided into six categories: meniscus injury, tendon injury, ligament injury, epiphyseal cartilage injury and synovial joint capsule loss. The human knee collaborative MRI image database is established, and the data set is divided into the training and validation sets. And test set. Establish a deep neural network, train the model using the training set and validation set, locate the knee joint injury location, and classify the specific injury type. The model’s validity was validated using the test set, and the model’s sensitivity, specificity, and mean accuracy for detecting lesions were evaluated. Results. In the test set, the accuracy of meniscus injury, tendon injury, ligament injury, bone and bone cartilage injury and synovial joint capsule injury were 83.2%, 89.0%, 88.0%, 85.9%, 85.6% and 83.5%, respectively, and the overall average accuracy value was 86.0%. The sensitivity and specificity of the model were 91.3% and 87.3%, respectively. Conclusion. The application of the deep learning method in the classification and detection of knee joint martial arts injuries can significantly improve the diagnosis effect, reduce the diagnosis time and misdiagnosis rate, and provide decision support for surgery.

The rapid development of the textile industry and improvement of people's living standards have led to the production of cotton textile and simultaneously increased the production of textile wastes. Cotton is one of the most common textile materials, and the waste cotton accounts for 24% of the total textile waste. To effectively manage the waste, recycling and reusing waste cotton are common practices to reduce global waste production. This paper summarizes the characteristics of waste cotton and high-value products derived from waste cotton (e.g., yarns, composite reinforcements, regenerated cellulose fibers, cellulose nanocrystals, adsorptive materials, flexible electronic devices, and biofuels) via mechanical, chemical, and biological recycling methods. The advantages and disadvantages of making high-value products from waste cotton are summarized and discussed. New technologies and products for recycling waste cotton are proposed, providing a guideline and direction for merchants and researchers. This review paper can shed light on converting textile wastes other than cotton (e.g., bast, silk, wool, and synthetic fibers) into value-added products.

Obstructive sleep apnea (OSA) has been demonstrated to be associated with an increase of oxidative stress. However, whether circulating malondialdehyde (MDA), a widely used biomarker of oxidative stress, could be reduced by the treatment of OSA by continuous positive airway pressure (CPAP) is debated. The present meta-analysis was performed to determine the effect of CPAP treatment on circulating MDA among patients with OSA. A systematic search of PubMed, Embase, and Web of Science was performed for literature covering the period between 1967 and August 2019. Standardized mean difference (SMD) was calculated to estimate the treatment effects of pre- and post-CPAP therapy. A total of 10 studies with 220 patients were included in this meta-analysis. A significant decrease in circulating MDA was observed after CPAP treatment (SMD = 1.164, 95% CI = 0.443 to 1.885, z = 3.16, p = 0.002) in OSA patients. Subgroup analyses revealed that CPAP therapy was associated with a significant decrease of circulating MDA in elder (SMD = 1.629, 95% CI = 0.265 to 2.994, z = 2.34, p = 0.019), more obese patients (SMD = 0.954, 95% CI = 0.435 to 1.473, z = 3.61, p = 0.000), more severe OSA patients (SMD = 0.879, 95% CI = 0.421 to 1.336, z = 3.76, p = 0.000), patients with therapeutic duration ≥ 3 months (SMD = 1.867, 95% CI = 0.563 to 3.172, z = 2.80, p = 0.005), and patients with good compliance (SMD = 1.004, 95% CI = 0.703 to 1.305, z = 6.54, p = 0.000). This meta-analysis suggested that CPAP therapy exerted significant lowering effects on circulating MDA, especially in elder, more obese, and more severe OSA patients and patients with good compliance as well as longer duration of CPAP application.

During the COVID-19 lockdown, atmospheric PM

Background Glioblastoma (GBM) has a high incidence rate, invasive growth, and easy recurrence, and the current therapeutic effect is less than satisfying. Pyroptosis plays an important role in morbidity and progress of GBM. Meanwhile, the tumor microenvironment (TME) is involved in the progress and treatment tolerance of GBM. In the present study, we analyzed prognosis model, immunocyte infiltration characterization, and competing endogenous RNA (ceRNA) network of GBM on the basis of pyroptosis-related genes (PRGs). Methods The transcriptome and clinical data of 155 patients with GBM and 120 normal subjects were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). Lasso (Least absolute shrinkage and selection operator) Cox expression analysis was used in predicting prognostic markers, and its predictive ability was tested using a nomogram. A prognostic risk score formula was constructed, and CIBERSORT, ssGSEA algorithm, Tumor IMmune Estimation Resource (TIMER), and TISIDB database were used in evaluating the immunocyte infiltration characterization and tumor immune response of differential risk samples. A ceRNA network was constructed with Starbase, mirtarbase, and lncbase, and the mechanism of this regulatory axis was explored using Gene Set Enrichment Analysis (GSEA). Results Five PRGs (CASP3, NLRP2, TP63, GZMB, and CASP9) were identified as the independent prognostic biomarkers of GBM. Prognostic risk score formula analysis showed that the low-risk group had obvious survival advantage compared with the high-risk group, and significant differences in immunocyte infiltration and immune related function score were found. In addition, a ceRNA network of messenger RNA (CASP3, TP63)–microRNA (hsa-miR-519c-5p)–long noncoding RNA (GABPB1-AS1) was established. GSEA analysis showed that the regulatory axis played a considerable role in the extracellular matrix (ECM) and immune inflammatory response. Conclusions Pyroptosis and TME-related independent prognostic markers were screened in this study, and a prognosis risk score formula was established for the first time according to the prognosis PRGs. TME immunocyte infiltration characterization and immune response were assessed using ssGSEA, CIBERSORT algorithm, TIMER, and TISIDB database. Besides a ceRNA network was built up. This study not only laid foundations for further exploring pyroptosis and TME in improving prognosis of GBM, but also provided a new idea for more effective guidance on clinical immunotherapy to patients and developing new immunotherapeutic drugs.

Background The prognosis of patients with advanced gastric cancer (GC) remains unsatisfactory owing to distant metastasis and resistance to concurrent systemic therapy. Cancer-associated fibroblasts (CAFs), as essential participators in the tumor microenvironment (TME), play a vital role in tumor progression. Thus, CAFs-targeting therapy is appealing for remodeling TME and sensitizing GC to conventional systemic therapy. Methods Amphiphilic SN38 prodrug polymeric micelles (PSN38) and encapsulated the hydrophobic esterase-responsive prodrug of Triptolide (TPL), triptolide-naphthalene sulfonamide (TPL-nsa), were synthesized to form PSN38@TPL-nsa nanoparticles. Then, CAFs were isolated from fresh GC tissues and immortalized. TPL at low dose concentration was used to investigate its effect on CAFs and CAFs-induced GC cells proliferation and migration. The synergistic mechanism and antitumor efficiency of SN38 and TPL co-delivery nanoparticle were investigated both in vitro and in vivo. Results Fibroblast activation protein (FAP), a marker of CAFs, was highly expressed in GC tissues and indicated poorer prognosis. TPL significantly reduced CAFs activity and inhibited CAFs-induced proliferation, migration and chemotherapy resistance of GC cells. In addition, TPL sensitized GC cells to SN38 treatment through attenuated NF-κB activation in both CAFs and GC cells. PSN38@TPL-nsa treatment reduced the expression of collagen, FAP, and α-smooth muscle actin (α-SMA) in tumors. Potent inhibition of primary tumor growth and vigorous anti-metastasis effect were observed after systemic administration of PSN38@TPL-nsa to CAFs-rich peritoneal disseminated tumor and patient-derived xenograft (PDX) model of GC. Conclusion TPL suppressed CAFs activity and CAFs-induced cell proliferation, migration and chemotherapy resistance to SN38 of GC. CAFs-targeted TPL and SN38 co-delivery nanoparticles exhibited potent efficacy of antitumor and reshaping TME, which was a promising strategy to treat advanced GC. Graphical Abstract

N1-methyladenosine (m1A), is a unique methyl group that confers post-transcriptional modification of gene expression, and plays important roles in various human diseases. However, the abundance of this modification and its effects on long non-coding RNAs (lncRNAs) in human colorectal cancer (CRC) remain unclear. In this study, methylated RNA immunoprecipitation sequencing was performed in three pairs of human CRC and nontumorous tissues to identify m1A peaks and its correlation with differential alterations of lncRNA expression in CRC. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment pathway analyses were applied to predict the potential roles of m1A on gene expression. We found that CRC and adjacent tissues had a noticeable difference in m1A distribution. Notably, HGGAGRA and WGGANGA were recognized as the most significantly enriched motifs, respectively. Co-analysis of methylation and RNA sequencing demonstrated downregulated lncRNAs along with m1A modification in CRC. GO and KEGG pathway analyses revealed that the unique distribution of m1A sites in lncRNAs had a significant correlation with CRC signaling pathways. In conclusion, our results delineated the distribution pattern of m1A methylation on lncRNAs, and provided potential roles of this modification in different pathways and tumor progression of CRC.

To observe the analgesic effect of auricular point sticking therapy during the perioperative stage in the patients with partial lung resection.A total of 92 patients with partial lung resection were randomized into an auricular point group (31 cases, 1 case dropped off), the sham-auricular point group (30 cases) and a medication group (31 cases, 1 case dropped off). The routine medication for analgesia was provided in all of the three groups. In the auricular point group, 1 day before operation, the auricular point sticking therapy was applied at shenmen (TFIn 8, 16, 24, 48 h and 72 h after operation, VAS scores in the auricular point group were lower than those in the sham-auricular point group and the medication group separately (Auricular point sticking therapy relieves perioperative pain, shortens analgesic time, releases anxious and depressive emotions and reduces postoperative adverse reaction in the patients with partial lung resection. The analgesic mechanism is probably related to the increase of plasma concentration of β-endorphin.

Senescent microenvironments play an important role in tumor progression. Here, we report that doxorubicin (DOX)‐pretreated or replicative senescent stromal cells (WI‐38 and HUVEC) promote colorectal cancer (CRC) cell growth and invasion in vitro and in vivo. These pro‐tumorigenic effects were attenuated by exogenous administration of Klotho, an anti‐aging factor. We subsequently identified several senescence‐associated secretory phenotype (SASP)‐associated genes, including CCL2, which were significantly upregulated in both types of senescent stromal cells during replication and DNA damage‐induced senescence. Importantly, we found that the secretion of CCL2 by senescent stromal cells was significantly higher than that seen in nonsenescent cells or in senescent cells pretreated with Klotho. Notably, CCL2 was found to accelerate CRC cell proliferation and invasion, while this effect could be blocked by administration of a specific CCR2 antagonist. We further show that Klotho can suppress NF‐κB activation during DOX‐induced senescence and thus block CCL2 transcription. Low expression of Klotho, or high expression of CCL2 in patient tumor tissues, correlated with poor overall survival of CRC patients. Collectively, our findings suggest that senescent stromal cells are linked to progression of CRC. Klotho can suppress the senescent stromal cell‐associated triggering of CRC progression by inhibiting the expression of SASP factors including CCL2. The identification of key SASP factors such as CCL2 may provide potential therapeutic targets for improving CRC therapy.

Twelve derivatives of artemisinin-piperazine-dithiocarbamate have been synthesised, and some of them showing good in vitro cytotoxic activity. Compound 3g exhibits the best inhibitory activity against SMMC-7721 cell lines with an IC50 of 0.0025 ± 0.04 μM for 72 h, but the toxicity was lower against LO2 cell lines with an IC50 of 0.18 ± 0.04 μM for 72 h. The results indicate that compound 3g is more cytotoxic towards cancer cell lines than towards benign cell lines compared with vincristine in vitro. And compound 3g also has good inhibitory activity against colon, breast and prostate cancer cells. Meanwhile, we have also proposed the six-member ring mechanism of DMSO in catalysing the esterification of hydroxyl and acyl chloride. Instead of using the hydroxyl, we can obtain the nucleophilic substitution production simply and efficiently without a Lewis acid, which has not been reported previously.

During a minimally invasive tumor resection procedure, it is still a challenge to rapidly and accurately trace tiny malignant tumors in real time. Fluorescent molecular imaging is considered an efficient method of localizing tumors during surgery due to its high sensitivity and biosafety. On the basis of the fact that γ-glutamyltranspeptidase (GGT) is overexpressed in ovarian cancer, we herein designed a highly sensitive ratiometric fluorescent GGT-responsive probe Py-GSH for rapid tumor detection. Methods: The GGT response probe (Py-GSH) was constructed by using GSH group as a response group and pyrionin B as a fluorescent reporter. Py-GSH was characterized for photophysical properties, response speed and selectivity of GGT and response mechanism. The anti-interference ability of ratiometric probe Py-GSH to probe concentration and excitation power was evaluated both in vitro and in tissue. The biocompatibility and toxicity of the ratiometric probe was examined using cytoxicity test. The GGT levels in different lines of cells were determined by ratiometric fluorescence imaging and cytometry analysis. Results: The obtained probe capable to rapidly monitored GGT activity in aqueous solution with 170-fold ratio change. By ratiometric fluorescence imaging, the probe Py-GSH was also successfully used to detect high GGT activity in solid tumor tissues and small peritoneal metastatic tumors (~1 mm in diameter) in a mouse model. In particular, this probe was further used to determine whether the tissue margin following clinical ovarian cancer surgery contained tumor. Conclusion: In combination of ratiometric fluorescence probes with imaging instrument, a point-of-care imaging method was developed and may be used for surgical navigation and rapid diagnosis of tumor tissue during clinical tumor resection.

BackgroundThe effect of a combination of a goal-directed fluid protocol and preoperative carbohydrate loading on postoperative complications in elderly patients still remains unknown. Therefore, we designed this trial to evaluate the relative impact of preoperative carbohydrate loading and intraoperative goal-directed fluid therapy versus conventional fluid therapy (CFT) on clinical outcomes in elderly patients following gastrointestinal surgery.MethodsThis prospective randomized controlled trial with 120 patients over 65 years undergoing gastrointestinal surgery were randomized into a CFT group (n = 60) with traditional methods of fasting and water-deprivation, and a GDFT group (n = 60) with carbohydrate (200 ml) loading 2 h before surgery. The CFT group underwent routine monitoring during surgery, however, the GDFT group was conducted by a Vigileo/FloTrac monitor with cardiac index (CI), stroke volume variation (SVV), and mean arterial pressure (MAP). For all patients, demographic data, intraoperative parameters and postoperative outcomes were recorded.ResultsPatients in the GDFT group received significantly less crystalloids fluid (1111 ± 442.9 ml vs 1411 ± 412.6 ml;p p p = 0.002) and oral intake (72 ± 16.9 h vs 85 ± 26.8 h;p = 0.011), as well as a reduction in the rate of postoperative complications (15 (25.0%) vs 29 (48.3%) patients;p = 0.013). However, postoperative hospitalization or hospitalization expenses were similar between groups (p > 0.05).ConclusionsFocused on elderly patients undergoing open gastrointestinal surgery, we found perioperative fluid optimisation may be associated with improvement of bowel function and a lower incidence of postoperative complications.Trial registrationChiCTR,ChiCTR1800018227. Registered 6 September 2018 - Retrospectively registered.

Obstructive sleep apnea (OSA) is a risk factor for atherosclerosis. Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is strongly linked to endothelial cell functions. However, the function of MALAT1 in intermittent hypoxia (IH) associated vascular endothelial injury has not been explored yet. The current study makes great attempts to investigate the function of MALAT1 in IH-induced endothelial injury and its latent control network.To mimic the effect of OSA, we cultured the human umbilical vein endothelial cells (HUVECs) under intermittent hypoxia. Western blot was applied to measure the expression level of associated proteins including capase-3, Bax, Bcl-2 while qRT-PCR was used in measurement of MALAT1 and miR-142-3p. Cell Counting Kit-8 (CCK-8) was carried out in assessing cell viability. Dual-luciferase reporter assay was applied to verify the relationships among high mobility group box (HMGB)1 and MALAT1, miR-142-3p.IH treatment significantly reduced cell viability but enhanced cell apoptosis in HUVECs. Concomitantly, MALAT1 was significantly upregulated in IH-treated HUVECs. Further experiment showed that MALAT1 knockdown augmented IH-induced injury of HUVECs. In addition, it was confirmed by dual-luciferase reporter assay that MALAT1 interacted with miR-142-3p directly. Besides, inhibition of miR-142-3p alleviated damage induced by MALAT1 knockdown in IH-treated HUVECs. Finally, miR-142-3p interacted with HMGB1 directly and inhibition of HMGB1 protein expression mediated by MALAT1 knockdown was reversed by miR-142-3p inhibitor.IH resulted in increased expression of MALAT1 in HUVECs. MALAT1 knockdown augmented IH-induced injury of HUVECs. MALAT1 exerted its effects on IH-treated HUVECs via miR-142-3p/HMGB1.

Background Some studies have reported a relationship between obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) in pediatric population. However, this issue remains controversial. Objectives The purpose of the present study was to investigate the association between OSA and NAFLD in pediatric population. Methods We systematically searched PubMed, Web of Science, Embase for eligible studies. The data involving markers of NAFLD including alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic inflammation, hepatic fibrosis of both OSA group and control group were extracted. Pooled standardised mean difference (SMD) and weighted mean difference (WMD) were appropriately calculated through a fixed or random-effect model. Results Nine cross-sectional studies with 1133 children and adolescents were included. OSA was significantly associated with ALT, AST, and NAFLD fibrosis stage, but not NAFLD inflammation grade. Subgroup analysis indicated that both mild OSA and severe OSA were significantly associated with elevated ALT and AST. Furthermore, in the studies with all main confounding factors (age, gender, and BMI) matched, OSA group had higher ALT and AST levels than control group. Conclusions This meta-analysis suggested that OSA was associated with NAFLD evidenced by elevated liver enzymes and progressive hepatic fibrosis in pediatric population. Screening and monitoring of NAFLD in pediatric patients with obesity-related OSA are necessary.

Background: Evidence shows that the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway participates in the pathogenesis of neuropathic pain. Our previous study revealed that electroacupuncture (EA) attenuated neuropathic pain via activation of alpha-7 nicotinic acetylcholine receptor (α7nAChR) in the spinal cord. However, whether 2 Hz EA alleviates neuropathic pain by regulating the downstream molecules JAK2/STAT3 has not been fully clarified. Methods: Paw withdrawal threshold (PWT) was used as a marker of mechanical allodynia in rats with spared nerve injury (SNI). After applying 2 Hz EA on day 3, 7, 14 and 21 post-surgery, spinal expression of JAK2, STAT3 and pro-inflammatory cytokine interleukin (IL)-6 was examined using quantitative reverse transcription and real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. Intrathecal injection of the α7nAChR antagonist alpha-bungarotoxin (α-Bgtx) was used to further explore the mechanism underlying the effects of 2 Hz EA on expression of JAK2/STAT3 in SNI rats. Results: It was found that levels of spinal STAT3 and IL-6 mRNA, as well as levels of phosphorylated (p)-JAK2, p-STAT3 and IL-6 protein, were markedly increased in SNI rats. 2 Hz EA attenuated the SNI-induced up-regulation of p-JAK2, p-STAT3 and IL-6 expression in the spinal cord. Furthermore, intrathecal injection of α-Bgtx (1.0 μg/kg) not only inhibited the effect of 2 Hz EA on mechanical hypersensitivity but also ameliorated the down-regulation of p-JAK2, p-STAT3 and IL-6 expression induced by 2 Hz EA. Conclusion: This study revealed that 2 Hz EA attenuated SNI-induced mechanical hypersensitivity and the concomitant up-regulation of spinal JAK2, STAT3 and IL-6 in SNI rats, suggesting that suppression of the JAK2/STAT3 signaling pathway might be the mechanism underlying the therapeutic effect of 2 Hz EA on neuropathic pain.

Background The epithelial-mesenchymal transition (EMT) plays a pivotal role in various physiological processes, such as embryonic development, tissue morphogenesis, and wound healing. EMT also plays an important role in cancer invasion, metastasis, and chemoresistance. Additionally, EMT is partially responsible for chemoresistance in colorectal cancer (CRC). The aim of this research is to develop an EMT-based prognostic signature in CRC. Methods RNA-seq and microarray data, together with clinical information, were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. A total of 244 differentially expressed EMT-related genes (ERGs) were obtained by comparing the expression between normal and tumor tissues. An EMT-related signature of 11 genes was identified as crucially related to the overall survival (OS) of patients through univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO), and Cox regression analysis. Finally, we established a clinical nomogram to predict the survival possibility of CRC patients by integrating clinical characteristics and the EMT-related gene signature. Results Two hundred and forty-four differentially expressed ERGs and their enriched pathways were confirmed. Significant enrichment analysis revealed that EMT-related signaling pathway genes were highly related to CRC. Kaplan-Meier analysis revealed that the 11-EMT signature could significantly distinguish high- and low-risk patients in both TCGA and GEO CRC cohorts. In addition, the calibration curves verified fine concordance between the nomogram prediction model and actual observation. Conclusion We developed a novel EMT-related gene signature for the prognosis prediction of CRC patients, which could improve the individualized outcome prediction in CRC.

Background Non-syndrome cleft lip with or without cleft palate (NSCL/P) is the most common congenital defect with a complex etiology involving both genetic and environmental factors. Our previous research has identified susceptibility genes of NSCL/P using whole-exome sequencing. The study was to determine the effects of small interfering RNA (siRNA)-mediated silencing of genes on cell proliferation and migration to confirm the roles of the genes in NSCL/P. Methods We silenced the genes by RNA interference (RNAi) with siRNA in human oral keratinocyte (HOK). We used the Cell Counting Kit-8 (CCK8) assay to determine cell proliferation and the wound healing assay to determine cell migration. Results Migration of HOK was inhibited by RNAi-induced silencing of adenosine triphosphate binding cassette transporter A4 (ABCA4), erythropoietin produces hepatocyte A receptor 3 (EPHA3), alpha-parvin (PARVA), and platelet-derived growth factor C (PDGFC). The change of proliferation was not found. Treated with siRNA-mediated silencing of type IV collagen (COL4A2), eukaryotic translation initiation factor 2B subunit (EIF2B3), fibroblast growth factor receptor 2 (FGFR2), kinesin family member 20B (KIF20B), β-lactamase serine-like protein (LACTB), SEC16 homolog A (SEC16A) and thyroid adenoma target gene (THADA) had no effects on cell proliferation and migration of HOK. Conclusions We suggest mutations of the four susceptibility genes ABCA4, EPHA3, PARVA and PDGFC are involved in NSCL/P through inhibiting cell migration. The study provides new candidates for future study of NSCL/P.

The effect of exosomes on receptor cells participating in intercellular communication has been extensively studied, but the effect of exosomes on donor cells remains unclear. It has been reported that exosomes secreted by renal proximal tubular epithelial cells (PTECs) under different stimuli accelerate acute and chronic kidney diseases. This study aimed to explore whether inhibiting exosomal secretion in PTECs by knocking out Rab27a, a key exosome regulatory gene, inhibits the excessive inflammatory response in PTECs and delays diabetic kidney disease (DKD). First, we proved that the bovine serum albumin (BSA)-induced inflammatory response in HK-2 cells was inhibited by knocking out Rab27a and that Rab27a, IL-6, TNF-α and COL-1 expression was markedly increased in an HFD/STZ-induced diabetic mouse model. Furthermore, miR-26a-5p expression in exosomes secreted by BSA-treated HK-2 cells was significantly increased but correspondingly decreased in the cells; after knocking out Rab27a, miR-26a-5p levels in the cells rebounded. Next, we confirmed that a miR-26a-5p mimic suppressed the inflammatory response, while a miR-26a-5p inhibitor accelerated the inflammatory response. Then, we found that miR-26a-5p targets the 3'-untranslated region (UTR) of CHAC1. Furthermore, the inflammatory response and NF-κB signalling pathway activation induction by the miR-26a-5p inhibitor were abolished by CHAC1 knockout. Therefore, we conclude that inhibiting exosome secretion by BSA-induced PTECs promotes miR-26a-5p expression in cells, thereby inhibiting the CHAC1/NF-κB pathways to prevent the inflammatory response in PTECs and delaying the development of DKD. This study provides new insight into the pathogenic mechanism of exosomes and a new therapeutic target for DKD.

Background Human defensin-5 (HD-5) is a key antimicrobial peptide which plays an important role in host immune defense, while the short half-life greatly limits its clinical application. The purpose of this study was to investigate the effects of an engineering probiotic producing HD-5 on intestinal barrier and explore its underlying mechanism Methods We constructed the pN8148-SHD-5 vector, and transfected this plasmid into Lactococcus lactis (L. lactis) to create the recombinant NZ9000SHD-5 strain, which continuously produces mature HD-5. NZ9000SHD-5 was administrated appropriately in a dextran sodium sulfate (DSS)-induced colitis model. Alterations in the wounded intestine were analyzed by hematoxylin–eosin staining. The changes of intestinal permeability were detected by FITC-dextran permeability test, the tight junction (TJ) proteins ZO-1 and occludin and cytokines were analyzed by western blotting or enzyme linked immunosorbent assay. In Caco-2 cell monolayers, the permeability were analyzed by transepithelial electrical resistance, and the TJ proteins were detected by western blotting and immunofluorescence. In addition, NF-κB signaling pathway was investigated to further analyze the molecular mechanism of NZ9000SHD-5 treatment on inducing intestinal protection in vitro. Results We found oral administration with NZ9000SHD-5 significantly reduced colonic glandular structure destruction and inflammatory cell infiltration, downregulated expression of several inflammation-related molecules and preserved epithelial barrier integrity. The same protective effects were observed in in vitro experiments, and pretreatment of macrophages with NZ9000SHD-5 culture supernatants prior to LPS application significantly reduced the expression of phosphorylated nuclear transcription factor-kappa B (NF-κB) p65 and its inhibitor IκBα. Conclusions These results indicate the NZ9000SHD-5 can alleviate DSS-induced mucosal damage by suppressing NF-κB signaling pathway, and NZ9000SHD-5 may be a novel therapeutic means for ulcerative colitis.

National Bureau of Statistics of China reports that the incidence of schistosomiasis has been increasing in recent years. To study dynamic behaviors of schistosomiasis transmission, based on practical experience of staff in Anhui Institute of Schistosomiasis, a mathematical schistosomiasis model with reinfection of recovered people is established in this paper. Metzler matrix theory and center manifold theorem are used to analyze stability of equilibria. Parameter estimation has been performed by combining model and monitoring data. It is found that the basic reproduction number is different every year. The most concern of Institute of Schistosomiasis is whether or when to kill snails every year. To answer this question, threshold value of snail density can be obtained. Once the snail density exceeds the threshold, the staff will need to kill snails. To find the best control measures, sensitivity analysis is used to find out sensitive parameters, and then control measures can be obtained by optimization control measures. The results show that combination of spraying molluscicide, publicity and education, improving the health facilities, and large-scale treatment of patient groups have the best effect. In additional, it is found that the number of patients does not change much when the reinfection rate of recovered people is very small. However, when the reinfection rate is slightly larger, the number of patients will suddenly increase to a large value.

Background Cleft lip with or without cleft palate (CL/P) is one of the most common congenital defects, which etiology involves both genetic and environmental factors. Previous studies have shown that miR-199a-5p may mediate the occurrence of CL/P. However, the key target genes regulated by miR-199a-5p are not clear. In this study, we employed a systematic bioinformatics analysis of target genes regulated by miR-199a-5p which may be involved in CL/P. Methods The miRBase, Human miRNA tissue atlas, miRecords, miRpathDB, miRWalk, miRTarBase, DIANA-TarBase (v7.0), Literature search, DAVID software, Cytoscape plugin ClueGO + Cluepedia app, MalaCards, TargetScanhuman7.1, Venny 2.1, STRING and GEO databases were comprehensive employed to identify the key genes regulated by miR-199a-5p associated with CL/P. Results Total 429 experimentally validated target genes were obtained from five miRNAs related databases. Expressions of miR-199a-5p and its experimentally validated target genes were elevated in bone, brain and skin. KEGG pathway analysis revealed that the target genes were enriched in focal adhesion, microRNAs in cancer and hippo signaling pathway. Biological process categorization revealed that significant portions of the target genes were grouped as transcription, DNA-templated. Total eight intersection genes were identified by using MalaCards and TargetScanhuman7.1. The target gene transforming growth factor alpha (TGFA) of miR-199a-5p involved in CL/P is screened and verified. Conclusion MiR-199a-5p may mediate CL/P by regulating key target gene TGFA. The study may contribute to a better understanding of the etiology of CL/P.

Ulcerative colitis (UC) is an independent risk factor of colorectal cancer (CRC). Both genetic and epigentic events induce a unique molecular profile during the development from UC to UC-related CRC (UCRC). These molecular changes play varied roles in DNA repair, immune response, cell metabolism, and interaction with the microbiota during the carcinogenesis process. This review will systmatically discuss the molecular characteristics of UCRC and point out the future perspectives in this research field.

Tubulointerstitial fibrosis (TIF) is crucial in the development of renal fibrosis in diabetic nephropathy(DN). Previous data shows that SIRT1 plays an important role on fibrosis, but the effect on TIF in DN and underlying mechanisms remains uncertain. In this study, we evaluated the vital role of SIRT1 and identified SIRT1 as a downstream target gene of microRNA-34a-5p (miR-34a-5p) in TIF of DN. The result revealed that expression of miR-34a-5p, fibronectin(FN),collagen type I (COL1) and transforming growth factor β1 (TGF-β1) were up-regulated accompanied by the corresponding down-regulation of SIRT1 in renal tissues of high fat diet and streptozotocin(HFD/STZ)induced diabetic mice with DN, and that the SIRT1 mRNA level was negatively correlated with miR-34a-5p expression in high glucose stimulated human proximal tubule cell line(HK-2) cells. We then demonstrated that overexpression of SIRT1 reduced, whereas small interfering RNA targeting SIRT1 enhanced the expressions of TGF-β1 and fibrosis-related genes including FN and COL1 in HK-2 cells. Furthermore, we identified that miR-34a-5p directly suppressed SIRT1 to increase the profibrogenic effects of TGFβ1 through targeting the 3'untranslated region of SIRT1. The functional correlation of miR-34a-5p induced SIRT1 decrease was supported by overexpression and inhibition of miR-34a-5p in HK-2 cells. All the results reveal that SIRT1 which is vital in the evolution of renal TIF in DN can be directly suppressed by miR-34a-5p, and suggest that miR-34a-5p is a new target for DN treatment.

Long non-coding RNAs (LncRNAs) exert their functions mainly by binding to their corresponding proteins. Runt-related transcription factor 3 (Runx3) is an important transcription factor that functions as a tumor suppressor in gastric cancer. Whether there is an interplay between LncRNAs and Runx3 remains unclear. RPISeq was applied to screen the LncRNAs that potentially bind to Runx3. The interaction between LncRNA HOX antisense intergenic RNA (HOTAIR) and Runx3 was validated by RNA Immunoprecipitation and RNA pull-down assays. The role of Mex3b in the ubiquitination of Runx3 induced by HOTAIR was assessed by immunoprecipitation. Pearson’s correlation between HOTAIR mRNA expression and Runx3 protein expression was analyzed. Cell migration and invasion were explored by transwell assays. We found that HOTAIR was bound to Runx3 protein and identified the fragment of HOTAIR spanning 1951–2100 bp as the specific binding site. In addition, mex-3 RNA binding family member B (Mex3b) was an E3 ligase involved in HOTAIR-induced ubiquitous degradation of Runx3. Silencing the expression of HOTAIR or Mex3b attenuated the degradation of Runx3. In human gastric cancer tissues, HOTAIR was negatively associated with the expression level of Runx3 protein (Pearson coefficient − 0.501, p = 0.025). Inhibition of HOTAIR significantly suppressed gastric cancer cell migration and invasion through upregulating claudin1, which could be reversed by co-deficiency of Runx3. These results uncovered the novel interaction between HOTAIR and Runx3, and provided potential therapeutic targets on the metastasis of gastric cancer.

Five new meroterpenes, 12α-Psoracorylifol F (1), 7β,8α-hydroxy-12β-Psoracorylifol F (2), 8-ketone-Cyclobakuchiol C (3), 7α,8β-hydroxy-12β-Cyclobakuchiol C (4) and 8α-hydroxy-Cyclobakuchiol C (5) together with six known compounds (6–11) were isolated from seeds of Psoralea corylifolia, and their structures were elucidated on the basis of spectroscopic and physicochemical analyses. All the isolates were evaluated for in vitro inhibitory activity against DGAT1/2. Among them, compounds 1–6 were found to exhibit selective inhibitory activity on DGAT1 with IC50 values ranging from 61.5 ± 1.1 to 89.1 ± 1.2 μM.

The insecticide cypermethrin has been considered as an endocrine-disrupting chemicals (EDCs) with anti-androgenic activity by interfering with interleukin-6 (IL-6) – induced ligand-independent AR signaling. The purpose of this study was to clarify whether the signal transducer and activator of transcription 3 (STAT3) was involved in the antagonism effect of cypermethrin. In this study, the Western blot was to test the level of STAT3 phosphorylation and the mammalian two-hybrid assay was developed to assess the AR–STAT3 interaction. The date showed that IL-6 increased the phosphorylation level of STAT3 and enhanced the AR–STAT3 interaction. Cypermethrin did not affect the phosphorylation level of STAT3 induced by IL-6, while suppressed the AR-STAT3 interaction induced by IL-6 significantly at the concentration of 10−5 M (p

Renal fibrosis is at the core of various renal diseases, including diabetic kidney disease (DKD). Long noncoding RNAs (lncRNAs) are known players in the regulation of renal fibrosis. However, their expression and function in DKD still need to be elucidated. The purpose of this study was to assess how lncRNA GAS5 regulates fibrosis and its mechanism in TGF-β1-treated renal proximal tubular cell.In this study, the lncRNA GAS5 was upregulated in both TGF-β1-treated HK-2 cells and the kidneys of HDF/STZ mice. Knockdown of GAS5 relieved renal tubular epithelial fibrosis. This effect was mediated by the downregulation and functional inactivation of miR-96-5p. Furthermore, miR-96-5p was downregulated in DKD mice, and this downregulation attenuated the repression of FN1(fibronectin, FN) and led to its upregulation. The decrease in miR-96-5p was partially attributed to the miRNA-sponge action of GAS5.Our research demonstrates that knockdown of lncRNA GAS5 leads to antifibrosis by competitively binding miR-96-5p, which inhibits the expression of FN1. These results indicate that targeting lncRNA GAS5 may be a promising therapeutic strategy for preventing DKD.

Background Currently, WeChat is widely used in disease education for patients with Crohn’s disease (CD) in China. It is beneficial for the patients to actively engage in their disease management. Methods In this study, we examined the source and expectations of disease information for Chinese CD patients, analysing the content of popular WeChat public accounts and their potential association with medication adherence. Results Between November 24th, 2017 and April 10th, 2018, online questionnaires were sent to CD patients from eight different large urban hospitals in China. In all, 436 patients with CD were surveyed, and 342 patients responded. Patients most frequently visited Baidu (65%), WeChat (61%) and medical websites such as Haodaifu (35%) when searching for IBD-related information. Among ten WeChat IBD public accounts, the China Crohn’s and Colitis Foundation (CCCF) (73%), “IBD Academic Officer” (21%) and “IBD in love” (21%) were the most popular. CD patients were most interested in information from the internet about diet and day-to-day health-related living with IBD (83%), an introduction to the disease (80%), and medication advances and side effects (80%). The correlation between the information provided by the top five WeChat public accounts and patients’ expectations was low. Additionally, most patients (64%) had greater confidence in overcoming the disease after learning about CD through their internet searches. Medical adherence was also related to internet access and income (p

To determine the associations of pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) with gestational diabetes mellitus (GDM).A prospective cohort of pregnant women were screened for GDM at 24-28 weeks of gestation between 2013 and 2015, resulting in a sample of 3 593 with GDM and 15 346 without GDM. The body mass, plasma glucose, and height data of the participants were collected by the local medical workers. Multivariate logistic regression analyses were performed to determine the associations of pre pregnancy body mass index and weight gain during pregnancy with GDM.The participants with pre pregnancy overweight [odds ratio(Pre pregnancy overweight and obesity and excessive GWG during early and second trimesters of pregnancy may increase the risk of GDM in women in Southwestern China.

MicroRNAs (miRNAs) play critical roles in the tumorigenesis and progression of gastric cancer (GC). However, the biological function of miR-4268 in GC and its mechanism remain unclear. In the present study, qTR-PCR found that the expression of miR-4268 was significantly downregulated in GC tissues and cell lines. The overexpression of miR-4268 inhibited GC cell proliferation and the cell cycle G1/S phase transition, and induced cell apoptosis. In contrast, inhibition of miR-4268 promoted cell proliferation and G1-S transition, and suppressed cell apoptosis. Further analyses revealed that miR-4268 expression was negatively correlated with Rab6B expression in GC tissues. Rab6B was verified to be a direct target of miR-4268. Notably, silencing Rab6B resulted in the same biological effects in GC cells as those induced by overexpression of miR-4268. Importantly, both miR-4268 overexpression and Rab6B silence inhibited the AKT/JNK signaling pathways, which modulated cell cycle regulators (Cyclin D1 and CDK4). In contrast, inhibition of miR-4268 promoted the AKT/JNK signaling pathways. MiR-4268 overexpression also promoted the p38 MAPK signaling pathway. Taken together, miR-4268 suppresses GC cell proliferation through inhibiting the AKT/JNK signaling pathways by targeting Rab6B and induces cell apoptosis through promoting the p38 MAPK signaling pathway. Our findings indicate a tumor-suppressor role of miR-4268 in GC pathogenesis and the potential of miR-4268 in GC theropy.

Purpose. The efficacy of obstructive sleep apnea (OSA) therapy with continuous positive airway pressure (CPAP) on uric acid (UA) yielded conflicting results. This meta-analysis was performed to assess whether OSA treatment with CPAP could reduce UA levels. Methods. The Web of Science, Cochrane Library, Embase, and PubMed were searched before March 2019. Information of patients, study design, and pre- and post-CPAP treatment of UA was utilized for analysis. The overall effects were analyzed via the standardized mean difference (SMD) with a 95% confidence interval (CI). Five studies were obtained and the meta-analysis was performed using Stata 12.0 and Review Manager 5.2. Results. A total of 5 studies with 6 cohorts (2 RCT and 3 observational studies) involving 270 patients were pooled into meta-analysis. There was no change of UA levels before and after CPAP treatment in OSA patients (SMD=‐0.20, 95% CI: -0.78 to 0.37, Z=0.69, p=0.49). Subgroup analysis showed that the outcomes were not affected by age of patients, gender distribution, baseline body mass index, daily duration, duration of CPAP treatment, sample size, and study design. Conclusions. This meta-analysis revealed that CPAP treatment has no effect on UA in OSA patients. Further well-designed, large-scale randomized controlled trials are required to address this issue.

For the first time, eight novel artemisinin-piperazine-furane ether hybrids (5a−h) were efficiently synthesized and investigated for their in vitro cytotoxic activity against some human cancer and benign cells. The absolute configuration of hybrid 5c was determined by X-ray crystallographic analysis. Hybrids 5a−h exhibited more pronounced growth-inhibiting action on hepatocarcinoma cell lines than their parent dihydroartemisinin (DHA) and the reference cytosine arabinoside (ARA). The hybrid 5a showed the best cytotoxic activity against human hepatocarcinoma cells SMMC-7721 (IC50 = 0.26 ± 0.03 μM) after 24 h. Furthermore, hybrid 5a also showed good cytotoxic activity against human breast cancer cells MCF-7 and low cytotoxicity against human breast benign cells MCF-10A in vitro. We found the cytotoxicity of hybrid 5a did not change when tumour cells absorb iron sulfate (FeSO4); thus, we conclude the anti-tumour mechanism induced by iron ions (Fe2+) is unclear.

// Liangjing Wang 1, 2, 3, * , Meng Xue 1, 2, 3, * , Daniel C. Chung 2, 3 1 Department of Gastroenterology, The Second Affiliated Hospital, School of Medicine, and Institute of Gastroenterology, Zhejiang University, Hangzhou, China 2 Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA 3 Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA * These authors contributed equally to this work Correspondence to: Daniel C. Chung, email: Chung.daniel@mgh.harvard.edu Keywords: c-Myc, HIF-2α, 5-FU, colon cancer Received: April 30, 2016 Accepted: October 17, 2016 Published: October 26, 2016 ABSTRACT Colorectal cancers (CRCs) invariably become hypoxic as they enlarge, and this places unique metabolic demands upon the tumor cells. Hypoxic stress can enhance the invasiveness of cancer cells and induce chemoresistance. c-Myc, an oncogene regulated by hypoxia inducible factors (HIFs), plays a critical role in cell proliferation and metabolism. However, the interplay between c-Myc and HIFs and its clinical significance in hypoxic adaptation in CRCs are unknown. We demonstrate that c-Myc mRNA and protein levels in colon cancer cells are induced within 2 h of hypoxic stress (1% O 2 ) but are then significantly downregulated when exposed to prolonged hypoxia. In chronic hypoxia (over 8 h at 1% O 2 ), HIF-2α but not HIF-1α gradually accumulated in colon cancer cells. Knockdown of HIF-2α increased levels of c-Myc and its downstream target cyclinD1 in chronic hypoxia, indicating that HIF-2α may function to downregulate c-Myc. Chronic hypoxia suppressed the expression of cyclinD1, CDK4, and CDK6, inducing G1 phase block and 5-flurouracil (5-FU) chemoresistance. Overexpression of c-Myc reversed the inhibition of cyclinD1, CDK4, and CDK6, which accelerated the G1/S phase transition under hypoxia and enhanced sensitivity to 5-FU. In contrast, knockdown of c-Myc impaired 5-FU chemosensitivity in colon cancer cells. In summary, HIF-2α plays an important role in regulating the expression of c-Myc in chronic hypoxia, and consequently controls the sensitivity of colon cancer cells to 5-FU treatment in this environment.

Upconversion luminescence nanomaterials have shown great potential in biological and physical applications because of their unique properties. However, limited research exists on the cooperative sensitization upconversion emission in Tb(3+) ions over Er(3+) ions and Tm(3+) ions because of its low efficiency. Herein, by optimizing the doping ratio of sensitizer and activator to maximize the utilization of the photon energy and introducing the CaF2 inert shell to shield sensitizer from quenchers, we synthesize ultrasmall NaYbF4:Tb@CaF2 nanoparticles with a significant enhancement (690-fold) in cooperative sensitization upconversion emission intensity, compared with the parent NaYbF4:Tb. The lifetime of Tb(3+) emission in NaYbF4:Tb@CaF2 nanoparticles is prolonged extensively to ∼3.5 ms. Furthermore, NaYbF4:Tb@CaF2 was applied in in vitro and in vivo bioimaging. The presented luminescence enhancement strategy provides cooperative sensitization upconversion with new opportunities for bioapplication.

The objective of the study was to investigate whether genetic polymorphisms of the anti-Mullerian hormone (AMH) and its specific receptor anti-Mullerian hormone type II receptor (AMHRII) were associated with the hormone disorder and phenotype of polycystic ovary syndrome (PCOS). This case-control study included 141 PCOS patients and 123 normal women. Two polymorphisms of AMH and AMHRII and the clinical characteristics of participants such as body mass index (BMI), serum luteinizing hormone (LH), estradiol levels (E2), total testosterone levels (T), and homeostasis model assessment of insulin resistance (HOMA-IR) were analyzed with the case-control sample. Gene–gene interactions of AMH and AMHRII genes were analyzed based multifactor-dimensionality reduction method. A significant difference of AMH gene polymorphisms were observed in IR-PCOS women and controls. The AMH and AMHRII gene polymorphisms were not found a significant difference in non-IR-PCOS and normal groups. To IR-PCOS women, genotypes of AMH were closely related to the serum levels of LH (P = 0.000), testosterone (P = 0.000) and HOMA-IR (P = 0.038), while in the non-IR-PCOS and normal groups, no relationship was found. No impact of AMH and AMHRII gene–gene interactions was demonstrated. Our research suggests that the diversity of AMH genotypes in the AMH signal pathway may be connected with the susceptibility and phenotype of PCOS with insulin resistance.

Objective. We have identified a gene YOD1 encoding deubiquitinating enzyme (DUB) responsible for nonsyndromic cleft lip with or without cleft palate (NSCL/P). We aimed to determine the effects of YOD1 RNA interference (RNAi) on cell proliferation and migration, playing an important role in lip and palate formation, and to clarify whether the mechanisms involved TGF-β3 signaling associated with NSCL/P. Methods. RNAi was applied to construct vectors expressing YOD1 small interference RNAs (siRNAs). The vectors were transfected into the human oral keratinocytes (HOK) cells. The cell proliferation and migration were evaluated by the cell counting kit-8 (CCK-8) assay and wound healing assay, respectively. The mRNA levels were detected by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). The protein levels were investigated by western blotting. Results. The proliferation of YOD1 siRNA-transfected HOK cells was remarkably inhibited. The migration rate was significantly decreased in the YOD1 siRNA-transfected HOK cells. The TGF-β3 mRNA and protein levels were decreased significantly by siRNA-mediated knockdown of YOD1. YOD1 RNAi reduced the phosphor-Smad2/3 levels significantly. Conclusions. YOD1 RNAi may inhibit cell proliferation and migration associated with the pathogenesis of NSCL/P through TGF-β3 signaling. The study indicates a novel role of YOD1 in regulating TGF-β3 signaling to affect cell proliferation and migration resulting in NSCL/P.