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Coronaviruses can have a devastating impact on the health of humans and animals. Porcine epidemic diarrhea virus (PEDV) causes extremely high fatality rates in neonatal piglets, whereas severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic in humans. As a critical component of the host antiviral innate immune response, type I interferon production and signaling play a very important role, especially in the initial phase of the antiviral responses. Coronaviruses have evolved multiple ways to counteract type I interferon responses. Although the primary functions of the nucleocapsid protein are to facilitate viral RNA replication and package viral genomic RNA into virions, recent studies have shown that the nucleocapsid protein is also involved in virus-host interactions. The aim of this review is to summarize our current understanding of how the nucleocapsid proteins of PEDV and SARS-CoV-2 modulate type I interferon responses. This knowledge will be useful for developing strategies to combat coronavirus infections.

The prolyl 3-hydroxylase family member 4 gene (P3H4) is involved in the development of human cancers. The association of P3H4 with bladder cancer (BC) prognosis is unclear. This study aimed to analyze the association of P3H4 with BC prognosis.RNA-Seq data were downloaded from The Cancer Genome Atlas project and BC microarray datasets (GSE13507, GSE31684, and GSE32548) were downloaded from the Gene Expression Omnibus database. We analyzed the differences in P3H4 expression levels between BC tumors and non-tumor tissues and between samples with different clinical information. The association of P3H4 and P3H4-related genes with BC prognosis and the possibility of using P3H4 expression as a prognostic biomarker in BC patients were also analyzed. RevMan was used to perform the meta-analysis.P3H4 was upregulated in BC tissues compared with the adjacent non-tumor tissues (p = 4.06e-08). Univariate Cox regression analysis and meta-analysis showed that high P3H4 expression level contributed to a poor BC prognosis (Hazard ratio, HR = 1.348, 95% CI 1.140-1.594, p = 4.89e-04; meta-analysis: HR = 1.45, 95% CI 1.10-1.91; p = 9.00e-03). Among the genes related to P3H4, the PLOD1 gene was closely associated with P3H4 expression (r = 0.620, p = 2.49e-44). Also, a meta-analysis showed that PLOD1 expression was associated with a poor prognosis in BC patients (HR = 1.77, 95% CI 1.31-2.38; p = 2.00e-04).The P3H4 and PLOD1 genes might be used as reliable prognostic biomarkers for BC.

Purpose The overall response of cisplatin-based chemotherapy in bladder urothelial carcinoma (BUC) remains unsatisfactory due to the complex pathological subtypes, genomic difference, and drug resistance. The genes that associated with cisplatin resistance remain unclear. Herein, we aimed to identify the cisplatin resistance associated genes in BUC. Experimental design The cytotoxicity of cisplatin was evaluated in six bladder cancer cell lines to compare their responses to cisplatin. The T24 cancer cells exhibited the lowest sensitivity to cisplatin and was therefore selected to explore the mechanisms of drug resistance. We performed genome-wide CRISPR screening in T24 cancer cells in vitro, and identified that the gene heterogeneous nuclear ribonucleoprotein U (HNRNPU) was the top candidate gene related to cisplatin resistance. Epigenetic and transcriptional profiles of HNRNPU-depleted cells after cisplatin treatment were analyzed to investigate the relationship between HNRNPU and cisplatin resistance. In vivo experiments were also performed to demonstrate the function of HNRNPU depletion in cisplatin sensitivity. Results Significant correlation was found between HNRNPU expression level and sensitivity to cisplatin in bladder cancer cell lines. In the high HNRNPU expressing T24 cancer cells, knockout of HNRNPU inhibited cell proliferation, invasion, and migration. In addition, loss of HNRNPU promoted apoptosis and S-phase arrest in the T24 cells treated with cisplatin. Data from The Cancer Genome Atlas (TCGA) demonstrated that HNRNPU expression was significantly higher in tumor tissues than in normal tissues. High HNRNPU level was negatively correlated with patient survival. Transcriptomic profiling analysis showed that knockout of HNRNPU enhanced cisplatin sensitivity by regulating DNA damage repair genes. Furthermore, it was found that HNRNPU regulates chemosensitivity by affecting the expression of neurofibromin 1 (NF1). Conclusions Our study demonstrated that HNRNPU expression is associated with cisplatin sensitivity in bladder urothelial carcinoma cells. Inhibition of HNRNPU could be a potential therapy for cisplatin-resistant bladder cancer.

This work aimed to investigate the molecular mechanism of the activation of hypoxia-inducible factors under different low oxygen partial pressures.Strictly follow in vitro aseptic culture of bladder cancer cell line UMUC3 and when the cells grow in the logarithmic phase, culture the cells under different low oxygen partial pressures. Among these groups, two groups of cells were transfected with small interfering-hypoxia inducible factor 1α (si-HIF-1α) liposome plasmids to silencing the HIF-1α expression.Cell cloning experiment showed that HIF-1α will increase cell adhesion and proliferation under hypoxia. Matrigel angiogenesis experiment showed that hypoxia has a negative impact on the angiogenesis of tumor cells. Cell scratch test indicated that hypoxia has a greater impact on the migration ability of cancer cells, and HIF-1α has a significant impact on the migration process. Cell invasion test proved that hypoxia has a greater impact on the invasion ability of cancer cells, and HIF-1α has a great impact on the invasion process.HIF-1α can target the regulatory gene vascular endothelial growth factor to promote tumor cell proliferation, migration, invasion, neovascularization and lymph node metastasis.Por lo tanto, este trabajo investiga el mecanismo molecular de la activación de factores inducibles por hipoxia bajo diferentes presiones parciales de oxígeno bajas.Siga estrictamente el cultivo aséptico in vitro de la línea celular de cáncer de vejiga UMUC3 y cuando las células crezcan en la fase logarítmica, cultive las células bajo diferentes presiones parciales de oxígeno bajas. Entre estos grupos, se transfectaron dos grupos de células con plásmidos de liposomas si-HIF-1α para silenciar la expresión de HIF-1α.El experimento de clonación celular mostró que HIF-1α aumentará la adhesión y proliferación celular bajo hipoxia. El experimento de angiogénesis de Matrigel mostró que la hipoxia tiene un impacto negativo en la angiogénesis de las células tumorales. La prueba de raspado celular indicó que la hipoxia tiene un mayor impacto en la capacidad de migración de las células cancerosas, y HIF-1α tiene un impacto significativo en el proceso de migración. La prueba de invasión celular demostró que la hipoxia tiene un mayor impacto en la capacidad de invasión de las células cancerosas y HIF-1α tiene un gran impacto en el proceso de invasión.HIF-1α puede dirigirse al gen regulador vascular endothelial growth factor para promover la proliferación, migración, invasión, neovascularización y metástasis en los ganglios linfáticos de las células tumorales.

Long noncoding RNAs have been known to play key roles in myocardial ischemia/reperfusion injury. This study was conducted to investigate whether upregulation of FGD5-AS1 can improve hypoxia/reoxygenation (H/R) injury of cardiomyocytes and its underlying mechanisms. Pc-FGD5-AS1 was used to overexpress FGD5-AS1 in cardiomyocytes. Cholecystokinin octapeptide and flow cytometry assays were performed to detect the effect of FGD5-AS1 on myocardial cell H/R injury. Quantitative real-time polymerase chain reaction and luciferase reporter assay were performed to assess the relationship between FGD5-AS1 and microRNA-106a-5p (miR-106a-5p) or miR-106b-5p. In patients with acute myocardial infarction and in H/R cardiomyocytes and ischemia/reperfusion myocardium, the expression levels of FGD5-AS1 were reduced, whereas the expression levels of miR-106a-5p and miR-106b-5p were increased. Overexpression of FGD5-AS1 increased the viability of H/R-treated cardiomyocytes and reduced the levels of apoptosis and creatine kinase-MB. In addition, FGD5-AS1 could bind to miR-106a-5p or miR-106b-5p and showed a mutual inhibitory effect between them. Furthermore, overexpression of miR-106a-5p or miR-106b-5p inhibited the expression of SMAD5. FGD5-AS1 upregulated the expression of SMAD5. In conclusion, FGD5-AS1 may be a potential therapeutic target for myocardial H/R injury, and its cardioprotective effect may be realized by reducing inflammatory response and cell apoptosis.

Background There is a lack of biomarkers for distinguishing non-obstructive azoospermia (NOA) patients with successful sperm retrieval (Sp+) from those with failed sperm retrieval (Sp-). This study aimed to determine the potential of extracellular vesicles tRNA-derived small RNA (tsRNA) as a novel non-invasive biomarker for successful sperm retrieval by microdissection testicular sperm extraction (mTESE). Methods The study included 18 patients with NOA with successful sperm retrieval (Sp+) and 23 patients with NOA with failed sperm retrieval (Sp-), 15 obstructive azoospermia (OA) patients, 5 idiopathic oligospermia (IO) patients, and 12 healthy people. Seminal plasma extracellular vesicles tsRNA levels were used in a two-stage case-control study (screened by tsRNA sequencing on Illumina NextSeq instrument and validated by qRT-PCR). The bioinformatic analysis was performed to determine the role of tsRNA in the pathogenesis of non-obstructive azoospermia. Results Two tsRNAs (tRF-Val-AAC-010: AUC = 0.96, specificity = 80%, sensitivity = 95%; tRF-Pro-AGG-003: AUC = 0.96, specificity = 87%, sensitivity = 95%) were found to have high predictive accuracy for distinguishing the origin of azoospermia. In addition, the extracellular vesicles tRF-Val-AAC-010 resulted in high predictive ability (AUC = 0.89, sensitivity = 72%, specificity = 91%, P Conclusions This study identified that the extracellular vesicles tRF-Val-AAC-010 and tRF-Pro-AGG-003 are biomarkers for the diagnosis of non-obstructive azoospermia, and that tRF-Val-AAC-010 as a potential non-invasive biomarker for predicting the presence of sperm in non-obstructive azoospermia testicular tissue.

A MXene-based heterostructure (BiOI/Ti

To evaluate the clinical effectiveness of micro-hand robot-assisted cholecystectomy (MRC) by comparing the clinical outcomes of patients with benign gallbladder disease treated with micro-hand or da Vinci robot-assisted cholecystectomy (DRC).This is a prospective, multi-centre, single-blind, and randomized controlled trial. In this study, 166 patients of benign gallbladder disease were randomized enrolled into two groups and received MRC or DRC (83 in the MRC group; 83 in the DRC group). The primary endpoint was surgical success rate. Secondary endpoints were the docking time, console time, total operation time, intraoperative blood loss, gallbladder breakage rate, postoperative pain, time of first flatus, the comprehensive complication index (CCI), and the hospital stay of the subjects. The duration of follow-up was 30 days.No conversion occurred. Compared with MRC, the DRC group showed longer docking time (12.04 min vs. 16.39 min, P = 0.025) and higher gallbladder breach rate (4.8% vs. 15.7%, P = 0.021). The MRC group showed higher postoperative pain scores compared to DRC (4.0 vs 3.0, P = 0.038). The console time, intraoperative blood loss, and gallbladder breach rate were comparable in these two groups (P gt; 0.05). No differences were observed in postoperative outcomes and complications between the two groups (P gt; 0.05).In patients with benign gallbladder disease, the MRC showed no obvious clinical disadvantage compared with the da Vinci surgical robot. MRC is effective and safe and provides more options for surgical treatment.This study was registered at ClinicalTrials.gov (NCT04122261). URL: https://clinicaltrials.gov/ct2/show/NCT04122261.

Background The main purpose of this study was to describe the all-inside arthroscopic technique for repairing anterior talofibular ligament (ATFL) avulsion fractures at the attachment points of the fibula and talus, and to evaluate the functional outcomes during long-term follow-up. Methods The data of 78 patients with ATFL avulsion fracture treated in our hospital from August 2013 to November 2016 were analyzed retrospectively. All patients underwent surgery. Patients were divided into two groups according to whether they had undergone all-inside arthroscopic treatment or open treatment. The American Orthopedic Foot and Ankle Society (AOFAS) score, Karlsson Ankle Functional Score (KAFS), Foot and Ankle Outcome Score (FAOS) and a 36-item Short Form Health Survey questionnaire (SF-36) were used to evaluate functional outcomes. Results The postoperative follow-up period was 24–48 months. All patients reported subjective improvements to ankle stability without any nerve, blood vessel or tendon complications. At the final follow-up, there was no significant difference in the AOFAS, SF-36 or sport participation rate between the arthroscopic group and the open group; however, the KAFS and FAOS were significantly higher in the arthroscopic group than in the open group. Conclusions For ATFL avulsion fractures, the all-inside ankle arthroscopic procedure produced better outcomes than did the open procedure. The all-inside ankle arthroscopic procedure provides a minimally invasive technique with acceptable long-term functional outcomes.

Aflatoxins have carcinogenic effect on human health, developing effective adsorbents for their enrichment and detection is particularly required. A magnetic hyper-crosslinked polymer (MHCP-TPE) was prepared and used as a magnetic sorbent to adsorb and isolate aflatoxins from rice and sorghum samples prior to high performance liquid chromatography-fluorescence detection. MHCP-TPE exhibited good magnetic separation ability and reusability, with fast adsorption kinetics and quite good adsorption efficiency for the aflatoxins. At optimized conditions, a sensitive and reliable method was established for the determination of four aflatoxins (B

Background Solanum nigrum L. decoction has been used as a folklore medicine in China to prevent the postoperative recurrence of bladder cancer (BC). However, there are no previous pharmacological studies on the protective mechanisms of this activity of the plant. Thus, this study aimed to perform a systematic analysis and to predict the potential action mechanisms underlying S. nigrum activity in BC based on network pharmacology. Methods Based on network pharmacology, the active ingredients of S. nigrum and the corresponding targets were identified using the Traditional Chinese Medicines for Systems Pharmacology Database and Analysis Platform database, and BC-related genes were screened using GeneCards and the Online Mendelian Inheritance in Man database. In addition, ingredient-target (I–T) and protein–protein interaction (PPI) networks were constructed using STRING and Cytoscape, Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted, and then the pathways directly related to BC were integrated manually to reveal the pharmacological mechanism underlying S. nigrum-medicated therapeutic effects in BC. Results Seven active herbal ingredients from 39 components of S. nigrum were identified, which shared 77 common target genes related to BC. I-T network analysis revealed that quercetin was associated with all targets and that NCOA2 was targeted by four ingredients. Besides, interleukin 6 had the highest degree value in the PPI network, indicating a hub role. A subsequent gene enrichment analysis yielded 86 significant GO terms and 89 significant pathways, implying that S. nigrum had therapeutic benefits in BC through multi-pathway effects, including the HIF-1, TNF, P53, MAPK, PI3K/Akt, apoptosis and bladder cancer pathway. Conclusions S. nigrum may mediate pharmacological effects in BC through multi-target and various signaling pathways. Further validation is required experimentally. Network pharmacology approach provides a predicative novel strategy to reveal the holistic mechanism of action of herbs.

This study aimed to determine the risk factors and establish a risk score for post-transjugular intrahepatic portosystemic shunt (TIPS) overt hepatic encephalopathy (OHE).Altogether 299 and 62 cirrhotic patients receiving TIPS from January 2015 to March 2018 were divided into the derivation and validation cohorts, respectively. The data of the derivation cohort were analyzed for risk factors of post-TIPS OHE. A risk score was established from the derivation cohort and verified by the validation cohort.During a median follow-up of 112.6 weeks, 52 (17.4%) patients in the derivation cohort experienced post-TIPS OHE. Logistic regression showed that alcoholic cirrhosis (odds ratio [OR] 3.068, 95% confidence interval [CI] 1.423-6.613, P = 0.004), stent diameter of 10 mm (OR 12.046 [95% CI 2.308-62.862], P = 0.003), portal pressure gradient (PPG) decrement ≥60% (OR 3.548 [95% CI 1.741-7.230], P 0.001), model for end-stage liver disease (MELD) score ≥10 (OR 2.695 [95% CI 1.203-6.035], P = 0.016), blood ammonia (OR 1.009 [95% CI 1.000-1.018], P = 0.043) and notable hydrothorax (OR 4.393 [95% CI 1.554-12.415], P = 0.005) were associated with an increased risk of post-TIPS OHE. The risk score reached a promising risk evaluation of post-TIPS OHE when verified by the validation cohort (sensitivity 71.4%, specificity 70.7%, accuracy 71.0%).Alcoholic cirrhosis and notable hydrothorax are independent risk factors for post-TIPS OHE in liver cirrhosis, together with the stent diameter of 10 mm, PPG decrement ≥60%, MELD score ≥10 and blood ammonia. The established risk score is reliable to identify high-risk individuals of developing post-TIPS OHE.

Tissue inhibitor of metalloproteinase-2 (TIMP2) is an inhibitor among the tissue inhibitors of metalloproteinase (TIMP) family members, is associated with the progression of a variety of tumors. However, the association of TIMP2 with cancer prognosis and tumor-infiltrating lymphocytes remains unclear. TIMP2 expression was analyzed by Tumor Immune Estimation Resource (TIMER), TNMplot, Gene Expression Profiling Interactive Analysis (GEPIA) database and 50 paired gastric cancer tissues. We evaluated the influence of TIMP2 on clinical prognosis using Kaplan-Meier plotter, the PrognoScan database, GEPIA and TCGA data. The correlation of TIMP2 with tumor immune infiltrates and with the set of gene markers of immune infiltrates was investigated by TIMER and GEPIA. TIMP2 is highly expressed in gastric cancer and low expressed in colon cancer. High TIMP2 expression was significantly correlated with poor overall survival (OS, hazard ratio [HR] = 1.38, 95% confidence interval [CI]: [1.16–1.63]; P = 0.0002) and progression-free survival (PFS, HR = 1.39, 95% CI: [1.14–1.7]; P = 0.0012) in gastric cancers. Specifically, high TIMP2 expression was associated with poorer OS and PFS, but not with OS and PFS in stage 1 (OS HR = 1.96, P = 0.29; PFS HR = 0.43, P = 0.19) and stage 2 (OS HR = 1.59, P = 0.12; PFS HR = 1.47, P = 0.2) and stage N0 patients (OS HR = 1.6, P = 0.35; PFS HR = 1.56, P = 0.38) of gastric cancer patients. There was a significant positive correlation between TIMP2 expression and different type of immune cells, including CD4 + T cells, CD8 + T cells, macrophages, Neutrophils, and dendritic cells in stomach adenocarcinoma (STAD) and colon adenocarcinoma (COAD). Moreover, TIMP2 expression was strongly correlated with different sets of immune markers. These results suggest that TIMP2 is associated with prognosis and level of immune infiltrating in a variety of cancers, especially colon and gastric cancer patients. Moreover, expression of TIMP2 potentially contributes to regulation of tumor-associated macrophages (TAMs), dendritic cells, T cell exhaustion and Tregs in colon and gastric cancer. These findings suggest that TIMP2 may serve as a prognostic biomarker for predicting prognosis and immune infiltration in gastric and colon cancer.

Background Bladder cancer (BC) seriously endangers public health, but effective biomarkers for BC diagnosis, particularly in the early stage, are still lacking. Identification of reliable biomarkers associated with early-stage BC is of great importance to early treatment and an improved outcome. Methods Differentially expressed genes (DEGs) were identified using four publicly available early-stage BC gene-expression profiles. Protein–protein interaction (PPI) and survival analysis for hub genes was evaluated. The correlation between methylation of genes and prognosis was evaluated using the MethSurv database. Co-expressed genes were explored using Cancer Cell Line Encyclopedia database and the corresponding expression were assessed in vitro. The competing endogenous RNA network and the immune cell infiltration in BC were generated using data of The Cancer Genome Atlas. Results Ten hub genes of the 213 integrated DEGs were identified, including CDH1, IGFBP3, PPARG, SDC1, EPCAM, ACTA2, COL3A1, TPM1, ACTC1, and ACTN1. CDH1 appeared to increase from tumor initiation stage and negatively correlated with methylation. Six methylated sites in CDH1 indicated a good prognosis and one site indicated an aberrant prognosis. High CDH1 expression was negatively correlated with infiltrations by most immune cells, such as plasmacytoid dendritic cells (pDCs), regulatory T cells, macrophages, neutrophils, DCs, and natural killer cells. CDH1 was highly positively correlated with EPCAM and appeared to be directly regulated by miR-383. Conclusions The identified oncogenic alterations provide theoretical support for the development of novel biomarkers to advance early-stage BC diagnosis and personalized therapy.

Background The clinical and molecular characteristics of osteofibrous dysplasia (OFD)-like adamantinoma (AD) differ from those of classic AD. Most reports about OFD-like AD are case reports or small case series. More cases from different centers are still warranted. Methods The orthopedic oncology database of our institution was searched to identify patients with AD. The cases of OFD-like and classic AD of the long bones were retrospectively analyzed. Between December 1999 and August 2016, 23 patients were treated for AD, comprising seven with OFD-like AD and 16 with classic AD. The outcomes were compared between AD subtypes. Results In the OFD-like AD group, four lesions were treated with extensive curettage, while three were treated with wide resection. The median follow-up duration in the OFD-like AD group was 66 months (range 43–131 months). At the end of follow-up, there was only one case of local recurrence (LR) in the OFD-like AD group, giving a LR rate of 14.3% (1/7). No distant metastasis or progression to classic AD was detected in the OFD-like AD group. In the classic AD group, the treatments were below-the-knee amputation in one patient with extensive tibial and fibular lesions, curettage with a bone graft in one patient who was diagnosed with OFD based on a core needle biopsy, hemi-cortical excision and reconstruction in two patients, and segmental resection and reconstruction in 12 patients. At the end of follow-up, there were three cases of LR in the classic AD group, giving a LR rate of 18.8% (3/16); two patients developed lung metastasis after LR and died of the disease at 88 and 126 months after the first surgery in our hospital, respectively. The classic AD group had a metastatic rate of 12.5% (2/16), a final limb salvage rate of 75%, and estimated 5- and 10-year survival rates of 88.9% and 77.1%, respectively. Conclusions OFD-like AD has a better outcome than classic AD. For OFD-like AD, extensive curettage is suggested if the tumor extent allows. For classic AD, aggressive resection with wide margins is essential to achieve local control. A long-term follow-up is necessary due to the possibility of late complications.

The prolyl 3-hydroxylase family member 4 (P3H4) (alias SC65) is implicated in a variety of physiological and pathological processes. However, little is known about the role of P3H4 in tumors. This study aimed to investigate the role of P3H4 in bladder cancer (BC) and the regulatory mechanisms that influence its expression. P3H4 was highly expressed in BC tissues. Knockdown of P3H4 inhibited BC cell proliferation, cell cycle, migration and invasion in vitro, and inhibited BC growth in vivo. We also found that ETV4 bound directly to the promoter region of P3H4 and activated its transcription. Furthermore, overexpression of ETV4 rescued the inhibition of proliferation and invasion induced by PH4 silencing. ETV4 was significantly overexpressed in the BC tissues. In conclusion, P3H4 functioned an oncogene role in BC progression, and ETV4 bound directly to the P3H4 promoter region to regulate its transcription.

ABO blood group has been associated with various disease phenotypes. However, ABO blood group to influence patients in risk of venous thromboembolic events (VTEs) and arterial thromboembolic events (ATEs) remains controversial after evaluation in several reports. To fully assess effects of ABO blood group on VTEs and ATEs, we conducted a cross-sectional study and investigated the interaction between blood group and age, and between blood group and sex on the prevalence of VTEs and ATEs. In addition, the effect of blood group on ATEs in patients with atrial fibrillation (AF) was observed. Detailed information of 7830 patients was collected. Multivariate logistic regression analyses were used to evaluate the association between blood group and VTEs, pulmonary embolism (PE) and myocardial infarction (MI). In those 7830 patients, the respective risk of VTEs and PE was higher for patients with blood group A compared with blood group O individually. In those 6713 patients with rheumatic heart disease, cardiomyopathy, myocarditis, constrictive pericarditis, or valvular heart disease excluded, blood group A was associated with the risk of MI. For VTEs, PE, and MI, blood group also exhibited significant interactions with sex and age, although there was no evidence of interaction between blood group and age for VTEs. In addition, interactions among blood group, age, and AF for the ATEs were observed. Similar to prior population studies an association of ABO blood group with susceptibility to VTEs and MI was found. Age and sex may modulate the association between ABO blood group and these thromboembolic diseases.

(1) Background: Nuclear factor κB (NF-κB) is an important transcriptional regulator that regulates the inflammatory pathway and plays a key role in cellular inflammatory and immune responses. The presence of a high concentration of NF-κB is positively correlated with the severity of inflammation. Therefore, the inhibition of this pathway is an important therapeutic target for the treatment of various types of inflammation; (2) Methods: we designed and synthesized 23 mollugin derivatives and evaluated their inhibitory activity against NF-κB transcription; (3) Results: Compound 6d exhibited the most promising inhibitory activity (IC50 = 3.81 µM) and did not show any significant cytotoxicity against the tested cell lines. Investigation of the mechanism of action indicated that 6d down-regulated NF-κB expression, possibly by suppressing TNF-α-induced expression of the p65 protein. Most of the compounds exhibited potent anti-inflammatory activity. Compound 4f was the most potent compound with 83.08% inhibition of inflammation after intraperitoneal administration, which was more potent than mollugin and the reference drugs (ibuprofen and mesalazine). ADMET prediction analysis indicated that compounds 6d and 4f had good pharmacokinetics and drug-like behavior; (4) Conclusions: Several series of mollugin derivatives were designed, synthesized, and evaluated for NF-κB inhibitory activity and toxicity. These results provide an initial basis for the development of 4f and 6d as potential anti-inflammatory agents.

Organic micropollutants (OMPs) in water resources are a growing threat to aquatic ecosystems and human health. Efficient removal of polar OMPs is very challenging because of their high hydrophility. Synthesizing novel adsorbent capable of high-efficiently removing hydrophilic and hydrophobic micropollutants is highly desirable for water remediation. Here, using natural proanthocyanidin as building units, a novel hydroxyl-functional porous organic framework (denoted as PC-POF) with amphiphilic feature was synthesized through facile azo coupling reaction. Five sulfonamide antibiotics were selected as model OMPs for adsorption study. Adsorption experiments demonstrated a more rapid and efficient sulfonamides capture ability of the PC-POF than that of the most reported adsorbents due to strong hydrogen bonding, π stacking and electrostatic interactions. The PC-POF can be easily recovered and reused at least 5 times without obvious decline in adsorption performance. Moreover, experiments conducted at environmentally relevant concentrations (μg L

Background Clear cell renal cell carcinoma (ccRCC) is one of the most lethal urological malignancies, but the pathogenesis and prognosis of ccRCC remain obscure, which need to be better understand. Methods Differentially expressed genes were identified and function enrichment analyses were performed using three publicly available ccRCC gene expression profiles downloaded from the Gene Expression Omnibus database. The protein-protein interaction and the competing endogenous RNA (ceRNA) networks were visualized by Cytoscape. Multivariate Cox analysis was used to predict an optimal risk mode, and the survival analysis was performed with the Kaplan-Meier curve and log-rank test. Protein expression data were downloaded from Clinical Proteomic Tumor Analysis Consortium database and Human Protein Atlas database, and the clinical information as well as the corresponding lncRNA and miRNA expression data were obtained via The Cancer Genome Atlas database. The co-expressed genes and potential function of candidate genes were explored using data exacted from the Cancer Cell Line Encyclopedia database. Results Of the 1044 differentially expressed genes shared across the three datasets, 461 were upregulated, and 583 were downregulated, which significantly enriched in multiple immunoregulatory-related biological process and tumor-associated pathways, such as HIF-1, PI3K-AKT, P53 and Rap1 signaling pathways. In the most significant module, 36 hub genes were identified and were predominantly enriched in inflammatory response and immune and biotic stimulus pathways. Survival analysis and validation of the hub genes at the mRNA and protein expression levels suggested that these genes, particularly complement component 3 (C3) and fibronectin 1 (FN1), were primarily responsible for ccRCC tumorigenesis and progression. Increased expression of C3 or FN1 was also associated with advanced clinical stage, high pathological grade, and poor survival in patients with ccRCC. Univariate and multivariate Cox regression analysis qualified the expression levels of the two genes as candidate biomarkers for predicting poor survival. FN1 was potentially regulated by miR-429, miR-216b and miR-217, and constructed a bridge to C3 and C3AR1 in the ceRNA network, indicating a critical position of FN1. Conclusions The biomarkers C3 and FN1 could provide theoretical support for the development of a novel prognostic tool to advance ccRCC diagnosis and targeted therapy.

Background To observe and explore the effect of metformin on the migration and proliferation of bladder cancer T24 and 5637 cells in vitro. Methods Bladder cancer T24 and 5637 cell lines were cultured in vitro, and were divided into group A (blank control group) and group B (metformin group: 5, 10, 15, and 20 mmol/L); both groups were plated on 6-well plates at the same time. Culture in 24-well plates was used for wound healing assays and in 96-well plates for Transwell migration and invasion, and Cell Counting Kit-8 proliferation experiments. We observed and detected the cell migration and proliferation ability of each group at 48 h, and calculated the cell migration area and survival rate. Flow cytometry was used to detect cell apoptosis in the groups. The apoptosis-related proteins, cleaved-caspase 3, cleaved-PARP, and the PI3K/AKT/mTOR signaling pathway member proteins PI3K, phosphorylated (p)-PI3K, AKT, p-AKT, mTOR, and p-mTOR were detected using western blotting. Results After 48 h of treatment with different concentrations of metformin, the cell migration and proliferation capabilities were significantly lower than those in the blank control group. The proliferation and migration abilities of T24 and 5637 cells decreased in a metformin concentration-dependent manner (P P P Conclusion Metformin inhibited bladder cancer T24 and 5637 cell migration and proliferation, and induced their apoptosis. The mechanism might involve inhibition of the activation of the PI3K/AKT/mTOR signaling pathway.

A 28-year-old female patient was hospitalized primarily because of “intermittent fever for 28 days aggravated by systemic rashes, oral ulcer, and edema in both eyelids for 5 days.” During treatment, convulsions and loss of consciousness occurred. Magnetic resonance imaging (MRI) of the head revealed an abnormal signal with shadows in the bilateral frontal, parietal, temporal, and occipital lobes; cerebellar hemispheres; and basal nodes, with high signal intensity on T2 weighted imaging (T2WI), on fluid-attenuated inversion-recovery, and of the apparent diffusion coefficient and low signal intensity on T1WI and diffusion weighted imaging. Therefore, the patient was diagnosed with systemic lupus erythematosus (SLE) with reversible posterior encephalopathy syndrome (RPES). Intravenous high-dose methylprednisolone and cyclophosphamide were administered for blood pressure control, which effectively controlled the disease. Therefore, when patients with SLE and hypertension or renal insufficiency or those receiving high-dose methylprednisolone or immunosuppressants suddenly present with neurologic abnormalities, a diagnosis of RPES must be considered, and head MRI is the first choice for diagnosis of this disease. In terms of treatment, the blood pressure should be quickly controlled, and the primary disease should be aggressively treated.

Bladder cancer (BCa) is a common malignancy in the urinary system. Ras-related protein Rab-27A (RAB27A) and Ras-related protein Rab-27B (RAB27B) have been verified to be closely related to the development of many tumors. Since the role of both RAB27A and RAB27B in BCa have not been reported, we intended to explore the function and mechanism of RAB27A and RAB27B in BCa development. Reverse transcription quantitative polymerase chain reaction revealed that RAB27A/B showed high expression in BCa tissues and cells. Cell counting kit-8, wound healing and Transwell assays as well as western blot analyses revealed that silencing RAB27A/B suppressed BCa cell proliferation, migration and invasion as well as the epithelial-mesenchymal transition (EMT) process. Based on bioinformatics analysis and our experiments, microRNA-186-5p (miR-186-5p) was found to be the upstream miRNA of RAB27A/B in BCa. MiR-186-5p expression was significantly downregulated in BCa cells and tissues. MiR-186-5p directly targeted the 3'-untranslated region (3'-UTR) of RAB27A/B and downregulated both mRNA and protein levels of RAB27A/B in BCa cells. MiR-186-5p overexpression suppressed BCa cell proliferation, migration and invasion as well as the EMT process in vitro and inhibited tumor growth in vivo. Overexpressing RAB27A/B rescued the inhibitory effect of miR-186-5p on malignant phenotypes of BCa cells. Furthermore, miR-186-5p inactivated the phosphatidylinositol 3-Kinase (PI3K)/mitogen-activated protein kinase (MAPK) signaling pathway by downregulating the expression of RAB27A/B, as shown in western blot analysis. Overall, miR-186-5p suppressed BCa cell proliferation, migration, invasion and EMT process and inhibited xenograft tumor growth by targeting RAB27A/B to inactivate the PI3K/MAPK signaling.

Background This study aimed to determine whether the enhancer of the rudimentary homolog (ERH) gene regulates cell migration and invasion in human bladder urothelial carcinoma (BUC) T24 cells and the underlying mechanism. Methods First, we knocked down ERH in BUC T24 and 5637 cells by shRNA and then used wound healing cell scratch migration assays, transwell cell migration assays, transwell cell invasion chamber experiments and nude mouse tail vein transfer assays to determine the migration and invasion ability after ERH was knocked down. Moreover, we used gene expression profiling chip analysis and further functional experiments to explore the possible mechanism through which ERH knockdown downregulated metastasis ability in T24 cells. Results Wound healing cell scratch migration assays, transwell cell migration assays, transwell cell invasion chamber experiments and nude mouse tail vein transfer assays all showed that the metastasis ability was significantly inhibited in human BUC T24 and 5637 cells with ERH knockdown. A gene expression profiling chip analysis in T24 cells showed that the MYC gene may be an important downstream target of the ERH gene, and the functional experiments showed that MYC is a functional target of ERH in BUC T24 cells. Conclusion ERH knockdown could inhibit the metastasis of BUC T24 cells in vitro and in vivo. This study further explored the mechanism of the ERH gene in the metastasis of the T24 human bladder cancer cell line and found that ERH may regulate MYC gene expression. The results of this research provide a basis for the clinical application of ERH as a potential target for BUC treatment. Electronic supplementary material The online version of this article (10.1186/s12885-019-5423-9) contains supplementary material, which is available to authorized users.

Prostate cancer (PCa) is one of the major cancers affecting males with high mortality around the world. Recent studies have found that some long noncoding RNAs play a critical part in the cellular processes of PCa. In our study, aberrant expressed lymphoid enhancer-binding factor-1 antisense RNA 1 (LEF1-AS1), microRNA-330-5p (miR-330-5p), and lymphoid enhancer-binding factor-1 (LEF1) were screened out from a microarray database, the role of the novel noncoding RNA regulatory circuitry in the initiation and development of PCa was investigated. LEF1-AS1 and LEF1 were highly expressed while miR-330-5p was poorly expressed in PCa. Following that, the PCa PC-3 cell line was adopted for subsequently experiments, in which the expression of LEF1-AS1 and miR-330-5p was subsequently altered by means of exogenous transfection. After that, the effects of up- or downregulation of LEF1-AS1 and miR-330-5p on epithelial-mesenchymal transition (EMT) and the cell ability for proliferation, invasion, migration in vitro, and tumorigenesis and lymph node metastasis (LNM) in vivo were evaluated. RNA crosstalk revealed that LEF1-AS1 bound to miR-330-5p and LEF1 was the target gene of miR-330-5p. Silenced LEF1-AS1 or elevated miR-330-5p exhibited inhibited EMT processes, reduced ability of proliferation, invasion and migration, coupling with decreased tumorigenesis and LNM in nude mice. The key findings of this study collectively propose downregulation of LEF1-AS1 competing with miR-330-5p to inhibit EMT, invasion and migration of PCa by LEF1 repression.

Background Different histological subtypes of non-small cell lung cancer (NSCLC) show different molecular characteristics and responses to therapeutic strategy. Identification of specific gene, clarification of its special roles and molecular mechanisms are crucial for developing new therapeutic approach for particular subtype patients. Methods Surgical specimens of 540 NSCLC patients were recruited. Immunohistochemistry was used to detect SOX30 expression, and correlations with clinical parameters were analyzed. Functional experiments and gene ontology analysis were performed to investigate roles of SOX30. Network analysis, TOP/FOP-Flash assays, luciferase reporter assays and ChIP-PCR assays were performed to determine the mechanism. Survival analyses were calculated by Kaplan-Meier and Cox regression. Recovery experiment was investigated the importance of the target of SOX30. Results SOX30 expression is closely associated with histological types of NSCLC, and metastasis of adenocarcinoma (ADC) patients but not of squamous cell carcinoma (SCC) patients. SOX30 strongly inhibits cancer cell migration and invasion in ADC cell lines, whrereas not affects cell migration and invasion in SCC cell lines. The genes associated with SOX30 preferentially enrich in metastasis process and Wnt-signaling in only ADC patients. Consistently, SOX30 is negatively associated with the expression of Wnt-signaling and metastasis-related gene CTNNB1 (β-catenin) in ADC, but not in SCC. At the molecular level, SOX30 represses Wnt-signaling by directly transcriptional inhibition of CTNNB1 in ADC, and also not in SCC. In the clinical, SOX30 is a favorable and independent prognostic factor in ADC patients, whereas is an unfavorable and independent prognostic factor in SCC patients. Moreover, SOX30 expression is a double face early-stage prognostic biomarker in ADC and SCC patients. In addition, forcible restoration of CTNNB1 indeed can inhibit the anti-metastatic role of SOX30 in ADC patients. Conclusions In early-stage ADC patients, elevated SOX30 expression inhibits tumor-metastasis by directly binding to CTNNB1 promoter resulting in a favorable prognosis of these patients. However, in early-stage SCC patients, SOX30 has no inhibitory role on tumor-metastasis due to not binding to CTNNB1 promoter leading to an unfavorable prognosis of the patients. This study highlights a special role and prognostic value of SOX30 in ADC, providing a novel therapeutic target for particular subtype NSCLC patients. Electronic supplementary material The online version of this article (10.1186/s12931-018-0952-3) contains supplementary material, which is available to authorized users.

Background Erectile dysfunction (ED) is a common complication of diabetes. This study aimed to explore the beneficial effect of Danshen injection on ED in a streptozotocin (STZ)-induced diabetic rat model and the underlying mechanism. Methods The diabetic rat model was established by an intraperitoneal injection of 60 mg/kg STZ in male Sprague-Dawley rats. The diabetic rats were intraperitoneally injected with Danshen solution (0.5 or 1 mL/kg/day) or the same volume of saline for 6 weeks. Age-matched rats served as controls. After 6 weeks, erectile function and histological morphology of the corpora cavernosum were assessed. Oxidative stress indicators, including superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and reactive oxygen species (ROS) levels, were measured in penile tissues. The expression levels of glucose-regulated protein 78 (Grp78), growth arrest and DNA damage-inducible gene 153 (GADD153/CHOP) were determined by immunohistochemistry, immunoblotting, and RT-PCR. Apoptosis was detected by a TUNEL assay. Results The erection times of diabetic rats were significantly less than those of control rats. Danshen injection could improve erectile function via increased erection times. Danshen injection was also found to ameliorate the morphological abnormalities of the corpora cavernosum, to reduce the number of apoptotic cells, and to suppress caspase-3 activation in penile tissue, accompanied by downregulation of the endoplasmic reticulum stress biomarkers Grp78 and CHOP. Danshen injection could increase SOD activity as well as reduce ROS and MDA levels in diabetic rats, indicating suppression of oxidative stress. Conclusion Danshen injection could rescue diabetes-associated ED, possibly via suppressing the oxidative stress and endoplasmic reticulum (ER) stress-induced apoptosis pathways.

Object: Intercellular adhesion molecule 1 (ICAM-1) is an adhesive protein involved in inflammatory responses and endothelial dysfunction. ICAM-1 expression is upregulated in cerebrovascular tissue affected by stroke. We investigated whether serum soluble ICAM-1 (sICAM-1) levels are associated with cerebral microbleeds (CMBs) and risk of hemorrhagic transformation (HT).Methods: 148 patients with acute ischemic stroke were enrolled. Serum sICAM-1 levels were measured and compared between patients and healthy controls. Multivariate logistic regression analysis was performed to estimate the relationship between serum sICAM-1 levels and the HT risk.Results: Serum sICAM-1 levels were significantly higher in ischemic stroke patients compared with healthy controls (p < .001), and higher in patients with CMBs (n = 81) compared with patients without CMBs (n = 67) (p < .001). Patients with high sICAM-1 levels (≥250.5 ng/mL) were more likely to have hypertension, diabetes mellitus, previous stroke, and CMBs compared with patients with low sICAM-1 levels. In stroke patients with CMBs, higher serum sICAM-1 levels were independently associated with increased HT risk.Conclusion: Serum sICAM-1 levels are associated with presence of CMBs and increased risk of HT in ischemic stroke patients.

Background Reconstruction after pelvic tumor resection of the acetabulum is challenging. Previous methods of hip transposition after acetabular resection have the advantages of reducing wound complications and infections of the allograft or metal endoprosthesis but were associated with substantial limb length discrepancy. We therefore developed a modification of this procedure, rotation hip transposition after femur lengthening, to address limb length, and we wished to evaluate its effectiveness in terms of complications and functional outcomes. Questions/purposes In this study, we asked: (1) What were the Musculoskeletal Tumor Society scores after this reconstruction method was used? (2) What complications occurred after this reconstruction method was used? (3) What proportion of patients achieved solid arthrodesis (as opposed to pseudarthrosis) with the sacrum and solid union of the femur? (4) What were the results with respect to limb length after a minimum follow-up of 2 years? Methods From 2011 to 2017, 83 patients with an aggressive benign or primary malignant tumor involving the acetabulum were treated in our institution. Of those, 23% (19 of 83) were treated with rotation hip transposition after femur lengthening and were considered for this retrospective study; 15 were available at a minimum follow-up of 2 years (median [range], 49 months [24 to 97 months]), and four died of lung metastases before 2 years. No patients were lost to follow-up before 2 years. During the period in question, the general indications for this approach were primary nonmetastatic malignant bone tumor or a locally aggressive benign bone tumor that could not be treated adequately with curettage. There were seven men and 12 women with a median age of 43 years. Nine patients underwent Zones I + II resection, eight patients had Zones I + II + III resection, and two received Zones II + III resection. After tumor resection, rotation hip transposition after femur lengthening reconstruction was performed, which included two steps. The first step was to lengthen the femur with the insertion of an allograft. Two methods were used to achieve limb lengthening: a "Z" osteotomy and a transverse osteotomy. The second step was to take the hip transposition and rotate the femoral head posteriorly 10° to 20°. The median (range) operative time was 510 minutes (330 to 925 minutes). The median intraoperative blood loss was 4000 mL (1800 to 7000 mL). We performed a chart review on the 15 available patients for clinical and radiographic assessment of functional outcomes and complications. Arthrodesis and leg length discrepancy were evaluated radiographically. Results The median (range) Musculoskeletal Tumor Society score was 21 points (17 to 30). Eleven of 19 patients developed procedure-related complications, including six patients with allograft nonunion, two with deep infection, two with delayed skin healing, and one with a hematoma. Two patients had minor additional surgical interventions without the removal of any implants. Local recurrences developed in four patients, and all four died of disease. All seven patients treated with a Z osteotomy had bone union. Among the eight patients with transverse osteotomy, bone union did not occur in six patients. After hip transposition, stable iliofemoral arthrodesis was achieved in seven patients. Pseudarthrosis developed in the remaining eight patients. The median (range) lower limb length discrepancy at the last follow-up visit or death was 8 mm (1 to 42 mm). Conclusion Although complex and challenging, rotation hip transposition after femur lengthening reconstruction with a Z osteotomy provides acceptable functional outcomes with complications that are within expectations for resection of pelvic tumors involving the acetabulum. Because of the magnitude and complexity of this technique, we believe it should be used primarily for patients with a favorable prognosis, both locally and systemically. This innovative procedure may be useful to other surgeons if larger numbers of patients and longer-term follow-up confirm our results. Level of evidence Level IV, therapeutic study.

The sensitive and selective determination of acetaminophen (AP) in the human body is highly desirable to ensure human health. In this work, nickel-doping nanoporous carbon (Ni/C) was fabricated by directly calcining Ni based metal-organic framework (Ni-MOF). The Ni/C based electrochemical sensor was developed for sensitive and selective determination of AP in human blood serum and urine samples. The prepared Ni/C composite possess plentiful catalytic active sites, ordered mesoporous structure and large specific surface area, which endow the constructed Ni/C sensor with a prominent performance for acetaminophen sensing. Under the optimal conditions, the developed method offered good linearity in the range of 0.20–53.75 μM with a low detection limit (S/N = 3) of 4.04 × 10−2 μM. The electrocatalytic performance of the sensor towards AP was further measured by differential pulse voltammetry and cyclic voltammetry. The results demonstrated that the Ni/C sensor can be feasibly employed for the determination of AP in human blood serum and urine samples with excellent anti-interference stability and good reproducibility. The research reveals a great promising of the Ni/C electrochemical sensor for clinical applications and paves a way for the construction of high-performance electrochemical sensors for AP determination.

To investigate the effects of dose reduction on image quality and lesion detectability of oncologicalA total of 33 pediatric patients (weight 8.5-58.5 kg; age 0.8-17.6 years) underwent total-body PET/CT using uEXPLORER scanner with anOur analysis shows that sufficient subjective image quality and lesion conspicuity could be maintained down to 1/30th (0.12 MBq/kg) of the administered dose ofThe total-body PET/CT might significantly decrease the administered dose upon maintaining the image quality and diagnostic performance of micro-lesions in pediatric patients. Data suggests that using total-body PET/CT, optimal image quality could be achieved with an administered dose-reduction down to 1/10-dose (0.37 MBq/kg).

Organic micropollutants have been extensively detected in environmental waters, posing severe hazards to organisms and humans. Effective detection of micropollutants in environmental water and food samples is of significant importance. Herein, a novel magnetic porous organic framework (labeled as M-Qu-POF) was synthesized using natural quercetin as building units via a facile azo-coupling reaction for the first time. Featuring with good magnetism, intrinsic porosity, high surface area and hydrophilic-lipophilic (amphiphilic) structure, the M-Qu-POF displayed high adsorption capacity for phenylurea herbicides (PUHs) pollutants. The adsorption mechanism was investigated by theory calculation, confirming that the hydrogen bonds interaction, π-π interactions and electrostatic interactions play an important role in the adsorption. With the M-Qu-POF as adsorbent, a magnetic solid phase extraction-high performance liquid chromatography method was first established for simultaneous enrichment and detection of six PUHs in environmental water, tea drink and cucumber samples. Under the optimized experimental conditions, good linear range, low detection limits and high enrichment factors were obtained. The method was successfully applied for determination of PUHs in environmental water, tea drink and cucumber samples with satisfactory recoveries (80.0–118%). The result demonstrates that the M-Qu-POF material has a good application prospect in the detection of other organic micropollutants.

The antitumor activity of Momordica anti-human immunodeficiency virus protein of 30 kDa (MAP30) has been proved. However, the role of MAP30 on tumor metastasis has not yet been identified. For this purpose, we investigated this effect and underlying mechanism of MAP30 in bladder cancer (BC). Here, we reported that MAP30 significantly inhibited the cell proliferation and clone formation of 5637 and T24 cells

Muscle-invasive bladder carcinoma (MIBC) accounts for 25% of newly diagnosed bladder carcinomas (BCs) and presents a high risk of progression and metastasis. This study aimed to identify reliable biomarkers associated with muscle invasion and prognosis to identify potential therapeutic targets for MIBC. Four gene datasets were downloaded from the Gene Expression Omnibus, and the integrated differentially expressed genes (DEGs) were then subjected to gene ontology (GO) terms and pathway enrichment analyses. Correlation analysis between the expression of the top-ranking DEGs and pathological T stages was performed to identify the genes associated with early muscle invasion. The corresponding prognostic values were evaluated, and co-expressed genes mined in the cBioPortal database were loaded into ClueGo in Cytoscape for pathway enrichment analysis. Using data mining from the STRING and TCGA databases, protein-protein interaction and competitive endogenous RNA networks were constructed. In total, 645 integrated DEGs were identified and these were mainly enriched in 26 pathways, including cell cycle, bladder cancer, DNA replication, and PPAR signaling pathway. S100A7 expression was significantly increased from the T2 stage and showed significantly worse overall survival and disease-specific survival in patients with BC. In total, 144 genes co-expressed with S100A7 in BC were significantly enriched in the IL-17 pathway. S100A7 was predicted to directly interact with LYZ, which potentially shows competitive binding with hsa-mir-140 to affect the expression of six lncRNAs in MIBC. In conclusion, high S100A7 expression was predicted to be associated with early muscle invasion and poor survival in patients with BC.

For the treatment of ejaculatory duct obstruction, transurethral seminal vesiculoscopy (TSV) is the most common method, but the success rate is much lower than studies that have reported. So we developed a new ultrasound-guided seminal vesicle radiography (UGSVR) combining CT three-dimensional reconstruction (CT-TR) technique to improve the success rate of TSV. Between June 2018 and November 2019, 32 patients were enrolled and randomly assigned to two groups: experimental group (UGSvR combining CT-TR) and control group (standard evaluation). Baseline information, including age, smoking history and body mass index (BMI), was compared preoperatively. Surgical parameters included success rates (SR), surgical time (ST), catheter days (CD), length of hospital stays (HS) and complications were compared between groups. There were no statistically significant differences in baseline data between the two groups (all p > .05). There were no significant differences in the CD, HS and complications between the two groups (all p > .05), but the differences in ST and SR were statistically significant (p < .05). In conclusion, this new technique of UGSvR combining CT-TR was achieving a satisfactory increase in the success rate of TSV, while not increasing the incidence of complications, compared to normal evaluation before TSV operation.

Hypoxia-inducible factor 1α (HIF-1α) is a known regulator of tumor cell proliferation, migration, and angiogenesis. The presence of a high concentration of HIF-1α is positively correlated with the severity of cancer. Therefore, the inhibition of this pathway represents an important therapeutic target for the treatment of various types of cancer. Here, we designed and synthesized 30 panaxadiol (PD) derivatives and evaluated their inhibitory activities against HIF-1α transcription. Of these, compound 3l exhibited the most promising inhibitory activity (IC50 = 3.7 µM) and showed significantly decreased cytotoxicity compared with PD. Compound 9e exhibited the strongest cytotoxic effect and may be considered for further preclinical development.

To investigate the insomnia status and relevant factors for the medical staff in the medical aid team for Hubei Province during the outbreak of coronavirus disease 2019.A convenient sampling survey was conducted among 1 056 medical staff in the national medical team of Hubei Province by using the Insomnia Severity Index (ISI) and the Regulatory Emotional Self-Efficacy (RES).The incidence from moderate to severe insomnia was 35.14%, and the total self-efficacy of emotion regulation was 3.60±0.91. Univariate analysis showed that the incidence of insomnia in female medical workers in Hubei Province was higher than that of male medical workers, which was increased with the elongation of work time and frequency. In addition, insomnia was associated with age, perceived ambient exposure and infection, and RES scores. Stepwise regression analysis showed that the occurrence of insomnia was mainly related to gender, perceived peripheral exposure, infection, and RES scores.Insomnia is very common among medical workers in Hubei Province during the COVID-19 epidemic. Insomnia is related to the medical work status, the gender and their own emotional management and regulation in the epidemic area.

Hypertrophic scars (HSs) are a type of pathological scar which are induced by surgery, burn injuries or trauma during the healing process. Due to the high recurrence rates and strong invasive properties, HSs have become a major clinical issue. Resveratrol has been identified as a potential agent to suppress scar formation; however, the underlying mechanism of action remains unclear. Therefore, the present study aimed to investigate the effect of resveratrol on HS-derived fibroblasts (HSFBs) in vitro. MTT assay was performed to evaluate cell viability following the resveratrol treatment. Western blot and RT-qPCR analysis was used to identify the expression levels and the relationship among autophagic markers, miR-4654 and resveratrol treatment. Finally, GFP-LC3 stable HSFBs cells were generated to further assess the effect of resveratrol. The results revealed that resveratrol significantly induced cell death in a dose-dependent manner and induced autophagy by downregulating the expression levels of Rheb in HSFBs. Notably, microRNA-4654 (miR-4654) was significantly decreased in the HSFBs and re-upregulated by resveratrol treatment dose-dependently. Through the bioinformatic analysis and luciferase assay, miR-4654 was identified to directly target Rheb. Transfection studies showed that miR-4654 negative correlated with Rheb expression, suggesting that the autophagic process may be altered by the miR-4654/Rheb axis under the control of resveratrol. In conclusion, the results of the present study suggested that resveratrol may promote autophagy by upregulating miR-4654, which in turn may suppress Rheb expression via directly binding to the 3′-untranslated region of Rheb. These findings provided a novel insight into the development of potential therapeutic targets for HSs.

Background Ureteral intussusception, a rarely reported unique condition, occurs primarily as a complication of ureteric tumours. Case presentation We present a case of ureteral intussusception accompanied with a large ureteral polyp periodically protruding into the bladder cavity occurring in a 56-year-old man who experienced vague flank pain and intermittent haematuria. The patient was successfully treated by ureteroscopic cauterization combined with partial ureterectomy with reanastomosis. Conclusions This is the first report that describes polyp-related ureteral intussusception using comprehensive and representative ureteroscopic images and video. Our findings suggest that ureteroscopy is vital for diagnosis. Extensive biopsies through ureteroscopy are less invasive, and make it easier to exclude the presence of ureteral malignancies. Ureteroscopic resection of the whole polyp with its stalk and intussusceptum using Holmium: YAG laser did not seem viable in this case. However, cauterization of partial polyp tissues followed by open surgery for segmental resection of the ureter with reanastomosis is helpful in controlling such patient well-being.

The effects of exercise interventions on blood pressure control in hypertensive patients have received extensive attention and recognition. However, the influence of exercise-related behaviors on the effects of blood pressure control and the management factors that affect exercise behaviors remain inconclusive. Therefore, this study aimed to explore the relationships between exercise and exercise-related behaviors and blood pressure control, expecting to provide a scientific basis for further improvement of exercise intervention programs for patients with hypertension. Long-term residents in a community in Fuzhou, Fujian Province, China who were diagnosed with hypertension at a medical facility were recruited for this study. Hypertensive patients with uncontrolled blood pressure were placed in the case group, and those with controlled blood pressure were placed in the control group. The count data were analyzed with the χ2 test based on α = 0.05. A univariate logistic regression analysis was performed to screen significant variables; independent variables were selected based on professional knowledge and were tested for co-linearity. These variables were incorporated into a non-conditional multivariate logistic regression analysis to analyze relevant factors for blood pressure control, while calculating odds ratio (ORs), 95% confidence intervals (CIs), and P values. Differences with a P

New potential biomarkers and therapeutic targets for ovarian cancer should be identified. The amplification in chromosomal region 5q31–5q35.3 exhibits the strongest correlation with overall survival (OS) of ovarian cancer. SOX30 coincidentally located at this chromosomal region has been determined as a new important tumor suppressor. However, the prognostic value, role and mechanism of SOX30 in ovarian cancer are unexplored. Here, we reveal that SOX30 is frequently overexpressed in ovarian cancer tissues and is associated with clinical stage and metastasis of ovarian cancer patients. High SOX30 expression predicts better OS and acts as an independent prognostic factor in advanced-stage patients, but is not associated with OS in early-stage patients. Based on the survival analyses, the advanced-stage patients with high SOX30 expression can receive platin- and/or taxol-based chemotherapy, whereas they should not receive chemotherapy containing gemcitabine or topotecan. Functionally, SOX30 strongly inhibits tumor cell migration and invasion in intro and suppresses tumor metastasis in vivo. SOX30 regulates some markers (E-CADHERIN, FIBRONECTIN, N-CADHERIN and VIMENTIN) and prevents the characteristics of epithelial–mesenchymal transition (EMT). SOX30 transcriptionally regulates the expression of E-CADHERIN, FIBRONECTIN and N-CADHERIN by binding to their promoters. Restoration of E-CADHERIN and/or N-CADHERIN when overexpressing SOX30 significantly reduces the anti-metastatic role of SOX30. Indeed, chemotherapy treatment containing platin or gemcitabine combined with SOX30 expression influences tumor cell metastasis and the survival of nude mice differently, which is closely associated with EMT. In conclusion, SOX30 antagonizes tumor metastasis by preventing EMT process that can be used to predict survival and incorporated into chemotherapeutics of advanced-stage ovarian cancer patients.

The protein containing the C2 domain has been well documented for its essential roles in endocytosis, cellular metabolism and cancer. Tac2-N (TC2N) is a tandem C2 domain-containing protein, but its function, including its role in tumorigenesis, remains unknown. Here, we first identified TC2N as a novel oncogene in lung cancer. TC2N was preferentially upregulated in lung cancer tissues compared with adjacent normal lung tissues. High TC2N expression was significantly associated with poor outcome of lung cancer patients. Knockdown of TC2N markedly induces cell apoptosis and cell cycle arrest with repressing proliferation in vitro, and suppresses tumorigenicity in vivo, whereas overexpression of TC2N has the opposite effects both in vitro and in vivo. Using a combination of TCGA database and bioinformatics, we demonstrate that TC2N is involved in regulation of the p53 signaling pathway. Mechanistically, TC2N attenuates p53 signaling pathway through inhibiting Cdk5-induced phosphorylation of p53 via inducing Cdk5 degradation or disrupting the interaction between Cdk5 and p53. Moreover, the blockade of p53 attenuates the function of TC2N knockdown in the regulation of cell proliferation and apoptosis. In addition, downregulated TC2N is involved in the apoptosis of lung cancer cells induced by doxorubicin, leading to p53 pathway activation. Overall, these findings uncover a role for the p53 inactivator TC2N in regulating the proliferation and apoptosis of lung cancer cells. Our present study provides novel insights into the mechanism of tumorigenesis in lung cancer.

Introduction In this article, we utilized Ingenuity® Pathway Analysis (IPA®) bioinformatics analysis software and Metascape® bioinformatics analysis website tools to analyse the possible mechanism of ERH affecting tumourigenesis (proliferation and apoptosis) in bladder cancer (BC) T24 cells. Methods The ERH gene was knocked down, and BC T24 cells were divided into ERH normal and knockdown groups. Affymetrix® gene expression microarrays were performed to obtain a differentially expressed gene list (DEGL) between the 2 groups. IPA® data analyses contain five modules: disease and function analysis, upstream analysis, regulator effects analysis, canonical pathway analysis and molecular network analysis. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were analysed by Metascape®. Results The results of the gene expression profiling chip and the DEGL showed that 344 genes were upregulated and 254 genes were downregulated. The IPA® and Metascape® pathway analyses showed that the ERH gene may affect proliferation and apoptosis by affecting the apoptosis, cell cycle, Toll-like receptor (TLR), NF-κB or TGF-beta signalling pathways. Upstream analysis determined that the ERH gene may regulate TNF and NK-κB in the BC T24 cell lines. The ERH gene may be involved in the “cell death and survival” molecular network in BC T24 cells. ERH may be a regulator of KITLG through TNF. Conclusions The ERH gene may affect apoptosis through the TLR, NF-κB, TNF or TGF-beta signalling pathways in BC T24 cells, and may be a regulator of KITLG to ultimately activate the growth of malignant tumours.

Background Whether reconstruction is more beneficial after iliosacral bone tumor resection remains controversial. Because of high rates of complications and recurrence, few patients benefit from reconstruction. The aim of this study is to assess functional outcomes and to reveal changes in the ipsilateral hip joint after partial iliosacral resection. Methods From 1998 to 2016, 21 patients aged 20–66 years underwent iliosacral resection, 18 without reconstruction (group 1) and 3 with reconstruction (group 2). Function was evaluated using the Musculoskeletal Tumor Society 1993 rating scale (MSTS 1993), and disability was measured using the Toronto Extremity Salvage Score (TESS). I-A distance was defined as the distance from the iliosacral joint to the upper line of the acetabulum along the curved line. Group 1 were subdivided into two groups: group 1A included the patients with a defect less than one-third of the I-A distance and group 1B the remainder. Acetabulum-head index (AHI) and center-edge angle (CE angle) were measured. The relationship between defect length and femoral head coverage was analyzed. Results The mean follow-up was 67.3 months. Eighteen patients were included in group 1 and three in group 2. Preoperative data of the 3 groups were statistically equivalent. In addition, no difference of postoperative functional outcome has been highlighted. The final average MSTS 1993 score was 93.6% in group 1 and 93.3% in group 2. The mean TESS was 98 in group 1 and 98.5 in group 2. AHI and CE angle between groups 1 and 2 were not different. The AHI was 80 ± 5.4% in group 1A and 67 ± 9.0% in group 1B (t = − 3.740, P = 0.002), while the CE angle was 29 ± 5.9° in group 1A and 20 ± 6.3° in group 1B (t = − 3.172, P = 0.006) at the last follow-up. Regarding the limb-length discrepancy, group 1 and 2 were similar whereas group 1A and 1B were statistically different (group 1A: 0.7 ± 0.7 cm; group 2: 2.6 ± 1.0 cm; t = − 4.324, P = 0.001). Conclusions Ilio-sacral resection without reconstruction removing more than one- third of the I-A distance leads to an impairement of the limb-length discrepancy and an increase of the defect of the acetabular coverage without altering the functional outcome. Nevertheless, iliosacral resection without reconstruction could serve as a viable treatment option for pelvic type I-IV tumors.

Previous studies have focused mostly on independent effects of the stroke risk factors, whereas little attention has been paid to interactions between individual factors which may be important for stroke prevention. We collected data related to the patients’ demographic characteristics, history of chronic diseases and lifestyle factors in 2258 patients with primary hypertension. Logistic regression models based on odds ratio (OR) with their associated 95% confidence interval (CI) were used to estimate an independent effect of homocysteine (Hcy) on the risk of stroke but also include the interactions between Hcy and other risk factors. Hcy was associated with an increased OR of the risk of stroke in both hypertension patients (OR, 1.027; 95% CI, 1.016–1.038; P

Intracranial aneurysm is a leading cause of stroke. Its treatment has evolved over the past 2 decades. This review summarizes the treatment strategies for intracranial aneurysms from 3 different perspectives: open surgery approach, transluminal treatment approach, and new technologies being used or trialed. We introduce most of the available treatment techniques in detail, including contralateral clipping, wrapping and clipping, double catheters assisting coiling and waffle-cone technique, and so on. Data from major trials such as Analysis of Treatment by Endovascular approach of Non-ruptured Aneurysms (ATENA), Internal Subarachnoid Trial (ISAT), Clinical and Anatomical Results in the Treatment of Ruptured Intracranial Aneurysms (CLARITY), and Barrow Ruptured Aneurysm Trial (BRAT) as well as information from other clinical reports and local experience are reviewed to suggest a clinical pathway for treating different types of intracranial aneurysms. It will be a valuable supplement to the current existing guidelines. We hope it could help assisting real-time decision-making in clinical practices and also encourage advancements in managing the disease.

Data on the sex-specific differences in risk of stroke among patients with H-type hypertension are limited. We aimed to analyze interactions between sex and other risk factors on stroke, including the sex-methylenetetrahydrofolate reductase (MTHFR) interaction. A retrospective analysis of baseline data from 2040 patients with hypertension and hyperhomocysteinemia (HHcy) included demographic characteristics, biomarkers, history of chronic diseases and lifestyle factors. Polymerase chain reaction-restriction fragment length polymorphism method was used to investigate the C677T polymorphism of MTHFR gene. We examined independent effects and interactions between sex and stratified factors on the risk of stroke by logistic regression model. A total of 1412 patients suffered stroke, and the prevalence of stroke was 70.65% in men and 66.53% in women. Both men and women had independent risk factors for stroke, including diabetes mellitus, atrial fibrillation, smoking, increased level of systolic blood pressure (SBP) and plasma total homocysteine (tHcy), as well as the decreased level of high-density lipoprotein cholesterol. Diastolic blood pressure (DBP) -specific risk of stroke was unique to men. Interactions between sex and other risk factors on stroke risk were statistically significant: age, fasting plasma glucose (FPG), SBP, DBP, triglycerides (TG) and tHcy. Furthermore, tHcy interacted with age, SBP and DBP in men, and age, SBP, DBP, FPG, and TG in women to modulate the risk of stroke. Although TT genotype did not have an independent effect on stroke, it could interact with sex and FPG, TG and SBP to increase stroke. In conclusion, sex-specific differences are useful to stratify the risk of stroke and assist clinicians in the decision to select a reasonable therapeutic option for high-risk patients.

To investigate the antitumor mechanism of MAP30 in human bladder cell line (T24) and its potential toxic effects in mice. In this study, the biological behavior of MAP30's influence on bladder cell was investigated to reveal the antitumor mechanism and role of MAP30 in bladder cancer. MAP30 gene sequence optimized by gene synthesis codon was inserted into the prokaryotic expression vector pET-28a to produce a large amount of target protein in Escherichia coli. The protein product was obtained after purification. Membrane hydration method was used to prepare MAP30 liposome in order to enhance its membrane permeability. The effects of MAP30 on the viability, apoptosis and migration of T24 cell were assessed using 3"‘(4,5"‘dimethyl"‘thiazol"‘2"‘yl)"‘2,5"‘diphenyl"‘2H"‘tetrazolium bromide (MTT), flow cytometric and TUNEL assays, respectively. Mice were transfected with bladder cancer cells for 48 h. The expressions of apoptotic and non-apoptotic proteins were determined using Western blotting. Changes in tumor volume and occurrence of metastasis were assessed using luciferase assay. After 7 days, liver and kidney were excised for histological examination. The levels of reactive oxygen species (ROS), malondialdehyde (MDA), and reduced glutathione (GSH), and activities of catalase and glutathione peroxidase (GPx) were determined in serum or homogenate using enzyme-linked immunosorbent assay (ELISA). The yield of MAP30 after purification was significantly increased. The results of MTT assay showed that MAP30 significantly and concentration-dependently inhibited the proliferation and migration of T24 cells (p < 0.05). The prepared liposomes had uniform hydrated particle size of 132.6 nm, with encapsulation efficiency of 78 %. The inhibitory effect of MAP30 liposome on T24 cells was significantly higher than that of MAP30, and MAP30 significantly increased the number of apoptotic cells (p < 0.05). Western blotting showed that MAP30 significantly promoted the expression of caspase 3 (p < 0.05), but did not significantly affect the expressions of bcl-2 and bax (p > 0.05). It also significantly down-regulated the expressions of NF-kB, JNK and MMP2 (p < 0.05). Tumor formation was significantly inhibited, and tumor volume reduced in bladder cancer-bearing mice after treatment with MAP30 (p < 0.05). Histological examination showed that MAP30 induced mild histological changes in the liver and kidney of mice, and significantly increased the level of MDA at day 1 (p < 0.05). It also significantly and time-dependently increased ROS, but reduced GSH levels and activities of catalase and GPx (p < 0.05). However, MAP30 had no significant effect on DNA (p > 0.05). The apoptotic effect of MAP30 in T24 cells is mediated via activation of caspase-3 signaling pathway. The protein produces mild histological changes in the liver and kidney of mice, but has no significant effect on DNA.

Background and aims Fargesin mainly functions in the improvement of lipid metabolism and the inhibition of inflammation, but the role of fargesin in atherogenesis and the molecular mechanisms have not been defined. We aimed to explore if and how fargesin affects atherosclerosis by regulating lipid metabolism and inflammatory response. Methods and results ApoE−/− mice were fed a high-fat diet to form atherosclerotic plaques and then administrated with fargesin or saline via gavage. Oil Red O, HE and Masson staining were performed to assess atherosclerostic plaques in apoE−/− mice. [3H] labeled cholesterol was used to detect cholesterol efflux and reverse cholesterol transport (RCT) efficiency. Enzymatic methods were performed to analyze plasma lipid profile in apoE−/− mice. Immunohistochemistry was used to analyze macrophage infiltration. THP-1-derived macrophages were incubated with fargesin or not. Both Western blot and qRT-PCR were applied to detect target gene expression. Oil Red O staining was applied to examine lipid accumulation in THP-1-derived macrophages. ELISA and qRT-PCR were used to examine the levels of inflammatory mediotors. We found that fargesin reduced atherosclerotic lesions by elevating efficiency of RCT and decreasing inflammatory response via upregulation of ABCA1 and ABCG1 expression in apoE−/− mice. Further, fargesin reduced lipid accumulation in THP-1-derived macrophages. Besides, fargesin increased phosphorylation of CEBPα in Ser21 and then upregulated LXRα, ABCA1 and ABCG1 expression in THP-1-derived macrophages. In addition, fargesin could reduce ox-LDL-induced inflammatory response by inactivation of the TLR4/NF-κB pathway. Conclusion These results suggest that fargesin inhibits atherosclerosis by promoting RCT process and reducing inflammatory response via CEBPαS21/LXRα and TLR4/NF-κB pathways, respectively.