Expression and significant roles of the long non-coding RNA CASC19/miR-491-5p/HMGA2 axis in the development of gastric cancer

BACKGROUND Gastric cancer(GC)is a common malignant tumor,long non-coding RNA and microRNA(miRNA)are important regulators that affect tumor proliferation,metastasis and chemotherapy resistance,and thus participate in tumor progression.CASC19 is a new bio-marker which can promote tumor invasion and metastasis.However,the mechanism by which CASC19 affects the progression of GC through miRNA is not clear.AIM To explore the role of the CASC19/miR-491-5p/HMGA2 regulatory axis in GC.METHODS To explore the expression and prognosis of CASC19 in GC through clinical samples,and investigate the effects of inhibiting CASC19 on the proliferation,migration,invasion and other functions of GC cells through cell counting Kit-8(CCK-8),ethynyldeoxyuridine,Wound healing assay,Transwell,Western blot and flow cytometry experiments.The effect of miR-491-5p and HMGA2 in GC were also proved.The regulatory relationship between CASC19 and miR-491-5p,miR-491-5p and HMGA2 were validated through Dual-luciferase reporter gene assay and reverse transcription PCR.Then CCK-8,Transwell,Wound healing assay,flow cytometry and animal experiments verify the role of CASC19/miR-491-5p/HMGA2 regulatory axis.RESULTS The expression level of CASC19 is related to the T stage,N stage,and tumor size of patients.Knockdown of the expression of CASC19 can inhibit the ability of proliferation,migration,invasion and EMT conversion of GC cells,and knocking down the expression of CASC19 can promote the apoptosis of GC cells.Increasing the expression of miR-491-5p can inhibit the proliferation of GC cells,miR-491-5p mimics can inhibit EMT conversion,and promote the apoptosis of GC cells,while decreasing the expression of miR-491-5p can promote the proliferation and EMT conversion and inhibit the apoptosis of GC cells.The expression of HMGA2 in GC tissues is higher than that in adjacent tissues.At the same time,the expression level of HMGA2 is related to the N and T stages of the patients.Reducing the level of HMGA2 can promote cell apoptosis and inhibit the proliferation of GC cells.Cell experiments and animal experiments have proved that CASC19 can regulates the expression of HMGA2 through miR-491-5p,thereby affecting the biological functions of GC.CONCLUSION CASC19 regulates the expression of HMGA2 through miR-491-5p to affect the development of GC.This axis may serve as a potential biomarker and therapeutic target of GC.

MicroRNA changes of bone marrow-derived mesenchymal stem cells differentiated into neuronal-like cells by Schwann cell-conditioned medium

Bone marrow-derived mesenchymal stem cells differentiate into neurons under the induction of Schwann cells. However, key microRNAs and related pathways for differentiation remain unclear. This study screened and identified differentially expressed microRNAs in bone marrow- derived mesenchymal stem cells induced by Schwann cell-conditioned medium, and explored targets and related pathways involved in their differentiation into neuronal-like cells. Primary bone marrow-derived mesenchymal stem cells were isolated from femoral and tibial bones, while primary Schwann cells were isolated from bilateral saphenous nerves. Bone marrow-derived mesenchymal stem cells were cultured in unconditioned (control group) and Schwann cell-conditioned medium (bone marrow-derived mesenchymal stem cell + Schwann cell group). Neuronal differentiation of bone marrow-derived mesenchymal stem cells induced by Schwann cell-conditioned medium was observed by time-lapse imaging. Upon induction, the morphology of bone marrow-derived mesencaymal stem cells changed into a neural shape with neurites. Results of quantitative reverse transcription-polymerase chain reaction revealed that nestin mRNA expression was upregulated from 1 to 3 days and downregulated from 3 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. Compared with the control group, microtubule-associated protein 2 mRNA expression gradually increased from 1 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. After 7 days of induction, microRNA analysis iden:ified 83 significantly differentially expressed microRNAs between the two groups. Gene Ontology analysis indicated enrichment of microRNA target genes for neuronal projection development, regulation of axonogenesis, and positive regulation of cell proliferation. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that Hippo, Wnt, transforming growth factor-beta, and Hedgehog signaling pathv/ays were potentially associated with neural differentiation of bone marrow-derived mesenchymal stem cells. This study, which carried out successful microRNA analysis of neuronal-like cells differentiated from bone marrow-derived mesenchymal stem cells by Schwann cell induction, revealed key microRNAs and pathways involved in neural differentiation of bone marrow-derived mesenchymal stem cells. All protocols were approved by the Animal Ethics Committee of Institute of Radiation Medicine, Chinese Academy of Medical Sciences on March 12, 2017 (approval number: DWLI-20170311).

Bioinformatics analysis of ferroptosis in spinal cord injury

Ferroptosis plays a key role in aggravating the progression of spinal cord injury(SCI),but the specific mechanism remains unknown.In this study,we constructed a rat model of T10 SCI using a modified Allen method.We identified 48,44,and 27 ferroptosis genes that were differentially expressed at 1,3,and 7 days after SCI induction.Compared with the sham group and other SCI subgroups,the subgroup at 1 day after SCI showed increased expression of the ferroptosis marker acyl-CoA synthetase long-chain family member 4 and the oxidative stress marker malondialdehyde in the injured spinal cord while glutathione in the injured spinal cord was lower.These findings with our bioinformatics results suggested that 1 day after SCI was the important period of ferroptosis progression.Bioinformatics analysis identified the following top ten hub ferroptosis genes in the subgroup at 1 day after SCI:STAT3,JUN,TLR4,ATF3,HMOX1,MAPK1,MAPK9,PTGS2,VEGFA,and RELA.Real-time polymerase chain reaction on rat spinal cord tissue confirmed that STAT3,JUN,TLR4,ATF3,HMOX1,PTGS2,and RELA mRNA levels were up-regulated and VEGFA,MAPK1 and MAPK9 mRNA levels were down-regulated.Ten potential compounds were predicted using the DSigDB database as potential drugs or molecules targeting ferroptosis to repair SCI.We also constructed a ferroptosis-related mRNA-miRNA-lncRNA network in SCI that included 66 lncRNAs,10 miRNAs,and 12 genes.Our results help further the understanding of the mechanism underlying ferroptosis in SCI.

Application value of biofluid-based biomarkers for the diagnosis and treatment of spinal cord injury

Recent studies in patients with spinal cord injuries(SCIs)have confirmed the diagnostic potential of biofluid-based biomarkers,as a topic of increasing interest in relation to SCI diagnosis and treatment.This paper reviews the research progress and application prospects of recently identified SCI-related biomarkers.Many structural proteins,such as glial fibrillary acidic protein,S100-β,ubiquitin carboxy-terminal hydrolase-L1,neurofilament light,and tau protein were correlated with the diagnosis,American Spinal Injury Association Impairment Scale,and prognosis of SCI to different degrees.Inflammatory factors,including interleukin-6,interleukin-8,and tumor necrosis factorα,are also good biomarkers for the diagnosis of acute and chronic SCI,while non-coding RNAs(micro RNAs and long non-coding RNAs)also show diagnostic potential for SCI.Trace elements(Mg,Se,Cu,Zn)have been shown to be related to motor recovery and can predict motor function after SCI,while humoral markers can reflect the pathophysiological changes after SCI.These factors have the advantages of low cost,convenient sampling,and ease of dynamic tracking,but are also associated with disadvantages,including diverse influencing factors and complex level changes.Although various proteins have been verified as potential biomarkers for SCI,more convincing evidence from large clinical and prospective studies is thus required to identify the most valuable diagnostic and prognostic biomarkers for SCI.

Nomogram established using risk factors of early gastric cancer for predicting the lymph node metastasis

BACKGROUND For the prognosis of patients with early gastric cancer(EGC),lymph node metastasis(LNM)plays a crucial role.A thorough and precise evaluation of the patient for LNM is now required.AIM To determine the factors influencing LNM and to construct a prediction model of LNM for EGC patients.METHODS Clinical information and pathology data of 2217 EGC patients downloaded from the Surveillance,Epidemiology,and End Results database were collected and analyzed.Based on a 7:3 ratio,1550 people were categorized into training sets and 667 people were assigned to testing sets,randomly.Based on the factors influencing LNM determined by the training sets,the nomogram was drawn and verified.RESULTS Based on multivariate analysis,age at diagnosis,histology type,grade,T-stage,and size were risk factors of LNM for EGC.Besides,nomogram was drawn to predict the risk of LNM for EGC patients.Among the categorical variables,the effect of grade(well,moderate,and poor)was the most significant prognosis factor.For training sets and testing sets,respectively,area under the receiver-operating characteristic curve of nomograms were 0.751[95%confidence interval(CI):0.721-0.782]and 0.786(95%CI:0.742-0.830).In addition,the calibration curves showed that the prediction model of LNM had good consistency.CONCLUSION Age at diagnosis,histology type,grade,T-stage,and tumor size were independent variables for LNM in EGC.Based on the above risk factors,prediction model may offer some guiding implications for the choice of subsequent therapeutic approaches for EGC.

Prognostic factors for disease-free survival in postoperative patients with hepatocellular carcinoma and construction of a nomogram model

BACKGROUND Hepatocellular carcinoma(HCC)is the most common type of liver cancer and has a high risk of invasion and metastasis along with a poor prognosis.AIM To investigate the independent predictive markers for disease-free survival(DFS)in patients with HCC and establish a trustworthy nomogram.METHODS In this study,445 patients who were hospitalized in The First Affiliated Hospital of Anhui Medical College between December 2009 and December 2014 were retrospectively examined.The survival curve was plotted using the Kaplan–Meier method and survival was determined using the log-rank test.To identify the prognostic variables,multivariate Cox regression analyses were carried out.To predict the DFS in patients with HCC,a nomogram was created.C-indices and receiver operator characteristic curves were used to evaluate the nomogram’s performance.Decision curve analysis(DCA)was used to evaluate the clinical application value of the nomogram.RESULTS Longer DFS was observed in patients with the following characteristics:elderly,I–II stage,and no history of hepatitis B.The calibration curve showed that this nomogram was reliable and had a higher area under the curve value than the tumor node metastasis(TNM)stage.Moreover,the DCA curve revealed that the nomogram had good clinical applicability in predicting 3-and 5-year DFS in HCC patients after surgery.CONCLUSION Age,TNM stage,and history of hepatitis B infection were independent factors for DFS in HCC patients,and a novel nomogram for DFS of HCC patients was created and validated.

Reoperation in an adult female with "right-sided" Hirschsprung's disease complicated by refractory hypertension and cough

Hirschsprung's disease(HD) is an intestinal malformation caused by the innate absence of ganglion cells in the neural plexus of the colorectal wall, and is most common in male infants. It is rare in adult, and is usually left-sided. Herein we reported based on the CARE guidelines a case of a 47-year-old adult female suffering from "right-sided" HD complicated by refractory hypertension and cough. The patient with a history of cesarean section and with digestive unfitness(abdominal pain, distention, and constipation) only since 20 years old had recurrence of HD after initial surgery due to the incomplete removal of the HD-affected bowel based on a diagnosis of "chronic ileus", leading to the relapse of the digestive symptoms and the emergence of some intractable circulatory and respiratory complications which could be hardly controlled by conservative treatment. During the long interval before coming to our department for help, she had been re-hospitalized for several times with various misdiagnoses and supplied merely with symptomatic treatment which could only achieve temporary symptomatic relief. At her admission to our department, the imaging examinations strongly indicated recurrent HD which was further supportedb y p a t h o l o g i c a l e x a m i n a t i o n s, a n d r i g h t h e m i-colectomy was performed to remove the remnant aganglionic intestinal segment. Intraoperative and postoperative pathology supported the completeness of the definitive resection. Post-operation, the patient's bowel motility significantly improved, and interestingly, the complications disappeared. For adult patients with long-term constipation combined with cough and hypertension, rare diseases like HD which requires definite surgery and which could be "right-sided" should not be overlooked. It is vital to diagnose and cure HD patients in childhood. Through the comparison of the two surgeries, it is noteworthy that for diagnosed HD, sufficient removal of the non-functional intestine confirmed by intraoperative pathology is essential.

Efficacy and outcome of extensive intraoperative peritoneal lavage plus surgery vs surgery alone with advanced gastric cancer patients

BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors.After resection,one of the major problems is its peritoneal dissemination and recurrence.Some free cancer cells may still exist after resection.In addition,the surgery itself may lead to the dissemination of tumor cells.Therefore,it is necessary to remove residual tumor cells.Recently,some researchers found that extensive intraoperative peritoneal lavage(EIPL)plus intraperitoneal chemotherapy can improve the prognosis of patients and eradicate peritoneal free cancer for GC patients.However,few studies explored the safety and long-term outcome of EIPL after curative gastrectomy.AIM To evaluate the efficacy and long-term outcome of advanced GC patients treated with EIPL.METHODS According to the inclusion and exclusion criteria,a total of 150 patients with advanced GC were enrolled in this study.The patients were randomly allocated to two groups.All patients received laparotomy.For the non-EIPL group,peritoneal lavage was washed using no more than 3 L of warm saline.In the EIPL group,patients received 10 L or more of saline(1 L at a time)before the closure of the abdomen.The surviving rate analysis was compared by the Kaplan-Meier method.The prognostic factors were carried out using the Cox appropriate hazard pattern.RESULTS The basic information in the EIPL group and the non-EIPL group had no significant difference.The median follow-up time was 30 mo(range:0-45 mo).The 1-and 3-year overall survival(OS)rates were 71.0%and 26.5%,respectively.The symptoms of ileus and abdominal abscess appeared more frequently in the non-EIPL group(P<0.05).For the OS of patients,the EIPL,Borrmann classification,tumor size,N stage,T stage and vascular invasion were significant indicators.Then multivariate analysis revealed that EIPL,tumor size,vascular invasion,N stage and T stage were independent prognostic factors.The prognosis of the EIPL group was better than the non-EIPL group(P<0.001).The 3-year survival rate of the EIPL group(38.4%)was higher than the non-EIPL group(21.7%).For the recurrence-free survival(RFS)of patients,the risk factor of RFS included EIPL,N stage,vascular invasion,type of surgery,tumor location,Borrmann classification,and tumor size.EIPL and tumor size were independent risk factors.The RFS curve of the EIPL group was better than the non-EIPL group(P=0.004),and the recurrence rate of the EIPL group(24.7%)was lower than the non-EIPL group(46.4%).The overall recurrence rate and peritoneum recurrence rate in the EIPL group was lower than the non-EIPL group(P<0.05).CONCLUSION EIPL can reduce the possibility of perioperative complications including ileus and abdominal abscess.In addition,the overall survival curve and RFS curve were better in the EIPL group.

Development and validation of a novel nomogram for predicting overall survival in gastric cancer based on inflammatory markers

BACKGROUND Nearly 66%of occurrences of gastric cancer(GC),which has the second-highest death rate of all cancers,arise in developing countries.In several cancers,the predictive significance of inflammatory markers has been established.AIM To identify clinical characteristics and develop a specific nomogram to determine overall survival for GC patients.METHODS Nine hundred and four GC patients treated at the First Affiliated Hospital of Anhui Medical University between January 2010 and January 2013 were recruited.Prognostic risk variables were screened for Cox analysis.The C index,receiver operator characteristic(ROC)curve,and decision curve analysis were used to evaluate the nomogram.RESULTS Tumor node metastasis stage,carcinoembryonic antigen,systemic immuneinflammation index,and age were identified as independent predictive variables by multivariate analysis.Systemic immune-inflammation index value was superior to that of other inflammatory indicators.The ROC indicated the nomogram had a higher area under the curve than other factors,and its C-index for assessing the validation and training groups of GC patients was extremely reliable.CONCLUSIONWe created a novel nomogram to forecast the prognosis of GC patients following curativegastrectomy based on blood markers and other characteristics. Both surgeons and patients canbenefit significantly from this new scoring system.

Model established based on blood markers predicts overall survival in patients after radical resection of types Ⅱ and Ⅲ adenocarcinoma of the esophagogastric junction

BACKGROUND In recent years, the incidence of types Ⅱ and Ⅲ adenocarcinoma of the esophagogastric junction(AEG) has shown an obvious upward trend worldwide. The prognostic prediction after radical resection of AEG has not been well established.AIM To establish a prognostic model for AEG(types II and III) based on routine markers.METHODS A total of 355 patients who underwent curative AEG at The First Affiliated Hospital of Anhui Medical University from January 2014 to June 2015 were retrospectively included in this study. Univariate and multivariate analyses were performed to identify the independent risk factors. A nomogram was constructed based on Cox proportional hazards models. The new score models was analyzed by C index and calibration curves. The receiver operating characteristic(ROC) curve was used to compare the predictive accuracy of the scoring system and tumor-node-metastasis(TNM) stage. Overall survival was calculated using the Kaplan-Meier curve amongst different risk AEG patients.RESULTS Multivariate analysis showed that TNM stage(hazard ratio [HR] = 2.286, P = 0.008), neutrophil-tolymphocyte ratio(HR = 2.979, P = 0.001), and body mass index(HR = 0.626, P = 0.026) were independent prognostic factors. The new scoring system had a higher concordance index(0.697),and the calibration curves of the nomogram were reliable. The area under the ROC curve of the new score model(3-year: 0.725, 95% confidence interval [CI]: 0.676-0.777;5-year: 0.758, 95%CI:0.708-0.807) was larger than that of TNM staging(3-year: 0.630, 95%CI: 0.585-0.684;5-year: 0.665,95%CI: 0.616-0.715).CONCLUSION Based on the serum markers and other clinical indicators, we have developed a precise model to predict the prognosis of patients with AEG(types II and III). The new prognostic nomogram could effectively enhance the predictive value of the TNM staging system. This scoring system can be advantageous and helpful for surgeons and patients.

Electric field manipulation of magnetic skyrmions

Magnetic skyrmions are vortex-like swirling spin textures that are promising candidates for carrying information bits in future magnetic memories or logic circuits.To build skyrmionic devices,researchers must electrically manipulate magnetic skyrmions to enable easy integration into modern semiconductor technology.This operation generally uses a spin-polarized current,which unavoidably causes high energy dissipation and Joule heating.Thus,the electric-field strategy is a hopeful alternative for electrically manipulating the skyrmions due to the strategy’s negligible Joule heating and low energy cost.In this review,we systematically summarize the theoretical and experimental development of the electricalfield manipulation of magnetic skyrmions over the past decade.We review the following magnetic systems and physical mechanisms:(ⅰ)ultra-thin multilayer films with accumulation and release of interfacial charge,(ⅱ)singlephase multiferroic material with magneto-electric coupling,(ⅲ)ferromagnetic/ferroelectric(FM/FE)multiferroic heterostructure with magneto-elastic coupling.Finally,we consider future developmental trends in the electric-field manipulation of magnetic skyrmions and other topological magnetic domain structures.