Objective To investigate the role of miRNAs in maternal amniotic fluid exosomes in development of isolated ventriculomegaly(VM)in fetuses.Methods Amniotic fluid samples were collected from 9 cases of moderate isolated VM and 8 normal control cases to extract exosomal miRNA,and miRNA sequencing technique was used to identify differentially expressed miRNAs between the two groups.Three miRNAs with significant differential expression between the two groups,whose high expression was associated with VM,were selected for verification with RT-qPCR.Dual luciferase reporter assays were used to verify the regulatory effect of miR-122-5p on its predicted target genes AKT3 and CCDC88C.Gene ontology(GO)and KEGG pathway analyses were performed to explore the possible roles of the top 40 significant differential miRNAs in the pathophysiology of VM.Results We identified a total of 272 differentially expressed miRNAs in VM cases,including 43 up-regulated and 229 down-regulated miRNAs.The target genes of these differential miRNAs were associated with DNA and transcription factor binding,transmembrane transporter and nucleic acid binding transcription factor activity,and cell developmental process.These miRNAs were mostly enriched in the MAPK,cGMP-PKG and Wnt signaling pathways.Verification with RT-qPCR showed that miR-122-5p expression level was significantly lower in VM group than in the control group(P<0.05),which was consistent with miRNA sequencing results;let-7b-5p expression level was significantly lower in VM group,which was contrary to miRNA sequencing result.Dual luciferase reporter assays showed that miR-122-5p was not capable of regulating AKT3 or CCDC88C expressions.Conclusions The highly abundant differentially expressed miRNAs in maternal amniotic fluid exosomes play important roles in the occurrence of fetal VM possibly by regulating the MAPK,PI3K-Akt,Wnt and cGMP-PKG signaling pathways.

Objective To investigate the feasibility,safety and efficacy of transcatheter drug-loaded microsphere embolization(DLME)in treating patients with advanced bladder cancer with bleeding(ABCB).Methods A total of 26 ABCB patients who underwent DLME for tumor supply arteries were retrospectively selected.The postoperative efficacy and related complications were observed.The recurrence of hematuria and survival situation were followed up.Results All 26 surgeries achieved success with a technical success rate of 100.0％.There were 21 cases(80.8％)of bilateral bladder artery embolism and 5 cases(19.2％)of unilateral bladder artery embolism.Three days after the operation,24 patients(92.3％)had hematuria remission.And the other two patients(7.7％)had no hematuria remission,they were relieved after interventional embolization again.Compared with that before operation,the blood transfusion rate,blood transfusion volume,hematocrit and hemoglobin at one week after operation were significantly improved(P＜0.05).One month after the last intervention,there were 2 cases of complete response,19 cases of partial response,3 cases of stable disease,and 2 cases of progressive disease.The objective remission rate was 80.8％,and the disease control rate was 92.3％.Compared with that before operation,the T stage was significantly improved at one month after operation(P＜0.05).No patients had severe complications such as ectopic embolism.After follow-up for 3-36 months,5 cases(19.2％)had a recurrence of hematuria.Conclusion Transcatheter DLME is feasible,safe,and effective in the treatment of patients with ABCB.It is an optional,minimally invasive palliative measure.

Objective To explore the clinical effect of endovascular stent-graft exclusion in the treatment of acute Stanford B-type aortic dissection(AD)with distal left subclavian artery(LSA)rupture accompanied by arch intramural hematoma.Methods A total of 12 patients with acute AD treated by the endovascular stent-graft exclusion alone were retrospectively selected.All patients had primary rupture at the distal end of LSA with arch intramural hematoma and received endovascular treatment after 2 to 3 weeks of conservative treatment.The technique success rate and related complications were observed.Postoperative computed tomography angiography(CTA)of the aorta was reviewed to evaluate the remodeling of the true and false lumen,the absorption of the arch intramural hematoma,to observe whether there was a new rupture and endoleak,and to understand the position and shape of the stent and the blood supply of the branch arteries.Results All patients completed the operation with a technical success rate of 100％.Two patients partially blocked the opening of LSA,and one patient had type Ⅰ internal leakage after the operation,but the amount of internal leakage was small and was not treated.Other patients did not had serious complications such as aortic rupture,new rupture,paraplegia,stent displacement,stroke,upper limb ischemia or vertebral artery ischemia,internal leakage,and abdominal organ ischemia during and after the operation.The patients were followed up for 19 to 66 months,with an average follow-up of(36.7±13.9)months.During the follow-up period,no patient died.The aortic remodeling was satisfactory in all patients,the arch intramural hematoma was absorbed,and there were no new rupture,internal leakage,upper limb ischemia or vertebral artery ischemia,or other serious complications.One patient with type Ⅰ internal leakage showed no significant change in internal leakage after regular postoperative reexamination.Conclusion Endovascular stent-graft exclusion is safe and feasible in the treatment of acute AD patients with distal LSA rupture accompanied by arch intramural hematoma,and it is worth promoting and applying clinically.

Objective To investigate the role of miRNAs in maternal amniotic fluid exosomes in development of isolated ventriculomegaly(VM)in fetuses.Methods Amniotic fluid samples were collected from 9 cases of moderate isolated VM and 8 normal control cases to extract exosomal miRNA,and miRNA sequencing technique was used to identify differentially expressed miRNAs between the two groups.Three miRNAs with significant differential expression between the two groups,whose high expression was associated with VM,were selected for verification with RT-qPCR.Dual luciferase reporter assays were used to verify the regulatory effect of miR-122-5p on its predicted target genes AKT3 and CCDC88C.Gene ontology(GO)and KEGG pathway analyses were performed to explore the possible roles of the top 40 significant differential miRNAs in the pathophysiology of VM.Results We identified a total of 272 differentially expressed miRNAs in VM cases,including 43 up-regulated and 229 down-regulated miRNAs.The target genes of these differential miRNAs were associated with DNA and transcription factor binding,transmembrane transporter and nucleic acid binding transcription factor activity,and cell developmental process.These miRNAs were mostly enriched in the MAPK,cGMP-PKG and Wnt signaling pathways.Verification with RT-qPCR showed that miR-122-5p expression level was significantly lower in VM group than in the control group(P<0.05),which was consistent with miRNA sequencing results;let-7b-5p expression level was significantly lower in VM group,which was contrary to miRNA sequencing result.Dual luciferase reporter assays showed that miR-122-5p was not capable of regulating AKT3 or CCDC88C expressions.Conclusions The highly abundant differentially expressed miRNAs in maternal amniotic fluid exosomes play important roles in the occurrence of fetal VM possibly by regulating the MAPK,PI3K-Akt,Wnt and cGMP-PKG signaling pathways.

Aim To investigate the effect of alfentanil on myocardial ischemia-reperfusion injury(MIRI)in rats and its regulatory mechanism on the sphingosine kinase 1(SphK1)/sphingosine-1-phosphate(S1P)signaling pathway dur-ing this process.Methods SPF grade SD male rats were randomly divided into sham surgery group,model group,positive drug group(compound salvia miltiorrhiza group),low dose alfentanil group,high dose alfentanil group,and high alfentanil+SphK1 agonist group(alfentanil+PMA group),with 20 rats in each group.Except the sham operation group,the MIRI model was reproduced by ligating the left anterior descending coronary artery and reperfusion.The activities of serum lactate dehydrogenase(LDH),creatine kinase(CK)and aspartate aminotransferase(AST)were detected by auto-matic biochemical analyzer;TTC was applied to detect the size of myocardial infarction in rats;HE staining was applied to observe the morphological characteristics of rat myocardial tissue;TUNEL staining was applied to detect myocardial cell ap-optosis in rats;ELISA was applied to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),inter-leukin-1β(IL-1β),and S1P;kits were applied to detect content of malondialdehyde(MDA)and activity of superoxide dismutase(SOD)in myocardial tissue;Western blot was applied to detect the expression level of SphK1 protein in myocar-dial tissue.Results Compared with the sham surgery group,the pathological damage to the myocardial tissue of rats was severe in the model group,the activities of serum central muscle injury markers LDH,CK,and AST,myocardial in-farction area,myocardial cell apoptosis rate,the levels of TNF-α,IL-6,IL-1β,MDA,S1P and the expression of SphK1 protein all increased,the activity of SOD decreased(P＜0.05).Compared with the model group,the myocardial tissue damage of rats was reduced in the positive drug group and the low and high dose alfentanil groups,the activities of serum central muscle injury markers LDH,CK,and AST,myocardial infarction area,myocardial cell apoptosis rate,the levels of TNF-α,IL-6,IL-1β,MDA,S1P and the expression of SphK1 protein all decreased,the activity of SOD increased(P＜0.05).The SphK1 agonist was able to reverse the impact of high-dose alfentanil on the above indicators(P＜0.05).Conclusion Alfentanil has protective effect on MIRI rats,and its mechanism may be related to the inhibition of SphK1/S1P signaling pathway.

The incidence of diabetes mellitus tends to increase, and clinical treatment is extremely challenging. Although drugs exert certain therapeutic effect on reducing blood glucose level, it remains impossible to achieve clinical cure of type 1 diabetes mellitus with a risk of blood glucose fluctuations. Islet cell transplantation is one of the efficacious methods to solve the problem of blood glucose fluctuation caused by insulin injection. However, there are several problems in the clinical practice of islet cell transplantation, including long time use of immunosuppressants in recipients and massive loss of pancreatic islet cells after transplantation, which limit its wide application in clinical practice. Islet cell encapsulation technology can reduce the loss of islet cells and decrease or eliminate the rejection, which is a key link to improve the survival of islet cells. In this article, the development course of islet cell encapsulation technology was briefly reviewed, the challenges in different islet cell encapsulation technologies were analyzed and subsequent research on this technology was projected, aiming to provide reference for promoting the development of islet cell.

In order to verify the correlation between Polygonum multiflorum-induced liver injury and HLA-B*35 : 01 alleles, six hospitalized patients diagnosed with Polygonum multiflorum-induced liver injury (PM-DILI) were selected, and their clinicopathological data were collected. Simultaneously, blood HLA-B* 35 : 01 allele detection was performed. Among the six PM-DILI cases, 4 were male, aged 38.83 ± 10.13 years old. The types of liver injury were hepatocellular injury types in all, and the severity of liver injury in five cases was grade 3. The histological presentations were acute hepatitis and acute cholestatic hepatitis. PM-DILI cases were all HLA-B*35:01 carriers, with a carrier rate of 100%. This finding indicates that PM-DILI is significantly correlated with HLA-B*35:01 alleles. Therefore, HLA-B*35 : 01 alleles can be used as an important predictive indicator for PM-DILI.

Obeticholic acid (OCA), the first FXR-targeting drug, has been claimed effective in the therapy of liver fibrosis. However, recent clinical trials indicated that OCA might not be effective against liver fibrosis, possibly due to the lower dosage to reduce the incidence of the side-effect of pruritus. Here we propose a combinatory therapeutic strategy of OCA and apoptosis inhibitor for combating against liver fibrosis. CCl-injured mice, d-galactosamine/LPS (GalN/LPS)-treated mice and cycloheximide/TNF (CHX/TNF)-treated HepG2 cells were employed to assess the effects of OCA, or together with IDN-6556, an apoptosis inhibitor. OCA treatment significantly inhibited hepatic stellate cell (HSC) activation/proliferation and prevented fibrosis. Elevated bile acid (BA) levels and hepatocyte apoptosis triggered the activation and proliferation of HSCs. OCA treatment reduced BA levels but could not inhibit hepatocellular apoptosis. An enhanced anti-fibrotic effect was observed when OCA was co-administrated with IDN-6556. Our study demonstrated that OCA inhibits HSCs activation/proliferation partially by regulating BA homeostasis and thereby inhibiting activation of HSCs. The findings in this study suggest that combined use of apoptosis inhibitor and OCA at lower dosage represents a novel therapeutic strategy for liver fibrosis.

Restless legs syndrome,as a common sleep disorder,has nowadays long been diagnosed by self-rating scale and polysomnography.In this paper,a domestic diagnosis system for early restless legs syndrome based on deep learning is proposed,which is suitable for early patients with unstable symptoms in routine diagnosis.The hardware system is installed in the bed.And the non-contact sleeping dynamic signal acquisition is realized based on the acceleration sensors.The software system uses deep learning to classify and recognize the signals.A Fully Connected Feedforward Network based on Keras framework is constructed to recognize seven kinds of activities during sleeping.The accuracy of comprehensive classification is 97.83%.Based on former results,the periodic limb movement index and awakening index were evaluated to make the diagnosis of restless legs syndrome.
Deep Learning ; Humans ; Movement ; Polysomnography ; Restless Legs Syndrome ; diagnosis ; Sleep

Objective To analysis the common abnormalities in fetus with ventriculomegaly and clinical significance. Methods Collected from March 2010 to December 2016,298 cases of pregnant women whose fetus with ventriculomegaly and accepted the prenatal diagnosis of pregnancy,including 109 cases of isolated cerebral ventriculomegaly(IVM),and 189 cases of non-isolated cerebral ventriculomegaly(NIVM).They were divided into mild groups(10.0-11.9 mm),moderate group(12.0-14.9 mm)and severe group(≥15.0 mm)according to the width of the lateral ventricle. Results(1)The most common abnormality of the NIVM were neurodevelopmental system(37.30%,94/252);The second was ultrasonic soft index(27.78%,70/252).(2)The most frequent combi-nation in mild group was ultrasonographic soft mark anomalies(44.76%,47/105),followed by other ultrasonic indi-cators(18.10%,19/105).The abnormal incidence of central nervous system was higher in middle group(45.16%, 42/93),followed by ultrasonic soft index abnormality(21.51%,20/93).The abnormality of the central nervous sys-tem was 62.96%(34/54)in severe group,followed by an abnormal(14.81%,8/54).(3)There was a difference in the nervous system and the ultrasonic-soft indicator between the non-isolated lateral ventricle dilation with different lateral ventricle widths(P<0.001).There was no difference in cardiovascular abnormalities. Conclusion Prena-tal ultrasound revealed that fetus with cerebral ventriculomegaly should carefully examine whether other abnormali-ties existed to determine the prognosis of the fetus and whether intervention should be taken.There was a difference between the different types of lateral ventricle and the prognosis.