BACKGROUND: Bile acids (BAs) facilitate the progression of gastric intestinal metaplasia (GIM). Long non-coding RNAs (lncRNAs) dysregulation was observed along with the initiation of gastric cancer. However, how lncRNAs function in GIM remains unclear. This study aimed to explore the role and mechanism of lncRNA PVT1 in GIM, and provide a potential therapeutic target for GIM treatment. METHODS: We employed RNA sequencing (RNA-seq) to screen dysregulated lncRNAs in gastric epithelial cells after BA treatment. Bioinformatics analysis was conducted to reveal the regulatory mechanism. PVT1 expression was detected in 21 paired biopsies obtained under endoscopy. Overexpressed and knockdown cell models were established to explore gene functions in GIM. Molecular interactions were validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (Ch-IP). The levels of relative molecular expression were detected in GIM tissues. RESULTS: We confirmed that lncRNA PVT1 was upregulated in BA-induced GIM model. PVT1 promoted the expression of intestinal markers such as CDX2 , KLF4 , and HNF4α . Bioinformatics analysis revealed that miR-34b-5p was a putative target of PVT1 . miR-34b-5p mimics increased CDX2 , KLF4 , and HNF4α levels. Restoration of miR-34b-5p decreased the pro-metaplastic effect of PVT1 . The interactions between PVT1 , miR-34b-5p, and the downstream target HNF4α were validated. Moreover, HNF4α could transcriptionally activated PVT1 , sustaining the GIM phenotype. Finally, the activation of the PVT1 /miR-34b-5p/ HNF4α loop was detected in GIM tissues. CONCLUSIONS BAs facilitate GIM partially via a PVT1/miR-34b-5p/HNF4α positive feedback loop. PVT1 may become a novel target for blocking the continuous development of GIM and preventing the initiation of gastric cancer in patients with bile reflux.
Humans ; RNA, Long Noncoding/metabolism* ; MicroRNAs/metabolism* ; Hepatocyte Nuclear Factor 4/genetics* ; Bile Acids and Salts ; Kruppel-Like Factor 4 ; Metaplasia/metabolism*

Bile acids are synthesized in the liver and then transported to the intestine,playing important roles in the digestion and absorption of lipids.They are mainly distributed in the gallbladder,liver,gastrointestinal tract and peripheral blood.Many studies have shown that bile acids are involved in the development of various gastrointestinal diseases,including irritable bowel syndrome,inflammatory bowel disease,and gastrointestinal tumors.Serum bile acids have been widely used in the liver function monitoring,liver diseases diagnosis,and prognosis assessment.This article summarized and analyzed the physiological functions and pathophysiology of abnormal metabolism of bile acids,and the research progress of serum bile acids and gastrointestinal diseases,in order to provide a reference for further exploration of their application in clinical diagnosis and evaluation of gastrointestinal diseases.

Bile acids are synthesized in the liver and then transported to the intestine,playing important roles in the digestion and absorption of lipids.They are mainly distributed in the gallbladder,liver,gastrointestinal tract and peripheral blood.Many studies have shown that bile acids are involved in the development of various gastrointestinal diseases,including irritable bowel syndrome,inflammatory bowel disease,and gastrointestinal tumors.Serum bile acids have been widely used in the liver function monitoring,liver diseases diagnosis,and prognosis assessment.This article summarized and analyzed the physiological functions and pathophysiology of abnormal metabolism of bile acids,and the research progress of serum bile acids and gastrointestinal diseases,in order to provide a reference for further exploration of their application in clinical diagnosis and evaluation of gastrointestinal diseases.

Objective    To assess the feasibility and safety of percutaneous transcatheter closure of atrial septal defect (ASD) guided by transthoracic echocardiography (TTE) in outpatients. Methods    From December 2016 to June 2018, 50 simple ASD patients underwent TTE-guided transcatheter closure in the outpatient operating room of our hospital (a TTE group) including 22 males and 28 females at the age of 16-48 (27.40±6.95) years. Fifty patients with simple ASD treated with the guidance of conventional fluoroscopy during the same period were treated as a control group, including 22 males and 28 females at the age of 15-48 (28.58±6.96) years. Both groups were re-examined by TTE during follow-up at 1 month, 3 months, 6 months and 1 year. Results    The mean age, body weight, the size of ASD and occluder and success rate had no statistical difference between the two groups (P>0.05). Compared with the control group, the TTE group had significantly lower mean operation time (P<0.01) and less cost (P<0.01) since patients need not to be hospitalized. No related complications were found in the TTE group during follow-up. Conclusion    Percutaneous transcatheter closure of ASD guided by TTE appears safe and effective for outpatients, and can significantly reduce the cost.

Objective To investigate whether emodin combined with 5AzA-cdR can enhance the demethylation of tumor suppressor genes p16,RASSF1A and ppENK in nude mice with subcutaneously transplanted pancreatic cancer.Methods Pancreatic cancer cells Panc1 burdened subcutaneous xenograft nude mice model was established,which were randomly divided into control group,emodin group,5AzA-cdR group and emodin combined 5AzA-cdR group (combined group).The growth of transplanted tumors wasobserved in each group.Methylation specific PCR (MSP) was used to detect the methylation levels of p16,RASSF1A and ppENK in the xenograft tumor tissue among three groups.The mRNA and protein expression of three tumor suppressor genes were detected by FQ-PCR and Western blotting,respectively.Results The weight of xenografts in the control group,emodin group,5AzA-cdR group,and combination group were (0.28 ±0.01),(0.17 ± 0.01),(0.12 ± 0.02),(0.08 ± 0.01)g,respectively.The tumor volume was (517 ±0.02),(382 ± 0.01),(232 ± 0.03),(169 ± 0.01) mm3.The methylation levels of p16 were 1.00 ± 0.00,0.89 ± 0.02,0.63 ± 0.02,and 0.19 ± 0.01;the methylation levels of RASSF1A were 1.00 ± 0.00,0.88 ± 0.02,0.51 ± 0.01,and 0.32 ± 0.01;the methylation degree of ppENK was 1.00 ± 0.00,0.92 ± 0.02,0.77 ± 0.02 and 0.31 ± 0.01,respectively.The expression of p16 mRNA was 1.00 ± 0.00,1.71 ±0.02,2.67 ± 0.02,3.81 ± 0.01.The expression of RASSF1A mRNA was 1.00 ± 0.00,1.92 ±0.02,2.73 ± 0.03,3.77 ± 0.01.The expression of ppENK mRNA was 1.00 ± 0.00,1.69 ± 0.03,2.17 ± 0.02 and 4.28 ± 0.01.The expression of p16 protein was 1.00 ± 0.00,1.71 ± 0.02,2.67 ± 0.02,3.81 ± 0.01;the expression of RASSF1A protein was 1.00 ± 0.00,1.92 ± 0.02,2.73 ± 0.03.3.77 ± 0.01;ppENK protein expression levels were 1.00 ±0.00,1.69 ±0.03,2.17 ±0.02,4.28 ±0.01.The weight and volume of xenografts in the three treatment groups were significantly smaller than those in the control group.The methylation of three tumor suppressor genes was lower than that of the control group,and the expression of tumor suppressor mRNA and protein was all significantly higher than the control group,which the combination drug group was also significantly stronger than that in emodin group and 5AzA-cdR group,and the differences were statistically significant (P ＜ 0.05 or ＜ 0.01).Conclusions The combination of emodin and 5AzA-cdR can enhance the demethylation effect of 5A6A-cdR on the tumor suppressor genes p16,RASSF1A and ppENK in the tumor tissue of pancreatic cancer xenograft model.

Objective: To investigate the safety and efficacy of percutaneous intervention of children with combined congenital heart abnormality solely guided by transthoracic echocardiography (TTE) . Methods: From September 2015 to June 2017, 21 children with combined congenital heart abnormality undergoing percutaneous interventional guided by TTE in Fuwai hospital were enrolled in our study, and the clinical data were retrospective analyzed. The atrial septal defect(ASD) closure, ventricular septal defect(VSD) closure, patent ductus arteriosus(PDA) closure or balloon pulmonary valvuloplasty were performed under the guidance of TTE. The procedural effect was evaluated by TTE after operation. The patients were followed up after discharged from the hospital. Results: The age was (37.3±11.6) months, and there were 9 male and 12 female patients. There were 4 cases with ASD and VSD, 6 cases with VSD and PDA, 6 cases with ASD and PDA, 2 cases with VSD and pulmonary stenosis, 3 cases with ASD and pulmonary stenosis. The operations were successfully performed in all patients. No one required extra X ray guidance or open heart surgery. The operation time was (44.6±7.5)min. All patients did not require blood transfusion, inotropic support, and analgesia. There were no complications such as peripheral vascular injury and pericardialeffusion after the operation. The length of hospital stay time was (3.5±0.6) days. All patients were recovered well. The follow-up was (17.6±5.2) months, and post-procedural conduction disturbances, residual shunts, occlude fall off, thrombosis, and new onset of valvular regurgitation were not observed in these patients. Conclusion Percutaneous interventional of children with combined congenital heart abnormality solely guided by TTE is safe and effective, and the procedure can avoid the potential injuries of X ray and contrast agent.

Objective    To assess the efficacy and safety of percutaneous closure of patent ductus arteriosus (PDA) solely under echocardiography guidance. Methods    We retrospectively analyzed the clinical data of 200 patients who received the percutaneous closure of PDA under echocardiography guidance in Fuwai Hospital from August 2013 to April 2016. According the different approach, they were divided into 2 groups: a femoral artery approach group (n=143) and a femoral vein approach group (n=57). In the femoral artery approach group, there were 42 males and 101 females aged 3.20±5.63 years. In the femoral vein group, there were 10 males and 47 females aged 7.30±11.36 years. All Patients were treated by percutaneous PDA closure solely under echocardiography guidance. The follow-up was performed at one month after the operation by echocardiography, chest radiograph and electrocardiogram. Results    All 200 patients were successfully treated with percutaneous closure of PDA. The patients’ gender, in-hospital stay, rates of occluder  detachment were similar between the two groups (P>0.05). Compared with the femoral vein approach group, the femoral artery approach group had a younger age (3.20±5.63 years vs. 7.30±11.36 years, P<0.001), less body weight (14.25±11.54 kg vs. 24.25±19.14 kg, P<0.001) and shorter diameter of PDA (3.06±0.79 mm vs. 5.93±0.68 mm, P<0.001) and PDA occluders (5.43±1.00 mm vs. 12.14±0.54 mm, P<0.001), but had higher hospitalization expenses (32 108.2±3 100.2 yuan vs. 25 120.7±3 534.1 yuan, P<0.001). In the femoral vein approach group, one patient was closed under radiation guidance because guide wires could not pass through PDA. One patient in the femoral artery approach group suffered from occluder detachment at one day after operation and was cured by transthoracic minimally invasive PDA occlusion. There were no complications of occluder detachment, residual shunt, pericardial effusion or left pulmonary stenosis during the follow-up. Conclusion    Echocardiography-guided percutaneous PDA closure is safe and effective, while the proper interventional approach should be chosen by the anatomical features of PDA.

Objective To investigate the efficacy and safety of percutaneous induced thrombosis closure on small patent ductus arteriosus (PDA) solely under echocardiography guidance.Methods From June 2013 to September 2016,276 PDA patients were treated by femoral artery retrograde approach under echocardiography guidance.Twenty-five patients (14 boys,11 girls) among them with small PDA received percutaneous induced thrombosis closure because the delivery sheath could not pass PDA,with mean age (3.7 ± 1.6) years,mean body weight (16.6 ±5.4) kg and the mean diameter of the most narrow PDA was (1.3 ± 0.4) mm.All patients were assessed by transthoracic echocardiography,chest radiography and electrocardiography preoperatively.The intraoperative and postoperative effects were evaluated by echocardiography.Outpatient assessment was performed at 1,3,6 and 12 months after operation with electrocardiography and echocardiography,and yearly thereafter.Results Twenty-five patients were successfully treated with percutaneous induced thrombosis closure solely under echocardiography guidance.The mean operation time was (35.2 ± 6.1) minutes.The immediate residual shunt rates and 24 hours after operation were 28.0％ (7/25 cases) and 16.0％ (4/25 cases),respectively.All patients recovered and were discharged from hospital.The average hospitalization stay was (3.0 ± 0.6) days.The mean follow-up was (16.8 ± 12.3) months,residual shunt was observed in 2 patients (8.0％),and it decreased from 1.5 mm and 2.0 mm preoperatively to 0.8 mm and 1.0 mm postoperatively,respectively.All patients survived without peripheral vascular injury,cardiac perforation,PDA rupture or thrombembolia.Conclusions Percutaneous induced thrombosis closure of small PDA solely under echocardiography guidance is safe and effective.It can avoid occluder implantation and radiation injury.However,the residual shunt after operation needs following up closely.

OBJECTIVETo investigate the clinical and genetics characteristics of patients with monosomal karyotype acute myeloid leukemia (MK-AML).

METHODSThe karyotypes of 3743 patients with newly-diagnosed de novo AML were analyzed, which had identified 153 cases with MK-AML, for whom the clinical and genetics characteristics were analyzed.

RESULTSThere were 2056 patients (54.9%) among all patients. A total of 153 patients fulfilling the criteria for MK-AML were identified, which comprised 93 males and 60 females, with a median age of 54. The median white blood cell count on presentation was 4.4×10 (9)/L. One hundred and forty-five cases (94.8%) have fulfilled the criteria for complex karyotype (≥ 3 chromosomal abnormalities). Although the monosomy could be found with all autosomes, chromosome 7 has been most frequently involved (38.56%, 59/153).

CONCLUSIONMK-AML is a distinct cytogenetic subtype of AML. Monosomy 7 is frequently detected among MK-AML patients. The monosomal karyotype is common among elder patients with AML.

Adult ; Aged ; Chromosomes, Human, Pair 7 ; genetics ; Female ; Humans ; Karyotype ; Leukemia, Myeloid, Acute ; genetics ; Male ; Middle Aged ; Monosomy ; Young Adult

OBJECTIVETo explore the clinical and laboratory features of chronic myeloid leukemia (CML) with atypical e14a3 and e19a2 BCR-ABL fusion gene subtypes.

METHODSWe retrospectively analyzed a cohort of CML patients with Ph chromosome positive confirmed by cytogenetic and FISH but classical e13a3(b2a2), e14a2(b3a2)and e1a2 fusion transcripts negative identified by conventional real-time quantification RT-PCR (RQ-PCR). Further RQ-PCR was done with the forward primer and reverse primer designed to detect rare atypical BCR-ABL fusion genes including e14a3 and e19a2 transcripts. Direct sequencing analysis was performed on the PCR products and mutations in the BCR-ABL kinase domain were detected. The clinical data of patients were retrospectively analyzed.

RESULTSSix CML patients were found to carry t(9;22) abnormality and BCR-ABL rearrangement confirmed by FISH but classical BCR-ABL fusion genes negative detected by RQ-PCR. Further RQ-PCR and sequencing analysis confirmed the fusion of BCR exon 14 and ABL exon 3 in five CML patients (case 1-5) and the fusion of BCR exon 19 and ABL exon 2 in one CML patient (case 6). E255K and I293T IM-resistant mutations were detected in case 1 and 2, respectively. Among five cases with e14a3 transcripts, four were CML-CP, one CML-AP. Four patients were male and one was female. The median age was 48 years. The patient (case 6) with e19a2 transcripts was 40-year-old female with a diagnosis of CML-CP and PLT count was more than 1 000×10⁹/L. Imatinib (IM) therapy was administer in case 1, 2, 3, 4 and hematopoietic stem cell transplantation (HSCT) was undergone in case 5 after hydroxyurea (Hu) or interferon failure. Case 1 who had E255K IM resistant mutation, responded poorly to IM but obtained a complete cytogenetic remission (CCyR) after a substitution of dasatinib for IM. Case 2 and 3 achieved CCyR 6 months later after IM treatment and had been maintained well with IM despite I293T mutation in case 2. Case 4 attained CCyR 3 months later after IM treatment but relapsed and died soon. Case 5 was still in CCyR after HSCT. Case 6 with e19a2 transcripts got complete hematologic response after Hu treatment and CCyR was achieved soon after IM therapy.

CONCLUSIONIncidence of CML with atypical transcripts is extremely low. They could benefit from tyrosine kinase inhibitors or HSCT. Rare and atypical BCR- ABL fusion gene subtypes could be missed by conventional RQ-PCR.

Adult ; Female ; Fusion Proteins, bcr-abl ; genetics ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; classification ; diagnosis ; genetics ; Male ; Middle Aged ; Retrospective Studies