Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by abdominal pain and changes in bowel habits. IBS is a multifactorial, stress-sensitive disease. Epigenetic changes include DNA methylation change, histone modification, and differential expressions of microRNA and long non-coding RNA. Explaining the changes in IBS from the perspective of epigenetics could bring new insights for the pathogenesis and treatment of the disease. This article reviewed the progress in research on the epigenetics of IBS.

Objective: To evaluate the safety and efficacy of chimeric antigen receptors T cells (CAR-T) in childhood acute B lymphoblastic leukemia (B-ALL) to probe the prognosis-related factors. Methods: Forty-eight children, 29 boys and 19 girls, aged 3-17years old (median age was 8 years old) , with recurrent or refractory CD19 positive B-ALL, were treated by the CD19 specific CAR-T cells. A total of 48 cases received 61 infusions. Flow cytometry or real-time quantitative polymerase chain reaction method were used to monitor micro residual disease (MRD) . The follow-up period was from 16 to 1 259 days with the median follow-up of 406 days. SPSS software was used to statistical analysis. Results: No adverse reaction was observed during 61 infusions. The most common adverse reaction after CAR-T cell infusions was cytokine-release syndrome (CRS) . Only 2 cases experienced level 3 CRS performance, including continuous high fever, convulsions, delirium, serous cavity effusion, and decreasing of blood pressure. Tocilizumab was given to release CRS performance. No treatment-related death occurred. Thirty-seven patients showed response during 7 to 28 days after infusions. The early response rate was 77.1%, with MRD before infusion less than 5% group higher than the MRD more than 5% group (87.1% vs 58.8%, χ²=4.968, P=0.036) . For the 37 patients who showed response to CAR-T cell infusions, univariate analysis identified that age, disease status at the time of treatment, MRD before infusion affected 2-year OS rate (P<0.05) . Multivariate prognostic analysis for EFS disclosed that the MRD before infusion more than 5% (RR=3.433, 95% CI 1.333-8.844, P=0.011) and not bridge to HSCT (RR=4.996, 95% CI 1.852-13.474, P=0.001) were the independent risk factors. Conclusion The fourth generation CAR-T cells directed against CD19 could effectively and safely treat relapsed and refractory B-ALL, which implicated that CAR-T therapy as a novel therapeutic approach could be useful for patients with relapsed or refractory B-ALL who have failed all other treatment options. Reducing MRD as far as possible by effective pretreatment chemotherapy was in favor of increasing the response rate. Bridging HSCT after CAR-T cell treatment might be a better therapeutic strategy for the patient with refractory or molecular relapsed B-ALL.

Objective To evaluate the applied value of septal cartilage combined with perpendicular plate of ethmoid bone graft in short nose plasty in Chinese people with insufficient septal cartilage.Methods From February 2015 to March 2017,thirty-five women with short noses underwent septal extension grafting in our institute.We used perpendicular plate of ethmoid bone to enhance the L-strut structure.An L-strut,comprising 0.6 cm segments of the caudal and dorsal cartilaginous septum,was left altered to harvest more cartilages for septal extension.The harvested septal cartilage was grafted on one side of the caudal septum.Then the alar cartilage was fixed at the end of the septal cartilage graft.Nasal lengths and nasolabial angles were measured pre-and postoperatively.Results The average nasal lengthening was (3.37±1.87) mm (P＜0.001).There was no infection,cerebral spinal fluid leakage,hemorrhage and other complications postoperatively.The average follow-up was 10 months (6 months to 2 years).After operation,33 patients were satisfied with the nasal contour,1 patient complained of high tip projection whereas one patient complained of low tip projection,and the dissatisfactions were corrected by revision surgeries.Conclusions Combining the septal cartilage with perpendicular plate of ethmoid bone graft presents an adequate nose lengthening and a decreased nostril show,even in patients with very little septal cartilage.With minimum complications,this novel technique provides promising clinical outcomes and high patient satisfaction.

OBJECTIVETo evaluate the safety and efficacy of chimeric antigen receptors T cells (CAR-T) in childhood acute B lymphoblastic leukemia (B-ALL).

METHODSA relapsed B-ALL child after allogeneic hematopoietic stem cell transplantation (allo-HSCT) was treated with CAR-T, and the related literatures were reviewed.

RESULTAn 11-year-old girl with TEL-AML1 fusion gene positive BALL who suffered a bone marrow relapse 28 months after remission from conventional chemotherapy. During the second remission, the patient received haploidentical allo-HSCT. She relapsed with detectable TEL-AML1 fusion gene even after chemotherapy and donor leukocyte infusions. She received an experimental donor-derived fourth generation CD19 CAR-T therapy. After infusion of 1 × 10(6)/kg CAR-T cells, she experienced only mild or moderate cytokine-release syndrome and the minimal residual disease turned negative. Then three maintenance of CAR-T cell infusions [(0.83-1.65)×10(6)/kg] was administered, and the disease-free survival had lasted for 10 months. However, the TEL-AML1 copies in her blood still increased and she died with leukemia relapse after additional CAR-T cell infusion.

CONCLUSIONTreatment of relapsed B-ALL with the fourth generation CAR-T cells directed against CD19 was effective and safe. CAR-T therapy is a novel therapeutic approach that could be useful for patients with relapsed and refractory B-ALL who have failed all other treatment options.

Bone Marrow ; Child ; Core Binding Factor Alpha 2 Subunit ; genetics ; Disease-Free Survival ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Neoplasm, Residual ; Oncogene Proteins, Fusion ; genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; therapy ; Receptors, Antigen, T-Cell ; genetics ; Recurrence ; Remission Induction ; T-Lymphocytes ; cytology ; Transplantation, Homologous

OBJECTIVETo investigate the effect of thalidomide on the development of bisphosphonate-related osteonecrosis of the jaws (BRONJ).

METHODSThirty-six rats were randomly divided into groups A, B and C, and treated with saline, zoledronate and zoledronate plus thalidomide, respectively. Three weeks later, the left maxillary first molars of the rats were extracted. Four and eight weeks after tooth extraction, samples were harvested for evaluation of osteonecrosis of the jaws, microvessel density, and cell apoptosis.

RESULTSAt both of the time points, no exposed dead bone was observed at the extraction socket areas in the rats except for some small fistulas in groups B and C. Histological examination confirmed the absence of dead bone in group A, whereas small areas of dead bone were observed around the extraction socket in groups B and C. Compared with those in group A, the percentage of empty lacunae and the area of dead bone were significantly increased (P<0.01), whereas bone lacunae density was significantly decreased (P<0.01) in groups B and C at both time points. Microvessel density in groups B and C were also significantly decreased (P<0.01) by 25.87% and 55.27% at week 4, and by 45.62% and 72.84% at week 8, respectively; the apoptotic cells in groups B and C increased by 54.80% and 87.89% at week 4 (P<0.01), and by 208.08% and 250.58% at week 8 (P<0.01), respectively.

CONCLUSIONThalidomide can aggravate zoledronate-induced early-stage BRONJ, and their osteonecrosis-inducing effect of the jaw may be attributed, at least partly, to the inhibition of angiogenesis.

Animals ; Apoptosis ; Bisphosphonate-Associated Osteonecrosis of the Jaw ; pathology ; Bone Density ; Diphosphonates ; Disease Models, Animal ; Imidazoles ; Molar ; Neovascularization, Physiologic ; Rats ; Thalidomide ; adverse effects ; Tooth Extraction

OBJECTIVETo screen differentially expressed genes and identify potential signaling pathway in Asian people with breast cancer.

METHODSFive gene microarray datasets of Asian people with breast cancer, GSE6367, GSE9309, GSE15852, GSE33447 and GSE45255, were downloaded from GEO. Microarrays with 318 breast cancer and 60 normal breast tissues were used for analysis of differentially expressed genes and pathway. 32 pairs of breast cancer patients' specimens were used to validate the differentially expressed genes by real-time PCR.

RESULTSAnalysis of the large sample of microarray data identified 436 differentially expressed genes in breast cancer tissues, while 259 of these genes were up-regulated and the other 177 down-regulated. Pathway analysis showed that metabolism-related signaling pathway may be involved in the development of breast cancer in Asian people. The expressions of KRT19, ADIPOQ, CFD, RBP4, LPL, ABCA8 and CD36 genes were confirmed by real-time PCR.

CONCLUSIONThis study shows differential gene expression profile and potential signaling pathway in Asian people with breast cancer. CD36 gene may be closely related to the Asian breast cancer. ABCA8 gene may be a new disease gene in Asian breast cancer.

Asian Continental Ancestry Group ; Breast Neoplasms ; genetics ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Oligonucleotide Array Sequence Analysis ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; Transcriptome

Objective To screen differentially expressed genes and identify potential signaling pathway in Asian people with breast cancer. Methods Five gene microarray datasets of Asian people with breast cancer, GSE6367, GSE9309, GSE15852, GSE33447 and GSE45255, were downloaded from GEO. Microarrays with 318 breast cancer and 60 normal breast tissues were used for analysis of differentially expressed genes and pathway. 32 pairs of breast cancer patients' specimens were used to validate the differentially expressed genes by real-time PCR. Results Analysis of the large sample of microarray data identified 436 differentially expressed genes in breast cancer tissues, while 259 of these genes were up-regulated and the other 177 down-regulated. Pathway analysis showed that metabolism-related signaling pathway may be involved in the development of breast cancer in Asian people. The expressions of KRT19, ADIPOQ, CFD, RBP4, LPL, ABCA8 and CD36 genes were confirmed by real-time PCR. Conclusion This study shows differential gene expression profile and potential signaling pathway in Asian people with breast cancer. CD36 gene may be closely related to the Asian breast cancer. ABCA8 gene may be a new disease gene in Asian breast cancer.

Objective To screen differentially expressed genes and identify potential signaling pathway in Asian people with breast cancer. Methods Five gene microarray datasets of Asian people with breast cancer, GSE6367, GSE9309, GSE15852, GSE33447 and GSE45255, were downloaded from GEO. Microarrays with 318 breast cancer and 60 normal breast tissues were used for analysis of differentially expressed genes and pathway. 32 pairs of breast cancer patients' specimens were used to validate the differentially expressed genes by real-time PCR. Results Analysis of the large sample of microarray data identified 436 differentially expressed genes in breast cancer tissues, while 259 of these genes were up-regulated and the other 177 down-regulated. Pathway analysis showed that metabolism-related signaling pathway may be involved in the development of breast cancer in Asian people. The expressions of KRT19, ADIPOQ, CFD, RBP4, LPL, ABCA8 and CD36 genes were confirmed by real-time PCR. Conclusion This study shows differential gene expression profile and potential signaling pathway in Asian people with breast cancer. CD36 gene may be closely related to the Asian breast cancer. ABCA8 gene may be a new disease gene in Asian breast cancer.

Objective To establish a convenient and specific molecular method for cytomegalovirus(CMV) surveillance in recipients of allogeneic hematopoietic stem cell transplantation(allo-HSCT) and ana-lyze the correlation between cytomegalovirus genotypes and transplant-related complication to decrease CMV-related mortality through restricted endoenzyme digestion.Methods 135blood samples were regularly col-lected from79consecutive patients who received allo-HSCT between April2001and April2003.Of the79 patients observed,median age was32(range from11to60) and the ratio of male and female was1.63∶1.DNA extracted from whole blood was amplified with CMV sequence using Nested PCR and gB genotypes were identified through restriction enzyme analysis.Results Among the135clinical isolates from79pa-tients,42cases(66specimens) were Positive.The gB genotype from42cases(45samples) were identified as gB1,21(46.7%);gB2,14(31.1%);gB3,7(15.6%);gB4,3(6.7%),respectively,by restric-tion enzyme analysis.Among them,3patients were successively infected with CMV gB1and gB2.The inci-dence of GVHD in groups of CMV(+) and CMV(-) was81.0% and32.4%,respectively(P

CMV related matrix protein pp65 antigenemia was screened in 100 Allo HSCT patients after transplantation. As control groups, samples from fourteen autologous HSCT patients, seventeen patients with various hematological malignant disorders, as well as twenty seven normal donors also were detected. CMV antigenemia was found in 91/100 Allo HSCT patients (91%) after transplantation. 56 % patients with antigenemia developed CMV disease. 54% patients developed acute GVHD. In 87 patients survived more than three months, 52 9% patients developed chronic GVHD. After follow up 18(4～36) months post transplantation, 21 patients died of CMV related diseases. Compared with autologous and non transplantation patients, CMV antigenemia and CMV diseases were particularly associated with Allo HSCT patients. It was obviously correlated with acute and chronic GVHD. CMV infection is a major factor affecting the clinical outcome of Allo HSCT patients.