Identification of TCF3-ZNF384 fusion by transcriptome sequencing in B cell acute lymphoblastic leukemia and its laboratory and clinical characteristics / 中华医学遗传学杂志

OBJECTIVE@#To detect fusion gene with pathological significance in a patient with refractory and relapsed acute B cell lymphoblastic leukemia (B-ALL) and to explore its laboratory and clinical characteristics.@*METHODS@#Transcriptome sequencing was used to detect potential fusion transcripts. Other laboratory results and clinical data of the patient were also analyzed.@*RESULTS@#The patient was found to harbor TCF3 exon 17-ZNF384 exon 7 in-frame fusion transcript. The minimal residual disease (MRD) has remained positive after multiple chemotherapy protocols including CD19-, CD22- targeted chimeric antigen receptor T cells immunotherapy. The patient eventually achieved complete remission and sustained MRD negativity after allogeneic hemopoietic stem cell transplantation (allo-HSCT).@*CONCLUSION@#Transcriptome sequencing can effectively detect potential fusion genes with clinical significance in leukemia. TCF3-ZNF384 positive B-ALL has unique laboratory and clinical characteristics, may not well respond to chemotherapy and immunotherapy, and is more likely to relapse. Timely allo-HSCT treatment may help such patients to achieve long-term disease-free survival. TCF3-ZNF384 positive B-ALL is not uncommon in pediatric patients but has not been effectively identified.

Outcomes of implanting porcine small intestinal submucosa mesh in rabbit vesicovaginal space / 中华妇产科杂志

Objective:To assess surgical outcomes of implanted porcine small intestinal submucosa (SIS) mesh in the rabbit vesicovaginal space (VVS) and explore its application value in pelvic floor reconstruction surgery.Methods:Sixteen male rabbits were randomly divided into four groups, and each group had four rabbits. All groups of rabbits were implanted with SIS mesh in the vesicovaginal space. They were humanely killed after a postoperative period of 7, 30, 90 and 180 days by group. The grafted area was removed with the surrounding bladder and vaginal tissues. The specimens were embedded in paraffin and then stained with HE and Masson's trichrome stains for visual observations, cells counts, and assessment of tissues and collagen fibers.Results:(1) After HE staining, a large number of inflammatory response cells mainly eosinophils and lymphocytes infiltrated around the SIS mesh in 7 days group, and neovascularization was observed, the infiltration area of inflammatory response cells further increased in 30 days group, the infiltration area of inflammatory response cells significantly reduced in 90 days group, while the inflammatory response basically subsided in 180 days group. (2) After Masson's trichromestaining, the collagen structure of SIS mesh in 7 days group was clear and intact. While, the collagen structure of SIS mesh was partially degraded in 30 days group, the SIS meshes of 4 rabbits were completely degraded, but the collagen fragments of SIS remained in 90 days group. In 180 days group, the SIS mesh of all rabbits was degraded, and one of them had the formation of new collagen fibers.Conclusions:SIS mesh implanted into the VVS of rabbits can lead to a transient non infective inflammatory reaction, which could be completely degraded and a small amount of new collagen fibers could be produced after 180 days of implantation. Which shown that SIS mesh should be used cautiously in pelvic floor reconstruction surgery.

Outcomes of implanting porcine small intestinal submucosa mesh in rabbit vesicovaginal space / 中华妇产科杂志

Objective@#To assess surgical outcomes of implanted porcine small intestinal submucosa (SIS) mesh in the rabbit vesicovaginal space (VVS) and explore its application value in pelvic floor reconstruction surgery.@*Methods@#Sixteen male rabbits were randomly divided into four groups, and each group had four rabbits. All groups of rabbits were implanted with SIS mesh in the vesicovaginal space. They were humanely killed after a postoperative period of 7, 30, 90 and 180 days by group. The grafted area was removed with the surrounding bladder and vaginal tissues. The specimens were embedded in paraffin and then stained with HE and Masson's trichrome stains for visual observations, cells counts, and assessment of tissues and collagen fibers.@*Results@#(1) After HE staining, a large number of inflammatory response cells mainly eosinophils and lymphocytes infiltrated around the SIS mesh in 7 days group, and neovascularization was observed, the infiltration area of inflammatory response cells further increased in 30 days group, the infiltration area of inflammatory response cells significantly reduced in 90 days group, while the inflammatory response basically subsided in 180 days group. (2) After Masson's trichromestaining, the collagen structure of SIS mesh in 7 days group was clear and intact. While, the collagen structure of SIS mesh was partially degraded in 30 days group, the SIS meshes of 4 rabbits were completely degraded, but the collagen fragments of SIS remained in 90 days group. In 180 days group, the SIS mesh of all rabbits was degraded, and one of them had the formation of new collagen fibers.@*Conclusions@#SIS mesh implanted into the VVS of rabbits can lead to a transient non infective inflammatory reaction, which could be completely degraded and a small amount of new collagen fibers could be produced after 180 days of implantation. Which shown that SIS mesh should be used cautiously in pelvic floor reconstruction surgery.

Clinical characteristics and prognosis of 34 cases of acute myeloid leukemia with FLT3 internal tandem duplication and MLL gene rearrangement / 中华血液学杂志

Objective@#To analyze the clinical characteristics and prognosis of 34 cases of acute myeloid leukemia (AML) with FLT3 internal tandem duplication (FLT3-ITD) and MLL gene rearrangement.@*Methods@#The clinical data of 34 AML patients with FLT3-ITD and MLL gene rearrangement was compared and analyzed for the therapeutic efficacy, prognostic factors when treated with chemotherapy, chemotherapy combined with targeted therapy or allogenic hematopoietic stem cell transplantation (allo-HSCT).@*Results@#Of the thirty-four cases with median age 41 (4-71) years old, 63.6% presented with white blood cells (WBC) greater than 30×109/L, 39.4% greater than 50 × 109/L respectively on admission. M5 (35.3%) made up the highest proportion. The cytogenetic abnormality reached 61.8%, of which the complex cytogenetic abnormality accounted for 11.8%. Eleven patients (32.35%) had both FLT3-ITD and MLL gene abnormalities. In addition to FLT3 and MLL abnormalities, 23 patients (67.6%) had one or more other gene abnormalities (multiple gene abnormalities). Of the 34 cases, 29.4% patients went into complete remission (CR) after two courses of chemotherapy. 20.6% (7 patients) went into CR after 3 or more courses of chemotherapy. The rate of early relapse in the CR group was 52.9%. Patients with WBC>50×109/L or multiple gene abnormalities had a lower remission rate (7.7%, 5.4%) after two courses of chemotherapy. CR rate for the patients with more than three gene abnormalities was 0. The total 2-year overall survival (OS) in the 34 patients was 28.8% (95% CI 13.5%-46.0%) and the disease-free survival (DFS) was 27.1% (95% CI 12.5%-44.0%). Of the 18 patients treated with chemotherapy alone or chemotherapy combined with targeted therapy, 17 cases died within 2 years and 1 lost follow-up after giving up treatment. For the 16 patients received allo-HSCT, the 3-year OS was 43.4% (95% CI 13.7%-70.4%) and DFS 42.7% (95% CI 13.4%-69.7%).@*Conclusion@#AML patients with FLT3-ITD and MLL gene rearrangement often presented with M5, accompanied by hyperleukocytosis, cytogenetic or multiple gene abnormalities. Those patients were observed to have low response rate and high early relapse when treated with chemotherapy without allo-HSCT. Patients had multiple gene abnormalities may be an important poor prognostic factor. Allo-HSCT is an effective treatment which could significantly improve the prognosis and survival of AML patients with FLT3-ITD and MLL gene abnormalities.

Relevance between expectations before treatment, new symptoms and satisfaction after treatment in patients with pelvic organ prolapse / 中华妇产科杂志

Objective To investigate the relevance between expectations before treatment, new symptoms and satisfaction after treatment of the pelvic organ prolapse (POP) patients. Methods Made a collection of 75 cases of POP patients at Peking University Third Hospital, who were affected by the POP symptoms and came to our clinic for treatment from January to December in 2013. Prospectively investigate the patients′expectations before treatment, which were the most troubling symptoms to be solved. According to treatment we divided the patients into surgery and pessary groups. Two groups were followed up with the degree to achieve the desired goals using patient global impression of improvement (PGI-I), new symptoms and satisfaction after treatment, try to find the relevance between expectations before treatment, new symptoms and satisfaction after treatment. Results There were 47 (63%, 47/75) patients in the surgical group and 28 (37%, 28/75) patients in the pessary group. The top three problems for patients were friction when walking (25%, 19/75), dysuria (23%, 17/75) and the feeling of vaginal prolapse (19%, 14/75). The follow-up rate was of 93% (70/75), follow-up time was (5 ± 4) months. Satisfaction score after treatment of surgical group was higher than that of pessary group [(4.9±0.4) versus (4.0±1.3) scores, P<0.01]. There was no statistically significant difference between two groups of PGI-I score [(6.7±0.6) versus (6.6±0.9) scores, P=0.886]. The top three new symptoms after treatment were increased secretion, urinary incontinence and dysuria. PGI-I and satisfaction scores was relevant (P=0.021). The availability of new symptoms and satisfaction scores was relevant (P=0.001). Conclusion When achieving higher expectations to the treatment and no more new symptoms, the satisfaction score after treatment is higher.

Factors influencing therapy decision in patients with severe pelvic organ prolapse / 中华妇产科杂志

Objective To investigate the factors influencing therapy decision of surgery or pessary in patients with severe pelvic organ prolapse (POP). Methods Totally 419 cases ofⅢtoⅣdegree POP patients were studied retrospectively. Patients were divided into surgery and pessary groups according to their own choice. Clinical characters were compared such as age, body mass index (BMI), age of onset and disease duration, POP stage, complications. Results 67.5%(283/419) patients were in the surgical group and 32.5%(136/419) patients in the pessary group. Patients in surgical group had higher BMI [(25.1 ± 3.5) versus (23.8±2.6) kg/m2], elder age of onset [(62±12) versus (57±11) years old], longer disease duration [(5± 8) versus (11±11) years] and higher POP staging of middle compartment and less cardiac disease [20.1%(57/283) versus 30.9% (42/136)] than those in pessary group, all had significant difference (P<0.05). Logistic regression analysis on the above factors showed a statistically significant difference between two groups, BMI, disease duration and POP staging of middle compartment were independent factors (OR=1.141, 0.932, 1.389;all P<0.01). Conclusions Patients with higher BMI, higher POP staging of middle compartment and less cardiac disease tended to choose surgery. Patients with younger age of onset and longer disease duration tended to choose pessary. Factors as age, POP staging of anterior and posterior compartment, history of POP surgery, complicated with hypertension and diabetes, showed no influence on treatment choice.

Clinical study on silicone pessary in the treatment of pelvic organ prolapse / 中华妇产科杂志

Objective To evaluate the therapeutic effect and influence factors of silicone pessary in treatment of pelvic organ prolapse ( POP).Methods From October 2005 to October 2010,132 with symptomatic POP managed by pessary were enrolled in this retrospective study.Validated prolapse quality of life questionnaire (pelvic floor distress inventory short form 20,PFDI-20),pelvic floor impact questionnaire short form 7 (PFIQ-7) and the patients' satisfaction degree were used to evaluate the therapeutic effect.Clinical characteristic of the patients with successful using for more than 6 months ( successful fitting group),giving up within 6 months (giving up group),unsuccessful fitting (unsuccessful fitting group)were compared.Factors influencing satisfaction degree and causing discontinuation were investigated.Results One hundred and six among 132 ( 106/132,80.3％ ) patients were in successful fitting group,26 (26/132,19.7％ ) patients were in the unsuccessful fitting group.In the successful fitting group,86.8％ (92/106) patients were followed up,the median follow-up time was 12.5 months.And 78.3％ ( 72/92 ) patients continued to use pessary with the wearing time ranged 3 -69 months; 21.7％ (20/92) patients discontinued with the wearing time ranged 1 -38 month,14 patients (14/20) gave up in the initial 6 months.The median scores of PFDI-20 and PFIQ-7 questionnaires before pessary use were 50.0 and 47.6,which decreased to 8.9 and 0.0 after pessary use (P＜0.05).And 87.1％ (61/70) patients were satisfied.There was no significantly difference among 3 groups on clinical characteristics,such as age,body mass index ( BMI ),pelvic surgery and so on (P ＞ 0.05 ).The main factor influencing satisfaction degree and causing discontinuation was difficulties in placing and removing.Conclusions Silicone pessary is effective for patients with POP.It could relieve discomfort symptoms and improve quality of life.The main factorinfluencing pessary use is difficulties in placing and removing.Thus,More suggestions are needed for patients in the initial 6 months.

An analysis of etiological and genetic factors of a patient with familial hemophagocytic lymphohistiocytosis / 中华内科杂志

Objective To analyze the etiological factor and genetic feature of a familial hemophagocytic lymphohistiocytosis patient with PRF1 mutation (FHL2) with human herpesvirus 7 (HHV7)infection and its family constellation. Methods Clinical characteristics, laboratory examinations of a FHL2 case with HHV7 infection were reported. HHV1-HHV8 virus DNA was screened by PCR; NK cell function was analyzed by flow cytometry; PRF1 gene mutations were analyzed by PCR and direct sequencing, structure of mutant PRF1 proteins were analyzed using ExPasy and I-TASSER server and genetics pedigree were analyzed. Results The patient's HHV7 viral was detected positive with DNA copy number of 350/106 peripheral nucleated cells. Flow cytometry analysis showed decrease both in proportion of perforin positive NK cells and perforin protein expression. Genetic testing showed PRF1 biallelic heterozygote mutations (c. 503G ＞ A/p. S168N and c. 1177T ＞ C/p. C393R) and pedigree analysis showed they were inherited. The patient was then treated with antivirus therapy, dexamethasone and VP16 therapy, but only achieved partial response. The patient was then followed by human leukocyte antigen 10/10 allele identical nonconsanguinity allogeneic hematopoietic stem cell transplantations (allo-HSCT) and soon the successful implantation of donor hematopoietic cells and persistent recovery was achieved. The patient was now surviving without recurrence for 9 months after allo-HSCT. Conclusions FHL is prone to be misdiagnosed as lymphoma. Genetic analysis of related gene mutation and herpes simplex virus detection will help in early and accurate diagnosis. Allo-HSCT is a fundamental treatment of FHL.

The study of gene mutations in unknown refractory viral infection and primary hemophagocytic lymphohistocytosis / 中华内科杂志

Objective To study the type and corresponding clinical characteristics of primary hemophagocytic lymphohistocytosis (HLH) associated immune gene mutations in the refractory virus infection or HLH of unknown causes. Methods From December 2009 to July 2010, the patients with refractory virus infection or HLH of unknown causes were screened for the primary HLH associated immune genes mutations by DNA sequence analysis, including PRF1, UNC13D, STX11, STXBP2, SH2D1A and XIAP. The clinical characteristics and outcomes were followed up. Results Totally 25 patients with refractory virus infection or HLH of unknown causes were investigated for the 6 genes and 13 cases were found carrying gene mutations, composing of 6 of PRF1 mutation, 3 of UNC13D, and each one of STX11,XIAP, SH2D1A and STXBP2, respectively. Among the 13 cases with gene mutations, 5 suffered from Epstein-Barr virus associated HLH( EBV-HLH), 1 human herpes virus 7 associated HLH (HHV7-HLH),1 HLH without causes, 4 chronic activated EB virus infection (CAEBV) with 1 progressing to Hodgkin's lymphoma carrying abnormal chromosome of t ( 15; 17 ) (q22; q25 ) and hyperdiploid, 2 EBV associated lymphoma. Among the other 12 patients without gene mutation, 4 suffered from EBV-HLH with 1 progressing to peripheral T lymphoma, 8 suffered from CAEBV. Conclusions Primary HLH associated immune gene mutations are critical causes of refractory virus infection of unknown causes, most patients manifest as HLH,some cases appear in CAEBV and EBV associated lymphoma. DNA sequence analysis is helpful to early diagnosis and correct decision-making for treatment.