Advances in Diagnosis and Treatment of Transplant-Associated Thrombotic Microangiopathy --Review / 中国实验血液学杂志

Transplantation-associated thrombotic microangiopathy (TA-TMA) is one of the serious complications mostly occurring within 100 days after hematopoietic stem cell transplantation (HSCT). Risk factors of TA-TMA include genetic predispositions, GVHD, and infections. The pathophysiological mechanisms of TA-TMA start with endothelial injury caused by complement activation, which leads to microvascular thrombosis, and microvascular hemolysis, ultimately resulting in multi-organ dysfunction. In recent years, the development of complement inhibitors has markedly improved the prognosis of TA-TMA patients. This review will give an update on risk factors, clinical manifestations, diagnosis, and treatment of TA-TMA, so as to provide references for clinical practice.

Effect of consolidation before allogeneic hematopoietic stem cell transplantation for non-favorable acute myeloid leukemia patients with first complete remisson and negative minimal residual disease / 中华血液学杂志

Objective: To probe the prognostic value of consolidation chemotherapy in non-favorable acute myeloid leukemia (AML) patients who were candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT) with first complete remission (CR(1)) and negative minimal residual disease (MRD(-)) . Methods: A retrospective analysis was conducted on 155 patients with non-favorable AML who received allo-HSCT in CR(1)/MRD(-) from January 2010 to March 2019. The survival data were compared between patients who received and those not received pre-transplant consolidation chemotherapy. Results: A total of 102 patients received pre-transplant consolidation chemotherapy (consolidation group) , and 53 cases directly proceeded to allo-HSCT when CR(1)/MRD(-) was achieved (nonconsolidation group) . The median ages were 39 (18-56) years old and 38 (19-67) years old, respectively. Five-year post-transplant overall survival [ (59.3±7.5) % vs (62.2±6.9) %, P=0.919] and relapse-free survival [ (53.0±8.9) % vs (61.6±7.0) %, P=0.936] were not significantly different between the two groups (consolidation vs nonconsolidation) . There was a weak relationship between consolidation therapy and cumulative incidence of relapse [consolidation: (21.9±5.4) % vs nonconsolidation: (18.3±6.0) %, P=0.942], as well as non-relapse mortality [consolidation: (22.4±4.3) % vs nonconsolidation: (28.4±6.5) %,P=0.464]. Multivariate analysis indicated that pre-transplant consolidation and the consolidation courses (< 2 vs ≥2 courses) did not have an impact on allo-HSCT outcomes. Conclusion: Allo-HSCT for candidate patients without further consolidation when CR(1)/MRD(-) was attained was feasible.

Clinical Significance of FGFR1 Gene Abnormalities in Blood Tumors / 中国实验血液学杂志

OBJECTIVE@#To study the potential significance and clinical application of FGFR1 gene abnormality in the diagnosis, clinical features, pathological mechanism and treatment in hematological tumors.@*METHODS@#Clinical data of total of 29 patient with chromosome of 8 short arm (8P) abnormality who had more comprehensive medical history from 2013 to 2018 were collected. The karyotype analysis of bone marrow chromosomes in patients was carried out by using chromosome R band banding technique. FGFR1 gene was detected by using fluorescence in situ hybridization (FISH).@*RESULTS@#Seven cases of FGFR1 gene abnormalities were decteted, including 3 cases of FGFR1 gene amplification, 2 cases of translocation, and 2 cases of deletion. Five patients with FGFR1 gene amplification or deletion not accompaned with eosinophilia, moreover the chromosome was a complex karyotype with poor prognosis; Two cases of FGFR1 gene translocation were non-complex chromosomal translocation and one of which survived for 6 years after bone marrow transplantation, the other chromosome karyotype showed no rearrangement of 8 short arm. However, FGFR1 gene rearrangement was confirmed by FISH analysis, which was a rare insertional translocation.@*CONCLUSION@#FGFR1 gene amplification or deletion often occur in cases with complex karyotype, which not accompany eosinophilia, moreover have poor prognosis. The patients with FGFR1 gene translocation accompany eosinophilia which is consistent with the clinical characteristics of myeloid / lymphoid neoplasms with FGFR1 abnormality. Karyotype analysis combined with FISH method can improve the detection of abnormal clones.

Prognostic value of donor chimerism at +90 days after allogeneic hematopoietic stem cell transplantation in young patients with intermediate-risk acute myeloid leukemia / 中华血液学杂志

Objective: To investigate the relationship between donor chimerism and relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: The clinical data of 105 patients with acute myeloid leukemia (AML) who underwent allo-HSCT and recurrence-free survival>90 days from January 2010 to January 2019 were retrospectively analyzed. The bone marrow samples were collected at 15, 30, 60, 90, 180, 270, 360 days after transplantation. Donor chimerism was detected by single nucleotide polymorphism (SNP) -PCR. Results: Of the 105 patients, 43 cases were male and 62 cases were female, with a median age of 38 (16-60) years. Till April 2019, the median follow-up was 843 (94-3 261) days. Ninety days after transplantation, 18 cases relapsed, 33 cases died, and 72 cases survived. The 3-year overall survival (OS) rate was (66.8±5.1) %, and the recurrence-free survival (RFS) rate was (65.1±5.0) %. Pre-transplant disease status, pre-transplant minimal residual disease (MRD) , and 90 day post-transplantation chimerism were independent risk factors related to RFS. The risk of recurrence was significantly increased in patients with a donor chimerism rate ≤97.24% at 90 days after transplantation[HR=6.921 (95%CI 2.669-17.950) , P<0.001], which was considered as a sign of early relapse. Conclusion: SNP-PCR is an applicable method for detecting donor chimerism in patients after allo-HSCT. Chimerism rate equal or less than 97.24% at 90 days after transplantation predicts a higher risk of relapse.

Clinical and prognostic values of TP53 mutation in patients with acute myeloid leukemia / 中华血液学杂志

Objective: To explore the clinical and prognostic values of TP53 gene mutation in patients with acute myeloid leukemia (AML) . Methods: A retrospective analysis of 265 newly diagnosed AML patients with next-generation sequencing (NGS) data in the Hematology Department of Changhai Hospital from January 2010 to January 2019 was performed. Mutation analysis was carried out by targeted sequencing technology including 200 hematological malignancy related genes. The association of TP53 mutation with clinical features was analyzed. Results: Alterations in TP53 were found in 20 (7.5%) patients, including 17 case (6.4%) of missense mutations, 2 cases (0.7%) of frame-shift deletion mutations and 1 case (0.4%) of splicing sites mutation. A total of 23 kinds of TP53 mutations were detected, most of them (16, 69.6%) were located in the DNA binding domain of exon 5-8, 4 in the DNA binding domain of exon 3-4, 2 in exon 10 and 1 in splice site, respectively. The median age of patients with TP53 alterations was higher than those without [52 (26-72) years old vs 45 (14-75) years old, P= 0.008]. The frequency of complex karyotypes was higher in patients with TP53 alterations than those without [45.0% (9/20) vs 6.1% (15/245) , P<0.001]. Median overall survival (OS) of patients with TP53 alterations was shorter than those without[14.1 (95%CI 6.78-21.42) months vs 31.4 (95%CI 13.20-49.59) months, P=0.029]. The OS of patients treated with "Decitabine + CAG" was superior than that of patients treated with "3 + 7" regimen [30.0 (95%CI 27.35-38.84) months vs 12.5 (95%CI 5.80-19.19) months, P=0.018]. Multivariate analysis indicated that TP53, DNMT3A and USH2A alterations, WBC ≥ 12.45×10(9)/L had negative impacts on OS. Conclusion: The frequency of TP53 mutation was 7.5% in our cohort. Most mutations were located in the DNA binding domain. TP53 alterations were strongly associated with older age, complex karyotype and shorter OS. Decitabine-based induction chemotherapy and hematopoietic stem cell transplantation may improve OS, more cases and/or multicenter randomized studies are needed for further confirmation.

Rosai-Dorfman disease: a clinicopathologic analysis and whole exome sequencing in 23 cases / 中华血液学杂志

Objective: To evaluate the clinicopathologic features of Rosai-Dorfman disease (RDD) , and elucidate the potential pathogenesis by whole exome sequencing (WES) . Methods: Clinico-pathological data of 23 RDD patients diagnosed between 2010 and 2018 in Changhai hospital were reviewed, and 9 paraffin-embedded specimens were performed for WES. Results: The median age of 23 RDD patients was 47 (10-79) years. Of them, 19 cases had extranodal lesions, 3 had nodal lesions, and 1 had nodal and extranodal lesions coincidently. All patients received surgery for lesion resection. Histiocytosis in lymph node sinuses or in extranodal tissues accompanied by lymphocyte phagocytosis are typical pathological features of RDD. Immunohistochemical staining shows histocytes are positive for S100, CD68 and CDl63, and negative for CD1a. mTOR, KMT2D and NOTCH1 mutations were detected with WES in these cases. Conclusion: Mutations in mTOR, KMT2D and NOTCH1 genes may be involved in the pathogenesis of RDD, and their clinical significance needs to be further studied.

Efficacy of Hyper-CVAD/MA and CHALL-01 regimens in the treatment of Philadelphia chromosome-positive adult acute lymphoblastic leukemia patients under 60 years old / 中华血液学杂志

Objective: To compare the difference of efficacy between traditional Hyper-CVAD/MA regimen and the adolescents inspired chemotherapy regimen, CH ALL-01, in treatment of adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) . Methods: In this study we retrospectively analyzed 158 Ph(+) ALL patients receiving Hyper-CVAD/MA regimen (n=63) or CHALL-01 regimen (n=95) in our center and Changzheng hospital from January 2007 to December 2017, excluding patients with chronic myeloid leukemia in blast crisis. Tyrosine kinase inhibitor (TKI) was administered during induction and consolidation chemotherapy. Patients who underwent hematopoietic stem cell transplantation received TKI as maintenance therapy. Results: Of them, 91.1% (144/158) patients achieved complete remission (CR) after 1-2 courses of induction. CR rate was 90.5% (57/63) for patients in Hyper-CVAD/MA group and 91.6% (87/95) for patients in CHALL-01 group. There was no difference in CR rates between the two groups (χ(2)=0.057, P=0.811) . The last follow-up was June 2018. A cohort of 134 CR patients could be used for further analysis, among them, 53 patients received Hyper-CVAD/MA regimen and other 81 patients received CHALL-01 regimen. The molecular remission rates were significantly higher in CHALL-01 group (complete molecular response: 44.4%vs 22.6%; major molecular response: 9.9% vs 18.9%) (χ(2)=7.216, P=0.027) . For the patients in Hyper-CVAD/MA group, the 4-year overall survival (OS) was 44.81% (95%CI: 30.80%-57.86%) and the 4-year disease free survival (DFS) was 37.95% (95%CI: 24.87%-50.93%) . For patients received CHALL-01 regimen, the 4-year OS was 55.63% (95%CI: 39.07%-69.36%) (P=0.037) and 4 year DFS was 49.06% (95%CI: 34.24%-62.29%) (P=0.015) , while there was no significant difference in 4 year cumulative incidence of relapse (CIR) (P=0.328) or cumulative incidence of nonrelapse mortality (CI-NRM) (P=0.138) . The rate of pulmonary infection was lower in patients received CHALL-01 regimen compared with patients received Hyper-CVAD regimen (43.4% vs 67.9%, χ(2)=7.908, P=0.005) . Conclusions: Outcome with CHALL-01 regimen appeared better than that with the Hyper-CVAD/MA regimen in Ph(+) ALL, which has lower incidence of pulmonary infection, higher molecular remission rate and better OS and DFS.

The value of narrow-band imaging with magnifying endoscopy in diagnosis of early gastric cancer: a meta-analysis / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To assess the diagnostic value of narrow-band imaging with magnifying endoscopy (NBI-ME) for early gastric cancer (EGC).</p><p><b>METHODS</b>We searched PubMed, Embase, Web of Science and the Cochrane Library for literature of NBI-ME in diagnosis of EGC, and then performed meta-analysis.</p><p><b>RESULTS</b>A total of 12 articles involving 2 278 samples from 2 048 patients were included. The overall sensitivity of NBI-ME for diagnosis of EGC was 0.84 [95% CI: 0.80~0.87], specificity was 0.96 (95% CI: 0.95~0.97),and area under the symmetric receiver operator characteristic curve (AUC) was 0.9592. The AUC value of the NBI-ME plus conventional white light endoscopy (C-WLE) subgroup (0.9706) was higher than that of NBI-ME alone (0.8162). The incremental yield of NBI-ME plus C-WLE over C-WLE was significant (IY = 9.4%, P = 0.011), while NBI-ME alone over C-WLE was not significant (IY = 0.8%, P = 0.498).</p><p><b>CONCLUSIONS</b>The results show that NBI-ME plus C-WLE is an effective and preferable method for diagnosis of EGC; however, NBI-ME alone is not superior to C-WLE.</p>

Adipose tissue sample preparation for scanning electron microscopy / 南方医科大学学报

Conventional sample preparation technique for adipose tissue is difficult to achieve satisfactory results for scanning electron microscopy (SEM). We adopted a strategy of postfix with osmium tetroxide to stabilize the fatty acids, phospholipids protein, and hence the membrane structure. Also by extending the dehydration time to fully replace the organic solvents, we achieved satisfactory results for SEM of adipose samples.

Anti-mycobacteria drugs therapy for periductal mastitis with fistula / 中华外科杂志

<p><b>OBJECTIVES</b>To study the etiology, clinical and pathologic characteristics of periductal mastitis with fistula and estimate the effect of anti-mycobacterial agents for periductal mastitis with fistula.</p><p><b>METHODS</b>Totally 27 patients of periductal mastitis with fistula received anti-mycobacteria drugs therapy from December 2008 to September 2011 were analyzed retrospectively. All of the patients were female. The mean age at onset was 28 years (range 15 to 40 years old). The main clinical manifestation of the 27 patients was breast fistula, including 21 patients with single fistula and 6 patients with multiple fistula. Three patients manifested with pure fistula, 14 patients with both fistula and lump, 10 patients with fistula, lump and abscess. The samples including pus or tissues of all patients were underwent bacteria culture and all patients core needle biopsy. All patients were given primary anti-mycobacteria drugs therapy, parts of patients received surgery based on the evaluation of medical treatment.</p><p><b>RESULTS</b>The common bacteria culture of all patients failed to demonstrate any causative microorganism. Four cases were selected randomly to undergo PCR of mycobacteria, only one case was identified as Massiliense in bacteria culture of mycobacteria. Twenty-seven patients with periductal mastitis with fistula were treated with anti-mycobacterial agents (isoniazid, rifampicin and ethambutol or pyrazinamide of triple oral drugs) for 1 to 3 months, the fistula of all 27 patients were closed well. Sixteen patients were treated with the agents only and cured. Eleven patients received surgical treatment after treated with the medical agents. None of the patients were given mastectomy. All patients had no reccurence until now.</p><p><b>CONCLUSIONS</b>The periductal mastitis with fistula has a closely relationship with the infection of nontuberculosis mycobacteria. Those patients could be treated with triple anti-mycobacterial agents and could also avoided mastectomy.</p>

Clinical and laboratory characteristics of hematological diseases associated with eosinophilia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical and laboratory characteristics of hematological diseases associated with eosinophilia.</p><p><b>METHODS</b>Karyotype analysis was performed by direct method and/or short-time culture of bone marrow cells for R-banding. Fluorescence in situ hybridization (FISH) was performed using PDGFRα, PDGFRβ and FGFR1 break-apart probes.</p><p><b>RESULTS</b>The clinical and hematological findings of 44 patients were diagnosed as hematological diseases associated with eosinophilia. Abnormal karyotypes were detected in 6 cases (13.64%) with karyotyping. The efficiency of the detection of abnormal clone was markedly increased to 29.55% (13/44) with FISH techniques, including 7 cases with FIP1L1-PDGFRα (F/P, 15.91%), 3(6.82%) PDGFRα rearrangement, 2 (4.55%) aberrant PDGFRβ gene and 1(2.27%) FGFR1 rearrangement. Patients being PDGFRα, PDGFRβ or FGFR1 positive (13 cases) or negative (31 cases) showed predominant difference in clinical and laboratory features. The incidence of gut involvement, the absolute count of eosinophils in peripheral blood and the percentage of immature eosinophils in bone marrow were significantly increased in positive patients (P < 0.05).</p><p><b>CONCLUSIONS</b>The hematological diseases associated with eosinophilia are characterized by unique clinical and laboratory features. Karyotyping should be a routine approach to detect the abnormal clone in these diseases. Screening for PDGFRα, PDGFRβ and FGFR1 gene with FISH can provide more genetic information.</p>

Study on differentiation of human umbilical cord-derived mesenchymal stem cells into human sweat gland cells in vitro and the relative signal pathway / 中华烧伤杂志

<p><b>OBJECTIVE</b>To study the differentiation potential of human umbilical cord-derived mesenchymal stem cells (UCMSC) into human sweat gland cells (hSGC) and the role of extracellular signal-regulated kinase (ERK) pathway.</p><p><b>METHODS</b>UCMSC and hSGC were isolated and cultured in vitro. The former was identified with expression of CD14, CD29, CD34, CD44, CD45, CD105, cytokeratin 7 (CK7), CK19, and carcinoembryonic antigen (CEA), while the latter was identified with expression of CK19 and CEA. UCMSC with density of 5 x 10(4) cells per well placed in lower compartment of Transwell chamber were divided into control group (C, cultured with nutrient solution without any stimulation), thermal injury group (TI, treated with heat-shocked hSGC with density of 1 x 10(4) cells per well inoculated into the upper compartment of Transwell chamber for indirect co-culture), thermal injury + EGF group (TIE, treated with indirect co-culture as used in TI group, with addition of 50 ng/mL EGF), thermal injury + PD98059 group (TIP, treated with indirect co-culture as used in TI group, with addition of 10 nmol/mL ERK specific inhibitor PD98059) according to the random number table. One week after culture, the positive expression rates of CK7 and CK19 in UCMSC were detected by flow cytometry, the expression of CK19 and CEA in UCMSC were examined with immunohistochemical staining and the positive expression rate of CEA was calculated, and the expression level of phosphorylated ERK (pERK) was determined by Western blotting. Data were processed with one-way analysis of variance.</p><p><b>RESULTS</b>(1) CD29, CD44, and CD105 were highly expressed in UCMSC, accompanied by low or negative expression of CD14, CD34, CD45, CK7, CK19, and CEA. The expression of CK19 and CEA were positive in hSGC. The two results showed that UCMSC and hSGC were pure. (2) Compared with those of C group [(2.2 +/- 1.5)%, (2.2 +/- 0.7)%, (3.3 +/- 0.7)%, 0.640 +/- 0.026], the expression levels of CK7, CK19, CEA, and pERK in UCSMC of TI group [(6.4 +/- 0.7)%, (5.7 +/- 0.3)%, (7.4 +/- 1.0)%, 0.790 +/- 0.049] and TIE group [(14.3 +/- 1.0)%, (12.6 +/- 1.1)%, (17.6 +/- 2.3)%, 1.200 +/- 0.032] were significantly increased (with F value respectively 78.49, 139.36, 87.13, and 191.74, P values all below 0.01), and those of TIE group were higher than those of TI group (with F value from 50.14 to 145.47, P values all below 0.01). There were no obvious difference in the 4 indexes between TIP group and C group (with F value from 0.00 to 0.13, P values all above 0.05).</p><p><b>CONCLUSIONS</b>UCMSC co-cultured with heat-shocked hSGC can differentiate into hSGC, and ERK signal pathway participates in the process of differentiation of UCMSC into hSGC.</p>

Comparison of protein expression profiles between bortezomib-resistant JurkatB cells with PSMB5 mutation and their parent cells / 中国实验血液学杂志

This study was purposed to investigate the differences of cyto biological characteristics and protein expression levels between bortezomib-resistant T-lymphoblastic lymphoma/leukemia cell lines JurkatB containing PSMB5 G322A mutation and their parent cell line Jurkat, The cytotoxicities of bortezomib and chemotherapeutic drugs to JurkatB5 cells (end selection concentration of bortezomib was 500 nmol/L), JurkatB8 (end selection concentration 800 nmol/L) and Jurkat cells were analyzed. The cell growth curves were drawn with viable cell counts by trypan blue assay, the colony formation rate were assayed by soft-agar colony culture, and the cell distributions in cell cycle were analyzed by flow cytometry, mRNA expression levels of multidrug resistance (MDR) genes MDR1, LRP and MRP were measured by real-time fluorescence quantitative RT-PCR, the differences of protein expression levels were detected by SpringBio antibody microarray containing 720 proteins. The results showed that the drug resistance multiples for 48 hours of JurkatB5 and JurkatB8 cells (relative to Jurkat) to bortezomib were increased by 33.52 and 39.04 times, respectively. JurkatB5 and JurkatB8 cells did not display significant cross-resistance to daunorubicin, adriamycin, vindesine, and etoposide after exposure for 48 hours. There were no significant differences in the cell growth curve, colony formation rate and cell distributions in cell cycle between JurkatB5, JurkatB8 and Jurkat cells (p > 0.05). There were no significant differences of mRNA expression levels of MDR1, LRP, MRP between JurkatB5 and Jurkat cells (p > 0.05). There were 264 analyzable expression points detected by antibody microarray. Among them, 252 protein expression levels were not significantly different between JurkatB5, JurkatB8 and Jurkat cells (< 2-fold), including 15 drug resistance-related proteins. 12 proteins were detected at higher or lower expression levels in JurkatB5 or JurkatB8 cells then that in Jurkat cells (cell division cycle protein 34, cell division cycle protein 37, CD34 Type II, matrix metalloproteinase-2, tenascin, Golgi complex, involucrin, histone deacetylase 1, perforin, prolactin, retinoic acid receptor β, integrin β-1), but no proteins were detected in JurkatB5 and JurkatB8 cells with higher or lower expression levels than that in Jurkat cells. It is concluded that there are no significant differences in the characteristics of cellular biology between Jurkat and JurkatB with bortezomib-resistant and PSMB5 G322A mutation. There are no significant phenotype change of MDR and overexpression of genes related to MDR in PSMB5 mutated cells. There are no significantly differential expressions of a majority of known proteins related to drug resistance, tumor cells growth, proliferation, apoptosis, malignancy degree, aggressiveness.

Reduced intensity conditioning regimen for related and unrelated allogeneic peripheral blood hematopoietic stem cell transplantation in chronic myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the overall efficacy and transplant-related mortality (TRM) of related and unrelated allogeneic peripheral blood hematopoietic stem cell transplantation (allo-PBSCT) in chronic myeloid leukemia (CML) patients conditioned with fludarabine-busulfan (FB) reduced intensity regimen.</p><p><b>METHODS</b>Forty-four patients received FB (Flud 30 mgxm(-2)xd(-1) x 5 d, BU 4 mgxkg(-1)xd(-1) x 3 d) conditioning followed by allo-PBSCT. Of them, 29 patients were transplanted with related donor and 15 unrelated donor (URD). All patients received mycophenolate mofetil (MMF), CsA and MTX for acute GVHD (aGVHD) prophylaxis. 5 mg/kg rabbit-antithymocyte globulin (ATG-Fresenius) was incorporated in 15 URD recipients.</p><p><b>RESULTS</b>All patients were successfully engrafted. The median times to ANC above 0.5 x 10(9)/L in related (RG) and unrelated groups (URG) were 13.7 (9 - 18) d and 13.6 (12 - 17) d, and PLT above 20 x 10(9)/L were 15.3 (9 - 20) d and 14.7 (10 - 26) d, respectively. Two patients in RG. 1 in URG developed graft rejection 5 - 8 months after transplantation. One of the two patients in RG received second transplantation and engrafted. The cumulative incidence of aGVHD and cGVHD were 13.8% (4/29) and 46.4% (13/28) in RG, and were 33.3% (5/15) and 57.1% (8/14) in URG respectively. Two patients in RG relapsed after transplantation, and obtained CR again after donor stem cell infusion (DSI). Median time of follow-up was 34.7 (2 - 73) months. Thirty-four patients were alive and 10 died. The main causes of death were IP, GVHD, graft rejection and infection. The 5-year overall survival (OS) probability was 77.0%, and the disease-free-survival (DFS) was 73.9%, of which, 79.0% and 74.1% were in RG, and 73.3% and 73.3% in URG, respectively.</p><p><b>CONCLUSIONS</b>Fludarabine-busulfan based reduced intensity conditioning for allo-PBSCT with either related or unrelated donors is a safe, less toxic and curative approach to CML.</p>

Influence of granulocyte colony-stimulating factor on cardiac function in patients with acute myocardial infarction and leukopenia after revascularization / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Granulocyte colony-stimulating factor (G-CSF) seems to improve cardiac function and perfusion when used systemically through mobilization of stem cells into peripheral blood, but results of previous clinical trials remain controversial. This study was designed to investigate safety and efficacy of subcutaneous injection of G-CSF on left ventricular function in patients with impaired left ventricular function after ST-segment elevation myocardial infarction (STEMI).</p><p><b>METHODS</b>Thirty-three patients (22 men; age, (68.5 +/- 6.1) years) with STEMI and with comorbidity of leukopenia were included after successful primary percutaneous coronary intervention within 12 hours after symptom onset. Patients were randomized into G-CSF group who received G-CSF (10 microg/kg of body weight, daily) for continuous 7 days and control group. Results of blood analyses, echocardiography and angiography were documented as well as possibly occurred adverse events.</p><p><b>RESULTS</b>No severe adverse events occurred in both groups. Mean segmental wall thickening in infract segments increased significantly at 6-month follow up compared with baseline in both groups, but the longitudinal variation between two groups had no significant difference (P > 0.05). The same change could also be found in longitudinal variation of wall motion score index of infarct segments (P > 0.05). At 6-month follow-up, left ventricular end-diastolic volume of both groups increased to a greater extent, but there were no significant differences between the two groups when comparing the longitudinal variations (P > 0.05). In both groups, left ventricular ejection fraction measured by echocardiography ameliorated significantly at 6-month follow-up (P < 0.05), but difference of the longitudinal variation between two groups was not significant (P > 0.05). When pay attention to left ventricular ejection fraction measured by angiocardiography, difference of the longitudinal variation between groups was significant (P = 0.046). Early diastolic mitral flow velocity deceleration time changed significantly at 6- month follow-up in both groups (P = 0.05).</p><p><b>CONCLUSIONS</b>Mobilization of stem cells by G-CSF after reperfusion of infarct myocardium is safe and seems to offer a pragmatic strategy for recovery of myocardial global function.</p>

Blocking ICOS-B7h signal pathway by ICOS-Ig fusion protein inhibits function of allogeneic T lymphocytes / 中国实验血液学杂志

Inducible costimulatory molecule (ICOS), a CD28 family member expressed on activated T cells, plays an important roles in T cell activation and effector function. This study was purposed to investigate the effect of blocking ICOS-B7h signal pathway by ICOS-Ig fusion protein on allogeneic reactive T cells and its mechanism. CHO cells stably and highly expressing ICOS-Ig were established, while the human ICOS-Ig fusion protein was harvested and purified from supernatant of CHO cells transfected with pSecTag2/Hygro A-ICOS-Ig. The CD4(+) cells from spleen of C57BL/6 mice were used as reactive cells, the bone marrow derived dendritic cells (DCs) from BALB/C mice were used as stimulatory cells, these cells were treated with different concentrations of ICOS-Ig or human Ig (h-Ig) as control. The results showed that the target protein with molecular weigh 54 kD and endotoxin level < 10 EU/ml was gained. The ICOS-Ig (> or = 10 microg/ml) could significantly inhibited the proliferative effect of allogeneic reactive T cells resulting from stimulation of DCs (p < 0.01). ICOS-Ig did not influence the activation of CD4(+) T cells. ICOS-Ig concentration positively related to the apoptosis of CD4(+) T cells. The percentages of CD4(+) Annexin V(+)PI(-) cells in simple stimulated group, ICOS-Ig 10 microg/ml group and ICOS-Ig 20 microg/ml group were 15.1%, 26.4% and 33.6% respectively. ICOS-Ig decreased secretion of TNFalpha and increased secretion of IL-4. It is concluded that the ICOS-Ig fusion protein has bioactivity of inhibiting T cell proliferation and altering the polarization of T helper cells to Th2 cells which promotes the apoptosis of allogeneic reactive T cells but had no effect on the activation of allo-reactive CD4(+) T cells.

Effects of anti-heparanase antibody on the growth and invasion of HCCLM6 human hepatocellular carcinoma cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effects of the self-developed anti-heparanase polypeptide antibodies on growth and invasion of human hepatocellular carcinoma HCCLM6 cells.</p><p><b>METHODS</b>Using MTT, flow cytometry, plate clone formation, transwell invasion and heparan degrading enzyme assay, the growth and invasion changes of human hepatocellular carcinoma HCCLM6 cells by co-culture with each of three self-developed rabbit anti-heparanase polyclonal antibodies were detected.</p><p><b>RESULTS</b>Compared with normal rabbit IgG, in the presence of each anti-heparanase polypeptide antibody, the growth, cell cycle and clone formation remained unchanged, and under the P1 or P2 anti-heparanase polypeptide antibody (with final concentration 100 microg/ml), the cell invasiveness was inhibited by 52.5% and 36.6%, respectively, and the heparanase activity was inhibited by 42.9% and 39.1%, respectively.</p><p><b>CONCLUSION</b>The P1 and P2 anti-heparanase polypeptide antibodies can effectively inhibit the invasion ability and heparanase activity of liver cancer HCCLM6 cells. However, All the three antibodies have no effects on its growth, cell cycle and clone formation.</p>

Risk factors of breast cancer in women in Guangdong and the countermeasures / 南方医科大学学报

<p><b>OBJECTIVE</b>To screen high-risk population of breast cancer by analyzing the risk factors of breast cancer in Guangdong Province.</p><p><b>METHODS</b>A case-control study was performed to identify the risk factors of breast cancer between premenopausal women and postmenopausal women. Chi-square test and unconditional logistic regression were used to analyze the data.</p><p><b>RESULTS</b>In premenopausal women, prophylactic, family history of breast cancer, bad mood, bad life incidence and work load were the risk factors, and breast hyperplasia history, breast tissue examination history, regular exercise and sleeping without bra were the protective factors. In postmenopausal women, family history of breast cancer was the risk factor, and breast hyperplasia history and mood adjustment were the protective factors.</p><p><b>CONCLUSION</b>The risk and protective factors of breast cancer differ between premenopausal and postmenopausal women, which highlights the importance of using different risk models to screen the high-risk populations.</p>

Feasibility study on CT guided percutaneous incisional needle biopsy for deep pelvic masses by different puncture approaches / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the feasibility of CT guided percutaneous incisional needle biopsy (PINB) for deep pelvic masses at different locations via various puncture approaches.</p><p><b>METHODS</b>PINBs under CT guidance were performed in 70 patients with 72 pelvic lesions through different puncture approaches. Their pathological findings and safety were evaluated after follow-up of a period of 1-34 months.</p><p><b>RESULTS</b>PINBs were performed through transpiriform-muscle in 27 cases, 16 through transgluteal approach, 5 through posterior oblique approach in prone position, 8 by anterior or lateral transabdominal route, 8 through iliopsoas muscle and 8 by direct transosseous approach, respectively. Sixty-four malignant lesions were confirmed by pathology, including 30 adenocarcinomas, 19 squamous cell carcinomas, 5 unclassified malignant tumors, 3 small cell carcinomas, 2 malignant giant cell tumors of bone, 2 hepatocellular carcinomas and 3 false negative lesions which were confirmed at the second PINBs as malignant tumors, respectively. Benign neoplasms were confirmed in 8 cases, including fibrosis tissue in 6 lesions, bone tuberculosis in 1 and ovarian cyst in 1. The sensitivity, specificity, and accuracy rate were 95.3% (61/64), 100% (8/8), and 95.8% (69/72), respectively. Twenty-two cases via transpiriform-muscle approach suffered from transient deep pelvic pain which radiated to the lower limbs of the same side. No hematoma, nerve damage, infection, and tumor transplantation in pelvic cavity developed after the PINB procedure.</p><p><b>CONCLUSION</b>CT guided percutaneous incisional needle biopsy through different puncture approaches is safe and feasible for the patients with deep masses at different locations in the pelvic cavity.</p>

Synergistic effects of arsenic trioxide and proteasome inhibitor bortezomib on apoptosis induction in Raji cell line / 中国实验血液学杂志

The aim of this study was to explore the synergistic effect of arsenic trioxide and bortezomib on apoptosis of Raji cell line. The cells were treated with arsenic trioxide, bortezomib, low-dose arsenic trioxide combined with bortezomib, respectively. The cell viability and proliferative curve were estimated by trypan blue dye exclusion. The cell apoptosis and cell cycle status were analyzed by flow cytometry. The apoptosis related elements such as caspase-3, BCL-2, BAX, JNK2 and IkappaB-alpha, were measured with Western blot. The results showed that compared with cells treated with mentioned above drugs alone, the proliferative potential of cells in combination group was significantly inhibited (p < 0.01), and apoptosis rate markedly increased (p = 0.001), while obvious cell cycle arrest was not observed. On the protein level, the expression of Caspase-3, BAX and IkappaB-alpha increased, while the expression of BCL-2, and JNK2 decreased. It is concluded that low-dose arsenic trioxide combined with bortezomib synergistically induced apoptosis in Raji cell line which may be mediated by inhibiting NK-kappaB and JNK2 signaling.