[Prognostic value of KIT and other clonal genetic mutations in core-binding factor acute myeloid leukemia].

Objective: To evaluate the prognostic significance of clonal gene mutations using next-generation sequencing in patients with core-binding factor acute myeloid leukemia (CBF-AML) who achieved first complete remission after induction chemotherapy. Methods: The study, which was conducted from July 2011 to August 2017 in First Affiliated Hospital of Soochow University, comprised 195 newly diagnosed patients with CBF-AML, including 190 patients who achieved first complete remission after induction chemotherapy. The cohort included 134 patients with RUNX1-RUNXIT1(+) AML and 56 patients with CBFß-MYH11(+) AML. The cohort age ranged from 15 to 64 years, with a median follow-up of 43.6 months. Overall survival (OS) and disease-free survival (DFS) were assessed by the log-rank test, and the Cox proportional hazards regression model was used to determine the effects of clinical factors and genetic mutations on prognosis. Results: The most common genetic mutations were in KIT (47.6% ) , followed by NRAS (20.0% ) , FLT3 (18.4% ) , ASXL2 (14.3% ) , KRAS (10.7% ) , and ASXL1 (9.7% ) . The most common mutations involved genes affecting tyrosine kinase signaling (76.4% ) , followed by chromatin modifiers (29.7% ) . Among the patients receiving intensive consolidation therapy, the OS tended to be better in patients with CBFß-MYH11(+) AML than in those with RUNX1-RUNXIT1 (+) AML (P=0.062) . Gene mutations related to chromatin modification, which were detected only in patients with RUNX1-RUNXIT1(+) AML, did not affect DFS (P=0.557) . The patients with mutations in genes regulating chromatin conformation who received allo-hematopoietic stem cell transplantation (allo-HSCT) achieved the best prognosis. Multivariate analysis identified KIT exon 17 mutations as an independent predictor of inferior DFS in patients with RUNX1-RUNXIT1(+) AML (P<0.001) , and allo-HSCT significantly prolonged DFS in these patients (P=0.010) . Conclusions: KIT exon 17 mutations might indicate poor prognosis in patients with RUNX1-RUNXIT1(+) AML. Allo-HSCT may improve prognosis in these patients, whereas allo-HSCT might also improve prognosis in patients with mutations in genes related to chromatin modifications.

[Influence of laparoscopic radical gastrectomy on immune function and coagulation function and prognosis].

Objective: To explore the influence of laparoscopic radical gastrectomy on patients'immune functions, coagulation functions and prognoses. Methods: Fifty-eight patients with gastric cancer who underwent laparoscopic radical gastrectomy (laparoscopic group) and 40 patients with gastric cancer who underwent traditional open surgery (traditional group) in Henan People's Hospital from May 2016 to May 2018 were selected as the subjects. The immune function and coagulation function were compared between the two groups before and after operation. The prognoses of patients underwent laparoscopic radical gastrectomy and the influencing factors were analyzed. Results: Three days after operation, the CD4(+) level and CD4(+) /CD8(+) ratio in laparoscopic group were (29.78±3.58)% and (1.01±0.18), higher than (27.23±3.47)% and (0.93±0.14) in control group (P<0.05). Three days after operation, the activated partial thromboplastin time (APTT) in laparoscopic group was (26.55±2.56) seconds, shorter than (27.86±2.73) seconds in traditional group, while the levels of fibrinogen (FIB) and D-dimer were (4.24±0.84) g/L and (377.91±47.19) µg/L, higher than (3.88±0.75) g/L and (330.28±45.11) µg/L in traditional group (P<0.05). The 5-year survival rate was 77.5% in traditional group and 72.4% in laparoscopic group, without significant difference (P>0.05). Multivariate analysis showed that lymph node metastasis was the independent risk factor for prognosis of laparoscopic radical gastrectomy (P<0.05). Conclusions: Laparoscopic radical gastrectomy can effectively reduce postoperative immunosuppression, but affect postoperative coagulation function. Lymph node metastasis is closely related to the prognosis of patient with gastric cancer. The patient's condition should be comprehensively evaluated before and after operation to determine whether the laparoscopic operation is suitable, for reducing postoperative complications and improving the prognosis.

Myeloablative conditioning regimens with combined of haploidentical and cord blood transplantation for myelodysplastic syndrome patients.

The purpose of this study was to evaluate the strategy of haploidentical (HID) stem cell combined with a small doses of umbilical cord blood (UCB) from a third-party donor transplantation (haplo-cord transplant) for treatment of myelodysplastic syndromes (MDS), by comparing with identical-sibling donor (ISD) transplantation. Eighty-five patients were included between January 2012 and December 2015, with a median 40 years old. Forty-eight patients received haplo-cord transplant and 37 patients received ISD transplant. Haplograft engraftment succeeded in all haplo-cord patients. For haplo-cord and ISD transplantation, adjusted cumulative incidences of grades 2-4 acute GvHD at 100 days were 27 and 11% (P=0.059); adjusted cumulative incidences of chronic GvHD at 2 years were 22 and 34% (P=0.215). The 2-year adjusted probabilities of overall survival were 64 and 70% (P=0.518), and of relapse-free survival were 56 and 66% (P=0.306). The 2-year adjusted cumulative incidences of relapse were 12 and 14% (P=0.743), and of non-relapse mortality were 33 and 23% (P=0.291). In conclusion, haplo-cord-HSCT achieves outcomes similar to those of ISD-HSCT for MDS and the haplo-cord-HSCT may potentially improve the outcome of HID- and UCB-HSCT alone. Thus, the haplo-cord transplantation may be a better valid alternative for MDS when an ISD is not available.

[Clinical analysis of 7 patients with Epstein-Barr virus encephalitis after allogeneic hematopoietic stem cell transplantation].

Objective: To summarize the clinical features, treatment and prognosis of patients with Epstein Barr virus (EBV) encephalitis after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: The clinical data of 7 patients with EBV encephalitis who had undergone allo-HSCT in the First Affiliated Hospital of Soochow University from January 2012 to December 2015 were reviewed. Results: The incidence of EBV encephalitis was 0.70% (7/998) , and the median time was 63 (10-136) d after allo-HSCT. Seven patients had fever and mental disorder, of whom 4 cases of brain MRI were positive. Two patients received HLA-matched unrelated transplantation, while other 5 ones received haploidentical allo-HSCT. In conditioning regimen process, 7 patients were combined with anti-thymocyte globulin (ATG) to prevent graft versus host disease (GVHD) , of whom 6 patients had grade Ⅱ-Ⅳ acute GVHD. All patients of EBV-DNA were negative in CSF after taking anti-virus agent Rituximab. Until the last follow-up, a total of 3 patients died, 2 died of leukemia recurrence, 1 EBV encephalitis progression. Conclusion: Once suspected EBV encephalitis after allo-HSCT, brain MRI and EBV-DNA in CSF should be detected, which could improve early diagnosis of EBV encephalitis. The usage of Rituximab was effective and well tolerated.

[A retrospective analysis of prognosis in favorable-risk acute myeloid leukemia patients with different consolidation regimens].

Objective: To explore the impact on prognosis in favorable-risk acute myeloid leukemia (AML) patients with different consolidation regimens after first complete remission (CR(1)). Methods: A total of 107 cases of non-refractory adult AML from January 2010 to June 2015 in single center were enrolled in the study. HD-Ara-C group (38 cases) as the control group, we explore the prognosis in three consolidation regimens, including micro-transplantation (16 cases) , autologous transplantation (auto-PBSCT, 14 cases) , allogeneic transplantation (allo-HSCT, 39 cases). Results: Of 107 patients (59 males and 48 females) , with a median age of 33 (16-59) years old and a median follow-up of 36.5 (5.3-79.1) months, the overall relapse rate was 20.6% (22/107) , and overall mortality rate was 18.7% (20/107). The 5 years cumulative relapse rate (CIR) of HD-Ara-C, micro-transplantation, auto-PBSCT and allo-HSCT group were 39.7%, 6.2%, 14.3% and 5.6%, respectively (P<0.001). The CIR of the observed group was lower than the HD-Ara-C group. The 5 years progression-free survival (PFS) rate of HD-Ara-C, micro-transplantation, auto-PBSCT and allo-HSCT group were 44.7%, 93.8%, 85.7% and 78.1%, respectively (P=0.011). The PFS of observed groups were similar, but superior to that in HD-Ara-C group. The 5-year overall survival (OS) in four groups was 54.9%, 100%, 92.9% and 77.4%, respectively (P>0.05). Multiple factors analysis showed that compared to HD-Ara-C regimen, allo-HSCT could improve PFS (HR=0.376, P=0.031) , but not OS (P>0.05) ; micro-transplantation and auto-PBSCT could not improve the PFS or OS (P>0.05). Conclusion: As compared with HD-Ara-C regimen, allo-HSCT could obviously decrease CIR, improve PFS, but treatment-related mortality is high. These results show that auto-PBSCT and micro-transplantation have similar outcomes, compared to HD-Ara-C regimen, so both can be used as a option of consolidation treatment for favorable-risk AML.

[Establishment and assessment of a nomogram for predicting the differentiation syndrome of acute promyelocytic leukemia].

Objective: By analyzing the risk factors for occurrence of differentiation syndrome (DS) during induction therapy in newly-diagnosed acute promyelocytic leukemia (APL) patients, a prediction nomogram for DS was established and the accuracy of this nomogram was validated. Methods: The modeling group was made up of 130 classical APL patients during the period of 1st January 2011 to 31st December 2013. After single factor screening of clinical variables, the logistic regression model was used to identify the final model variables. A nomogram subsequently established by R software was validated by Bootstrap resampling as internal validation. Concordance index (C-index) was used for the accuracy evaluation of the nomogram, and calibration curves were painted to test the actual observation and the nomogram-prediction of occurrence rate of DS. Results: Occurrence rate of DS in 130 APL patients was 30.0%; In multivariate analysis, body mass index (BMI) ≥24 kg/m2 and without using steroids for prevention of DS were identified as independent risk factors. The C-index of the nomogram for predicting DS was 0.818 (95% CI 0.741-0.895). The calibration curves showed good concordance of occurrence rate of DS between nomogram-prediction and actual observation. Conclusion: The nomogram was successfully established as a more accurate and visible tool for predicting the occurrence rate of DS in APL patients.

Genetic variations in the UTR of genes related to molting in Eriocheir sinensis.

Crab grows by periodic molting, which is controlled by molt-inhibiting hormone (MIH) and ecdysteroids. Untranslated regions (UTRs) play crucial roles in the posttranscriptional regulation of gene expression. In this study, using crab collected from Changjiang (Yangtze), Huanghe (Yellow), Liaohe, and Yalujiang rivers, 33 haplotypes of the 3ꞌ-UTR of ecdysteroid-regulated protein (ERP) gene were identified, of which 14 haplotypes were observed in more than one individual. One hundred and forty clones of haplotype h2 (41.5%) were observed in samples from all the 4 rivers. Three haplotypes were observed to be insertions. For the whole crab sample, we found a positive Tajima's D value and a negative Fu's Fs test (Tajima's D value = 0.98726; Fu's Fs test = -27.382), although the P values were not significant (P > 0.10). The network profile of these 33 haplotypes presented a single core pattern with h2 as the core. In this study, we found that the UTR of ERP gene had a considerably high genetic polymorphism among crab from regions south to north of China. Furthermore, we observed a relatively high genetic divergence among different haplotypes, which would suggest a high diversity of the crab gene pool.

A C-type lectin fold gene from Japanese scallop Mizuhopecten yessoensis, involved with immunity and metamorphosis.

C-type lectins are a superfamily of Ca(2+)-dependent carbohydrate-recognition proteins that are well known for their participation in pathogen recognition and clearance. In this study, a putative C-type lectin fold (MyCLF) gene was identified from the Japanese scallop Mizuhopecten yessoensis. The full-length of MyCLF was 645 bp, encoding a polypeptide of 167 amino acids. MyCLF carried a signal peptide of 20 amino acid residues, and a single carbohydrate recognition domain, having relatively high amino acid sequence conservation with C-type lectins reported for other bivalves. The expression of MyCLF mRNA transcripts in adult tissues, after bacterial challenge and during different developmental stages was determined using real-time quantitative RT-PCR. MyCLF was mainly distributed in the mantle, gill, and kidney. The expression of MyCLF clearly increased 3 h after Vibrio anguillarum challenge, and dropped to a minimum level after 9 h compared to the control group. During embryonic development, the expression level increased in the gastrulae, trochophore and early D-shaped larvae, decreased in D-shaped larvae, and then increased hundreds of times in metamorphosing larvae. The results suggested that MyCLF was involved in an immune response and it may play important roles during the metamorphosis phase of M. yessoensis.

IL-8 -251T/A polymorphism is associated with susceptibility to acute pancreatitis.

We conducted a case-control study to clarify the asso-ciations between inflammatory cytokine, including interleukin (IL)-1b, IL-6, IL-8, and IL-10, polymorphisms and risk of acute pancreatitis. Genotyping analyses of IL-1ß+3954 C/T (rs1143634), IL-1ß-511 C/T (rs16944), IL-6 -174 G/C (rs1800795), IL-6 -634 C/G (rs1800796), IL-8 -251T/A (rs4073), IL-10 -1082A/G (rs1800896), and IL-10 -819C/T (rs1800871) were conducted using polymerase chain reaction-restriction fragment length of polymorphism. Unconditional logistic regression analysis was utilized to assess the potential association be-tween genotype frequencies and risk of acute pancreatitis. Multivari-ate regression analyses showed that subjects carrying the IL-8 -251 AA genotype had a significantly increased risk of acute pancreatitis, with an adjusted odds ratio (95% confidence interval) of 1.55 (1.02-2.36). However, we found no significant association between IL-1ß +3954 C/T, IL-1ß -511 C/T, IL-6 -174 G/C, IL-6 -174 G/C, IL-6 -634 C/G, IL-10 -1082A/G, or IL-10 -819C/T polymorphisms and risk of acute pancreatitis. We found that the IL-8 -251T/A polymorphism was associated with a higher susceptibility to acute pancreatitis in a Chinese population.

Identification and expression analysis of cDNA encoding chitinase-like protein (CLP) gene in Japanese scallop Mizuhopecten yessoensis.

Chitinase-like proteins (CLP) are important members of the glycoside hydrolase family 18 (GH18) and are involved in growth control and remodeling processes. In this study, a CLP transcript was isolated and sequenced from the Japanese scallop (Mizuhopecten yessoensis) after screening expressed sequence tags. The full-length complementary DNA of M. yessoensis CLP (My-Clp1) was 1555 bp in length, consisting of a 75-bp 5'-untranslated region (UTR), a 160-bp 3'-UTR, and a 1320-bp open reading frame bearing characteristics of the GH18 family. The My-Clp1 protein was well conserved, with similar domain structures and architecture across species (e.g., from mollusks to mammals). Expression analysis in healthy tissues and across developmental stages revealed a strong preference for expression; My-Clp1 was abundantly expressed in the mantle and throughout metamorphosis, which suggests the involvement of My-Clp1 in the synthesis of extracellular components, and tissue degeneration and remodeling. My-Clp1 expression was induced after infection with a bacterial pathogen, Vibrio anguillarum, suggesting its involvement in immunity against this intracellular pathogen.

Meta-analysis of the differentially expressed colorectal cancer-related microRNA expression profiles.

OBJECTIVES: Unique microRNAs (miRNAs) have been identified in colorectal cancer in recent studies which can be used to accurately diagnose the presence of colorectal cancer and help predict disease recurrence. Differential expression of specific miRNAs in tissues or blood offers the prospect of their use in early detection and screening for colorectal cancer. However, the experiments under different environments would produce different results. The purpose of this study was to get a reliable result on differentially expressed miRNAs related to colorectal cancer by integrating different studies. MATERIALS AND METHODS: A meta-analysis was performed to review three miRNA microarray datasets from three published literatures that compared the microRNAs expression profiles in colorectal cancer tissues with those in normal colorectal tissues. The R VennDiagram package was applied to identify the overlapping miRNAs with differential expression among these three studies. RESULTS: A total of 175 differentially expressed miRNAs were reported in the three miRNA expression profiling studies that compared colorectal cancer tissues with normal tissues, of which 25 miRNAs were reported at least by two studies including 15 up-regulated miRNAs and 10 down-regulated miRNAs. Among the 25 miRNAs, 15 ones were differentially expressed between early stage colorectal cancer and normal tissues including 11 up-regulated miRNAs and 4 down-regulated miRNAs, of which hsa-miR-195 (down-regulated) and hsa-miR-20a (up-regulated) were shared by these three studies. CONCLUSIONS: The 15 differentially expressed miRNAs, especially hsa-miR-195 and hsa-miR-20a may be used as potential biomarkers for early detection and screening of colorectal cancer.