OBJECTIVE: To provide clinical basis for the diagnosis and treatment of chronic neutrophilic leukemia (CNL) and to provide possible molecular targets for the treatment. METHODS: By summarizing the clinical data of 14 patients with CNL, the clinical characteristics, gene mutation types and possible prognostic factors were analyzed. RESULTS: Among the 14 patients with CNL, males (9 cases) were more than females (5 cases), with a median age of 57 years old. The detection rate of CSF3R mutation was 92.86% (13/14), including 12 cases (85.71%) with T318I mutation and 1 case of Y799X mutation, and only 1 case was not detected for mutation of CSF3R. The ASXL1 mutation was detected in 42.86% (6/14) of the patients, all of which were nonsense mutations, including 4 cases with R693X and 2 cases with E705X, and 14.29% (2/14) of the patients was detected for SETBP1 mutation, all of which were with D868N mutation. No patients with simultaneous ASXL1 and SETBP1 mutations were found, and JAK2 and CALR mutations were not detected. All of the patients had normal karyotypes. These patients' median survival time was 30 months (95%CI 13.19-46.80), and the influence of age over 60 years old was statistically significant (21.83 months vs 35.35 months) (P＜0.05). CONCLUSION It is difficult to diagnose CNL. CSF3R T618I mutation is its specific mutation, and ASXL1 mutation and SETBP1 mutation have auxiliary diagnostic significance for CNL. The age＞60 years old at diagnosis is a factor of unfavourable prognosis.

OBJECTIVE: To delineate laboratory and clinical characteristics of a case with chronic myelogenous leukemia (CML) and co-occurrence of t(9;22)(q34;q11) and t(8;21)(q22;q22). METHODS: The patient was subjected to cytogenetic, molecular, morphological and immunophenotypic analyses. RESULTS: Cytogenetic analysis revealed presence of t(8;21)(q22;q22) in addition to t(9;22)(q34;q11) in the patient. Chimeric BCR/ABL and AML1/ETO genes were detected by fluorescence in situ hybridization (FISH). Transcripts of BCR/ABL210 and AML1/ETO fusion genes were detected by relative quantity PCR. Morphological study suggested that the patient was at the chronic phase of CML. No significant immunophenotypic abnormality was detected by flow cytometry. CONCLUSION Co-occurrence of t(8;21)(q22;q22) and t(9;22)(q34;q11) is rare in CML. Only 5 similar cases have been described previously. This case suggested that chromosomal alterations may precede morphological, flow cytometric and clinical changes and accelerate progression of the disease.
Chromosome Aberrations ; Chromosomes, Human ; Fusion Proteins, bcr-abl ; Humans ; In Situ Hybridization, Fluorescence ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; Translocation, Genetic

OBJECTIVE: Identification of new risk factors is needed to improve prediction of adverse outcomes in patients with three-vessel disease (TVD). The present study aimed to evaluate the prognostic values of serum chloride and sodium levels in patients with TVD. METHODS: We used data from a prospective cohort of consecutive patients with angiographically confirmed TVD. The primary endpoint was all-cause death. Cox proportional hazard regression was used to analyze the relationship of serum chloride and sodium levels with long-term outcomes of TVD patients. RESULTS: A total of 8,318 participants with available serum chloride and sodium data were included in this analysis. At baseline, patients in the low tertiles group of serum chloride level (⪕ 102.0 mmol/L) or serum sodium level (⪕ 139.0 mmol/L) had more severe disease conditions. During a median follow-up of 7.5-year, both low serum chloride level and low serum sodium level were found to be associated with an increased risk for mortality in univariate analysis. However, when both parameters were incorporated into a multivariate model, only low serum sodium level remained to be an independent predictor of all-cause death (hazard ratio: 1.16, 95% confidence interval: 1.01-1.34, P = 0.041). Modest but significant improvement of discrimination was observed after incorporating serum sodium level into the Synergy between percutaneous coronary intervention (PCI) with Taxus and Cardiac Surgery score. CONCLUSION Serum sodium level is more strongly associated with long-term outcomes of TVD patients compared with serum chloride level. Low serum sodium level is an independent risk factor for mortality, but only provides modest prognostic information beyond an established risk model.
Aged ; China ; epidemiology ; Chlorides ; blood ; Coronary Artery Disease ; blood ; diagnosis ; mortality ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Sodium ; blood

OBJECTIVE: To explore clinical effect of VSD technology, coverage of artificial dermis and autograft for the treatment of limb skin soft tissue defect combined with bone or tendon exposed wound. METHODS: Eighteen patients suffered from limb skin soft tissue defect combined with bone or tendon exposed wound treated by three-step sequential method from January 2013 to June 2015. Among them, including 13 males and 5 females aged from 23 to 72 years old with an average of 34.6 years old; the time from injury to operation ranged from 1.5 to 5.0 hours with an average of 2.5 h. The area of skin and soft tissue injury ranged from 4.2 cm×3.1 cm to 7.4 cm×5.2 cm. Wound recovery and taken skin wound recovery were observed to evaluate clinical results. RESULTS: All patients were followed up from 5 to 16 months, with an average of 7.6 months. Deep bone tendon tissue of wounds were effectively recovered, artificial dermis survived, and quality of healed wound was tough and shape was good. Wound transplant flap was survived, no obvious scar tissue formation, appearance was flat, skin color was a little deeper than normal skin, the overall effect was satisfactory. CONCLUSIONS Three-step sequential method has good curative effect for patients suffered from limb skin soft tissue defect with bone or tendon exposed wound and refused to repair the flap, and has advantage of simple operation, operation risk, less invasive.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; Skin Transplantation ; Soft Tissue Injuries ; Surgical Flaps ; Tendons ; Treatment Outcome ; Young Adult

OBJECTIVE: To analyze the incidence, hemogram, genetics, clinical manifestations, therapeutic efficacy and outcome of patients with myeloproliferative neoplasms(MPN) so as to provide much more therapeutic basis for clinically studying the pathogenesis, diagnosis, and treatment as well as evaluating the prognosis of MPN patients. METHODS: The clinical data and related laboratory test results in 208 cases of BCR/ABL fusion gene regative MPN were collected and analyzed retrospectively. RESULTS: The MPN could occur at any age, but the highest incidence was observed in patients aged 40-79. Among 208 patients with MPN, the patients with essential thrombocythemia(ET) accounted for 48.56%(101/208), the patients with polycythemia vera(PV) accounted for 25.96%(54/208), and the patients with primary myelofibrosis(PMF) accounted for 25.48(53/208). The clinical manifestation of MPN varied, the first manifestations was no-specific, onset of disease presented slow. The JAK2V617F gene mutation existed in 130 out of 208 patients with MPN, total mutation rate was 62.5%;JAK2V617F mutation rate in PV patients was 81.5%(44/54), while that in ET and PMF patients was 58.4%(59/101) and 50.9%(27/53) respectively, the detected rate of this mutation in PV patients was significantly higher than that in ET and PMF patients (P<0.05), while there was no significant difference between ET and PMF patients(P>0.05). In PV group, the WBC count of JAK2V617F positive patients was significantly enhanced (P<0.01), while there were no statistical differences of hemoglobin level and platelet count (P>0.05); in ET and PMF groups, the JAK2V617F positive patients had a higher WBC count and hemoglobin level(P<0.05), while the difference of platelet count was no significant(P>0.05). The most common vascular event in patients with MPN was ischemic cerebrovascular disease. The JAK2V617F mutation related with risk of thrombosis (OR=2.222, 95% CI=1.101 to 4.486). The difference in the incidence of vascular event between ET and PV patients was no statistically significant (P>0.05), but the incidence of vascular event in ET and PV patients was higher than that in PMF patients(P<0.05). The disease conversion much more easily happened in JAK2V617F positive patients. After treatment, the MPN could be controlled, yet the maintained treatment is needed. CONCLUSION The MPN can occur almost at any age, but more commonly occures in middle-aged and elderly persons. The onset of MPN varies, the clinical manifestation was similar, a high detected rate of JAK2V617F mutation is observed in MPN patients and relates closely with onset of MPN; moreover, JAK2V617F mutation rate relates with type of MPN. The MPN patients with JAK2V617F mutation have higher WBC count and higher incidence of thrombosis. After treatment, the MPN can be better controlled, and need maintenance treatment. So as to avoid the reccurence of disease, control the complications and obtain the longterm survival.
Adult ; Aged ; Fusion Proteins, bcr-abl ; Humans ; Middle Aged ; Mutation ; Myeloproliferative Disorders ; Retrospective Studies

OBJECTIVE: To explore surgical methods and clinical effects of three different types of mini skin flap transplantation for repairing finger soft tissue with bone defect. METHODS: Thirty-three patients with finger soft tissue or bone defect were treated from December 2014 to October 2016, including 24 males and 9 females aged from 21 to 52 years old with an average of (36.42±5.70) years old, and soft tissue defect area ranged from 1.3 cm×1.8 cm to 2.3 cm×4.2 cm. According to damage degree, nature and patients' options, 15 finger of 15 cases were adopted retrograde dorsal metacarpal artery perforators fascia flap, 10 fingers of 9 cases were treated with free foot artery descending branch wrist skin flap, 9 fingers of 9 cases were treated with free the second toe details phalanges compound flap. Survival rate, postoperative complications and finger function assessed by Dargan functional criteria at the latest follow up were observed. RESULTS: All flaps were survived, both of donor site and recipient site were without deep infected. The donor site of one patient occurred necrotic, and the distal donor site of one patient occurred surface necrotic, then healed by active dressing change. All patients were followed up from 6 to 16 months with an average of(8.34±1.28) months. Two points of finger recognition were restored between 8 and 12 mm with an average of (8.84±0.43) mm, and the appearance, texture and sensory functions of skin flap were restored. No obvious complications were observed on the donor site. According to Dargan function evaluation of finger joints, 18 patients got excellent results, 14 moderate and 1 good. CONCLUSIONS Three kinds of mini skin flap could receive good results in repairing soft tissue of finger or bone defect. Reverse dorsal metacarpal artery perforator fascia flap is not necessary with anastomosing blood vessels and has advantages of safe, simple and high survival rate. Descending branch of superior cutaneous branch of free ulnar artery could cut multiple other perforator flaps simultaneously, and the scar is small and hidden. Dissociated the second toe combined metatarsal phalangeal flap could repair shape and function of finger to the maximum extent and donor site is hidden.
Adult ; Female ; Finger Injuries ; Humans ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; Skin ; Skin Transplantation ; Soft Tissue Injuries ; Treatment Outcome ; Young Adult

OBJECTIVETo examine one young female patient with hereditary FVII deficiency and her family members, to observe the gene mutation and clinical phenotype, and to investigate the molecular mechanism of the dysfunction.

METHODSProthrombin time (PT), activated partial thromoploastin time (APTT), fibrinogen (Fg) and FVII activity (FVII:C) and FVII antigen (FVII:Ag) were tested. The gene mutations were sought by DNA sequencing for all of the exons and flanks, 5' and 3' non-translation region of F7 gene. To confirm the role of the found gene mutation, the reverse sequence were determined with Chromas software. To infer the influence of the mutation on the synthesis and function of FVII protein, the FVII protein molecule model containing the found mutation was constructed and the function prediction was performed by the signal peptide prediction database.

RESULTSCompared with the normal population, the proband's PT value was significantly prolonged, and the ratio % FVII:C and that of FVII:Ag were significantly decreased by 1.1% and 0.9%, respectively. The PT, APTT, FVII:C and FVII:Ag of the proband's parents were both normal. Heterozygous 556th nucleotide mutations T/G were found in the proband's and his father's exon lA of F7 gene, with codon CTG turning into CGG, corresponding leucine (L) into arginine (R), i.e Leu12Arg. Function prediction showed that L12R mutations affected the segmentation of different parts of the signal peptide and its corresponding function, which could result in the decline in the mature protein synthesis and its activity obviously. In addition, a spontaneous 3' untranslated region c11814-insAA heterozygous mutation was detected in the proband's F7 gene, while her parents didn't possess this mutation.

CONCLUSIONA new hererozygous mutation (L12R) located in signal peptide of F7 gene is the primary molecular basis of the case with hereditary FVII deficiency. At the same time, the proband's spontaneous 3' non-translation region c11814-insAA mutation may lead to the further reduetion of the FVII synthesis.

OBJECTIVETo explore the effects of lentiviral-mediated CXC chemokine receptor-4（CXCR-4）gene over-expression on the homing capacity of mesenchymal stem cells（MSC）in vivo.

METHODSThe MSC overexpressing CXCR-4 were constructed by using the lentiviral vector-mediated mouse MSC overexpressing the CXCR-4 gene. The BALB/c mice were divided into 3 group: simple radiation group（TBI）in which mice exposed to total body irradiation, then were infused with normal saline; EGFP-MSC group in which mice were infused with MSC（5×10）transducted by EGFP via tail vein after TBI; and CXCR-4-MSC group in which mice were infused with MSC (5×10) simultaneously carraying EGFP and CXCR-4 gene via tail vein after TBI. The mice were sacrified at 24 hours after infusion, the frozen sections were prepared to detect the distribution of infused MSC. Furthermore, the numbers of MSC homing into spleen and bone marrow was detected by flow cytometry, and the level of stromal cell-derived factor-1(SDF-1) was detected by ELISA.

RESULTSThe frozen section showed that the CXCR-4 over-expression could significantly enhance the efficacy of MSC homing into lung, liver and spleen; the flow cytonetry detection slowed that the number of over-expressed CXCR-4 MSC homing into spleen and bone matrow was sigmificantly higher than that in EGFP-MSC group（P<0.05）, the ELISA showed that the SDF-1 level in peripheral blood and bone marrow after 24 hours of irradiation significantly incrtaoed （P<0.05）, moreover, the SDF-1 level increase was associcted with horming efficacy of MSC with CXCR-4 overexpression.

CONCLUSIONoverexpression CXCR-4 gene mediated by lentiviral vector can prmote the efficacy of MSC homing into spleen and bone marrow.

BACKGROUNDPatients with premature triple-vessel disease (PTVD) have a higher risk of recurrent coronary events and repeat revascularization; however, the long-term outcome of coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), and medical therapy (MT) alone for PTVD patients is controversial. The aim of this study is to evaluate the long-term outcome of PTVD patients among these three treatment strategies, to find out the most appropriate treatment methods for these patients.

METHODSOne thousand seven hundred and ninety-two patients with PTVD (age: men ≤50 years and women ≤60 years) were enrolled between 2004 and 2011. The primary end point was all-cause death. The secondary end points were cardiac death, myocardial infarction, stroke, or repeat revascularization.

RESULTSPCI, CABG, and MT alone were performed in 933 (52.1%), 459 (25.6%), and 400 (22.3%) patients. Both PCI and CABG were associated with lower all-cause death (4.6% vs. 4.1% vs. 15.5%, respectively, P < 0.01) and cardiac death (2.8% vs. 2.0% vs. 9.8%, respectively, P < 0.01) versus MT alone. The rate of repeat revascularization in the CABG group was significantly lower than those in the PCI and MT groups. After adjusting for baseline factors, PCI and CABG were still associated with similar lower risk of all-cause death and cardiac death versus MT alone (all-cause death: hazard ratio [HR]: 0.35, 95% confidence interval [CI]: 0.23-0.53, P < 0.01 and HR: 0.35, 95% CI: 0.18-0.70, P = 0.003, respectively, and cardiac death: HR: 0.32, 95% CI: 0.19-0.54, P < 0.01 and HR: 0.36, 95% CI: 0.14-0.93, P = 0.03, respectively).

CONCLUSIONSPCI and CABG provided equal long-term benefits for all-cause death and cardiac death for PTVD patients. Patients undergoing MT alone had the worst long-term clinical outcomes.

TRIAL REGISTRATIONClinicalTrials.gov; Identifier: NCT02634086. https://www.clinicaltrials.gov/ct2/show/record/NCT02634086?term=NCT02634086&rank=1.

Aim To evaluate the effects of salvianolic acid B ( Sal B ) on bone metabolism and its potential mechanism in high fat diet ( HFD) mice.Methods Thirty C57BL/6J male mice were divided into three groups with 10 mice each, namely normal , HFD and HFD+Sal B.HFD and HFD+Sal B mice were treated with HFD, and HFD+Sal B group mice were also with Sal B (125 mg· kg -1· d-1).After 12 weeks' treat-ment, femurs were harvested .The effects of Sal B on biomechanical strength were evaluated by biomechani-cal tests, and the effects of Sal B on bone microstruc-ture were evaluated by Safranin O/fast green staining and hematoxylin and eosin staining .The expression of nuclear factor-kappa B ( NF-κB)-p65 and NADPH ox-idase 4 ( Nox4 ) and cathepsin K in femurs was deter-mined by immunohistochemical staining . Results Maximum load and elastic load significantly decreased ,and the trabeculae became thinner and irregular in the femurs of HFD mice , while Sal B treatment could re-verse the descending biomechanical strength and the disorganized femurs bone micro-structures in HFD mice.In addition, the expressions of Nox4, NF-κB-p65 and cathepsin Kmarkedly increased in HFD mice , and Sal B possessed the ability to down-regulate the ex-pression of Nox4, NF-κB-p65, and cathepsin K in the femurs triggered by HFD .Conclusions Sal B treat-ment improves bone metabolism via regulating Nox 4/NF-κB/cathepsin K signaling pathway in HFD mice . The findings contribute to the understanding and exten-sion of the applications of Salvia miltiorrhiza and its constituents on osteoporosis .