Objective To analyze the treatment outcome and related influencing factors of Tibet- an nationality new smear-positive pulmonary tuberculosis patients in Qinghai Province，so as to provide evidence for tuberculosis control and treatment among Tibetan population． Methods Statistical analysis was conducted on 5 564 Tibetan nationality new smear-positive pulmonary tuberculosis cases in Qinghai province who were reported in the China Tuberculosis Information Management System and approved to receive treatment from 2008 to 2017． The main influencing factors were detected by unconditional Logistic regression model analysis，dependent variable was successful treatment or not，independent variables were other factors related to the treatment outcome． Ｒesults The treatment success rate of Tibetan nationality new smear-positive pulmonary tuberculosis cases was 87. 1% ( 4 848 /5 564) ，and the adverse outcome rate was 12. 9% ( 716 /5 564) ． Unconditional Logistic regression model analysis indicated that non-full- course supervision management，living in agricultural and pastoral area，having severe disease，floating population，and age older than 60 years were risk factors of adverse outcome． The odds ratio( OＲ) 95% confidence interval( CI) of the above risk factors were 13. 044( 10. 671-15. 944) ，2. 305( 1. 703-3. 119) ， 2. 090( 1. 346-3. 243) ，1. 967( 1. 443-2. 682) ，and 1. 909( 1. 410-2. 586) ． Clinical consultation，farmers and herdsmen were protective factors． The OＲ( 95% CI) were 0. 451( 0. 375-0. 543) ，and 0. 786( 0. 627- 0. 985) ． Conclusions Treatment success rate of Tibetan nationality new smear positive pulmonary tuberculosis cases was low． Therefore，the directly observed treatment short-course ( DOTS) strategy should be strictly implemented and the full-course supervision management should be strengthened to improve the treatment success rate． More attention should be paid to the elderly，severe，floating，agricultural and pastoral populations among the Tibetan population．

Objective To investigate the effects of vitamin D mediated mitogen-activated protein kinase(MEK)/extracellular signal-regulated kinase(ERK)pathway on myocardial injury in rats with gestational diabetes mellitus.Methods Fifty SD rats were divided into control group,model group,experimental-L group,experimental-M group and experimental-H group,and the gestational diabetes rat model was established.After successful modeling,experimental-L,experimental-M,experimental-H groups were given intragastric administration of 0.05,0.10 and 0.15 μg·kg-1 concentration of vitamin D,while control group and model group were given intragastric administration of 0.9％NaCl at the same dose once a day for 2 weeks.Fasting blood glucose concentration and insulin level were detected before intervention,1 week and 2 weeks after intervention.Echocardiography was used to detect cardiac function[left ventricular ejection fraction(LVEF),maximum rate of rise(+dp/dtmax)and maximum rate of decline(-dp/dtmax)of left ventricular pressure].Myocardial enzyme indexes[troponin Ⅰ(cTn Ⅰ)kit,creatine kinase isoenzyme(CK-MB)]and inflammatory factors[tumor necrosis factor-α(TNF-α),C-reactive protein(CRP)]in serum and myocardial tissue of rats were detected by enzyme-linked immunosorbent assay(ELISA),and MEK/ERK pathway protein expression was detected by western blot.Results The levels of cTn Ⅰ in cardiac tissue of control group,model group,experimental-L group,experimental-M group,experimental-H group were(10.50±1.08),(42.26±4.30),(31.85±2.44),(23.31±2.15)and(14.85±1.19)ng·mL-1;serum cTn Ⅰ levels were(23.79±3.46),(63.59±5.52),(51.02±4.27),(42.75±3.19)and(29.20±2.11)ng·mL-1;myocardial tissue levels of CK-MB were(8.52±0.90),(17.65±1.75),(15.62±1.27),(13.11±1.24)and(9.85±0.87)ng·mL-1;serum levels of CK-MB were(11.32±0.98),(21.24±1.45),(18.75±1.32),(15.11±1.02)and(12.27±1.11)ng·mL-1;phosphorylated-MEK protein expression were 0.24±0.03,0.85±0.09,0.72±0.06,0.57±0.07 and 0.35±0.04;phosphorylated-ERK1/2 protein expression were 0.18±0.02,0.66±0.07,0.52±0.06,0.40±0.07 and 0.24±0.05,respectively.There were statistically significant differences of above indexes between control group and model group(all P＜0.05);the difference between model group and experimental-L,experimental-M,experimental-H groups were all statistically significant(all P＜0.05).Conclusion Vitamin D may reduce myocardial injury in rats with gestational diabetes by inhibiting the activation of MEK/ERK pathway.

Hepatitis E, an acute infectious disease transmitted via the fecal-oral route, is caused by hepatitis E virus. However, no effective treatment currently exists for hepatitis E, and the only epidemic control approach is vaccination. But so for there are no commercial vaccine for hepatitis E available in the world. To find a new expression system to develop recombinant hepatitis E vaccine, in this study the expression system of methylotrophic yeast Hansenula polymorpha was used to express the gene encoding amino acid 112 - 607 of the open reading frame 2 (ORF2) of hepatitis E virus (HEV) genotype IV. In order to achieve high expression level, the coding sequence was optimized according to codon usage bias of Hansenula polymorpha and synthesized through overlapping PCR. Subsequently the gene was subcloned into the multi-copy expression vectors of Hansenula polymorpha, which include pDGXHP1.0 (MOX promotor), pDGXHP2.0 (MOX promotor) and pDGXHP2.1 ( FMD promotor). The series of one-copy and multi-copy recombinant plasmids were transformed into ATCC26012(Ura3-) by electroporation. The transformants were cultured in selection media MDL and screened for the existence of foreign gene by PCR. Then the strains were induced in MM media and the expression products were detected by SDS-PAGE, ELISA and Western blot assays to select the high-level expression strains. The result of SDS-PAGE showed that the HEV ORF2 expression product was accumulated up to 12% of total cellular protein and its molecular weight is 56kD. The expression product showed high immunoreactivity detected by ELISA and the highest titer is 1:2048. The result of Western blot demonstrated that the expression product could be specifically recognized by the polyclonal antibody against HEV. The successful expression of HEV ORF2 protein in Hansenula polymorpha provides foundation for the further development of recombinant subunit vaccine against hepatitis E.
Blotting, Western ; Electrophoresis, Polyacrylamide Gel ; Enzyme-Linked Immunosorbent Assay ; Gene Expression Regulation, Viral ; Genotype ; Hepatitis E ; immunology ; virology ; Hepatitis E virus ; genetics ; immunology ; metabolism ; Humans ; Pichia ; genetics ; Polymerase Chain Reaction ; Recombinant Proteins ; immunology ; metabolism ; Viral Hepatitis Vaccines ; immunology ; Viral Proteins ; genetics ; immunology ; metabolism

OBJECTIVETo evaluate the incidence and risk factors for severe retinopathy of prematurity (ROP) in preterm infants.

METHODSBetween May, 2008 and May, 2011, a total of 957 preterm infants at 4-6 weeks of chronological age or 32 weeks of postmenstrual age underwent retinal evaluation by RetCamII in our center, and the data of infants with ROP in any stage were analyzed.

RESULTSAmong the 957 preterm infants, we found 86 (8.99%) infants to have ROP in different stages, including 60 (6.27%) with mild ROP and 26 (2.72%) with severe ROP. The birth weight and gestational age of the infants with severe ROP averaged 1 420.40∓328.64 g and 29.88∓1.67 weeks, as compared to 1 593.28∓339.30 g and 31.78∓2.53 weeks in those with mild ROP, respectively, showing a significant difference between the two groups (P<0.005). The significant variables for severe ROP included gestational age (P=0.001), birth weight (P=0.035), 1 min Apgar score (P=0.001), 5 min Apgar score (P=0.005), number of blood transfusions (P=0.032), and the presence of apnea (P=0.04) and retinal hemorrhage (P=0.000). Gestational age and retinal hemorrhage were the independent risk factors for severe ROP (OR=0.353, 95%CI 0.163-0.763, P=0.008; OR=26.133, 95%CI 3.042-224.501, P=0.035).

CONCLUSIONSevere ROP tends to have a decreasing incidence and occurs more often in more mature preterm infants. The affected infants have the characteristics of the first epidemics. Gestational age and retinal hemorrhage are independent predictive factors for severe ROP.

Birth Weight ; China ; epidemiology ; Female ; Gestational Age ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Logistic Models ; Male ; Neonatal Screening ; Retinal Hemorrhage ; complications ; Retinopathy of Prematurity ; epidemiology ; etiology ; Retrospective Studies ; Risk Factors

Objective To analyze the epidemic situation and characteristics of spatial autocorrelation and spatiotemporal regular of hand，foot and mouth disease( HFMD) in Yunnan Province during the period from 2014 to 2018，thus to provide theoretical basis for HFMD prevention and control． Methods Descriptive epidemiologic method was used to analyze the epidemic situation of HFMD，spatial autocorrela- tion was used to analyze the spatial cluster aggregation，and discrete Possion model in spatio－temporal in scan was used to detect HFMD＇s spatio－temporal clustering condition． Ｒesults The incidence of HFMD in Yunnan Province had been risen rapidly during the past 5 years． Cases mainly occurred among the group of male，0－4 years old group and scattered children． The predominant pathogen had changed，Other enterovir- us gradually replaced enterovirus 71( EV71) to be the predominant． HFMD cases and pathogen showed sig- nificant spatial clustering aggregation，HFMD cases hot spots mainly concentrated in the central and south－ central part of Yunnan Province． The amount of EV71 cases hot spots increased gradually，and the hot spot areas augmented and extended to the central and south－central part of Yunnan Province． There was obvious spatial－temporal aggregation of HFMD，annual scan results detected 3 first－level cluster areas and 1 second －level cluster area． Clustering time was mainly concentrated in April to October of each year． Conclusions Distribution characteristics of HFMD among people in Yunnan Province did not change significantly during the period from 2014 to 2018，while the proportion of pathogenic spectrum changed significantly． The key areas of HFMD control and prevention were still in the central and central－south part of Yunnan Province，while the aggregation and break of HFMD in these areas from April to October should be concerned．

Objective To identify differentially expressed proteins in cerebrospinal fluid (CSF) of Parkinson's disease (PD), so as to provide clues for investigating PD biomarkers. Methods Two-dimensional difference gel electrophoresis (2D DIGE) technique, in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), was used to determine the differentially expressed CSF proteins in PD patients in comparison with control subjects. Results The levels of 20 protein spots were significantly altered in PD CSF. Of them, 11 spots were up-regulated and 9 spots were down-regulated. Of the 8 proteins identified in the profile of differentially expressed protein spots between patients and controls, an isoform of apolipoprotein A-I, myosin phosphatase target subunit 1 (MYPT1), and 3 unknown proteins were down-regulated, whereas an apolipoprotein A-I isoform, proapolipoprotein, and lipoprotein were up-regulated. Conclusions MYPT1 is related with synapse function and proapolipoprotein, lipoprotein and apo A-I are associated with cholesterol metabolism. These proteins may have links with the pathogenesis of PD and may be identified as CSF biomarks in PD.

OBJECTIVETo explore the impact of IFN-γ + 874 polymorphisms on the outcome in HLA matched sibling HSCT.

METHODSWe used PCR-sequence-specific primer analysis (PCR-SSP) to analyze the polymorphisms of IFN-γ + 874 T/A in 80 recipient and donor pairs from October 2005 to March 2008.

RESULTSRecipients having donors who possessed IFN-γ + 874 A/A genotype had significantly earlier neutrophil recovery compared with those having donors with non-A/A genotype (15 (11 - 27) days vs 18 (12 - 30) days, P = 0.029). And IFN-γ + 874 A/A in both recipients and donors further facilitated neutrophil recovery compared with others (13 (11 - 25) days and 19 (12 - 31) days, P = 0.019). Besides, IFN-γ + 874 A/A in recipients increased the probability of grade II-IV acute graft versus disease (aGVHD) and cytomegalovirus viraemia compared with IFN-γ + 874 T/A or T/T genotype (20% vs 4% P = 0.041, 43.6% vs 16.0% P = 0.032), which lead to increased 5-year transplant-related mortality (TRM) (33.7% ± 6.8% vs 12.0% ± 6.5%, P = 0.050) and decreased 5-year event free survival (EFS) \[(58.2 ± 6.7)% vs (84.0 ± 7.3)%, P = 0.032\] compared with the latter. IFN-γ + 874 A/A in both recipients and donors also significantly increased the probability of grade II-IV aGVHD and cytomegalovirus viraemia compared with the other (21.7% vs 5.9%, P = 0.050; 45.7% vs 20.6%, P = 0.020), which caused increased 5-year TRM \[(31.6 ± 7.5)% vs (13.6 ± 6.5)%, P = 0.048\] and decreased 5-year EFS \[(56.8 ± 7.3)% vs (79.4 ± 6.9)%, P = 0.037\] compared with the other.

CONCLUSIONIn HLA-matched sibling HSCT setting, the presence of IFN-γ + 874 T allele in recipients or in both recipients and donors significantly decreased the risk of grade II-IV aGVHD and CMV infection and increased EFS. While IFN-γ + 874 A/A in donors or in both recipients and donors was associated with shorter duration to neutrophil recovery.

Adolescent ; Adult ; Alleles ; Child ; Child, Preschool ; Female ; Genotype ; HLA Antigens ; immunology ; Hematologic Diseases ; genetics ; therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Interferon-gamma ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Siblings ; Tissue Donors ; Transplantation, Homologous ; Treatment Outcome ; Young Adult

Chronic myeloid leukemia (CML) at advanced and blastic phase is a disease with poor prognosis, for which allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment choice with curative potential. This study was purposed to investigate the therapeutic efficacy of allo-HSCT and prognosis of advanced CML patients. The 28 cases of CML in accelerated phase or blast crisis received allo-HSCT were analysed retrospectively in terms curative efficacy, basic characteristics before transplant and prognosis, therapeutic strategy before transplant and prognosis, events after transplant and prognosis. The results indicated that 10 out of 28 patients were in complete remission, showing a 3-year overall survival and disease-free survival rate of 34.9% and 35.7% respectively; 18 patients died. Univariate analysis revealed that the clonal evolution and blast amount are baseline risk factor of poor prognosis, and combination of them can be used to predict the outcome of patients; application of imatinib before transplant and achievement of complete hematologic remission could not improve the prognosis; severe aGVHD among post-transplant events was proven to be a negative prognostic factor. It is concluded that for advanced CML patients received allo-HSCT, clonal evolution and blast percentage are prognostic factors, and the pre-transplant use of imatinib did not influence the outcome.
Adolescent ; Adult ; Benzamides ; Child ; Child, Preschool ; Female ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; surgery ; therapy ; Male ; Middle Aged ; Piperazines ; therapeutic use ; Prognosis ; Pyrimidines ; therapeutic use ; Retrospective Studies ; Young Adult

OBJECTIVETo investigate the incidence, risk factors, prognosis and high risk patients of invasive fungal infections (IFI) in patients with hematological diseases.

METHODS: Over 2-week hospitalized patients from January 2007 to December 2008 were retrospectively reviewed. Logistic regression was used to analyze the risk factors of IFI, and recursive partitioning to reveal high risk patients. Incidence of IFI was estimated by cumulative incidence function, and the prognosis by Kaplan-Meier method.

RESULTSA total of 1048 assessable treatment cycles were recorded and 93 cases of IFI were diagnosed, with an incidence of 8.87 per 100 treatment cycles. Multivariate logistic regression revealed the following risk factors: age (OR 1.025, 95% CI 1.010-1.041, P = 0.002), duration of neutropenia (OR 1.028, 95% CI 1.014-1.042, P < 0.0001) and uncontrolled underlying diseases (OR 2.620, 95% CI 1.608-4.268, P = 0.0001). Recursive partitioning found two groups of high risk patients: (1) patients with uncontrolled underlying diseases and neutropenia duration > or = 58 days (7/12, 58.3%), (2) patients with uncontrolled underlying diseases and age > or = 33 years (40/208, 19.2%). At the end of follow-up, 111 cases of IFI were recorded in 451 patients, with a 1-year cumulative incidence of 27.1%. In patients with established IFI, overall survival rate and IFI related mortality rate at 12 weeks after diagnosis were 83.4% and 13.5% respectively.

CONCLUSIONAge, duration of neutropenia and uncontrolled underlying diseases are risk factors of IFI; patients with uncontrolled underlying diseases and age > or = 33 years were at high risk of IFI and need major concern. IFI has a better prognosis and a lower related mortality in this study.

Female ; Hematologic Diseases ; diagnosis ; microbiology ; therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Incidence ; Logistic Models ; Male ; Multivariate Analysis ; Mycoses ; epidemiology ; Prognosis ; Retrospective Studies ; Risk Factors

This study was purposed to evaluate the outcome of patients with acute myeloid leukemia (AML) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in complete remission, and to study the prognostic factors. 75 cases of AML in complete remission receiving allo-HSCT from January 2000 to December 2007 were retrospectively analyzed. Major end points of study included overall survival (OS), disease free survival (DFS), relapse rate and transplantation related mortality (TRM). The results showed that 3-year OS and DFS of the study population reached to 58.4% and 53.9% respectively, and the relapse rate and TRM leaded to 16.9% and 29.9% respectively. Incidence of acute GVHD was 59.6%, with 18.7% II-IV aGVHD. Different prognosis was observed between HSCT recipients of alternative donor and HLA-matched related donor (MRD) (3-year DFS was 34.3% vs 60.0%, p = 0.019), between patients of refractory leukemia and the control (3-year DFS was 35.7% vs 58.2%, p = 0.048), between recipients with and without severe aGVHD (3-year DFS was 35.7% vs 54.4%, p = 0.059). Further analysis revealed significantly high TRM in recipients receiving allo-HSCT of alternative donor (p = 0.033) and high rate of severe aGVHD (p = 0.010). Multivariate analysis revealed three negative prognostic factors: donor availability (alternative vs MRD) (p = 0.049, RR = 2.09, 95%CI 1.01 - 4.36), refractory leukemia (p = 0.038, RR = 2.33, 95%CI 1.05 - 5.20) and severe aGVHD (p = 0.040, RR = 2.33, 95%CI 1.04 - 5.20). It is concluded that allo-HSCT is a choice for the AML case at complete remission and TRM is the major cause of the transplantation failure. Donor availability, refractory leukemia and severe aGVHD are confirmed as risk factors of poor prognosis for allo-HSCT patients with AML in CR.
Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Graft vs Host Disease ; etiology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Humans ; Leukemia, Myeloid, Acute ; mortality ; surgery ; Male ; Middle Aged ; Prognosis ; Recurrence ; Risk Factors ; Treatment Outcome ; Young Adult