Risk factors and treatment outcomes of rifampicin-resistant tuberculosis in Guizhou Province from 2014 to 2018 / 中华传染病杂志

Objective:To explore the risk factors and the treatment outcomes of rifampicin-resistant tuberculosis (RR-TB) in Guizhou Province.Methods:The clinical data of 16 548 pulmonary tuberculosis patients with drug sensitivity test results registered in the Tuberculosis Information Management System in China from designated tuberculosis hospitals of 88 counties (cities, districts) in Guizhou Province from January 2014 to December 2018 were collected. The gender, age, occupation, ethnicity, patient registration classification, molecular biology or Lowenstein-Jenden (L-J) solid culture results of positive sputum culture patients, and treatment outcomes were retrospectively analyzed. Cohen′s kappa coefficient was used to analyze the consistency between molecular biology and L-J solid culture in detecting rifampin resistance. Chi-square test and non-conditional logistic regression model were used to analyze the risk factors of mono-rifampicin resistance tuberculosis and multidrug-resistant tuberculosis (MDR-TB) and the factors affecting treatment outcomes.The measurement data were compared by chi-square test or Fisher exact test. Results:The detection rate of RR-TB in the newly diagnosed cases was 6.79%(807/11 883), and that in the retreated cases was 30.01%(1 400/4 665). The drug sensitivity tests of 184 sputum culture positive RR-TB samples were performed by both L-J solid culture and molecular biology, and the rifampicin resistance detection rates were 20.65%(38/184) and 16.85%(31/184), respectively. The consistency between two methods was good ( kappa=0.697, 95% confidence interval ( CI) 0.564-0.830, P<0.01). Multivariate logistic regression analysis showed that patients aged 20 to 39 years old (odds ratio ( OR)=1.679, 95% CI 1.134-2.487) and aged 40 to 60 years old ( OR=1.526, 95% CI 1.019-2.283) were the high risk groups for MDR-TB. Treatment failure ( OR=27.753, 95% CI 22.455-34.300; OR=2.982, 95% CI 1.544-5.760, respectively), relapse and return ( OR=5.381, 95% CI 4.563-6.346; OR=3.897, 95% CI 2.901-5.234, respectively) were both high risk factors for MDR-TB and mono-rifampicin resistance tuberculosis. The treatment rate of RR-TB patients was 39.96% (396/991) from 2014 to 2016. Among 396 treatment cases, 138(34.85%) were cured and 16(4.04%) died. The patients aged>60 years old had lower cure rate (12.68%(9/71) vs 39.69%(129/325)) and higher death rate (11.27%(8/71) vs 2.46%(8/325)) than those aged ≤60 years. The differences were both statistically significant ( χ2=18.732, P<0.01; Fisher′s exact test, P=0.003). Conclusions:The RR-TB patients in Guizhou Province are mainly re-treated. Young and middle-age (20-60 years old) and treatment history are risk factors for RR-TB. The patients over 60 years old have a low cure rate and a high mortality rate. It is suggested to strengthen the screening, treatment and management of RR-TB to reduce the spread of tuberculosis.

The relationship between benign paroxysmal positional vertigo and cerebrovascular disease in the elderly / 中华老年医学杂志

Objective To investigate the relationship between benign paroxysmal positional dizziness (BPPV) and cerebrovascular disease and to promotethe practice of evidence bases medicinein thediagnosis,treatment and recurrenceprevention of BPPV in the elderly.Methods A total of 80 elderly patients were consecutively recruited from the Dizziness Outpatient Clinic from January 2013 to June,2014,with 80 non-BPPV elderly individuals receiving routine physical checkups during the same period serving as the control group.Clinical characteristics,lab test results and imaging data were compared between the two groups.Single factor and multivariate logistic regression analyses were conducted to identify independent risk factors for BPPV in the elderly.Results The experimental group showed higher rates of lacunar infarction,leukoaraiosis and intracranial artery stenosis than the control group(x2 =10.180,4.606 and 3.956,respectively;P=0.001,0.032 and 0.047,respectively).The prevalences of hyperlipidemia and type 2 diabetes were higher in the BPPV group than in the control group(x2 5.013 and 6.041,respectively;P=0.025 and 0.014,respectively).Differences in number of carotid atherosclerotic plaque cases,total cholesterol,triglyceride,homocysteine and uric were found between the two groups (x2 =11.237,t=2.862,2.230 and 4.270,respectively;P=0.001,0.005,0.027 and 0.000,respectively).Multivariate logistic regression analysisfound that blood uric acid,hyperglycemia,type 2 diabetes and hypertension were independent risk factors for BPPV (OR=1.006,7.104,3.152 and 3.273,respectively;P=0.005,0.000,0.004 and 0.002,respectively).The existence of carotid atherosclerotic plaques also increased the risk of BPPV (OR =384.570,95 ％ CI:46.935～ 3151.055,P =0.000).Conclusions BPPV in the elderlyis closely associated with cerebrovascular disease and its risk factors.Therefore,it is of great clinical significance to assess cerebrovascular function and carotid atherosclerotic plaque development for improved prognosis and effective prevention of recurrence of BPPV in the elderly.

The relationship between benign paroxysmal positional vertigo and cerebrovascular disease in the elderly / 中华老年医学杂志

Objective To investigate the relationship between benign paroxysmal positional dizziness (BPPV) and cerebrovascular disease and to promotethe practice of evidence bases medicinein thediagnosis,treatment and recurrenceprevention of BPPV in the elderly.Methods A total of 80 elderly patients were consecutively recruited from the Dizziness Outpatient Clinic from January 2013 to June,2014,with 80 non-BPPV elderly individuals receiving routine physical checkups during the same period serving as the control group.Clinical characteristics,lab test results and imaging data were compared between the two groups.Single factor and multivariate logistic regression analyses were conducted to identify independent risk factors for BPPV in the elderly.Results The experimental group showed higher rates of lacunar infarction,leukoaraiosis and intracranial artery stenosis than the control group(x2 =10.180,4.606 and 3.956,respectively;P=0.001,0.032 and 0.047,respectively).The prevalences of hyperlipidemia and type 2 diabetes were higher in the BPPV group than in the control group(x2 5.013 and 6.041,respectively;P=0.025 and 0.014,respectively).Differences in number of carotid atherosclerotic plaque cases,total cholesterol,triglyceride,homocysteine and uric were found between the two groups (x2 =11.237,t=2.862,2.230 and 4.270,respectively;P=0.001,0.005,0.027 and 0.000,respectively).Multivariate logistic regression analysisfound that blood uric acid,hyperglycemia,type 2 diabetes and hypertension were independent risk factors for BPPV (OR=1.006,7.104,3.152 and 3.273,respectively;P=0.005,0.000,0.004 and 0.002,respectively).The existence of carotid atherosclerotic plaques also increased the risk of BPPV (OR =384.570,95 ％ CI:46.935～ 3151.055,P =0.000).Conclusions BPPV in the elderlyis closely associated with cerebrovascular disease and its risk factors.Therefore,it is of great clinical significance to assess cerebrovascular function and carotid atherosclerotic plaque development for improved prognosis and effective prevention of recurrence of BPPV in the elderly.

The Analyses of Auditory Brainstem Pathway Encoding of Speech Sounds in Healthy Post -Menopause Women / 听力学及言语疾病杂志

Objective The aim of this study was to compare the basic characters of the speech - evoked audi‐tory brainstem response (speech - ABR) in healthy young women with that in post - menopause women and to get the changes of the probable factors for the auditory brainstem pathway encoding of speech sounds in healthy post -menopause women .Methods Speech - ABR of forty - seven normal hearing subjects including twenty - seven young women and twenty post - menopause women were recorded .The speech syllable /da/ as stimulus sound was trans‐mited to right ear by the insert earphones in speech - ABR test .Results The response waves of speech - ABR in post - menopause women were similar to those in young women ,which containal the onset responses (peak V and A) ,the transition (peak C) ,the frequency following responses (peak D ,E and F) and the offset response (peak O) .Except wave C ,the latency of wave V (6 .99 ± 0 .34ms) ,wave A (8 .32 ± 0 .49 ms) and wave O (48 .86 ± 0 .50 ms) in post - menopause women were evidently longer than those of in young women (the waveV :6 .60 ± 0 .25 ms ,wave A :7 .56 ± 0 .31 ms and wave O :47 .88 ± 0 .31 ms) ,while the amplitude of wave A ( - 0 .16 ± 0 .06 μV ) and O ( - 0 .12 ± 0 .06 μV ) in post - menopause women were obviously lower (modulus) than those of in young women (the wave A : - 0 .27 ± 0 .08 μV and O : - 0 .18 ± 0 .07 μV)(P< 0 .05) .In the FFR of speech - ABR ,the latency of wave D (23 .27 ± 0 .67 ms) ,wave E (31 .88 ± 0 .58 ms) and F (40 .61 ± 1 .22 ms) in post - menopause women were also longer than those of in young women (the wave D :22 .40 ± 0 .44 ms ,wave E :31 .00 ± 0 .43 ms and F :39 .53 ± 0 .61 ms) .Besides ,the amplitudes of wave D ( - 0 .12 ± 0 .04 μV ) and F ( - 0 .08 ± 0 .06 μV ) in post -menopause women were visibly lower (modulus) than those of in young women (the wave D : - 0 .17 ± 0 .08 μV and F : - 0 .16 ± 0 .07 μV)(P< 0 .05) . ④ The V /A slope also showed very significant difference ,the V/A slope in young women was much bigger than that in post - menopause women (P< 0 .05) .Conclusion The synchronism and phase locking of auditory brainstem pathway to processing and encoding capability in healthy post - menopause women is poorer than those of in young women .It may suggest that the growth of the age and the decrease of hor‐mone will weaken the ability to processing of speech sounds in women .

Bortezomib improves progression-free survival in multiple myeloma patients overexpressing preferentially expressed antigen of melanoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Significant efforts have been made to identify factors that differentiate patients treated with novel therapies, such as bortezomib in multiple myeloma (MM). The exact expression pattern and prognostic value of the cancer/testis antigen preferentially expressed antigen of melanoma (PRAME) in MM are unknown and were explored in this study.</p><p><b>METHODS</b>The transcript level of PRAME was detected in bone marrow specimens from 100 newly diagnosed MM patients using real-time quantitative polymerase chain reaction, and the prognostic value of PRAME was determined through retrospective survival analysis. PRAME expression higher than the upper limit of normal bone marrow was defined as PRAME overexpression or PRAME (+).</p><p><b>RESULTS</b>Sixty-two patients (62.0%) overexpressed PRAME. PRAME overexpression showed no prognostic significance to either overall survival (n = 100) or progression-free survival (PFS, n = 96, all P > 0.05) of patients. The patients were also categorized according to regimens with or without bortezomib. PRAME overexpression tended to be associated with a lower two-year PFS rate in patients treated with non-bortezomib-containing regimens (53.5% vs. 76.9%, P = 0.071). By contrast, it was not associated with the two-year PFS rate in patients with bortezomib-containing regimens (77.5% vs. 63.9%, P > 0.05). When the patients were categorized into PRAME (+) and PRAME (-) groups, treatment with bortezomibcontaining regimens predicted a higher two-year PFS rate in PRAME (+) patients (77.5% vs. 53.5%, P = 0.027) but showed no significant effect on two-year PFS rate in PRAME (-) patients (63.9% vs. 76.9%, P > 0.05).</p><p><b>CONCLUSION</b>PRAME overexpression might be an adverse prognostic factor of PFS in MM patients treated with non-bortezomib-containing regimens. Bortezomib improves PFS in patients overexpressing PRAME.</p>

A multicenter study on the validation of conversion factor for the conversion of BCR-ABL (P210) transcript levels to the international scale in chronic myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To validate the conversion factor (CF) for the conversion of BCR-ABL (P210) transcript levels to the international scale in chronic myeloid leukemia (CML).</p><p><b>METHODS</b>In 2012, the international reference laboratory in Adelaide, Australia (IMVS) sent two batches of RNA samples, 30 samples per batch, to Peking University People's Hospital (PKUPH). By comparing BCRABL (P210) transcript levels reported by the two laboratories, CF of PKUPH was calculated and validated by IMVS. In 2013, PKUPH prepared the exchange samples for validation of CF of 9 hospitals who have calculated CFs before. The fresh BCR-ABL (P210) (+) cells were serially diluted by BCR-ABL (P210) (-) cells to prepare 22 kinds of samples with different BCR-ABL transcript levels, each kind had 10 parallel samples. Trizol reagent was added in each tube. Ten hospitals tested BCR-ABL transcript levels of one set of 22 samples. Agreement between BCR-ABL transcript levels of each laboratory and PKUPH was assessed by the Bland-Altman method.</p><p><b>RESULTS</b>PKUPH successfully validated its CF with bias 1.1 fold and 95% limits of agreement between -4.7 and 4.9 fold. Of 9 hospitals whose validation performed by sample exchanges with PKUPH, 6 hospitals successfully validated their CF with bias ≤±1.4 fold and 95% limits of agreement within ±6 fold.</p><p><b>CONCLUSION</b>Validation of CF examined the stability of the detection of BCR-ABL (P210) transcript levels, which was necessary for the valid conversion of BCR-ABL (P210) transcript levels to the international scale in CML.</p>

The relationship between PCSK9 gene I474V polymorphism and ischemic stroke of Uygur and Han ethnic groups in Xinjiang Uygur Autonomous Region / 中华神经科杂志

Objective To investigate the frequency distribution of proprotein convertase subtilisin/kexin 9 (PCSK9) gene I474V polymorphisms and their relationship with patients with ischemic stroke (IS)of Uygur and Han ethnic groups in Xinjiang Uygur Autonomous Region.Methods The I474V polymorphism was identified by polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) in 407 patients with IS(including 219 Hans and 188 Uygurs)and 425 health controls (including 255 Hans and 170 Uygurs),and some specimens were sequenced.Results (1) Between IS group and control group,the genotypes Ⅱ and Ⅳ had no statistically significant differences in the levels of triglycerides (TG),high-density lipoprotein cholesterol (HDL-C) ; Total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C) levels had statistically significant differences; LDL-C levels had also statistically significant differences.Between IS and control groups,TC,LDL,HDL-C levels of genotype Ⅱ showed statistically significant difference.In the IS group,TC,LDL-C levels of Ⅳ genotype were significantly higher than the control group,the difference being statistically significant.(2) There was statistically significant difference in the genotype distribution between IS and control groups (9.5％ (77/814) vs 4.5％ (38/850),x2 =16.09,P =0.000).And the distribution of allele frequency was statistically different (18.9％ (77/407) vs 8.9％ (38/425),x2 =17.38,P =0.000).(3) The differences of I474V loci Ⅳ genotype frequency distribution in Xinjiang Uygurs and Hans were statistically significant (27.7％ (52/188) vs 11.4％ (25/219),x2 =17.40,P =0.000; 12.9％ (22/170) vs 6.3％ (16/255),x2 =5.57,P =0.018) ; So did the Ⅴ allele frenquency distribution (13.8％ (52/376) vs 5.7％ (25/438),x2 =15.58,P =0.000; 6.5％ (22/340) vs 3.1％ (16/510),x2 =10.44,P =0.001).(4) There was statistically significant difference in the genotype distribution and allele frenquency distribution between IS group and control group in the Xinjiang Uygurs (27.7％ (52/188) vs 12.9％ (22/170),x2 =11.79,P =0.001 ; 13.8％ (52/376) vs 6.5％ (22/340),x2 =10.44,P =0.001) ; But there was no statistically significant difference in the Hans.Conclusions Ⅱ and Ⅳ genotypes are dominant in the I474V polymorphism loci of PCSK9 gene.The genotype of PCSK9 gene I474V polymorphism is correlated with increasing serum levels of TC and LDL-C.I474V polymorphism is associated with cerebral IS course in Xinjiang region.There is statistically significant difference in the genotype I474V distribution between Uygur and Han groups.I474V polymorphism has a relationship with the occurrence of IS in Xinjiang Uygurs.Ⅳ may be a susceptible genotype and Ⅴ may be a genetic susceptible allele of the Xinjiang Uygurs.

The Correlation between the Degree of Pathogenetic Condition and Cognitive Impairment in Young OSAHS Patients / 听力学及言语疾病杂志

Objective To investigate the correlation between the degree of pathogenetic condition and cogni-tive impairment in young OSAHS patients. Methods Sixty-three patients (18～44 years old) were divided into 3 groups according to the assessment criteria regarding the degrees of pathogenetic conditions of hypoxemia and its persistence time: mild group(the lowest SaO2 ≥ 85 %, n = 20 ), moderate group (the lowest SaO2 : 65 ～ 84 %, n =24), and severe group (the lowest SAO2<65%, n= 19). Twenty-five healthy young adults were selected as the control group. All the subjects were tested with event-related potential, namely P300, the polysomnogram and the mini-mental state examination scale(MMSE). Results P300 latency in patients of three OSAHS groups was sig-nificantly prolonged as 326.1±12.7, 346.9±19.1, and 34.9±18.3 ms, as compared with those of control group: 311.9±18.3 ms (P< 0.05, respectively). In severe group, P300 latency was markedly increased compared with mild and moderate groups(P<0.01, P<0.05, respectively). No obvious differences were observed between mild and moderate groups(P=0. 095). The difference of hypoxemia lasting time could influence the P300 latency, such as when the hypoxemia lasting time was 4～60 seconds, the latency was 338. 12±13.7 ms, and when the hypoxemia lasting time increased to 60 ～ 140 s, the latency was prolonged to 354.74±16.7 ms(P = 0. 031 ). There was no difference among all groups in the P300 amplitudes. The MMSE scores for all patients were within normal limits andthere were differences between serve and control group(RA -RB=9. 91, P= 0. 003). Conclusion Among patients with OS-AHS, the impairment of cognitive function is con'anon. The degrees of pathogenetic conditions of hypoxemia and its lasting time may be used to evaluate the impairment degree of cognitive function in patients with OSAHS.

Influence of Nictinamide on endotheline in patients with pulmonary arterial hypertension / 中国综合临床

Objective To study the influence of Nictinamide on the endotheline(ET-1)in patienta with pulmonary arterial hypertension(PAH).Methods 66 cases of PAH were divided randomly into two groups (n=33for each):the Nictinamide treatment group and the control group.The changes of endotheline were compared before and after treatment.Results After treatment serum endotheline was significantly lower in the treatment group(P＜0.01),but there was no difference in the control group before and aftertreatment(P＞0.05).The significant difference was observed between treatment group and control group(P＜0.01).Conclusion Nictinamide will reduce the level of endothellne and confers some degree therapeutic and preventive value for PAH.

Activation of nuclear factor kappaB of monocyte in patients with chronic obstructive pulmonary disease / 新乡医学院学报

Objective To investigate the role of NF-κB activation in the inflammatory mechanism of chronic obstructive pulmonary disease (COPD).Methods Monocyte were collected from patients with COPD and were cultured,and stimulated with lipopolysaccharide (LPS) ; NF-κB p65 activation was measured by immunohistochemistry; SOD ,MDA and IL-8 and lung function were determined synchronously.Results The NF-κB p65 was induced by LPS in monocyte in all subjects, but it was most markedly done in COPD patients with exacerbateions; There was positive correlation between the NF-κB p65 activation of monocytes and levels of IL-8 and MDA in circulation, but it was negative correlation to SOD.Conclusion NF-κB plays a vital role in regulating product of IL-8 in monocyte in COPD.

Inhibition of K562 cell growth and tumor angiogenesis in nude mice by antisense VEGF(121) cDNA transfection / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of antisense vascular endothelial growth factor (VEGF)(121) cDNA transfection on the growth of K562 cells in nude mice.</p><p><b>METHODS</b>K562 cells transfected with the antisense (AS) or sense (S) VEGF(121) cDNA, and the vector (V, pcDNA3) alone were transplanted subcutaneously into nude mice and the growth of the transfected cells in vivo was investigated. The effects of transfected K562 cells on human bone marrow endothelial cells (BMEC) were analyzed by MTT assay, the microvessel density (MVD) in tumor mass by vWF immunohistochemistry stain.</p><p><b>RESULTS</b>K562/V tumor grew more slowly [(207.5 +/- 192.9) mm(3) vs (445.0 +/- 150.9) mm(3), P < 0.05] and K562/S tumor more rapidly than K562/V tumor did [(1 174.6 +/- 508.7)/mm(3) vs (445.0 +/- 150.9) mm(3), P < 0.01]. K562/S cell culture supernatant was more strongly in promoting the proliferation of BMEC than K562/V supernatant did, but K562/AS supernatant resulted in a marked decrease of the promoting effect as compared with K562/V's. The MVDs in K562/AS, K562/S, and K562/V tumors were [(11.0 +/- 7.6)/0.72 mm(2) vs (50.8 +/- 11.7)/0.72 mm(2) vs (18.9 +/- 7.0)/0.72 mm(2)], respectively.</p><p><b>CONCLUSIONS</b>Antisense VEGF(121) cDNA transfected K562 cells show growth retardation in transplanted nude mice, decrease of tumor MVD, and decrease of promoting BMEC proliferation capacity.</p>

The Function of Dendritic Cells Derived from Chronic Myeloid Leukemia / 中国实验血液学杂志

The purpose of this study was to investigate the function of dendritic cells derived from chronic myeloid leukemia (CML-DC). Mononuclear cells were prepared from bone marrow and peripheral blood of 24 patients with CML, and the DCs were obtained by incubation of MNCs with media containing GM-CSF, IL-4 and TNF-alpha. The phenotype of CML-DCs was identified by flow cytometry. FITC-dextran uptake, (3)H-TdR incorporation or MTT assay and lactate dehydrogenase release assay were used to detect uptake of exogenous antigen in immature DCs, the antigen presenting ability in mature DCs and specific cytotoxicity of CTL to leukemic cells, respectively. The DCs with high expression of CD1a, CD86, CD80, HLA-DR, CD54 and CD4 were obtained from marrow and blood of patients with CML. The uptake of FITC-DX was observed in early DCs. There was a potent stimulation to allo-MLR in DCs cultured for 7 - 10 days, and a lightly lower stimulation to auto-MLR. CML-DCs can induce the generation of specific cytotoxic T cells. These results suggest that CML-DCs are functional DCs with the ability to induce anti-leukemia effect.

beta1 Integrin Dysfunction in Adult Chronic Myeloid Leukemia Bone Marrow Cells / 中国实验血液学杂志

According to our previous experiments, Ph(+) chronic myeloid leukemia (CML) cell line K562 cells have defects in beta 1 integrin activation. In order to search the same regularity in Ph(+) CML bone marrow cells, bone marrow mononuclear cells (BMMNC) from 12 cases of Ph(+) CML and 10 cases of normal individuals were studied. Their expression rate of 9EG7 epitope on beta1 integrin post treatment by 8A2 or GM- or G-CSF and cell adhesion ability with soluble fibronectin (FN) were evaluated by flow cytometry; in addition, the effects of CGP57148B, a highly specific ABL tyrosine kinase inhibitor, were observed. Our results showed that 9EG7 expression rate and FN binding rate were very low in all the inactivated cells. The parameter increased markedly post 8A2 activation in both NBMMNCs and CMLBMMNCs, but the degree of increase in CMLBMMNCs was significantly lower than that in NBMMNCs; GM-CSF or G-CSF could significantly increase the parameters in NBMMNCs while had no effects on that in CMLBMMNCs. CGP57148B could increase the beta1 integrin activation potential of CMLBMMNCs but had no effects on that of NBMMNCs. The results indicate that decreased activation potential of beta1 integrin in CMLBMMNCs is the major cause of adhesion defects of Ph(+) CML cells; beta1 integrin functional insufficiency in CMLBMMNCs could not be directly reversed by ABL tyrosine kinase inhibitor CGP57148B.

Clinical Efficacy of Nalmefene for Chronic Type Ⅱ Respiratory Failure / 中国药房

OBJECTIVE: To study the clinical efficacy of Nalmefene in the treatment of chronic type Ⅱrespiratory failure. METHODS: A total of 40 patients with chronic type Ⅱ respiratory failure were randomly divided into treatment group and the control group: the treatment group received Nalmefene (1.0 mg) plus 5% GS (250 mL) q.d by iv gtt. in addition to the routine treatment, and the control group received 1.875 g Nikethamide plus 5% GS (250 mL) q.d by iv gtt. After 5-day treatment, the clinical symptom, physical signs, adverse drug reactions, lung function testing and blood gas analysis in two groups were evaluated. RESULTS: The overall response rate was 95.0% in the treatment group vs. 60.0% in the control group(P