Progress on diagnosis and treatment of latent tuberculosis infection / 浙江大学学报·医学版

One fourth of the global population has been infected with Mycobacterium tuberculosis, and about 5%-10% of the infected individuals with latent tuberculosis infection (LTBI) will convert to active tuberculosis (ATB). Correct diagnosis and treatment of LTBI are important in ending the tuberculosis epidemic. Current methods for diagnosing LTBI, such as tuberculin skin test (TST) and interferon-γ release assay (IGRA), have limitations. Some novel biomarkers, such as transcriptome derived host genes in peripheral blood cells, will help to distinguish LTBI from ATB. More emphasis should be placed on surveillance in high-risk groups, including patients with HIV infection, those using biological agents, organ transplant recipients and those in close contact with ATB patients. For those with LTBI, treatment should be based on the risk of progression to ATB and the potential benefit. Prophylactic LTBI regimens include isoniazid monotherapy for 6 or 9 months, rifampicin monotherapy for 4 months, weekly rifapentine plus isoniazid for 3 months (3HP regimen) and daily rifampicin plus isoniazid for 3 months (3HR regimen). The success of the one month rifapentine plus isoniazid daily regimen (1HP regimen) suggests the feasibility of an ultra-short treatment strategy although its efficacy needs further assessment. Prophylactic treatment of LTBI in close contact with MDR-TB patients is another challenge, and the regimens include new anti-tuberculosis drugs such as bedaquiline, delamanid, fluoroquinolone and their combinations, which should be carefully evaluated. This article summarizes the current status of diagnosis and treatment of LTBI and its future development direction.

Therapeutic effect of anti-IL-12/IL-23 p40 on experimental autoimmune uveitis and its mechanism / 中华实验眼科杂志

Objective:To explore the therapeutic effect of anti-interleukin (IL)-12/IL-23 p40 antibody on experimental autoimmune uveitis (EAU) and its mechanism.Methods:Sixty-six SPF female C57BL/6N mice aged 6-8 weeks were selected.EAU model was established in 24 mice through immunization with the interphotoreceptor retinoid-binding protein (IRBP) 651-670.The 24 mice were sacrificed before immunization, and on the 3rd, 12th, and 18th day after immunization, with 6 at each time point.Flow cytometry was used to detect the proportion of IL-17A + interferon-γ (IFN-γ) + CD4 + T cells in the spleen, lymph nodes and eyeballs.Another 6 mice were selected to establish EAU model, and fundus images of the mice were taken with a small animal imaging instrument and optical coherence tomography (OCT) 18 days after immunization.The 6 mice were sacrificed after OCT examination and the eyeballs were collected.Hematoxylin-eosin staining was used to observe the retinal inflammation and morphological changes in tissue structure.Flow cytometry was employed to detect the proportion of IL-17A + IFN-γ + CD4 + T cells in lymph nodes.The 6 mice were divided into IL-17A + IFN-γ + highly expressed group and IL-17A + IFN-γ + lowly expressed group according to flow cytometry results, and the retinal injury was compared between the two groups.EAU model was established in another 36 mice, which were divided into anti-IL-12/IL-23 p40 group and IgG group by random number table method, with 18 mice in each group.Anti-IL-12/IL-23 p40 or IgG was injected by tail vein at a 3-day inteval according to grouping.On the 12th and 18th day after immunization, 6 mice were selected from each group to collect lymph nodes and eyeballs, and the proportion of T cell subsets was detected by flow cytometry.Eyeballs of 6 mice in each group were extracted on the 24th day after immunization and retinal damage was observed by hematoxylin-eosin staining.The induced differentiation of CD4 + T cells in vitro was assayed by flow cytometry.The expressions of IL-17 and IFN-γ were detected by enzyme-linked immunosorbent assay (ELISA) after induced differentiation of IL-17A + IFN-γ + CD4 + T cells.The relative expression levels of Th1 transcription factor T-bet and Th17 transcription factor retinoid acid-related orphan nuclear receptor γt (ROR-γt) after induced differentiation of IL-17A + IFN-γ + CD4 + T cells were detected by real-time quantitative PCR.The use and care of animals followed the ARVO statement and this study protocol was approved by an Ethics Committee of Experimental Animals of Tianjin Medical University Eye Hospital (No.TJYY2019111019). Results:There were significant differences in the proportion of IL-17A + IFN-γ + CD4 + T cells in lymph nodes, spleen and eyeballs between wild-type mice and EAU mice at the 3rd, 12th and 18th day after immunization ( H=9.642, 16.531, 10.385; all at P<0.05). Compared with before immunization, the proportion of IL-17A + IFN-γ + CD4 + T cells was significantly increased in lymph nodes of EAU mice on the 12th day following immunization and was significantly increased in spleen and lymph nodes on day 18 after immunization (all at P<0.05). Severe retinal exudation, retinal detachment, severe inflammatory cell infiltration and extensive retinal folds were detected in IL-17A + IFN-γ + highly expressed mice.Mild retinal edema, focal inflammatory cell infiltration and mild retinal folds were found in IL-17A + IFN-γ + lowly expressed mice.The proportion of CD3 and IL-17A + IFN-γ + CD4 + T cells in the eyeballs of anti-IL-12/IL-23 p40 group was lower than that in IgG group at the 18th day after immunization, and the differences were statistically significant ( t=15.304, 8.080; both at P<0.05). On day 12 after immunization, the percentage of IL-17A + IFN-γ + CD4 + T cells in anti-IL-12/IL-23 p40 group was (0.33±0.18)%, which was significantly lower than (4.83±0.45)% in IgG group ( t=15.974, P<0.001). Compared with IgG group, the percentage of Th1, Th17, IL-17A + IFN-γ + CD4 + T cells and the expression levels of IL-17, IFN-γ, T-bet, ROR-γt in anti-IL-12/IL-23 p40 group were significantly decreased, with statistical significances (all at P<0.05). Conclusions:Anti-IL-12/IL-23 p40 has a therapeutic effect on EAU by inhibiting IL-17A + IFN-γ + CD4 + T cells.

Research progress in HER2-low breast cancer / 中国医师杂志

The latest statistics show that breast cancer (BC) has become the cancer with the highest incidence in the world, seriously affecting women′s physical and mental health, and has become a hot research topic in the medical field. Accordingly, its treatment has also entered the molecular era. According to its molecular classification, BC is mainly divided into Luminal A, Luminal B, simple human epidermal growth factor receptor 2 (HER2)-positive and triple negetive breast cancer (TNBC). Obviously, correct judgment of HER2 expression status is very important for cancer typing and treatment of breast cancer. With the further development of research, some scholars have recently put forward new viewpoints and views on the interpretation of HER2 expression and cancer typing in breast cancer. This review will introduce the HER2-low breast cancer combined with the current frontier viewpoint and research findings, hoping to provide a reference for the precision treatment of breast cancer in the later stage and related further research.

Effects of intravenous injection of human umbilical cord mesenchymal stem cells-derived small extracellular vesicles on experimental autoimmune uveitis in mice / 中华实验眼科杂志

Objective:To explore the therapeutic effects of intravenous injection of small extracellular vesicles (sEVs) derived from human umbilical cord mesenchymal stem cells (MSCs) on experimental autoimmune uveitis (EAU) in mice.Methods:MSCs from human umbilical cord were cultured and the supernatant was collected.The sEVs were isolated by ultracentrifugation method and a NanoSight instrument was used to analyze the particle size.The expression of surface markers sEVs, CD9, CD81 and CD63 was determined via Western blot.The morphology of sEVs was observed with a transmission electron microscope.Forty-eight 7-week-old female C57BL/6 mice were seclected to establish the EAU model through immunization with interphotoreceptor retinoid-binding protein peptide 651-670 (IRBP 651-670). The mice were divided into sEVs treatment group and phosphate buffer solution (PBS) control group using a random number table, with 24 mice in each group.The mice in the sEVs treatment group were injected with 50 μg of MSCs-derived sEVs via tail vein on the 11th day after modeling.In the PBS control group, the mice were injected with the same volume of PBS.Six mice in each group were randomly selected to observe the inflammation of the retina after mydriasis with an ophthalmoscope every other day from 8th day following modeling and the inflammation scores were evaluated.Six mice were randomly selected and sacrificed on the 14th day and 6 on the 18th day following modeling in each group, and both eyeballs of the mice were enucleated.Retinal tissue sections of the 6 mice sacrificed on the 18th day were stained with hematoxylin-eosin and the pathological scores were evaluated.The infiltration of helper T 1 (Th1) cells and Th17 cells in the eyeballs of the 6 mice sacrificed on the 18th day following modeling was detected by flow cytometry.T cells were isolated from spleen and lymph nodes of the 6 mice sacrificed on the 14th day, and the proliferation of T cells under different concentrations of IRBP 651-670 (0, 1, 10 and 20 μg/ml) was detected using a 5-bromodeoxyuridine (BrdU) method.To further study the effects of MSCs-derived sEVs on Th1/Th17 cells differentiation, naive T cells of spleen from another 3 normal mice were isolated by magnetic bead negative sorting and incubated with 10 μg/ml MSCs-derived sEVs or 10 μg/ml PBS, and then were cultured under Th1/Th17 cell differentiation conditions, respectively.Flow cytometry was used to measure the differentiation of naive T cells into Th1/Th17 cells.This study protocol complied with the regulations of the care and use of laboratory animals in China and was approved by an Ethics Committee of Tianjin Medical University (No.TJYY2019103022). Results:The isolated human MSCs-derived sEVs was with an average diameter of (102.4±33.6) nm and showed a double-layer membrane vesicle structure under the transmission electron microscope.The CD9, CD63 and CD81 proteins were highly expressed in sEVs.The inflammation scores of the sEVs treatment group were significantly lower than those in the control group on day 14, 16, 18, 20 and 22 after modeling (all at P<0.05). The pathological score of mice in the sEVs treatment group was significantly lower than that of PBS control group on the 18th day following modeling ( P<0.05). The flow cytometry results showed that on day 18 after modeling, the proportions of Th1 and Th17 cells in eyeballs in the sEVs treatment group were (15.55±2.03)% and (15.67±2.15)%, respectively, which were significantly lower than (21.35±0.72)% and (20.90±1.10)% in the PBS control group ( t=6.58, 5.31; both at P<0.01). BrdU results showed that when the IRBP 651-670 concentration was 20 μg/ml, the T cell proliferation ability in the sEVs treatment group was inhibited obviously compared with the control group ( P<0.05). The proportions of naive T cells differentiated into Th1 cells and Th17 cells in the sEVs treatment group were (28.15±1.32)% and (11.60±2.23)% respectively, which were significantly lower than (31.58±1.75)% and (23.52±1.76)% of the PBS control group, and the differences were statistically significant ( t=3.93, 10.26; both at P<0.05). Conclusions:Intravenous injection of human umbilical cord MSCs-derived sEVs can reduce the inflammation in EAU mice.The mechanism may be related to inhibiting the differentiation of naive T cells to Th1 and Th17 cells, and reducing the infiltration of Th1 and Th17 cells in the eyeballs.

Rate of capsular contracture among different breast implants in the last two decades: a meta-analysis / 中华医学美学美容杂志

Objective:To study the rate of capsule contracture after operation of the textured surfaces breast implants and the smooth surfaces breast implants, to provide evidence for plastic surgeons to select the type of breast implants during breast augmentation.Methods:This study started from January 2018 to May 2019. Chinese and English databases including Wanfang Science and Technology Periodical Full-text Database, VIP Chinese Science and Technology Periodical Full-text Database (VIP) and CNKI, PubMed, Cochrane Library, Web of Science, Science Drirect Online were searched by computer. Some relevant studies were collected for this meta-analysis.Results:We identified 9 studies including a total of 13165 subjects for the meta-analysis. The OR value of the study was 0.43 (95% CI: 0.35, 0.51), and the incidence rate of capsule contracture in the experimental group was lower than that in the control group. In cumulative meta-analysis and sensitivity test, the conclusion was stable. And there was no publication bias found by Egger regression test. Conclusions:The textured surfaces breast implants are better than the smooth surfaces breast implants in terms of incidence rate of capsule contracture after augmentation mammoplasty.

Retrospective study of low-to-moderate dose glucocorticoids on viral clearance in patients with novel coronavirus pneumonia / 中华临床感染病杂志

Objective@#To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance time in patients with COVID-19.@*Methods@#A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, School of Medicine, Zhejiang University were recruited. All patients received oral abidol and/or combined lopinavir/ritonavir, darunavir antiviral, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg·kg-1·d-1) (glucocorticoid treatment group), and 21 patients who did not use glucocorticoid were the control group. The time of stable virologic conversion insputumand the time of radiologic recovery in lungsince onset were compared between the two groups and among the normal patients.The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups.@*Results@#The median ages of the glucocorticoid group and the control group were 52 [interquartile range (IQR):45, 62] years and 46 (IQR: 32, 56)years, and the differences were significant (P<0.05). The clinical conditions at hospital admission were different between the two groups (P<0.01). There were 52.0% critical ill patients in the glucocorticoid treatment group, compared to that of 71.4% normal patients in the control group. The median times from the onset tostable virologic conversion to negative in the two groups were 15 (IQR:13,20) days and 14 (IQR:12,20) days (P>0.05), and the difference was no statistically significant. The median times from onset to radiologic recovery were 13 (IQR: 11,15) days and 13 (IQR:12,17) days in the two groups, and there was no difference (P>0.05). In ordinary patients, the median timesfrom the onset tostable virologic conversion insputum were no difference (P>0.05), with 13 (IQR:11,18) days in the glucocorticoid group and 13 (IQR:12,15) days in the control group; The median times from onset to radiologic recovery in lungwere also no difference (P>0.05), with 12 (IQR: 10,15)days in the glucocorticoid group and 13 (IQR: 12,17) days inthe control group.@*Conclusions@#Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19. The glucocorticoid is not recommended since no effectiveness on accelerating the improvement of radiologic recovery in lung has been observed.

Effect of low-to-moderate dose glucocorticoids on viral clearance in COVID-19: a retrospective study / 中华临床感染病杂志

Objective:To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance in patients with COVID-19.Methods:A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, Zhejiang University School of Medicine were recruited. All patients received oral arbidol and combination of lopinavir/ritonavir or darunavir/cobistitat for antiviral therapy, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg·kg -1·d -1) (glucocorticoid treatment group), and 21 patients did not use glucocorticoid (control group). The time of virologic negative conversion in sputum and the time of radiologic recovery in lung since onset were compared between the two groups. The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups. Results:The median ages of the glucocorticoid group and the control group were 52 (45, 62) and 46 (32, 56) years ( χ2=4.365, P<0.05). The clinical conditions at hospital admission were different between the two groups ( P<0.01). The severe cases accounted for 52.0%, while moderate cases in the control group accounted for 71.4%. The median times from the onset to virologic negative conversion in the two groups were 15 (13, 20) and 14 (12, 20) days ( P>0.05). The median times from onset to radiologic recovery were 13 (11, 15) and 13 (12, 17) days in the two groups ( P>0.05). In moderate cases, the median times from the onset to virologic conversion in sputum were 13 (11, 18) days in the glucocorticoid group and 13 (12, 15) days in the control group ( P>0.05). The median times from onset to radiologic recovery in lung were 12 (10, 15) and 13 (12, 17) days, respectively ( P>0.05). Conclusions:Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19, and also no effect on accelerating radiologic recovery in lung, so it is not recommended.

Effects of rat mesenchymal stem cell-derived exosomes on rat experimental autoimmune uveitis / 中华眼底病杂志

Objective To observe the effects of exosomes derived from rat mesenchymal stem cells (MSC-exosomes) on the rat experimental autoimmune uveitis (EAU) model.Methods Twelve Lewis rats were randomly divided into experimental group and control group by random number table,with 6 rats in each group.Rats in the experimental group were established with EAU model,100 μl of MSC-exosomes (50 μg) were periocular injected on the 9th day after modeling while the control rats were injected with the same volume of phosphate buffer.At different time points after modeling,the retinal structure was observed by hematoxylin and eosin (HE) staining,and the clinical and pathological manifestations were evaluated.T cells from the two groups were analyzed by flow cytometry,Immunohistochemical staining was used to observe the expression of macrophage surface marker CD68.The effect of MSC-exosomes on T cells was measured by lymphocyte proliferation assays.And flow cytometry was used to detect Th 1,Th 17 and regulatory T cells Variety.Electroretinogram (ERG) was used to evaluate the retinal function.Data were compared between the two groups using the t test.Results HE staining showed that the retina structure of the experimental group was more complete than that of the control group on the 15th day after modeling.Immunohistochemical staining showed that the positive expression of CD68 in the experimental group was significantly less than that in the control group.On the 15th day after modeling,the retinal pathological score of the experimental group was lower than that of the control group.On the 9th to 13th day after modeling,compared to the control group,the average clinical scores of the retina in the experimental group were lower,and the difference was statistically significant (t=3.665,3.21,3.181,4.121,3.227;P＜0.01).The results of T cell proliferation assay showed that exosomes (1.0,10.0 μg/ml) inhibited the proliferation of T cells under different concentrations of R16 (1,10,30 μg/ml),and the difference was statistically significant (F=1 1.630,4.188,6.011;P＜0.05).The results of flow cytometry showed that the number ofThl,Th17 and Treg cell subsets in the experimental group was decreased compared with the control group,and the difference was statistically significant (t=7.374,4.525,6.910;P＜0.01).There was no difference in the proportion of cells in the T cells and lymph nodes (t=1.126,0.493,0.178;P=0.286,0.632,0.862).The results of ERG showed that,compared with the control group,the amplitudes of 0.01,3.0 cd/m2 a wave and b wave of the experiment group were all increased on the 15th day after modeling,and the differences were statistically significant (t=3.604,4.178,4.551,2.566,P＜0.05).Conclusions MSC-exosomes can reduce the clinical and pathological manifestations of EAU,protect retinal function,reduce ocular macrophage infiltration,down-regulate the proportion of inflammatory cells in the eye,and inhibit T cell proliferation.

Effect of porcine epidemic diarrhea virus nsp1 on type Ⅰ interferon response / 生物工程学报

Porcine epidemic diarrhea virus (PEDV) inhibits the host typeⅠinterferon and cellular antiviral response, but its inhibition mechanism is unclear, and the roles of PEDV nonstructural proteins in regulating typeⅠinterferon responses have been seldom studied. To study the effect of nsp1 on typeⅠinterferon response, nsp1 gene was cloned into a eukaryotic expression vector pCAGGS. The expression of nsp1 in transfected cells was determined by Western blot and indirect immunofluorescence assay. The effects of nsp1 on the induction of typeⅠinterferon were evaluated by dual luciferase reporter gene assay, ELISA and VSV bioassay. Western blot and indirect immunofluorescence assay showed that nsp1 was highly expressed in transfected cells and PEDV-infected cells. Dual luciferase reporter gene assay results indicated that nsp1 strongly inhibited the IFN-β promoter activity, and the inhibitory effect was nsp1 dose-dependent. ELISA results showed that nsp1 significantly inhibited the expression of IFN-β in protein level. And VSV replication-inhibition bioassay revealed that nsp1 significantly inhibited typeⅠIFN antiviral activities induced by poly(I:C). Our results implied that nsp1 was a highly conserved protein of PEDV and exhibited antagonistic function on interferon promoter activity. The results have laid a foundation for further understanding the immune evasion mechanism of PEDV and for developing new effective vaccine against PEDV.

Reproducibility of VERION Digital Guidance System and its comparability with iTrace, Lenstar LS900 and manual keratometer in measuring keratometry and astigmatism / 眼科新进展

Objective To analyze the reproducibility of keratometry and astigmatism measured by the VERION Digital Guidance System and the comparability of VERION with iTrace,Lenstar LS900 and manual keratometer.Methods The keratometry of 62 cataract patients were measured using four different devices.The steep keratometry (Ks),flat keratometry (Kf),astigmatic magnitude,astigmatic axis,cylinder at 0-degree meridian (vector component,J0) and cylinder at 45-degree meridian (vector component,J45) from each machine were recorded and analyzed.The three repeated measurements and the results of VERION system with other three devices were compared to analyze the reproducibility and comparability of VERION system.Results Reproducibility:Intraclass correlation coefficients and Cronbach's alpha values were higher than 0.9 for Ks,Kf,astigmatic magnitude,astigmatic axis,J0 and J45 measured by the VERION system (all P ＜ 0.001).Comparability:The results of Ks and magnitude of astigmatism of VERION were larger than the iTrace (all P ＜ 0.05) in the paired-samples t test.There was no statistical difference for the rest of parameters (all P ＞ 0.05).The Bland-Altman graphs revealed the 95％ limits of agreement (LOA) of J0,J45 and the astigmatic axis between VERION and iTrace were (-0.31-0.35) D,(-0.25-0.31) D and-13.5 °-12.3 °,respectively;There was no statistical differences for all parameters except for J45 in the paired-samples t test between the VERION and Lenstar LS900 (all P ＞ 0.05).The Bland-Altman graphs revealed the 95％ LOA of J0,J45 and the astigmatic axis were (-0.25-0.31)D,(-0.27-0.36) D and-13.5°-11.0°,respectively;There were statistical differences for the results of Kf and magnitude of astigmatism between the VERION and manual keratometer (all P ＜ 0.05).The Bland-Altman graphs revealed the 95％ LOA of J0,J45 and the astigmatic axis between VERION and manual keratometer were (-0.38-0.35) D,(-0.41-0.42) D,-12.6°-16.4°,respectively.Conclusion The VERION system is a reliable system for the measurement of keratometry and astigmatism.The keratometry and astigmatic magnitude of the VERION system have a good agreement with the iTrace,Lenstar LS900 and manual keratometer.However,the astigmatic axis measurements are significantly different among the four devices.

Application of iTrace aberration in measuring lens alignment after Toric intraocular lens implantation / 眼科新进展

Objective To research and evaluate measuring Toric intraocular lens (Toric IOL) alignment by iTrace aberration without mydriasis.Methods Forty-five eyes of 35 patients underwent phacoemulsification in Tianjin Medical University Eye Hospital from June 2015 to February 2016 were enrolled.Follow-up and iTrace aberration examination were performed at postoperative 1 week.The internal optics aberration astigmatism axis was transformed into postoperative Toric IOL alignment.The result and the Toric IOL alignment measured by tradition slitlamp method were compared by linear correlation and difference.Results At postoperative 1 week,the uncorrected distant visual acuity and corrected distant visual acuity were (0.19 ± 0.12)LogMAR and (0.10 ±0.09) LogMAR.The UCVA was 20/40 or better in 42 eyes (93.3％).The mean IOL misalignment measured by slitlamp was (3.13 ± 2.86) degrees (ranged 0-9 degrees) and by the iTrace aberration was (4.44 ± 3.42) degrees(ranged 0-13 degrees),there was statistical significant difference (t =-2.321,P =0.025).The mean difference in the error of the Toric intraocular lens alignment measured by iTrace aberration and the slitlamp was (3.67 ± 3.59) degrees (ranged 0-14 degrees).The results showed that there was less than 5 degrees of difference between the two methods in 32 eyes (71.1％),locate 5 to 10 degrees in 9 eyes (20％),more than 10 degrees in 4 eyes (8.9％).The correlation between the 2 methods showed significant linear relationship (r =0.926,P ＜ 0.01).Conclusion Using iTrace aberration can accurately measure Toric intraocular lens alignment without mydriasis,the result has some reference value.

The relationship of PALB2 and AR expression in triple negative breast cancer and its clinical significance / 实用医学杂志

Objective Discussion the relationship of PALB2 and AR expression in triple negative breast cancer and its clinical pathological features. Methods The SP immunohistochemical staining was adopted to detect the expression of PALB2 and AR in 178 cases of TNBC, PALB2 divided into two groups according to the expression of different, and to analyze the clinical pathological features and prognostic impact of different AR expression status. Results 178 cases of TNBC, that PALB2 missing expression 47 cases (26.4%), AR expression of 60 cases (33.7%), between of them were negatively correlated (-1≤r<1, P<0.05), in PALB2 negative group, AR expression associated with family history, lymph node metastasis, clinical stage and recurrence and metastasis (P<0.05), and 5-year disease-free survival lower than AR negative expression, Log rank = 4.453, P = 0.035. Conclusion PALB2 negative expression while AR positive expression in TNBC have synergistic effect with disease progression, PALB 2 and AR combined detection may provide a new basis for the prognosis of TNBC interpretation, and recommending take further studies to confirm.

The differences inexpressions of EGFR and VEGF between Han and Uygur triple-negative breast cancer patients / 中国癌症杂志

Background and purpose:Triple-negative breast cancer (TNBC) is currently the focus of breast cancer research. Researches demonstrated that the molecular biological characteristics of different ethnic groups are not the same. This study mainly probed into the expression of endothelial growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in Han and Uygur TNBC patients, and the relationship between the expression and prognosis of patients.Methods:From Jan. 2007 to Jan. 2009, 167 patients were admitted. Among those, 121 were Han and 46 were Uygur patients. The expressions of EGFR, and VEGF were detected by PV-9000 immunohistochemical staining, and compared with lymph node metastasis and clinical staging. The results were analyzed by SPSS 18.0 statistical software.Results:Five-year disease-free survival (DFS) of two groups had no indifferent (P>0.05). EGFR and VEGF positive rate of Han patients was lower than that of Uygur patients (P0.05). Uygur TNBC patients might have a different prognostic factor as compared with Han patients. Further studies need to be carried out.

External use of recombinant human granulocyte-macrophage colony stimulating factor hydrogel to repair thick skin graft donor sites / 中国组织工程研究

BACKGROUND:There are less reports about the external use of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) hydrogel to repair thick skin graft donor sites. By now, relevant self-control studies have not been retrieved. OBJECTIVE:To observe the effect of rhGM-CSF on the repair of thick skin graft donor sites. METHODS:Sixty patients with burns and scar hyperplasia undergoing autologous thick skin grafting were enroled, 47 males and 13 females, aged 18-65 years. The thigh was selected as donor sites. According to the depth of donor sites, the patients were divided into 0.4 mm and 0.55 mm groups, with 30 cases in each group. Wounds on the symmetric areas with equal area and same depth were selected or wounds with same depth were selected and divided equaly. The wounds were randomly assigned into treatment group and control group. The treatment group was treated with rhGM-CSF hydrogel externaly; the control group was only given vaseline dressing. At postoperative 3, 7, 10, 14 days, the fresh dressing was changed. Then, the wound appearance, healing time, healing rate and adverse effects were observed in the two groups. RESULTS AND CONCLUSION:At 14 days after operation, the wound surface was smoother and the pigmentation was relatively less in the treatment group compared with the control group; the degree of wound pain was less in the treatment group than the control group during dressing change (P < 0.05). At 10 and 14 days after operation, the healing rate and healing time were better in the treatment group than the control group (P < 0.05). No general malaise or hypersensitivity cases were reported, and local issue hyperplasia was also not found. Al the above indicate that the external use of the rhGM-CSF hydrogel can evidently shorten the healing time and improve the healing condition when it is applied in the thick skin graft donor sites.

Clinical significance of BRCA1/2 mutation in breast cancer patients with different malignant tumor family history in Xinjiang region / 实用医学杂志

Objective To investigate the clinical significance of BRCA1/ 2 mutation in breast cancer patients with different malignant tumor family history. Methods We studied 98 cases of diagnosed breast cancer patients with malignant tumor family history. BRCA1/2 screening was performed by PCR-DHPLC sequencing method. All mutations were confirmed by using direct DNA sequencing. Results The prevalence of BRCA1/2 germline mutation was 20.41%.The BRCA1/2 mutation was 55.6% in patients with family breast and ovarian cancer, and was 20.0% and 17.9% in patients with family breast and in patients with ovarian cancer, respectively. In correspondence to 2 and 3 and 4 people withof the breast or ovarian cancer in family , the BRCA1/2 mutation was 16.25%、33.3%、66.67% ,respectively. Conclusion The BRCA1/2 mutation rate increased in the patients with breast and ovarian cancer family history, and the detection of BRCA1/2 mutation increased with the number of patients with cancer in a family.

Association between single nucleotide polymorphisms of ER β gene and susceptibility of breast cancer in Xinjiang Uygur / 肿瘤研究与临床

Obiective To investigate the association between single nucleotide polymorphisms (SNPs) of ER β gene and susceptibility of breast cancer in Uygur women in Xinjiang.Methods A case-control study was designed to explore the genotypes of Rsa Ⅰ (G/A) of ER β gene,detected by PCR-restriction fragment length polymorphism (PCR-RFLP) assay,in 112 breast cancer cases of Uygur women and 139 medical health cases of Uygur women.The association between SNPs of ER β gene and risk of breast cancer in Uygur women was analyzed by unconditional Logistic regression model.Results The frequencies of genotypes of Rsa Ⅰ (G/A) of ER β gene in cancer group and control group were 83.0 ％ and 17.0 ％,73.4 ％ and 26.6 ％,respectively.Rsa Ⅰ (G/A) locus allele frequency were 91.5 ％ and 8.5 ％,86.7 ％ and 13.3 ％,respectively.There were no statistically differences between the cancer cases and control cases (x2 =3.335,P =0.068.x2 =2.917,P =0.088).Presence of estrogen exposure history of two groups for genotypes distribution were 74.2 ％ and 25.8 ％,86.4 ％ and 13.6 ％,respectively.Any family history of cancer in the two groups for the genotypes distribution were 100 ％ and 0,72.8 ％ and 27.2 ％ respectively.There were statistically significant difference between two groups (P =0.046,P =0.001).Compared with wild-type genotype GG,the GA type with estrogen exposure and without a family history of cancer showed a lower incidence of breast cancer in Uygur women (OR =0.385,95 ％ CI 0.148-0.999.OR =0.285,95 ％ CI 0.134-0.605).Conclusions ER β gene SNP is associated with breast cancer of estrogen exposure and no family history of cancer factors.GA genotype may be a protective factor for Uygur women with breast cancer.

The early dynamics study of cerebrospinal fluid bacterial in a rabbit model of bacterial meningitis / 中华传染病杂志

Objective To study the dynamics changes of cerebrospinal fluid (CSF) bacterial load within 48 h after infection in a rabbit meningitis model, and provide information for diagnosis,treatment and prognosis of this disease. Methods Taking New Zealand white rabbit as the study object, meningitis model was established via cerebellar cistern puncture with different concentrations of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) to explore the relationship between the mortality of animals and the subarachnoid inoculation dosage. The dynamics study of CSF bacterial load was conducted with proper inoculation bacterial dosage. Forty-eight rabbits were separated into four groups (12 each group): E. coli meningitis model group, E. coli meningitis + ceftriaxone treated group, S. aureus meningitis model group and S. aureus meningitis + vancomycin treated group. At 0,12, 24, 36 and 48 h of inoculation, CSF and blood samples were obtained for CSF bacterial quantitative culture, CSF leukocyte count and peripheral blood leukocyte count. Finally, the relationships between the early mortality of animals, the efficacy of antibiotics, CSF leukocyte counts and the dynamics changes of CSF bacterial load were analyzed in the bacterial meningitis rabbit model.The CSF bacterial load and the white blood cell count curve were compared by analysis of covariance (ANOVA). Correlation test was done using correlate partial analysis. Results The relationship between subarachnoid inoculation dosage and the mortality of rabbits presented S-curve correlation.The bacterial load in subarachnoid space peaked in 12-24 h after infection and then gradually decreased. Effective antibiotic therapy could significantly speed up the decline of this process. There were significantly different between E. coli meningitis model group and E. coli meningitis+ceftriaxone treated group (F= 27. 10, P<0. 01), between S. aureus meningitis model group and S. aureus meningitis + vancomycin treated group (F=5. 97, P = 0. 016). There was a positive correlation between CSF bacterial load and CSF leukocyte count in E. coli and S. aureus meningitis model groups (r=0. 89, 0.84, respectively; P = 0.046, 0.049, respectively). Conclusions In the treatment of bacterial meningitis, effective and sufficient antibiotics should be used as soon as possible to control the CSF bacterial load and reduce the mortality. The CSF leukocyte count can be used as indicator of CSF bacterial load and guide the antibiotic treatment in clinical bacterial meningitis.

Dynamic changes of high-sensitive C-reactive protein and visfatin in patients with acute traumatic injury of brain / 中华急诊医学杂志

Objective To observe the dynamic changes of high-sensitive C-reactive protein (hs-CRP) and visfatin in patients with acute traumatic injury of brain. Method A total of 120 patients with equal number in each gender ( n = 60) and with average age of (43.2 ± 6.2) years were admitted and treated by the neurosurgical department of ICU from August 2009 to June 2010. All patients were eligible to the diagnostic criteria of craniocerebreal injury. The clinical conditions of patients were assessed with Glasgow coma scale (C CS) at admission,and as per the scores of GCS, the patients were classified into mild degree (13- 15, n = 40), moderate degree (9 - 12, n = 40) and severe degree (3 - 8, n = 40). Another 60 subjects from those asking for health care by physical examination as control with equal number in each gender and their average age was (42.2±6.7) years.Blood samples were collected from fasted patients within 12 hours, 1d, 3d, 7d and 15 days after admission, and the levels of hs-CRP and visfatin in peripheral blood were detected. Results The levels of hs-CRP and visfatin were significantly higher in brain injury group than those in control group on the admission day (both P ＜ 0.01 ),and they both had positive relationships with severity of injury. The level of hs-CRP increased to peak on the first day of admission and visfatin increased to the peak on the 3rd day after admission. There was a correlation between levels of hs-CRP and visfatin ( r = 0.63, P ＜ 0.01 ). Conclusions hs-CRP and visfatin levels are related to the severity of acute traumatic injury of brain.

The Study of Morphological Distributions of Lymphatic Vessels in Peripheral Areas of Uterine Cervix Cancer and Metastasis / 医学研究杂志

Objective To investigate the metastasis mechanism by observing morphological distributions of lymphic vessels in peripheral areas of the different development of uterine cervix cancer. Methods Cancer tissues from the center, peripheral and normal areas of uterine cervix cancer respectively were collected. The paraffin sections and semithin sections which were stained with HE were applied to those tissues for exploring the configurations and distributions of lymphic vessels of the cancer under a microscope. And the ultrathin sections were applied to those tissues for exploring under a electronic microscope. Results Under the microscope, the basement membrane had been destroyed by cancer cell, which continued to infiltrate interstitial tissue. Lymphic vessels were increased and dilated in peripheral areas of uterine cervix cancer than those in normal areas. Moreover, the walls of lymphic vessels were hazy and broken. Conclusion The increase and morphologic changes of lymphic vessels in peripheral areas of uterine cervix cancer will play an important role in lymphatic metastasis.

Clinical study of docetaxel and capecitabine(xeloda)combination in the treatment of patients with metastatic breast cancer and previously treaded with anthracyslines / 中国癌症杂志

Background and purpose:With widely use of anthracyclines,patients are easily failed to respond to anthracyclines baseal regimens chemotherapy.Docetaxel and capecitabine(xeloda)are usually considered as the most active agents in breast cancer and are often used as adjuvant chemotherapy.In this study,we evaluated the efficacy and toxicity of docetaxel and xeloda combination regimen in the treatment of patients with metastatic breast cancer and previously treated with anthracyslines.Methods:64 patients who previously failed to respond to adriamycin based chemotherapy received docetaxel and xeloda combination regimen,docetaxel 75 mg/m2 ivgtt,day 1;xeloda 1 250 mg/m2,twice daily,day 1-14.The regimen was repeated every 21 days and the clinical response was recorded after 2 cycles.The effective patients received at least four cycles.Results:In 64 patients,the overall response rate was 60.9%,with 6 patieuts CR and 33 patients PR.The most frequent treatment-related adverse events were leukopenia, fatigue,nausea,vomiting and hand-foot syndrome.The main reactions were myelosuppression,Ⅲ-Ⅳwas 45.8%. Conclusion:Good clinical efficacy were achieved in the therapy of metastatic breast cancer with docetaxel and xeloda combination regimen and toxic reactions are tolerable.