Objective To investigate the distribution of T follicular helper(Tfh)cell subsets in hepa-titis B patients at different immune stages and to clarify the relationships between the level of CXCL13 and the distribution of Tfh cell subsets. Methods Flow cytometry analysis was performed to detect the distribution of Tfh cells. Enzyme-linked immunosorbent assay(ELISA)was performed to measure the levels of CXCL13 in ser-um samples collected from hepatitis B patients. RT-PCR and Western blot assay were used to analyze the expres-sion of CXCL13 in HepG2 and HepG2. 2. 1. 5 cells. Results The percentages of Tfh1 cells were significantly up-regulated at the immune activation(IA)stage,while those of Tfh2 cells were significantly raised at the im-mune tolerance(IT)stage. The percentages of Tfh17 cells in patients at the stage of IT were similar to those in patients at the stage of IA,but were higher than those in responders with HBsAg seroconversion(RP)or healthy controls(HC). The expression of CXCL13 was positively correlated with the percentage of Tfh2 cells. More over,hepatitis B virus(HBV)enhanced the expression of CXCL13 at both transcriptional and translational lev-els. Conclusion HBV might up-regulate the percentage of Tfh2 cells through promoting the expression of CXCL13,which resulted in the induction of immune tolerance. Elucidating the functions of Tfh1,Tfh2 and Tfh17 cells and understanding the type conversion mechanism among the three subsets are important for further researches on HBV-induced immunosuppression.

Objective To explore the relationship between airway responsiveness and bronchial asthma inhalation therapy .Meth-ods Select 50 asthmatic patients as research subjects ,Fluorine given inhaled salmeterol 50 mcg/fluticasone propionate 250 micro-grams ,1-2 times a day ,Respectively before treatment ,after treatment ,3 months ,6 months ,12 months ,conventional pulmonary function tests and bronchial provocation test ,Determination of peak expiratory flow (PEF) ,and a second forced expiratory volume (FEV1 ) ,maximum mid-expiratory flow (MMEF) and specific airway conductance decreased 35% or above to inhaled methacholine the concentration(PC35sGaw) .Results Three months after the majority of patients with clinical symptoms before treatment ,after treatment ,significant improvement ,PEF ,FEV1 increased significantly in all cases of bronchial provocation test is still positive ,six months after treatment ,more than 80% of patients with asthma ,complete control ,lung function returned to normal follow-up prov-ocation test positive cases of 38 cases ,up to 76% after 12 months of treatment ,more than 90% of patients with lung function re-turned to normal .29 cases(58% ) stimulation test positive .Conclusion Asthma clinical indicators have reached complete control to achieve the desired level of time earlier than the airway responsiveness ,airway responsiveness index value in the long-term follow-up of the combination therapy ,and adjust the treatment plan is superior to clinical symptoms and lung function ,is a serious assessment of asthmadegree of judgment and withdrawal of drug treatment of one of the indicators .

Objective To evaluate the techniques and efficacy of artery embolization in the treatment of benign prostatic hyperplasia(BHP).Methods This study included 12 patients(age range,61-82 years) who were diagnosed to have BHP by clinical manifestations,CT and B-ultrasound,with the disease course of 2-16 years.The relevant parameters were as follows:mean residual urine(RU) of 138 ml,Qmax of 9.6 ml/s,mean IPSS of 24.2 and QOL of 4.8.In these patients,the prostate blood-supply arteries were confirmed by super-selective arteriography,and were embolized by injection of PVA and Gelfoam via artery catheters.The pre-and post-operative IPSS,QOL,Qmax and RU were compared.Meanwhile the changes of prostate volume and blood supply were evaluated by CT and B-ultrasound.In addition,the change of urethral diameter was evaluated by urethrography.Results In the 12 patients,21 prostate blood-supply arteries were embolized,including 5 branches of internal iliac artery,9 branches of inferior vesical artery,5 branches of internal pudendal artery,2 branches of obturator artery.The arteries were embolized bilaterally in 9 patients and embolized unilaterally in 3 patients.Postoperatively,the mean IPSS was 4.8;QOL,1.3;Qmax,18.9 ml/s;RU,0-3 ml,which indicated that the urethral obstruction was obviously improved after operation.CT and B-ultrasound showed that the prostate volume was obviously decreased from 127 ml to 90 ml on average with a reduction rate of 71%,and the urethral stricture disappeared on X-ray examination.Color Doppler imaging showed that the blood supply inside the prostate was reduced.Conclusions The artery embolization for the treatment of BHP is a new method with several virtues of less trauma, marked effect,better safety and fewer complications.

Objective To investigate the expression and significance of caveolin-1 in breast carcinoma.Methods Using immunohistochemical method the protein expression of caveolin-1 were analyzed in 105 cases of breast carcinoma and 50 cases of non-cancerous breast tissues.The relationship between caveolin-1 expression and CK5/6,EGFR,and E-cadherin expression was investigated.Clinical data of 105 cases of breast carcinoma were retrospectively analyzed.Results Among 105 cases of breast carcinoma,there were 20 cases of basal-like subtype,22 cases of luminal subtype A,23 cases of luminal subtype B,23 cases of HER2 over-expressing subtype,17 cases of normal breast-like subtype.Positive rate of caveolin-1 was significantly lower in breast carcinoma than in non-cancerous breast tissues (24.8％ vs.88.0％,P ＜ 0.05).Positive rate of caveolin-1 (75.0％) was higher in breast carcinoma than in luminal subtype A ( 4.8％ ),luminal subtype B ( 17.4％ ),HER2 over-expressing subtype ( 17.4％ ) or normal breast-like subtype( 11.8％ ),all P ＜0.05.Caveolin-1 expression was associated with expression of CK5/6 and EGFR(P ＜0.01 ).In univariate analysis,positive caveolin-1 was associated with higher lymph node metastasis rate (18/26,69.2％ )than negative (37/79,46.8％ ),P =0.047,and shorter 5-year-disease-free survival (38.46％ vs.74.68％,P =0.0004 ),but in multivariate analysis caveolin-1 was not an independent predictor of 5-year- disease-free survival (P ＞ 0.05).Conclusions Caveolin-1 can be seen as a screening mark of basal-like breast carcinoma,it may promote the invasiveness of breast cancer cells,but it is not an independent prognostic predictor of breast cancer patients.

Objective To examine the expressions of IKKε protein in the specimens and cells of epithelial ovarian cancer and investigate the effect of IKKε inhibitor on cell proliferation and apoptosis. Methods (1) A total of 118 cases of patients with the median age of 59 who have accepted surgical treatment due to ovarian cancer in the First Affiliated Hospital of Dalian Medical University from January 2006 to April 2013 were selected. Twenty cases of patients with the median age of 55 who have accepted hysterectomy and salpingo-oophorectomy due to uterine leiomyoma during the same period were selected as the control. The expressions of IKKε protein were detected by immunohistochemistry in normal ovarian tissues and epithelial ovarian cancer specimens,and the relationship between the expressions of IKKε and the clinical features of patients was analyzed. IKKε protein was determined by western blot in various ovarian cancer cells, including SKOV3, OV2008, C13, A2780S, A2780CP, OV4, OV5, OV8, and CAOV3 treated with or without IKKε inhibitor. The cellular proliferation and apoptosis of ovarian cancer cells after 48 hours treatment of IKKε inhibitor were analyzed by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively. Results (1) The immunohistochemical results showed that IKKε was highly expressed in epithelial ovarian cancer specimens with the expression rate 66.1% (78/118), compared with normal ovarian tissue with the expression rate 35.0% (7/20), which exhibited statistically significant difference (χ2=6.993, P=0.008). The expression of IKKε protein was correlated with International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade, the level of CA125 in preoperative serum and distribution of the tumor (P<0.05), but no correlation with age, histological type, the incidence pattern, and tumor size (all P>0.05). (2) IKKε was widely overexpressed in different levels in SKOV3, OV2008, C13, A2780S, A2780CP, OV4, OV5, OV8, and CAOV3 cells, and the expression of IKKε decreased as the increase of the concentration of IKKε inhibitor (0.1 and 0.5 μmol/L) in OV2008, C13, A2780S, and A2780CP cells after 48 hours treatment. Different concentrations of IKKε inhibitor (0.05, 0.1, 0.5, 1, 5, 10, and 25 μmol/L) significantly inhibited the proliferation of OV2008, C13, A2780S, A2780CP, and SKOV3 cells in a concentration-dependent manner (P<0.05), and the half maximal inhibitory concentration (IC50) was 0.43, 0.86, 0.10, 0.19, and 0.24 μmol/L, respectively. The cell apoptotic rate of OV2008, C13, A2780S, A2780CP, and SKOV3 cells was significantly increased after 48 hours treatment of IKKεinhibitor with the concentration of 0.1 and 0.5 μmol/L (P<0.05). Conclusions The IKKε protein in epithelial ovarian cancer specimens and cells is overexpressed. IKKε inhibitor could inhibit cellular proliferation and induce apoptosis in a concentration-dependent manner. Together, the result indicated that IKKε may be a candidate target for the treatment of ovarian cancer in future.

Objective To investigate the roles of glutamate signaling pathway in the activation of human peripheral blood lymphocytes(PBLs) and pathogenesis of vitiligo.Methods Peripheral blood lymphocytes (PBLs) isolated from 5 patients with generalized vitiligo and 5 healthy controls were cultured in vitro.Flow cytometry was performed to quantify the expression of CD25 and interferon-γ on PBLs derived from healthy controls and treated with MK801 (a non-competitive antagonist of N-methyl-D-aspartic acid receptor,NMDAR) at 100 μmol/L or phosphate buffered saline (PBS) for 48 hours,as well as the level of reactive oxygen species (ROS) in the controlderived PBLs treated with MK801 at 100 μmol/L,NMDA (an agonist of N-methyl-D-aspartic acid receptor) at 0.5 mmol/L or PBS for 48 hours.The protein and mRNA expressions of NMDAR1 and NMDAR2A were measured by flow cytometry and real-time PCR,respectively,in PBLs from the healthy controls and vitiligo patients.Immunohistochemistry was used to observe the expressions of NMDAR1 and NMDAR2A in tissue specimens from depigmented and postinflammatory hyperpigmentation lesions of the patients with vitiligo and from normal skin of the healthy controls.Results Compared with the PBS-treated PBLs from the healthy controls,the MK801-treated PBLs showed a downregulated expression of CD25 (7.28％ ± 0.18％ vs.16.02％ ± 0.42％,P ＜ 0.01),but an upregulated proportion of CD25+IFN-γ+ lymphocytes (1.79％ ± 0.09％ vs.0.78％ ± 0.06％,P ＜ 0.01),and the NMDA-treated PBLs displayed a higher ROS level (101.1 ± 3.50 vs.69.80 ± 2.08,P＜ 0.01 ).The protein expression of NMDAR1 in PBLs was significantly higher in vitiligo patients than in the healthy controls (3.85 ± 2.17 vs.0.97 ±0.55,P ＜ 0.05).Conclusion Glutamate signaling pathway may be involved in the immunopathogenesis of vitiligo via affecting the secretion of interferon-γ by,and ROS level in,activated lymphocytes.

Neuroendocrine tumors(NET) is a rare tumor with high heterogeneity.Pancreatic NET is the most common type in China. European Neuroendocrine Tumor Society(ENETS) has launched the ENETS guidelines since 2006 and published the ENETS standard of care in 2009. With the newly targeted therapies and further research on NET, 2017 new edition of the ENETS standard of care has changed a lot in the diagnosis and treatment of NET. This article explains the update of pancreatic NET in the 2017 edition of the ENETS standard of care, and introduces pancreatic NET from pathology, imaging examination, surgery, systemic therapy, etc., and deepens the understanding of the diagnosis and treatment of pancreatic NET.

Objective To investigate the potential heart sparing effects of tangential volumetric modulated arc therapy (T-VMAT) by comparing its dosimetric properties with conventional wedged tangential fields (W-TF) technique and 6-field intensity-modulated radiotherapy (6F-IMRT) in the locoregional radiotherapy of left breast cancer after conserving surgery,including internal mammary nodal irradiation.Methods Fifteen patients with left breast cancer were enrolled in this study.Three plans were generated for each patient:W-TF,6F-IMRT and T-VMAT with two arc segments of 50°.The prescription dose to planning tumor volume (PTV) was 50 Gy in 25 fractions.Dose-volume parameters and indices of conformity were calculated and compared for the PTV and organs at risk (OAR).Results Compared with W-TF,T-VMAT not only significantly decreased D D and the high dose areas (above 10 Gy) of the heart and left anterior descending branch (LAD) (P ＜ 0.05),but also had the trend of sparing the V5Gy although there was statistically significant difference (P ＞ 0.05).T-VMAT also significantly decreased Dmean V5Gy,V10Gy and V20Gy of the heart,as well as the D V5Gy and V10 Gy of LAD (P ＜ 0.05),compared to 6F-IMRT.Furthermore,T-VMAT did not result in higher V20Gy of ipsilateral lung and higher V5Gy of contralateral breast compared with W-TF (P ＞ 0.05).T-VMAT achieved distinctly better target coverage and conformity,meanwhile obviously lowered hot volume of V110 compared to W-TF (P ＜ 0.05).Conclusions T-VMAT not only significantly decreased the high dose areas,but also had the trend of sparing the low dose area for the heat and LAD.Moreover,there was no significant difference for V20Gy of ipsilateral lung and V5Gy of contralateral breast between T-VMAT and W-TF.

Objective:To compare the dosimetric differences between volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) on planning target volume (PTV) and organ-at-risk (OAR) for breast cancer after modified radical mastectomy, aiming to provide evidence-based reference for clinical practice.Methods:According to strict inclusion and exclusion criteria, literature search was performed in PubMed, Cochrane Library, FMRS, CNKI, Wanfang Data and VIP full text databases from the inception of databases up to March 2020. The controlled clinical trials of dosimetric comparison between VMAT and IMRT for breast cancer following modified radical mastectomy were selected. The meta-analysis was performed using Stata14 software.Results:The meta-analysis included 281 patients from 13 observational studies. Compared with IMRT, VMAT significantly increased the PTV dose coverage D 95%( P<0.001) and significantly improved the PTV homogeneity index (HI, P<0.001) and conformity index (CI, P=0.004). Compared with IMRT, VMAT more effectively decreased the ipsilateral lung V 20Gy (WMD=1.332, P=0.027) and contralateral lung V 10Gy ( P=0.003). There were no significant differences in theD mean, V 5Gy, V 10Gy and V 30Gy of the ipsilateral lung, D mean and V 5Gy of the contralateral lung, D mean, V 10Gy and V 30Gy of the heart between VMAT and IMRT (all P>0.05). Compared with VMAT, IMRT reduced the cardiac V 5Gy ( P=0.001). However, sensitivity analysis of included literature on cardiac V 5Gy showed that the P value was reversed, indicating that the stability of the results was poor. VMAT significantly shortened the delivery time ( P<0.001) and the number of monitor units ( P<0.001) compared to IMRT. Conclusion:Compared with IMRT, VMAT can achieves superior target dose coverage, HI and CI, better protection for the ipsilateral and contralateral lung, fewer monitor units and shorter delivery time.