1.Frequency and suppressor function of CD4+CD25+T cells in ascites and blood of patients with ovarian cancer
Hairong YAO ; Jing TIAN ; Yingchun LI ; Wenqi ZHANG ; Quan HAO
Chinese Journal of Clinical Oncology 2014;(12):787-792
Objective:CD4+CD25+regulatory T cells (Treg) may contribute to tumor progression by suppressing antitumor im-munity. The function of Treg in antitumor immunity regulation in the peritoneal microenvironment of ovarian cancer (OC) was investi-gated and compared with the circulating Treg to elucidate OC immune escape. Methods: Flow cytometry was used to determine the proportion of CD4+CD25+T cells in CD4+T cells in ascites of 27 patients with OC and in peripheral blood lymphocytes of 28 patients with OC. The samples were analyzed and classified in three stages:primary disease (PD), after chemotherapy (AC), and recurrence dis-ease (RD), according to the clinical conditions of the OC patients upon donating the samples. The percentage of Treg in the three groups was determined in ascites and blood. CD4+CD25+T cells were isolated from ascites and peripheral blood of patients with OC us-ing magnetic sorting (MACS) system. The cells were then tested for regulatory function through coculture with carboxyfluorescein diac-etate succinimidyl ester-labeled autologous CD4+ CD25- responder cells. Results:The proportion of CD4+ CD25+T cells in CD4+T cells significantly increased in ascites (28.25%± 14.06%) compared with that in blood (14.6%± 4.74%;P<0.0001). The Treg in ascites and blood in AC showed higher proportion (P<0.0001) than those in the PD and RD;the proportion in RD was higher than that in PD (P<0.0001). Moreover, the Treg in ascites mediated a significantly higher suppression compared with the Treg in peripheral blood (P<0.001). Conclusion:The frequency and suppressor function of Treg were significantly higher in ascites than in peripheral blood. This finding suggests more possibility for escape immune surveillance in the peritoneal microenvironment. Moreover, the proportion of Treg in AC was higher than that in PD or RD;the proportion in RD was higher than that in the PD. Chemotherapy may favor the expansion of Treg, which may promote the recurrence of cancer.
2.High-mobility group protein B1 (HMGB1) and its potential in diagnosis and treatment of ovarian cancer
Yingchun LI ; Jing TIAN ; Hairong YAO ; Wenqi ZHANG ; Quan HAO
Chinese Journal of Clinical Oncology 2014;(7):425-429
Objective:The objective of this research is to study the serum level of the high-mobility group protein B1 (HMGB1) in human ovarian tumor (OvCa) and in a healthy control. This study also aims to identify different HMGB1 levels before and after sur-gery and to explore the inhibitory effect of HMGB1 gene silencing in the proliferation and invasion ability of OvCa. Methods: En-zyme-linked immunosorbent assay was used to measure the serum level of HMGB1 in OvCa patients and healthy subjects. Lentivirus vector with HMGB1 shRNA was constructed and used to infect OvCa cells. The expressions of HMGB1 mRNA and protein were test-ed by real-time PCR and Western blot. Cell proliferation was detected using the Cell Counting Kit-8 assay, whereas cell invasion and migration were detected by Transwell assay. Results:The serum level of HMGB1 was more elevated in patients with malignant diseas-es compared with individuals with benign diseases and the control groups. In the malignant group, the serum level of HMGB1 de-creased noticeably after therapy. Down-regulation of HMGB1 expression resulted in the inhibition of the biological behavior and metas-tasis of ovarian cancer cells. Conclusion: HMGB1 is closely associated with clinicopathologic features of OvCa. Knockdown of HMGB1 expression can significantly inhibit cell proliferation, cell migration, and cell invasion of OvCa. These findings indicate that HMGB1 can function as a therapeutic target for ovarian neoplasm in the future.
3.Immuno-suppression and mechanism of CD4+CD25+T cells in ascites of ovarian cancer patients
Hairong YAO ; Jing TIAN ; Yingchun LI ; Wenqi ZHANG ; Quan HAO
Chinese Journal of Clinical Oncology 2014;(9):560-565
Objective: This research explores the relationship between the immuno-suppression function of regulatory T cells (Treg) in the ascites of ovarian cancer (OC) patients, the clinico-pathologic features of these patients, and the correlation of the function of Treg with initial treatment and relapse status of the patients to further investigate the specific mechanism of immuno-regulatory func-tion of CD4+ CD25+ Treg in the ascites of OC. Methods: Immuno-magnetic activated cell sorting (MACS) was conducted to sort CD4+CD25+Treg and autologous CD4+CD25-Treg from the ascites of 28 OC patients. Carboxyfluorescein-diacetate succinimidyl ester (CFSE) was used to label the autologous CD4+CD25-Treg. These labeled cells were then used as controls and co-cultured with autologous CD4+CD25+Treg at the ratio of 1∶1 or 1∶2. The mean inhibition ratio of Treg in specimens to the proliferation of autolo-gous CD4+ CD25-Treg was calculated after the flow cytometry of the CFSE expression and Modfit software analysis of the CD4+CD25-Treg proliferation index (PI) were performed. Anti-IL-10 and/or anti-TGF-β1 antibodies were neutralized to investigate whether the CD4+CD25+Treg-mediated immuno-suppression escaped through the ascites can produce a marked effect by the inhibitory cyto-kine IL-10 or TGF-β1. Results: The mean inhibition ratio of CD4+ CD25- Treg in the ascites of stage Ⅲ to Ⅳ OC patients was (75.72±17.04)%, which is significantly higher than that of stageⅠtoⅡOC patients (59.61±16.97)%;P<0.05. In addition, Treg in the as-cites of OC patients with recurrent disease showed a significantly higher inhibition ratio than that of patients with primary disease;P<0.001. Moreover, Treg in groups added into neutralizing anti-IL-10 and/or anti-TGF-β1 antibodies displayed significantly lower depres-sant effect than the control group;P<0.05. Conclusion:The immuno-suppression of CD4+CD25+Treg in the ascites of OC patients is correlated with the tumor staging and status of the primary or recurrent diseases. Moreover, Treg may indicate a suppressor function by secreting cytokine IL-10 and TGF-β1.
4.Effects of delivery mode on postpartum fecal incontinence and urinary incontinence in Chinese women
Hongxia ZHANG ; Xin YANG ; Hairong YAO ; Rui WANG ; Xiaohua LI ; Haiyang YU ; Huixia YANG ; Yue DONG
Chinese Journal of Perinatal Medicine 2011;14(10):598-602
Objective To investigate the prevalence and associated factors of fecal incontinence (FI) and urinary incontinence (UI) in postpartum Chinese women.Methods Questionnaires about FI and UI symptoms were completed via telephone interviews conducted within six months after delivery.Multi-variant Logistic analysis was applied for relation between delivery mode and FI or UI.Results (1) Two thousand and twelve postpartum women were admitted into this study,among which 14 (0.7%) had FI within 6 months after delivery.Logistic regression analysis showed that FI was significantly associated with forceps delivery (OR =20.09,95 % CI:3.64-110.90,P =0.000),and mediolateral episiotomy (OR=6.11,95% CI:1.29-28.80,P=0.024).(2) Among the 2012 women,the prevalence of UI,stress urinary incontinence (SUI),urgent urinary incontinence (UUI)and mixed urinary incontinence (MUD was 10.04% (n=202),8.15% (n=164),0.94% (n=19)and 0.94 % (n =19),respectively.Logistic regression analysis found that SUI prevalence was related to maternal age (OR =1.07,95% CI:1.04-1.11,P =0.000),maternal weight before delivery (OR=1.04,95% CI:1.02-1.06,P=0.001),neonatal head circumference (OR=1.20,95% CI:1.05-1.39,P =0.010),mediolateral episiotomy (OR =4.96,95 % CI:3.05-8.07,P =0.0005 ),spontaneous vaginal delivery (OR=5.22,95% CI:2.53-10.76,P=0.000) and forceps delivery (OR=9.20,95% CI:4.07-20.79,P=0.000).UUI was related to maternal weight before delivery (OR=1.51,95% CI:1.12-2.05,P=0.008).MUI was related to maternal weight before delivery (OR=1.06,95% CI:1.00-1.11,P=0.049),duration of second stage of labor (OR=1.01,95% CI:1.00-1.03,P =0.010),mediolateral episiotomy (OR =7.76,95% CI:1.42-42.52,P=0.017) and forceps delivery (OR=15.21,95% CI:1.61-143.44,P=0.018).(3) The prevalence of SUI was higher at 4 days and 42 days after delivery (7.95% and 9.10%).Conclusions (1) F1 and UI prevalence is lower in this study than in other reports.(2) Vaginal delivery is a risk factor for women's FI and UI,especially forceps delivery and mediolateral episiotomy.(3) Maternal age,pre-delivery weight,newborn head circumference,spontaneous vaginal delivery,forceps delivery and mediolateral episiotomy might increase the risk of UI.
5.Effect of Mg-Zn alloy on integrin beta-1 expression in osteoblasts
Yan ZHANG ; Hairong TAO ; Yaohua HE ; Yao JIANG ; Shaoxiang ZHANG ; Xiaonong ZHANG
Chinese Journal of Tissue Engineering Research 2009;13(38):7531-7534
BACKGROUND: A novel biodegradable Mg-Zn alloy is designed which the density and the Young's modulus are proximal to human bone. At the same time, it depletes the toxicity of aluminium and rare earth element in commercial magnesium alloys. OBJECTIVE: To observe the effect of Mg-Zn alloy (Mg-6%Zn) on the integrin βi expression of preosteoblasts MC3T3-E1. DESIGN, TIME AND SETTING: A contrast study was performed at the Central Laboratory of the Sixth People's Hospital Affiliated to Shanghai Jiao Tong University between March and May 2008. MATERIALS: The Mg-6% Zn was prepared by School of Materials Science and Engineering of Shanghai Jiao Tong University, which the density was 1.82 g/cm~3 and the Young's modulus was nearly 44 GPa. Poly-L-lactic acid (PLLA) was used as the controls. MC3T3-E1 cells were provided by Chinese Academy of Science Type Culture Collection. METHODS: The cell attachment was observed after cultured with Mg-Zn and PLLA at 2, 24 and 48 hours under scanning electron microscope; the integrin β1 mRNA expression of MC3T3-E1 cultured with Mg-Zn and PLLA was estimated by real-time fluorescent quantitative polymerase chain reaction (real-time PCR) at days 1, 3, 6, 9,12 and 15 after culture. MAIN OUTCOME MEASURES: The MC3T3-E1 cells attachment on the material surface and the integrin β1 mRNA expression. RESULTS: MC3T3-E1 cell adhesion was better on the Mg-Zn alloy surfaces than on the PLLA surface; The integrin (31 mRNA of osteoblasts on Mg-Zn kept on expressing during experiment and increased with time (P < 0.01), but there was no significantly difference between the two groups at the same time (P > 0.05). CONCLUSION: MC3T3-E1 cell adhesion is better on the Mg-Zn alloy surfaces than on the PLLA surface, but it is not mediated by inducing the integrin p1 mRNA expression.
6.Cephal CT scanning for distinguishing tumor-like inflammatory demyelinating diseases from glioma or primary central nervous system lymphoma
Jianguo LIU ; Xiaokun QI ; Sheng YAO ; Feng QIU ; Hairong QIAN ; Wenluo ZHANG ; Wei WANG ; Zengmin TIAN
Chinese Journal of Neurology 2010;43(1):14-19
Objective To explore the value of brain CT scanning for distinguishing tumor-like inflammatory demyelinating diseases (TIDD) from glioma or primary central nervous system lymphoma.Methods The brain CT features in 20 patients with TIDD(10 female,10 male;mean age (35.6±14.0)years;range,6-51 years)and 32 gliomas(16 female,16 male;mean age(42.0±19.8)years;range,12-75 years)and 6 lymphomas(3 female,3 male;mean age(53.8±11.8)years;range,32-68 years)were retrospectively reviewed and compared between brain tumors and TIDD.Results (1)Among the 38 primary brain tumors,there were 19 cases(50%,14 gliomas,5 lymphomas)with hyperdense lesions,10 cases(26.3%,9 gliomas,1 lymphomas)with isodense lesions,and 9 glionms (23.7%)with hypodense lesions.In contrast,the brain unenhanced CT manifestation of 20 TIDD all showed with hypodense lesions.(2)On unenhanced CT the lesions of 6 lymphomas all were hyperdense or isodense,like 90% of 20 high grade gliomas(WHO grade Ⅲ and Ⅳ),but this rate for grade Ⅱ was only 41.7%.(3)According to the shape of hyperdense lesions of the 19 primary brain tumors with,7 cages(6 gliomas,1 lymphomas)manifested with asymmetric hyperdense small-patches,4 cases(1 gliomas,3 lymphomas)with symmetric hyperdense large-patches,4 cases(3 gliomas,1 lymphomas)with diffused hyperdensed lesions,and 4 cases(4 gliomas)with ring-shaped hyperdensed lesions.Furthermore,4 primary brain tumors(4 lymphomas)underwent CT enhanced scanning and all the cases showed strong enhancement(3 cases with hyperdense lesions and 1 with isodense lesions on unenhanced CT),but only 3 cases of 7 TIDD showed mild enhancement in contrast.(4)By Spearman's relevant analysis,hyperdense and isodense on unenhanced CT was proved to have significant positive correlation between the grade of gliomas(r=0.435,P=0.013).Therefore,the frequency of hyperdense and isodense lesions in lymphomas and WHO grade Ⅲ and Ⅳ astrocytoma was higher in contrast with low grade astrocytoma.Conclusions Brain CT as a simple,economical and practical examination method has significant meaning for differentiating TIDD from glioma or PCNSL and could be used as an adjuvant method for MRI and magnetic resonance spectroscopy.Patients with hyperdense or isodense on unenhanced CT or strong enhancement could be excluded from TIDD.
7.The clinical features, neuroimaging findings and pathological characteristics of 26 patients with pathologically proven tumor-like inflammatory demyelinating diseases
Xiaokun QI ; Jianguo LIU ; Hairong QIAN ; Feng QIU ; Sheng YAO ; Changqing LI ; Yaming WANG
Chinese Journal of Internal Medicine 2010;49(9):750-753
Objective To summarize the clinical features, neuroimaging findings and pathological characteristics of 26 patients with tumor-like inflammatory demyelinating diseases (TIDD) confirmed by histopathology for better diagnosis and differential diagnosis. Methods The clinical features, neuroimaging findings and pathological characteristics of 26 patients (14 male, 12 female) with pathologically proven TIDD(24 brain-type and 2 spinal cord-type ) were retrospectively analysed. Results The mean onset age was 6-69 (36.7±13.8) years. Twenty-one patients had good prognosis with a median followed-up duration of 51.0 months. Two patients were died of post-operative complication and pulmonary infection respectively and the remaining 3 patients were lost to followed up. The TIDD patients almost showed monophasic clinical setting. Headache, indifference accompanied with hypomnesis were the commonest initial symptoms. The positive or abnormol rates of cerebrospinal fluid oligoclonal bands (OCB) and myelin basic protein (MBP)in TIDD patients were high. The involvements of bilateral and multi-lesions were commonest in TIDD (61.5%, 65.4% respectively). Twenty-two patients with CT unenhanced scanning showed hypodense lesions. Long T1 and long T2 signal intensity was showed on MRI and most cases apeared round-like lesion in shape. Acccording to the shape of enhancement of the 23 patients performed with contrast agents, 11 were shown with open-ring enhancement, 4 cases (including 2 accompanied with open-ring enhancement) with complete ring enhancement, 3 with asymmetrical dotted enhancement, 2 with diffused even enhancement,and no enhancement was seen in the other 6. Furthermore, 14 cases with DWI and 12 with FLAIR all appeared hyperdensity. The typical pathological changes were demyelinating, perivascular inflammatory cells infiltration and reactive gliosis. Occationally, the Creutzfeuldt cells were also found in brain tissue of some patients. Conclusions TIDD is a distinct demyelinating disease entity. In spite of being apt to be confused with the neoplasm in brain and spinal cord. TIDD has its own-features, for example, OCB is frequently positive in patients with TIDD and the level of MBP may be significantly increased. Furthermore, the involvements of bilateral and multi-lesions are the common in TIDD, and most cases showed open-ring enhancement or complete rim enhancement on MRI. In addition, all cases present hypodense lesions on unenhanced CT and patients with hyperdense seemed not to be considered as TIDD.
8.Leukoencephalopathy with cerebral calcification and cysts: a case report and review of literature
Hairong QIAN ; Yuhong MENG ; Qiuping GUI ; Kuihong ZHENG ; Sheng YAO ; Xiaokun QI
Chinese Journal of Internal Medicine 2013;(5):403-406
Objective To improve the diagnostic ability of leukoencephalopathy with cerebral calcifications and cysts (LCC),a rare central nervous system disease.Methods The clinical manifestations,neuroimages and neuropathological features of a 19-year-old male patient were analyzed.A total of 20 cases from 14 literatures were reviewed.Results The patient was admitted with right limb weakness,cognitive decline,headache and blurred eyesight.Head CT scan showed multiple calcifications,cysts formation and leukoencephalopathy.Brain MRI showed several cysts in bilateral hemisphere,basal ganglia,thalamus and paraventricular areas.A mural nodule was noted inside one of the cyst,which was enhanced on the contrasted MRI.The wall of the cysts was partially enhanced,but not with the fluid inside the cysts.The corresponding CT calcifications foci showed on T1 and T2 with either both hyperintensity or both hypointensity,which was also partial enhanced.Extensive leukoencephalopathy was formed around the cysts and the ventricles.But neither Cho nor NAA changed a lot on MRS.Amplitude diagram of SWI series exhibited multiple round small dark signals all over the affected areas with mixed signals showed in the phase diagram,which indicated both calcifications and microbleedings at the lesions.Neuropathological examinations found no tumor cells in the operated cyst,and showed angiomatous small blood cells were dominant in the cyst wall.Hyaline degenerations,microcalcifications and hemosiderin deposition were observed.No obvious demyelination was discovered,while gliosis,numerous Rosenthal fibers and fibrinoid vascular necrosis were found around the lesions.The clinical,neuroimaging and pathological features of this patient were in accordance with the cases reported in the literatures.Conclusions Neuroimaging is the most important method for the diagnosis of LCC.As small vessel lesions are probably closely related to the pathophysiology of LCC,SWI could be recommended to further reveal the etiology of LCC.
9.Degradation of dicalcium phosphate dihydrate-coated Mg-Zn alloy and bone formation in vivo
Hairong TAO ; Jianhua GU ; Yaohua HE ; Yan ZHANG ; Shaoxiang ZHANG ; Yang SONG ; Jianan LI ; Changli ZHAO ; Yao JIANG ; Xiaonong ZHANG
Journal of Shanghai Jiaotong University(Medical Science) 2009;29(12):1410-1414
Objective To investigate the degradation of dicalcium phosphate dehydrate-coated Mg-Zn alloy in vivo and bone formation. Methods Left femoral condyles were drilled in 72 New Zealand rabbits, and were randomly divided into experiment group (n=24, implanted with dicalcium phosphate dehydrate-coated Mg-Zn alloy rods), Mg-Zn alloy control group (n=24, implanted with Mg-Zn alloy rods) and poly-L-lactide acid rod group (n=24, implanted with poly-L-lactide acid rods). Serum concentrations of Mg~(2+) were examined 1 d pre-operation, and 1 d, 1 week, 2 weeks, 5 weeks and 10 weeks post-operation in experiment group and Mg-Zn alloy control group. Operation sites were examined by X-rays at 3, 6, 12 and 18 weeks post-operation. After X-ray examination at each time point, 6 rabbits in each group were sacrificed, and subjected to histopathological observation of live and kidney tissues by HE staining. Tissues from condyles of femur were observed by HE staining and 2, 4, 6-trinitrophenol rosein staining, and mineral apposition rate of bone was calculated. Results There was no significant difference in the concentrations of serum Mg~(2+) at each time point between Mg-Zn alloy control group and experiment group (P>0.05). X-ray examination revealed gas emerged near the implants 3 weeks after surgery in Mg-Zn alloy control group. However, there was no obvious histological abnormality in liver and kidney tissues. The mineral apposition rate was higher and the degradation of material was lower in experiment group than those in the other two groups. Conclusion Dicalcium phosphate dehydrate-coated Mg-Zn alloy has a favourable biocompatibility, and degrades more slowly in vivo.
10.Long-term survival trends for liver cancer in Qidong: 1972 to 2011.
Hairong YAO ; Hao CHEN ; Jianguo CHEN ; Jian ZHU ; Yonghui ZHANG
Chinese Journal of Hepatology 2014;22(12):921-925
OBJECTIVETo determine the survival rates of liver cancer in Qidong during the years 1972-2011, according to the data from a population-based cancer registry, in order to assess the long-term trends for prognosis of this cancer type.
METHODSThe deadline of the last follow-up for survival status of the 28, 398 registered cases was April of 2012. Cumulative observed survival (OS) and relative survival (RS) rates were calculated using Hakulinen's method performed by the SURV3.01 software developed by the Finnish Cancer Registry.
RESULTSThe 1-, 3-, 5-, 10-and 15-year OS rates were 15.18%, 6.23%, 4.26%, 2.79% and 2.39%, respectively; the 1-, 3-, 5-, 10-and 15-year RS rates were 15.47%, 6.60%, 4.69%, 3.41% and 3.29%, respectively. For males, these OS rates were 14.95%, 6.05%, 4.06%, 2.67% and 2.26%, and these RS rates were 15.23%, 6.41%, 4.47%, 3.26% and 3.12%, respectively. For females, these OS rates were 15.89%, 6.79%, 4.87%, 3.17% and 2.80%, and these RS rates were 16.20%, 7.20%, 5.37%, 3.87% and 3.82%, respectively. No statistical differences were found between the male and female groups (P>0.05). The 5-year RS rates for age groups 15-34, 35-44, 45-54, 55-64, 65-74 and 75+ years-old were 4.42%, 4.29%, 4.96%, 4.67%, 4.67% and 6.35%, and the 10-year RS rates were 3.17%, 2.98%, 3.44%, 3.47%, 3.75% and 11.27%, respectively. Remarkable improvement was seen for the 1-, 3-, 5-, 10-and 15-year OS rates in this setting since the 1980s.
CONCLUSIONThe survival outcome from Qidong registered cases with liver cancer has shown gradual progress over the past four decades. Early detection and improvement of therapies may be responsible for the improved prognosis of liver cancer. While the disparity gap of survival between this area and developed countries is narrowing, there is still a need for improving the survival in Qidong.
Adolescent ; Adult ; Aged ; Female ; Humans ; Liver Neoplasms ; Male ; Middle Aged ; Prognosis ; Software ; Survival Rate ; Time Factors ; Young Adult