Objective To investigate the cytidylyl phosphate guanosine(CpG) islands methylation status of E-cadherin (E-cad) promoter region in human ovarian carcinoma cell lines (ES-2,3 AO, SKOV3 ), and the effect of 5-azacytidine-2 '-deoxycytidines (5-Aza-CdR ) on the cell proliferative ability, invasion and the expression of E-cad protein. Methods Methylation specific PCR(MSP) was used to detect CpG islands methylation status of E-cad promoter region in ES-2,3AO and SKOV3 cell lines. After treated with different concentrations of 5-Aza-CdR, morphological changes of cell lines were observed under microscope. The proliferative ability was evaluated by methyl thiazolyl tetrazolium(MTT) assay. E-cad protein expression was detected by western-blot and cellular invasion was investigated by 24-well matrigel invasion chambers. Results Hypermethylatian status of CpG islands of E-cad promoter region was observed in ES-2 and SKOV3 cell lines, but not in 3AO cell lines. After treated with 5-Aza-CdR (0.1,1.0,10.0 μmol/L), ES-2 and SKOV3 cell lines displayed morphological evidence of differentiation. 5-Aza-CdR was found to decrease proliferation as evidenced by cell growth curve , to increase the level of E-cad protein expression (P ＜ 0.01 ), and effectively inhibit the ability of cell invasion(P ＜0.01 ). Conclusions CpG hypermethylation is an important mechanism of E-cad gene inactivation in ES-2 and SKOV3 cell lines. 5-Aza-CdR be found to inhibit proliferation and invasion, and increase the expression of E-cad probably by the inhibition of hypermethylation.

Objective A distintegrin and metalloproteinase 33 (ADAM33) is one of the asthma susceptibility gene, which is closely related to the pathogenesis of asthma and airway hyperreactivity.The aim of this study was to evaluate the expression of serum ADAM33 in patients with different severity of asthma and the relation to airway chronic inflammation through clinical trials.MethodsPatients diagnosed as mild-to-moderate asthma (n=54), severe asthma (n=35) and healthy controls (n=30) were recruited from May 2015 to May 2016.The serum IgE, ADAM33, IL-4 and IL-13 1evels and Eosinophil (EOS) in peripheral blood were detected, and the correlation analysis was performed Results The serum levels of ADAM33 in mild-to-moderate asthma group, severe asthma group and healthy control group were 23.8±6.21pg/mL,64.8±12.8pg/mL and 18.3±4.49pg/mL, respectively.The ADAM33 levels in mild-to-moderate asthma group and severe asthma group were higher than those in control group (P<0.05).The ADAM33 levels in severe asthma group were higher than those in mild to moderate asthma group.(P<0.05).The correlation analysis showed that ADAM33 had positive correlation with IL-4 and IL-13(r=0.79 and r=0.81), but no correlation with EOS and IgE(r=0.54 and r=0.46).Conclusion The expression of serum ADAM33 was up-regulated in asthmatic patients along with the severity of asthma.ADAM33 was positively correlated with serum IL-4 and IL-13, implying that the expression of ADAM33 may be regulated by Th2 type cytokines.

Objective To study the tumor targeting ability and application of farnesylthiosalicylic Acid (FTS) and heptamethine carbocyanine fluorescent dye-mediated near-infrared imagine in living animals, and confirm the inhibitory effect of this compound on growth of tumor cells.Methods Human breast cancer cell line MCF-7, glioma cell line U251 and prostate cancer cell line PC3 were cultured to logarithmic growth phase, and different concentrations of FTS and FTS-IR783 were added, respectively.We observed the inhibitory effect of those two compounds on the growth of tumor cells.Under fluorescence microscopy, specific accumulation of FTS-IR783 in these tumor cells was observed.The tumor cells (1×106) were transplanted subcutaneously into nude mice.These mice were subjected to intraperitoneal injection of FTS-IR783 (10 nmol/mouse) two weeks later.In the in vivo imaging, near infrared fluorescence signal and tumor volume were measured and their correlation was analyzed.Results Compared with FTS, FTS-IR783 significantly inhibited the growth of MCF-7, U251 and PC3 cells in vitro.FTS-IR783 was specifically uptaken by these three kinds of tumor cells, showing strong near infrared fluorescence in cell agglomerates.After subcutaneous injection of FTS-IR783, the correlation between fluorescence intensity and tumor volume was 0.987, 0.998 and 0.971, respectively.Conclusions The compound of FTS conjugated with near infrared fluorescent dye IR-783 can specifically recognize tumor cells, in both in vitro and in vivo imaging.At the same time, the compound can significantly inhibit the growth of tumor cells, and may be expected to become a new potential targeted drug.

Objective:To investigate the effect of body mass index (BMI) on clinical pregnancy and neonatal outcomes in patients with polycystic ovary syndrome (PCOS) during frozen-thawed embryo transfer.Methods:A total of 650 patients with PCOS who received routine in vitro fertilization or intracytoplasmic sperm injection treatment for frozen-thawed embryo transfer from June 2014 to June 2019 in Tianjin Central Hospital of Gynecology Obstetrics were retrospectively analyzed. According to BMI, PCOS patients were divided into group A (18.5≤BMI<23 kg/m 2, n=253), group B (23≤BMI<25 kg/m 2, n=167), and group C (BMI≥25 kg/m 2, n=230). The general information, clinical pregnancy outcomes, pregnancy complications, the incidence of macrosomia and low-birth-weight infants were compared in the three groups, and the influencing factors of neonatal birth weight were analyzed. Results:The embryo implantation rate, clinical pregnancy rate, and ongoing pregnancy rate all showed downward trend with the increase of BMI, but the differences were not statistically significant (all P>0.05). The live birth rate in group C [47.0% (108/230)] was significantly lower than those in groups A and B, with statistical significance ( χ2 =7.43, P=0.024). The late miscarriage rate was higher in group C [9.4% (13/139)] than in groups A and B ( χ2 =7.66, P=0.022). The birth rates of macrosomia in groups B [22.2% (16/72)] and group C [21.1% (16/76)] were significantly higher than that in group A, and the difference was statistically significant ( χ2 =14.15, P=0.001). There was no statistically significant difference in the incidence of gestational diabetes between the three groups ( χ2 =3.81, P=0.149). The incidence of hypertension disorders complicating pregnancy increased with the increase of BMI, and the difference was not statistically significant ( P>0.05). Regression analysis showed that macrosomia was significantly associated with maternal pre-pregnancy BMI and gestational weeks, and the risk of macrosomia increased by 15% (95% CI: 3%-28%) for every increase in maternal BMI. Conclusions:The embryo implantation rate, clinical pregnancy rate, and ongoing pregnancy rate of PCOS patients in frozen-thawed embryo transfer cycles show downward trend with the increase of BMI. Obese patients with PCOS have a significant increase in late miscarriage rate and a significant decrease in live birth rate. The incidence of hypertension disorders complicating pregnancy in PCOS patients in the obese group has an increasing trend, and the birth rate of macrosomia has increased significantly. Therefore, it is recommended that obese women with PCOS lose weight scientifically before pregnancy to improve pregnancy and neonatal outcomes.

Objective: To compare clinical characteristics and prognosis between patients with primary (PTL) and secondary thyroid lymphoma (STL) . Methods: A retrospective analysis was performed on 46 patients with thyroid lymphoma (PTL 19, STL 27) from January 2002 to October 2018. Results: ①PTL group included 4 males and 15 females, with a median age of 57 years. The STL group included 10 males and 17 females, with a median age of 61 years. Diffuse large B-cell lymphoma (DLBCL) was the main pathological subtype in both PTL and STL groups, with 14 cases (73.7%) and 20 cases (74.1%) respectively. In terms of clinical manifestations, goiter was the most common symptom in PTL patients 100.0% (19/19) , while 29.6% (8/27) STL had goiter (P<0.001) . The incidences of increased thyroglobulin antibody (TRAb) /thyroid peroxidase antibody (TPO) were 81.3% (13/16) in PTL group and 43.8% (7/16) in STL group (P=0.028) respectively. Concerning the clinical features of patients, only two PTL patients (10.5%) with advanced Ann Arbor stage (Ⅲ/Ⅳ) , while 21 (77.8%) STL experienced advanced Ann Arbor stage (P<0.001) . Elevated serum β₂-MG were appeared in 1 (7.1%) PTL and 9 (47.4%) STL patients (P=0.013) , and advanced IPI score (3-5) was more common in STL than PTL (59.3% vs 5.3%, P<0.001) . ②Among the 17 PTL patients who received treatments, 15 (88.2%) achieved remission; as for STL patients received treatments, 23/25 (92.0%) were in remission. The 5-year overall survival (OS) rates of PTL (n=17) and STL groups (n=25) were (87.4±8.4) % and (70.0±13.1) % (P=0.433) respectively. ③The 5-year OS rate in 41 patients with B-cell thyroid lymphoma was (81.1±7.5) %. Univariate analysis showed that IPI score of 3-5 (P=0.040) and high level of serum IL-8 (P=0.022) were significantly associated with poor outcome. Conclusion DLBCL was the most common subtype in both PTL and STL, and goiter was the major symptom in PTL. IPI score of 3-5 and high level of serum IL-8 were unfavorable prognostic factors for patients with B-cell thyroid lymphoma.

Objective: To investigate the efficacy of RCDOP (Rituximab, cyclophosphamide, liposome doxorubicin, vincristine and prednisone) regimen in patients with de novo diffuse large B-cell lymphoma (DLBCL), especially in those patients with multiple extra-nodal involvement or Bulky diseases. Methods: A total of 87 newly diagnosed DLBCL patients who received RCDOP regimen from October 2012 to October 2017 were enrolled into this study. Survival functions were estimated using the Kaplan-Meier method and compared by the log-rank test, and χ² tests were used for categorical data. Results: Among the 87 DLBCL patients treated with RCDOP regimen, 81 patients achieved complete remission (CR) or partial remission (PR), with ORR as 93.1%. Patients were further classified into groups, according to the risk factors, such as IPI scores, multiple extra-nodal involvement, bulky disease, age>60, tumor Ki-67>80%, elevated serum LDH level and advanced Ann Arbor stage. The progression-free survival (PFS, P=0.084) and overall survival (OS, P=0.515) had no statistical difference among the IPI low risk (0-1 score) group, intermediate risk (2-3 scores) group and high risk (4-5 scores) group. Similarly, no statistical difference were fou nd in PFS and OS of patients with extra-nodal involvements ≥2 (P=0.303 and P=0.624), with bulky disease (P=0.518 and P=0.466), with age>60 (P=0.600 and P=0.183), with elevated serum LDH level (P=0.054 and P=0.880), with advanced Ann Arbor stage (P=0.075 and P=0.286), and with tumor Ki-67 over 80% (P=0.190 and P=0.109), when compared with those of patients without these risk factors. Conclusion RCDOP can improve the therapeutic effect and prognosis of DLBCL patients with certain high risk factors, such as intermediate and high IPI risks, multiple extra-nodal involvements, bulky disease, age over 60, elevated LDH level, advanced Ann Arbor stage and tumor Ki-67 over 80%.

Objective To explore the relationship between geriatric nutritional risk index(GNRI)and adverse outcomes in elderly patients undergoing maintenance hemodialysis(MHD).Methods A prospective cohort trial was conducted on 337 MHD patients aged ≥60 years in hemodialysis centers of 11 hospitals in Beijing from April to June 2017.Their baseline data were collected,and they were divided into non-malnutrition(GNRI≥98,226 cases),mild malnutrition(92≤GNRI＜98,81 cases),and major malnutrition groups(GNRI＜92,30 cases).All of them were followed up until June 2018.The endpoint events were all-cause mortality and cardiovascular disease(CVD)mortality.Kaplan-Meier survival analysis was used to compare the cumulative survival rate among the 3 groups.Multivariate Cox regression model was employed to analyze the relationship of GNRI with all-cause and CVD mortality.Results The mild and major malnutrition groups had significantly lower BMI,serum albumin level and GNRI(P＜0.01).During the median follow-up of 52(4.4-52.0)weeks,56(16.6％)patients died of all-cause death and 25(44.6％)of CVD death.Kaplan-Meier survival curve showed significant differences in all-cause mortality(x2=30.484,P＜0.01)and CVD mortality(x2=22.398,P＜0.01)in the 3 groups.Multivariate Cox regression analysis indicated that,as a continuous variable,elevated GNRI was a protective factor for all-cause mortality(HR=0.910,95％CI:0.870-0.952,P=0.000)and CVD mortality(HR=0.895,95％CI:0.852-0.940,P=0.000),and as a categorical variable,mild and major malnutri-tion were independently correlated with all-cause and CVD mortality(P＜0.05).Conclusion GNRI is an independent risk factor for all-cause and CVD mortality in elderly MHD patients.Mo-nitoring the nutritional status using GNRI can predict the risk of adverse prognosis.

Objective:To explore the relationship between geriatric nutritional risk index (GNRI) and modified creatinine index (mCI) and all-cause mortality in maintenance hemodialysis (MHD) patients.Methods:It was a prospective cohort study. The MHD patients aged≥50 years old at hemodialysis centers of eleven hospitals in Beijing from April to June 2017 were selected as subjects. Baseline clinical data of the patients were collected. The patients were divided into high GNRI group (≥98) and low GNRI group (<98), and high mCI group (≥20.16 mg·kg -1·d -1) and low mCI group (<20.16 mg·kg -1·d -1), and further divided into 4 groups: G1 group (high GNRI and high mCI), G2 group (high GNRI and low mCI), G3 group (low GNRI and high mCI) and G4 group (low GNRI and low mCI). The differences of clinical characteristics among the four groups were compared. The patients were followed-up until June 2018 or death or loss, and the endpoint event was all-cause mortality. Kaplan-Meier survival analysis was used to compare the differences of the cumulative survival rates among the four groups. A multivariate Cox regression model was used to analyze the relationship between GNRI and mCI and all-cause mortality. Results:A total of 613 patients were included in the study, aged (63.65±7.78) years old (ranged from 50 to 81 years old), with 355 males (57.91%). The GNRI and mCI were (99.35±5.75) and (20.16±2.79) mg·kg -1·d -1, respectively. There were 232 patients (37.85%) in the G1 group, 177 patients (28.87%) in the G2 group, 95 patients (15.50%) in the G3 group, and 109 patients (17.78%) in the G4 group. There were statistically significant differences in age, sex, proportion of diabetes, proportion of coronary heart disease, body mass index, serum albumin and serum creatinine among the four groups (all P<0.05). A total of 69 patients (11.26%) died during a median follow-up time of 52(4, 52) weeks. Kaplan-Meier survival curve results showed that the mortality of patients with low GNRI was higher than that of patients with high GNRI (log-rank χ 2=26.956, P<0.001), and the mortality of patients with low mCI was higher than that of patients with high mCI (log-rank χ 2=25.842, P<0.001). The mortality was 3.45% in group G1, 10.73% in group G2, 9.47% in group G3, and 30.28% in group G4, and the differences among the four groups were statistically significant (log-rank χ 2=57.153, P<0.001). Multivariate Cox regression analysis results showed that as continuous variables, GNRI ( HR=0.911, 95% CI 0.882-0.941, P<0.001) and mCI ( HR=0.873, 95% CI 0.797-0.956, P=0.003) were correlated with all-cause death. As categorical variables, compared with high GNRI group and high mCI group, patients with low GNRI ( HR=3.469, 95% CI 2.125-5.665, P<0.001) and low mCI ( HR=3.255, 95% CI 1.879-5.640, P<0.001) had higher risks of death. Compared with G1 group, patients in G2 group ( HR=2.488, 95% CI 1.079-5.738, P=0.033) and G4 group ( HR=9.449, 95% CI 4.362-20.470, P<0.001) had higher risks of death. Conclusions:GNRI and mCI are independent predictive factors of all-cause mortality in MHD patients. The combination of GNRI and MCI can more accurately predict the risk of all-cause death in middle-aged and elderly MHD patients.

Objective:To investigate the association between body mass index (BMI) and waist circumference (WC) with all-cause mortality in middle-aged and elderly patients receiving maintenance hemodialysis (MHD).Methods:It was a prospective cohort study. The clinical data of MHD patients aged ≥50 years old from eleven hemodialysis centers from April to June 2017 in Beijing were analyzed. The patients were divided into low BMI group [body mass index (BMI)<18.5 kg/m 2], normal BMI group (18.5 kg/m 2≤BMI <24.0 kg/m 2), overweight group (24.0 kg/m 2≤BMI<28.0 kg/m 2) and obesity group (BMI≥28.0 kg/m 2) by BMI, and central obesity group (male ≥85 cm, female ≥80 cm) and normal WC group (male <85 cm, female <80 cm) by WC. Kaplan-Meier survival analysis method was used to compare the difference of all-cause mortality between those groups. Multivariate Cox regression model was used to analyze the association of BMI and WC with all-cause mortality. Results:A total of 613 MHD patients were enrolled, with age of (63.82±7.14) years old and 258 (42.09%) females. There were 46 (7.50%) patients in the low BMI group, 303 (49.43%) patients in the normal BMI group, 227 (37.03%) patients in the overweight group and 37 (6.04%) patients in the obesity group. In addition, 346 (56.44%) patients were categorized as central obesity. Kaplan-Meier survival analysis results showed that the all-cause mortality rates of low BMI group (log-rank χ2=13.571, P<0.001) and obesity group (log-rank χ2=6.664 P=0.010) were higher than that of normal BMI group, and the all-cause mortality rate of central obesity group was higher than that of normal WC group (log-rank χ2=5.698, P=0.017). Multivariate Cox regression analysis results showed that，besides the low BMI group and obesity group (with normal BMI group as a reference, HR=5.289, 95% CI 2.318-12.067, P<0.001; HR=5.360, 95% CI 2.088-13.760, P<0.001, respectively), normal BMI and overweight combined with central obesity were also independently correlated with all-cause mortality (with normal WC group as a reference, HR=2.605, 95% CI 1.199-5.663, P=0.016; HR=1.787, 95% CI 1.026-3.732, P=0.031, respectively). Conclusions:Lower and higher BMI or combined central obesity are independently associated with all-cause mortality in the middle-aged and elderly patients receiving MHD.

Objective:To investigate the changes and associated factors of cerebral blood flow in middle-aged and elderly patients undergoing maintenance hemodialysis (MHD).Methods:This was a prospective observational study. End-stage renal disease (ESRD) patients undergoing MHD aged over 50 years at Beijing Shijitan Hospital, Capital Medical University from January 2023 to June 2023 were included. General clinical data of the selected individuals were collected, and dialysis related indicators were recorded and calculated. Mean flow velocity (MFV) of the middle cerebral arterial was measured by transcranial Doppler sonography (TCD) to represent cerebral blood flow throughout dialysis. Hemodialysis-related variables were collected. The MFV values of bilateral middle cerebral artery were measured through temporal windows at 7 time points: 15 minutes before dialysis (T1), 15 minutes (T2), 30 minutes (T3), 60 minutes (T4), 120 minutes (T5), 180 minutes (T6) during dialysis, and the endpoint of dialysis (T7), and the average values were recorded. The ΔMFV was calculated as pre-minus endpoint values of MFV. The Spearman rank correlation method was used to analyze the correlations between ΔMFV and dialysis-related variables, and multiple linear regression method was used to analyze the related factors of the changes in MFV.Results:This study included a total of 123 patients undergoing MHD, aged (63.63±8.44) years (range 50-85 years), including 99 males (80.5%). TCD examination demonstrated a decline trend in MFV throughout dialysis. The MFV at T7 was significantly lower than that at T1 ( Z=-7.650, P<0.001). The Spearman correlation analysis showed that the decline in MFV was correlated with ultrafiltration volume ( r=0.356), ultrafiltration rate ( r=0.371), the difference in systolic pressure (pre-analysis minus post-dialysis, r=0.251), the difference in mean arterial pressure (pre-dialysis minus post-dialysis, r=0.194), combined diabetes ( r=0.293), dialysis vintage ( r=0.220), Kt/V ( r=0.287), and serum albumin ( r=-0.295). Multiple linear regression analysis showed that combined with diabetes ( B=3.889, 95% CI 1.373-6.405, P=0.003), decreased serum albumin ( B=-0.456, 95% CI -0.877--0.036, P=0.034), increased ultrafiltration rate ( B=11.099, 95% CI 6.402-15.797, P<0.001) and the decline in systolic pressure ( B=0.062, 95% CI 0.008-0.116, P=0.026) were significantly associated with the decline in MFV throughout dialysis. Conclusions:In middle and elderly patients with ESRD undergoing hemodialysis, there is a decline trend in cerebral blood flow during hemodialysis. The combination of diabetes, lower serum albumin, higher ultrafiltration rate, and intradialytic systolic pressure decline are the risk factors influencing the intradialytic decline of cerebral blood flow.