Objective To evaluate the effect of oxycodone on migration of human colon cancer cells and the role of μ and κ receptors.Methods The human colon cancer HCT116 cells at the logarithmic growth phase were seeded in 24-well or in 6-well plates at a density of 1 × 106 cells/mnl (0.5 ml/well or 2 ml/well,144 wells in total).The cells were divided into 6 groups (n=24 each) using a random number table:control group (group C),1,5 and 10 μmol/L oxycodone groups (group O1,group O2 and group O3),oxycodone plus μ receptor antagonist CTOP group (group O2+CTOP) and oxycodone plus κ receptor antagonist nor-binaltorphimine group (group O2+BNI).The cells were incubated for 24 h with oxycodone 1,5 and 10 μmol/L in O1,O2 and O3 groups,respectively.The cells were incubated for 24 h with 5 μmol/L oxycodone plus 20 μmol/L CTOP and 5 μmol/L oxycodone plus nor-binahorphimin 20 μmol/L in O2+CTOP and O2+BNI groups,respectively.The invaded and migrated cells were counted,and the levels of Ras homolog gene family member A (RhoA),Rho-associated protein kinase 1 (ROCK1),matrix metalloproteinase-2 (MMP-2) and MMP-9 were detected.Results Compared with group C,the number of invaded and migrated cells was gradually decreased,and the levels of RhoA,ROCK1,MMP-2 and MMP9 were gradually decreased in O1,O2 and O3 groups (P＜0.05),and no significant change was found in the parameters mentioned above in group O2+BNI (P＞0.05).Compared with group O2,the number of invaded and migrated cells was significantly increased,and the levels of RhoA,ROCK1,MMP-2 and MMP9 were increased in group O2 + BNI (P＜0.05),and no significant change was found in the parameters mentioned above in group O2+CTOP (P＞0.05).Conclusion Oxyc odone can inhibit the migration of human colon cancer cells,and the mechanism is totally related to inhibition of RhoA/ROCKl signaling pathway activation after activating κ receptors,but not related to μ receptors.

Objective To investigate the expression of macrophage migration inhibition factor (MIF) and cell cycle regulating factor Cyclin D1 in hepatocellular carcinoma tissue and the interaction between MIF and Cyclin D1 in hepatocellular carcinoma cell cycle controlling. Methods Using quantitative real-time PCR and Western blotting to detect mRNA and protein expression of MIF and Cyelin DI in HCC tissues and tumor adjacent tissues. Specific small interfering RNA(siRNA) targeting MIF gene was transfccted at doses of 50 nmol/L and 100 nmoL/L into HCC cell lines of PLC and HepG2 with lipofeetamine 2000 methods to knockdown the expression of M1F gene and to investigare the the interaction between M1F and Cyclin D1. Results MIF and Cyclin D1 protein and mRNA were overexpressed in HCC tumor tissues. The relative expression of MIF,Cyclin D1 protein and mRNA were 0.825±0.13,0.843± 0.104 and 7.31±1.85 folds、4.27±1.05 folds, compared with the tumor adjacent tissues (FMIF= 15.5, P<0.01;FCyclin D1=87.5,P <0.01). In MIF siRNA treated PLC and HepG2 cells, MIF mRNA down regulation 71.2%±7.2%, 87.4%±2.9% ,74.3%±8.9% and 88.4%±4.6% respectively (FPLC = 315.5 ,P < 0.01 ; FHepG2= 201.2 P < 0.01). While MIF protein expression were significandy reduced to 0.33±0.03,0.11±0.02, 0.81±0.08 and 0.36±0.02 in a dose-dependent manner (FPLC= 43.9, P <0.01 ;FHepG2 = 133.4 P <0.01). Cyclin D1 mRNA was significantly down-regnlated in MIF siRNA treated PLC and HepG2 cell lines when compared with control group(P <0.01). In 50 nmol/L and 100 nmol/L groups, Cyclin DI mRNA levels were respectively decreased by 68.2%±3% and 78.1%±1.4% in PLC cell, 65.8%±4.7% and 77.3%±2.6% in HepG2 cell (FPLC= 1569, P < 0.01 ; FHepG2= 480.4, P <0.01). Compared with control groups, Cyclin D1 protein levels significantly reduced to 0.28±0.06、0.15±0.03 and 0.44 ±0.04、0.13±0.02 in the PLC and HepG2 after M IF siRNA treatment(FPLC= 35.5, P < 0.01 ; FHepG2 = 114.7, P < 0.01). Conclusions MIF and Cyclin D1 mRNA and protein were overexpressed in HCC tumor tissues and participated in tumor cell cycle regulation. MIF may up-regnlate the expression of Cyclin DI via ERK signalling and precipitate in carcinogenesis of hepatocellular carcinoma.

Objective To evaluate the application of exponential apparent diffusion coefficient (eADC)value in differentiating benign from malignant thyroid nodules.Methods Routine MR sequences and axial diffusion weighted imaging (DWI)sequences with different b-values(0, 300,500,800 s/mm2)were performed in 46 patients with 51 histopathologically confirmed thyroid nodules,including 35 malignant nodules and 1 6 benign nodules.The eADC values of each thyroid nodules’solid component with different b-values were measured and assessed by independent samples t test.Receiver operating characteristic (ROC)curves were drawn and used to determine the diagnostic threshold and assess the screen test.Results The eADC values of the malignant nodules were higher than that of benign nodules (P<0.05)in all of the three different b-values.The eADC values of the malignant nodules and the benign nodules were 0.618±0.080 and 0.492±0.071 (b=300 s/mm2),0.520±0.104 and 0.371±0.077 (b=500 s/mm2)and 0.407±0.114 and 0.286±0.097 (b=800 s/mm2)respectively. According to the ROC curve,the area under the curve(AUC)was 0.883,0.890 and 0.824 when the b-value was set as 300,500 and 800 s/mm2respectively.When the b-value was set as 500 s/mm2and the diagnostic threshold was 0.454,the sensitivity,specificity, positive predictive value,negative predictive value and Youden index were 74.3%,93.8%,96.3%,60.9% and 0.68,respectively.Conclusion The eADC value is helpful in differentiating benign from malignant thyroid nodules,and the best result can be obtained by using DWI with b-value of 500 s/mm2.

Objective To evaluate the cost-utility of different hepatitis E vaccination strategies in women aged 15 to 49.Methods The Markov-decision tree model was constructed to evaluate the cost-utility of three hepatitis E virus vaccination strategies.Parameters of the models were estimated on the basis of published studies and experience of experts.Both methods on sensitivity and threshold analysis were used to evaluate the uncertainties of the model.Results Compared with non-vaccination group,strategy on post-screening vaccination with rate as 100％,could save 0.10 quality-adjusted life years per capital in the women from the societal perspectives.After implementation of screening program and with the vaccination rate reaching 100％,the incremental cost utility ratio (ICUR) of vaccination appeared as 5 651.89 and 6 385.33 YuaWQALY,respectively.Vaccination post to the implementation of a screening program,the result showed better benefit than the vaccination rate of 100％.Results from the sensitivity analysis showed that both the cost of hepatitis E vaccine and the inoculation compliance rate presented significant effects.If the cost were lower than 191.56 Yuan (RMB) or the inoculation compliance rate lower than 0.23,the vaccination rate of 100％ strategy was better than the post-screening vaccination strategy,otherwise the post-screening vaccination strategy appeared the optimal strategy.Conclusion Post-screening vaccination for women aged 15 to 49 from social perspectives seemed the optimal one but it had to depend on the change of vaccine cost and the rate of inoculation compliance.

Objective To investigate the efficacy and safety of new oral anticoagulants(NOACs)rivaroxaban and dabigatran versus warfarin in the treatment of the patients with non-valvular atrial fibrillation combined with diabetes mellitus.Methods A retrospective study was performed on 119 cases of patients with non-valvular atrial fibrillation combined with diabetes mellitus from outpatient and inpatient of the Ninth People's Hospital of Suzhou City from Jan 2019 to June 2021.According to the use of anticoagulants,patients were divided into rivaroxaban 10 mg group(Group A,n=25),rivaroxaban 15 mg group(Group B,n=30),dabigatran group(Group C,n=29),and warfarin group(Group D,n=35).All patients were treated continuously for at least 6 months.The incidence of embolism and bleeding events,the changes of coagulation indicator,blood glucose,liver and kidney function indexes were compared before and after treatment among the four groups.Results Thromboembolic events:1 cases(4.00%)of stoke or thromboembolic events occurred in Group A;2 cases(6.67%)occurred in Group B;2 cases(6.90%)occurred in Group C,and 5 cases(14.28%)occurred in Group D.Bleeding events:1 cases(4.00%)of bleeding events occurred in Group A;1 cases(3.33%)occurred in Group B;2 cases(6.90%)occurred in Group C,and 8 cases(22.85%)occurred in Group D.There was no statistically significant difference among the four groups of stoke or thromboembolic events(P>0.05).The incidence of bleeding events in Group A and B were both statistically lower than Group D(P<0.05),and the risk of bleeding events of Group C was similar to Group D(P>0.05)and there was also no statistically significant difference among Group A,B and C(P>0.05).The activated partial thromboplastin time(APTT)of all patients was significantly prolonged after treatment compared with before treatment(P<0.05),but none of them exceeded the upper limit of the normal value by 2 times.The APTT and international normalized ratio(INR)values of Group A and B,INR values of Group C were all statistically better than those of Group D(P<0.05)after the treatment.There were no statistically significant difference in the comparison of blood glucose,liver and kidney function index as well(P>0.05).Conclusion The new oral anticoagulants rivaroxaban and dabigatran showed similar effects in prevention of stroke or thromboembolic events,but better safety profiles with lower risks of bleeding events compared to warfarin in patients with non-valvular atrial fibrillation combined with diabetes mellitus.Dabigatran is comparable in efficacy and safety when compared with rivaroxaban and deserves to be promoted for clinical use.

Objective:To investigate the efficacy of hemodiafiltration combined with hemoperfusion in the treatment of secondary hyperparathyroidism (SHPT) in patients undergoing maintenance hemodialysis (MHD).Methods:A total of 40 patients with SHPT undergoing MHD who received treatment at the Blood Purification Center of The First Affiliated Hospital of Anhui University of Science and Technology from February 2021 to March 2023 were included in this prospective cohort study. They were randomly divided into a control group and an observation group ( n = 20/group).The control group received a single high flux hemodialysis, while the observation group used a combination of hemodialysis filtration and hemoperfusion for 3 months. In both groups, the changes in hemoglobin, blood urea nitrogen, serum creatinine, serum calcium, serum phosphorus,and parathyroid hormone levels were compared before and after dialysis. Results:After dialysis, the hemoglobin level in the observation group was (119.45 ± 5.27) g/L, which was significantly higher than (106.30 ± 6.52) g/L in the control group ( t = -7.02, P < 0.001). The serum phosphorus level in the observation group was (1.18 ± 0.17) mmol/L, which was significantly lower than (1.52 ± 0.22) mmol/L in the control group ( t = 5.49, P < 0.001). The parathyroid hormone level in the observation group was (122.14 ± 40.57) ng/L, which was significantly lower than (168.78 ± 78.27) ng/L in the control group ( t = 2.39, P = 0.023). Conclusion:Hemodiafiltration combined with hemoperfusion can reduce clinical symptoms, increase hemoglobin level, and reduce phosphorus and parathyroid hormone levels in patients with SHPT undergoing MHD, which deserves clinical promotion.

Objective:To investigate the association between body mass index (BMI) trajectories in children and adolescents and subclinical renal damage (SRD) in adulthood.Methods:4 623 participants aged 6-18 years old were recruited from the ongoing cohort of Hanzhong adolescent hypertension study in 1987, and the subjects were followed up in 1989, 1992, 1995, 2005, 2013 and 2017, respectively. Group-based trajectory modeling was used to identify distinct BMI trajectories in longitudinal analysis. Generalized linear model was applied to examine the association between different BMI trajectories and SRD incidence in adulthood.Results:A total of 2 678 subjects from childhood to adulthood were enrolled in this study. All subjects were divided into three groups according to three distinct BMI trajectories: low-increasing BMI group ( n=1 017), moderate-increasing BMI group ( n=1 353), and high-increasing BMI group ( n=308). Over follow up for 30 years, a total of 248 participants (9.3%) developed SRD. Urinary albumin-to-creatinine ratio (uACR) in low to high-increasing BMI group was 0.9(0.6, 1.4), 1.0(0.7, 1.7), 1.6(0.8, 3.2), respectively ( P trend<0.001), and estimated glomerular filtration rate was 98.5(87.6, 111.6) , 96.2(86.4, 109.7), 95.3 (87.5, 125.0) ml·min -1·(1.73 m 2) -1, respectively ( P trend=0.025). The generalized linear model analysis showed that uACR was increased linearly from low to high-increasing BMI group [ β=3.16(95% CI 1.02-5.31), Ptrend=0.004]. There was no correlation or linear trend between BMI trajectory and estimated glomerular filtration rate [ β=-2.30(95% CI-5.18-0.57), Ptrend=0.117]. Compared with the low-increasing BMI group, the high-increasing BMI group had greater odds of experiencing SRD in adulthood after adjusting for multiple confounders such as age, gender, medical history and lifestyle ( OR=2.83, 95% CI 1.84-4.36, Ptrend<0.001). Conclusions:Higher BMI trajectorie is correlated with higher level of uACR and risk of SRD in middle age. Identifying long-term BMI trajectorie from early age may assist in predicting individuals′ renal function in later life.

OBJECTIVETo explore the anti-inflammatory and analgesia mechanism of electroacupuncture (EA) device of point injection (PI) on rats of inflammatory pain.

METHODS48 Sprague Dawley (SD) rats were randomly assigned into a control group, a model group, an EA+PI group, an EA device of PI (EAPI) group, an EA group and a PI group, eight rats in each one. The rats in the control group were subcutaneously injected with 50 μL of liquid paraffin oil solvent into the dorsum of left hindpaw, while rats in the remaining groups were treated with 50 μL of complete freund's adjuvant (CFA) at identical location to induce the model of inflammatory pain. After model establishment, the rats in the EA+PI group, EAPI group, EA group and PI group were treated with EA+PI,EA device of PI, EA and PI, respectively, once every other day (the 2nd day, 4th day and 6th day). Each treatment was given for 30 min. The mechanical withdrawal threshold, thermal withdrawal threshold and foot swelling before and 1 d to 6 d after model establishment were observed; the western blotting method was applied to measure IL-1β expression in inflammatory tissue of skin.

RESULTSAfter model establishment, compared with the control group, the mechanical withdrawal threshold and thermal withdrawal threshold were reduced (all<0.05) and the foot swelling was increased in the rest groups (all<0.05). After treatment, the mechanical withdrawal threshold and thermal withdrawal threshold in the EAPI group were significantly increased compared with those in the EA+PI group, EA group and PI group (all<0.05), but the foot swelling was reduced (all<0.05). The IL-1β expression in the model group was higher than that in the control group (<0.05); after treatment, the IL-1β expression in the EAPI group was lower than that in the model group, EA group and PI group (all<0.05), but no significantly different from that in the EA+PI group (>0.05).

CONCLUSIONSThe efficacy of EA device of PI on inflammatory pain is superior to EA combined with PI, EA alone and PI alone, which is suitable for further popularization and application.

【Objective】 Based on our previously established salt-sensitive hypertension cohort, we conducted chronic salt loading and potassium supplementation interventions, aiming to examine the association between genetic variants in renalase and blood pressure (BP) responses to dietary interventions of salt and potassium intake. 【Methods】 In 2004, 514 subjects from 126 families were recruited in Shaanxi Province to establish the salt-sensitive hypertension study cohort. Among them, 334 non-parent subjects were selected and sequentially maintained on a low-salt diet for 7 days, then a high-salt diet for 7 days and a high-salt diet with potassium supplementation for another 7 days. Ten single nucleotide polymorphisms (SNPs) in the renalase gene were genotyped on the MassARRAY platform. 【Results】 SNP rs2576178 of the renalasegene was significantly associated with systolic BP (SBP) and mean arterial pressure (MAP) responses to low-salt intervention (SBP: β=-2.730, P<0.05; MAP: β=-1.718, P<0.05). In addition, SNP rs12356177 was significantly associated with diastolic BP response to low-salt diet (β=-1.608, P<0.05). However, we did not find any association for the renalase SNPs with BP response to high-salt diet with potassium supplementation reached nominal statistical significance. 【Conclusion】 Genetic variants in renalase gene are significantly associated with BP response to low-salt diet, suggesting that renalase may be mechanistically involved in BP salt-sensitivity.

【Objective】 Dyslipidemia has shown to be associated with cardiovascular, metabolic and renal diseases. This study aimed to investigate the association between residual cholesterol and the risk of subclinical renal damage (SRD). 【Methods】 A total of 2 342 participants were recruited from the previously established Hanzhong Adolescent Hypertension Study cohort. According to estimated glomerular filtration rate(eGFR) and urinary albumin-to-creatine ratio(uACR), the subjects were divided into SRD group and non-SRD group. The associations of residual cholesterol with eGFR, uACR, and the risk of SRD were analyzed by multiple linear and Logistic regression analyses. 【Results】 Residual cholesterol was positively correlated with uACR(r=0.081, P<0.001) but negatively correlated with eGFR (r=-0.091, P<0.001). Multiple linear regression analysis revealed that residual cholesterol was an influencing factor of uACR (β=0.075, P<0.001) and eGFR (β=-0.027, P<0.001) after adjustment for gender, age, smoke, alcohol, exercise, BMI, hypertension, diabetes and serum uric acid. In addition, Logistic regression analysis revealed that residual cholesterol was significantly associated with the risk of SRD independently of potential confounders [OR(95% CI)=1.387 (1.113-1.728), P<0.001]. Further subgroup analysis showed that residual cholesterol was significantly associated with the risk of SRD in women but not in men. 【Conclusion】 Residual cholesterol is a contributing factor in the risk of subclinical renal damage with gender-specific association.