Objective To investigate the effect of nimesulide(NIM) on human breast cancer cell lines, including MDA?- MB?- 231(estrogen receptor?- negative) and MCF?- 7 (estrogen receptor?- positive). Methods MDA?- MB?- 231 and MCF?- 7 human breast carcinoma cell lines were treated with NIM in vitro. Cell proliferation was evaluated by MTT assay, distribution of cell cycle and rate of apoptosis were determined by flow cytometry, meanwhile the rates of apoptosis were estimated on the basis of Annexin V apoptosis detection. The apoptosis was confirmed by ultrastructural alternations. Results The inhibitory effects of NIM on proliferation of MDA?- MB?- 231 and MCF?- 7 cells were associated with cell cycle arrest in G0/G1 phase and with induction of apoptosis, in a time and dose?- dependent manner. Simultaneously, NIM may also inhibit proliferation and stimulate apoptosis of MCF?- 7 cells. Conclusions NIM inhibits proliferation and induces apoptosis not only in ER?- positive, but also in ER?- negative breast cancer cells. There were two different mechanisms underlying the anti?- carcinogenic action of NIM, namely, dependent on the expression of COX?- 2 protein or not.

Objective To observe the effect of nimesulide (NIM) on DMBA-induced mammary tumors and to investigate possible mechanisms of inhibiting tumors. Methods The Wistar rats were randomly divided into four groups: DMBA group, NIM+DMBA group, NIM+diet group and diet group. The incidence and mean latent phase of mammary tumors were observed. The number and volume of tumors in every rat were measured. The apoptosis index and proliferation index were evaluated by TUNEL assay and PCNA immunohistochemical staining respectively.Results The latent phases of mammary tumors in NIM+DMBA group were strikingly longer than those in DBMA group 〔(115?14.8) d vs (84?15.6) d, P

Objective To evaluate the effects of different analgesics combined with propofol of intravenous anesthesia on postoperative analgesia and emotion in patients of artificial abortion. Methods One hundred and twenty-two patients who had underwent painless artificial abortion were selected. The patients were divided into 4 groups by random digits table method: simple propofol group (C group, 29 cases), fentanyl combined with propofol group (F group, 30 cases), oxycodone combined with propofol group (Q group, 30 cases) and sufentanil combined with propofol group (S group, 33 cases). The induced dose of propofol was 2.5 mg/kg. When patients had limb movement during operation, a single addition of propofol 0.5 mg/kg was added until the body movement disappeared. The changes of mean arterial pressure (MAP), heart rate and respiratory rate before and after operation were compared among the 4 groups. The emotional status was assessed with affective scale before operation and 1 h after operation. The visual analog scale (VAS) was used to evaluate the degree of abdominal pain at 10, 30 and 60 min after palinesthesia. The propofol dose, operation time, recovery time and adverse reaction were recorded. Results No obvious adverse reactions were found during the operation. There was no statistical difference in operation time among 4 groups (P>0.05). The propofol dose, recovery time, body movement and the VAS score at 10, 30, 60 min after palinesthesia in F group, Q group and S group were significantly lower than those in C group, and there were statistical differences (P<0.05);but there were no statistical difference among F group, Q group and S group (P>0.05). The MAP, heart rate and respiratory rate at beginning of the surgery and during the surgery were significantly lower than that before anesthesia in the 4 groups, and there were statistical differences (P<0.05); but there were no statistical differences in MAP, heart rate and respiratory rate among 4 groups (P>0.05). The positive affective score after operation in C group, F group, Q group and S group was significantly higher than that before operation: (24.6 ± 5.6) scores vs. (21.7 ± 6.2) scores, (24.6 ± 3.1) scores vs. (20.6 ± 4.6) scores, (28.3 ± 6.3) scores vs. (20.8 ± 5.3) scores and (25.2 ± 5.4) scores vs. (19.9 ± 4.8) scores, and the negative affective score after operation in C group, F group, Q group and S group was significantly lower than that before operation: (17.0 ± 5.3) scores vs. (29.7 ± 7.4) scores, (17.2 ± 3.0) scores vs. (30.8 ± 5.0) scores, (16.1 ± 5.1) scores vs. (30.4 ± 4.9) scores and (17.9 ± 4.0) scores vs. (32.1 ± 5.5) scores, and there were statistical differences (P<0.05). The positive affective score after operation in Q group was significantly higher than that in C group, F group and S group, and there was statistical difference (P<0.05). There was no statistical difference in negative affective score after operation among 4 groups (P>0.05). Conclusions The fentanyl, sufentanil and oxycodone combined with propofol of intravenous anesthesia in patients underwent artificial abortion can reduce propofol dose, shorten recovery time, improve positive affective score, decrease negative affective score and strengthen the analgesic effect, and doesn't increase the adverse reaction. The respiratory and circulatory inhibition effects of different analgesics combined with propofol of intravenous anesthesia were similar, but oxycodone can increase positive affective score.

Objective To analyse the frequeney and pattern of lymph node metastasis in bilateral papillary thyroid microcarcinoma (PTMC), and establish the optimal surgical strategy for patients. Methods From March 2006 to August 2008, 58 bilateral PTMC patients received surgical treatment and the tumour characteristics, the frequency and pattern of lymph node metastasis and surgical management of these patients were retrospectively analysed. Results Forty-four patients received total thyroideetomy and 14 patients received near-totsl thyroideetomy, 47 patients received central compartment (level VI ) dissection and cervical level Ⅱ,Ⅲ, IV node exploration by internal jugular vein exposure,10 patients received level Ⅵdissection and unilateral cervical dissection and 1 patient received bilateral cervical dissection. The mean tumor diameter was (6.28 + 2.23) mm and 26 patients (44.8%) had node involvement, 88.5%(23/26) pa-tients had only level Ⅵ node involvement. Only 1 patient had node involvement in the jugular chain without level Ⅵ node involvement, 2 patients with level Ⅵ node involvement were associated with another cervical compartment nodes involvement. Conclusions Bilateral PTMC has high incidence of lymph node metasta-sis. The cervical level Ⅵ is the most common site of node involvement for bilateral PTMC and the surgical strategy for bilateral PTMC should include the cervical level Ⅵ dissection routinely.

Background and purpose: Death-associated protein kinase-1(DAPK) is a pro-apoptosis protein,and plays a important role in oncogenesis and development.This study is to investigate the expression of mRNA of DAPK1 and its association with apoptosis in papillary thyroid carcinoma(PTC).Methods:The expression of DAPK1 mRNA was detected by in situ hybridization in 45 cases of PTC and 45 cases of normal thyroid tissues next to tumors that consist of three part of tissue: normal thyroid tissue,nodular goiter and follicular adenoma.The apoptosis in corresponding issues was tested by TUNEL assay and the apoptosis index(AI) was evaluated.Results:The positive rate of DAPK1mRNA in PTC and para-PTC tissues were 37.78% and 71.11%,respectively.The positive rate of DAPK1 mRNA in counterpart thyroid issues was higher than that in tumor tissues(P0.05).Conclusions:As an apoptosis promoter,DAPK1 may function as an inhibitor of tumor,and low expression or loss DAPK1 gene may be involved in the oncogenesis of PTC.The detection of the expression of DAPK1 may be helpful for judging metastasis and prognosis of PTC.

Objective To investigate the protective effect of hypoxia-inducible factor-1α(HIF-1 α) on the neurovascular unit in rats with traumatic brain injury (TBI).Methods The fluid percussion model was applied to induce TBI in rats.A total of 600 rats were divided into sham operation group,TBI group,TBI + HIF-1 α silence group and TBI + control virus group according to the random number table,with 150 rats in each.Virus-mediated HIF-1 α silence gene and control virus were delivered 24 h before the fluid percussion injury.After 3,7 and 14 d,brain injury area and morphological changes in injured region were detected by HE staining,expressions of vascular endothelial cell markers (vWF) and HIF-1 α were detected by Western blot method,and expressions of vascular endothelial growth factor (VEGF),matrix metalloproteinase-9 (MMP-9),tumor necrosis factor-α (TNF-α),interleukin 6 (IL-6) and nuclear factor-κB (NF-κB) in peripheral blood and brain tissue were detected by ELISA method.Rat neural function was dynamically assessed using the modified neurological severity score (mNSS).Results (1) Brain injury area and edema area in TBI + HIF-1 α silence group were higher than those in TBI group at all time points (P ＜ 0.05).(2) Compared with sham operation group and TBI + control virus group,expression of HIF-1α in TBI group gradually increased and remained high at 7 and 14 d postinjury (P ＜ 0.05).Compared with TBI group,expression of vWF in TBI + HIF-1αsilence group decreased at all time points (P ＜ 0.05) and inhibited angiogenesis.(3) TBI + HIF-lα silence group versus TBI group showed remarkably decreased VEGF at all time points,increased expressions of TNF-α,IL-6 and NF-κB at all time point,and increased expression of MMP-9 at 7 and 14 d postinjury (all P ＜0.05).(4) TBI + HIF-1α silence group versus TBI group showed significant difference in mNSS at 7 and 14 d postinjury (all P ＜ 0.05).Conclusions After TBI,high expression of HIF-1αcan facilitate vascular formation and inhibit inflammatory reaction related factor expression,inducing the mitigation of brain edema and brain injury.Therefore,promoting HIF-1α expression may become a new means to improvement of neurovascular function after TBI.

Objective To study the effects of α-melanocyte-stimulating hormone (α-MSH) on excessive inflammatory response of patients to traumatic brain injury (TBI) so as to prevent against the development of the secondary injury by observing the changes of α-MSH level in the serum of patients with TBI,and the relationships of the levels of serum α-MSH with the severity of TBI,and with the levels of tumor necrosis factor-α (TNF-α).Methods A total of 48 patients with acute TBI were divided into three groups according to GCS score:severe group with GCS 3-8 (n =18),moderate group with GCS 9-12 (n =16),and mild group with GCS 13-15 (n =14).Ten healthy volunteers were recruited as a control group.The blood samples were collected within 24 h and 3 d,5 d,7 days after injury.The concentrations of α-MSH and TNF-α in the separated serum were measured by double antibody sandwich enzyme-linked immunosorbent assay (ELISA).All variables were presented as ((x)±s).Repeated measures and analysis of variance and further multiple comparisons were carried out to compare variables.When necessary,the Student's t test was utilized.Pearson correlation analyses were performed to determine the correlations between variables.Results The serum α-MSH levels in the three TBI groups were lower than that in the control group (P ＜ 0.05).And the severer injury was,the lower α-MSH level was.The lowest α-MSH levels dropped to the trough on the 3rd day or the 5th day after TBI [severe group:(9.65 ±4.21) pg/mL,moderate group:(10.69 ±4.30) pg/mL,mild group:(18.89 ±7.19) pg/mLvs.control:(45.67 ± 10.95) pg/mL].While the serum TNF-α levels in three TBI groups were higher than that in the control group (P ＜ 0.05),and the TNF-α level was higher in the severer group.The peak values of TNF-α in the three TBI groups reached on the 3rd day after TBI [severe group:(37.24 ± 18.28) pg/mL,moderate group:(26.19 ±6.78) pg/mL,mild group:(18.60 ±7.83) pg/mL vs.control:(10.74 ± 1.71) pg/ mL].There were negative correlations between the levels of serum α-MSH and TNF-α at four intervals.Conclusions In patients with TBI,the serum levels of α-MSH decreased,and the lowest levels of α-MSH dropped to the trough on the 3rd day or the 5th day after TBI.While the levels of TNF-α increased,and the peak values reached on the 3rd day after TBI.And as the injury was more severe,these changes were more significant.There were negative correlations between the serum α-MSH levels and TNF-α levels in general.

Objective To establish an efficient HPLC method for the determination of uric acid in plasma of hyperuricemia model mice,and the evaluation of uric acid lowering effect of Lesinurad.Methods The Laballiance Series Ⅲ HPLC system was adopted with Kromasil C18 column (100 mm × 4.6 mm,5 μm).The mobile phase consisted of methanol-0.5％ acetic acid (10:90) for isocratic elution with a flow rate of 0.4 mL/min.The detection wavelength was set at 283 nm.The established HPLC method was used to detect the plasma uric acid level of mice at 0.5,1.0,and 2.0 h time points after which being ip injected with 250 and 500 mg/kg uric acid.Lesinurad of 250 and 500 mg/kg was ig given to mice,0.5 h later,mice were ip injected with 500 mg/kg uric acid to establish hyperuricemia model,and 1 h later,the established HPLC method was used to detect the plasma uric acid level of mice.Results There was a good linear relationship between peak area and the concentration of plasma uric acid in the range of 7.5-150 μg/mL (r =0.997).The specificity,repeatability,precision,stability,and recovery of the established HPLC method was in accordance with the guiding rules of biological sample determination.Compared with the endogenous serum uric acid concentration of control group mice,serum uric acid concentration of 250 mg/kg dose group was significantly increased 0.5 h after ip administration with uric acid (P ＜ 0.01),and serum uric acid concentration of 500 mg/kg dose group was significantly increased 0.5,1.0,and 2.0 h after ip administration with uric acid.Compared with model group,the concentration of uric acid in plasma decreased significantly in low dosage group administered with Lesinurad (P ＜ 0.05),while decreased more significantly in high dosage group (P ＜ 0.01).Conclusion This convenient,rapid,and accurate method can be applied to the determination of uric acid in mouse plasma and the evaluation of relative drugs,which provide an efficient analysis way for establishing hyperuricemia model and screening relative drugs.

Objective:To investigate the occurrence and predictors of hypopituitarism after traumatic brain injury (TBI) .Methods:A prospective study was conducted on 185 patients with severe TBI in the Emergency Department of the First Hospital of Shanxi Medical University from Jan. 2020 to May. 2022, of whom 108 were male and 77 were female; age ranged from 18 to 79 years, mean (51.32±9.34) years. Pituitary function was assessed within 3-7 d after the onset of TBI, and the occurrence of hypopituitarism after severe TBI was counted. 41 cases in the hypopituitarism group, 26 males and 15 females, aged (52.76±9.83) years, were divided into the hypopituitarism group (hypopituitarism occurred) and the non-hypopituitarism group (hypopituitarism did not occur) according to whether hypopituitarism occurred. In the non-decompensated group, there were 144 cases, 82 males and 62 females, aged (50.91±9.27) years. The clinical data of the decompensated and non-decompensated groups were compared, and the factors influencing the occurrence of hypopituitarism were analysed, and a logistic prediction model was constructed based on the relevant influencing factors. The value of this model in predicting the occurrence of hypopituitarism after severe TBI was evaluated by using the receiver operating characteristic (ROC) curve.Results:The prevalence of hypopituitarism in the 185 patients with severe TBI in this study was 22.16%; the Glasgow coma scale (GCS) score on admission was lower in the decompensated group than in the non-decompensated group [ (6.36±1.04) vs (7.48±0.59) ], the percentage of hyperbaric oxygen therapy was lower than in the non-decompensated group (21.95% vs 49.31%) , the percentage of intracranial pressure (82.93% vs 49.31%) , midline displacement ≥5 mm (78.05% vs 29.86%) , skull base fracture (34.15% vs. 17.36%) , diffuse cerebral edema (19.51% vs 4.17%) , and serum brain derived neurophic factor (BDNF) . Brain derived neurophic factor (BDNF) was higher than that in the non-reduced group [ (6.35±1.29) ng/ml vs (4.51±1.06) ng/ml], and neuronal-specific enolase (NSE) was higher than that in the non-reduced group [ (33.06±5.42) μg/L vs (23.15±4.97) μg/L]. (4.97) μg/L]. Vascular epithelial growth factor (VEGF) was higher than that in the non-reduced group [ (312.07±24.35) pg/ml vs (226.80±20.96) pg/ml], tumor necrosis factor-α (TNF-α) was higher than that in the non-reduced group [ (281.24±38.91) ng/L vs (186.91) pg/ml], and tumor necrosis factor-α (TNF-α) was higher than that in the non-reduced group (186.55±35.72) ng/L (all P<0.05) . Increased intracranial pressure, midline displacement ≥5 mm, diffuse cerebral edema, serum BDNF, NSE, VEGF, and TNF-α levels were all independent risk factors for the development of hypopituitarism after severe TBI, with admission GCS score and hyperbaric oxygen therapy as protective factors ( P<0.05) ; a logistic prediction model was constructed based on the influencing factors as: Logit ( P) = 5.264-0.880×admission GCS score + 1.618×increased intracranial pressure + 1.941×midline displacement ≥5 mm + 1.289×diffuse cerebral edema+1.306×BDNF+1.426×NSE+1.781×VEGF+1.615×TNF-α-0.758×hyperbaric oxygen therapy; the model predicted the occurrence of severe TBI after the area under the curve (AUC) of hypopituitarism was 0.930 (95% CI 0.883-0.962) , with a predictive sensitivity and specificity of 90.24% and 89.19%, respectively. Conclusions:The incidence of hypopituitarism is higher after severe TBI. Increased intracranial pressure, midline displacement ≥5 mm, diffuse cerebral edema, serum BDNF, NSE, VEGF and TNF-α levels are all used as predictors of hypopituitarism.

Objective:To evaluate the changes in the electrical conduction of ventricular myocardium during hypothermic ischemia-reperfusion (I/R) in rats with arrhythmia.Methods:Healthy clean-grade adult male Sprague-Dawley rats, aged 2-3 months, weighing 200-300 g, were studied.The hearts were removed and retrogradely perfused with oxygenated K-H solution in a Langendorff apparatus. Sixteen isolated hearts were divided into 2 groups ( n=8 each) using a random number table method: normal control group (group C) and hypothermic I/R group (group I/R). In group C, the heart was perfused with K-H solution at 37 ℃ for 120 min.In group I/R, the heart was perfused with K-H solution at 37 ℃ for 30 min, and then perfusion was stopped, cardiac arrest was induced through injecting Thomas solution (4 ℃), the area around the heart was protected with low temperature (4 ℃) Thomas solution, and hearts were perfused with 4 ℃ Thomas solution at 30 min after cardiac arrest and with 37 ℃ K-H solution for 30 min staring from 60 min after cardiac arrest.The rats in group I/R were further divided into high-risk subgroup (I/R-H subgroup) and low-risk subgroup (I/R-L subgroup). The time of spontaneous recovery of heart beat and development of arrhythmia were recorded.At the end of reperfusion, the atrioventricular conduction 2∶1 block point (2∶1B) and ventricular electrical conduction velocity (CV) were measured and recorded by program-controlled electrical stimulation. Results:Compared with group C, CV and 2∶1B were significantly decreased in IR-L and IR-H subgroups ( P<0.05). Compared with IR-L subgroup, the time for restoration of spontaneous heart beat was significantly prolonged, the incidence of ventricular fibrillation and arrhythmia score were increased, and CV and 2∶1B were decreased in IR-H subgroup ( P<0.05). Conclusion:The electrical CV of ventricular myocardium is decreased during hypothermic I/R, which may be the mechanism of reperfusion-induced ventricular arrhythmia in rats with arrhythmia.