Objective:To investigate the effect of Smac mimetic compound SM-164 on the radiosensitivity of cervical cancer cells and its underlying mechanisms.Methods:Human cervical cancer cell lines HeLa and SiHa were treated with different concentrations of SM-164 (0.05, 0.1, 0.2, 0.4 μmol/L) for 24 hours, followed by irradiation with 6 MV X rays at different doses (0, 2, 4, 6, 8 Gy). Clone formation assay was used to detect the survival fraction of HeLa and SiHa cells. The cells were divided into the negative control (NC) group, 4 Gy ionizing radiation (IR) group, 4 Gy combined with 0.2 μmol/L SM-164 treatment (IR+SM-164) group, and Caspases (Casp) broad-spectrum inhibitor Z-VAD blocking (IR+SM-164+Z-VAD) group. CCK-8 assay was adopted to assess cell proliferation, flow cytometry was used to detect cell apoptosis, and Western blot was employed to assess the changes in apoptosis-related proteins cleaved (C)-Casp9/Casp9, C-Casp3/Casp3, C-poly(ADP ribose) polymerase (PARP)/PARP, and DNA damage marker phosphorylated-histone H2A family member X (γH2AX)/H2AX ratios. One-way ANOVA was used for the comparison of means among multiple groups, and the SNK- q test was used for pairwise comparisons between two groups. Results:Compared with the NC group, the survival rates of HeLa and SiHa cells were significantly decreased after the combined treatment of IR and SM-164 (both P<0.01), and different concentrations of SM-164 enhanced cell radiosensitivity (all P<0.05). Compared with the NC group, cell proliferation activity was significantly decreased in the IR, IR+SM-164 and IR+SM-164+Z-VAD groups (all P<0.01), while apoptosis rate and the ratios of C-Casp9/Casp9, C-Casp3/Casp3, C-PARP/PARP, and γH2AX/H2AX were significantly increased (all P<0.01). Compared with the IR group, the proliferation activity in the IR+SM-164 group was significantly decreased ( P<0.05), whereas apoptosis rate and related protein ratios were significantly increased (all P<0.05). The γH2AX/H2AX ratio was increased in the IR+SM-164+Z-VAD group ( P<0.05). Compared with the IR+SM-164 group, the proliferation activity in the IR+SM-164+Z-VAD group was increased ( P<0.05), while the apoptosis rate and related protein ratios were significantly decreased (all P<0.05). Conclusion:SM-164 enhances the radiosensitivity of cervical cancer cells by inducing Casp activation.

Objective:To investigate the effect of Smac mimetic compound SM-164 on the radiosensitivity of cervical cancer cells and its underlying mechanisms.Methods:Human cervical cancer cell lines HeLa and SiHa were treated with different concentrations of SM-164 (0.05, 0.1, 0.2, 0.4 μmol/L) for 24 hours, followed by irradiation with 6 MV X rays at different doses (0, 2, 4, 6, 8 Gy). Clone formation assay was used to detect the survival fraction of HeLa and SiHa cells. The cells were divided into the negative control (NC) group, 4 Gy ionizing radiation (IR) group, 4 Gy combined with 0.2 μmol/L SM-164 treatment (IR+SM-164) group, and Caspases (Casp) broad-spectrum inhibitor Z-VAD blocking (IR+SM-164+Z-VAD) group. CCK-8 assay was adopted to assess cell proliferation, flow cytometry was used to detect cell apoptosis, and Western blot was employed to assess the changes in apoptosis-related proteins cleaved (C)-Casp9/Casp9, C-Casp3/Casp3, C-poly(ADP ribose) polymerase (PARP)/PARP, and DNA damage marker phosphorylated-histone H2A family member X (γH2AX)/H2AX ratios. One-way ANOVA was used for the comparison of means among multiple groups, and the SNK- q test was used for pairwise comparisons between two groups. Results:Compared with the NC group, the survival rates of HeLa and SiHa cells were significantly decreased after the combined treatment of IR and SM-164 (both P<0.01), and different concentrations of SM-164 enhanced cell radiosensitivity (all P<0.05). Compared with the NC group, cell proliferation activity was significantly decreased in the IR, IR+SM-164 and IR+SM-164+Z-VAD groups (all P<0.01), while apoptosis rate and the ratios of C-Casp9/Casp9, C-Casp3/Casp3, C-PARP/PARP, and γH2AX/H2AX were significantly increased (all P<0.01). Compared with the IR group, the proliferation activity in the IR+SM-164 group was significantly decreased ( P<0.05), whereas apoptosis rate and related protein ratios were significantly increased (all P<0.05). The γH2AX/H2AX ratio was increased in the IR+SM-164+Z-VAD group ( P<0.05). Compared with the IR+SM-164 group, the proliferation activity in the IR+SM-164+Z-VAD group was increased ( P<0.05), while the apoptosis rate and related protein ratios were significantly decreased (all P<0.05). Conclusion:SM-164 enhances the radiosensitivity of cervical cancer cells by inducing Casp activation.

Objective: To investigate the effects of postoperative analgesia with Dexmedetomidine combined with Sufentanil on pulmonary infection complications and immune function in patients with lung cancer. Methods: A total of 200 patients with lung cancer who underwent radical lung cancer in our hospital from July 2014 to June 2018 were randomly divided into the group A(n=100, receiving Sufentanil analgesia)and group B(n=100, receiving Sufentanil combined with Dexmedetomidine analgesia)according to the random number table method.The analgesic effect, pulmonary complication incidence and immune function were compared between the two groups. Results: The analgesic and sedative effects were better in the group B than in the group A at 4, 8, 12 and 24 hours after surgery, respectively(P<0.05). The visual analogue scale(VAS)and Ramesay score had statistically significant differences between the two groups at 4, 8, 12 and 24 hours after surgery, respectively(VAS: t=4.137, 2.575, 3.869, 12.676 and 9.945, all P<0.05; Ramesay score: t=6.771, 5.647, 16.763, 21.154 and 6.556, all P<0.05). The pulmonary infection, acute lung injury, focal lung infiltration, atelectasis and respiratory failure occurred in 1, 0, 1, 1 and 0 case in the group B and 3, 2, 3, 1 and 1 case in the group A, respectively.The incidence of pulmonary complications was lower in the group B than in the group A(3% or 3/100 vs.10% or 10/100, χ²=4.031, P=0.045). There were no significant difference in the levels of CD3⁺, CD4⁺, CD8⁺ and CD4⁺ /CD8⁺ cells before surgery between the two groups(P>0.05). The levels of CD3⁺, CD4⁺, CD8⁺ and CD4⁺ /CD8⁺ cells were higher in group B than in group A at 1 day after surgery(t=7.419, 7.867, 11.968 and 8.755, P=0.000). Conclusions Postoperative Dexmedetomidine combined with Sufentanil analgesia not only helps to reduce the incidence of pulmonary complications, but also improves the analgesic effect and immune function in patients with lung cancer undergoing radical surgery.

Objective To discuss the effects of lidocaine infusion on perioperative immune function by evaluating the levels of stress hormone and natural killer (NK) cell cytotoxicity.Methods Thirty-five patients of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,aged 35-65 yr,undergoing elective radical hysterectomy,were randomized into lidocaine group (group L)and control group (group C).Fifteen minutes before anesthesia induction,a bolus of 1.5 mg/kg of lidocaine was administered iv.to each patient in group L and followed by a continuous infusion at 1.5 mg·kg-1 ·h-1 lasting to the end of surgery.Meanwhile,the patients in group C received the same volume of saline.Venous blood samples were collected individually 24 h before the operation,the end of the operation and 48 h after the operation.Levels of prostaglandin,epinephrine and norepinephrine were assayed by ELISA kits.NK Cells were obtained by CD56 antibody magnetic isolation.The cytotoxicity of NK cell was detected by LDH releasing assay,and phosphor-protein kinase A (p-PKA)and protein kinase A (PKA) were detected by Western blotting.Results There were no significantly different in the plasm levels of PGF2,EP1 and NE.The plasm levels of prostaglandin (562.5±98.2 vs.663.2±119.0) pg/ml,epinephrine (24.9±4.8 vs.29.7±3.5) pg/ml and norepinephrine (408.3 ±47.2 vs.499.6±45.6) pg/ml in patients of group L were lower than those in group C (P＜0.05)48 h after the surgery.The cytotoxicity of NK cell was higher in group L than that in group C (44.1 ±5.0 vs.37.1±5.5)％ (P＜0.05) 48 h after the surgery.The ratio of p-PKA/PKA was lower in group L than that in guoup C (0.060±0.008 vs.0.099±0.011) (P＜0.05) at the end of the surgery.Conclusion Perioperative intravenous lidocaine infusion can reduce the level of plasma catecholamine and PGE2,and protect the cytotoxicity of NK cell,possibly via inhibiting of cAMP-PKA signaling pathway.

AIM: To investigate the effects of pseudolaric acid B on the growth and apoptosis of glioblastoma cell line U87.METHODS: The cell morphological changes were observed under inverted microscope.The cell viability was evaluated by MTS assay.The cell cycle was analyzed by flow cytometry and Western blot.The cell apoptosis was de-tected by flow cytometry.The changes of apoptosis-related proteins cleaved PARP, caspase-3, procaspase-9 and caspase-8 were determined by Western blot.RESULTS: Pseudolaric acid B inhibited the viability of U87 cells, arrested U87 cells in mitosis.Apoptosis of U87 cells was induced by pseudolaric acid B.The caspase pathway was activated.CONCLUSION:Pseudolaric acid B induces glioblastoma cell line U87 mitotic arrest and apoptosis.

Objective To compare the clinical effect of manual aspiration thrombectomy versus systemic thrombolysis for acute lower extremity deep venous thrombosis of mixed type.Methods The clinical data of 380 patients with acute lower extremity deep venous thrombosis of nixed type was analyzed retrospectively,who were classified into two groups according to treatment methods.Group A (229 cases):the ipsilateral femoral vein was accessed under local anesthesia,a 12-14 F sheath was introduced via a guide wire to aspirate iliofenoral thrombus.As for the femoropopliteal thrombus,a Fogarty balloon catheter was introduced to pull thrombus to iliac vein,then mechanical aspiration thrombectomy was performed.One hundred and thirteen patients with stenosis or occlusion of comnon iliac vein were treated with adjunctive PTA and stenting.As for the residual thrombus bclow popliteal vein,a small dose urokinase vas given to thrombolysis and heparin anticoagulation after procedure.Group B(151 cases) were treated by systemic thrombolysis and anticoagulation with heparin.Results The swelling and pain of affected limbs of group A began to relief after operation immediately,but these times of group B was 3-7 days after operation.The thrombus was eliminated completely(Grade Ⅰ):goup A was better than group B (63.32％ vs 37.09％) (x2 =20.53,P =0.002).Conclusions The manual aspiration thrombectomy was superior to simple systemic thrombolysis in treating acute lower extremity deep venous thrombosis of mixed type,especially in protecting the normal valve function that was better than thrombolysis,aspiration thrombectomy with adjunctive iliac vein angioplasty was a more reasonable method to treat acute LEDVT.

Objective To investigate the effects of different doses of lidocaine on acute liver injury in septic rats.Methods Fifty male Wistar rats,weighing 200-250 g,aged 8-10 weeks,were randomly divided into 5 groups(n =10 each):sham operation group(group S),sepsis group(group CLP),and different doses of lidocaine groups(groups L1-3).Sepsis was induced by cecal ligation and puncture(CLP)in anesthetized rats.At 0,1 and 2 h after CLP,lidocaine 5,10 and 20 mg/kg(in normal saline 0.5 ml)were injected intraperitoneally in groups L1-3 respectively,while normal saline 0.5 ml was given in groups S and CLP.At 24 h after CLP,blood samples were taken for determination of the plasma alanine aminotran sferase(ALT)concenlralion.The rats were then sacrificed,and the liver was removed for microscopic examination and determination of the hepatic high-mobility group box 1 protein(HMGBI)mRNA expression.Results Compared with group S,the plasma ALT concentration was significandy increased and hepatic HMGBI mRNA expression was up-regulated in groups CLP and L1-3(P ＜ 0.05).Compared with group CLP,HMGBI mRNA expression was down-regulated in groups 14-3,while the plasma ALT concentration was decreased in groups L2 and L3(P ＜ 0.05),The plasma ALT concentration was significantly decreased and HMGBI mRNA expression was down-regulated in groups L2 and L3 com pared with group L1,and in group L3 compared with group L2(P ＜ 0.05).The microscopic examination showed that the pathologic changes were attenuated in groups L1-3,and the changes were least severe in group L3.Concluslon Lidocaine can reduce acute liver injury in septic rats,this effect is dose-related,and inhibition of hepatic HMGBI mRNA expression is involved in the mechanism.

Objective To investigate the role of high mobility group protein box 1 (HMGB1) in pulmonary vascular remodeling in a rat model of acute lung injury (ALI).Methods Thirty healthy pathogen free male Wistar rats weighing 220-250 g were randomly divided into 3 groups (n =10 each) ∶ group control (group C) ;group LPS (group M) and group LPS + HMGB1 antibody (group H).The animals were anesthetized with intraperitoneal 10％ chloral hydrate 7 ml/kg.ALI was induced with LPS 1 mg/kg infused iv over 30 min in groups M and H.In group H HMGB1 antibody 2 mg/kg was injected iv at 12,24 and 36 h after LPS administration respectively.The animals were sacrificed at 72 h after LPS administration.The left lung was removed for microscopic examination,measurement of the thickness of the medial layer (tunica media) of pulmonary arterioles and determination of the expression of PCNA (by immune-histochemistry) and HMGB1 protein (by Western blotting).Results The medial layer of pulmonary arterioles was significantly thicker and the expression of PCNA and HMGB1 higher in group M than in group C.LPS also induced significant inflammatory cell infiltration within the alveoli and damage to the septa.In group H HMGB1 antibody significantly attenuated the above-mentioned LPS-induced changes.Conclusion HMGB1 may play an important role in the LPS-induced pulmonary vascular remodeling.

Objective To investigate the effect of different doses of lidocaine on expression of the high mobility group box 1 protein (HMGB1) in small intestine in septic rats.Methods Fifty adult male Wistar rats weighing 200-250 g were randomly divided into 5 groups ( n =10 each):sham operation group (group S),sepsis group( group Sep ) and different doses of lidocaine group (group L1～3 ).Group S were not applied cecal ligation and puncture (CLP).Sepsis intestinal damage model was performed in group Sep by CLP.Group L1～3 were given intraperitoneally lidocaine in a dose ofS,10 and 20 mg/kg at immediately,1 and 2 h after CLP,respectively.Isometric normal saline was given intraperitoneally in group S and group Sep.The small intestine tissues were taken at 24 and 48 h after CLP.The small intestine morphology was observed with optical microscope.The expression of the HMGB1 mRNA were examined by PCR and the activity of diamine oxidase (DAO) were determined by ELISA.Results Compared with group S,the expression of HMGB1 mRNA was increased and the activity of DAO decreased in group Sep and groups L1～3 at 24 and 48 h after CLP ( P ＜ 0.05 ).Compared with group Sep,the expression of HMGB1 mRNA was decreased and the activity of DAO increased in a dose-dependent manner in groups L1～3 ( P ＜0.05),The injury of pathology of small intestine was slighter in groups L1～3 than in group Sep.Conclusion Lidocaine can reduce samll intestine injury through inhibiting HMGB1 expression in septic rats by a dose-dependent manner.

[Objective] To investigate the association between -31C/G polymorphism in the promoter of survivin gene and the susceptibility to sporadic colorectal cancer in southern Chinese population. [Methods] Survivin-31C/G genotypes were determined by polymerase chain reaction-restriction fragment length polymorpbism (PCR-RFLP) in 711 healthy controls and 702 CRC cases. [Results] The number of CRC patients carrying with CC genotype was much higher than those of controls (36.5 % vs. 26.12%, X~2=17.89, P<0.001). Compared with CC genotypes, CG, GG genotypes and G allele carriers had a significantly decreased risk of CRC, with the decrease being 0.61-fold (95% CI=0.46-0.81, P<0.001), 0.52-fold (95% CI=0.38-0.71, P<0.001) and 0.58-fold (95% CI=0.45-0.74, P<0.001), respectively. [Conclusion] Survivin gene -31C/G polymorphism is associated with sporadic CRC risk, the G variant genotypo is the independent protective factors against sporadic CRC in soutbem Chinese population.