Pyroptosis is a kind of programmed cell death,which is not only related to colorectal cancer,bladder cancer,gastric cancer,breast cancer and other tumors,but also related to cervical cancer,ovarian cancer and endometrial cancer.In recent years,the diagnosis and treatment of gynecological tumors have been improved,but their incidence and mortality are still high,which seriously threaten women's health.The current difficulty in treating gynecological tumors is reflected in the chemotherapy resistance of cervical cancer,the difficulty in early detection of ovarian cancer,the rapid progression and easy recurrence of late stage ovarian cancer,and the poor prognosis of late stage endometrial cancer.Therefore,this article reviews the roles of pyroptosis in the occurrence and development of gynecologic tumors,in order to provide clues for early diagnosis and treatment of gynecological tumors.

Pyroptosis is a kind of programmed cell death,which is not only related to colorectal cancer,bladder cancer,gastric cancer,breast cancer and other tumors,but also related to cervical cancer,ovarian cancer and endometrial cancer.In recent years,the diagnosis and treatment of gynecological tumors have been improved,but their incidence and mortality are still high,which seriously threaten women's health.The current difficulty in treating gynecological tumors is reflected in the chemotherapy resistance of cervical cancer,the difficulty in early detection of ovarian cancer,the rapid progression and easy recurrence of late stage ovarian cancer,and the poor prognosis of late stage endometrial cancer.Therefore,this article reviews the roles of pyroptosis in the occurrence and development of gynecologic tumors,in order to provide clues for early diagnosis and treatment of gynecological tumors.

Objective To explore the mechanism of thymoquinone (TQ) on NSCLC cytotoxicity.Methods SK-MES-1 was inoculated into 96-well plates and cultured at 20,40,60,80 and 100 μmol/L TQ for 24 h,and the IC50 of TQ was calculated.SK-MES-1 was cultured in close proximity to IC50 concentration TQ,and time-dependent was observed.The ERK inhibitor U0126 and the p38 inhibitor SB203580 were applied to SK-MES-1 and 95-D,respectively,then TQ-activated MAPK-mediated cytotoxicity were observed.The SK-MES-1 expression of p-p38,p38,p-ERK1/2,ERK1/2,pJNK and JNK protein were detected by U0126 pretreatment for 1 h and TQ-cultured for 30 min.Results ① TQ was used to mediate NSCLC cells in a concentration and time-dependent manner,and the viability of NSCLC cells was decreased.② The cell viability of 30 μmol/L TQ and 10 μmol/L U0126 +30 μmol/L TQ showed significant differences (P =0.000),but no significant difference was found when compared with 10 μmol/L SB203580 + 30 μmol/L TQ (P =1.00).10 μmol/L SB203580 + 30 μmol/L TQ was significantly different from 10 μmol/L U0126 + 30 μmol/L TQ (P =0.000).60μmol/LTQ,10μmol/LU0126 + 60μmol/LTQ,10μmol/LSB203580 + 60 μmol/L TQ showed no significant differences between every two groups (P ＞ 0.0 5).With the increase of TQ concentration,the protective effect of SB203580 on 95-D cells gradually decreased,and 10 μmol/L SB203580 +40 μmol/L TQ group was significantly different from 40 μmol/L TQ group (P =0.033).③ Western blot analysis showed that U0126 could significantly inhibit the phosphorylation of ERK1/2,phosphorylated p38 increased with the increasing of TQ concentration.However,ERK1/2 phosphorylation decreased,and JNK phosphorylation did not change significantly.Conclusion TQ can mediate NSCLC cytotoxicity through phosphorylation of p38 pathway,but not ERK1/2 pathway.

Objective To explore the mechanism of thymoquinone (TQ) on NSCLC cytotoxicity.Methods SK-MES-1 was inoculated into 96-well plates and cultured at 20,40,60,80 and 100 μmol/L TQ for 24 h,and the IC50 of TQ was calculated.SK-MES-1 was cultured in close proximity to IC50 concentration TQ,and time-dependent was observed.The ERK inhibitor U0126 and the p38 inhibitor SB203580 were applied to SK-MES-1 and 95-D,respectively,then TQ-activated MAPK-mediated cytotoxicity were observed.The SK-MES-1 expression of p-p38,p38,p-ERK1/2,ERK1/2,pJNK and JNK protein were detected by U0126 pretreatment for 1 h and TQ-cultured for 30 min.Results ① TQ was used to mediate NSCLC cells in a concentration and time-dependent manner,and the viability of NSCLC cells was decreased.② The cell viability of 30 μmol/L TQ and 10 μmol/L U0126 +30 μmol/L TQ showed significant differences (P =0.000),but no significant difference was found when compared with 10 μmol/L SB203580 + 30 μmol/L TQ (P =1.00).10 μmol/L SB203580 + 30 μmol/L TQ was significantly different from 10 μmol/L U0126 + 30 μmol/L TQ (P =0.000).60μmol/LTQ,10μmol/LU0126 + 60μmol/LTQ,10μmol/LSB203580 + 60 μmol/L TQ showed no significant differences between every two groups (P ＞ 0.0 5).With the increase of TQ concentration,the protective effect of SB203580 on 95-D cells gradually decreased,and 10 μmol/L SB203580 +40 μmol/L TQ group was significantly different from 40 μmol/L TQ group (P =0.033).③ Western blot analysis showed that U0126 could significantly inhibit the phosphorylation of ERK1/2,phosphorylated p38 increased with the increasing of TQ concentration.However,ERK1/2 phosphorylation decreased,and JNK phosphorylation did not change significantly.Conclusion TQ can mediate NSCLC cytotoxicity through phosphorylation of p38 pathway,but not ERK1/2 pathway.

One of the purposes for the improvement of forages efficient utilization in rumens was to adjust the physiological function of ruminant in Tibet,and to improve the disadvantage influences under the altitude environment.The electrocardiography,rumen electromyography and tension in the rumen were drawn the before and after catgut embedding in the liumai acupuncture point to the Tibet sheep.The result showed that catgut embedding in the liumai acupuncture point could promoted the blood circulation,alleviated the overload of myocardial and remedied the right deviation of heart electrical axis up to 40°.The VPP and RA of rumen were significantly lower and the tension of rumen decreased 1/3 after catgut embedding.The result indicated that it could relaxed the right ventricular hypertrophy,reduced the tension of rumen,improved the function of gastrointestinal tract and blood circulation,ensured sufficient time to digest the forage in rumen.

Objective To investigate the effect of coupled plasma filtration adsorption (CPFA) on plasma cytokines:TNF-α,IL-1β,IL-6,cellular immunity,blood lactate acid concentration,heart rate,respiration rate,oxygenation index,hemodynamics,blood cells counts,and prognosis in patients with multiple organ dysfunction syndromes (MODS).Methods This was a prospective,randomized clinical trial in 45 patients diagnosed as MODS.Patients were randomly assigned to hemoperfution with resin adsorption (HP) + continuous venous-venous hemofiltration (CVVH) group,CPFA group and CVVH group.The general clinical data,APACHE Ⅱ score,number of failure organ and previous mentioned biomarkers were documented.Blood samples were collected before and after blood filtration with any one of these procedures.The plasma samples were isolated and stored with frozen at-60 ℃.Data were statistically analyzed with SPSS 13.0 version software.Results In CPFA group,plasma cytokines,TNF-α、IL-1β、IL-6,decreased markedly after plasma adsorption for two hours (P ＜ 0.01);and plasma concentrations of IL-6 were further descended after subsequent CVVH for 10 hours (P ＜ 0.05).In HP + CVVH group,plasma cytokines,TNF-α、IL-1β、IL-6,decreased markedly after HP (P ＜ 0.01),and plasma concentrations of IL-6 were further descended after subsequent CVVH for 10 hours (P ＜ 0.05).In CVVH group,plasma cytokines,TNF-α、IL-1β、IL-6,decreased after CVVH for 12 hours (P ＜ O.05).Blood lactate acid concentration,heart rate,respiration rate,oxygenation index,T-lymphocytes subgroups (CD3 +,CD4 +,CD8 +,CD4 +/CD8 + ratio),clinical symptoms were improved and dose of vasoactive agent was reduced in the patients of three groups without differences among them.The counts of red blood cells,white blood cells and platelets after CPFA and CVVH showed no significant changes.There was no significant difference in blood cell counts between CPFA and CVVH groups.After HP + CVVH,there was a trend of decrease in platelet count (P ＜ 0.05).Platelet counts were significanfly higher in patients treated with CPFA and CVVH group than those in patients treated with HP + CVVH group (P ＜ 0.05).There were 6 patients died in HP + CVVH group,6 patients died in CPFA group and 5 patients died in CVVH group within 28days.Conclusions The comparison of efficacy of blood filtration among 3 modalities of HP + CVVH,CPFA and CVVH showed CPFA had higher capacity of Inflammatory medium scavenging than CVVH,and had less damage effect on blood visible component,especially on platelet compared with HP + CVVH.CPFA was an effective and safety modality in the treatment of the patients with multiple organ dysfunction syndrome.

BACKGROUNDAltered immunoresponse is associated with tumorigenesis and cancer progression. This study assessed the levels of tumor-infiltrating CD3 + or CD8 + T lymphocytes and interleukin-2 (IL-2) protein in radically resected non-small cell lung cancer (NSCLC) tissues to predict overall survival (OS) of the patients.

METHODSParaffin-embedded tissue specimens from 129 NSCLC patients were retrospectively collected for immunostaining of CD8 + , CD3 + , and IL-2 expression. Clinicopathological and survival data were collected and analyzed using the Chi-squared test, Kaplan-Meier curves, and the log-rank test or the Cox regression model.

RESULTSThe data showed a significant inverse association between CD8 + T lymphocyte levels and IL-2 expression (r = -0.927; P = 0.000) and between the levels of CD8 + and CD3 + T lymphocytes (r = -0.722; P = 0.000), but a positive association between CD3 + T lymphocyte levels and IL-2 expression (r = 0.781; P = 0.000) in NSCLC tissues. Furthermore, the levels of CD3 + and CD8 + T lymphocytes and IL-2 expression were associated with tumor stage (P = 0.023, 0.006, and 0.031, respectively) and the level of CD8 + T lymphocytes was associated with the patient gender (P = 0.024). In addition, the levels of CD8 + T lymphocytes were associated with an unfavorable 5-year OS, whereas patients with high levels of CD3 + T lymphocytes in tumor lesions and IL-2-expressing tumors had significantly better 5-year OS rates than patients with low levels.

CONCLUSIONSThe levels of CD8 + T cells in tumor lesions and IL-2 expression were both independent predictors of OS for these NSCLC patients. Thus, the detection of tumor-infiltrating CD3 + or CD8 + T lymphocytes and IL-2 expression could be useful to predict the prognosis of radically resected NSCLC patients.

CD3 Complex ; metabolism ; CD8-Positive T-Lymphocytes ; metabolism ; Female ; Humans ; Immunohistochemistry ; Interleukin-2 ; metabolism ; Lung Neoplasms ; immunology ; metabolism ; Lymphocytes, Tumor-Infiltrating ; metabolism ; Male ; Prognosis

Objective To study the clinical value of nipple discharge detection in the early diagnosis of breast cancer,CA153 ,CEA levels were measured both in nipple discharge and serum. Methods 153 consecutive patients with nipple discharge in Rizhao hospital were studied,among them there were 91 cases with breast cancer and 62 cases with benign disease. The nipple discharged and serum from the 153 cases with nipple discharged were collected and CA153, CEA levels were measured with electrochemiluminescence method. Results The CA153, CEA levels of nipple discharge in breast cancer were significantly higher than the control group(CA153:t =28.949,33.844;CEA:t = 19.773,16.623, all P ＜ 0.01). The positive rate of CA153, CEA in nipple discharge were significantly higher than in the serum (P ＜ 0.05). Conclusion The positive rate of CA153, CEA in nipple discharge were significantly higher than in the serum. The detection of CA153 ,CEA had important value in the early diagnosis of breast cancer.

Objective To investigate the change rule and correlation of heme oxygenase-1(HO-1)/carbon monoxide(CO)and the influence of simvastatin and amlodipine in athemsclemtic progress.Methods The rabbits received 1％cholesterol diet(n=24)for eight weeks.After eight weeks,rabbits were fed with normal diet for eight weeks.The rabbits in model group(n=8)were administrated with cholesterol diet.The rabbits in simvastatin group(n=8)were administrated with simvastatin.The rabbits in amlodipine group(n=8)were administrated with amlodipine.The levels of serum lipids and plasma carbon monoxide were obtained at the beginning,the 8th week and the 16th week.The expression of heme oxygenase-1 in the thoraoia aortic tissue were observed with immunohistochemistry technique.Results By the end of 16th week,the levels ofserum lipids and plasma carbon monoxide in model group were obviously increased,however,the expression of heine oxygenase-1 were markedly decreased.Compared with model group.The levels～rurfl lipi&and plasma carbon monoxide in simvastatin group were significantly decreased,while the expression of heme oxysenase-1 in aortic great reduced.The levels flerum lipids in amlodipine group were not significant ckmged,the levels of plasma carbon monoxide were obviously decreased,while tlle expression ofheine oxygenase-1 in aortic great reduced.Conclusions In atheresclerofic progress,heme oxygenase-1(HO-1)/carbon monoxide(CO)appared the reciprocal relationship,and amlodipine may suppress athemsclemtie progress by decreasing the system.