Obj ectiev The purpose of this study is to assess the impact of bone metastasis on survival in non-small cell lung cancer(NSCLC),Which were treated with gefitinib for more than 6 months,and to identify the prognostic factors of patients with NSCLC presenting bone metastasis .Methods We compared the overall survival(OS), progression-free survival(PFS),1-year2,-year and 3-year survival rates between two cohorts based on bone metastasis ,as well as the prognostic factors in the patients with bone metastasis .Results In total, 76 patients were included in the study ,in which there are44 patients with no bone metastasis and32 patients with bone metastasis.The cohorts were similar in OS (19.000 ±3.317 months vs.26.000 ±2.121 months,P =0.625)as well as PFS (14.000 ±1.843 months vs.16.000 ±1.411 months,P=0.328).The 1-year survival rate was 63.6%in no bone metastasis cohort,but was increased to 96.9%in the other cohort.The survival rates at 2 years(34.1%vs.56.3%,P=0.054)and 3 years(18.2%vs.18.4%,P=0.950)were similar.The univa-riate analysis showed that a worse prognosis was more likely existed in elderly patients ( aged >60 years) and with pulmonary progression ,whereby factors including gender ,pathology s,moking index ,brain metastases ,bone related events and the application of radiotherapy ,bisphosphonates might not be independently associated with the surviv -al late.Analysis of multiple variables indicated a favorable prognosis for patients with no pulmonary progression . Conclusion This retrospective study shows that bone metastasis may not shorten the survival in patients whose pulmonary lesion was controlled by gefitinib .On the contrary ,pulmonary progression may be more likely the cause of death in patients with bone metastasis .Non suggestion is given to discontinue gefitinib when the bone metastasis appears.

OBJECTIVETo evaluate the therapeutic effect of Liujunzi decoction combined with Zuojin pills in treating the radioactive duodenitis and their mechanism, and compare with clinical routine acid suppressants combined with mucous membrane protective preparations to study the mechanism of their efficacy.

METHODAccording to the study of Williams J P and characteristics of duodenitis, and by reference to the radiation enteritis modeling standard, we took the lead in establishing the mouse radioactive duodenal injury model. The model mice were randomly divided into the control group (n = 26), traditional Chinese medicine (TCM) group (n = 16) and the western medicine (oral administration with famotidine 0.5 mL + almagate suspension 0.3 mL per mouse, once a day) group (n = 16). After the standard administrating, such objective indexes as general condition, weight, changes in health score, pathology and expression of inflammatory factors were observed to evaluate the efficacy.

RESULTThe radioactive duodenitis model of mice was successfully established with 12 Gy. Mice in the control group suffered from weight loss, anorexia, low fluid intake, loose stools, and occasionally mucous bloody stool, poor spirit, dim fur, lack of exercise and arch back. Mice in drug intervention groups were generally better than those in the pure irradiation group. The IL-6, IL-1beta, TNF-alpha mRNA expressions in spleen and mesenteric lymph node tissues in TCM and western medicine groups showed a declining trend compared with the control group. Their concentrations in peripheral blood serum also slightly changed. The TCM group revealed notable advantage in reducing inflammatory factors. The microscopic observation showed that a better mucosa repair in intervention groups than the pure irradiation group. The improved Chiu's scoring method showed a statistical significance in the difference between TCM and western medicine groups (P < 0.05).

CONCLUSIONLiujunzi decoction combined with Zuojin pills could treat acute radiation enteritis, regulate organic immunity, and inhibit acute injury, promote local tissue repair, with the potential to resist such adverse effects as radiation intestinal fibrosis. The regulation of inflammatory factor release is one of efficacy generation mechanisms.

Animals ; Cobalt Radioisotopes ; adverse effects ; Drug Interactions ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Duodenitis ; blood ; drug therapy ; Interleukin-1beta ; blood ; Interleukin-6 ; blood ; Mice ; Mice, Inbred BALB C ; Mucous Membrane ; drug effects ; radiation effects ; Radiation Injuries, Experimental ; blood ; drug therapy ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVESTo construct small interfering (siRNA) Sox9 expression plasmid and transfer it into human chondrosarcoma cells HTB-94, and to check the mRNA and protein expression of Sox9 and cell growth and apoptosis of HTB-94 human chondrosarcoma cells.

METHODSsiRNA(Sox9) expression plasmid was designed and synthesized. And it was transferred into HTB-94 human chondrosarcoma cells. Then the expression of the mRNA and protein of Sox9, cell growth and apoptosis in transferred HTB-94 human chondrosarcoma cells were checked.

RESULTSThe recombinant plasmid was confirmed by enzyme digestion analysis and DNA sequencing. The expression of the mRNA and protein expression of Sox9 in transferred HTB-94 were significantly reduced. The cell growth of HTB-94 was inhibited, and the apoptosis of HTB-94 was remarkably increased.

CONCLUSIONsiRNA (Sox9) expression plasmid could be transferred into HTB-94 human chondrosarcoma cells. And it can reduce the mRNA and protein expression of the HTB-94, inhibit the cell growth and cause the apoptosis of the tumor cells.

Apoptosis ; Cell Proliferation ; Chondrosarcoma ; metabolism ; pathology ; Genetic Vectors ; Humans ; Plasmids ; genetics ; RNA, Messenger ; genetics ; RNA, Small Interfering ; genetics ; SOX9 Transcription Factor ; genetics ; metabolism ; Transfection ; Tumor Cells, Cultured

BACKGROUNDDermatomyositis (DM) and polymyositis (PM) are common inflammatory myopathies whose immunopathogenic mechanisms remain poorly understood. The NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome is a type of cytoplasmic multiprotein inflammasome and is responsible for the activation of inflammatory reactivations. Responding to a wide range of exogenous and endogenous microbial or sterile stimuli, NLRP3 inflammasomes can cleave pro-caspase-1 into active caspase-1, which processes the pro-inflammatory cytokines pro-interleukin (IL)-1β and pro-IL-18 into active and secreted IL-1β and IL-18. The NLRP3 inflammasome is implicated in infectious and sterile inflammatory diseases. However, it remains unclear whether it is involved in the pathogenesis of DM/PM, which we aim to address in our research.

METHODSIn this study, 22 DM/PM patients and 24 controls were recruited. The protein and RNA expression of IL-1β, IL-18, NLRP3, and caspase-1 in serum and muscle samples were tested and compared between the two groups.

RESULTSThe serum IL-1β and IL-18 levels were significantly higher in DM/PM patients than those in the controls by enzyme linked immunosorbent assay (ELISA, DM vs. control, 25.02 ± 8.29 ng/ml vs. 16.49 ± 3.30 ng/ml,P < 0.001; PM vs. control, 26.49 ± 7.79 ng/ml vs. 16.49 ± 3.30 ng/ml,P < 0.001). Moreover, the real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) showed that DM/PM patients exhibited higher RNA expression of IL-1β, IL-18, and NLRP3 in the muscle (for IL-1β, DM vs. control, P= 0.0012, PM vs. control, P= 0.0021; for IL-18, DM vs. control, P= 0.0045, PM vs. control, P= 0.0031; for NLRP3, DM vs. control, P= 0.0017, PM vs. control, P= 0.0006). Moreover, the protein expression of NLRP3 and caspase-1 in muscle samples of DM/PM patients were also significantly elevated compared to that in the muscles of the controls.

CONCLUSIONSOur findings demonstrate that the NLRP3 inflammasome is implicated in the pathogenesis of DM/PM. High NLRP3 expression led to elevated levels of IL-1β and IL-18 and could be one of the factors promoting disease progress.

Adult ; Caspase 1 ; analysis ; genetics ; Dermatomyositis ; etiology ; Female ; Humans ; Inflammasomes ; physiology ; Interleukin-18 ; analysis ; genetics ; Interleukin-1beta ; analysis ; genetics ; Male ; Middle Aged ; NLR Family, Pyrin Domain-Containing 3 Protein ; analysis ; genetics ; physiology ; Polymyositis ; etiology

Congresses as Topic ; Humans ; Rhinitis ; Rhinitis, Allergic, Perennial

OBJECTIVETo investigate the effects and mechanism of postoperative insulin resistance in gastrectomy patients with preoperative oral carbohydrate.

METHODSFrom April to October 2011, 60 consecutive gastric cancer patients met inclusion criteria were divided into oral carbohydrate group and placebo group by randomized double-blind principles. Resting energy expenditure (REE), fasting blood glucose, insulin and triglyceride level were detected in 4 hours preoperatively. The 500 ml carbohydrate or placebo were administrated orally 2-3 hours before anaesthesia. Two group patients underwent radical distal subtotal gastrectomy under epidural compounded intravenous anesthesia. After laparotomy and before the abdomen was closed, a piece of rectus abdominis was taken and fixed in 3% glutaraldehyde. REE, fasting blood glucose, insulin and triglyceride level were detected immediately after surgery. The changes of insulin resistance index, blood triglycerides level, REE and respiratory quotient were compared pre- and post-operatively. The changes of rectus abdominis mitochondrial ultrastructure were observed by transmission electron microscopy respectively.

RESULTSThere were 48 patients (34 males and 14 females) completed the trial. The 24 and 24 patients in oral placebo and carbohydrate groups respectively. In oral placebo group, post-operative insulin resistance index, REE, respiratory quotient, serum triglyceride level and the rectus abdominis mitochondrial damage index were 12.68 ± 3.13, (1458 ± 169) kcal/d, 0.73 ± 0.42, (0.53 ± 0.24) g/L and 1.14 ± 0.33, respectively. And the above items were 5.67 ± 1.40, (1341 ± 110) kcal/d, 0.79 ± 0.22, (1.04 ± 0.97) g/L and 0.92 ± 0.19 in oral carbohydrate groups respectively. All difference was statistically significant (t = 6.646, 2.851, 6.546, 2.542 and 2.730, all P < 0.05). Oral placebo group showed a markedly swollen mitochondria, steep membrane was not clear, mitochondria appeared vacuolated changes.

CONCLUSIONSPreoperative oral carbohydrate could reduce the insulin resistance and REE, improve the material metabolism status in radical gastrectomy patients. The possible mechanisms should be related to promotion of insulin release and protection of mitochondrial function.

Administration, Oral ; Aged ; Basal Metabolism ; Carbohydrates ; administration & dosage ; therapeutic use ; Double-Blind Method ; Female ; Gastrectomy ; Humans ; Insulin Resistance ; Male ; Middle Aged ; Mitochondria ; ultrastructure ; Postoperative Complications ; prevention & control ; Stomach Neoplasms ; surgery

After treating with chemotherapy or immunosuppressant, malignant diseases of hematopoietic system such as leukemia, malignant lymphoma and aplastic anemia usually induced severe infection such as sepsis. Sepsis which is hard to be diagnosed causes high death rate. This study was purposed to establish an experimental sepsis mouse model so as to provide a basis for pathogenesis and intervention study. A classic caecal ligation and puncture (CLP) was used to establish experimental sepsis model. ELISA was used to detect levels of C5a, IL-6, TNFalpha, and IFN-gamma. Flow Cytometry was applied to measure apoptosis of lymphocytes in thymus and mesentery. The pathologic changes of thymus and spleen were confirmed by HE staining. The results showed that almost 70%-80% mice died at 72 hours after CLP. Only approximate 20% animal survived during finite time, mice in CLP group had significant weight lose. Meanwhile large release of different inflammatory mediators which are related with sepsis (C5a, IL-6, TNF-alpha, and IFN-gamma) was observed after CLP. Apoptosis of lymphocytes in thymus and mesentery lymphonodus was enhanced markedly after CLP. Significantly pathologic injury was also observed in thymus and spleen. It is concluded that a mouse model of experimental sepsis was successfully established by caecal ligation and puncture which can well mimic the clinical symptom of sepsis. The experimental sepsis mouse model provides an excellent tool for exploring the pathogenesis and intervention ways for sepsis accompanied with complicated malignant hematological diseases in vivo.
Animals ; Apoptosis ; Cecum ; injuries ; Complement C5a ; metabolism ; Disease Models, Animal ; Interferon-gamma ; metabolism ; Interleukin-6 ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Sepsis ; metabolism ; pathology ; Spleen ; pathology ; Thymus Gland ; pathology ; Tumor Necrosis Factor-alpha ; metabolism

AIMTo improve the profile of 20 (S)-camptothecin, a series of 20-O-linked camptothecin phenoxyacetic acid ester derivatives have been designed.

METHODSThese derivatives were synthesized by the method of acylation. Their chemical structures were confirmed with 1HNMR, IR, MS, and HRMS. The cytotoxicities of the compounds were tested by MTT assay. The in vivo antitumor activities of these esters were evaluated against mouse liver tumor H22 in mice.

RESULTSTwelve derivatives of camptothecin ester are new compounds.

CONCLUSIONIn vitro and in vivo antitumor activity has indicated that some derivatives appeared significantly more effective than topotecan in the H22 mouse liver tumoral model.

Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Camptothecin ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; drug effects ; Esters ; chemistry ; Female ; Humans ; Inhibitory Concentration 50 ; Liver Neoplasms ; pathology ; Mice ; Mice, Inbred ICR ; Molecular Structure ; Neoplasm Transplantation ; Topotecan ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays

Objective:To clarify the causal relationship between obesity and male infertility through Mendelian randomization(MR)study.Methods:We assessed the causal effect of genetically predicted body mass index(BMI)on the risk of male infertility via a two-sample MR analysis,with the BMIs of 99 998 cases and 12 746 controls as the exposure factor and genetic information on male infertility obtained from a genome-wide association study of 73 479 Europeans.In the univariable MR(UVMR)analysis of the causal relationship,we mainly used inverse variance weighting(IVW),with MR-Egger regression and weighted median filtering as the supplementary methods.Sensitivity analyses including the Cochran's Q test,Egger intercept test,MR-PRESSO,leave-one-out analysis and funnel plot were performed to verify the robustness of the MR results.To evaluate the direct causal effects of BMI on MI risk,mult-ivariable MR(MVMR)was performed.Results:UVMR indicated a causal relationship between genetically predicted BMI and an in-creased risk of male infertility(OR:1.237,95%CI:1.090-1.404,P=0.001).Sensitivity analysis revealed little evidence of bias in the current study(P>0.05).With such risk factors as type 2 diabetes,alcohol consumption and smoking adjusted,MVMR confirmed a direct causal effect of genetically predicted BMI on the risk of male infertility(P<0.05).Conclusion:Genetically pre-dicted BMI may be associated with an increased risk of male infertility.Further studies are expected to explore the underlying mecha-nisms of this association and provide some new strategies for the prevention and treatment of BMI-related male infertility.

Objective We aimed to compare the efficacy and prognosis of percutaneous coronary intervention(PCI)in complex and high-risk patients with coronary heart disease(CHD)treated with extracorporeal membrane oxygenation(ECMO)combined with intra-aortic balloon pump(IABP)assistance,and explore the application value of combined use of mechanical circulatory support(MCS)devices in complex PCI.Methods A total of patients who met the inclusion criteria and underwent selective PCI supported by MCS at the Department of Cardiology,the First Affiliated Hospital of the Air Force Medical University from January 2018 to December 2022 were continuously enrolled.According to the mechanical circulatory support method,the patients were divided into ECMO+IABP group and IABP group.Clinical characteristics,angiographic features,in-hospital outcomes,and complications were collected.The intra-hospital outcomes and major adverse cardiovascular events(MACE)at one month and one year after the procedure were observed.The differences and independent risk factors between the two groups in the above indicators were analyzed.Results A total of 218 patients undergoing elective PCI were included,of which 66 patients were in the ECMO+IABP group and 152 patients were in the IABP group.The baseline characteristics of the two groups of patients were generally comparable,but the ECMO+IABP group had more complex lesion characteristics.The proportion of patients with atrial fibrillation(6.1％vs.0.7％,P=0.030),left main disease(43.9％vs.27.0％,P=0.018),triple vessel disease(90.9％vs.75.5％,P=0.009),and RCA chronic total occlusion disease(60.6％vs.35.5％,P＜0.001)was higher in the ECMO+IABP group compared to the IABP group.The proportion of patients with previous PCI history was higher in the IABP group(32.9％vs.16.7％,P=0.014).There was no statistically significant difference in the incidence of in-hospital complications between the two groups(P=0.176),but the incidence of hypotension after PCI was higher in the ECMO+IABP group(19.7％vs.9.2％,P=0.031).The rates of 1-month MACE(4.5％vs.2.6％,P=0.435)and 1-year MACE(7.6％vs.7.9％,P=0.936)were comparable between the two groups.Multivariate analysis showed that in-hospital cardiac arrest(OR 7.17,95％CI 1.27-40.38,P=0.025)and after procedure hypotension(OR 3.60,95％CI 1.10-11.83,P=0.035)were independent risk factors for the occurrence of 1-year MACE.Conclusions Combination use of ECMO+IABP support can provide complex and high-risk coronary heart disease patients with an opportunity to achieve coronary artery revascularization through PCI,and achieve satisfactory long-term prognosis.