Colorectal cancer is one of the common malignant tumors and the overall prognosis is poor. The search for a more effective treatment for colorectal cancer has never stopped. The current interaction between the modulated immune system and the tumor microenvironment is a hot topic in the treatment of colorectal cancer. The achievements involve immune checkpoint inhibition, cytokine therapy, toll?like receptors and autologous cell therapy. It has been proved that these methods have mild effect on tumor loading reduction. However, significant breakthrough has been achieved with the use of checkpoint inhibitors targeting cytotoxic T lymphocyte associated antigen?4 (CTLA?4),programmed death?1 (PD?1) and programmed death receptor ligand 1 (PD?L1). Immunotherapy is promising in the treatment of patients with refractory tumors. The success of this current immunotherapy approach is largely limited to tumors with high mutation amplification, such as melanoma,renal cell carcinoma ( RCC) and non?small cell lung cancer. However,this discovery has led the development of checkpoint inhibitors in the treatment of colorectal cancer with highly mutated amplification of mismatch repair gene to a new era.

A mutation of intron 7, the point mutation in exon 9 was synonymous. Conclusion Two novel mutations of KEL gene are identified.

The effects of selenium-enriched yeast (Sey) on DTH in immunosuppressive mice have been investigated. It was found that Sey (30, 60, 90 mg?kg-l?d-1?6 d, ig) was able to antagonize lowered DTH by cyclophospha-mide (Cy); Meanwhile, the thymus and spleen weights were increased by Sey (30, or 60 mg?kg-1?d-1) in immunosuppressive mice. Sey also potentiated the lowered ConA and LPS-indu-ced proliferation of splenocytes in DTH mice at the doses of 30, 60, or 90 mg ?kg-1 and 60 or 90 mg?kg-1 respectively. These results suggested that Sey could enhance the functions of lymphocytes.

Objective To investigate the signaling mechanisms underlying synergistic induction of MUC5AC mucin by nontypeable Haemophilus influenzae(NTHi)and epidermal growth factor (EGF).Methods The expression of MUC5AC was measured by real-time quantitative polymerase chain reaction(PCR)and Luciferase assay.Western blot was performed to examine the synergistic induction of phosphorylation of P38,extracellular signal-regulated kinase(ERK)and P21-activated kinase(PAK)4 or the effect of dominant negative mutant of PAK4 on the synerglstic induction of phosphorvlation of P38 mitogen-activated protein kinase(P38MAPK)and ERK in HM3 cells treated with NTHi and EGF.Luciferase asgay was also performed to examine the effect of P38,ERK inhibitors or dominant negative mutants of P38MAPK and ERK on synergistic enhancement of NTHi-induced MUC5AC up-regulation by EGF at transcriptional level.Real-time quantitative PCR was performed to examine the effect of PAK4 siRNA on synergistic induction of NTHi-induced MUC5AC up-regulation by EGF.ResuIts NTHi induced MUC5AC mucin expression at both mRNA and transcriptional levels.Synergistic induction of phosFIhorylation of P38MAPK,ERK and PAK4 were observed in HM3 cells treated with NTHi and EGF.Either SB203580,a specific inhibitor for P38MAPK or PD98059,a specific inhibitor for ERK inhibited synergistic induction of MUC5AC at transcription level.Furthmore, overexpressing dominant negative mutant of P38MAPK and ERK also inhibited synergistic induction of MUC5AC at transcription level. PAK4 siRNA inhibited the synergistic induction of MUC5AC by NTHi and EGF. Overexpressing dominant negative mutant of PAK4 also reduccd synergistic induction of phosphorylation of P38 and ERK. Conclusion Synergistic induction of MUC5AC mucin by NTHi is up-regulated by EGF via PAK4-dependent P38MAPK and ERK pathways.

Objective To investigate the changes of ultrastructure and Bax,Bcl-2 expression of cerebral cortex in lymphostatic encephalopathy(LE).Methods LE models were established by occluding and removing both the shallow and deep cervical lymph nodes in rats.Ultrastructural changes of the cerebral cortex were observed at 1 d,2 d,3 d,5 d,7 d and 14 d after operation.Expression of Bax and Bcl-2 were examined by Western blot.Results Brain edema appeared under electron microscope in LE model group.The perivascular spaces in the cortex were enlarged and full of fluid,the dropsical nerve fibers had swelling and fragmented myelin sheath.Some neurons showed apoptotic conformation and some had characters of necrosis.The changes mentioned above were the most serious at day 5.The protein expression of Bax,Bcl-2 and the ratios of Bax/Bcl-2 in LE 3 d,5 d,7 d groups were significantly higher than those in normal control group(all P

Animal models of rheumatoid arthritis(RA)especially adjuvant arthritis(AA)in rats and collagen induced arthritis(CIA)in mice have much character similar to human RA in pathological mechanism,clinical representation and so on. The models are more ideal in investigating RA and selecting drugs of anti inflammation and immunity. To discuss the pathological mechanism and the relation between animal models of RA and clinic will be important not only to research RA in pathology,physiology,nervous endocrine immunity and so on,but also to find out safety and effective drugs of treatment RA. The articl summarizes several animal models of RA in establishment,pathological and clinical changes,inflammatory immune regulation and so on.

Objective To evaluate the efficacy and toxicity of oxaliplatin in combination with calcium folinate and flrDrouracil in treatment of advanced esophageal carcinoma. Methods 61 patients with advanced esophageal cancer were divided into treatment group ( 30 cases) and control group (31 cases). Treatment group was given oxaliplatin combined with calcium folinate and flrorouracil; control group was given cisplatin and calcium folinate and flrorouracil. Results The overall response rate was 43.3% in the treatment group and 41.9% in control group(P＞0.05).The median time to progression( TTP) was 8.1 months vs.7.9 months(P＞0.05).Compared with control group,the treatment group, the side effects of myelosuppression, stomasitis and alopecia were not significant difference (P ＞ 0. 05 ) , grade Ⅰ -Ⅳ nausea and vomiting( P = 0. 028 ) , diarrhea (P = 0. 039 ) and renal toxicity ( P = 0.044 ) were lower,while the peripheral nerve toxicity ( P = 0. 010) was higher. Conclusion The effect of oxaliplatin combined with calcium folinate and flrorouracil had satisfactory effect in the treatment of advanced esophageal carcinoma, and the poisonous side effect was low. It could be used as first-line chemotherapy regimen.

Physiology experiment can effectively stimulate the enthusiasm of the students to explore the scientific truth by providing the opportunity to observe real physiological phenomena,analyze,discuss and solve practical problems.Lab-based learning (LBL) and theory teaching have complementary advantages,promoting each other and can maximize the use of teaching resources.During the process of physiological LBL,training of students' thinking ability by creating problem situation,inspiration and guidance,carrying out exploring experiments can develop students' intelligence,promote innovation,improve the teaching effect.

BACKGROUND:Studies have found that sodium arsenite can cause the malignant transformation and tumorigenicity of HaCaT cels, but whether low concentrations of sodium arsenite can cause the malignant transformation is rarely reported.
OBJECTIVE:To study the effect of sodium arsenite on the malignant transformation of human immortalized keratinocyte cel lines.
METHODS:HaCaT cels were treated with different concentrations of sodium arsenite. MTT assay was used to determine the effect of sodium arsenite on HaCaT cel morphology and proliferation, flow cytometry used to detect the effect of sodium arsenite on HaCaT cel cycle, and soft agar colony formation experiments assay used to determine the effect of sodium arsenite on HaCaT cel colony formation capacity.
RESULTS AND CONCLUSION: HaCaT cels grew wel when the concentration of sodium arsenite was 5 mol/L, but the cel growth was inhibited under intervention with 10 and 50 mol/L sodium arsenite. HaCaT cels treated with 0.1 mol/L sodium arsenite were passaged to the 20th generation, and cel morphology had no notable changes; cels at passage 25 exhibited enlarged size and multiple nucleoli, which had a continued proliferation trend. Compared with the primarily cultured cels, 0.1 mol/L sodium arsenite-treated HaCaT cels at passages 15 and 25 had an increased proportion at S phase and G2/M phase, with strengthened proliferation ability and increased colony-forming efficiency, and moreover, the proliferation ability and colony-forming efficiency of passage 25 cels were higher than those of passage 15 cels. These experimental data show that high concentrations of sodium arsenite reduce HaCaT cel viability, and low concentrations of sodium sulfite have a certain influence on the morphology, cel cycle, proliferation ability and colony-forming efficiency of HaCaT cels, and moreover, the proliferation ability and colony-forming efficiency of human immortalized keratinocytes wil be strengthened with the increase of passage.

Objective To explore the association between urinary lactate/creatinine ratio and neonatal asphyxia,and to clarify the application value of urinary lactate/creatinine ratio in forecasting the hypoxie-ischemic encephalopathy (HIE)in neonates.Methods Using case-control study design method,40 cases of neonatal asphyxia infants were selected as asphyctic group and 40 healthy infants were used as control group.The urinary lactate/creatinine ratio in the first day after birth, urinary N-Acetyl-β-D-glucosaminidase (NAG)/creatinine and the score of Apgar of 80 infants were detected.The relationship between the urinary lactate/creatinine ratio,urinary NAG/creatinine ratio, as well as the score of Apgar and HIE were analyzed and compared in asphyctic group and control group.Results The Apgar scores at 1 and 5 min in asphyctic group were significantly lower than those in control group (P<0.01). The urinary lactate/creatinine ratio and urinary NAG/creatinine ratio in asphyctic group 1 d after birth were significantly higher than those in control group(P<0.01).There was significantly negative correlation between the urinary lactate/creatinine ratio and the 1-min and 5-min Apgar scores(r=-0.636,P<0.001;r=-0.883,P<0.01),but there was a significantly positive correlation between the urinary lactate/creatinine ratio and urinary NAG/creatinine ratio(r=0.433,P<0.01).Conclusion The urinary lactate/creatinine ratio may have decisive roles in prognosis evaluation of neonatal asphyxia,and so as the important foundation for the prediction of HIE.