Purpose:To study whether the inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt survival pathway could sensitize the response of tumor cells to some chemotherapyeutic agents. Methods:The different tumor cells has been treated with the combination of isoform specific Akt inhibitor and either adriamycin or camptothecin; the quantitation of the induction of apoptosis by drugs has been estimated with caspase 3 assay; immunoprecipitation western blotting has been used to evaluate the inhibition of the phosphorylation of different isoforms of Akt after the treatment. Results:①The inhibitors could reduce the phosphorylation of Threonine 308 and Serine 473 of isoform specific Akt. ②The inhibition of any one isoform specific Akt could not reverse the resistance of tumor cells tested to chemotherapeutic drugs, but it is not the same case if blocking of two isoforms of both Akt1 and Akt2 was done at the same time. ③The synergistic effects of Akt inhibitors is maybe relative to the level of endogenous PTEN(phosphatase and tensin homolog deleted on chromosome 10) expression. Conclusions:It is required to inhibit two isoforms of both Akt1 and Akt2 in order to maximally sensitize the tumor cells to chemotherapy.

Objective To study the role of caspase 3 in ischemic brain damage of rats, and further understand the molecular mechanisms of ischemic cerebral vascular disease.Methods Rat models of the left middle cerebral artery (MCA) occlusion/reperfusion were made using a modification of the intraluminal sature method of Longa established by Belayev, infarct zones were confirmed by 2,3,5 triphenyltetrazolium chloride (TTC) staining, and caspase 3 expression on brain sections at the mRNA and active protein level was detected with in situ hybridization and immunohistochemistry technique, respectively.Results After 2 hours of left MCA ischemia followed by 24 hours of reperfusion, obvious infarct in the MCA dominate regions was confirmed by TTC staining; low levels of caspase 3 mRNA, and fewer of its active protein expression was found in normal brains, sham brains and contralateral brains of MCAO rats; both caspase 3 mRNA and activated protein expression in ipsilateral region were increased after 24 hours of recirculation, and even higher levels were detected at 48 hours of reperfusion.Conclusion Apoptotic mechanism might involve in delayed neuronal death after cerebral ischemia, and caspase 3 might play an important role in ischemic neuronal injury.

Objective: To study caspase-3 activities and the neuroprotective effect of caspase-3 inhibitor Ac-DEVD-CMK in primary cultures of rat hippocampal neurons during hypoxia/reoxygenation (H/R). Methods: After pretreated with Ac-DEVD-CMK or the vector DMSO fo 1 h, primary cultures of rat hippocampal neurons were induced to hypoxia for 3 h, followed by 12 to 48 h of reoxygenation. The neuronal viability was estimated by MTT assay, and caspase-3 cellular activities were measured by a colorimetric method using Ac-DEVD-pNA as a substrate. Results: During H/R, the cultured rat hippocampal neuronal viability gradually decreased, and caspase-3 activities in the primary cultures of rat hippocampal neurons were significantly increased, and peaked at 24 h of reoxygenation. Caspase-3 activities were decreased in the neurons pretreated with Ac-DEVD-CMK in a dose dependent manner. Conclusion: Delayed neuronal death is detected in cultured hippocampal neurons during H/R, and apoptosis mediated by caspase-3 may play an important role in it, and caspase-3 inhibitor has a neuroprotective effect on them.

Objective To explore an effective method for preventing and treating oral mucosal complications of radiotherapy for head and neck cancer. Methods Fifty head and neck cancer patients who were receiving radiotherapy were enrolled between March, 2008 and March, 2010. These patients were randomly assigned to the treatment group and the control group. During the radiotherapy, patients in the treatment group were given IL-11 in the form of atomization inhalation,whereas patients in the control group were not. Results IL-1 1 was well tolerated by the patients. It significantly decreased the level of oral mucosal complications and pains and improved patients' appetites ( P < 0.05 ). In addition, the duration of pain was significantly ( P <0.05 ) reduced from 4.5 ± 1.3 days ( in control group) to 2.3 ± 1.0 ( in treatment group), and the healing period was also significantly ( P < 0.05) reduced from 7.3 ± 1.5 days ( in control group) to 4.1 ± 1.7 ( in treatment group). Conclusion IL-11 is effective in preventing and treating oral mucosal complications of radiotherapy for head and neck cancer,relieving associated pains, and therefore improving patients' quality of life.

Objective: To analyze the characteristics of individuals positive for SARS-CoV-2 nucleic acid in a centralized isolation site for people entering China in Huzhou City of Zhejiang Province from December 18, 2021 to January 12, 2022, so as to provide insights into the prevention and control of overseas imported COVID-19. Methods: The basic characteristics, nucleic acid detection and epidemiological investigations were collected from individuals positive for SARS-CoV-2 nucleic acid in a centralized isolation site for people entering China from December 18, 2021 to January 12, 2022, and the temporal distribution, population distribution, source of importation, and virus typing were descriptively analyzed. Results : From December 18, 2021 to January 12, 2022, a total of 2 974 individuals in 19 flights were recorded in this centralized isolation site, and 33 cases were tested positive for SARS-CoV-2 nucleic acid, including 21 confirmed cases with common type, 9 confirmed cases with mild type, and 3 cases with asymptomatic infections. There were 11 cases with Omicron infections ( 33.33% ), 5 cases with Delta infections ( 15.15% ), and 17 cases with infection of unidentified types ( 51.52% ). The median interval ( interquartile range ) from the time of entry to the time of a positive test was 4.0 ( 7.0 ) days among all positive cases, 0 ( 4.0 ) day among cases with Omicron infections and 4.5 ( 8.5 ) days among cases with infections of Delta and unidentified types. The positive cases had a mean age of ( 36.97±8.58 ) years, and included 27 men (81.82%). There were 30 cases ( 90.91% ) receiving two and more doses of COVID-19 vaccines, and 7 cases ( 21.21% ) with a previous history of SARS-CoV-2 infections. There were 19 cases ( 57.58% ) from African countries, and 7 of 11 cases with Omicron infections were imported from African countries. Conclusion Omicron infection was predominant among individuals positive for SARS-CoV-2 nucleic acid in this centralized isolation site for people entering China from December 18, 2021 to January 12, 2022, with no severe cases detected, and most positive cases were imported from African countries.

Objective To investigate the growth inhibition effect of evodiamine (Evo) on renal carcinoma 786-0 cells and to explore its molecular mechanism. Methods After treated with Evo, methyl thiazolyl tetrazolium ( MTT) assay was used to detect the vitality of 786-0 cells, flow cytometry was employed to examine the cell cycle distribution in 786-0 cells, and immunoblotting was utilized to determine the expression levels of target proteins related to cell cycle progression. Results Evo remarkably inhibited 786-0 cells vitality in dose-dependent manner. Cell cycle analysis indicated that 786-0 cells were arrested in G2/M phase followed by Evo treatment. Furthermore, the results of immunoblotting showed that Evo up-regulated the protein expression levels of P53, P21 and its downstream target gene CyclinB1 in 786-0 cells. Conclusion Evo treatment can induce 786-0 cell cycle G2/M arrest, and its underlying mechanism might be dependent on the P53/P21 signal pathway.

Objective To study the effects of MF59 in combination with heat-killed BCG ( hBCG) as adjuvant on the immunogenicity of Mycobacterium tuberculosis fusion protein PstS1-LEP.Methods BALB/c mice were divided into six groups from group 1 through group 6.They were immunized with PstS1-LEP+MF59 ( group 1 ) , PstS1-LEP+MF59/hBCG ( group 2 ) , PstS1-LEP+hBCG ( group 3 ) , MF59 ( group 4 ) , PstS1-LEP (group 5) and hBCG (group 6) for three times at intervals of two weeks , respectively.The mice were sac-rificed two weeks after the last immunization .The serum samples were collected for antibodies detection .The splenic lymphocytes and peritoneal macrophages were isolated and cultured with PstS 1-LEP.Indirect ELISA and sandwich ELISA were used to detect PstS 1-LEP-specific antibodies and cytokines in the supernatants of culture , respectively.Results The level of IFN-γ, IL-1β, IgG, IgG1 and IgG2a in group 1 were higher than those in groups 4, 5 and 6 (P<0.05).The level of IL-2 and IL-4 in group 1 were higher than those in groups 4 and 6 (P<0.05).The level of IFN-γ, IL-1β, IL-12, IgG, IgG1 and IgG2a in group 2 were higher than those in groups 4, 5 and 6 (P<0.05).The level of IL-2 was higher in group 2 than that in groups 4 and 6 (P<0.05). The level of IL-4 in group 3 was higher than that in group 4 ( P=0.05 ) .The level of IL-1βin group 3 were higher than that in groups 4 and 5 ( P<0.05 ) .The level of IgG was higher in group 3 than that in groups 4 and 6 (P<0.05).IgG1 level in group C was up-regulated in comparison with that in groups 4, 5 and 6 (P<0.05 ) .Conclusion hBCG as PstS1-LEP adjuvant induces a shift towards Th 2-type immune response , while MF59 induces Th1/Th2-type immune response.The combination of MF59 and hBCG inhibits the secretion of IL-4 by spleen lymphocytes , but enhances the secretion of IL-12 by macrophage .

Objective:To investigate the correlation factors of complete clinical response in idiopathic inflammatory myopathies(IIMs)patients receiving conventional treatment.Methods:Patients diagnosed with IIMs hospitalized in Peking University People's Hospital from January 2000 to June 2023 were in-cluded.The correlation factors of complete clinical response to conventional treatment were identified by analyzing the clinical characteristics,laboratory features,peripheral blood lymphocytes,immunological indicators,and therapeutic drugs.Results:Among the 635 patients included,518 patients finished the follow-up,with an average time of 36.8 months.The total complete clinical response rate of IIMs was 50.0％(259/518).The complete clinical response rate of dermatomyositis(DM),anti-synthetase syn-drome(ASS)and immune-mediated necrotizing myopathy(IMNM)were 53.5％,48.9％and 39.0％,respectively.Fever(P=0.002)and rapid progressive interstitial lung disease(RP-ILD)(P=0.014)were observed much more frequently in non-complete clinical response group than in complete clinical re-sponse group.The aspartate transaminase(AST),lactate dehydrogenase(LDH),D-dimer,erythrocyte sedimentation rate(ESR),C-reaction protein(CRP)and serum ferritin were significantly higher in non-complete clinical response group as compared with complete clinical response group.As for the treat-ment,the percentage of glucocorticoid received and intravenous immunoglobin(IVIG)were significantly higher in non-complete clinical response group than in complete clinical response group.Risk factor analysis showed that IMNM subtype(P=0.007),interstitial lung disease(ILD)(P=0.001),eleva-ted AST(P=0.012),elevated serum ferritin(P=0.016)and decreased count of CD4+T cells in peripheral blood(P=0.004)might be the risk factors for IIMs non-complete clinical response.Conclu-sion:The total complete clinical response rate of IIMs is low,especially for IMNM subtype.More effec-tive intervention should be administered to patients with ILD,elevated AST,elevated serum ferritin or decreased count of CD4+T cells at disease onset.