T cell plays a pivotal role in immune system. Not only direct antigen stimulation, but also costimulation signal transducted through cell/cell membrane molecule interactions are needed in the procedure of T cell activation. Besides B7/CD28, CD40/CD40L signal is another important costimulatory pathway, and plays critical roles in many physiologic processes. The disorders of CD40/CD40L costimulatory pathway always lead to serious pathologic phenomena. In this article, the role of CD40/CD40L interactions and therapeutic potentials of blockade of it are discussed.

To establish murine graft versus host disease (GVHD) model, in order to evaluate the efficacy of human CD40 Ig fusion protein treatment. To establish murine GVHD model, 2 5?10 7 or 5 0?10 7 /L spleen cells of male C57BL/6 mice were intravenously injected into female BALB/c mice, as receipt, respectively, after sub lethally irradiation by 60 Co source. After the induction of GVHD, human CD40 Ig fusion protein was intravenously injected three times at a dose of 50?g, 150?g and 450?g on day 0, 2 and 4, respectively. The results showed that the typical expressions of GVHD were observed 4 or 5 days after the injection of donor spleen cells, and specific male Y chromosome fragment was amplified by genomic PCR in female BALC/c receipts. The mean survival time (MST) of GVHD induced mice was significantly prolonged by the treatment of human CD40 Ig fusion protein. It is suggested that Murine GVHD model successfully established can be used in evaluating the effects of anti GVHD therapies.

Objective Toinvestigatetherelationbetweenserumneuron-specificenolase(NSE), bilirubinandcerebraldysfunction,prognosisafterlarge-arteryatheroscleroticstroke.Methods According to the Trial of Org 10172 in Acute Stroke Treatment (TOAST)criteria,all the 73 patients with large artery atherosclerotic stroke were divided into the test group (41 cases ) and control group (32 cases ) according to the elevated or normal levels of serum NSE and total bilirubin. At the first day of their hospitalization,the National Institutes of Health Stroke Scale (NIHSS)score was conducted,their serum NSE,bilirubin (total bilirubin,direct bilirubin,indirect bilirubin)levels were detected,and were compared with the reevaluation of 7 and 14 days of their hospitalization and reexamination results. The modified Rankin Scale (mRS)was use to assess the recovery of their neurological function at day 30 after onset/admission. The prognosis of the patients was followed up at 1 year after onset/admission. The Kaplan-Meier product-limit method was used to conduct the analysis of the good outcome rate,and the good outcomes of both groups/interlayers (different bilirubin and NSE levels)were tested with Log-rank test. Results (1)The NIHSS scores,the levels of serum bilirubin and NSE at day 1,7,and 14 in the test group were significantly higher than those of a control group (all P<0. 01). The levels of serum bilirubin and NSE at day 7 and 14 were lower than those at day 1. (2)The mRS score at day 30 between the test group and the control group was singnificantly different (Z =3. 286,P =0. 001). (3)At day 1,the CT detection rate of large area cerebral infarction of the test group was significantly higher than that of the control group (56. 1%[n=23]vs. 28. 1%[n=9]). There was significant difference (χ2 =5. 712,P=0. 017). (4)The analysis result of Kaplan-Meier showed that there was no significant difference in its good outcome no matter grouped by the test or by serum NSE level stratification of the patients on admission (the accurateχ2valueswere4.063and4.685respectively,P=0.044and0.030respectively).Conclusion Early high-level serum NSE and hyperbilirubinemia can be used as the indexes of early identification of poor prognosis in patients with large-artery atherosclerotic stroke.

Objective To explore the effect of HDAC1 deacetylase inhibition on the proliferation differentiation and invasion in human gastric cancer stem cells (GCSCs) .Methods The GCSCs were selected as CD44 marker by using flow cytometry .RT-qPCR and Western Blot were used to detect the expression of HDAC 1 in GCSCs and non GCSCs .The effect of proliferation and in-vasion in GCSCs were observed by CCK-8 assay ,colony formation and transwell assay after the cells were treated with TSA .The expression of proteins related apoptosis ,differentiation and invasion were detected by using RT-qPCR and Western blot .Results The expression of HDAC1 in GCSCs was higher than that in non GCSCs .The capacities of proliferation and invasion in experimen-tal group were attenuated compared to the control group .The proteins related differentiation was down regulated ,and epithelial mesenchymal transition was mediated .Conclusion After the deacetylation of HDAC1 was inhibited ,the proliferation ,differentia-tion and invasion of GCSCs were reduced .

CD40/CD40L, besides B7/CD28, is an alternative important costimulation signal transduction pathway. It plays a pivotal role in T cell activation. Moreover, it may play a critical role at many levels of sensitization and effector phases of allograft rejection. In order to get the fusion protein of human CD40 extracelluar region and IgG 1 Fc fragment, and investigate the potential role of blocking CD40/CD40L costimulation pathway in immunotherapy, total RNA was extracted from human lymphoma cell line Daudi, and CD40 gene extracelluar region was amplified by RT-PCR. The PCR products were inserted into pGEM T Easy vector, and the cloning vector pGE40 was obtained. The DNA sequence was analyzed by automatic DNA sequencer. After sequencing, the transient expressing vector was constructed by inserting correct fragment into pIG vector, which contains the genomic human IgG1 Fc (hinge, CH2 and CH3) gene. Hence the recombinant fusion expression vector was constructed successfully, and named after pIG/40 Ig. Then, COS-7 cells were transfected through DEAE-Dextran/chloroquine method. The CD40-Ig fusion protein expressed in COS-7 cell culture supernatant was identified by sandwich ELISA and Western blot. Result showed that the CD40-Ig fusion protein can be detected by sandwich ELISA in the cell culture supernatant. Western blot analysis also showed that it could react with McAbs of mouse anti-human CD40 G28-5 and mouse anti-human Ig gamma chain. There is only one obvious band at the position of relative molecular weight 50 kD, and it is equivalent to the expected value. Above all, the recombinant fusion expression vector pIG/40 Ig was constructed, and CD40-Ig fusion protein gene was expressed in COS-7 cells successfully. It could be laid a foundation to investigate the potential role of CD40/CD40L pathway as the target of GVHD prevention and therapy.

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.