Chimeric antigen receptor T cell(CAR-T)immunotherapy is the most potential adoptive immunotherapy for malignant tumors,which needs no antigen presenting cells(APC)and is not limited by major histocompatibiliy complex(MHC). CAR-T immunotherapy not only recognizes and kills tumor cells directly,but also forms memory T cells and establishs long-term anti-tumor mechanism,of which the effect in leukemia,multiple myeloma and other non-solid tumors as well as the great potential in solid tumors have been widely verified. However,a variety of adverse reactions such as cytokine release syndrome(CRS),neurotoxicity(NT)and miss target effect are produced during CAR-T immunotherapy,of which the occurrence of CRS and NT may be related to the abnormal level of cytokines. Remarkable increase of cytokine level is a major characteristics of CRS. However,the increase of cytokines is neither the root cause nor the only result of CAR-T adverse reaction. CAR-T immunotherapy has a high incidence of adverse reaction which may even endanger the life of patients. Cytokine targeted drugs such as Anakinra and Tocilizumab may decrease the incidence of adverse reaction and improve the prognosis of patients. This paper reviews the correlation of cytokines with CRS and NT in CAR-T immunotherapy and the effect of cytokine targeting drugs,so as to provide a reference for the basic research,quality control and clinical application of CAR-T immunotherapy.

OBJECTIVE: To study the effects of Salvia miltiorrhiza on serum levels of cytokines including interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) in patients with severe acute pancreatitis (SAP). METHODS: Thirty-six SAP patients were randomly divided into Salvia miltiorrhiza-treated group and non-Salvia miltiorrhiza-treated group with eighteen patients in each group. Fourteen age-matched healthy volunteers were assigned to control group. Serum levels of IL-6, IL-8, and TNF-alpha were tested within 24 hours of admission and 7 days after admission. RESULTS: Compared with those of the healthy volunteers, serum levels of the three cytokines of the SAP patients were significantly elevated (P<0.05). Serum levels of the three cytokines were significantly decreased in both Salvia miltiorrhiza-treated group and non-Salvia miltiorrhiza-treated group after 7-day treatment (P<0.05). The declining of the serum levels of the three cytokines in Salvia miltiorrhiza-treated group was more obvious than that in non-Salvia miltiorrhiza-treated group. CONCLUSION: Salvia miltiorrhiza can treat SAP patients by reducing the serum levels of IL-6, IL-8, and TNF-alpha.

Objective To analyze the clinical and laboratory features of acute pulmonary embolism for diagnosis as possible as early.Methods For 15 patients of pulmonary embolism,who have not history of heart-lung disease and have been diagnosed by high speed multislice CT, the clinical and other laboratory data of these patients were retrospectively analyzed.Results The clinical manifestations were dyspnea ,chest distress, palpitation;the signs including tachypnea, systole murmur, tachycardia etc. The examinations were mainly color Dopple echocardiography and blood gas analysis. In some cases of embolism were found in their pulmonary artery; in all cases tricuspid regurgitation were found by color Dopple echocardiography and their pulmonary systole pressure were all over normal value(42～76mmHg).The blood gas analysis showed that PaO 2 was obviously lower than normal value(30～65mmHg).Conclusions The patient who has symptoms of dyspnea and palpitation must be examined by high speed multislice CT , color Dopple echocardiography and other measurements to get an immediate diagnosis . The first choice is color Dopple echocardiography when there is no high speed multislice CT. The patients can get exact diagnosis and prompt treatment by manifestation of pulse spectral of pulmonary artery, increase of pulmonary artery pressure, right ventricular enlargement.

Objective To evaluate the relationship between endoplasmic reticulum stress and cell apoptosis during liver cold ischemia-reperfusion(I/R)in rats. Methods Thirty-two SPF healthy adult male Sprague-Dawley rats,weighing 200-250 g,were divided into 2 groups(n=16 each)using a random number table:sham operation group(group S)and liver cold I/R group(group I/R).In group I/R,the liver was perfused through the portal vein with 4 ℃ lactated Ringer′s solution 6-8ml/min for 30min after liver ischemia,and the liver blood flow was restored after the end of perfusion. At 6 h of reperfusion in group I/R or at 6 h after peritoneum closure in group S,blood samples from the inferior vena cava were collected for determination of serum alanine transaminase and aspartate transaminase concentrations. After blood sampling,liver tissues were obtained for examination of pathological changes and for determination of malondialdehyde content(by thiobarbituric acid method),superoxide dismutase activity(using xanthine oxidase method),cell apoptosis(using TUNEL),expression of endoplasmic reticulum protein 46(ERP46),immunoglobulin heavy chain binding protein(BiP)and caspase-12(by immunohistochemistry),and expression of ERP46,BiP and caspase-12 mRNA(using quantitative real-time polymerase chain reaction).The pathological changes were scored. Apoptosis rate was calculated. Results Compared with group S,the serum alanine transaminase and aspartate transaminase concentrations,pathological scores,malondialdehyde content and apoptosis rate were significantly increased,the activity of superoxide dismutase was decreased,and the expression of ERP46,BiP and caspase-12 protein and mRNA was up-regulated in group I/R(P<0.05).Conclusion The mechanism of cell apoptosis during liver cold I/R may be related to excessive activation of endoplasmic reticulum stress in rats.

Objective To investigate the effect of glutathione on serum IL-6, IL-8 and TNF-α levels in severe acute pancreatifis (SAP). Methods Thirty-six patients with SAP were randomly divided into glutathione treatment group and non-glutathione treatment group. Age-matched controls were enrolled from healthy volunteers. Serum levels of IL-6, IL-8, and TNF-α were measured within 24 h of admission and the seventh day after admission. Results The serum levels of IL-6, IL-8, and TNF-α in SAP patients were (81.34±5.99)ng/L, (97.81±15.61) ng/L and (28.21±1.53)ng/L, respectively, which were significantly higher than (16.69±2.86) ng/L, (26.42±1.59) ng/L and (15.89±1.41) ng/L in control group (P＜0.05). Seven days later, the serum levels of IL-6, IL-8, and TNF-α in glutathione treatment group were (31.21±3.88)ng/L, (35.51±1.27)ng/L and (16.15±1.31)ng/L, respectively, and those in non- glutathione treatment group were (53.88±6.21 ) ng/L, (51.91±9.88) ng/L, (17.88±1.51 ) ng/L, redpectively. The serum levels of IL-6, IL-8, and TNF-α at the seventh day after treatment were lower than those before treatment and the decrease in glutathione treatment group was more significant (P＜0.05). Conclusions Glutathione may reduce the serum levels of IL-6, IL-8, and TNF-＜ and may play a role in the treatment of SAP.

Objective To summarize cardiopulmonary bypass management in open heart surgery of children with congenital heart disease. Methods The clinical data of 80 children with age less than 4 years old underwent open heart surgery under cardiopulmonary bypass from January,2005 to January,2009 were retrospectively analyzed. Results The operations of all 80 cases were basically smoothly and no severe complications associated with extracorporeal circulation occurred. After cross-clamping releasing,automatically re-beating occurred in 75 cases,and 5 re-beat after electric shock. There was no postoperative death. Conclusions Open heart surgery under cardiopulmonary bypass is safe and efficacy in children with congenital heart disease.

[Objective]To construct the recombinant adenovirus vector co-expressing human vascular endothelial growth factor 165(VEGF165) and angiogenin-1(Ang-1),and to observe the expression of target gene after transfection.[Method]Molecular biologic techniques were used to clone the genes of VEGF165 and Ang-1,and PCR was used to amplify the DNA sequence of IRES(internal ribozyme entry site) from pIRES2-EGFP.The genes of VEGF165,IRES and Ang-1 were subcloned to pTrack-CMV one by one to get the plasmid named pTrack-CMV-VIA,which contained all the three genes.The linearized shuttle plasmid was cotransformed into BJ5183 bacteria with backbone vector AdEasy-1.Further the recombinant plasmid was packaged and amplified in QBI-293A cells after Pac I digestion to get adenovirus vector pAd-VIA.The expression of the gene of interests was evaluated by fluorescence microscopic analysis of GFP expression and enzyme linked immunosorbent assay(ELISA).[Result]The recombinant adenovirus plasmid was consistent with that shown by sequencing and restriction endonucleases digestion.The recombinant pAd-VIA vector was packaged and amplified successfully in QBI-293A cells.The titer was 2?1010 PFU/ml after amplifying.High positive GFP was expressed in the field through fluorescence microscopy after being transfected by recombinant pAd-VIA.ELISA indicated the expression of the target genes.The difference between the tansfected and non-transfected group was significant(P

Objective To evaluate the effect of hydrogen on the endoplasmic reticulum stress during liver cold ischemia-reperfusion (I/R) in rats.Methods Twenty-four SPF healthy adult male Sprague-Dawley rats,weighing 200-250 g,were divided into 3 groups (n=8 each) using a random number table:sham operation group (group S),liver cold I/R group (group I/R) and hydrogen-saturated lactated Ringer's solution group (group HL).After occlusion of the liver blood flow,livers were perfused through the portal vein with 4 ℃ hydrogen-saturated lactated Ringer's solution 6-8 ml/min for 30 min.The liver blood flow was restored after the end of perfusion.At 6 h of reperfusion in I/R and HL groups or at 6 h after peritoneum closure in group S,blood samples from the inferior vena cava were collected for determination of serum alanine transaminase (ALT) and aspartate transaminase (AST) concentrations.After blood sampling,liver tissues were obtained for examination of pathological changes and for determination of cell apoptosis (using TUNEL),malondialdehyde (MDA) content (by thiobarbituric acid method),superoxide dismutase (SOD) activity (using xanthine oxidase method),expression of endoplasmic reticulum protein 46 (ERP46),immunoglobulin heavy chain binding protein (BiP) and caspase-12 (by immunohistochemistry),and expression of ERP46,BiP and caspase-12 mRNA (using quantitative real-time polymerase chain reaction).The pathological changes were scored.Apoptosis rate was calculated.Results Compared with group S,the serum ALT and AST concentrations,pathological scores,apoptosis rate and MDA content were significantly increased,the SOD activity was decreased,and the expression of ERP46,BiP and caspase-12 protein and mRNA was up-regulated in I/R and HL groups (P＜0.05).Compared with group I/R,the serum ALT and AST concentrations,pathological scores,apoptosis rate and MDA content were significantly decreased,the SOD activity was increased,and the expression of ERP46,BiP and caspase-12 protein and mRNA was down-regulated in group HL (P＜0.05).Conclusion The mechanism by which hydrogen reduces cell apoptosis may be related to inhibition of endoplasmic reticulum stress during liver cold I/R in rats.

Objective: To study the comprehensive utilization of Herba Ephedrae resources during the extraction process of ephedrin, that is the extracting of porphyrin compound.Methods: The process conditions for preparing sodium copper porphyrin were optimized by the two preparation processes and twice orthogonal tests. Results: Herba Ephedrae was powdered, steeped and boiled in alcohol, saponified, then extracted with xylene. The ephedrin was extracted from the upper layer of xylene extraction solution and sodium copper porphyrin was obtained from the lower layer by copper substituton, acidulation and alkalization. Conclusion: The optimum preparation process for producing sodium copper porphrin of Herba Ephedrae which is superior to porphyrin in the stability and colour is ascertained.

Objective Identify CT signs of breast cancer and evaluate the value of the shaded-surface display technique in spiral CT diagnosis of breast cancer.Material:33 cases of breast cancer were analysed.Methods All of patients underwent spiral CT contrast enhanced scans in SSD technique.Results The CT appearances of breast cancer were round or irregular mass,spiculated border,duct retraction,involved coopers lignment,microcalcification,deformed adipose space and axillary lymph nodes contained metastases.Conclusion The SSD technique has proved to be of great value in spiral CT diagnoses and differential diagnoses of breast cancer.