1.Changes of Th1/Th2 balance in multiple organ dysfunction syndrome
Xian SHEN ; Chen CHAI ; Fu-Lin LIN ; Jun-Yi SHI ; Guo-En FANG ;
Academic Journal of Second Military Medical University 1999;0(12):-
Objective:To explore the pathogenesis of multiple organ dysfunction syndrome(MODS)with respect to the bal- ance of Th1/Th2.Methods:Eighteen healthy male minipigs,weighing 22-30 kg,were randomly divided into two groups: MODS group and control group.Double-hit method including hemorrhagic shock and endotoxiemia was used to establish the porcine MODS model.The peripheral vein blood samples were collected at different time-points(before bloodletting,before en- dotoxin injection,1 h,24 h,48 h and 72 h after endotoxin injection)in the two groups.The spleen samples were collected after death of the animals.Plasma levels of IFN-?and IL-4 were detected by enzyme-linked immunosorbent assay(ELISA).Real- time PCR was used to detect the expression of IFN-?,IL-4,T-bet and GATA-3 mRNA(The latter 2 were the key transcription factors associated with Th1/Th2 response)in the spleen samples.Results:The plasma levels of IFN-?and IL-4 quickly reached the peak values 1 h after the endotoxin injection,then the level of IFN-?decreased quickly.The ratio of IFN-?/IL-4 was signifi- cantly lower than the baseline value 72 h after endotoxin injection(P=0.000).The ratio of IFN-?/IL-4 mRNA in MODS group was obviously lower than that in the control group(P=0.020);the ratio of T-bet/GATA-3 was also lower in MODS group (P=0.038).Conclusion:The shift from Th1 to Th2 occurs in the progress of MODS.
3.Expression and significance of major histocompatibility complex classⅡgene in multiple organ dysfunction syndrome
Chen CHAI ; Guo-En FANG ; Xian SHEN ; Fu-Lin LIN ; Ming-Ming NIE ; Tian-Hang LUO ; Yang YUAN ; Jian-wei BI
Chinese Journal of Trauma 2003;0(11):-
Objective To investigate the expression and significance of major histocompatibility complex classⅡgene in multiple organ dysfunction syndrome.Methods Two-hit porcine model of MODS was duplicated in 18 swine that were randomly assigned into experimental group(Group M,n=9) and control group(Group C,n=9).The Group M was given compound factors including hemorrhagic shock,reperfusion injury and endotoxemia,and the Group C only underwent anesthesia and arterious/ve- nous eannula.After seven days,the animals were killed to remove splenic tissues fro extracting total RNA by Trizol method.The primer of SLA-DQA(MHC classⅡgene of swine)was designed to construct cD- NA by reverse transcription and the quantity of SLA-DQA mRNA detected with real time fluorescent quan- titative polymerase chain reaction(real time FQ-PCR).The standard curve was described by UVP com- puter image analysis system.Results The mortality of Group M was 78%(7/9),and the incidence rate of MODS was 89%(8/9).The expressing quantity of Group M was(1.376?1.006)?10~3,signifi- cantly lower than(5.330?3.053)?10~3 of Group C(P<0.01).Conclusion Duplication of por- cine MODS model is satisfactory.Down-regulation of MHC classⅡgene may be due to control of classⅡtransactivator(CⅡTA)and release of multiple eytokine,such as TNF-?and IL-10.
4.DJ-1 expression in laryngeal squamous cell carcinoma and its relationship with tumor recurrence and metastasis
Xiao-Lin ZHU ; Wei-Ping WEN ; Wen-Bin LEI ; Li-Ping CHAI ; Wei-Jian HOU ; Yi-Hui WEN ; Xian-Ren WANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2010;45(6):497-501
Objective To detect the expression of DJ-1 in laryngeal squamous cell carcinoma (LSCC) and to study the relationship between DJ-1 expression and clinical indexes of LSCC. Methods The expressions of DJ-1 protein in 71 LSCC samples and 9 cases control samples from laryngeal mucosa tissues of non-LSCC patients were detected using streptavidin peroxidase immunohistochemistry stainin and the relationships between DJ-1 protein expression and clinicopathologic characteristics were analyzed. Results ( 1 ) The positive expression rate of DJ-1 protein in LSCC was 85.9% (61/71), which was significantly higher than the rate (55.5% ,5/9) in control laryngeal mucosa tissues (P<0.05). (2) DJ-1 expression was related to tumor recurrence (P <0. 05) ,but not to sex,age,primary cancer position,T stage, clinical stage, lymph node metastasis and tumor differentiation. Tumor recurrence rate (53. 3% ) in the patients with higher expression of DJ-1 protein was higher than the rate ( 26. 8% ) in the patients with lower expression of DJ-1 protein ( X2 = 5. 164, P < 0. 05 ). (3 ) With Kaplan-Meier curves and Cox regression analysis,the cumulative 5-year survival rates were correlated with DJ-1 expression levels in laryngeal cancer tissues or cervical lymph node metastasis (all P < 0. 05 ), but not to sex, age, primary cancer position, T stage, clinical stage and tumor differentiation. Conclusions The expression of DJ-1 protein in LSCC is higher than that in control laryngeal mucous tissues. Overexpression of DJ-1 is associated with poor overall survival in ISCC patients.
5.A rapid health technology assessment of camrelizumab in combina-tion with chemotherapy for the first-line treatment of locally ad-vanced/metastatic non-small cell lung cancer
Yanjun CUI ; Tian MA ; Yi LIU ; Ling JIAO ; Aijun CHAI ; Rongrong FAN ; Yanguo LIU ; Xing-Xian LUO ; Lin HUANG ; Xiaohong ZHANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(7):775-784
AIM:To evaluate the efficacy,safety,and economy of camrelizumab(CAM)combined with platinum-containing chemotherapy(CT)for the first-line treatment of locally advanced/meta-static non-small cell lung cancer(NSCLC).METH-ODS:Chinese and English databases such as Pubmed,the Cochrane Library,China Knowledge Network,Wanfang Data,and other related web-sites were systematically searched.After literature screening,quality assessment,and data extraction of the literature according to the inclusion and ex-clusion criteria,two researchers conducted a rapid health technology assessment(HTA).RESULTS:A total of 7 systematic evaluations/Meta-analyses and 17 economics evaluations were included.In terms of effectiveness,compared to docetaxel che-motherapy,CAM+CT significantly prolonged the overall survival(OS),progression-free survival(PFS),and improved the objective remission rate(ORR)of mutation-negative patients with locally ad-vanced/metastatic NSCLC.Compared with CT and pembrolizumab(PEM),CAM+CT significantly pro-longed the PFS,and improved the ORR of mutation-negative patients with locally advanced/metastatic NSCLC.Subgroup analysis showed that CAM+CT significantly prolonged PFS in patients with PD-L1 ≥1%and PD-L1 ≥ 50%compared with CT.Compared with CT,CAM+CT significantly prolonged the OS and PFS of mutation-negative patients with locally advanced/metastatic squamous NSCLC.Compared with sintilimab(SIN),CAM+CT significantly pro-longed the PFS of mutation-negative patients with locally advanced/metastatic squamous NSCLC.Sub-group analysis showed that CAM+CT significantly prolonged OS in patients with PD-L1<1%com-pared with CT.In terms of safety,CAM+CT was comparable in terms of the occurrence of all grades of adverse events,but the incidence of grade 3 or higher treatment-related adverse events was significantly increased compared with CT and PEM for mutation-negative locally advanced/meta-static NSCLC patients.CAM+CT was significantly in-creased the occurrence of all grades of adverse events compared with CT,but was comparable in terms of the occurrence of grade 3 or higher treat-ment-related adverse events.In terms of economy,CAM+CT has a cost-effectiveness advantage over CT for patients with mutation-negative advanced/metastatic squamous NSCLC.CAM+CT has a cost-effectiveness advantage over CT and PEM+CT;and CAM+CT does not have a cost-effectiveness ad-vantage over SIN+CT for patients with mutation-negative locally advanced/metastatic non-squa-mous NSCLC.CONCLUSION:CAM+CT has good ef-ficacy and cost-effectiveness for the first-line treat-ment of locally advanced/metastatic NSCLC,and the safety aspect is compared with CT,PEM or slightly worse.
6.Preparation,Characterization and in vitro Evaluation of PTMAc-PEG-PTMAc Hydrogel for Ocular Drug Carrier of Pirfenidone
Wei PENG ; Yang-fan YANG ; Xian-chai LIN ; Tao WANG ; Da-ping QUAN ; Kai-li WU ; Min-bin YU
Journal of Sun Yat-sen University(Medical Sciences) 2019;40(2):219-227
【Objective】To form a new PTMAc- PEG- PTMAc triblock(PPP)copolymerhydrogel and to evaluate its sustained released performance and antiproliferative effects as an ocular drug carrier of Pirfenidone(PFD)【Methods】One type triblockcopolymers PPP hydrogel was chosen. The morphology of the material was evaluated by scanning electron microscopy(SEM). The swelling properties of the PPP hydrogel was analyzed in PBS solution(37 ℃ ,pH 7.4). The in vitro drug release of the pirfenidone loaded hydrogels were evaluated with non-dialysis method and the curves of drug release were drawed. We evaluated the adhesion,survival of human Tenon′s capsule fibroblasts(HTF)around hydrogels. The cell cytotoxicity of hydrogels and antiproliferative effects were evaluated through CCK-8 assay.【Results】The hydrogel has stable gelation conditions. The swelling rate decreased by increasing hydrogel concentration.The SEM images indicated the fibrous and porous structure. We also observed that the encapsulated pirfenidone were sustained released from hydrogels with an initial burst release at early stage(within 4 d)and then the release rate were declined for all hydrogels during the following 14 d. The PPP hydrogel can inhibit cell adhesion. The cell viability in hydrogels at four time point(24,48,72 and 96 h)were 85.7% ,93.0% ,82.0% ,81.6%. The inhibition rate of drug loaded hydrogel with two drug concentration(1 mg/mL or 2 mg/mL)are 25.8%,21.8%,55.4%,25.6%;44.6%,35.9%,55.5%,31.4%. While that of drug solution are 28.9% ,29.7% ,7.8% ,7.7%. The suppressive effects of the PFD loaded hydrogels on HTF proliferation followed a dose-dependent fashion and time-dependent fashion.【Conclusions】Such biocompatible copolymers hydrogel can be effectively used as an drug sustain released system. It can induce significant inhibition of HTF proliferation. With equal amount of drug,the inhibition effect of drug loaded gel was longer than that of drug solution.