PD-1/PD-L1 signaling pathway as a T cell immune response co-stimulatory signaling pathway plays an important role in adaptive immunity. PD-1 is a major co-receptor expressing on T cells, binding with its ligands(PD-L1 and PD-L2), PD-1 can inhibit T cell activation and protect the body against the attacks from its own immune system. In addition to adjusting and maintaining autoimmune tolerance, in tumor cells PD-L1 expression is up-regulated, while in the virus-infected T cells PD-L1 expression is also upregulated. PD-1 / PD-L1 are involved in the tumor and infectious pathogen immune evasion, thus blocking the PD-1 / PD-L1 signaling pathway has become a hot research of cancer and chronic diseases. Currently, there are several anti-PD-1 or PD-L1 monoclonal antibodies approved by the FDA to enter clinical studies, which have shown significant anti-cancer effect.

Objective To study the intrinsic relationships between the binding energy of the antibody light and heavy chains and the conformational characteristics , physical and chemical properties , and to establish a corresponding mathemat-ical model and evaluate the thermal stability of the antibody molecules , which contribute to the antibody design , optimiza-tion and affinity maturation .Methods Based on bioinformatics and computational biology methods , the antibody′s structur-al information with the crystal diffraction data was analyzed .The conformational character of the variable domain of the antibody was studied using distance geometry and computer graphics technology .With the aid of the intermolecular hydrogen bond formation theory and the reaction free energy theory , the dynamic structure and energy characteristics be-tween the heavy and light chain variable regions of the antibody were studied .Furthermore , using nonlinear fitting and regression analysis, a mathematical model was set up .Results According to simulation and statistic analysis , there was a linear relationship between the binding energy and the number of the intermolecular hydrogen bonding , Van der Waals interaction of the heavy and light chains of the antibody .There was polynomial correlation between the binding energy and the physicochemical properties of the antibody .Using the frequency of amino acid position and the established model , the humanized anti-ricin antibody , which could not obtain the stable engineering cell line , was evaluated and optimized .The stable engineering cell line of the humanized anti-ricin antibody was obtained in the experiment .Conclusion The self structure of the antibody variable region ( conformation and physicochemical properties ) has much effect on its stability . The antibody stability can be improved by structural optimization .

OBJECTIVE To investigate the effect of amifostine(Amf)on the differentiation of human megakaryocyte cell line-Dami. METHODS Dami cells were treated with Amf 0.01-5.0 mmol · L-1 for 12 d. Dami cells were counted every day for the growth curve:only cells with a diameter>20μm. The platelet demarcation membrane system was observed by transmission electron microscopy. The expression of CD33,CD34,CD41a and DNA ploidy was detected by flow cytometry. RESULTS Amf 0.1-1.0 mmol · L-1 promoted the differentiation of Dami cells ,but inhibited their proliferation at a concentration>1.0 mmol · L-1. When these cells were treated with Amf 1.0 mmol · L-1 for 12 d,the platelet demarcation membrane system was observed,the percentage of cells with a diameter >20 μm was increased by 24.6%(P<0.01),the expression of CD41a was increased by 11.9%,while the expression of CD33 was decreased by 13.6%(P<0.05). Polyploidy cells(16N)were observed,and 4N,8N and 16N cells were increased to 31.56%,8.83% and 3.43%,respectively(P<0.05). CONCLUSION Amf 0.1-1.0 mmol · L-1 can promote the differentiation of Dami cells,but inhibit their proliferation at a high concentration(>1.0 mmol·L-1).

Objective To investigate the safety and efficacy of mechanical thrombectomy (MT) compared with In?tra-arterial Thrombolysis (IAT) treatment in patients with severe acute ischemic stroke (AIS) caused by large cerebral ar?tery occlusion. Method The patients with AIS caused by large cerebral artery occlusion and underwent MT or IAT from 2005 May to 2014 May was included. A retrospective analysis was conducted on the onset to emergency(OTE)time, emergency to acupuncture(ETA)time, acupuncture to recanalization (ATR) time, stroke severity as measured by the Na?tional Institutes of Health Stroke Scale (NIHSS) score, and site of arterial occlusion on magnetic resonance angiography (MRA). A comparison was made between MT and IAT patients in rates of recanalization, symptomatic intracranial bleed?ing (SIB), mortality, and functional outcome. Three-month favourable outcome was defined as a modified Rankin Scale (mRS) score≤2. Result One hundred and two AIS patients were treated with MT and 50 with IAT. There was no differ?ence between MT and IAT groups with regard to demographics, onset NIHSS score (13.37±6.95 vs. 12.70±6.11;P=0.572) and discharge NIHSS score (8.40 ± 6.69 vs. 7.53 ± 7.28, P= 0.522) and the change of NIHSS score (3.87 ± 7.14 vs. 4.26 ± 5.42, P=0.766). There were significantly differences between MT and IAT groups in the OTE time (Median 300 min vs. 120 min,Z=-5.704,P=0.000) , ATR time (Median 30 min vs. 65 min,Z=-5.011,P=0.001) ,recanalization (91.2%vs. 60.0%,P =0.01),the rate of AIB(21.7% vs. 36.0%,P =0.046),3-month mortality (16.6% vs. 26.0%,P =0.043). The above parameters were better in MT group than in the IAT group. There were no significant differences between MT and IAT groups in the rate of SIB (12% vs. 16%,P =0.055), the NIHSS change(Median 3 vs. 4,Z =-0.236,P =0.823) and mRS score on 90d ( 48.2%vs. 46.0%, P=0.823). MT patients had significantly higher percentages of stent use (22.5%vs. 8%,P=0.018) . The Recanalization for ICA(81.8%vs. 55.6%,P=0.048),BA(93.1%vs. 55.6%,P=0.032)and MCA( 97.5% vs. 60.0%,P =0.026)was higher in MT group than in IAT group .The SIB rate for ICA(13.8% vs. 33.3%,P =0.000),BA(13.8%vs. 33.3%,P=0.000)was lower in MT group than in IAT group . The mortality rate of was significant?ly lower in MT than in IAT group for MCA (2.5%vs. 20.0%,P=0.000) . the good outcome rate for BA was higher in MT group than in IAT group(41.3%vs. 22.2%,P﹤0.01). Conclusions Compared to IAT,MT can provide broader time win?dow,higher recanalization rate and better outcome in patients with severe acute ischemic stroke (AIS) caused by large ce?rebral artery occlusion.

Objective:To investigate the correlation between thyroid tumor volume ratio to lymph node metastasis in papillary thyroid carcinoma (PTC).Methods:The ratio of thyroid tumors volume to resected thyroid volume was measured by imaging methods before surgery, and the correlation between volume ratio and other clinicopathological features and lymph node metastasis in 134 patients with single focal PTC was analyzed.Results:The number of lymph node metastases was associated with age <45 years and invasion of the capsule ( r<0.300, P<0.05), and weakly correlated with gender, maximum tumor diameter, tumor volume and volume ratio. Among them, the correlation between patho-volume ratio was strongest ( r=0.379, P<0.001). Male genter was an independent risk factor for central cervical lymph node metastasis (χ 2=13.597 P<0.05). The co-predictions of sex and volume ratio was AUC=0.760, sensitivity=0.574 and specificity=0.818. Conclusion:Compared to the maximum diameter of tumors, the volume ratio in papillary thyroid carcinoma better predicts the metastasis of lymph nodes of papillary thyroid carcinoma in the central region.

Autoimmune hepatitis(AIH)is a type of chronic hepatitis caused by the attack of hepatocytes by the autoimmune system,and with the prolongation of disease course,it may gradually progress to liver cirrhosis and even hepatocellular carcinoma.Although great achievements have been made in the understanding and treatment of AIH,its etiology and pathogenesis still remain unclear.T cells play a crucial role in the development and progression of AIH,and by focusing on follicular helper T cells,this article elaborates on the research advances in follicular helper T cells in AIH,in order to provide new ideas and strategies for the clinical treatment of AIH.

Autoimmune hepatitis(AIH)is chronic hepatitis caused by the attack of live cells by the immune system,and at present,the pathogenesis of AIH remains unclear.Inflammasomes are important components of innate immunity and are involved in a variety of pathophysiological processes.Studies have shown that inflammatory response associated with nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)plays an important role in the pathogenesis of AIH,which mainly mediates the release of proinflammatory factors and pyroptosis,thereby participating in the pathophysiological process of AIH.Therefore,the development and progression of AIH can be delayed by inhibiting the activation of NLRP3 inflammasomes,which provides new ideas for the prevention and treatment of AIH.

Autoimmune hepatitis （AIH） is a type of chronic hepatitis caused by the autoimmune system attacking hepatocytes， and its chronic progression may lead to liver cirrhosis and even hepatocellular carcinoma. Currently， pharmacotherapy and liver transplantation are the main treatment methods for AIH， but both methods have their own limitations， which limits the clinical benefits of patients. Therefore， it is a critical issue to search for new therapeutic agents and methods. Recent studies have shown that mesenchymal stem cells （MSC） and their exosomes can improve the symptoms of patients with AIH by suppressing inflammatory response， enhancing the regeneration of hepatocytes， and regulating the immune system and thus have wide application prospects in the treatment of AIH. By summarizing related articles， this article reviews the possible mechanisms and application of MSC and their exosomes in the treatment of AIH， in order to provide new ideas for the clinical treatment of AIH.

The incidence rate of drug-induced liver injury （DILI） is increasing year by year with unknown mechanisms， and the treatment methods for DILI mainly include drugs， liver support systems， and liver transplantation， all of which have certain limitations. Therefore， the search for safer and more effective treatment methods has become a research hotspot at present. Studies have shown that mesenchymal stem cells and their exosomes can alleviate liver injury by reducing liver inflammation， promoting hepatocyte proliferation and regeneration， inhibiting the apoptosis of hepatocytes， improving oxidative stress， and regulating immunity. This article briefly reviews the role of mesenchymal stem cells and their exosomes in the treatment of DILI， so as to provide a reference for further research.

Clinical advances in the treatment of intracranial hemorrhage (ICH) are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury. Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases. Our results indicated a significant increase in the level of acrolein after ICH in mouse brain. In primary neurons, acrolein induced an increase in mitochondrial fragmentation, loss of mitochondrial membrane potential, generation of reactive oxidative species, and release of mitochondrial cytochrome c. Mechanistically, acrolein facilitated the translocation of dynamin-related protein1 (Drp1) from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission. Further studies found that treatment with hydralazine (an acrolein scavenger) significantly reversed Drp1 translocation and the morphological damage of mitochondria after ICH. In parallel, the neural apoptosis, brain edema, and neurological functional deficits induced by ICH were also remarkably alleviated. In conclusion, our results identify acrolein as an important contributor to the secondary brain injury following ICH. Meanwhile, we uncovered a novel mechanism by which Drp1-mediated mitochondrial oxidative damage is involved in acrolein-induced brain injury.