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.

Objective:To explore the effect and safety of local spraying tranexamic acid after thyroidectomy.Methods:Randomized double-blind placebo-controlled study method was used. Sixty-four patients underwent scheduled thyroidectomy from December 2022 to August 2023 in Baotou Cancer Hospital were selected. The patients were divided into tranexamic acid group and control group by random digits table method with 32 cases each. Before closing the wound during surgery, 16 ml of tranexamic acid injection with concentration of 25 mg/ml was used to wash the wound and 1 ml of tranexamic acid injection (tranexamic acid 100 mg) used to locally spray in tranexamic acid group; 16 ml of the sterile water for injection was used to wash the wound and 1 ml of sterile water for injection was used locally spray in control group, and then the drainage tube was clipped for 20 min. The neck drainage volume on the first to fourth day after surgery and complication were recorded; the C-reactive protein level before and after surgery was detected.Results:Two patients in each group withdrew from the study midway. The drainage volume on the first, second and third day and total drainage volume in tranexamic acid group were significantly lower than those in control group: (29.10 ± 8.04) ml vs. (38.50 ± 8.67) ml, (18.00 ± 7.33) ml vs. (27.20 ± 10.66) ml, (10.70 ± 5.75) ml vs. (14.60 ± 6.83) ml and (69.20 ± 24.48) ml vs. (96.70 ± 31.90) ml, and there was statistical difference ( P<0.01); there was no statistical difference in the drainage volume on the fourth day after surgery between two groups ( P>0.05). There was no statistical difference in C-reactive protein before and after surgery between two groups ( P>0.05). There was 1 case of fever (body temperature 37.5 ℃) in the control group, and there were no complications such as intermuscular thrombosis, venous thrombosis, incision infection and delayed wound healing in both groups. Conclusions:Local application of tranexamic acid after thyroidectomy can reduce postoperative drainage volume and does not increase the risk of thrombosis, infection and delayed healing.

N-acetyl-p-aminophenol （APAP） is an antipyretic analgesic commonly used in clinical practice， and APAP overdose can cause severe liver injury and even death. In recent years， the incidence rate of APAP-induced liver injury （AILI） tends to increase， and it has become the second most common cause of liver transplantation worldwide. Autophagy is a highly conserved catabolic process that removes unwanted cytosolic proteins and organelles through lysosomal degradation to achieve the metabolic needs of cells themselves and the renewal of organelles. A large number of studies have shown that autophagy plays a key role in the pathophysiology of AILI， involving the mechanisms such as APAP protein conjugates， oxidative stress， JNK activation， mitochondrial dysfunction， inflammatory response and apoptosis. This article elaborates on the biological mechanism of autophagy in AILI， in order to provide a theoretical basis for the treatment of AILI and the development of autophagy regulators.

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.