To address the current issue of low performance in predicting the binding affinity between antigenic peptides and specific MHC class II molecules, which fails to meet clinical requirements, we proposed T5MHCII, a deep learning-based prediction model for the affinity of MHC II class molecules to peptides. The model employed the knowledge previously acquired from the protein language model ProtT5 to extract the amino acid sequences via a transfer learning approach, thereby generating high-quality characterizations. This knowledge was then integrated with the robust learning abilities of deep learning to develop a novel model with enhanced predictive capabilities. The results of the five-fold cross-validation demonstrated that the model exhibited superior performance compared to NetMHCIIpan-3.2, PUFFIN, DeepMHCII, and RPEMH, with an AUC of 0.893±0.003 and a PCC of 0.780±0.006. The leave-one-out cross-validation (LOOCV) further demonstrated that the model exhibited enhanced generalization capabilities. This study proposes a novel approach to enhance the precision of peptide-MHCII prediction in the context of limited data affinity through the application of deep learning techniques.

To enhance the anti-tumor activity of tumor vaccine targeting PD-L1 based on the nitrated T-epitope(PD-L1-NitraTh),this research compared several adjuvants with different mechanisms to screen out the adjuvant most suitable for PD-L1-NitraTh.The results showed that Poly(I:C),CPG1018,swollen knotted polysaccharide SGP2 and GM-CSF could enhance the immunogenicity of PD-L1-NitraTh when used as adjuvants,with the Poly(I:C)group inducing the highest antibody titer.The results of qPCR for T cell differentiation-related cytokines showed that Poly(I:C)reduced the expression of GATA3 and FoxP3,indicating a strong effect on CD4+T cell differentiation.Besides,compared with other adjuvants,Poly(I:C)could assist PD-L1-NitraTh to increase the infiltration of T cells as well as CD11b+cells within tumor,suggesting that Poly(I:C)may be the suitable adjuvant for tumor vaccines based on the nitrated T epitopes.

Incretin promotes insulin secretion through a glucose-dependent mechanism, involving glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). Therefore, their correspondingly specific receptors GLP-1R and GIPR are suitable targets for the treatment of type 2 diabetes. Based on the oral hypoglycemic peptide OHP2 designed by our team, we further designed a new oral hypoglycemic peptide, ODA to reduce glucose. Compared with OHP2, ODA exhibited better lipophilicity as well as the enhanced endocytosis and transcytosis in Caco-2 cells. In addition, ODA remained the ability to activate GLP-1R and enhanced the binding ability to GIPR. The hypoglycemic efficacy of the low-dose ODA (0.53 mg/kg) is comparable to that of OHP2 (1.06 mg/kg). These results indicated that ODA could be a new oral drug with potential for the treatment of type 2 diabetes.

Several programmed cell death protein 1 (PD-1) or its ligand (PD-L1) immune checkpoint blocking antibodies are available for clinical treatment, but only some patients show clinical response, so an alternative strategy for tumor immunotherapy is needed.A therapeutic tumor vaccine targeting PD-L1 is a meaningful attempt.In this study, we designed an epitope peptide vaccine targeting PD-L1, and then screened the immunogenic PD-L1 epitope peptide based on the humanized immune system (HIS) mouse model and further investigated its anti-tumor activity.The results show that the designed and screened PD-L1-B1 epitope peptide vaccine not only successfully induced PD-L1-specific humoral and cellular immunity, but also exhibit anti-tumor activity.In addition, immunotherapy increased T-lymphocyte infiltration of tumors and reshaped the tumor immunosuppressive microenvironment.In conclusion, PD-L1-B1 epitope peptide vaccine exhibits potent anti-tumor activity and may be an effective alternative immunotherapeutic strategy for patients insensitive to PD-1/PD-L1 blockade.

OBJECTIVE To help to realize high-quality development of clinical pharmacy education in China by exploring new reform paths of high-level talents training in clinical pharmacy. METHODS The concept definition and key links of high-level talents training in clinical pharmacy were consulted by expert consultation， and the literature analysis and empirical methods were used to prepare a questionnaire to conduct online research on clinical pharmacy professionals in universities and hospitals. RESULTS A total of 637 effective electronic questionnaires were received. Totally 95.13% of the respondents believed that the cultivation of high-level talents in clinical pharmacy was very or relatively important； 51.96% expressed different degrees of dissatisfaction with the current situation of training； 88.85% regarded “rational clinical use of drugs” and 88.70% regarded “clinical research of drugs” as one of the main training objectives and service orientation； precision pharmacy， evidence-based pharmacy， medication therapy management， therapeutic drug monitoring and evaluation， clinical discovery and evaluation of new drugs were considered as important core specialty knowledge and competences， which were different from those high-level talents in clinical medicine；62.01% agreed that “academic degree+professional degree” dual degree training was the main degree type for high-level talents training in clinical pharmacy； 79.28% thought it was very necessary or relatively necessary to adopt the “long schooling” education mode； 98.58% thought that the core courses of clinical pharmacy such as clinical pharmacotherapy were very important or relatively important；59.81% believed that college or department of clinical pharmacy was the most important educational management organization that played the most important role； 87.13% agreed with the dual tutor structure of “college teachers+ pharmacists” and “pharmacists+physicians”. CONCLUSIONS Starting with the target orientation， core knowledge and competence， academic degree system， curriculum system and faculties， it is necessary to speed up the exploration of new reform paths of talent training and build a high-level talent training system of clinical pharmacy with Chinese characteristics and world level.

Objective:To investigate the significance of MLH1 protein expression and MLH1 gene methylation rate between metastatic solid pseudopapillary tumor of pancreas (SPT) and non-metastatic SPT, and to explore the correlation between MLH1 gene methylation and SPT metastasis.Methods:Twelve metastatic SPT patients admitted to Peking University People's Hospital, Rizhao Central Hospital and Chaoyang Central Hospital of Liaoning Province from January 2009 to May 2022 were studied retrospectively, including 3 males and 9 females, with a median age of 47 years old, ranging from 21 to 73 years old. Thirty non-metastatic SPT patients with clear diagnosis, clear medical history and complete follow-up data from pathological database of Peking University People's Hospital from January 2009 to May 2017 were selected as the control group, including 12 males and 18 females, with a median age of 42 years old, ranging from 34 to 69 years old. Clinical data such as gender, age and pathological data were collected. Immunohistochemical expression of MLH1 protein and methylation of MLH1 gene were detected by pathological paraffins.Results:There was no significant difference in general data between the two groups (all P>0.05). Among the 12 metastatic SPT patients, 4 cases metastasized to liver, 2 to spleen, 2 to lung, 2 to lymph nodes, 1 to mediastinum, and 1 to sacrum. Compared with the non-metastatic tissue, the MLH1 protein deletion in metastatic pancreatic lesions (metastatic SPT-P) and metastatic lesions (metastatic SPT-M) were increased [both 33.3%(4/12)], and the difference was statistically significant (both Chi square=5.00, both P=0.041). Compared with 0 (0/30) MLH1 gene methylation rate in non-metastatic SPT tissues, the methylation rate of MLH1 gene in metastatic SPT-M and metastatic SPT-P tissues [both 30% (3/10)] were higher, with statistical significance (both Chi square=0.96, both P=0.032). Conclusion:Compared with non-metastatic SPT, the loss rate of MLH1 protein expression and MLH1 gene methylation are increased in metastatic SPT. MLH1 methylation may occur before metastasis, which can be used as a predictor of SPT metastasis.

China Pharmaceutical University proposed and established the first second-level discipline of pharmaceutical pedagogy in China under the first-level discipline of pharmacy in 2021.Through exploring the value of pharmaceutical pedagogy and clarifying its connotation and development path, the construction of the discipline will be firmly pushed forward with a good start, laying a solid foundation for the connotative and high-quality development of pharmaceutical education in China.Using comparison, literature review and historical survey, iconic discipline factors in similar disciplines of pharmaceutical pedagogy, like medical pedagogy, nursing pedagogy, health education and social & administrative pharmacy were investigated.Our researches showed that pharmaceutical pedagogy in its narrow sense refers to the discipline of studying the phenomena and problems of pharmaceutical education with the cultivation of pharmaceutical talents as the core, and revealing the laws and characteristics of pharmaceutical education.The construction of pharmaceutical pedagogy should be further promoted with more academic achievements, stronger academic teams, organizations and journals with better and higher platforms of academic research.It was suggested that pharmaceutical pedagogy should be guided by Marxist philosophy in improving its academic system, academic institutions, academic teams and ability in participating in academic governance independently and openly.Pharmaceutical pedagogy is expected to accelerate the construction of theoretical system and discourse system of pharmaceutical education with Chinese characteristics, aiming to provide stronger intellectual support and knowledge contribution for pharmaceutical education in China and for China.

Based on the current laws and regulations framework of China， combined with practical cases， this paper systematically and comprehensively analyzes the supervision attributes， clinical trial supervision model and existing problems of tumor neoantigen vaccine， aiming to provide reference for the construction of the supervision system of clinical trial of tumor neoantigen vaccine in China. The results showed that， at present， the clinical trials of tumor neoantigen vaccine in China adopt a dual-track supervision model： clinical trials initiated by pharmaceutical enterprises and clinical trials initiated by researchers. This supervision model lags behind the development speed of the industry， mainly in the following aspects： challenges brought by dual- track supervision； the clinical trial data initiated by researchers are not effectively connected with new drug research applications； the guiding principles of clinical trial supervision need to be improved. Relevant medical institutions， regulatory authorities and cooperative enterprises can help the development of the regulatory system for clinical trials of tumor neoantigen vaccine in China from the above aspects.

As numerous connections between oncogenic signalling pathways and metabolic activities emerge, the importance of metabolic reprogramming in cancer is being increasingly recognized. During tumorigenesis, breast cancer cells undergo metabolic reprogramming, which generally includes enhanced glycolysis, tricarboxylic acid cycle activity, glutaminolysis and fatty acid biosynthesis. The extension and functional importance of these metabolic alterations may diverge according to breast cancer subtypes.Besides, aberrant metabolism of breast cancer cells remodels tumor microenvironment, promoting cancer vascularization and inhibiting anti-tumor immunity, and thus accelerates tumor progression.This review addresses current knowledge on the metabolic reprogramming and breast cancer microenvironment, which provides some reference for the development of metabolic target drugs for each breast cancer subtype.

Early postoperative hemorrhage (EPOH) is a common complication of pancreaticoduodenectomy (PD) and a main cause of death. The cause of EPOH is related to inappropriate vascular treatment during the operation, which may be recognized as a technical failure and avoided theoretically. PD is characterized by varieties of tissues that need to be separated and resected, large wound surface, many operations such as vascular separation, dissection, resection and reconstruction, and complex anastomoses. Therefore, the causes of EPOH are complex and varied. The most effective measure to prevent EPOH is to handle the vessels carefully and properly during the operation. In this paper, we systematically summarized the blood vessels involved in PD procedure, and the treatment strategies of these potential bleeding sites, and the clinical thinking and treatment principles of EPOH, so as to improve the quality of vascular treatment in PD procedure and to prevent EPOH.