Objective To identify the influencing factors for rural doctors′ training effect,and suggest on the improvement of such training.Methods On the basis of rural doctors′ survey,the theory of pre-intervention was used to probe into the influencing factors for such training in five dimensions of attention notice,mega-cognitive strategies,advance organizer,goal orientation,and preparatory information.Results 73.2% of the groups were found with satisfying effect.In the single factor analysis,comparison of training effect involving such factors as age,gender,length of work life and pre-intervention revealed statistical significance(P<0.05).As shown in the logistic regression analysis,High motivation in meta-cognitive strategies,Clear goals in goal orientation,Tiered and categorized training in advance organizers,and Practical learning in preparatory information,as well as variants like age would influence rural doctors′ training effect significantly.Conclusions The key to better training effect lies in better motivation of the trainee,setting correct training goals,emphasis on the practicability of training contents and,the pertinence of the training objects.

Immunotherapies targeting cancer neoantigens are safe, effective, and precise. Neoantigens can be identified mainly by genomic techniques such as next-generation sequencing and high-throughput single-cell sequencing; proteomic techniques such as mass spectrometry; and bioinformatics tools based on high-throughput sequencing data, mass spectrometry data, and biological databases. Neoantigen-related therapies are widely used in clinical practice and include neoantigen vaccines, neoantigen-specific CD8+ and CD4+ T cells, and neoantigen-pulsed dendritic cells. In addition, neoantigens can be used as biomarkers to assess immunotherapy response, resistance, and prognosis. Therapies based on neoantigens are an important and promising branch of cancer immunotherapy. Unremitting efforts are needed to unravel the comprehensive role of neoantigens in anti-tumor immunity and to extend their clinical application. This review aimed to summarize the progress in neoantigen research and to discuss its opportunities and challenges in precision cancer immunotherapy.

At present, the cultivation of exploratory thinking and the ability to use medical public big data is easy to be ignored, which leads to the obvious lack of the ability of graduate students in oncology to use public big data to discover and confirm new clinical phenomena and new laws in scientific research. This study introduces the access and download tools of common medical big databases such as TCGA, introduces the learning method of repeated classic analysis cases, and proposes research methods to verify clinical hypothesis using public big data. It is expected to provide useful enlightenment and reference for improving the research ability of graduate students in oncology specialty to find clinical problems and summarize scientific laws.

Utilizing of the WeChat Mini Programs (WMPs) in optimizing the paradigm of Continuing Medical Education (CME) is a promising avenue to improve training mode for physician. Here, we introduce the development status of WMP, and classify them into professional societies, hospital departments, academic institutions, pharmaceutical technology companies and individuals according to the operation subjects. This paper also analyzes the advantages and disadvantages of WMPs, and puts forward the establishment of authoritative and highly recognized mini programs that can be awarded CME credits. Through the "Internet plus medical care" strategy, we should integrate network resources to enhance the overall level of continuing medical education, so as to provide a good platform for related medical workers.

AIM:To investigate the molecular mechanism underlying ferroptosis induced by celastrol(Cel)in huamn pancreatic cancer cell line PANC-1.METHODS:The viability of PANC-1 cells was analyzed by MTT assay,and the effects of Cel on cell proliferation were analyzed using EdU and colony formation assays.Flow cytometry and fluores-cence microscopy were used to assess and observe changes in lipid reactive oxygen species(ROS)levels,respectively,while the levels of malondialdehyde(MDA),glutathione(GSH)and Fe2+were measured using specific kits.The protein expression of glutathione peroxidase 4(GPX4)was evaluated by Western blot,and GPX4 ubiquitination was measured by immunoprecipitation.RESULTS:It was found that the viability,proliferation and colony formation in PANC-1 cells de-creased gradually as the concentration of Cel increased.Addition of Cel alone to the cells reduced both cell rounding and viability,while treatment with ferrostatin-1(Fer-1)alone or in combination with Cel had no effect on either cell morpholo-gy or viability.Fluorescence staining of lipid ROS with BODIPYTM 581/591 C11 followed by flow cytometry analysis showed significantly increased levels of green fluorescence indicative of oxidized lipid ROS,which were further increased after treatment of the cells with Cel.Treatment of the cells with both Cel and Fer-1 reduced the green fluorescence and lip-id ROS levels.Treatment with Cel also increased the levels of MDA and Fe2+,relative to the controls,which reducing the levels of GSH,while addition of both Cel and Fer-1 to the cells restored the levels of MDA,Fe2+,and GSH to those of the control group.CONCLUSION:Treatment with Cel reduces the proliferation of pancreatic cancer cells by inducing fer-roptosis through promoting the ubiquitination and degradation of GPX4.

The tumor immune microenvironment (TIME) is broadly composed of various immune cells, and its heterogeneity is characterized by both immune cells and stromal cells. During the course of tumor formation and progression and anti-tumor treatment, the composition of the TIME becomes heterogeneous. Such immunological heterogeneity is not only present between populations but also exists on temporal and spatial scales. Owing to the existence of TIME, clinical outcomes can differ when a similar treatment strategy is provided to patients. Therefore, a comprehensive assessment of TIME heterogeneity is essential for developing precise and effective therapies. Facilitated by advanced technologies, it is possible to understand the complexity and diversity of the TIME and its influence on therapy responses. In this review, we discuss the potential reasons for TIME heterogeneity and the current approaches used to explore it. We also summarize clinical intervention strategies based on associated mechanisms or targets to control immunological heterogeneity.

Objective To make a comprehensive analysis of the satisfaction and preferences of rural doctors'incentive measures,and to identify the incentives that need to be optimized.Methods The method of multi-stage stratified random sampling was used to investigate the rural doctors in Shandong province in 2015.This survey called into play the sample mean and standard deviation for descriptive analysis.And according to Maslow's Hierarchy of Needs theory, the scoring and ranking of different levels and specific incentive measures were calculated.The important quadrant model which combined with motivational preference and satisfaction of incentive measures was used to analysis them.Results The top preference for rural doctors was survival demand,scoring 4 284.Among the specific incentives,the top wss lower medical practice risk,scoring 945.75.In combination with satisfaction analysis, 7 incentive measures, including improving welfare and policy assurance, were now in the state of low satisfaction and high preference. Conclusions In terms of demand level,the survival incentive factor tops the needs of rural doctors.In the specific incentive measures, the seven incentives, such as lower practice risk, deserve more attention. Relevant departments should actively improve and implement these seven measures in order to maximize their motivation for rural doctors.

Objective To explore the sensitizing effect of manganese for radiotherapy against tumors and its possible mechanisms.Methods A total of 300 male C57BL/6 mice(6～8 weeks old,weighing 20～23 g)with subcutaneous tumor were randomly divided into 4 groups:control group,radiotherapy group,manganese treatment group,and combined radiotherapy and manganese treatment group.Nasal drip with 10 μg manganese adjuvant was applied to the mice from the latter 2 groups on day 9 of tumor bearing,then single dose of 20 Gy radiation was locally administered on day 10.Tumor growth and mouse survival were monitored regularly.The sensitizing effect of manganese on radiotherapy was determined by monitoring and comparing the tumor growth among different unilateral mouse models.Bilateral tumor-bearing model was used to examine the effect of manganese on abscopal effects induced by radiotherapy.Flow cytometry was used to illustrate the changes in tumor-infiltrating immune cells in unilateral tumor bearing model.Immunohistochemical staining was employed to evaluate the spleen function in unilateral tumor bearing mice.Results Based on repeated validation of 3 different unilateral tumor-bearing models,radiotherapy combined with manganese therapy significantly inhibited tumor growth and prolonged survival of mice(P＜0.05).The results of bilateral tumor-bearing model showed that manganese therapy enhanced abscopal effects of radiotherapy,and significant regression was observed in both side of tumor under radiotherapy or not(P＜0.05).Flow cytometry revealed that manganese further increased radiation-induced CD8+T infiltration(P＜0.05)and decreased radiation-induced infiltration of Treg cells and myeloid-derived suppressor cells(MDSCs)(P＜0.05).Furthermore,manganese increased lymphocyte reserve pool of the spleen and improved its function.Conclusion Manganese adjuvant could act as a sensitizing agent for radiotherapy,by improving the function of spleen and reprogramming the tumor microenvironment synergistically.

Objective To establish an animal model and evaluation system for lymph node metastasis of breast cancer.Methods A total of 60 female BALB/c mice(6～8 weeks old)were subjected,and then 6 models of lymph node metastasis(n=10)were constructed through injection at different parts in the mice with cell suspension of 4T1 breast cancer cells.Transgenic mice(n=5)of mouse mammary tumor virus-polyoma middle T antigen(MMTV-PyMT)were employed and served as model of spontaneous tumor metastasis.Then the advantages and disadvantages of different lymph node metastasis models were comprehensively evaluated from multiple aspects,such as operability,histomorphology and pathological detection,tumor growth rate and mouse survival.Results Among the 7 metastasis models,4 models of lymph node metastasis were successfully established.Among them,the PyMT mouse spontaneous tumorigenesis model showed the best clinical reproduction,with a tumorigenesis rate of up to 100％,but had a disadvantage of poor experimental standardization.The hind paw-popliteal lymph node model had the fastest lymph node metastasis,easy operation and high repeatability,and a tumorigenesis rate of 100％,indicating its suitable for lymph node metastasis related research.The thigh subcutaneous-inguinal lymph node model also successfully simulated lymph node metastasis,with simple operation and high repeatability,a tumorigenesis rate of up to 100％,but its metastasis time was slightly longer than the hind paw-popliteal lymph node model.The inguinal lymph node-contralateral lymph node model was also a successful lymph node metastasis model,but with difficult operation,only 50％tumor-bearing rate,and poor repeatability.Lymph node metastasis model was not successfully established in the other 3 tumor-bearing models(under the tongue-internal jugular scapular tongue muscle lymph node model,bone marrow-inguinal lymph node model and right upper back skin-axillary lymph node model)in a short time,with no tumor cells observed in the pathological sections.Conclusion Through the comprehensive comparison of multiple models,mouse hind paw-popliteal lymph node model is the most suitable for conducting related research.