In recent years, immunotherapy with immune checkpoint inhibitor (ICI) as the representative drug has become an important treatment method for advanced malignant tumors. Preclinical studies have found that disorders of the gut microbiota can reduce the clinical benefit of patients treated with ICI. The latest data indicate that antibiotics may further affect the occurrence and development of tumors and the efficacy of immunotherapy by changing the abundance and composition of intestinal microbiota. To sum up the role of anti-biotics in the immunotherapy of advanced malignant tumor may provide a new idea for the optimization of treatment strategies for patients with advanced cancer.

Objective To explore the effects of visfatin in glucose metabolism by testing the expression of visfatin in liver of rats in different glucose metabolic statuses .Methods SD rats were randomly divided into five groups :normal control group (NC group) ,diet induce obesity group (DIO group) ,diabetes mellitus group (DM group) ,diabetes controlled by insulin group (INS group)and diabetes controlled by metformin group (MET group) .Tested the data of blood glucose (FPG) ,triglyceride(TG) ,total cholesterol(TC) ,free fat acid(FFA) ,fasting insulin(Fins) .The liver of rats was used to test visfatin ,glucose‐6‐phosphatase(G‐6‐pase) mRNA by RT‐PCR and visfatin ,AMP‐activated protein kinase‐α (AMPKα) ,phosphor‐AMP‐activated protein kinase‐α (p‐AMPKα) protein by Western blot .Results FBG of group DM increased than group NC and DIO (P< 0 .01) ;FBG of group INS and MET decresed than group DM (P < 0 .01) ;HOMA‐IR of group DIO and DM increased than group NC (P < 0 .01) ;HOMA‐IR of group DM increased than group DIO (P< 0 .01) .ISI of group DIO and DM decresed than group NC (P< 0 .01) ;ISI of group DM de‐creased than group DIO(P< 0 .01) .TG of group DIO increased than group NC (P< 0 .01) .TG of group INS and MET decreased than group DM (P< 0 .05) .The level of TG and TC of group DM ,INS and MET increased than group NC (P< 0 .05) .The level of serum FFA of group DM ,INS and MET were significantly higher than group NC (P < 0 .05) ;FFA of group DM increased than group DIO(P< 0 .05) .The expression of visfatin mRNA of group DM increased than group NC and DIO (P< 0 .05) ;visfatin mRNA of group INS and MET decreased than group DM (P< 0 .01) .Group DM ,INS and MET had a significantly higher level of G‐6‐Pase mRNA of than group DIO( P < 0 .05) ;Group MET had a significantly lower level of G‐6‐Pase mRNA of than group DM (P <0 .05) .The expression of visfatin protein of group DM ,INS and MET increased than group NC ( P < 0 .05) .The expression of AMPKα protein of group DM ,INS and MET decresed than group NC(P< 0 .05) ;AMPKα of group DM decresed than group DIO (P<0 .05) .The expression of p‐AMPKα protein of group DIO ,DM ,INS and MET decresed than group NC (P< 0 .01) .Conclusion The ex‐pression of visfatin in liver of SD rats might have something to do with insulin resistance and diabetes .We could′t consider that visfatin can affect the pathway of metformin activated AMPK to decrease blood glucose .

N 6-methyladenosine (m 6A) methylation modification is defined as the methylation at the N 6 position of adenosine. This dynamic process is regulated by writer, eraser and reader. Accumulating evidence indicates that m 6A methylation modification is involved in the initiation and development of various digestive system neoplasms including proliferation, invasion, metastasis and chemoresistance. A further understanding about the role of m 6A methylation modification in digestive system neoplasms will benefit the development of a novel precise diagnostic and therapeutic strategy and finally improve the overall prognosis of patients.

In the treatment of non-small cell lung cancer (NSCLC), immunotherapies represented by immune checkpoint inhibitors are developing rapidly. It is the premise of precise treatment to clarify the influencing factors of NSCLC immunotherapy. In the course of immunotherapy for advanced NSCLC, elderly patients can obtain specific effect from immunotherapy; male patients benefit more from monotherapy; when steroid hormones are used for related symptoms caused by tumors, they are poor prognostic factors for patients. The occurrence of immune-related adverse events is a favorable prognostic factor while driving gene mutations and the use of antibiotics will reduce the efficacy of immunotherapy.

Objective:To evaluate the effects of proton pump inhibitors (PPIs) on the clinical outcomes for advanced solid tumor patients treated with immune checkpoint inhibitors (ICIs).Methods:A total of 204 patients with advanced solid tumors who received ICIs in the Affiliated Hospital of Yangzhou University from November 2016 to December 2020 were retrospectively analyzed. The patients were divided into PPIs group ( n=73) and Non-PPIs group ( n=131) according to whether they received PPIs within 1 month before or after the initiation of ICIs treatment. The correlations between the uses of PPIs and the clinical characteristics of patients were explored, and the clinical efficacy of the two groups was evaluated. Kaplan-Meier survival curve was applied to analyze the effects of PPIs uses on overall survival (OS) and progression-free survival (PFS) of patients. The Cox proportional hazards model was used to clarify whether PPIs was an independent indicator of patients′ prognosis. Results:During ICIs treatment of advanced solid tumors, the use of PPIs was not correlated with the patients′ gender, age, tumor type, the score of the United States Eastern Collaborative Group, types of immunotherapy drugs and treatment strategy (all P>0.05). The objective response rate of the Non-PPIs group was better than that of the PPIs group (45.0% vs. 24.7%, χ2=8.286, P=0.004). The disease control rate of the Non-PPIs group was better than that of the PPIs group (75.6% vs. 52.0%, χ2=11.755, P=0.001). In patients with advanced solid tumors, the median OS (3.4 months vs. 6.1 months) and median PFS (2.8 months vs. 4.0 months) in the PPIs group were shorter than those in the Non-PPIs group ( χ2=9.563, P=0.002; χ2=5.761, P=0.016). Univariate analysis showed that among patients with advanced solid tumors treated with ICIs, PPIs uses was significantly correlated with OS ( HR=1.85, 95% CI: 1.24-2.76, P=0.003); PPIs uses( HR=1.65, 95% CI: 1.09-2.51, P=0.019) and age ( HR=1.56, 95% CI: 1.05-2.32, P=0.029) were significantly correlated with PFS. Multivariate analysis showed that PPIs uses was an independent prognostic factor affecting OS ( HR=1.90, 95% CI: 1.27-2.85, P=0.002) and PFS ( HR=1.73, 95% CI: 1.12-2.65, P=0.013). Meanwhile, subgroup analysis discovered that in the course of ICIs treatment of lung cancer patients, the median OS (3.2 months vs. 6.2 months) and median PFS (2.2 months vs. 3.8 months) in the PPIs group ( n=64) were shorter than those in the Non-PPIs group ( n=34) ( χ2=16.187, P<0.001; χ2=5.106, P=0.020). Univariate analysis showed that PPIs uses was associated with OS ( HR=2.97, 95% CI: 1.70-5.22, P<0.001) and PFS ( HR=1.97, 95% CI: 1.09-3.55, P=0.025) in lung cancer patients treated with ICIs. Multivariate analysis showed that PPIs uses was an independent prognostic factor for OS ( HR=3.38, 95% CI: 1.87-6.11, P<0.001) and PFS ( HR=2.31, 95% CI: 1.22-4.38, P=0.010) in lung cancer patients treated with ICIs. Conclusion:The use of PPIs reduces the effect of ICIs in the treatment of advanced solid tumor, especially in lung cancer. PPIs should be used cautiously in patients with advanced solid tumors treated with ICIs.

Objective:To develop an implementation protocol of clinical decision-support system about pediatric parenteral nutrition administration based on Guideline Implementation with Decision Support Checklist.Methods:From November to December 2021, using 4 dimensions and 16 items of Guideline Implementation with Decision Support Checklist, an multidisciplinary expert consultation was conducted, based on the previous clinical decision-support system and implementation protocol draft, to identify qualitative suggestions and quantitative assessment, and form the final protocol.Results:According to the Guideline Implementation with Decision Support Checklist, experts evaluated the implementation protocol draft, ranked the scores of 4 dimensions, system, content, context, and implementation, successively. Based on 12 updated suggestions, the final protocol included 4 dimensions and 12 interventions, including CDS updates, preparation before launching, experimental application and promotion, and systematic monitoring.Conclusions:The development of Guideline Implementation with Decision Support Checklist-based implementation protocol of clinical decision-support system about pediatric parenteral nutrition administration facilitated the thorough and structured consideration and agreement of multidisciplinary team, thus to optimize protocol and provide foundation for clinical practice.

Objective: To investigate the sleep quality and influencing factors of the first batch of college students returning to school during COVID-19 epidemic, so as to provide scientific basis for taking corresponding measures. Methods: An anonymous self-administered questionnaire survey was conducted among the first batch of college students returning from a certain university by cluster sampling, which included general demographic characteristics, Trait Coping Style Questionnaire (TCSQ) and Pittsburgh Sleep Quality Index(PSQI). Results: The detection rate of sleep disorders was 19.33%(522/2 701). The mother s education level was high school or technical secondary school or below(OR=2.24, 95%CI=1.47-3.41), never eat breakfast(OR=3.25, 95%CI=1.86-5.68), families were damaged during the outbreak (OR=1.48, 95%CI=1.17-1.87) and negative coping (OR=1.15, 95%CI=1.12-1.17) were risk factors for sleep disorders(P<0.05). Compared to having a very poor relationship with parents, the relationship between parents was average(OR=0.23, 95%CI=0.06-0.89), better(OR=0.23, 95%CI=0.06-0.87), very good (OR=0.19, 95%CI=0.05-0.74) were protective factors for sleep disorders(P<0.05). Exercise once or twice a week during the epidemic(OR=0.76, 95%CI=0.58-1.00), positive coping (OR=0.93, 95%CI=0.91-0.96) were protective factors for sleep disorders(P<0.05). Conclusion In this COVID-19 epidemic, the sleep quality of returning college students was affected to different extent, and the relationship between parents, sports, mother s education, breakfast habits, and family damage during the COVID-19 were factors affecting their sleep quality. Targeted psychological intervention measures should be given to returning college students in the early stage.

Family physicians on contract for rural families play an important role in primary medical and health services. This research raises for the first time the practical function and position of rural family physicians on contract. On this basis, a theoretical competency model of rural family physicians was constructed by referring to McClelland′s competency dictionary, relevant policy documents in China and literatures at hand. The model included six level-1 dimension indicators: achievement, management, service, cognition, influence, and self-efficacy, as well as 17 level-2 dimension indicators. At the same time, the paper explained in detail these indicators and compared them with the international indicators of family physicians, highlighting the working characteristics and practical needs of family physicians on contract in rural China.

Objective: To analyze the school adaptation and behavioral performance of the first batch of students who return to school during the COVID-19 epidemic, and to provide a theoretical basis for further development of corresponding intervention measures. Methods: The method of cluster sampling was adopted to conduct anonymous questionnaire survey on the first batch of college students who have returned to a certain university. The survey contents included the basic information of the students, the adaptability of the school after returning to school and the corresponding behavior performance. Results: Male students reported high lever of satisfaction than female students on the dormitory environment health (t=10.28, P<0.01), but low satisfaction on school security and logistical support (t=2.26, P=0.02), rural students marked higher score than urban students for the school closed management system (t=2.82, P=0.01), in terns of school security, Logistics, the degree of school s attention to the epidemic prevention and epidemic prevention, non only-child gave high score than the only children; In terms of their own behavior, the rate of seek medical treatment immediately when they develop COVID-19 related symptoms (68.1%) was lower than that of others (81.3%)(χ 2=223.88，P<0.01)；In addition, the percentage of respondents who chose to report COVID-19 related symptoms (79.5%) was lower than that of others (88.7%)(χ 2=97.49，P<0.01). A total of 2 671 college students (98.9%) were able to wear masks every day and 2 457 (90.9%) chose to improve their diet to improve their immunity. Conclusion The first batch of college students who return to school have a high level of satisfaction on school management, and can take active measures to adapt to the life back to school and commit self-protection, however targeted measures to are still needed further strengthen students health education.

Objective: To understand the current situation and influencing factors of Internet addiction among college students after returning to school during the COVID-19 epidemic, and to provide scientific basis for timely intervention measures to adjust the risk factors of Internet addiction. Methods: A cluster sampling method was adopted to conduct a questionnaire survey among 2 700 college students who firstly returned to college using general condition questionnaire and Internet Addiction scale. Results: The detection rate of Internet addiction disorder was 32.4% among returning college students, moreover, the detection rate of Internet addiction in male students(36.0%) was higher than that in female students (31.2%) (χ 2=5.42,P<0.05). The degree of Internet addiction was negatively correlated with the physical health score (r-s=-0.20) and mental health score (r-s=-0.24) of college students (P<0.01). Multivariate Logistic regression analysis showed that compared with introversion, neutral (OR=0.67, 95%CI=0.55-0.82) and extroverted college students (OR=0.59, 95%CI=0.48-0.74) were protective factors for Internet addiction; compared with no exercise, physical exercise ≥3 times or more per week (exercise 3-4 times：OR=0.67, 95%CI=0.51-0.87; ≥5 times：OR=0.67, 95%CI=0.50-0.90) were the protective factors for Internet addiction among college students; family loss during the epidemic was a risk factor for Internet addiction among college students (OR=1.34, 95%CI=1.12-1.60); the risk of Internet addiction was 2.13 times higher for college students who actively sought psychological help than for those who did not seek psychological help (95%CI=1.14-3.96); college students who did not want to go back to school had 1.50 times the risk of Internet addiction as those who did (95%CI=1.26-1.77). Conclusion The current situation of college students online behaviors during COVID-19 is not optimistic, and should arouse sufficient attention from society and universities. In addition, college students returning to school should take more physical exercises and psychological counseling to detect and intervene in psychological problems in time, reduce their psychological burden, and enhance their psychological quality.