Amino acids are essential nutrients for the survival of all cells in the body,and their metabolic processes are closely associ-ated with tumor development and progression.The metabolic changes of the essential amino acid tryptophan have a significance impact on tumor microenvironment.Tryptophan is mainly metabolized to kynurenine(KYN)by indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase,and the accumulation of KYN and the deficiency of tryptophan cause alterations in the immune status in tumor micro-environment,which in turn affects tumor development and progression.Based on the current studies on tryptophan,this article system-atically discusses the influence of abnormal tryptophan metabolism on tumors and the interventions targeting this pathway,in order to provide a reference for subsequent tumor therapy.

Tumor microenvironment(TME)is the cellular environment for tumor development,growth,and metastasis.Adenosine(ADO)is an immunosuppressive metabolic product that is continuously upregulated in TME,with various types and wide distribution of receptors.The complex and dynamic interactions between ADO and tumor cells constantly influence tumor progression.ADO can di-rectly or indirectly promote tumor development and progression by promoting tumor generation and metastasis,mediating the immune escape of tumor,and modulating tumor-infiltrating immune cells.Based on the characteristics of ADOs in TME,this article reviews the latest advances in the dynamic alterations of ADO in TME,in order to provide insights into tumor treatment targeting the ADO pathway.

Cholesterol,as an important component of cell membranes,plays a multifaceted role in mediating tumor immunomodulation and drug intervention.In case of cholesterol metabolic imbalance,the accumulation of cholesterol metabolic intermediates,the changes in concentrations,and the regulation of related signaling pathways can affect tumor immunity by promoting inflammation and inhibiting immune cell function.Preclinical and clinical studies have shown that controlling cholesterol metabolism can inhibit tumor growth,re-shape body immune regulation,and enhance antitumor immunity.A deep understanding of the association between immune cells and cholesterol metabolic pathways in the tumor microenvironment can help to develop novel drugs targeting cholesterol metabolism.This article reviews the multifaceted role of cholesterol and its derived metabolites in the tumor microenvironment by regulating various types of immune cells such as myeloid-derived suppressor cells,tumor-associated macrophages,dendritic cells,and T-lymphocytes,as well as the characteristics of tumor immunomodulation mediated by cholesterol metabolism and the advances in pharmaceutical re-search on improving the immune function of the body by intervening against cholesterol,in order to further provide new ideas and a thera-peutic basis for cholesterol modulation and intervention in tumor im-munotherapy.

OBJECTIVE To develop a questionnaire of the Knowledge-Attitude-Practice （KAP） for patients receiving oral anticoagulant therapy. METHODS Under the guidance of the theory of KAP， literature analysis and interview method were used to design the initial KAP questionnaire for patients treated with oral anticoagulants. Delphi method was adopted to consult the initial questionnaire and modify the questionnaire based on expert suggestions to form the final questionnaire. RESULTS Two rounds of consultation were conducted with 18 experts， and 18 questionnaires were sent out and recovered in each round， so the positive coefficient of experts was 100%. The expert authority coefficient was 0.94. The average importance scores for all dimensions， factors， and items of the questionnaire in both rounds were ≥4 points. The coefficient of variation was ≤0.25. The Kendall’s concordance coefficient for the overall questionnaire and the three dimensions of knowledge， attitude， and practice ranged from 0.09 to 0.34 （all P＜0.05）. Following the first round of expert consultation， four items were modified， two items were deleted， and five items were added； after the second round of expert consultation， ten items were modified. The final version of the questionnaire included three dimensions （knowledge， attitudes， and practice）， 17 questionnaire factors， and 40 items. CONCLUSIONS The questionnaire has high reliability and scientific validity with relatively concentrated expert opinions. It is suitable for assessing the knowledge， attitudes， and practice status of patients receiving oral anticoagulant therapy.

Objective:To investigate the effectiveness of the S-PAL model (combining a student standardized patient with peer assisted learning) in experimental teaching of physical diagnostics.Methods:Eighty-four undergraduate students of grade 2022 in clinical medicine of Chongqing Medical University were divided into experimental group ( n=44, experimental class teaching combined with S-PAL model-based autonomous practice) and control group ( n=40, experimental class teaching combined with traditional autonomous practice). Performance evaluation and teaching feedback and satisfaction survey were conducted. SPSS 27.0 was used to perform the t-test, chi-square test, and Fisher's exact test. Results:There were no significant differences between the two groups in terms of age, sex, the grade point average, and pre-training theoretical scores. The academic assessment score of the experimental group (66.34±15.45) was significantly higher than that of the control group (55.12±15.02). The experimental group was superior to the control group in clinical skills assessed with the mini-clinical evaluation exercise. The experimental group had a higher degree of satisfaction with teaching than the control group. The experimental group highly accepted autonomous practice based on the S-PAL model.Conclusions:The S-PAL model can improve medical undergraduates' academic performance and satisfaction with teaching in physical diagnostics, and also promote their doctor-patient communication skills, which is a good self-learning model as a complement to physical diagnostics teaching.

To evaluate the advantages of using PBL case library in teaching circulatory system diseases to clinical medicine undergraduate students, a PBL case library was established and applied in teaching practice in the reform of circulatory system teaching. The PBL case library achieved the characteristics of combining theories with cases, morphology with functions, and basic knowledge with clinical knowledge. The PBL case library also realized the informatization, query, and update of cases. Preliminary application showed that the median practical score of students in the case library group was 94.00 points, which was significantly higher than the 92.00 points in the control group ( P=0.005). The average lesson preparation time for teachers in the case library group was (5.00±1.00) hours, which was significantly shorter than the (6.89±0.42) hours in the control group ( P<0.001). The difficulty score for lesson preparation among teachers in the case library group was significantly lower than that of the control group [(1.89±1.05) vs. (3.22±0.44), P<0.001]. However, there were no significant difference in theoretical scores and student satisfaction with teachers and courses. These results suggest that the construction of case library can improve practical teaching effectiveness and enhance the efficiency of lesson preparation for teachers.

Atherosclerosis is a lipid-driven chronic inflammatory disease that typically forms plaques in large and medium-sized arteries and is a major cause of ischemic heart disease and stroke.Recent studies have found that during the progression of atherosclerosis,the level of cellular glycolysis in plaques increases,leading to excessive production and excretion of lactate and acidification of the extracellular environment,which may further affect the development of athero-sclerosis through multiple mechanisms.This article reviews the research progress on the role of lactate metabolism in ath-erosclerosis,which may provide new therapeutic targets and directions for the prevention and treatment of atherosclerosis.

Objective:To investigate the effect of ultrasound-guided midline catheter placement on the incidence of catheter-related bloodstream infection (CRBSI) in severe emergency patients.Methods:Five hundred and twenty-nine patients were chosen as the research objects from March 2018 to December 2019 at Emergency Intensive Care Unit, which was divided into the experimental group ( n=278) and the control group ( n=251). In the experimental group, ultrasound-guided midline catheter was used as central venous catheter (CVC) removal method of sequential, and in the control group, peripheral venous indwelling needle was used as sequential method after removal of CVC. CVC, midline catheter and the indwelling time of indwelling needle were counted. The utilization rate of CVC was compared between the two groups. Kaplan-Meier survival curve was plotted to describe the CVC indwelling time of the two groups and log-rank test was performed. Cox regression analysis was performed to analyze the influencing factors of CVC indwelling time and compare the incidence of CRBSI and other catheter-related complications. Results:The CVC indwelling time of the experimental group was significantly shorter than that of the control group (8 d vs. 13 d, P=0.000). The CVC utilization rate of the experimental group was significantly lower than that of the control group (49.83% vs. 80.45%, P=0.000). Multivariate Cox regression analysis showed that difficult intravenous access, length of ICU stay, the site of catheter placement, and midline catheter implantation without ultrasound-guidance were independent risk factors for prolonged CVC indwelling time ( P=0.000). The CRBSI rate of the experimental group was significantly lower than that of the control group (0.571‰ vs. 3.802‰, P=0.038). There was no significant difference in the incidence of other catheter-related complications between the two groups ( P=0.403). Conclusions:Ultrasound-guided midline catheter implantation can shorten the indwelling time of CVC, reduce the utilization rate of CVC, and reduce the incidence of CRBSI, which is worthy of clinical promotion.

Objective:To investigate the effects of poly (ADP-ribose) polymerase-1(PARP-1) in intestinal mucosal barrier injury in rat model with severe acute pancreatitis (SAP).Methods:Twenty healthy male Wistar rats were divided into four groups ( n=5 each group) using a random table method: control, SAP, 3-aminobenzamide (3-AB), and 3-AB control groups. The SAP model was induced by intraperitoneal injection of cerulean with lipopolysaccharide. At 30 min, the rats were treated with the PARP-1 inhibitor, 3-AB, or normal saline,separately. After 12 h, all rats were sacrificed to harvest pancreas tissues, intestines tissues, and blood from the hearts for index detection. Serum amylase (AMY) and interleukin (IL)-6 levels were measured using an automatic biochemical instrument and enzyme-linked immunosorbent assay (ELISA), respectively.The protein expression of PARP-1 and nuclear factor (NF-κB) were measured using Western blot and that of occludin was measured using an immunohistochemical test. One-way analysis of variance was used for comparison of multiple groups of variables. Non-parametric tests of rank conversion were used when variances were not uniform. A P <0.05 was considered statistically significant. Results:Compared to the control group, the following indexes in the SAP group were significantly increased: ascites (with serious hemorrhage and necrosis in the pancreas and disordered intestinal villi),serum AMY and IL-6 levels, and the expression of PARP-1 and NF-κB. However, Occludin expression was significantly decreased. There was no significant difference between 3-AB group and 3-AB control group. Compared to the SAP group, the severity of SAP and pancreatitis-associated intestinal injury was significantly attenuated with the administration of 3-AB. Serum AMY and IL-6 levels were significantly decreased (serum AMY: 1 879.25 ± 736.6 U/L vs 5 569.33 ± 1993.48 U/L; IL-6: 77.98 ± 20.65 pg/mL vs 209.14 ± 79.08 pg/mL, both P<0.05), but the expression of PARP-1 and NF-κB were significantly increased (PARP-1: 1.44 ± 0.09 vs 1.49 ± 0.13; NF-κB: 0.63 ± 0.09 vs 0.96±0.08, both P<0.05). Similarly, Occludin expression was significantly decreased (6.7±1.5 vs 3.2±1.1, P<0.05). Conclusions:Inhibition of PARP-1 has protective effects on SAP associated intestinal mucosal barrier damage. The mechanism may be related to the inhibition of NF-κB signaling pathway and increase intestinal mucosal Occludin protein expression.

Objective To compare the intestinal microbiota of septic shock patients and healthy subjects,and study the composition of the intestinal microbiota and its effect on septic shock patients in the intensive care unit (ICU).Methods A total of 15 stool samples were prospectively collected from septic shock patients admitted to the ICU in the First Affiliated Hospital of Zhengzhou University between June 2015 and February 2016,while 15 samples from healthy subjects served as controls.Bacterial DNA was submitted for 16S rDNA gene sequencing.The association between gut microbiota composition and clinical parameters was evaluated.Shannon index was used to assess the bacterial diversity.Results Compared with the healthy subjects,the composition of intestinal microbiota in septic shock patients changed significantly.The abundance of Proteobacteria and Fusobacteria were significantly higher in septic shock patients than in healthy subjects (23.71％ vs 3.53％,P=0.000 6;1.27％ vs 0.12％,P=0.059,respectively).In this study,29 species were identified,and the composition of intestinal microbiota in each patient was highly individualized.There was no significant difference in Shannon index between septic shock patients and healthy subjects (P=0.12).Conclusions The composition of intestinal microbiota in septic shock patients was characterized by high diversity and individualization,but there was the phenomenon of overproduction of single bacteria genus.The relationship between the composition of intestinal microbiota and clinical outcomes requires further exploration by large sample studies.