Background and purpose:Cytotoxic T lymphocyte (CTL) plays a vital role in the process of anti-tumor immunology. The aim of this study was to investigate whether changes in concentration of IL-2 (50, 200 and 1 000 U/mL) would affect the sub-population and cytotoxic function of cells cultivated by peptide-specific CTL induction systemin vitro and also observe whether using the concentration of IL-2 at a range of 50-1 000 U/mL isbeneifcial to regulatory cells (Tregs) enrichment.Methods:Peripheral blood from 10 healthy donors and 10 cancer patients that were HLA-A2 positive, were collected in the study. HLA-A2 restricted CTL epitope P321 (ILIGETIKI) derived from COX-2 pulsed with different concentrations of IL-2 were used to induce peptides-speciifc CTLin vitro. Flow cytometry was performed to analyze the proliferative capability, the proportion of different T-cell subsets, and secretion of perforin, granzyme B and IFN-γ. IFN-γ secretion was assessed by ELISpot assay.Results:High concentration of IL-2 increased the proliferative activity. The percentage of CD4+ T cells of cancer patient group was signiifcantly higher than that of healthy donor group, while the percentage of CD8+ T cells of cancer patient group was signiifcantly lower than that of healthy donor group. And there was no signiifcant difference in the percentages of CD4+ T cells, CD8+ T cells and Tregs among groups with different IL-2 concentrations. No difference was seen in cytokine (perforin, granzyme B, IFN-γ) secretion capacity of CD8+ T cells. ELISpot study revealed that high-dose IL-2 resulted in the increasing of IFN-γ secretion.Conclusion:The sub-population and the function of cells cultured by peptide-speciifc CTL induction systemin vitro are not affected by different concentrations of IL-2. Furthermore, high concentrations of IL-2 (50-1 000 U/mL) do not provide the enrichment for Tregs. Higher concentration of IL-2 is likely to cause high secretion of IFN-γ in ELISpot assay. In order to exclude the distraction of NK cells or NKT cells, the concentration of 50 U/mL is better choice.

Objective:To observe and analyze the function of intestinal barrier in patients with pouchitis, and to explore the role of nucleotide oligomerization domain 2 (NOD2) in ileal pouchitis, so as to provide new ideas for the pathogenesis of pouchitis.Methods:From January 2011 to December 2016, the clinical pathological data of patients with ileal pouch-anal anastomosis who underwent pouch mucosa biopsy at the Endoscopy Center of General Hospital of Tianjin Medical University were retrospectively analyzed. According to the disease activity index of pouchitis, patients were divided into pouchitis group (20 cases) and non-pouchitis group (30 cases). In addition, UC patients who did not undergo surgery were selected as the control group (10 cases). The intestinal structure of patients of the pouchitis group and non-pouchitis group was observed under transmission electron microscope. The positive expression rates of occludin, alpha human defensin and NOD2 in the control group, non-pouchitis group and pouchitis group were detected and calculated by immunohistochemistry. Levene test, independent sample t test and Spearman correlation analysis were used for statistical analysis. Results:Under the transmission electron microscope, the tight junction epithelial structure and microvilli of intestinal mucosal of patients in the pouchitis group were severely injured. The results of immunohistochemistry showed that the positive expression rates of occludin, alpha human defensin and NOD2 in the intestinal mucosa of patients in the pouchitis group were all lower than those of the control group and non-pouchitis groups ((19.3±0.4)% vs. (84.0±0.3)% and (77.9±0.5)%; (60.0±1.3)% vs. (85.0±0.1)% and (77.3±0.4)%; (46.1±1.6)% vs. (72.0±0.7)% and (60.7±0.5)%), and the differences were statistically significant ( t=-8.451, -7.514, -3.943, -2.970, -5.115 and -2.982, all P<0.05). The correlation analysis showed that the expression level of NOD2 was positively correlated with occludin and alpha human defensin ( r=0.671 and 0.628, both P<0.01). Conclusions:Intestinal barrier function is impaired in patients with ileal pouchitis, and NOD2-related intestinal barrier injury may play an important role in the pathogenesis of ileal pouchitis.

HMGB1's role in tumors is complex and diverse,and it exerts its biological function by combining with different receptors.One of the receptors is called RAGE,which is localized to the cell membrane and binds to HMGB1 released outside the cell.The HMGB1/RAGE axis promotes tumor development,moreover,tumor development and its drug resistance are closely related to inflammation.This article mainly reviews the molecular mechanism of HMGB1/RAGE axis in pro-inflammatory and protumor effects in pancreatic,colorectal and liver cancers.We also summarize the research progress of papaverine and its derivatives for the treatment of HMGB1/RAGE axis in tumor inflammation,with aims of providing new ideas for exploring the molecular mechanism of action in tumor inflammation,and providing a new theoretical basis for the research of HMGB1/RAGE axis therapeutics.

Objective:To evaluate the value of preoperative prediction of vessel invasion (VI) of locally advanced gastric cancer by machine learning model based on the venous phase enhanced CT radiomics features.Methods:A retrospective analysis of 296 patients with locally advanced gastric cancer confirmed by pathology in the First Affiliated Hospital of Zhengzhou University from July 2011 to December 2020 was performed. The patients were divided into VI positive group ( n=213) and VI negative group ( n=83) based on pathological results. The data were divided into training set ( n=207) and test set ( n=89) according to the ratio of 7∶3 with stratification sampling. The clinical characteristics of patients were recorded, and the independent risk factors of gastric cancer VI were screened by multivariate logistic regression. Pyradiomics software was used to extract radiomic features from the venous phase enhanced CT images, and the minimum absolute shrinkage and selection algorithm (LASSO) was used to screen the features, obtain the optimal feature subset, and establish the radiomics signature. Four machine learning algorithms, including extreme gradient boosting (XGBoost), logistic, naive Bayes (GNB), and support vector machine (SVM) models, were used to build prediction models for the radiomics signature and the screened clinical independent risk factors. The efficacy of the model in predicting gastric cancer VI was evaluated by the receiver operating characteristic curve. Results:The degree of differentiation (OR=13.651, 95%CI 7.265-25.650, P=0.003), Lauren′s classification (OR=1.349, 95%CI 1.011-1.799, P=0.042) and CA199 (OR=1.796, 95%CI 1.406-2.186, P=0.044) were independent risk factors for predicting the VI of locally advanced gastric cancer. Based on the venous phase enhanced CT images, 864 quantitative features were extracted, and 18 best constructed radiomics signature were selected by LASSO. In the training set, the area under the curve (AUC) of XGBoost, logistic, GNB and SVM models for predicting gastric cancer VI were 0.914 (95%CI 0.875-0.953), 0.897 (95%CI 0.853-0.940), 0.880 (95%CI 0.832-0.928) and 0.814 (95%CI 0.755-0.873), respectively, and in the test set were 0.870 (95%CI 0.769-0.971), 0.877 (95%CI 0.788-0.964), 0.859 (95%CI 0.755-0.961) and 0.773 (95%CI 0.647-0.898). The logistic model had the largest AUC in the test set. Conclusions:The machine learning model based on the venous phase enhanced CT radiomics features has high efficacy in predicting the VI of locally advanced gastric cancer before the operation, and the logistic model demonstrates the best diagnostic efficacy.

Purpose To observe the right ventricle and left ventricle blood pool T2 map in chronic thromboembolic pulmonary hypertension(CTEPH)and healthy controls,and to analyze the value of T2 mapping technique in evaluating CTEPH.Materials and Methods A total of 42 patients with CTEPH and 42 healthy volunteers had been prospectively recruited from January 2020 to January 2022 in China-Japan Friendship Hospital.All CTEPH patients underwent cardiac magnetic resonance with T2 mapping and right heart catheterization.Cardiac magnetic resonance was performed on healthy controls.Diastolic T2 mapping was performed in cardiac magnetic resonance,and then the ratio of right ventricular to left ventricular T2 values(RVT2/LVT2)between the CTEPH group and the healthy group was calculated and compared.Meanwhile,the correlation between RVT2/LVT2 and hemodynamic parameters in the CTEPH group was analyzed.Results RVT2/LVT2 in the CTEPH group was significantly lower than that in the healthy group(0.74±0.16 vs.0.86±0.12;t=3.673,P<0.001).RVT2/LVT2 in CTEPH group was negatively correlated with pulmonary vascular resistance(r=-0.534,P<0.001);while it was positively correlated with cardiac index,right atrium oxygen saturation,right ventricle oxygen saturation and pulmonary arteries oxygen saturation(r=0.600,0.603,0.648,0.582,P<0.001).Conclusion RVT2/LVT2 in the CTEPH group is positively correlated with right cardiac oxygen saturation and negatively correlated with pulmonary vascular resistance.T2 mapping may be a noninvasive evaluation of hemodynamics in CTEPH.

Objective:To explore the contents and methods of clinical comprehensive evaluation of microecologics, with the example of Bifidobacterium quadruple viable tablet, in order to provide evidence for clinical rational use of microecologics, and microecologics research, development and related decision-making, and to promote rational use of medications. Methods:Based on the research data collected from systematic literature search, health technology assessment methods such as evidence-based medicine and pharmacoeconomics evaluation were used to estimate the safety, efficacy, economics, suitability, accessibility and innovation of Bifidobacterium quadruple viable tablet. Results:In terms of efficacy, Bifidobacterium quadruple viable tablet showed significant therapeutic effects in the treatment of pediatric diarrhea, antibiotic-related diarrhea, diarrhea-predominant irritable bowel syndrome, and secondary diarrhea caused by diseases such as ulcerative colitis, as well as constipation and functional dyspepsia. It can also be used in the treatment of various diseases such as Helicobacter pylori related gastritis, liver cirrhosis, non-alcoholic fatty liver disease. In terms of safety, the incidence of adverse effects of this medication was low, and most were mild to moderate and transient symptoms. In terms of economics, compared with mesalazine alone in the treatment of ulcerative colitis, the incremental cost-effectiveness ratio of combination of Bifidobacterium quadruple viable tablet and mesalazine was 1 743.2. Besides, the daily treatment cost of Bifidobacterium quadruple viable tablet was lower than that of combination of Bifidobacterium triple viable and Bacillus licheniformis (1.87 to 2.80 yuan vs. 2.08 to 5.78 yuan). In terms of innovation, this medication had multiple patents and had been identified as a high-tech product in Zhejiang Province. In terms of suitability, the overall suitability of use and technical characteristics of medication were good. It could be further improved in the aspects of dosage form and system. In terms of accessibility, the price of the medication was stable, affordable and accessible to the general public. Conclusions:Based on the existing evidence, Bifidobacterium quadruple viable tablet presented effective with supported evidences, good safety, accessibility and innovation. The suitability can be further optimized. However, more in-depth and targeted research is needed in terms of economics and innovation in different clinical applications, and there is space for optimization in medication suitability.

Objectives:To investigate the prevalence,clinical characteristics and risk factors of coronavirus disease-2019(COVID-19)in patients with pulmonary hypertension(PH). Methods:A questionnaire survey was conducted from December 30,2022 to January 6,2023 through the WeChat official account of the PH Patients Mutual Aid Organization.PH patients aged≥18 years from 26 province(municipality/autonomous region)were recruited to fill in the electronic survey questionnaire. Results:A total of 293 valid questionnaires were collected from PH patients.The mean age of patients was(40.6±12.7)years,and 226 patients(77.1%)of them were female.The vaccination rate was 59.7%(175/293),117 patients(39.9%)received three or more doses of vaccine,145 patients(49.5%)received inactivated vaccine.242 patients(82.6%)had COVID-19.The most common symptoms during infection were fever(85.5%),cough(77.7%),and fatigue(66.5%).10.7%of the patients had severe or critical COVID-19.Age(OR =1.057,95%CI:1.027-1.087,P<0.001)and comorbid pulmonary disease(OR=3.341,95%CI:1.215-9.184,P=0.019)were associated with severe or critical COVID-19.After adjusting for confounding factors,age was an independent risk factor for severe or critical COVID-19(OR=1.049,95%CI:1.019-1.080,P=0.001).Severe or critical COVID-19 was an independent risk factor for worsening heart failure in PH patients during COVID-19 pandemic(OR=10.522,95%CI:4.311-25.682,P<0.001). Conclusions:The immunization coverage of PH patients is insufficient.PH patients have a higher risk of developing severe or critical COVID-19 than general population.Ageing is an independent risk factor for severe or critical COVID-19,and the risk of worsening heart failure in PH patients with severe or critical COVID-19 is significantly increased during COVID-19 pandemic.

OBJECTIVE： To establish the fingerprint of Mahai zhitan capsule， to determine the contents of main components， and to provide scientific basis for the stability and quality control of the preparation technology. METHODS： The determination was performed on Inertsil ODS-3 column with acetonitrile-0.1％ phosphoric acid as mobile phase （gradient elution） at the flow rate of 1.0 mL/min. The detection wavelength was set at 250 nm （0-23 min and 31-120 min） and 230 nm （23-31 min）. The column temperature was set at 30 ℃. HPLC fingerprint for 10 batches of Mahai zhitan capsule was established by using “similarity evaluation software for chromatographic fingerprint of traditional chinese medicine” （2012 edition） and the similarity was evaluated. The chromatographic peaks were assigned and identified with reference substance， negative samples without ingredient and substance control respectively， and the identified main components were quantitatively analyzed. RESULTS： The similarity of 10 batches of sample was more than 0.99； 20 common peaks were found， and 10 common peaks were identified. Among them， No. 1，13，14，15，16，17，18，19，20 chromatographic peaks originated from Rheum palmatum； No. 3，4，6，7 chromatographic peaks originated from processed Strychnos nuxvomica； No. 8 chromatographic peaks originated from Angelica sinensis； the corresponding source of medicinal materials was not found in No. 2，5，9，10，11，12 chromatographic peaks. By comparing the reference substances， No. 1，4，6，7，8，16，17，18，19 and 20 chromatographic peaks were identified as gallic acid， loganin acid， strychnine， brucine， ferulic acid， aloe-emodin， rhein， emodin， chrysophanol and emodin methyl ether， respectively. In the determination of identified five main components （loganin， strychnine， brucine， emodin and chrysophanol）， the methodological investigation met the relevant standards. In 10 batches of samples， the contents of loganin， strychnine， brucine， emodin and chrysophanol were 2.477 1-2.785 9， 1.746 1-1.946 0， 1.374 6-1.505 8， 1.573 2-1.824 1 and 0.232 1-0.261 7 mg/g， respectively. CONCLUSIONS： The established method is reliable， accurate， stable and simple， which could provide reference for the preparation technology and quality control of Mahai zhitan capsule.

【Objective】 To analyze the correlation of whole body tumor burden of ¹⁸F-prostate specific membrane antigen positron emission computed tomography （¹⁸F-PSMA PET/CT） with prostate specific antigen （PSA） and Gleason score so as to evaluate the value of ¹⁸F-PSMA PET/CT whole body tumor burden for predicting serum PSA progression in prostate cancer. 【Methods】 We retrospectively recruited 213 patients with prostate cancer who underwent ¹⁸F-PSMA PET/CT scanning from March 2019 to April 2021. The serum PSA and Gleason score were collected. Whole body tumor burden was measured by a semi-automatic method. The correlation of tumor burden with serum PSA and Gleason score was analyzed. After radical prostatectomy， the patients were divided into groups according to negative or positive ¹⁸F-PSMA PET/CT. PSA differences between groups were compared， and the receiver operating characteristic curve （ROC） of the subjects was drawn so as to obtain the threshold value of PSA to predict the positive rate of ¹⁸F-PSMA PET/CT. The patients were followed up for PSA after radical surgery， divided into groups according to the progress of PSA， and the differences in tumor burden between groups were compared. 【Results】 In Gleason score ≤7， =8， and ≥9 groups， whole body tumor burden was correlated with PSA in each group （P=0.001）， and tumor burden significantly differed between the groups （P<0.001）. In initial diagnosis and treatment group， biochemical recurrence group， and medication group， the correlation between tumor burden and PSA was statistically significant （P=0.001）. The Gleason score of primary prostate lesion was significantly correlated with systemic tumor burden （P<0.001）. The area under ROC curve of PSA predicting the positive rate of ¹⁸F-PSMA PET/CT after radical prostatectomy was 0.821； when PSA>0.577 ng/mL， the sensitivity and the specificity were 66.7% and 96.8%， respectively. The mean whole body tumor burden in ¹⁸F-PSMA PET/CT positive patients with PSA progression was higher than that in patients without PSA progression. 【Conclusion】 The whole body tumor burden of ¹⁸F-PSMA PET/CT is significantly correlated with PSA， which is helpful in predicting the serum PSA progression in prostate cancer. PSA can predict the positive rate of ¹⁸F-PSMA PET/CT to a certain extent. At the same time， PSA can also predict positive results of ¹⁸F-PSMA PET/CT to a certain extent， and guide clinical rational selection of this examination.

【Objective】 To investigate the value of prostate-specific antigen （PSA） level， Gleason score， and PSMA PET/CT maximum standardized uptake value （SUVmax） in predicting prostate cancer （PCa） metastasis and the treatment option of oligometastatic PCa. 【Methods】 We retrospectively recruited 170 patients with PCa confirmed by pathology， 97 of whom were untreated， and divided them into nonmetastatic group， oligometastatic group （metastasis≤5）， and polymetastatic group. In addition， 28 patients with oligometastatic PCa underwent radical prostatectomy and 45 patients underwent androgen-deprivation therapy. We compared the differences in SUVmax， PSA， and Gleason scores between the three sub-groups of untreated patients， and also analyzed the correlation between SUVmax of local cancer lesions， Gleason score and PSA level. We further compared the differences in SUVmax and PSA levels between radical prostatectomy and androgen-deprivation therapy of oligometastatic PCa patients. According to Gleason score， patients with oligometastatic PCa were divided into two groups （low-intermediate risk group with Gleason score ≤7 and high-risk group with Gleason score ≥8）， and the levels of SUVmax and PSA between the groups were compared. 【Results】 With the increasing number of metastases， SUVmax， PSA levels and Gleason scores all showed an upward trend， and there were significant differences among the three groups （P=0.029， P=0.001， P=0.046）. The post-hoc test found significant difference in Gleason score between the oligometastatic group and the other two groups （P=0.043， P=0.002） as well as correlation of SUVmax level of the primary tumor with Gleason score and PSA （P=0.002， r=0.315； P<0.001， r=0.430）. There was significant difference in PSA level between the two groups after radical prostatectomy and androgen-deprivation therapy （P=0.017）. The difference in PSA between the two treatments persisted in the low-intermediate risk groups （P=0.021）. 【Conclusion】 PSA level， Gleason score and SUVmax have some value in predicting PCa metastasis. Radical prostatectomy is an effective treatment strategy for patients with oligometastatic PCa， especially those with low-intermediate Gleason score.