Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Objective:To analyze the drug resistance characteristics of Klebsiella pneumoniae in the nasopharynx of hospitalized patients in North China from 2022 to 2023. Methods:From November 2022 to July 2023, nasopharyngeal swabs were collected from 100 inpatients in Affiliated Hospital of North China University of Science and Technology, and Klebsiella pneumoniae was isolated and cultured. At the same time, the clinical data of the patients were collected, including gender, age, department, clinical diagnosis of disease type, etc. The minimum inhibitory concentration of strains was detected by an automatic bacterial drug sensitivity system. The drug resistance genes, ST types, capsule serotypes and population structure of the strains were analyzed by whole genome sequencing and data analysis. Results:Klebsiella pneumoniae was isolated from 55 nasopharyngeal swabs of 100 inpatients(55.00%). Among the 55 inpatients with Klebsiella pneumoniae in the nasopharynx, 70.91% (39/55) were male, with an age distribution concentrated between 61 and 80 years old (58.18%, 32/55), and 50.91% (28/55) were in intensive care units (ICU). The main underlying disease type was nervous system disease (49.09%, 27/55). The results of drug sensitivity showed that the non-susceptibility rates of 55 strains of Klebsiella pneumoniae to cephalosporins, quinolones, aztreonam and nitrofurantoin were all more than 80.00%. Twenty-eight carbapenem-resistant Klebsiella pneumoniae strains (50.91%), 47 extended-spectrum β-lactamase producing strains (85.45%), and 48 multi-drug-resistant strains (87.27%) were detected. A total of 11 antibiotic resistance genes were detected, including carbapenems (carrying rate 76.36%) and extended-spectrum β-lactamase (carrying rate 96.36%). The 55 strains could be divided into 17 ST types, and the most common type was ST11 (25.45%). The 55 strains were divided into 18 capsular serotypes, among which K102 was the most prevalent (23.64%). OXA-1_ST307_K102 (21.82%) and KPC-2_ST5492_K125 (18.18%) were the dominant clones, distributed in the Department of Neurosurgery and ICU. The result of whole genome sequence analysis showed that there were four clusters with high homology among the 55 strains. The strains from the ICU formed two independent clusters, and strains from the Neurology ICU and Neurosurgery department formed one cluster respectively. Conclusion:The carrying rate of Klebsiella pneumoniae in the nasopharynx of inpatients is high, and the drug resistance of the strains is serious. There are many types of drug-resistant genes.

Objective:To analyze the drug resistance characteristics of Klebsiella pneumoniae in the nasopharynx of hospitalized patients in North China from 2022 to 2023. Methods:From November 2022 to July 2023, nasopharyngeal swabs were collected from 100 inpatients in Affiliated Hospital of North China University of Science and Technology, and Klebsiella pneumoniae was isolated and cultured. At the same time, the clinical data of the patients were collected, including gender, age, department, clinical diagnosis of disease type, etc. The minimum inhibitory concentration of strains was detected by an automatic bacterial drug sensitivity system. The drug resistance genes, ST types, capsule serotypes and population structure of the strains were analyzed by whole genome sequencing and data analysis. Results:Klebsiella pneumoniae was isolated from 55 nasopharyngeal swabs of 100 inpatients(55.00%). Among the 55 inpatients with Klebsiella pneumoniae in the nasopharynx, 70.91% (39/55) were male, with an age distribution concentrated between 61 and 80 years old (58.18%, 32/55), and 50.91% (28/55) were in intensive care units (ICU). The main underlying disease type was nervous system disease (49.09%, 27/55). The results of drug sensitivity showed that the non-susceptibility rates of 55 strains of Klebsiella pneumoniae to cephalosporins, quinolones, aztreonam and nitrofurantoin were all more than 80.00%. Twenty-eight carbapenem-resistant Klebsiella pneumoniae strains (50.91%), 47 extended-spectrum β-lactamase producing strains (85.45%), and 48 multi-drug-resistant strains (87.27%) were detected. A total of 11 antibiotic resistance genes were detected, including carbapenems (carrying rate 76.36%) and extended-spectrum β-lactamase (carrying rate 96.36%). The 55 strains could be divided into 17 ST types, and the most common type was ST11 (25.45%). The 55 strains were divided into 18 capsular serotypes, among which K102 was the most prevalent (23.64%). OXA-1_ST307_K102 (21.82%) and KPC-2_ST5492_K125 (18.18%) were the dominant clones, distributed in the Department of Neurosurgery and ICU. The result of whole genome sequence analysis showed that there were four clusters with high homology among the 55 strains. The strains from the ICU formed two independent clusters, and strains from the Neurology ICU and Neurosurgery department formed one cluster respectively. Conclusion:The carrying rate of Klebsiella pneumoniae in the nasopharynx of inpatients is high, and the drug resistance of the strains is serious. There are many types of drug-resistant genes.

Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8⁺ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8⁺ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy.

Objective To investigate the effects of different dietary patterns on brachial ankle pulse wave velocity in northern industrial cities. Methods According to the selection criteria,from 2014 to 2015, 22436 health checkup persons were selected as the subjects of Kailuan Group,they were followed up with health examination and questionnaire investigation, at the same time, the brachial ankle pulse wave velocity was detected. According to the dietary advice given by the Chinese dietary guidelines,the proportion of animal and plant food in the food frequency questionnaire and the supply of nutrients are divided into 4 groups,which are the traditional Chinese diet group (3 585 cases),the Western diet group (13 639 cases),the balanced diet group (1 309 cases),the Mediterranean diet group (3 903 cases). Logistic multivariate regression analysis was used to analyze he risk factors of atherosclerosis. Results The mean value of brachial ankle pulse wave velocity in 22 436 cases was ( 1 462. 46 ± 320. 69) cm/s, and the incidence of peripheral arteriosclerosis was 50. 78%(11 392/22 436). The incidence of arteriosclerosis around the balanced diet group, the Mediterranean diet group,the traditional Chinese diet group and the Western diet group were 48. 82%( 639/1 309), 49. 12%(1 917/3 903),50. 49%(1 810/3 585),51. 51%(7 026/13 639),and the difference between the groups was statistically significant (P＝0. 024); after adjusting other related risk factors,compared with the balanced diet group,the risk of peripheral arteriosclerosis in the Mediterranean diet group,the traditional diet group and the Western diet group was 121(95%CI:0. 557～2. 258),1. 015(95%CI:0. 663～1. 554),1. 033(95%CI:0. 677～1. 575), respectively. Conclusion The incidence of peripheral arteriosclerosis increased gradually in the balanced diet group,the Mediterranean diet group,the Chinese traditional diet group and the Western diet group, but there was no statistical significance in the risk of peripheral arteriosclerosis after adjusting other related risk factors. This Conclusion requires more large samples,long-term follow-up study to further confirm.

Objective To explore the impact of rituximab on Th17 cells and related cytokines in patients with diffuse large B-cell lymphoma (DLBCL) in vitro and its significance.Methods 20 cases of DLBCL untreated patients and 20 healthy subjects were enrolled in the name of DLBCL group and health control group, respectively.4 peripheral blood samples were collected from every case to separate peripheral blood mononuclear cells (PBMCs), which were assigned to 4 subgroups according to different culture conditions: blank subgroup(subgroup A), rituximab subgroup (subgroup B), rituximab and serum subgroup (subgroup C) and polarization subgroup (subgroup D) (added IL-6 and TGF-β).After cultured in vitro, the percentage of Th17 cells in each subgroup was tested by flow cytometry, and the cytokine IL-17 in the abovementioned culture fluid was measured by enzyme-linked immunosorbent assay (ELISA).Results In health control group, the percentage of Th17 cells and the level of IL-17 in subgroup D [(17.12 ± 4.90) ％ and (45.735±10.012) pg/ml] were significantly higher than those in subgroup A, B, C (P ＜ 0.05), and there was no difference in each other subgroup A, B, C (P ＞ 0.05).The percentage of Th17 cells and the level of IL-17 in the DLBCL subgroup A were significantly lower than those in health control subgroup A [(0.69±0.24) ％ and (6.012±1.312) pg/ml vs (2.43±0.61) ％ and (8.217±1.681) pg/ml (P ＜ 0.05)].In DLBCL group, after cultured with rituximab, the percentages of Th17 cells in subgroup B, C, D were (2.34±0.48) ％, (2.31±0.53) ％ and (16.92±4.81) ％, and the levels of IL-17 were (7.944±1.538) pg/ml, (7.957±1.533) pg/ml and (44.417±9.881) pg/ml, respectively, which were all significantly higher than those in subgroup A.Besides, the percentage of Th17 cells and the level of IL-17 in DLBCL subgroup D were significantly higher than those in subgroup B, C (P ＜ 0.05), while there was no difference between subgroup B and subgroup C.Conclusion Experiments in vitro confirmed that the percentage of Th17 cells in PBMCs of DLBCL patients was lower than that in healthy persons, and rituximab could elevate the percentage of Th17 cells in PBMCs of DLBCL patients.

There are many discussions and researches on the positive role of security and negative role of insecurity. However, from the view of biology and evolution, insecurity should be exist when people were born. It makes human to think, then produce relevant behaviors. Just these thinking and behaviors produce culture, maintain psychological individual balance and realize personal value.

Objective To explore the effect of recombinant human granulocyte colony stimulating factor (rhG-CSF) mobilization on TH17/Treg cells and its impact on suppressor of cytokine signaling-3 (SOCS3) gene expression in CD4+ T cells in donors' peripheral blood.Method Sixteen donors were injected subcutaneously with rhG-CSF 5 μg/kg every day for 5 consecutive days for peripheral blood stem cells mobilization.At the first 0,3,5 day,the mononuclear cclls (MNCs) in peripheral blood or graft and serum specimens were taken.The CD4 + T cells in MNCs were sorted using immuno-magnetic beads.The ratio of TH 17 and Treg cells in MNCs,cytokines concentrations of IL-17A,IL-21,ID23 and TGFβ1 in serum,and SODC3 gene expression in CD4+ T cells were detected by using flow cytometry,ELISA,and reverse transcription real-time quantitative PCR (RT-qPCR),respectively.Results (1)The ratio of Th17 cells (CD3+ CD8 CD17+) and Treg cells (CD4+ CD25+ Foxp3+) in MNCs in peripheral blood and graft at the first 0,3 and 5 days after mobilization was (2.69 ± 0.81) ％,(0.91 ± 0.33) ％,(0.35 ± 0.12) ％,(0.21 ± 0.05) ％,and (0.56 ± 0.24) ％,(0.72 ± 0.22％),(1.59 ± 0.54) ％,(3.38 ± 0.52) ％,respectively,showing a significant declining and increasing trend respectively (P＜0.05); (2)The cytokine concentrations in serum at the first 0,3 and 5 days after mobilization were 7.33 ± 0.89,5.78 ± 1.03 and 3.32 ± 0.84 μg/L for IL-17A; 124.56 ± 15.18,117.12 ± 14.45 and 64.94 ± 11.25 μg/L for IL-21 ; 183.52 ± 59.35,280.49 ± 69.75 and 393.62 ± 57.25μg/L for TGF-β1 (P＜0.01) ; and 45.89 ± 6.95,46.25 ± 7.44 and 47.45 ± 10.75 μg/L for IL-23,respectively.The IL-17A and IL-21 concentrations showed significant declining trend,contrarily TGF-β1 with an increasing trend,while IL-23 concentration had no change.After rhG-CSF mobilization,the SOCS3 gene expression in CD4 + T cells of peripheral blood and graft at the first 0,3,5 days was gradually increased.Conclusion rhG-CSF suppresses Th17 cells and promotes regulatory T cells generation,meanwhile decreases IL-17A and IL-21 and elevates serum TGF-β1 concentrations,and contributes to CD4 + T cells differentiation to Tregs,probably by elevating SOSC3 gene expression in CD4+ T cells.

Objective To explore clinical features of chemotherapy-induced graft-versus-host disease and to observe the dynamical changes of Th17/Treg ratio and related cytokines in one relapsed acute T-lymphoblastic leukemia after allo HSCT.Methods Twenty health volunteers were healthy controls.One patient achieved complete haematologic remission after two courses of chemotherapy and underwent matched HLA identical sibling allogenic peripheral blood stem cell transplantation,donor cell implanted state,disease recurrence and graft-versus-host disease were observed and Th17/Treg cells and its related factors in the peripheral blood were detected in different periods dynamically changes by methods of flow cytometry and ELISA.Results The patient achieved complete donor chimerism (FDC) at day +27 after transplantation.Hematopoietic function was fully recovered at day +34.Chronic GVHD (cGVHD) occurred at day +110.Thereafter,extramedullary relapse occurred in cGVHD state at day +264.After one course of Hyper-CVAD chemotherapy,patient complicated overlap syndrome with cGVHD of oral cavity ulcer and degree Ⅳ intestinal aGVHD at day +294 and day +347,respectively.Th17 cell ratio in CD+4 T cells (1.7 ％) in the overlap syndrome slightly increased,compared with control group [(0.56±0.35) ％].The ratio of Treg cells in CD+4 T cells (4.66 ％) with cGVHD increased compared with normal control group [(0.59±0.33) ％],recurrence (0.39 ％),and hematopoietic stem cell implantation (1.15 ％),but the ratio of Treg cells increased significantly when patient complicated overlap syndrome (7.83 ％).The ratios of Th17/Treg were more than 1 at relapse stage and less than 1 at GVHD stage.The IL-17A level in serum significantly increased in cGVHD (6.114 pg/ml)and overlap syndrome (6.805 pg/ml) stage compared with normal control group [(5.19±0.77) pg/ml].TGF-β1 levels were significantly higher at different periods after transplantation compared with control group [(48.81±4.9) ng/ml].Conclusion Chemotherapy can induce GVHD in relapsed acute leukemia patients after hematopoietic stem cell transplantation,and the imbalance of the Th17/Treg cells and its cytokines maybe related with disease relapse and GVHD.

Objective To understand the changes of Th17 cells and related cytokines in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab and its significances.Methods Patients were assigned to 4 groups,there were 20 cases in the control group,31 cases in the initial treatment group,31 cases in CHOP group and 25 cases in RCHOP group.The percentage of Th17 cells in the peripheral blood of each group was tested by flow cytometry,the related cytokines IL-17,IL-21,IL-23,TGF-β in the peripheral blood were measured by enzyme-linked immunosorbent assay.Results The percentage of Th17 cells and the levels of IL-17,IL-21,IL-23 in the initial treatment group [(0.67±0.21) ％,(5.929±1.342) pg/ml,(130.632±17.945)pg/ml,(51.681±9.808) pg/ml] and the CHOP-CR group [(1.07±0.37) ％,(6.526±0.538) pg/ml,(132.119±7.700)pg/ml,(50.245±7.668) pg/ml] were both significantly lower than those in the control group[(2.53±0.63) ％,(8.435±2.031) pg/ml,(149.265±12.316) pg/ml,(55.303±7.778) pg/ml] (P ＜ 0.05).The level of TGF-β in the initial treatment group [(370.615±98.444) pg/ml] was significantly higher than that in the control group [(311.895±73.365) pg/ml] (P ＜ 0.05).The percentage of Th17 cells and the levels of IL-17,IL-21,IL-23 in the RCHOP-CR group [(2.38±0.59) ％,(7.724±0.780) pg/ml,(148.412±7.355) pg/ml,(55.668±7.532) pg/ml] were significantly higher than those in the initial treatment group [(0.67±0.21) ％,(5.929±1.342) pg/ml,(130.632±17.945) pg/ml,(51.681±9.808) pg/ml] and the CHOP-CR group [(1.07±0.37) ％,(6.526±0.538) pg/ml,(132.119±7.700) pg/ml,(50.245±7.668) pg/ml] (P ＜ 0.05).The level of TGF-β in the RCHOP-CR group[(283.904±59.223) pg/ml] was significantly lower than that in the CHOP-CR group [(341.481±95.597) pg/ml] (P ＜ 0.05).Conclusion Th17 cells might be negatively correlated with the DLBCL development,the reduced IL-23 and elevated TGF-β might suppress the differentiation of Th17 cells.Rituximab could elevate the percentage of Th17 cells in DLBCL patients,and it is related with the effect of chemotherapy.