1.Proportions of memory T cells and expression of their associated cytokines in lymph nodes of mice infected with Echinococcus multilocularis
Yinshi LI ; Duolikun ADILAI ; Bingqing DENG ; Ainiwaer ABIDAN ; Sheng SUN ; Wenying XIAO ; Conghui GE ; Na TANG ; Jing LI ; Hui WANG ; Tao JIANG ; Chuanshan ZHANG
Chinese Journal of Schistosomiasis Control 2025;37(2):136-143
Objective To investigate the effects of Echinococcus multilocularis infection on levels of memory T (Tm) cells and their subsets in lymph nodes of mice at different stages of infection, so as to provide new insights into immunotherapy for alveolarechinococcosis. MethodsTwenty-four C57BL/6J mice aged 6 to 9 weeks were randomly divided into the infection group and the control group, of 12 mice in each group. Mice in the infection group were administered with 3 000 E. multilocularis protoscoleces via portal venous injection, while animals in the control group were administered with an equal volume of physiological saline. Three mice from each group were sacrificed 4, 12 weeks and 24 weeks post-infection, and lymph nodes were sampled and stained with hematoxylin and eosin (HE) to investigate the histopathological changes of mouse lymph nodes in the infection group. The expression and localization of T lymphocyte surface markers CD3, CD4, and CD8 were observed in mouse lymph nodes using immunohistochemical staining. In addition, lymphocyte suspensions were prepared from mouse lymph nodes in both groups at different time points post-infection, and the levels of Tm cell subsets and their secreted cytokines were detected using flow cytometry. Results HE staining showed diffuse structural alterations in the subcapsular cortical and paracortical regions of mouse lymph nodes in the infection group 4 weeks post-infection with E. multilocularis. Immunohistochemical staining detected CD3, CD4 and CD8 expression in mouse lymph nodes in both groups. Flow cytometry revealed higher proportions of CD4+ Tm cells [(55.3 ± 4.8)% vs. (38.8 ± 6.1)%; t = -4.259, P < 0.05] and CD4+ tissue-resident Tm (Trm) cells [(57.7 ± 3.7)% vs. (34.1 ± 11.2)%; t = -3.990, P < 0.05] in mouse lymph nodes in the infection group than in the control group 4 weeks post-infection, and higher proportions of CD4+ Tm cells [(34.6 ± 3.2)% vs. (23.3 ± 7.5)%; t = -2.764, P < 0.05] and CD4+ Trm cells [(44.0 ± 1.9)% vs. (31.2 ± 1.5)%; t = -4.039, P < 0.05] in mouse lymph nodes in the infection group than in the control group 24 weeks post-infection. The proportions of CD8+ Tm cells were higher in the infection group than in the control group 4 weeks [(56.8 ± 2.7)% vs. (43.9 ± 5.2)%; t = -4.416, P < 0.01] and 12 weeks post-infection [(25.4 ± 2.7)% vs. (12.0 ± 2.6)%; t = -2.552, P < 0.05], while the proportions of tumor necrosis factor (TNF)-α+ CD4+ T cells [(15.7 ± 5.0)% vs. (49.4 ± 6.4)%; t = 7.150, P < 0.01], TNF-α+CD8+ T cells [(20.7 ± 5.5)% vs. (57.5 ± 8.4)%; t = -6.694, P < 0.01], and TNF-α+ CD8+ Tm cells [7.0% (1.0%) vs. 31.0% (11.0%); Z = -2.236, P < 0.05] were lower in the infection group than in the control group 24 weeks post-infection. Conclusions Tm cells levels are consistently increased in lymph nodes of mice at different stages of E. multilocularis infection, with Trm cells as the predominantly elevated subset. The impaired capacity of CD8+ Tm cells to secrete the effector molecule TNF-α in mouse lymph nodes at the late-stage infection may facilitate chronic parasitism of E. multilocularis.
2.Carthamus tinctorius L.extract ameliorates alcoholic liver disease by modulating PI3K/Akt/FoxO signaling pathway
Wen-Xuan WANG ; Xiang-Lei FU ; Man QI ; Fu-Rong FAN ; Fu-Rong ZHU ; Yuan-Chuang WANG ; Kai-Yue ZHANG ; Min LIU ; Sheng-Hui CHU
Chinese Pharmacological Bulletin 2024;40(6):1137-1145
Aim To investigate the effects of Cartham-us tinctorius L.extract(CTLE)on oxidative stress,lipid metabolism,and apoptosis levels of mice with al-cohol-induced liver injury and its mechanism of action.Methods The mouse model of alcohol-associated liver disease was established by chronic alcohol feeding and acute alcohol gavage.Mice were randomly divided into four groups.During the modeling period,the state changes of mice were observed every day,and their weight was recorded.At the end of modeling,blood and liver tissues were collected from each group of mice.The blood of mice was analyzed biochemically,and HE staining and Oil Red O staining were used to evaluate further the degree of pathological damage in the liver of mice.Quantitative real-time PCR(qPCR)and Western blot were applied to detect the mRNA and protein expression levels of p-PI3K,PI3K,p-Akt,Akt,p-mTOR,mTOR,p-FoxO1,FoxO1,p-FoxO3a,FoxO3a,p-FoxO4,FoxO4,BCL and BAX factors.Results Compared to the model group,the CTLE administration group showed improved hepatic patho-logical injury and reduced lipid deposition.The bio-chemical indexes in serum and liver,such as ALT,AST,TG,TC,and MDA levels were reduced,while GSH and SOD levels increased.Regulating the PI3K/Akt/FoxO pathway resulted in increased production of SOD,which reduced damage and apoptosis caused by reactive oxygen species(ROS).Conclusions CTLE can exert anti-oxidative stress and anti-apoptotic effects through the PI3K/Akt/FoxO pathway and attenuates alcoholic liver injury in mice,providing new ideas for the treatment of alcoholic liver disease and the develop-ment of related drugs.
3.LncRNA-CCRR regulates arrhythmia induced by myocardial infarction by affecting sodium channel ubiquitination via UBA6
Fei-Han SUN ; Dan-Ning LI ; Hua YANG ; Sheng-Jie WANG ; Hui-Shan LUO ; Jian-Jun GUO ; Li-Na XUAN ; Li-Hua SUN
Chinese Pharmacological Bulletin 2024;40(8):1437-1446
Aim To investigate the regulatory mecha-nism of arrhythmia of sodium channel ubiquitination af-ter MI and to study the electrophysiological remodeling mechanism of lncRNA-CCRR after MI for the preven-tion and treatment of arrhythmia after MI.Methods LncRNA-CCRR transgenic mice and C57BL/6 mice injected with lncRNA-CCRR overexpressed adeno-asso-ciated virus were used.Four weeks after infection,the left anterior descending branch of the coronary artery was ligated for 12 h to establish a mouse acute myocar-dial infarction model,and the incidence of arrhythmia was detected by programmed electrical stimulation.Ln-cRNA-CCRR overexpression/knockdown adeno-associ-ated virus and negative control were transfected into neonatal mouse cardiomyocytes(NMCMs),and the model was prepared by hypoxia for 12 h.LncRNA-CCRR expression was detected by FISH,Nav1.5 and UBA6 protein and Nav.1.5 mRNA expression were de-tected by Western blot and real-time quantitative poly-merase chain reaction(qRT-PCR),Nav1.5 and UBA6 expressions were detected by immunofluores-cence,and the relationship between lncRNA-CCRR and UBA6 was detected by RIP.INa current density af-ter CCRR overexpression and knockdown was detected by Whole-cell clamp patch.Results In MI mice,the expression of lncRNA-CCRR decreased,the incidence of arrhythmia increased,the expression of CCRR and Nav1.5 mRNA was down-regulated,the protein ex-pression of Nav1.5 was down-regulated,and the pro-tein expression of UBA6 was up-regulated compared with sham group.Overexpression of CCRR could re-verse the above changes.AAV-CCRR could reverse the down-regulated CCRR and Nav1.5 mRNA levels af-ter hypoxia,and improve the expression of Nav1.5 and UBA6 protein.The direct relationship between ln-cRNA-CCRR and UBA6 was identified by RIP analy-sis.The INa density increased after transfection with AAV-CCRR.The INa density decreased after transfec-tion with AAV-si-CCRR.Conclusions The expres-sion of lncRNA-CCRR decreases after MI,and ln-cRNA-CCRR can improve arrhythmia induced by MI by inhibiting UBA6 to increase the protein expression level of Nav1.5 and the density of INa.
4.Progress in study of multifunctionality of DPP4 and mechanism of action of related drug targets
Lei WANG ; Zhi-Hui YANG ; Yang ZHENG ; Ying ZHANG ; Tie-Jian ZHAO ; Wei-Sheng LUO ; Tian-Jian LIANG ; Jia-Hui WANG
Chinese Pharmacological Bulletin 2024;40(12):2212-2217
DPP4 is a serine exopeptidase that is immobilized on the cell membrane and plays a crucial regulatory role in various physiological and pathological activities within the human body.In addition to acting as a transcription factor to regulate the tran-scription and expression of downstream target genes,DPP4 also functions as a transcription-independent regulator through pro-tein-protein interactions.In recent studies,DPP4 has been strongly linked to various diseases,and several substances with the potential to target DPP4 have been identified.This paper mainly reviews the multifunctionality of DPP4 in regulating vari-ous aspects of energy metabolism,inflammation,tissue repair and carcinogenesis in the body.It also reviews the screening of in vitro inhibitors of DPP4 and its research progress in regulating chronic liver disease,based on the pathological development process of chronic liver disease.
5.Accuracy and clinical efficacy of robot-assisted transiliac-transsacral screw placement for posterior pelvic ring frac-tures
Xue-Lin WANG ; Zheng-Jie WU ; Yan-Hui ZENG ; Can-Hui LI ; Jian-Sheng ZHOU ; Shi HONG
China Journal of Orthopaedics and Traumatology 2024;37(6):605-608
Objective To explore accuracy and clinical effect of robot-assisted implantation of sacroiliac penetrating screw in orthopedic surgery for posterior pelvic ring fracture.Methods The clinical data of 24 patients with posterior pelvic ring frac-ture treated with robot-assisted sacroiliac penetration screws from August 2022 to August 2023 were retrospectively analyzed,including 10 males and 14 females;aged from 21 to 73 years old with an average of(49.29±14.48)years old;according to Tile pelvic fractures,13 patients were type B and 11 were type C.The effect of screw placement was evaluated according to Gras criteria based on postoperative CT scan results.At the final follow-up,fracture healing was evaluated according to Matta score,and functional recovery was evaluated by Majeed score.Results All patients were followed up for 3 to 13 months with an aver-age of(6.00±3.28)months.Totally 36 sacroiliac penetrating screws,18 S1 penetrating screws,18 S2 penetrating screws were inserted,a total of 29 were excellent and 7 good according to Gras standard.Screw adjustment times was 0.00(0.00,0.75)times.At the final follow-up,Matta score was excellent in 18 patients,5 good and 1 moderate,and the maximum displacement distance was 2.55(0.00,5.65)mm.Majeed score was 84.37±8.38,15 patients were excellent,7 good and 2 moderate.Con-clusion Robot could accurately and safely assist in the placement of sacroiliac joint screws for the treatment of posterior pelvic ring fractures,and promote postoperative functional recovery of patients.
6.The Role of NK Cells in Allogeneic Hematopoietic Stem Cell Micro-Transplantation for Acute Myeloid leukemia
Ru-Yu LIU ; Chang-Lin YU ; Jian-Hui QIAO ; Bo CAI ; Qi-Yun SUN ; Yi WANG ; Tie-Qiang LIU ; Shan JIANG ; Tian-Yao ZHANG ; Hui-Sheng AI ; Mei GUO ; Kai-Xun HU
Journal of Experimental Hematology 2024;32(2):546-555
Objective:To explore the role of NK cells in allogeneic hematopoietic stem cell micro-transplantation(MST)in the treatment of patients with acute myeloid leukemia(AML).Methods:Data from 93 AML patients treated with MST at our center from 2013-2018 were retrospectively analyzed.The induction regimen was anthracycline and cytarabine combined with peripheral blood stem cells transplantation mobilization by granulocyte colony stimulating factor(GPBSC),followed by 2-4 courses of intensive treatment with medium to high doses of cytarabine combined with GPBSC after achieving complete remission(CR).The therapeutic effects of one and two courses of MST induction therapy on 42 patients who did not reach CR before transplantation were evaluated.Cox proportional hazards regression analysis was used to analyze the impact of donor NK cell dose and KIR genotype,including KIR ligand mismatch,2DS1,haplotype,and HLA-Cw ligands on survival prognosis of patients.Results:Forty-two patients received MST induction therapy,and the CR rate was 57.1%after 1 course and 73.7%after 2 courses.Multivariate analysis showed that,medium and high doses of NK cells was significantly associated with improved disease-free survival(DFS)of patients(HR=0.27,P=0.005;HR=0.21,P=0.001),and high doses of NK cells was significantly associated with improved overall survival(OS)of patients(HR=0.15,P=0.000).Donor 2DS1 positive significantly increases OS of patients(HR=0.25,P=0.011).For high-risk patients under 60 years old,patients of the donor-recipient KIR ligand mismatch group had longer DFS compared to the nonmismatch group(P=0.036);donor 2DS1 positive significantly prolonged OS of patients(P=0.009).Conclusion:NK cell dose,KIR ligand mismatch and 2DS1 influence the therapeutic effect of MST,improve the survival of AML patients.
7.Effectiveness of payment method reform for traditional Chinese medicine advantageous diseases:An empirical study from city S based on interrupted time series analysis
Xiao-Yu ZHANG ; Li-Li WANG ; Shi-Wen ZHANG ; Hui-Wen ZHANG ; Sheng JI ; Li-Mei JING
Chinese Journal of Health Policy 2024;17(10):17-22
Objective:To empirically assess the effectiveness of the payment reform for traditional Chinese medicine(TCM)advantageous diseases and provide a scientific foundation for optimizing the payment method in TCM.Methods:Data on TCM cases of patients discharged from January 2022 to August 2023 were collected from all TCM hospitals piloting the payment reform for TCM advantageous diseases in city S.Cases were screened according to the TCM disease codes of the 22 pilot diseases.An interrupted time series model was constructed based on the time point of reform implementation to analyze the effect of the reform in the pilot hospitals vertically.Additionally,the model compared the differences in effect between second-and third-tier TCM hospitals horizontally.Results:In secondary hospitals,the bed day cost increased by 219.05 yuan during the reform period,and both the average hospitalization cost per admission and average TCM cost per admission showed an upward trend after the reform.In tertiary hospitals,the average out-of-pocket cost per admission and bed day cost decreased following the reform,while the average length of hospital stay and average TCM cost per admission increased.These trends were more pronounced in comparison to secondary hospitals.Conclusion:The reform effects varied across different hospital levels.It is recommended to dynamically adjust the payment standards for disease categories,establish differentiated evaluation metrics,and continuously monitor the long-term outcomes of the reform to further optimize the payment methods for TCM advantageous diseases.
8.Network pharmacology-based strategy for predicting therapy targets of apigenin on thyroid carcinoma
Shu-Bin LIANG ; Zhen LI ; Sheng-Nan WANG ; Yun-Hui WANG
Chinese Journal of Current Advances in General Surgery 2024;27(8):594-598
Objective:To explore the potential therapeutic targets of apigenin in the treat-ment of thyroid carcinoma by network pharmacology.Methods:The targets of apigenin were screened by HIT(High Throughput),Binding Database,SEA(Similarity Ensemble Approach),STITCH(Search Tool for Interactions of Chemicals),PharmMapper.Thyroid carcinoma related targets were mined from TTD(Therapeutic Target Database),DrugBank,CTD(Comparative Toxicogenomics Da-tabase),DisGeNET databases.The String database and Cytoscape 3.2.1 software were used to identify and screen out the hub targets of apigenin for thyroid carcinoma.The David database was used for Gene Ontology(GO)enrichment and KEGG signal pathway enrichment analysis of hub tar-gets.Finally,the Kaplan-Meier Plotter database was used to analyze the prognosis of hub targets.Results:175potential targets of apigenin and 168 potential targets related to thyroid carcinoma were included.37 overlapping targets of apigenin and thyroid carcinoma were obtained.32 hub targets were finally selected by network topology analysis.These hub targets of apigenin in the treatment of thyroid carcinoma were mainly enriched in involving HIF-1 signaling pathway,path-ways in cancer,etc.Finally,8 targets were screened to be associated with the survival and prog-nosis of thyroid carcinoma patients.Conclusion:Our study suggested that ALB,CCNA2,CCND1,CYP2C19,TERT,TTR,BCL2,CBR1 might be potential therapeutic targets for apigenin in the treatment of thyroid carcinoma.
9.Construction and application of fourth-level surgery composite evaluation index of tertiary public hospitals: fourth-level surgery contribution degree
Juan YAN ; Xiaoyu ZHAO ; Hui DAI ; Sheng HUANG ; Weizhong ZHANG ; Xiaodong WANG
Chinese Journal of Hospital Administration 2024;40(8):599-603
Objective:To construct a composite evaluation index of fourth-level surgical, for references for horizontal comparison of fourth-level surgical between clinical departments of hospital and hospital performance appraisal.Methods:The data were extracted from the medical record information system and disease diagnosis related group information system of a tertiary public hospital, including the number of surgical patients, the number of fourth-level surgical patients, the case mix index (CMI), and the average length of hospital stay for 23 surgical departments from 2019 to 2023. Based on disease diagnosis related groups, the average length of hospital stay for patients undergoing fourth-level surgery was standardized to obtain the time cost index; Multiply the CMI and time cost index by the fourth-level surgical ratio to obtain the quality coefficient. This coefficient was used to weight the number of fourth-level surgeries to establish the contribution degree of fourth-level surgeries, which was used for the comprehensive evaluation of fourth-level surgery quality and quantity for each surgical department.Results:A total of 329 177 surgical patients were included in this study, including 139 704 patients with fourth-level surgery. From 2019 to 2023, the top 3 departments in terms of the proportion of fourth-level surgery were department J, B and A, and the proportion of fourth-level surgery in departments with high surgical difficulty, such as C and I, ranked 8th and 16th. The top 3 departments with the contribution degree of fourth-level surgery were department A, B and C, I rosed to the 9th, and J felled to the 11th.Conclusions:The fourth-level surgery contribution degree combined the four factors of surgical composition, difficulty, cost and quantity, which could objectively evaluate fourth-level surgeries in different departments.
10.Research on the regulation of the MAPK signaling pathway by Suzi Jiangqi decoction to improve the inflammatory state of COPD patients
Xuxing YE ; Shuangshuang MA ; Lin SHENG ; Hui CHEN ; Xiaobo WANG
China Modern Doctor 2024;62(32):82-86,126
Objective To explore the impact of Suzi Jiangqi decoction(SJD)on the inflammatory state of patients with chronic obstructive pulmonary disease(COPD)through the regulation of the mitogen-activated protein kinase(MAPK)signaling pathway.Methods A total of 70 patients with stable COPD,treated from April 2023 to April 2024 at the Department of Traditional Chinese Medicine and Department of Respiratory outpatient clinic of Affiliated Jinhua Hospital,School of Medicine Zhejiang University were selected and randomly divided into observation group and control group,with 35 cases in each group.The control group received tiotropium bromide powder inhalation combined with budesonide/formoterol powder inhalation treatment,while the observation group was given SJD in addition to treatment of control group.After 12 weeks of treatment,the therapeutic effects were evaluated by assessing lung function,airway mucus hypersecretion,levels of interleukin(IL)-17,IL-6,and tumor necrosis factor(TNF)-α,CT quantitative parameters of the lung,as well as the expression levels of IL-17,p38MAPK,nuclear factor kappa-B(NF-κB)and C-X-C motif chemokine ligand 8(CXCL8)mRNA in sputum.Results Following treatment,there was a significant improvement in lung function indicators such as first second expiratory volume/forced vital capacity%,cough score,sputum difficulty score,sputum quality score,and sputum volume score for patients in both groups,with more pronounced improvements observed in observation group(P<0.05).The levels of serum cytokines IL-17,IL-6 and TNF-αdecreased in both groups after treatment,with observation group showing a more significant reduction(P<0.05).Additionally,the percentage ratio of low attenuation area to lung area(LAA%),emphysema index of lung CT in observation group significantly decreased after treatment(P<0.05).Similarly,the expression levels of IL-17,p38MAPK,NF-κB and CXCL8 mRNA in sputum were also significantly reduced after treatment in observation group(P<0.05).Conclusion SJD may improve lung function and inflammatory status in COPD patients by regulating the MAPK signaling pathway mediated by IL-17,demonstrating a positive therapeutic effect on the treatment of COPD.

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