1.Bioinformatics Reveals Mechanism of Xiezhuo Jiedu Precription in Treatment of Ulcerative Colitis by Regulating Autophagy
Xin KANG ; Chaodi SUN ; Jianping LIU ; Jie REN ; Mingmin DU ; Yuan ZHAO ; Xiaomeng LANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):166-173
ObjectiveTo explore the potential mechanism of Xiezhuo Jiedu prescription in regulating autophagy in the treatment of ulcerative colitis (UC) by bioinformatics and animal experiments. MethodsThe differentially expressed genes (DEGs) in the colonic mucosal tissue of UC patients was obtained from the Gene Expression Omnibus (GEO), and those overlapped with autophagy genes were obtained as the differentially expressed autophagy-related genes (DEARGs). DEARGs were imported into Metascape and STRING, respectively, for gene ontology/Kyoto Encyclopedia of Genes and Genomics (GO/KEGG) enrichment analysis and protein-protein interaction (PPI) analysis. Finally, 15 key DEARGs were obtained. The core DEARGs were obtained by least absolute shrinkage and selection operator (LASSO) regression and receiver operating characteristic curve (ROC) analysis. The CIBERSORT deconvolution algorithm was used to analyze the immunoinfiltration of UC patients and the correlations between core DEARGs and immune cells. C57BL/6J mice were assigned into a normal group and a modeling group. The mouse model of UC was established by free drinking of 2.5% dextran sulfate sodium. The modeled mice were assigned into low-, medium-, and high-dose Xiezhuo Jiedu prescription and mesalazine groups according to the random number table method and administrated with corresponding agents by gavage for 7 days. The colonic mucosal morphology was observed by hematoxylin-eosin staining. The protein and mRNA levels of cysteinyl aspartate-specific proteinase 1 (Caspase-1), cathepsin B (CTSB), C-C motif chemokine-2 (CCL2), CXC motif receptor 4 (CXCR4), and hypoxia-inducing factor-1α (HIF-1α) in the colon tissue were determined by Western blot and real-time fluorescence quantitative polymerase chain reaction, respectively. ResultsThe dataset GSE87466 was screened from GEO and interlaced with autophagy genes. After PPI analysis, LASSO regression, and ROC analysis, the core DEARGs (Caspase-1, CCL2, CTSB, and CXCR4) were obtained. The results of immunoinfiltration analysis showed that the counts of NK cells, M0 macrophages, M1 macrophages, and dendritic cells in the colonic mucosal tissue of UC patients had significant differences, and core DEARGs had significant correlations with these immune cells. This result, combined with the prediction results of network pharmacology, suggested that the HIF-1α signaling pathway may play a key role in the regulation of UC by Xiezhuo Jiedu prescription. The animal experiments showed that Xiezhuo Jiedu prescription significantly alleviated colonic mucosal inflammation in UC mice. Compared with the normal group, the model group showed up-regulated protein and mRNA levels of caspase-1, CCL2, CTSB, CXCR4, and HIF-1α, which were down-regulated after treatment with Xiezhuo Jiedu prescription or mesalazine. ConclusionCaspase-1, CCL2, CTSB, and CXCR4 are autophagy genes that are closely related to the onset of UC. Xiezhuo Jiedu prescription can down-regulate the expression of core autophagy genes to alleviate the inflammation in the colonic mucosa of mice.
2.Associations between serum NLRP3, NEK7 level and pulmonary fibrosis among patients with coal workers' pneumoconiosis
HUANG Jingying ; HANG Wenlu ; BO Yun ; ZUO Shurun ; XIN Lihong ; ZHAO Jie
Journal of Preventive Medicine 2025;37(8):827-831
Objective:
To explore the association between serum nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), NIMA-related kinase 7 (NEK7) and pulmonary fibrosis among patients with coal workers' pneumoconiosis, so as to provide a basis for the assessment of the degree of pulmonary fibrosis.
Methods:
Coal workers with pneumoconiosis hospitalized in the Second Affiliated Hospital of Xuzhou Medical University from July 2022 to July 2023 were selected by simple random sampling. Data such as age, stage of pneumoconiosis, and dust-exposure duration were collected through the hospital's electronic medical record management system. Venous blood was collected to detect the levels of serum NLRP3 and NEK7. High-resolution computed tomography (HRCT) image data of the chest were obtained through the hospital's imaging reporting system. The left and right lungs were divided into 6 pulmonary regions according to the upper, middle, and lower parts. The pulmonary fibrosis score was quantified according to the proportion of the pulmonary area occupied by HRCT manifestations of pulmonary fibrosis, including reticular shadows, pleural and interlobular septal thickening, traction bronchiectasis, and honeycombing. The association between the levels of serum NLRP3, NEK7, and pulmonary fibrosis was analyzed using a multiple linear regression model.
Results:
A total of 81 patients with coal workers' pneumoconiosis were included, all of whom were male, with a mean age of (71.46±11.69) years. There were 48, 28, and 5 cases in stage Ⅰ, stage Ⅱ, and stage Ⅲ of pneumoconiosis pathological staging, accounting for 59.26%, 34.57%, and 6.17%, respectively. There were 45 cases of tunneling and coal mining, accounting for 55.56%. There were 41 cases with dust exposure years of ≥30 years, accounting for 50.62%. The median serum NLRP3 and NEK7 in patients with coal workers' pneumoconiosis were 2.01 (interquartile range, 2.33) ng/mL and 0.98 (interquartile range, 0.83) ng/mL. The median score of pulmonary fibrosis was 5.00 (interquartile range, 5.50) points. After adjusting for age, stage of pneumoconiosis, type of work and dust-exposure duration, multiple linear regression analysis showed that serum NLRP3 (β'=0.649) and NEK7 (β'=0.346) were positively correlated with the pulmonary fibrosis score.
Conclusion
The increase in the levels of serum NLRP3 and NEK7 in patients with coal workers' pneumoconiosis is related to the increase in the degree of pulmonary fibrosis.
3.The protective effect of icaritin on D-galactose-induced TM4 cell junctional function damage
Zhi-Li YAO ; Hai-Xia ZHAO ; Xiao-Yu MA ; Guo-Qing FU ; Jie WU ; Lai-Xin SONG ; Chang-Cheng ZHANG
Chinese Pharmacological Bulletin 2024;40(9):1634-1641
Aim To investigate the mechanism of icar-itin(ICT)on D-galactose(D-gal)-induced TM4 ser-toli cell junctional function damage in vitro.Methods TM4 cells were divided into the normal control group and D-gal treatment group with different concentra-tions.The expression changes of TM 4 cell junction function-related proteins(ZO-1,Occludin,β-catenin and Cx43)and ERα/FAK signaling pathway-related proteins(ERα,FAK and pY397-FAK)were detected by Western blot.The concentration of ICT was screened by MTT method.TM4 cells were divided into normal control group,D-gal treatment group,and D-gal treatment+different concentrations of ICT group.The expression levels of the above proteins were detected by Western blot.Molecular docking was used to study the interaction between ERα and ICT,meanwhile predict the affinity between them.Finally,TM4 cells were di-vided into normal control group,D-gal treatment group,ERα inhibitor group,D-gal+ICT group,and ERα inhibitor+ICT group.The expression levels of the above proteins were detected by Western blot.Re-sults Compared with the normal control group,the ex-pression of junctional function-related proteins(ZO-1,Occludin,β-catenin and Cx43)and ERα/FAK signa-ling pathway-related proteins(ERα,FAK and pY397-FAK)were significantly down-regulated.After treat-ment with ICT,the expression of above proteins were significantly up-regulated.The docking results of ERα and ICT molecules revealed the formation of two hydro-gen bonds between Asp351 amino acid residue of ERα and ICT,with bond distances measuring 3.4? and 2.4?.Additionally,the docking binding energy be-tween them was found to be lower than-7 kcal·mol-1.After TM4 cells were treated with ERα inhibi-tor,the expression of above proteins and ERα/FAK signaling pathway-related proteins were significantly down-regulated,while the expression levels of the a-bove proteins did not change significantly after being given ICT protected group.Conclusions D-gal can cause damage to the junctional function of TM4 cells,and ICT can improve this damage,which may be related to the up-regulation of ERα/FAK signaling pathway.
4.Construction,identification and efficiency detection of CX3CR1GFP reporter gene mice
Xin-Xin ZHAO ; Rong HUANG ; Lu-Yun CHEN ; Chun-Mei HUANG ; Jia-Jie TU ; Xin-Ming WANG
Chinese Pharmacological Bulletin 2024;40(12):2392-2398
Aim To construct CX3CR1GFP transgenic mice based on the Cre/Loxp system,and to analyze the expression efficiency of CX3CR1GFP.Methods Targeted vectors were designed using restriction enzyme-based cloning technology to create a linearized targeted vector for transfecting embryonic stem cells(ES).The ES cells with a deletion of the neomycin resistance gene(neo)were then cloned into blastocysts to generate chimeric CX3CR1+/GFPmice.These mice were subsequently bred with wild-type mice(WT),and repeated backcrossing was performed to obtain CX3CR1GFP/GFP mice.DNA and mRNA from WT and CX3CR1GFP mice were extracted and genotyped using agarose gel electrophoresis.The expression level of CX3CR1 in various tis-sues of the mice was detected by RT-qPCR.Western blot analy-sis was used to analyze the expression of GFP protein in periph-eral blood mononuclear cells(PBMC)and various tissues.The labeling efficiency of immune cells in bone marrow was detected by flow cytometry.The expression of GFP in different mouse tis-sues was observed by immunofluorescence.Results The results of agarose gel electrophoresis showed that the transgenic mouse genotype was CX3CR1GFP/GFP homozygote.RT-qPCR and West-ern blot showed that EGFP were targeted to replace CX3CR1 gene,so CX3CR1 expression was very low in CX3CR1GFP mice,while GFP expression was significantly upregulated.Flow cytom-etry and immunofluorescence showed that GFP effectively marked CX3CR1GFP mice,expressed in various tissues and cells with different expression levels.Conclusion This study con-structs and identifies the CX3CR1GFP genetic reporter mice,and GFP is stably expressed in mice,which provides a foundation for further research into the potential mechanisms of CX3CR1 in im-mune regulation.
5.Interpretation of Nursing Standards for Clinical Operation Techniques in Critical Care Ultrasound
Mingxi ZHAO ; Jianhua SUN ; Hongbo LUO ; Zunzhu LI ; Xin LI ; Jie JING ; Qing ZHANG ; Xinjuan WU ; Xiaoting WANG
Chinese Journal of Modern Nursing 2024;30(5):584-588
This paper interprets the background, content overview and characteristics, clinical practice significance and disciplinary development of Nursing Standards for Clinical Operation Techniques in Critical Care Ultrasound (hereinafter referred to as the Standards) and puts forward reflections on the clinical application of the Standards, aiming to improve the critical care ultrasound techniques of clinical nursing staff, solve nursing challenges and make clinical nursing ultrasound techniques more scientific, standardized and homogenized.
6.Construction of a practical training course system for critical ultrasound nursing
Jianhua SUN ; Mingxi ZHAO ; Hongbo LUO ; Zunzhu LI ; Jie JING ; Xin LI ; Jinbang LIU ; Xiaoting WANG
Chinese Journal of Modern Nursing 2024;30(23):3117-3122
Objective:To comprehensively search and summarize the evidence on critical ultrasound nursing practice training courses, with the aim of providing a basis for critical ultrasound nursing practice training.Methods:Taking the evidence-based clinical translation model of Fudan University Centre for Evidence-based Nursing as the theoretical framework, the evidence was retrieved, evaluated, and summarized to determine the evidence to be introduced into clinical practice, forming a training program for critical ultrasound nursing practice. From July to August 2023, 25 experts from 10 provinces/municipalities across the country were selected for two rounds of consultation to determine the practical training course system for critical ultrasound nursing.Results:A total of 14 articles were included, including one clinical decision, nine expert consensus, and four systematic reviews. In the two rounds of consultation, the positive coefficients of experts were 90.0% (27/30) and 92.6% (25/27), the authority coefficients of experts were 0.956 and 0.964, and the coefficients of Kendall's harmony were 0.303 and 0.350 ( P<0.01), respectively. The final practical training course system for critical ultrasound nursing included five first-level indicators, 25 second-level indicators, and 67 third-level indicators. Conclusions:Ultrasound examination is a complex skill. The construction method of the practical training course system for critical ultrasound nursing is scientific, reasonable, with strong practicality in content, which can provide reference for the development and evaluation of critical ultrasound nursing training courses.
7.The Preventive Effect of Levofloxacin Combined with G-CSF or Only G-CSF Supportive Therapy on Infection in Autologous Hematopoietic Stem Cell Transplantation
Xin-Wei WANG ; Li-Ping YANG ; Qiong YAO ; Jie ZHAO ; Shao-Long HE ; Liang-Ming MA ; Jun-Ni WEI ; Wei-Wei TIAN
Journal of Experimental Hematology 2024;32(3):906-910
Objective:To investigate the role of levofloxacin combined with recombinant human granulocyte colony-stimulating factor(G-CSF)or only G-CSF supportive therapy in preventing infection in autologous hematopoietic stem cell transplantation(ASCT),and to analyze the length of hospital stay,hospitalization cost and post-transplant survival of the patients.Methods:A retrospective analysis was performed in the patients with hematological malignancies who accepted ASCT at our hospital from January 2012 to July 2022,the febrile neutropenia,the incidence of bacterial infection and the use rate of intravenous antibiotics in the levofloxacin+G-CSF group and only G-CSF support group during ASCT were observed.The length of hospital stay,total cost during hospitalization and survival after 90 days of transplantation between the two groups were compared.Results:A total of 102 cases were included in this study,including 57 cases of multiple myeloma,36 cases of acute leukaemia,7 cases of lymphoma,3 cases of myelodysplastic syndrome,1 case of light chain amyloidosis,and 1 case of POEMS syndrome.47 patients received levofloxacin+G-CSF antibacterial prophylaxis,and 55 patients received G-CSF supportive therapy.In the levofloxacin+G-CSF group,40 cases(85.11%)developed febrile neutropenia,and 13 cases(27.66%)were confirmed as bacterial infection.In the G-CSF group,44 cases(80.00%)developed febrile neutropenia,and 16 cases(29.09%)were bacterial infection.There was no statistically significant difference in the incidence of febrile neutropenia and bacterial infection between the two groups(x2=0.46,P=0.50;x2=0.03,P=0.87).The use rate of intravenous antibiotics in the levofloxacin+G-CSF group was 85.11%(40/47),which was not statistically different from 85.45%(47/55)in the G-CSF group(X2=0.04,P=0.84).The detection rates of levofloxacin-resistant bacteria in the levofloxacin+G-CSF group and G-CSF group were 8.57%(3/35)and 21.43%(6/28),respectively,with no statistical difference(x2=0.65,P>0.05).The median length and median cost of hospitalization in the levofloxacin+G-CSF group and G-CSF group were 25 d vs 22 d and 78 216.24 yuan vs 80 724.38 yuan,with no statistically significant differences(t=3.00,P=0.09;t=0.94,P=0.09).Within 90 days after transplantation,two cases(4.26%)died in the levofloxacin+G-CSF group and one case(1.82%)died in the G-CSF group,with no statistically significant difference between the two groups(x2=0.53,P=0.47).Conclusion:Application of levofloxacin+G-CSF showed no significant benefit compared to G-CSF support for the prevention of bacterial infections during ASCT.
8.Clinical Significance of the Levels of Peripheral Blood Tregs and Cytokines IL-35,TGF-β and IL-10 in Hemophilia A Patients with FⅧ Inhibitor
Hong-Xia HE ; Yan-Yan XIE ; Qing-Yun SUN ; Lin-Hong WANG ; Yi-Wen ZHU ; JIE LI ; Xin WANG ; Zhao-Ling DENG ; Mei-Rong YANG ; Zhen-Yu YAN
Journal of Experimental Hematology 2024;32(4):1197-1200
Objective:To explore the levels of regulatory T cells(Tregs)and cytokines IL-35,TGF-β and IL-10 in peripheral blood of hemophilia A(HA)patients with F Ⅷ inhibitor and their clinical significance.Methods:43 HA patients admitted to the Hematology Department of the Affiliated Hospital of North China University of Science and Technology from October 2019 to December 2020 were selected,including 6 cases with F Ⅷ inhibitor and 37 cases without FⅧ inhibitor.In addition,20 healthy males who underwent physical examinations were selected as healthy controls.Flow cytometry was used to detect the levels of CD4+CD25+CD127-Tregs in peripheral blood of the HA patients and healthy controls,and ELISA assay was used to detect the expression levels of IL-35,TGF-β and IL-10 in serum,and their differences between different groups were compared.Results:Compared with the healthy control group,the level of Tregs in HA patients was decreased,and the level of Tregs in the FⅧ inhibitor positive group was the lowest,the difference was statistically significant(P<0.05).There was no significant difference in the expression level of Tregs in HA patients of different severity levels.The serum IL-35,TGF-β,and IL-10 levels in both FⅧ inhibitor negative and positive groups were significantly lower than those in healthy control group,and those in FⅧ inhibitor positive group were significantly lower than those in FⅧ inhibitor negative group(all P<0.05).Conclusion:The decrease of Tregs,IL-35,TGF-β,and IL-10 levels in HA patients may be related to the formation of FⅧ inhibitors.
9.Clinical Characteristics and Risk Factors of Infection in Hospitalized Patients with Multiple Myeloma with New Generation Therapies
Li-Ping YANG ; Xin-Yi LU ; Xin-Wei WANG ; Qiong YAO ; Lin-Yu LI ; Jie ZHAO ; Shao-Long HE ; Wei-Wei TIAN
Journal of Experimental Hematology 2024;32(6):1790-1797
Objective:To evaluate the clinical characteristics and risk factors of infections occurring during hospitalization in patients with multiple myeloma (MM) treated with new generation therapies (including immuno-modulatory drugs,proteasome inhibitors and monoclonal antibodies).Methods:The clinical data were collected from 155 patients with multiple myeloma who were treated in Shanxi Bethune Hospital from March,2017 to March,2022 and were retrospectively analyzed.For this study,the following therapies were considered to be new generation therapies:lenalidomide,pomadomide,bortezomib,ixazomib,daratumumab. The clinical characteristics and risk factors of infection were analyzed.Results:A total of 155 patients were included in this study.The median follow-up time was 20 months.Of 155 patients with MM,242 infection episodes were identified.Among the 242 infections,the incidence of clinically defined infection (CDI)was the highest (186,76.86%),followed by microbiologically defined infection (MDI)in 50 cases (20.66%),and fever at unknown focus (FUF)in 6 cases (2.48%).35 cases (14.46%)of bacteria,10 cases (4.13%)of viruses,and 5 cases (2. 07%)of fungi were clearly infected.The most common site of infection was the lower respiratory tract in 90 cases (37.19%),the upper respiratory tract in 83 cases (34.30%),and the digestive tract in 27 cases (11.16%).All-cause mortality was 8.39%(13/155).In univariate analysis,there was a higher correlation between ISS stage Ⅲ,the number of treatment lines ≥2,frail and infected patients with multiple myeloma.In multivariate analysis,ISS stage Ⅲ(OR=2.96,95%CI:1.19-7.40,P=0.02),the number of treatment lines ≥2 (OR=2.91,95%CI:1.13-7.51,P=0.03)and frail (OR=3.58,95%CI:1.44-8.89,P=0. 01)were risk factors for infection in patients with multiple myeloma in the era of new drugs.Conclusion:Patients with multiple myeloma treated with new agents are prone to bacterial infection during hospitalization.ISS stage Ⅲ,lines of therapy(≥2)and frail were associated with high risk for infection.
10.Comparison of patient trust patterns between tertiary hospitals and primary healthcare institutions:A mixed research based on interviews and survey experiment
Xi-Yang TONG ; Hong-Yu LI ; Jun SU ; Jin-Xin ZHANG ; Shi-Chao ZHAO ; Xiao-Jie SUN
Chinese Journal of Health Policy 2024;17(4):38-44
Objective:This study utilizes a hybrid research design,integrating interviews with experimental surveys,to investigate the variances in patient trust models between tertiary hospitals and primary healthcare institutions.Methods:Thirty-eight residents participated in semi-structured interviews,which were then analyzed using content analysis.The experimental survey segment divided participants into two groups:"Tertiary Hospitals"and"Primary Healthcare Institutions,"resulting in 648 valid questionnaires.These questionnaires were subjected to variance analysis to assess differences.Results:Patients exhibit greater systemic trust in tertiary hospitals than in primary healthcare facilities,while interpersonal trust is stronger in primary healthcare settings.Suggestions:Therefore,strategies should be developed to bolster systemic trust at the primary level and emphasize the advantages of interpersonal trust.Moreover,specific measures are required to reshape patients'interpersonal trust in tertiary hospitals.


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