Objective:To analyze the expression of zinc homeostasis-related genes and related cells in the intestinal mucosa of inflammatory bowel disease (IBD) patients at the single-cell level and to evaluate their value in predicting the response to anti-tumor necrosis factor (TNF) therapy in IBD patients.Methods:Single-cell RNA sequencing data from 75 ileal or colorectal biopsy samples, including those from patients with Crohn's disease (CD), ulcerative colitis (UC), and normal controls (NC), were collected from four gene expression omnibus (GEO) databases. Unsupervised clustering analysis in R language was employed to classify IBD cells, zinc homeostasis-related gene scores were used to assess the zinc homeostasis status of different cell clusters, and the cell clusters closely related to zinc homeostasis-related genes, namely metallothionein-associated macrophages (MT Mph), were identified. Then the colon tissues from IBD patients and healthy individuals treated at the First Affiliated Hospital of Sun Yat-sen University were collected for immunofluorescence (IF) staining to compare the differences in MT Mph numbers between IBD and NC tissues. To further explore the function and origins of MT Mph, the characteristic genes of MT Mph and non- metallothionein-associated macrophages (non-MT Mph) from database were compared, the Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis was further used to enrich the characteristic genes, cell communication analysis was used to investigate the communication mechanisms between MT Mph and different cells, Quasi-time sequence was used to explore the origin of MT Mph and related signaling pathways, and the differences in transcription factors among monocytes, MT Mph and non-MT Mph were analyzed in R language. Single sample gene set enrichment analysis (ssGSEA) was used to evaluate the expression of MT Mph characteristic genes, and ssGSEA combined with the response to anti-TNF were used to construct the model in order to explore the predictive value of MT Mph characteristic genes for the response to anti-TNF therapy in IBD patients.Results:IBD cells were clustered and annotated into seven major cell clusters, namely T cells, B cells, plasma cells, myeloid cells, fibroblasts, endothelial cells, and epithelial cells. The results of zinc homeostasis-related gene scores showed that the scores of IBD myeloid cells were higher than those of the NC group. Myeloid cells could be divided into monocytes, macrophages, neutrophils, and dendritic cells. Based on the expression of zinc homeostasis genes, especially the high expression of metallothionein genes, the macrophages were divided into MT Mph and non-MT Mph, and the number of MT Mph in the IBD intestine was significantly increased compared to the NC group. IF validation showed that the number of CD68 +MT1G + cells (MT Mph) in both UC and CD were significantly higher than that in the NC group under per high-power field of view (UC vs. NC: 30.80 ± 7.29 vs. 9.80 ± 1.80, P < 0.001; CD vs. NC: 36.00 ± 9.30 vs. 9.80 ± 1.80, P < 0.001). KEGG pathway enrichment analysis revealed that the differential genes of MT Mph were enriched in key genes of inflammation-related pathways, especially the TNF signaling pathway. Cell communication analysis showed that the TNF signaling pathway between MT Mph and other cells in IBD was significantly enhanced compared to NC. Quasi-time sequence analysis results showed that monocytes could differentiate into MT Mph, and the expression of metallothionein genes ( MT2A, MT1X, MT1H and MT1G) was significantly upregulated during the differentiation process. Transcription factor analysis showed that the transcription factors SMARCB1 and ZMYND8 of MT Mph were significantly higher than those of monocytes, and the classical inflammatory transcription factors HIF1A, STAT3, and NFKB1 were significantly higher than those of non-MT Mph. Prediction models for CD and UC were constructed respectively based on ssGSEA and TNF treatment response [CD: area under the curve (AUC) = 0.966, P < 0.01; AUC = 0.793, P < 0.01]. Validation results showed that the model could not predict the response of CD and UC patients to vedolizumab therapy (both P > 0.05). Conclusions:There is a zinc homeostasis imbalance in IBD intestine, and MT Mph are a group of cells with high expression of zinc homeostasis-related genes, which are closely related to the TNF inflammatory pathway. The prediction model constructed based on the characteristic genes of MT Mph may be able to predict the response to anti-TNF therapy in IBD.

Objective:To analyze the expression of zinc homeostasis-related genes and related cells in the intestinal mucosa of inflammatory bowel disease (IBD) patients at the single-cell level and to evaluate their value in predicting the response to anti-tumor necrosis factor (TNF) therapy in IBD patients.Methods:Single-cell RNA sequencing data from 75 ileal or colorectal biopsy samples, including those from patients with Crohn's disease (CD), ulcerative colitis (UC), and normal controls (NC), were collected from four gene expression omnibus (GEO) databases. Unsupervised clustering analysis in R language was employed to classify IBD cells, zinc homeostasis-related gene scores were used to assess the zinc homeostasis status of different cell clusters, and the cell clusters closely related to zinc homeostasis-related genes, namely metallothionein-associated macrophages (MT Mph), were identified. Then the colon tissues from IBD patients and healthy individuals treated at the First Affiliated Hospital of Sun Yat-sen University were collected for immunofluorescence (IF) staining to compare the differences in MT Mph numbers between IBD and NC tissues. To further explore the function and origins of MT Mph, the characteristic genes of MT Mph and non- metallothionein-associated macrophages (non-MT Mph) from database were compared, the Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis was further used to enrich the characteristic genes, cell communication analysis was used to investigate the communication mechanisms between MT Mph and different cells, Quasi-time sequence was used to explore the origin of MT Mph and related signaling pathways, and the differences in transcription factors among monocytes, MT Mph and non-MT Mph were analyzed in R language. Single sample gene set enrichment analysis (ssGSEA) was used to evaluate the expression of MT Mph characteristic genes, and ssGSEA combined with the response to anti-TNF were used to construct the model in order to explore the predictive value of MT Mph characteristic genes for the response to anti-TNF therapy in IBD patients.Results:IBD cells were clustered and annotated into seven major cell clusters, namely T cells, B cells, plasma cells, myeloid cells, fibroblasts, endothelial cells, and epithelial cells. The results of zinc homeostasis-related gene scores showed that the scores of IBD myeloid cells were higher than those of the NC group. Myeloid cells could be divided into monocytes, macrophages, neutrophils, and dendritic cells. Based on the expression of zinc homeostasis genes, especially the high expression of metallothionein genes, the macrophages were divided into MT Mph and non-MT Mph, and the number of MT Mph in the IBD intestine was significantly increased compared to the NC group. IF validation showed that the number of CD68 +MT1G + cells (MT Mph) in both UC and CD were significantly higher than that in the NC group under per high-power field of view (UC vs. NC: 30.80 ± 7.29 vs. 9.80 ± 1.80, P < 0.001; CD vs. NC: 36.00 ± 9.30 vs. 9.80 ± 1.80, P < 0.001). KEGG pathway enrichment analysis revealed that the differential genes of MT Mph were enriched in key genes of inflammation-related pathways, especially the TNF signaling pathway. Cell communication analysis showed that the TNF signaling pathway between MT Mph and other cells in IBD was significantly enhanced compared to NC. Quasi-time sequence analysis results showed that monocytes could differentiate into MT Mph, and the expression of metallothionein genes ( MT2A, MT1X, MT1H and MT1G) was significantly upregulated during the differentiation process. Transcription factor analysis showed that the transcription factors SMARCB1 and ZMYND8 of MT Mph were significantly higher than those of monocytes, and the classical inflammatory transcription factors HIF1A, STAT3, and NFKB1 were significantly higher than those of non-MT Mph. Prediction models for CD and UC were constructed respectively based on ssGSEA and TNF treatment response [CD: area under the curve (AUC) = 0.966, P < 0.01; AUC = 0.793, P < 0.01]. Validation results showed that the model could not predict the response of CD and UC patients to vedolizumab therapy (both P > 0.05). Conclusions:There is a zinc homeostasis imbalance in IBD intestine, and MT Mph are a group of cells with high expression of zinc homeostasis-related genes, which are closely related to the TNF inflammatory pathway. The prediction model constructed based on the characteristic genes of MT Mph may be able to predict the response to anti-TNF therapy in IBD.

Objective:The emergence of polymyxin-resistant Klebsiella pneumoniae(KPN)in clinical settings necessitates an analysis of its antibiotic resistance characteristics,epidemiological features,and risk factors for its development.This study aims to provide insights for the prevention and control of polymyxin-resistant KPN infections. Methods:Thirty clinical isolates of polymyxin-resistant KPN were collected from the Third Xiangya Hospital of Central South University.Their antibiotic resistance profiles were analyzed.The presence of carbapenemase KPC,OXA-48,VIM,IMP,and NDM was detected using colloidal gold immunochromatography.Hypervirulent KPN was initially screened using the string test.Biofilm formation capacity was assessed using crystal violet staining.Combination drug susceptibility tests(polymyxin B with meropenem,tigecycline,cefoperazone/sulbactam)were conducted using the checkerboard method.Polymyxin-related resistance genes were detected by PCR.Multi-locus sequence typing(MLST)was performed for genotyping and phylogenetic tree construction.The study also involved collecting data from carbapenem-resistant(CR)-KPN polymyxin-resistant strains(23 strains,experimental group)and CR-KPN polymyxin-sensitive strains(57 strains,control group)to analyze potential risk factors for polymyxin-resistant KPN infection through univariate analysis and multivariate Logistic regression.The induction of resistance by continuous exposure to polymyxin B and colistin E was also tested. Results:Among the 30 polymyxin-resistant KPN isolates,28 were CR-KPN,all producing KPC enzyme.Four isolates were positive in the string test.Most isolates showed strong biofilm formation capabilities.Combination therapy showed additive or synergistic effects.All isolates carried the pmrA and phoP genes,while no mcr-1 or mcr-2 genes were detected.MLST results indicated that ST11 was the predominant type.The phylogenetic tree suggested that polymyxin-resistant KPN had not caused a hospital outbreak in the institution.The use of two or more different classes of antibiotics and the use of polymyxin were identified as independent risk factors for the development of polymyxin-resistant strains.Continuous use of polymyxin induced drug resistance. Conclusion:Polymyxin-resistant KPN is resistant to nearly all commonly used antibiotics,making polymyxin-based combination therapy a viable option.No plasmid-mediated polymyxin-resistant KPN has been isolated in the hospital.Polymyxin can induce resistance in KPN,highlighting the need for rational antibiotic use in clinical settings to delay the emergence of resistance.

Early-stage diagnosis of liver cancer is challenging, with an overall poor prognosis. The tumor microenvironment of primary liver cancer is complex, exhibiting significant heterogeneity both interpersonally and intratumorally. Therefore, it is of paramount importance to dynamically analyze biological markers in the tumor microenvironment of primary liver cancer in vivo. In recent years, significant progress has been made in the imaging diagnosis and treatment of liver cancer with the development of molecular imaging. Molecular imaging techniques utilize specific nano-imaging probes to evaluate pathological changes of liver cancer at the molecular and cellular levels in real-time. These techniques enable precise imaging to reveal key molecular biomarkers involved in the occurrence and progression of liver cancer, exploring their associations with cancer progression and outcomes. This article focuses on molecular imaging, emphasizing the current research status and latest advancements in the field of liver cancer diagnosis and therapy using techniques such as CT, MRI, optical imaging, PET imaging, and multimodal imaging. It also identifies important future directions and significant challenges for further development.

Objective: To analyze the correlation between plasma trough level of generic imatinib and its metabolism and clinical outcomes in Chinese patients with chronic myeloid leukemia in chronic phase (CML-CP) . Methods: The 21 patients with CML-CP who enrolled in a clinical trial YMTN 1.0 from Oct 11^th, 2012 to May 8^th, 2013 and received generic imatinib were as study subjects. The correlation between steady plasma trough levels of imatinib and its metabolism with clinical response, age, weight and body surface area (BSA) were evaluated. Results: ①The mean steady plasma trough level of generic imatinib and its metabolism was (1 185.07±417.91) μg/L and (251.53±76.50) μg/L, respectively. ②Age, weight and BSA has no significant effects on plasma trough level of generic imatinib and its metabolism (P>0.05) . ③Patients with steady plasma trough level of generic imatinib more than 1 000 μg/L are possible to have higher major molecular response (MMR) /complete molecular response (CMR) rate than those below 1 000 μg/L (42% vs 0, P<0.05) . Conclusion Plasma trough levels of generic imatinib varied in CML patients. The steady plasma trough levels of generic imatinib is maybe related to molecular response in CML patients.

Objective To analyze the topological characteristics of the brain structural network in primary angle-closure glaucoma (PACG) patients by applying graph theoretical approaches.Methods From October 2015 to April 2017, nineteen PACG patients and nineteen gender-and age-matched healthy controls (HCs) were enrolled to undergo MRI scan. The whole brain was parceled into 90 regions by automated anatomical labeling template, and the brain structural network was constructed by the fiber distribution of continuous tracking method.Both the weighted and unweighted network analyses were performed.The global and regional properties were computed by graph theoretical analysis.To compare the brain network regional properties between two groups, two-sample t-test was utilized.The correlations between the brain structural network properties and clinical parameters were further analysed. Results Both two groups were found to follow the efficient small-world characteristics. Compared to HCs, the brain structural network in PACG patients showed no statistical significance in the small-worldness, average shortest path, clustering coefficient, global efficiency and local efficiency(P＞0.05). Compared to the HCs, the PACG patients showed decreased nodal efficiency in the right superior frontal gyrus, right inferior frontal gyrus, left median cingulate and paracingulate gyri, left amygdala and left cuneus(P＜0.05). Compared to HCs, the PACG patients showed decreased node degree in left superior frontal gyrus, medial orbital, right inferior frontal gyrus, left amygdala, left cuneus and left lingual gyrus(P＜0.05). Compared with the hub regions in healthy controls'network, we found that two hub regions disappeared.Those hubs were right inferior parietal lobule and left middle temporal gyrus. Node degree in left amygdala showed negatively correlated with visual ability (r=-0.679, P=0.001). Node degree in left lingual gyrus showed negatively correlated with vertical CDR(r=-0.791, P=0.001),which showed positively correlated with visual acuity(r=0.538, P=0.018).Conclusions The brain structural network in PACG patients showed small-worldness properties as HCs group. The alterations of local properties in visual, emotion-cognition brain regions were observed, manifesting that PACG can affect the topology properties of the structural brain network.

By sorting out 2005-2015's literature on the mechanism of acupuncture and moxibustuion treatment for lumbar intervertebral disc herniation, this article concludes that the studies focused mainly on six aspects: improvement in nail fold microcirculation, improvement in neural ultrastructure, regulation of bodily autoimmunity, improvement in hemorheological indicators, regulation of neuroelectrophysiology and regulation of chemical neuroinflamma- tory mediators. A summary is made from the six aspects.

Capsules ; China ; Drugs, Generic ; Humans ; Imatinib Mesylate ; Leukemia, Myeloid, Chronic-Phase

Objective To explore hemopurification clinical nurse specialist's effects and barriers,in order to provide evidences to define their value,to remove their barriers,to promote their effects.Methods A qualitative study was adopted in this study.In-depth interviews were conducted on 3 charge nurses in hemopurification and 10 hemopurification clinical nurse specialists.Results The effects of hemopurification clinical nurse specialist can be concluded as effects to patients,to nursing,to medical systems and to hemopurification clinical nurse specialist themselves.Barriers of hemopurification clinical nurse specialist can be concluded as medical environments,the process of nursing developing,ambiguous role of clinical nurse specialist.Conclusions The practice of hemopurification clinical nurse specialists have played various effects,but there were some barriers in their practice.The roles of clinical nurse specialist should be clarified,and guarantees in managements and regulations should be provided for their practice.

OBJECTIVETo explore the prognostic significance of Ph-positive and/or BCR-ABL positive acute lymphoblastic leukemia (Ph⁺ ALL).

METHODSA retrospective analysis of 72 patients with Ph⁺ ALL to probe prognostic factors including sex, age, high white cell counts at diagnosis, additional chromosome abnormality, BCR-ABL transcripts type, imatinib based therapy, allo-HSCT and complete remission (CR) after one-course induction on the outcomes of Ph⁺ALL patients.

RESULTSOf 72 patients with median age 40.5 (13-68) years, 38 patients received imatinib plus chemotherapy. With median follow-up of 11 (0.2-96) months, total CR rate in patients receiving imatinib plus chemotherapy was higher than of patients receiving chemotherapy only (97.4% vs 62.3%, P=0.019). High white blood counts at diagnosis or additional chromosome abnormality had no effects on CR rate. 2-year overall survival (OS) and disease free survival (DFS) in imatinib plus chemotherapy group were (28.9±7.4) % and (25±7.4) %, respectively, which were higher than those in chemotherapy group (P<0.001). OS rate in HSCT group was significantly higher than that in non-HSCT group[ (61.1±11.5) % vs (5.6±3.1) %, P<0.001]. Multivariate prognostic analysis for OS showed that imatinib-based therapy [RR=0.413 (95% CI 0.237-0.721), P=0.002], allo-HSCT [RR=0.175 (95% CI 0.075-0.389), P=0.000] and CR after one-course induction [RR=0.429 (95% CI 0.245-0.750), P=0.003] were of importance for survival.

CONCLUSIONallo-HSCT was an optimal choice for Ph⁺ALL patients. Imatinib-based therapy could increase CR rate, maintain CR duration and decrease relapse, resulting in more chance of HSCT. Imatinib improved the outcomes of Ph⁺ALL patients who were not eligible for HSCT.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Benzamides ; therapeutic use ; Disease-Free Survival ; Female ; Fusion Proteins, bcr-abl ; antagonists & inhibitors ; Hematopoietic Stem Cell Transplantation ; Humans ; Imatinib Mesylate ; Male ; Middle Aged ; Philadelphia Chromosome ; Piperazines ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; genetics ; therapy ; Prognosis ; Protein Kinase Inhibitors ; therapeutic use ; Pyrimidines ; therapeutic use ; Retrospective Studies ; Young Adult