ObjectiveTo explore the effects of hypoxia on the migration ability of human oligodendrocyte precursor cells （hOPCs） and its regulatory mechanisms. MethodsBased on the variations in oxygen concentration within the culture system， three experimental groups were set up： the 21%O₂ group （normoxic control group）， the 5%O₂ group， and the 2%O₂ group. The migration ability of hOPCs under normoxia （21%O₂）， 5%O₂， and 2%O₂ conditions was detected through the Transwell migration assay. RT-qPCR， transcriptome sequencing， and flow cytometry were used to detect the expression changes of genes and proteins such as hypoxia-inducible factor 1 alpha （HIF-1α） and chemokine （C-X-C Motif） receptor 4 （CXCR4）. Bioinformatics analysis was combined to analyze the KEGG pathways related to migration， so as to explore the effects of different oxygen concentrations on the migration ability of hOPCs and their possible mechanisms. ResultsHypoxia treatments at concentrations of 5%O₂ and 2%O₂ could both promote the in vitro migration of hOPCs， and the promoting effect of migration was more significant at the 2%O₂ concentration （P<0.001）. After hypoxia treatment， the mRNA expression levels of HIF-1α， CXCR4， etc. in hOPCs significantly increased （P<0.001）. Compared with the 5%O₂ concentration， the expression of CXCR4 in cells was higher at the 2%O₂ concentration （P<0.000 1）. Flow cytometry analysis detection showed that the expression of CXCR4 increased significantly after hypoxia treatment （P<0.01）， and with the decrease of oxygen concentration， its expression level further increased （P<0.000 1）. Ordinary transcriptome sequencing analysis indicated that hypoxia treatment could activate the PI3K-Akt signaling pathway and the Axon guidance pathway. ConclusionHypoxia treatment can enhance the in vitro migration ability of hOPCs， and this effect is negatively correlated with the oxygen concentration. Its mechanism may be related to the up-regulation of the expression of genes such as HIF-1α and CXCR4， and the activation of the migration related signaling pathway including PI3K-Akt signaling pathway and axon guidance pathway.

ObjectiveTo investigate the mechanism of action of modified Chaihu Shugan Powder in the treatment of abnormal gallbladder relaxation in gallbladder cholesterol stone （CS） with liver depression syndrome， and to provide a basis for clinical medication. MethodsMice were given a high-fat lithogenic diet combined with chronic unpredictable mild stress （CUMS） to establish a model of CS. A total of 45 male C57BL/6 mice were randomly divided into blank group （6 mice fed a normal diet） and CS group （39 mice fed a high-fat lithogenic diet）. After CS modeling， the CS group was further randomly divided into four subgroups of CS group， CS liver depression group， traditional Chinese medicine group （treated with modified Chaihu Shugan Powder）， and Western medicine group （treated with ursodeoxycholic acid）， with 9 mice in each group. All subgroups were fed with the high-fat lithogenic diet， and all mice except those in the CS group were given 21 days of CUMS for modeling. Samples were collected after intervention. The serum levels of cholecystokinin （CCK）， liver function parameters， and blood lipid profiles were measured； HE staining was performed for liver and gallbladder tissue； qPCR and Western blot were used to measure the mRNA and protein expression levels of G protein-coupled bile acid receptor 1 （TGR5） and glucagon-likepeptide-1/2 （GLP-1/2） in the intestine and TGR5 and glucagon-like peptide-2 receptor （GLP-2R） in gallbladder； metabolomics methods were used to determine bile acid composition in intestinal contents. The independent-samples t-test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test or the Games-Howell method was used for further comparison between two groups. ResultsCompared with the blank group， the CS group showed significant gallstone formation， bile turbidity， hepatic steatosis， abnormal gallbladder wall structure， and significant increases in anxiety- and depression-like behaviors based on behavioral tests； significant increases in the level of total cholesterol in bile and the serum levels of alanine aminotransferase， aspartate aminotransferase， and low-density lipoprotein and significant reductions in the level of total bile acid （TBA） in bile and the serum levels of CCK and high-density lipoprotein （HDL） （all P<0.05）； significant increases in the mRNA expression levels of GLP-1/2 and TGR5 in the intestine and the protein expression levels of GLP-2R and TGR5 in the gallbladder and significant reductions in the mRNA expression levels of GLP-2R and TGR5 in the gallbladder （all P<0.05）； significant changes in multiple bile acid components in intestinal contents （all P<0.05）. Compared with the CS group， the CS liver depression group had further aggravation of pathological and behavioral manifestations， changes in bile acid composition， significant increases in the protein and mRNA expression levels of TGR5 and GLP-1/2 in the intestine， and significant increases in the protein and mRNA expression levels of TGR5 and GLP-2R in the gallbladder （all P<0.01）. Compared with the CS liver depression group， both treatment groups had an improvement in gallbladder morphology， alleviation of stones and liver injury， and recovery of liver function and blood lipid levels， as well as significant reductions in the protein and mRNA expression levels of TGR5 and GLP-1/2 in the intestine and TGR5 and GLP-2R in the gallbladder （all P<0.05）； the traditional Chinese medicine group showed significant increases in glycodeoxycholic acid （GDCA）， tauro-α-muricholic acid （T-α-MCA）， and taurochenodeoxycholic acid （TCDCA） （all P<0.05）， while the Western medicine group showed significant increases in taurohyodeoxycholic acid， T-α-MCA， TCDCA， GDCA， and glycoursodeoxycholic acid （all P<0.05）. Compared with the Western medicine group， the traditional Chinese medicine group had significantly greater behavioral improvements， significantly higher levels of TBA in bile and serum HDL （both P<0.01）， significant reductions in the protein expression levels of TGR5 and GLP-1/2 in the intestine and TGR5 and GLP-2R in the gallbladder， and a significant reduction in the mRNA expression level of TGR5 in the intestine （all P<0.01）， as well as a significant increase in tauroursodeoxycholic acid and significant reductions in glycoursodeoxycholic acid， taurohyodeoxycholic acid， TCDCA， and taurolithocholic acid （all P<0.05）. ConclusionModified Chaihu Shugan Powder can improve liver function and abnormal gallbladder relaxation in CS with liver depression syndrome by regulating the bile acid-TGR5 axis， thereby exerting the therapeutic effect of soothing the liver， resolving depression， moving Qi， and promoting bile flow.

Objective:To study the prevalence and spatio-temporal distribution characteristics of Keshan disease in Qingyang City, Gansu Province, and provide scientific basis for formulating targeted prevention and control strategies and optimizing resource allocation.Methods:The data of patients with Keshan disease from January 2022 to December 2024 were obtained from the Qingyang Center for Disease Control and Prevention, and the population data were obtained from the Statistics Bureau of Qingyang City. Global and local spatial autocorrelation analysis was performed using GeoDa 1.16.0 software to identify four spatial clustering areas: high-high, low-low, low-high, and high-low. Spatio-temporal aggregation analysis was conducted using SaTScan 10.1.3 software.Results:The prevalence rates of Keshan disease in Qingyang City from 2022 to 2024 were 7.11/100 000, 6.68/100 000, and 6.14/100 000, respectively. Global spatial autocorrelation analysis showed that the prevalence rates of Keshan disease in Qingyang City from 2022 to 2024 showed a positive spatial correlation (Moran′s I > 0, Z > 1.96, P < 0.05), with the highest spatial correlation in 2024 (Moran′s I = 0.46, Z = 8.02, P = 0.001). Local spatial autocorrelation analysis showed that from 2022 to 2024, the number of townships (towns) exhibiting high-high clusters of Keshan disease in Qingyang City was 15, 11, and 11, respectively. These clusters were primarily concentrated in the southeastern townships (towns) of Qingyang City that boder the Ziwu Mountain. Low-low clusters were primarily concentrated in most townships (towns) of Zhenyuan County and Xifeng District of Qingyang City, as well as some townships (towns) in the northwest of Huachi County. Spatio-temporal scanning analysis showed that the high prevalence rate cluster was concentrated in 2022, covering 44 townships (towns) in 5 counties, mainly distributed in the southeast of Qingyang City. The low prevalence rate cluster was concentrated in 2024, covering 26 townships (towns) in 3 counties (districts), and distributed in the western of Qingyang City. Conclusion:There is a significant spatial clustering of Keshan disease in Qingyang City, and the high prevalence rate cluster is located in the southeast of Qingyang City, which is a key area for prevention and control of Keshan disease in the future.

Objective:To explore the clinical application value of MRI ultra-short echo time sequence (MRI-UTE) in the diagnosis of pulmonary nodules.Methods:This study was a cross-sectional study. A total of 101 consecutive patients were recruited prospectively from January to August 2024 at Huazhong Fuwai Hospital of Zhengzhou University. All of the included patients were diagnosed with pulmonary nodules by chest CT examination and intended for treatment. All patients underwent low-dose CT examination and MRI-UTE examination. The number, classification, and lung imaging reporting and data system (lung-RADS) grading of the pulmonary nodules were analyzed. Nodules classification was determined as solid nodules or sub-solid nodules, and sub-solid nodules included part-solid nodules and pure ground-glass nodules. Taking the evaluation results of radiologists with 10 and 12 years of experience in chest imaging diagnosis as the reference standard, the Kappa test was used to analyze the agreement of CT and MRI-UTE in terms of the accurate diagnosis, classification, and lung-RADS grading of pulmonary nodules. Results:Among the 101 patients, a total of 216 pulmonary nodules were identified. MRI-UTE accurately diagnosed 180 pulmonary nodules, while 203 pulmonary nodules were detected by CT. The concordance was moderate ( Kappa=0.48, P<0.001). In terms of nodule classification, CT correctly classified 167 nodules as solid and 36 as sub-solid, whereas MRI-UTE correctly classified 153 as solid and 23 as sub-solid, with good agreement (weighted Kappa=0.73, P<0.001). For lung-RADS grading, CT correctly graded 186 nodules, with 85 graded as category 2, 46 as category 3, 33 as category 4A, 12 as category 4B, and 10 as category 4X; MRI-UTE correctly graded 155 nodules, with 74 graded as category 2, 30 as category 3, 30 as category 4A, 12 as category 4B, and 9 as category 4X. The agreement between the two modalities in determining lung-RADS grade was also good (weighted Kappa=0.74, P<0.001). Conclusion:MRI-UTE demonstrates good agreement with CT in the accurate diagnosis, classification, and lung-RADS grading of pulmonary nodules, indicating certain clinical application value.

BACKGROUND:Compared with conventional repetitive transcranial magnetic stimulation,Theta burst transcranial magnetic stimulation(TBS)has attracted extensive attention from scholars in various fields due to its advantages of short stimulation time,high efficiency,good safety and long-lasting effect,and the research popularity continues to rise.OBJECTIVE:Through the visual bibliometrics analysis of international TBS research in the past 20 years,to sort out the development context of TBS research,summarize the research status,reveal research hotspots and development trends,and provide reference for subsequent research.METHODS:Relevant studies on TBS from January 2005 to June 2024 were searched in the Web of Science Core Collection database.CiteSpace software was used to perform annual publication volume analysis,co-occurrence analysis of countries,institutions and authors,and co-citation analysis of references,journals and authors,keywords co-occurrence,clustering,time evolution and emergence analysis,and so on,and draw the visual knowledge map.RESULTS AND CONCLUSION:(1)After screening,a total of 1914 papers were included in the study,and the amount of TBS research has shown an overall increasing trend over the past 20 years,and it is expected to continue to be a hot topic of research in the future.(2)The top three countries in terms of number of publications are the United States,China and Italy,and the top three institutions are the University of Toronto,the University of London and Harvard Medical School.Pascual-leone Alvaro from Harvard Medical School has the most research achievements,and HUANG YZ from Chang Gung University has the most citations.NEURON is the most influential core journal.(3)Analyses of high-frequency keywords,highly cited references and clustering topics showed that the research hotspots of TBS in the past 20 years mainly focus on the mechanism of TBS on synaptic plasticity and neurophysiological activity,the effect of TBS on stimulating targets in different brain regions(including the motor cortex,dorsolateral prefrontal cortex,anterior cingulate cortex and cerebellum,etc.),and the therapeutic effect of TBS on neurological and psychiatric diseases(including depression,Parkinson's disease movement disorder,post-stroke movement disorder and cognitive impairment,and Alzheimer's disease memory disorders).(4)Keyword burst,literature emergence and keyword temporal evolution analyses showed that"major depression,application guidelines,rating scale,efficacy,disorder,refractory depression,meta-analysis,etc."are not only current research hotspots,but also future research trends.(5)In the future,TBS research should strengthen the regional cooperation of core authors and institutions,explore the clinical application in the treatment of refractory diseases,and realize the precision,personalization and optimization of TBS application by combining cutting-edge technologies and optimizing stimulus parameters,so as to solve more clinical problems.

BACKGROUND:Compared with conventional repetitive transcranial magnetic stimulation,Theta burst transcranial magnetic stimulation(TBS)has attracted extensive attention from scholars in various fields due to its advantages of short stimulation time,high efficiency,good safety and long-lasting effect,and the research popularity continues to rise.OBJECTIVE:Through the visual bibliometrics analysis of international TBS research in the past 20 years,to sort out the development context of TBS research,summarize the research status,reveal research hotspots and development trends,and provide reference for subsequent research.METHODS:Relevant studies on TBS from January 2005 to June 2024 were searched in the Web of Science Core Collection database.CiteSpace software was used to perform annual publication volume analysis,co-occurrence analysis of countries,institutions and authors,and co-citation analysis of references,journals and authors,keywords co-occurrence,clustering,time evolution and emergence analysis,and so on,and draw the visual knowledge map.RESULTS AND CONCLUSION:(1)After screening,a total of 1914 papers were included in the study,and the amount of TBS research has shown an overall increasing trend over the past 20 years,and it is expected to continue to be a hot topic of research in the future.(2)The top three countries in terms of number of publications are the United States,China and Italy,and the top three institutions are the University of Toronto,the University of London and Harvard Medical School.Pascual-leone Alvaro from Harvard Medical School has the most research achievements,and HUANG YZ from Chang Gung University has the most citations.NEURON is the most influential core journal.(3)Analyses of high-frequency keywords,highly cited references and clustering topics showed that the research hotspots of TBS in the past 20 years mainly focus on the mechanism of TBS on synaptic plasticity and neurophysiological activity,the effect of TBS on stimulating targets in different brain regions(including the motor cortex,dorsolateral prefrontal cortex,anterior cingulate cortex and cerebellum,etc.),and the therapeutic effect of TBS on neurological and psychiatric diseases(including depression,Parkinson's disease movement disorder,post-stroke movement disorder and cognitive impairment,and Alzheimer's disease memory disorders).(4)Keyword burst,literature emergence and keyword temporal evolution analyses showed that"major depression,application guidelines,rating scale,efficacy,disorder,refractory depression,meta-analysis,etc."are not only current research hotspots,but also future research trends.(5)In the future,TBS research should strengthen the regional cooperation of core authors and institutions,explore the clinical application in the treatment of refractory diseases,and realize the precision,personalization and optimization of TBS application by combining cutting-edge technologies and optimizing stimulus parameters,so as to solve more clinical problems.

BACKGROUND:Oligodendrocyte precursor cells are seed cells for the treatment of white matter damage diseases.Establishing an efficient and stable in vitro differentiation method is an important prerequisite for clinical translational research.OBJECTIVE:To investigate the effect of fibronectin on biological characteristics such as proliferation,migration,and differentiation of oligodendrocyte precursor cells derived from human neural stem cells.METHODS:Human neural stem cells cultured in suspension were digested into single cells using Accutase.The expression of specific markers Nestin,Sox2,Vimentin,CD133,and Musashi was detected by flow cytometry.The single cells of human neural stem cells were resuspended in oligodendrocyte precursor cell medium and seeded in six-well plates coated with different concentrations of fibronectin(0,1,2.5,5,and 10 μg/mL).Accutase digestion was performed after 7 days of culture.Cells were counted by trypan staining.Fibronectin-coated group with the strongest amplification ability and the oligodendrocyte precursor cells without fibronectin-coated group were selected for further tests.The migration ability of the two groups of cells was detected by Transwell.Flow cytometry was used to detect the expression of Olig2,Sox10,and PDGFR-α.Oligodendrocyte precursor cells were induced to differentiate into oligodendrocytes for 3 weeks,and the expression of Galc in differentiated cells was detected by immunofluorescence staining.RESULTS AND CONCLUSION:(1)H uman neural stem cells grew in suspension spheres.Flow cytometry showed that human neural stem cells highly expressed Nestin,Sox2,Vimentin,CD133,and Musashi.(2)The cell bodies of oligodendrocyte precursor cells induced by human neural stem cells were round or oval,with strong refractive nature and bipolar or tertiary protrusions.Compared with the 0 μg/mL fibronectin coating group,there was a significant difference in the amplification ability of oligodendrocyte precursor cells in the 2.5,5,and 10 μg/mL fibronectin coating groups(P＜0.05).The amplification ability of oligodendrocyte precursor cells was the strongest when the fibronectin concentration was 10 μg/mL.(3)Flow cytometry results showed that the oligodendrocyte precursor cell markers 0Iig2,Sox10,and PDGFR-α were highly expressed in the 0 and 10 μg/mL fibronectin coating groups,and there was no significant difference between the two groups(P＞0.05).(4)Transwell chamber assay results showed that compared with the 0 μg/mL fibronectin-coated group,the migration ability of oligodendrocyte precursor cells in the 10 μg/mL fibronectin-coated group was increased(P＜0.01).(5)After 3 weeks of differentiation into oligodendrocytes,oligodendrocyte precursor cells showed complex morphology with multiple branches,grids or membrane sheets.Immunofluorescence staining results showed that there was no statistical difference in the Galc positive rate of oligodendrocytes between the two groups(P＞0.05).These findings indicate that when the concentration of fibronectin coated well plate is 10 μg/mL,the proliferation and migration of oligodendrocyte precursor cells are the strongest,but it does not affect the expression of oligodendrocyte precursor cells-specific markers Olig2,Sox10,and PDGFR-α and their differentiation into oligodendrocytes.

AIM:We investigated the survival,migration and differentiation abilities of human oligodendro-cyte precursor cells(hOPC)in the brains of mice with vascular dementia(VaD),the effects of hOPC on cerebral white matter,and the underlying mechanisms.METHODS:Mouse VaD model was constructed using the bilateral common ca-rotid artery stenosis method,and the mice were randomly divided into sham,VaD and hOPC groups.Eight weeks after model establishment,the mice in VaD and hOPC groups received equal volume of vehicle(PBS)and hOPC solution,re-spectively,through the corpus callosum.Survival,migration and differentiation of hOPC in the brain were observed by im-munofluorescence staining at 4 and 12 weeks after transplantation.Twelve weeks after transplantation,the effects of hOPC on mouse brain white matter were detected by immunofluorescence staining of myelin basic protein(MBP),myelin-associ-ated glycoprotein(MAG),neurofilament protein 200(NF200)and non-phosphorylated neurofilament H(using monoclo-nal antibody SMI32),and by water maze experiments.Paracrine signaling by hOPC was explored using immunofluores-cence staining for vascular endothelial growth factor(VEGF).RESULTS:The hOPC survived in the brains of VaD mice for 12 weeks,migrated to damaged white matter areas,and partially differentiated into mature oligodendrocytes(approxi-mately 64%).Twelve weeks after transplantation,hOPC significantly increased the fluorescence intensity of MBP,MAG,and NF200(P<0.05 or P<0.01)and decreased the fluorescence intensity of SMI32(P<0.01).The VEGF expression in hOPC-treated mice was significantly higher than that in sham and VaD groups(P<0.01).The difference in water maze test performance between hOPC and sham groups was not statistically significant(P>0.05).The mice in hOPC group had a shorter latency than those in VaD group(P<0.05 or P<0.01),and performed more platform crossings than those in VaD group(P<0.05).CONCLUSION:The hOPC can survive,migrate and differentiate in the brains of VaD mice,attenuate cerebral white matter lesions,and improve cognitive function.These improvements may be attributed to cell replacement and paracrine effects.

Objective To analyze the risk factors of multi-drug resistant bacterial infection of urinary system in type 2 diabetes mellitus(T2DM)patients and establish a decision tree model.Methods A total of 371 patients with T2DM were selected and divided into infected(IF,n=47)group and non-infected(NIF,n=324)group.The influencing factors of multi-drug resistant urinary system infection were analyzed in patients with T2DM.IBM SPSS Modeler was used to establish a decision tree model for predicting multi-drug resistant urinary system infection.Results The infection rate of multidrug resistant bacteria in urinary system was 12.67%.Age,female proportion,DM duration,use of antibiotics before admission,length of hospital stay,and hemoglobin A1c(HbA1c)in IF group were higher than that in NIF group(P<0.05).Logistic regression analysis showed that age≥60 years old(OR 2.629,95%CI 1.349～5.125,P=0.005),woman(OR 3.044,95%CI 1.506～6.151,P=0.002),DM duration≥10 years(OR 3.320,95%CI 1.671～6.593,P=0.001),length of hospital stay>15 days(OR 2.406,95%CI 1.237～4.682,P=0.010)and HbA1c>8.02%(OR 2.363,95%CI 1.210～4.617,P=0.012)were influencing factors for multidrug-resistant bacteria infection of urinary system.Decision tree model showed that sex was the most important factor in urinary multidrug-resistant infections.Receiver operating characteristic curve results showed that the area under the curve value of Logistic regression model was slightly higher than that of decision tree(Z=1.465,P=0.143).Conclusions Age,sex,DM duration,length of hospital stay,and HbA1c are the influencing factors of T2DM patients complicated with urinary multi-drug resistant bacteria infection,the decision tree model established in this study has good risk prediction efficiency,which is helpful for early clinical identification of high-risk patients with multi-drug resistant bacteria infection of urinary system.

Traditional manual testing of ventilator performance is labor-intensive, time-consuming, and prone to errors in data recording, making it difficult to meet the current demands for testing efficiency in the development and manufacturing of ventilators. Therefore, in this study we designed an automated testing system for essential performance parameters of ventilators. The system mainly comprises a ventilator airflow analyzer, an automated switch module for simulated lungs, and a test control platform. Under the control of testing software, this system can perform automated tests of critical performance parameters of ventilators and generate a final test report. To validate the effectiveness of the designed system, tests were conducted on two different brands of ventilators under four different operating conditions, comparing tidal volume, oxygen concentration, and positive end expiratory pressure accuracy using both the automated testing system and traditional manual methods. Bland-Altman statistical analysis indicated good consistency between the accuracy of automated tests and manual tests for all respiratory parameters. In terms of testing efficiency, the automated testing system required approximately one-third of the time needed for manual testing. These results demonstrate that the designed automated testing system provides a novel approach and means for quality inspection and measurement calibration of ventilators, showing broad application prospects.
Ventilators, Mechanical/standards* ; Equipment Design ; Humans ; Automation