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.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective To investigate the current situation of the attitude and practical ability of hospice care in the terti-ary cancer hospital of Zhejiang Province,so as to provide reference for managers to explore more effective hospice care support.Methods Using convenience sampling selected 278 clinical nurses from Zhejiang Cancer Hospital.From June to August 2024,the general data questionnaire,hospice care attitude scale and self-assessment practice scale of hospice care were used to survey nurses with questionnaires,and the related factors affecting practical ability and the correlation between attitudes and practical a-bility were analyzed.Results The hospice attitude score of 278 nurses in the hospice co-photography mode was(88.43±12.01),and the average score of entries was(3.54±0.48).The total score of the hospice Practical ability scale was(61.87±12.42),and the average score of the items was(3.64±0.73).Nurses'age,education background,previous experience in ca-ring for end-stage patients and their families,and self-assessment of competence in hospice care were the main influencing factors of nurses'practical ability score(all P＜0.05).There was a positive correlation between clinical nurses'practice ability score and hospice attitude score,the correlation coefficient r=0.176,P＜0.05.Conclusion Under the mode of hospice co-care,the attitude of nurses in Zhejiang Province is above the middle level,and the practical ability of nurses needs to be further improved,the higher the attitude of nurses,and the nurses'practical ability of hospice care is strong.Nursing managers should carry out professional training to promote the attitude of nursing staff,so as to improve the practical ability of nurses in hospice care.

Objective: To investigate the distribution patterns and risk factors for multidrug-resistant bacterial pulmonary infections in patients with oral squamous cell carcinoma (OSCC) undergoing flap reconstruction surgery, and to provide evidence for infection prevention and treatment in this population. Methods: This study was approved by the institutional medical ethics committee. We retrospectively analyzed sputum culture results, antimicrobial susceptibility testing data, and clinical records of 109 OSCC patients undergoing flap reconstruction. Chi-square tests were employed to identify pathogens and risk factors for multidrug-resistant bacteria (MDR) in postoperative pulmonary infections. Multivariate logistic regression analysis was conducted to determine MDR risk factors and establish a nomogram prediction model. The model’s discriminatory power, accuracy, and clinical utility were evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results: Among the 109 patients, 52 had negative sputum cultures and 57 tested positive, of whom 14 developed multidrug-resistant (MDR) pulmonary infections. Chi-square analysis revealed that blood transfusion, pre-existing pulmonary diseases, operation time ≥ 490 min, intraoperative blood loss ≥ 400 mL, and abnormal BMI were significant risk factors for postoperative MDR infections (P < 0.05). Multivariate logistic regression identified pre-existing pulmonary diseases, intraoperative blood loss ≥ 400 mL, abnormal BMI, and operative duration ≥ 490 min as independent risk factors for MDR infections (P < 0.05). The nomogram prediction model for MDR infections demonstrated an area under the ROC curve (AUC) of 0.874 (95% CI: 0.775-0.973). The calibration plot showed good agreement between predicted and observed outcomes. DCA indicated a net clinical benefit when the threshold probability for high-risk MDR infections ranged from 0.000 to 0.810. Common MDR pathogens included MDR Pseudomonas aeruginosa, MDR Klebsiella pneumoniae, carbapenem-resistant Acinetobacter baumannii (CRAB), and methicillin-resistant Staphylococcus aureus (MRSA). Conclusion Among OSCC patients undergoing flap reconstruction, MDR pulmonary infections were predominantly caused by gram-negative bacteria (including CRAB, MDR Pseudomonas aeruginosa, and MDR Klebsiella pneumoniae along with the gram-positive pathogen MRSA. Pre-existing pulmonary comorbidities, prolonged surgery duration (≥ 490 min), significant intraoperative blood loss (≥ 400 mL), and abnormal BMI were confirmed as independent risk factors for these MDR infections. The nomogram predictive model incorporating these four variables demonstrated clinically reliable accuracy in risk stratification for postoperative MDR pulmonary infections in this patient population.

Objective To explore the mechanism by which the sanguis draconis flavones(SDF)regulates the reactive oxygen species(ROS)/thioredoxin-interacting protein(TXNIP)pathway to mediate cell pyroptosis and improve cerebral ischemia-reperfusion injury(CIRI)in rats.Methods The experimental rats were randomly divided into the control group(Ctrl),the CIRI group,the low-dose SDF group(SDF-L),the high-dose SDF group(SDF-H),and the SDF-H+ROS/TXNIP pathway activator,trimethylamine oxide(TMAO)group(SDF-H+TMAO).Among them,except for the control group,the remaining rats all needed to establish the CIRI rat model by the modified suture method.Zea Longa scoring was performed on rats from each group.ELISA was used to detect the levels of serum inflammatory factors interleukin(IL)-1β,IL-18 and oxidative stress-related factors superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px).Flow cytometry was used to measure the ROS levels.Cerebral edema was detected.Cerebral infarction was detected by 2,3,5-triphenyl tetrazolium chloride(TTC)staining.HE staining was used to detect the pathological changes of brain tissue.Immunohistochemistry was used to detect the expression of pyrolytic effector protein dermolin D(GSDMD).Western blotting was used to detect the expression of proteins related to the ROS/TXNIP pathway.Results Compared with the control group,a large area of cerebral infarctions were observed in the brain tissue of the CIRI group,accompanied by mild hemorrhage and obvious infiltration of inflammatory cells.Neuronal cells underwent degeneration and necrosis,with sparse and disordered arrangement.The phenomena of nuclear condensation and nucleolus lysis were obvious.The Zea Longa score,cerebral infarction volume,brain tissue water content,levels of IL-1β,IL-18,ROS,MDA,and the expressions of GSDMD,TXNIP,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),apoptosis-related punctate protein(ASC),and Caspase-1 increased,while the activities of SOD and GSH-Px decreased(P＜0.05).Compared with the CIRI group,the pathological damage of brain tissues in the SDF-L group and the SDF-H group was significantly improved.The Zea Longa score,cerebral infarction volume,brain tissue water content,levels of IL-1β,IL-18,ROS,MDA,and the expressions of GSDMD,TXNIP,NLRP3,ASC,and Caspase-1 decreased.The activities of SOD and GSH-Px increased(P＜0.05);TMAO treatment partially reversed the improvement effect of SDF on CIRI in rats.Conclusion SDF ameliorates cerebral CIRI in rats by inhibiting ROS/TXNIP pathway-mediated pyroptosis.

Objective To analyze the basic conditions and pathological characteristics of the samples in the Human Brain Bank of Hebei Medical University,which were pathologically diagnosed as cerebral amyloid angiopathy,and to provide reference for the research of related diseases.Methods The basic data of gender,age,apolipoprotein E genotype,pathological classification of cerebral amyloid angiopathy,Alzheimer's disease-related pathological change score,comorbidities and other pathological information were analyzed.Results Up to October 2024,twenty samples were confirmed by pathological diagnosis,with a male to female ratio of 3:1 and an average age of(80.90±8.08)years.Involve three kinds of apolipoprotein E subtype,5 kinds of genotypes(ε2/ε3 xε2/ε4、ε3/ε3 xε3/ε4、ε4/ε4);There were 2 pathologic types,including 6 cases of type 1 and 14 cases of type 2.The pathological grade included 3 grades.The severity grade and subtype classification of cerebral amyloid vascular disease were correlated with the degree of pathological changes of Alzheimer's disease.Cerebral amyloid angiopathy samples could coexist with other degenerative diseases with high comorbidity.Conclusion The incidence of cerebral amyloid angiopathy is higher in the aged samples collected based on Brain Bank,which coexists with conditions such as Alzheimer's disease and microbleeds,etc.It provides more detailed pathological diagnosis basis for further scientific research sharing of samples.

The morphological characteristics of hepatocellular carcinoma(HCC)tumor margins are pivotal in influencing patient's prognosis and the selection of therapeutic strategies.This paper re-viewed the classification methods of HCC tumor margins,ranging from traditional macroscopic classifi-cations to refined classification systems based on multi-omics analysis,and analyzed the role of these classification methods in guiding the formulation of personalized treatment plans.Additionally,this paper emphasized the crucial role of three-dimensional imaging techniques in assessing tumor margin morphology and outlined future research directions,including validating the effectiveness of multi-omics classification systems and developing new imaging and molecular biomarkers to achieve more precise treatment plans and prolong patient survival.

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.

Objectives:There is a lack of long-term follow-up study results on severe microvascular complications in a larger Chinese population with diabetes.This study aims to explore long-term impact of newly diagnosed diabetes(NDD)on the incidence and risk of severe microvascular complications.Methods:A total of 598 NDD and 493 normal glucose tolerance(NGT)subjects were included in this study in 1986.By questionnaire and systematic case review,the occurrence of severe microvascular complications,including severe diabetic retinopathy,severe diabetic nephropathy,and severe diabetic neuropathy,was followed up and collected over a period of 34 years.Results:The cumulative incidence of severe microvascular complications in the NDD population was 65.03%(95%CI:58.90%-70.48%)over 34 years,significantly higher than that in the NGT population(16.8%,95%CI:12.64%-20.11%).After adjusting for related risk factors,the risk of severe microvascular complications in the NDD population was 7.08 times than that of the NGT population(HR=7.08,95%CI:5.09-9.84,P<0.0001).Stratified analysis by sex showed that the cumulative incidence and risk of severe microvascular complications were slightly higher in male NDD population(68.02%,95%CI:57.27%-76.61%;HR=9.45,95%CI:5.78-15.47,P<0.0001)than in female NDD population(63.37%,95%CI:55.69%-70.09%;HR=5.86,95%CI:3.75-9.16,P<0.0001);however,the cumulative incidence increased more rapidly in women during the follow-up period of 10-25 years.Conclusions:The incidence and risk of severe microvascular complications in diabetes were significantly higher than those in the NGT population;and the incidence of severe vascular complications increased rapidly after the duration of diabetes exceeded 10 years,indicating that strict control of blood glucose in the early stage of diabetes is of vital importance.

Chrysophanol(Chr)and physcion(Phy)are primary active ingredients of a well-known traditional Chinese medicine namely rhubarb(Chinese name:Dahuang),and their glucuronides have been revealed as the dominant forms presenting in rats after oral administration.Either Chr or Phy has two glycosylation sites,resulting in a pair of positional isomers for glucuronides of either compound(CG1&CG2 and PG1&PG2).To confirmatively identify these glucuronides,energy-resolved mass spectrometry(ER-MS)was used to pursue the fragmentation trajectories of the targeted fragment ions,and the resultant breakdown graphs that were described by the optimal collision energy(OCE)were expected to exhibit the differences of glycosidic bond cleavage between the isomers.Quantum chemical calculation was thereafter conducted to produce the bond dissociation energy(BDE)of the glycosidic bonds.The isomers were unambiguously identified through applying the positive correlation rule between OCE and BDE.Fortunately,the glucuronides of Chr and Phy in vivo were observed through liver microsomes incubationin vitro.ER-MS was utilized to collect the Gaussian-shaped breakdown graphs in response to the neutral loss of 176 Da,and the absolute values of OCE were compared between positional isomers.The results revealed that CG1(-32.31 eV)>CG2(-31.61 eV),and nonetheless,PG1(-30.00 eV)Chr-8-GluA(-48.787 kJ/mol),and nonetheless,Phy-1-GluA(-48.672 kJ/mol)