Purpose Based on multimodal imaging combined with a variety of histological techniques,to visually evaluate the changes of rats brain metabolic microenvironment after cerebral hypoxia and ischemia of prematurity,and to discuss the effects of abnormal lactate metabolism in the brain on oligodendrocyte precursor cells,so as to provide a basis for the early diagnosis and treatment of premature white matter injury(PWMI).Materials and Methods A total of 36 SPF-grade healthy 3-day-old Sprague-Dawley neonatal rats were randomly assigned to the sham surgery(Sham)group and the model(PWMI)group using a random number table method,with 18 rats in each group.A neonatal rat PWMI model was established by hypoxia-ischemia method.Twenty-four hours after modeling,laser speckle imaging was used to monitor cerebral blood flow and blood oxygen changes.Multimodal imaging was used to observe the changes in brain tissue microstructure and metabolism after PWMI.HE staining was used to observe the morphological changes of nerve cells in the white matter of the brain.Enzyme-linked immunosorbent assay was used to detect the changes of lactate content and lactate dehydrogenase activity in the white matter region of the brain after PWMI in neonatal rats.PDGFR-α immunofluorescence staining was used to observe the dynamic changes of the number of oligodendrocyte precursor cells in the subependymal zone after PWMI in neonatal rats.Results Twenty-four hours after modeling,the multimodal imaging results showed that the T2WI and diffusion-weighted imaging on the injured side of the PWMI group showed high intensity,and the relative cerebral blood flow,relative oxygen saturation,relative apparent diffusion coefficient and amide proton transfer(APT)Lorentzian difference value were lower than those in the Sham group(t=29.466,23.522,59.006,54.778,10.263,all P<0.001),and the lactate content was higher than that in the Sham group(t=-7.521,P<0.001).The results of HE staining and enzyme-linked immunosorbent assay showed that the arrangement of nerve cells in the white matter area of the injured side of the brain in the PWMI group was loose and disordered.The lactate content and lactate dehydrogenase activity were higher than those in the Sham group(t=-6.079,-10.548,both P<0.001).The results of immunofluorescence staining showed that the number of PDGFR-α+cells in the subependymal zone of the damaged side of the PWMI group was higher than that of the Sham group at 24 hours after modeling,and lower than that in the Sham group at 11 days after modeling(t=-8.386,6.676,both P<0.001).The correlation analysis between the lactate content and APT Lorentzian difference value in the brain and the number of oligodendrocyte precursor cells in the brain 11 days after modeling showed that the number of oligodendrocyte precursor cells in the subependymal zone was positively correlated with the APT Lorentzian difference value(r=0.821,P=0.001 1),and negatively correlated with the lactate content in the brain(r=-0.880,P=0.000 2).Conclusion Multimodal imaging can monitor the early brain metabolism changes of PWMI in neonatal rats,especially the changes of lactate,and provide a visual basis for their early diagnosis.The level of lactate in the brain increases after cerebral hypoxia and ischemia in prematurity,and oligodendrocyte precursor cells increase transiently and then decrease,resulting in PWMI.

Objective To analyze the relationship between clinical drug utilization and the risk of nosocomial infections among hospitalized patients,and provide evidence for the prevention and control of nosocomial infections.Methods This study adopted a retrospective case-control design.The case group included 209 patients with nosocomial infection reported from January 2023 to December 2023 in a tertiary hospital.The control group included 209 patients without nosocomial infection during the same period.The patients in the control group were selected by stratified sampling based on Charlson Comorbidity Index(CCI).Results Univariate analysis showed that proton pump inhibitors,antacids,immunosuppressants and prior antimicrobial combination therapy increased the risk of nosocomial infection(P＜0.05).Multivariate log-binomial regression analysis showed that proton pump inhibitors,immunosuppressive drugs,and prior antimicrobial combination therapy were correlated with nosocomial infection.The corresponding relative risk(RR)was 1.31(95％CI:1.07-1.60),1.40(95％CI:1.02-1.91),and 1.66(95％CI:1.01-2.74),respectively.Further analysis indicated that the patients with nosocomial infection had longer time in use of proton pump inhibitors and prior antimicrobial combination therapy than the patients in the control group(Z=-6.331,P＜0.001;Z=-2.667,P=0.008).The trend Chi-square test showed that there was a dose-response relationship for proton pump inhibitors(x2=73.869,P＜0.001),immunosuppressive drugs(x2=16.530,P＜0.001),and prior antimicrobial combination therapy(x2=35.107,P＜0.001).Conclusions The use of immunosuppressants,proton pump inhibitors and antimicrobial combination therapy increases the risk of nosocomial infections in hospitalized patients.The prolonged use of these drugs will further increase the risk of nosocomial infection.

Objective To analyze the relationship between clinical drug utilization and the risk of nosocomial infections among hospitalized patients,and provide evidence for the prevention and control of nosocomial infections.Methods This study adopted a retrospective case-control design.The case group included 209 patients with nosocomial infection reported from January 2023 to December 2023 in a tertiary hospital.The control group included 209 patients without nosocomial infection during the same period.The patients in the control group were selected by stratified sampling based on Charlson Comorbidity Index(CCI).Results Univariate analysis showed that proton pump inhibitors,antacids,immunosuppressants and prior antimicrobial combination therapy increased the risk of nosocomial infection(P＜0.05).Multivariate log-binomial regression analysis showed that proton pump inhibitors,immunosuppressive drugs,and prior antimicrobial combination therapy were correlated with nosocomial infection.The corresponding relative risk(RR)was 1.31(95％CI:1.07-1.60),1.40(95％CI:1.02-1.91),and 1.66(95％CI:1.01-2.74),respectively.Further analysis indicated that the patients with nosocomial infection had longer time in use of proton pump inhibitors and prior antimicrobial combination therapy than the patients in the control group(Z=-6.331,P＜0.001;Z=-2.667,P=0.008).The trend Chi-square test showed that there was a dose-response relationship for proton pump inhibitors(x2=73.869,P＜0.001),immunosuppressive drugs(x2=16.530,P＜0.001),and prior antimicrobial combination therapy(x2=35.107,P＜0.001).Conclusions The use of immunosuppressants,proton pump inhibitors and antimicrobial combination therapy increases the risk of nosocomial infections in hospitalized patients.The prolonged use of these drugs will further increase the risk of nosocomial infection.

Purpose Based on multimodal imaging combined with a variety of histological techniques,to visually evaluate the changes of rats brain metabolic microenvironment after cerebral hypoxia and ischemia of prematurity,and to discuss the effects of abnormal lactate metabolism in the brain on oligodendrocyte precursor cells,so as to provide a basis for the early diagnosis and treatment of premature white matter injury(PWMI).Materials and Methods A total of 36 SPF-grade healthy 3-day-old Sprague-Dawley neonatal rats were randomly assigned to the sham surgery(Sham)group and the model(PWMI)group using a random number table method,with 18 rats in each group.A neonatal rat PWMI model was established by hypoxia-ischemia method.Twenty-four hours after modeling,laser speckle imaging was used to monitor cerebral blood flow and blood oxygen changes.Multimodal imaging was used to observe the changes in brain tissue microstructure and metabolism after PWMI.HE staining was used to observe the morphological changes of nerve cells in the white matter of the brain.Enzyme-linked immunosorbent assay was used to detect the changes of lactate content and lactate dehydrogenase activity in the white matter region of the brain after PWMI in neonatal rats.PDGFR-α immunofluorescence staining was used to observe the dynamic changes of the number of oligodendrocyte precursor cells in the subependymal zone after PWMI in neonatal rats.Results Twenty-four hours after modeling,the multimodal imaging results showed that the T2WI and diffusion-weighted imaging on the injured side of the PWMI group showed high intensity,and the relative cerebral blood flow,relative oxygen saturation,relative apparent diffusion coefficient and amide proton transfer(APT)Lorentzian difference value were lower than those in the Sham group(t=29.466,23.522,59.006,54.778,10.263,all P<0.001),and the lactate content was higher than that in the Sham group(t=-7.521,P<0.001).The results of HE staining and enzyme-linked immunosorbent assay showed that the arrangement of nerve cells in the white matter area of the injured side of the brain in the PWMI group was loose and disordered.The lactate content and lactate dehydrogenase activity were higher than those in the Sham group(t=-6.079,-10.548,both P<0.001).The results of immunofluorescence staining showed that the number of PDGFR-α+cells in the subependymal zone of the damaged side of the PWMI group was higher than that of the Sham group at 24 hours after modeling,and lower than that in the Sham group at 11 days after modeling(t=-8.386,6.676,both P<0.001).The correlation analysis between the lactate content and APT Lorentzian difference value in the brain and the number of oligodendrocyte precursor cells in the brain 11 days after modeling showed that the number of oligodendrocyte precursor cells in the subependymal zone was positively correlated with the APT Lorentzian difference value(r=0.821,P=0.001 1),and negatively correlated with the lactate content in the brain(r=-0.880,P=0.000 2).Conclusion Multimodal imaging can monitor the early brain metabolism changes of PWMI in neonatal rats,especially the changes of lactate,and provide a visual basis for their early diagnosis.The level of lactate in the brain increases after cerebral hypoxia and ischemia in prematurity,and oligodendrocyte precursor cells increase transiently and then decrease,resulting in PWMI.

Objective:The neurovascular unit(NVU)damage in rats with cerebral ischemia-reperfusion injury(CI-RI)was evaluated based on multimodal MRI combined with multiple histological techniques to provide visual evidence for clinical assessment of CIRI.Methods:28 healthy male Sprague-Dawley rats were randomly divided into sham-oper-ated(Sham)group and CIRI group.At 24 h after modeling,rats underwent head T2-weighted imaging,diffusion-weighted imaging,water extraction with phase-contrast arterial spin labeling magnetic resonance imaging(MRI),and cerebral blood bleeding oxygen monitoring.Hematoxylin-eosin(HE)staining was used to observe the morphological changes of nerve cells in cerebral cortex.Immunofluorescence staining and transmission electron microscopy were used to observe the changes of NVU after CIRI.The endothelial tight junction proteins(claudin-5 and ZO-1)and matrix metalloproteinase-9(MMP-9)were detected by immunohistochemical staining and Western Blot analysis,to evaluate blood-brain-barrier(BBB)disruption in CIRI rats.Results:The MRI results showed that the brain tissue of the CIRI group was edematous,and the blood perfusion significantly decreased and the BBB permeability significantly increased compared with that of the Sham group(P＜0.01).The results of cerebral blood hemoglobin oxygen monitoring showed that the hemoglobin oxygen saturation of the cerebral cortex on the injured side was significantly lower than that of the Sham group(P＜0.05).HE staining showed the neuronal cells of the injured cerebral cortex were disordered and the nuclei shrank.Immunofluorescence staining results showed the number of NeuN and CD31 positive cells in the cerebral cortex of the injured side was significantly lower than that in the Sham group(P＜0.01),and the number of TUNEL positive cells in the cerebral cortex and striatum was significantly higher than that in the Sham group(P＜0.05).Transmission electron microscopy revealed the tight junctions of cerebral cortical endothelial cells were damaged,neuro-nal nucleus contraction,and astrocyte body edema.Immunohistochemical staining showed that the number of claudin-5 and ZO-1 positive cells in the cerebral cortex on the injured side was significantly lower than that in the Sham group,and the expression of MMP-9 was significantly higher than that in the Sham group(P＜0.01).Conclusion:CIRI re-sults in NVU injury,BBB disruption,and exacerbation of brain damage in rats.Multimodal MRI combined with various histopathological techniques effectively assesses NVU injury after CIRI.

Objective:Using T2-weighted imaging(T2WI),diffusion-weighted imaging(DWI),pulsed gradient spin echo(PGSE)multiparametric magnetic resonance imaging combined with various histopathological techniques to observe the effects of reperfusion after different times of cerebral ischemia(CIRI)on the cytotoxic edema of brain tis-sues in rats.This provides a solid foundation for the establishment of ischemic stroke models and clinical diagnosis and treatment.Methods:Healthy adult male Sprague Dawley rats were randomly allocated to four groups:the sham-opera-ted(Sham)group,the ischaemia 60 min reperfusion(IR-60 min)group,the IR-120 min group,and the IR-180 min group.CIRI rat model was prepared by modified Zea Longa method.Laser doppler flowmetry combined with hematoxy-lin-eosin(HE)staining was employed to identify the model.Multiparametric magnetic resonance imaging,combined with water content of brain,immunofluorescence staining of aquaporin-4(AQP4),and Western Blot were performed to observe cytotoxic edema of brain tissues and tumour necrosis factor alpha(TNF-α),interleukin 1β(IL-1β)in brain tissue of rats in each group.Results:HE staining and determination of brain tissue water content prove that as ischemia time prolongs,the degree of cerebral cortex edema on the ischemic side increases.The T2WI results showed that the injury in the IR-60 min group began to affect the cerebral cortex,the injury in the IR-120 min group had completely affected the cerebral cortex,and the injury in the IR-180 min group was the most severe(P＜0.05),with a significant shift of the midline of the brain towards the opposite side.The relative apparent diffusion coefficient and water exchange time of the cerebral cortex on the ischemic side of the rats were found to be significantly lower than those of the sham group,with an declining trend(P＜0.05).Additionally,the values of cell membrane permeability of the cerebral cor-tex on the ischemic side of the rats were observed to be significantly higher than those of the sham group in all groups(P＜0.05).The expression of AQP4,IL-1 β and TNF-α in the cerebral cortex of ischemic side was significantly higher than that in the sham group,and showed an upward trend(P＜0.05).Conclusion:Reperfusion following 60,120 and,180 minutes of middle cerebral artery ischemia in rats can result in brain damage.Prolongation of ischemia time has been shown to exacerbate the toxic edema of brain cells and brain damage.Ischemia of 120 minutes reperfusion has been identified as the optimal modeling time for ischemic stroke.Multiparametric MRI can be utilized to monitor the mi-crostructural changes of brain tissue in rats following CIRI in vivo,providing a foundation for the visualization of early clinical diagnosis and treatment.

Objective:Using T2-weighted imaging(T2WI),diffusion-weighted imaging(DWI),pulsed gradient spin echo(PGSE)multiparametric magnetic resonance imaging combined with various histopathological techniques to observe the effects of reperfusion after different times of cerebral ischemia(CIRI)on the cytotoxic edema of brain tis-sues in rats.This provides a solid foundation for the establishment of ischemic stroke models and clinical diagnosis and treatment.Methods:Healthy adult male Sprague Dawley rats were randomly allocated to four groups:the sham-opera-ted(Sham)group,the ischaemia 60 min reperfusion(IR-60 min)group,the IR-120 min group,and the IR-180 min group.CIRI rat model was prepared by modified Zea Longa method.Laser doppler flowmetry combined with hematoxy-lin-eosin(HE)staining was employed to identify the model.Multiparametric magnetic resonance imaging,combined with water content of brain,immunofluorescence staining of aquaporin-4(AQP4),and Western Blot were performed to observe cytotoxic edema of brain tissues and tumour necrosis factor alpha(TNF-α),interleukin 1β(IL-1β)in brain tissue of rats in each group.Results:HE staining and determination of brain tissue water content prove that as ischemia time prolongs,the degree of cerebral cortex edema on the ischemic side increases.The T2WI results showed that the injury in the IR-60 min group began to affect the cerebral cortex,the injury in the IR-120 min group had completely affected the cerebral cortex,and the injury in the IR-180 min group was the most severe(P＜0.05),with a significant shift of the midline of the brain towards the opposite side.The relative apparent diffusion coefficient and water exchange time of the cerebral cortex on the ischemic side of the rats were found to be significantly lower than those of the sham group,with an declining trend(P＜0.05).Additionally,the values of cell membrane permeability of the cerebral cor-tex on the ischemic side of the rats were observed to be significantly higher than those of the sham group in all groups(P＜0.05).The expression of AQP4,IL-1 β and TNF-α in the cerebral cortex of ischemic side was significantly higher than that in the sham group,and showed an upward trend(P＜0.05).Conclusion:Reperfusion following 60,120 and,180 minutes of middle cerebral artery ischemia in rats can result in brain damage.Prolongation of ischemia time has been shown to exacerbate the toxic edema of brain cells and brain damage.Ischemia of 120 minutes reperfusion has been identified as the optimal modeling time for ischemic stroke.Multiparametric MRI can be utilized to monitor the mi-crostructural changes of brain tissue in rats following CIRI in vivo,providing a foundation for the visualization of early clinical diagnosis and treatment.

Objective:The neurovascular unit(NVU)damage in rats with cerebral ischemia-reperfusion injury(CI-RI)was evaluated based on multimodal MRI combined with multiple histological techniques to provide visual evidence for clinical assessment of CIRI.Methods:28 healthy male Sprague-Dawley rats were randomly divided into sham-oper-ated(Sham)group and CIRI group.At 24 h after modeling,rats underwent head T2-weighted imaging,diffusion-weighted imaging,water extraction with phase-contrast arterial spin labeling magnetic resonance imaging(MRI),and cerebral blood bleeding oxygen monitoring.Hematoxylin-eosin(HE)staining was used to observe the morphological changes of nerve cells in cerebral cortex.Immunofluorescence staining and transmission electron microscopy were used to observe the changes of NVU after CIRI.The endothelial tight junction proteins(claudin-5 and ZO-1)and matrix metalloproteinase-9(MMP-9)were detected by immunohistochemical staining and Western Blot analysis,to evaluate blood-brain-barrier(BBB)disruption in CIRI rats.Results:The MRI results showed that the brain tissue of the CIRI group was edematous,and the blood perfusion significantly decreased and the BBB permeability significantly increased compared with that of the Sham group(P＜0.01).The results of cerebral blood hemoglobin oxygen monitoring showed that the hemoglobin oxygen saturation of the cerebral cortex on the injured side was significantly lower than that of the Sham group(P＜0.05).HE staining showed the neuronal cells of the injured cerebral cortex were disordered and the nuclei shrank.Immunofluorescence staining results showed the number of NeuN and CD31 positive cells in the cerebral cortex of the injured side was significantly lower than that in the Sham group(P＜0.01),and the number of TUNEL positive cells in the cerebral cortex and striatum was significantly higher than that in the Sham group(P＜0.05).Transmission electron microscopy revealed the tight junctions of cerebral cortical endothelial cells were damaged,neuro-nal nucleus contraction,and astrocyte body edema.Immunohistochemical staining showed that the number of claudin-5 and ZO-1 positive cells in the cerebral cortex on the injured side was significantly lower than that in the Sham group,and the expression of MMP-9 was significantly higher than that in the Sham group(P＜0.01).Conclusion:CIRI re-sults in NVU injury,BBB disruption,and exacerbation of brain damage in rats.Multimodal MRI combined with various histopathological techniques effectively assesses NVU injury after CIRI.