ObjectiveTo investigate the regulatory effects of Huanglian Jiedutang （HLJDT） on immune cell migration， blood-brain barrier protection， and cellular functional recovery in a model of ischemic stroke. MethodsA transient middle cerebral artery occlusion （tMCAO） model was established in mice to induce ischemic stroke. Cerebral blood flow and neurological function were evaluated using laser speckle imaging and neurological deficit scoring. Histopathological damage in brain tissues was assessed by hematoxylin-eosin （HE） and Nissl staining. Mice were divided into a sham group， a model group， an HLJDT group， and a Ginkgo biloba extract （GBE） group. After one week of acclimatization， intragastric administration was initiated. The sham and model groups received normal saline， the HLJDT group received HLJDT at 1.82 g·kg^-¹， and the GBE group received GBE at 0.432 g·kg^-¹. Administration was continued for 5 consecutive days， and the tMCAO model was established after the final dose on day 6. Single-cell RNA sequencing was performed on brain tissues and peripheral immune cells. UMAP and odds ratio （OR） indices were used to analyze cell distribution. Differential expression analysis was conducted to evaluate the effects of HLJDT on endothelial cells， pericytes， and macrophages， combined with CellChat and decoupler to analyze cell-cell communication and transcription factor regulation. Finally， PCR and ELISA were used to validate the mRNA and protein expression of relevant genes. ResultsCompared with the sham group， the model group showed significantly increased neurological deficit scores （P<0.01） and significantly decreased cerebral blood flow （P<0.01）， accompanied by cortical structural disorder， aggravated cytoplasmic vacuolization， and increased numbers of Nissl bodies. Compared with the model group， both the HLJDT and GBE groups exhibited significantly reduced neurological deficit scores （P<0.01） and markedly improved cerebral blood flow （P<0.01）， along with amelioration of cortical structural disorder， alleviated cytoplasmic vacuolization， and reduced numbers of Nissl bodies. Single-cell analysis showed that HLJDT protected endothelial cells and pericytes by preventing their reduction， restored the expression of functional genes in these cells （e.g.， PECAM1 and NOS3）， and downregulated the expression of chemokines and adhesion-related factors （e.g.， CCL2 and CXCL2）. In macrophages， HLJDT reduced their recruitment to the central nervous system and downregulated the expression of chemokine receptors and inflammatory factors （e.g.， IL-6， CCR2， and CXCR2）. Cell-cell communication analysis further indicated that HLJDT， through the above mechanisms， alleviated damage to pericytes and endothelial cells， reduced their recruitment of macrophages， and decreased ligand-receptor interactions in chemokine signaling pathways （including CCL， CXCL， and CSF3） between pericytes/endothelial cells and macrophages， thereby preventing secondary injury. Compared with the sham group， the model group showed significantly upregulated mRNA expression levels of IL-1β， IL-6， TNF-α， CCL2， CXCL2， and CSF3 （P<0.01）， while mRNA expression levels of endothelial- and pericyte function-related genes （RGS5， PECAM1， VEGFB， and NOS3） were significantly downregulated （P<0.01）. In contrast， compared with the model group， the HLJDT and GBE groups exhibited significantly decreased mRNA expression levels of IL-1β， IL-6， TNF-α， CCL2， CXCL2， and CSF3 （P<0.01）， and significantly increased expression of RGS5， PECAM1， VEGFB， and NOS3 （P<0.01）. At the protein level， compared with the sham group， the model group showed significantly increased expression of IL-1β， IL-6， and TNF-α （P<0.01）， whereas these protein levels were significantly reduced in the HLJDT and GBE groups compared with the model group （P<0.01）. ConclusionHLJDT reduces neuronal damage in ischemic stroke by protecting endothelial cells and pericytes， while inhibiting their interaction with macrophages， thereby mitigating secondary injury in the central nervous system.

ObjectiveTo evaluate the therapeutic effects of Huanglian Jiedutang on cerebral infarction injury in a mouse model of middle cerebral artery occlusion （MCAO） and to explore its mechanism of action on oligodendrocytes， particularly its potential in myelin repair. MethodsMultiple experimental approaches were used to evaluate cerebral ischemic injury and the effects of drug intervention. Laser speckle imaging was used to detect changes in cerebral blood flow， 2，3，5-Triphenyltetrazolium chloride （TTC） staining was used to measure infarct volume， and neurological function was scored according to the Zea-Longa criteria. Brain tissues were routinely embedded in paraffin and subjected to HE and Nissl staining to observe tissue structure and neuronal damage. Animals were divided into a sham group （n=24）， model group （n=24）， Huanglian Jiedutang group （n=24）， and Ginkgo biloba extract （GBE） group （n=18）. After 1 week of acclimatization， intragastric administration was initiated. The sham and model groups received normal saline， the Huanglian Jiedutang group was administered 1.82 g·kg^-1， and the GBE group was administered 0.432 g·kg^-1 after preparation as a 2.16 g·L^-1 solution. All groups were treated for 5 consecutive days at a dose of 0.2 mL·（10 g）^-¹·d^-¹. The MCAO model was established after the final administration on day 6. Single-cell RNA sequencing was used to analyze brain tissue cellular composition and changes in oligodendrocyte subpopulations. Distinct subpopulations were identified by Uniform manifold approximation and projection （UMAP） dimensionality reduction and unsupervised clustering， and marker gene expression was analyzed. Pathway enrichment and causal inference were further performed using IPA. Finally， real-time quantitative PCR was used to verify mRNA expression changes of myelin-related genes. ResultsCompared with the sham group， the model group showed significantly increased neurological function scores （P<0.01）， significantly impaired blood flow （P<0.01）， significantly enlarged cerebral infarct area （P<0.01）， and pathological changes including disordered cortical structural arrangement， aggravated cytoplasmic vacuolization， and increased Nissl bodies. Compared with the model group， the Huanglian Jiedutang and GBE groups showed significantly decreased neurological function scores （P<0.01）， markedly restored blood flow levels （P<0.01）， significantly reduced cerebral infarct area （P<0.01）， and improvement in cortical structural disorder， alleviation of cytoplasmic vacuolization， and a reduction in Nissl bodies. Single-cell data showed that a myelin-associated oligodendrocyte （Mye-OL） subpopulation existed among oligodendrocytes， which was closely related to myelin generation. Compared with the sham group， the number of Mye-OL cells decreased in the model group. Compared with the model group， the number of Mye-OL cells increased in the Huanglian Jiedutang group. This subpopulation promoted the expression of myelin-related genes， including MOG， MBP， and MAG， via transcription factors such as OLIG1， OLIG2， NKX2-2， and SOX10， thereby regulating myelin generation， restoring cognition， and exerting therapeutic effects on acute cerebral infarction. Compared with the sham group， the mRNA expression levels of OLIG1， OLIG2， NKX2-2， and SOX10 were significantly downregulated in the model group （P<0.01）， and the mRNA expression levels of myelin-related genes， including MOG， MBP， and MAG， were also significantly downregulated （P<0.01）. In contrast， compared with the model group， the Huanglian Jiedutang and GBE groups showed significantly upregulated mRNA expression levels of OLIG1， OLIG2， NKX2-2， and SOX10 （P<0.01）， and significantly upregulated mRNA expression levels of myelin-related genes， including MOG， MBP， and MAG （P<0.01）. ConclusionHuanglian Jiedutang exerts therapeutic effects on acute cerebral infarction by regulating the OLIG1/2-NKX2-2-SOX10 signaling pathway to promote myelin generation by Mye-OL cells.

ObjectiveTo investigate the characteristics of metabolic reprogramming during cerebral ischemia-reperfusion injury using single-cell transcriptome sequencing， analyze the heterogeneity of microglial populations， and evaluate the interventional effects of Huanglian Jiedutang on metabolic abnormalities and neuroinflammation. MethodsA transient middle cerebral artery occlusion （tMCAO） model was used to establish ischemic stroke in mice. Local cerebral blood flow changes were monitored by laser speckle imaging. Neurological impairment was evaluated using the Zea-Longa score， and histopathological damage in brain tissue was observed by HE and Nissl staining. Animals were divided into a sham group， model group， Huanglian Jiedutang group， and Ginkgo biloba extract （GBE） group. After 1 week of acclimatization， intragastric administration was initiated. The sham and model groups received normal saline， the Huanglian Jiedutang group was administered 1.82 g·kg^-1， and the GBE group was administered 0.432 g·kg^-1 after preparation as a 2.16 mg/mL solution. All groups were treated for 5 consecutive days （0.2 mL/10 g/day）， and the tMCAO model was established on day 6 after the final administration. At the molecular level， single-cell RNA sequencing was performed on ischemic hemisphere tissue. Non-negative matrix factorization （NMF） was used to cluster microglial subpopulations， combined with differential expression analysis， metabolic reprogramming assessment， and inflammatory factor correlation analysis to elucidate their functional characteristics in ischemia-reperfusion injury. Transcription factor enrichment analysis was further conducted to identify key regulatory nodes. Finally， PCR was used to detect mRNA expression changes of relevant genes to validate the single-cell sequencing results. ResultsCompared with the sham group， the model group showed increased neurological function scores （P<0.01）， decreased blood flow levels （P<0.01）， disordered cortical structure， increased cytoplasmic vacuolization， and increased Nissl bodies. Compared with the model group， the Huanglian Jiedutang and GBE groups showed decreased neurological function scores （P<0.01）， increased blood flow levels （P<0.01）， alleviated cortical structural disorder， reduced cytoplasmic vacuolization， and decreased Nissl bodies. Single-cell analysis showed that microglia could be divided into five subpopulations. Among them， clusters 3 and 5 exhibited significant pro-inflammatory phenotypes， with marked activation of hypoxia and NF-κB signaling pathways， and were identified as pro-inflammatory subpopulations. Clusters 1 and 2 were enriched in Wnt/β-catenin and transforming growth factor（TGF）-β signaling pathways and exhibited prominent anti-inflammatory and reparative characteristics. Meanwhile， glycolysis-related genes， such as HK2， PFKP， and LDHA， were significantly upregulated in the pro-inflammatory subpopulations. Correlation analysis showed that the expression levels of inflammatory molecules were positively correlated with glycolysis-related gene expression levels， whereas the expression levels of reparative and anti-inflammatory molecules were negatively correlated with glycolysis-related gene expression levels， indicating that microglia rely on the glycolytic pathway for energy acquisition under ischemic conditions. Further single-cell transcriptome analysis revealed that Huanglian Jiedutang effectively downregulated key genes driving metabolic reprogramming （such as HK2， PFKP， and LDHA）， significantly reduced the proportion of microglial subpopulations accompanied by glycolytic reprogramming， and inhibited their transformation toward a damage phenotype， thereby reducing inflammatory injury. Meanwhile， compared with the sham group， the mRNA expression levels of interleukin （IL）-1β， IL-6， tumor necrosis factor（TNF）-α， CCL2， CXCL2， and CSF3 were significantly upregulated （P<0.01） in the model group， whereas the mRNA expression levels of endothelial- and pericyte-related functional genes， including RGS5， PECAM1， VEGFB， and NOS3， were significantly downregulated （P<0.01）. In contrast， compared with the model group， the Huanglian Jiedutang and GBE groups showed significantly decreased mRNA expression levels of IL-1β， IL-6， TNF-α， CCL2， CXCL2， and CSF3 （P<0.01）， and significantly increased mRNA expression levels of endothelial- and pericyte-related functional genes， including RGS5， PECAM1， VEGFB， and NOS3 （P<0.01）. ConclusionHuanglian Jiedutang exerts neuroprotective effects by regulating the metabolic reprogramming state of microglia and modulating their inflammatory levels， thereby inhibiting neuroinflammatory injury.

ObjectiveTo evaluate the therapeutic effects of Huanglian Jiedutang on cerebral infarction injury in a mouse model of middle cerebral artery occlusion （MCAO） and to explore its mechanism of action on oligodendrocytes， particularly its potential in myelin repair. MethodsMultiple experimental approaches were used to evaluate cerebral ischemic injury and the effects of drug intervention. Laser speckle imaging was used to detect changes in cerebral blood flow， 2，3，5-Triphenyltetrazolium chloride （TTC） staining was used to measure infarct volume， and neurological function was scored according to the Zea-Longa criteria. Brain tissues were routinely embedded in paraffin and subjected to HE and Nissl staining to observe tissue structure and neuronal damage. Animals were divided into a sham group （n=24）， model group （n=24）， Huanglian Jiedutang group （n=24）， and Ginkgo biloba extract （GBE） group （n=18）. After 1 week of acclimatization， intragastric administration was initiated. The sham and model groups received normal saline， the Huanglian Jiedutang group was administered 1.82 g·kg^-1， and the GBE group was administered 0.432 g·kg^-1 after preparation as a 2.16 g·L^-1 solution. All groups were treated for 5 consecutive days at a dose of 0.2 mL·（10 g）^-¹·d^-¹. The MCAO model was established after the final administration on day 6. Single-cell RNA sequencing was used to analyze brain tissue cellular composition and changes in oligodendrocyte subpopulations. Distinct subpopulations were identified by Uniform manifold approximation and projection （UMAP） dimensionality reduction and unsupervised clustering， and marker gene expression was analyzed. Pathway enrichment and causal inference were further performed using IPA. Finally， real-time quantitative PCR was used to verify mRNA expression changes of myelin-related genes. ResultsCompared with the sham group， the model group showed significantly increased neurological function scores （P<0.01）， significantly impaired blood flow （P<0.01）， significantly enlarged cerebral infarct area （P<0.01）， and pathological changes including disordered cortical structural arrangement， aggravated cytoplasmic vacuolization， and increased Nissl bodies. Compared with the model group， the Huanglian Jiedutang and GBE groups showed significantly decreased neurological function scores （P<0.01）， markedly restored blood flow levels （P<0.01）， significantly reduced cerebral infarct area （P<0.01）， and improvement in cortical structural disorder， alleviation of cytoplasmic vacuolization， and a reduction in Nissl bodies. Single-cell data showed that a myelin-associated oligodendrocyte （Mye-OL） subpopulation existed among oligodendrocytes， which was closely related to myelin generation. Compared with the sham group， the number of Mye-OL cells decreased in the model group. Compared with the model group， the number of Mye-OL cells increased in the Huanglian Jiedutang group. This subpopulation promoted the expression of myelin-related genes， including MOG， MBP， and MAG， via transcription factors such as OLIG1， OLIG2， NKX2-2， and SOX10， thereby regulating myelin generation， restoring cognition， and exerting therapeutic effects on acute cerebral infarction. Compared with the sham group， the mRNA expression levels of OLIG1， OLIG2， NKX2-2， and SOX10 were significantly downregulated in the model group （P<0.01）， and the mRNA expression levels of myelin-related genes， including MOG， MBP， and MAG， were also significantly downregulated （P<0.01）. In contrast， compared with the model group， the Huanglian Jiedutang and GBE groups showed significantly upregulated mRNA expression levels of OLIG1， OLIG2， NKX2-2， and SOX10 （P<0.01）， and significantly upregulated mRNA expression levels of myelin-related genes， including MOG， MBP， and MAG （P<0.01）. ConclusionHuanglian Jiedutang exerts therapeutic effects on acute cerebral infarction by regulating the OLIG1/2-NKX2-2-SOX10 signaling pathway to promote myelin generation by Mye-OL cells.

ObjectiveTo investigate the characteristics of metabolic reprogramming during cerebral ischemia-reperfusion injury using single-cell transcriptome sequencing， analyze the heterogeneity of microglial populations， and evaluate the interventional effects of Huanglian Jiedutang on metabolic abnormalities and neuroinflammation. MethodsA transient middle cerebral artery occlusion （tMCAO） model was used to establish ischemic stroke in mice. Local cerebral blood flow changes were monitored by laser speckle imaging. Neurological impairment was evaluated using the Zea-Longa score， and histopathological damage in brain tissue was observed by HE and Nissl staining. Animals were divided into a sham group， model group， Huanglian Jiedutang group， and Ginkgo biloba extract （GBE） group. After 1 week of acclimatization， intragastric administration was initiated. The sham and model groups received normal saline， the Huanglian Jiedutang group was administered 1.82 g·kg^-1， and the GBE group was administered 0.432 g·kg^-1 after preparation as a 2.16 mg/mL solution. All groups were treated for 5 consecutive days （0.2 mL/10 g/day）， and the tMCAO model was established on day 6 after the final administration. At the molecular level， single-cell RNA sequencing was performed on ischemic hemisphere tissue. Non-negative matrix factorization （NMF） was used to cluster microglial subpopulations， combined with differential expression analysis， metabolic reprogramming assessment， and inflammatory factor correlation analysis to elucidate their functional characteristics in ischemia-reperfusion injury. Transcription factor enrichment analysis was further conducted to identify key regulatory nodes. Finally， PCR was used to detect mRNA expression changes of relevant genes to validate the single-cell sequencing results. ResultsCompared with the sham group， the model group showed increased neurological function scores （P<0.01）， decreased blood flow levels （P<0.01）， disordered cortical structure， increased cytoplasmic vacuolization， and increased Nissl bodies. Compared with the model group， the Huanglian Jiedutang and GBE groups showed decreased neurological function scores （P<0.01）， increased blood flow levels （P<0.01）， alleviated cortical structural disorder， reduced cytoplasmic vacuolization， and decreased Nissl bodies. Single-cell analysis showed that microglia could be divided into five subpopulations. Among them， clusters 3 and 5 exhibited significant pro-inflammatory phenotypes， with marked activation of hypoxia and NF-κB signaling pathways， and were identified as pro-inflammatory subpopulations. Clusters 1 and 2 were enriched in Wnt/β-catenin and transforming growth factor（TGF）-β signaling pathways and exhibited prominent anti-inflammatory and reparative characteristics. Meanwhile， glycolysis-related genes， such as HK2， PFKP， and LDHA， were significantly upregulated in the pro-inflammatory subpopulations. Correlation analysis showed that the expression levels of inflammatory molecules were positively correlated with glycolysis-related gene expression levels， whereas the expression levels of reparative and anti-inflammatory molecules were negatively correlated with glycolysis-related gene expression levels， indicating that microglia rely on the glycolytic pathway for energy acquisition under ischemic conditions. Further single-cell transcriptome analysis revealed that Huanglian Jiedutang effectively downregulated key genes driving metabolic reprogramming （such as HK2， PFKP， and LDHA）， significantly reduced the proportion of microglial subpopulations accompanied by glycolytic reprogramming， and inhibited their transformation toward a damage phenotype， thereby reducing inflammatory injury. Meanwhile， compared with the sham group， the mRNA expression levels of interleukin （IL）-1β， IL-6， tumor necrosis factor（TNF）-α， CCL2， CXCL2， and CSF3 were significantly upregulated （P<0.01） in the model group， whereas the mRNA expression levels of endothelial- and pericyte-related functional genes， including RGS5， PECAM1， VEGFB， and NOS3， were significantly downregulated （P<0.01）. In contrast， compared with the model group， the Huanglian Jiedutang and GBE groups showed significantly decreased mRNA expression levels of IL-1β， IL-6， TNF-α， CCL2， CXCL2， and CSF3 （P<0.01）， and significantly increased mRNA expression levels of endothelial- and pericyte-related functional genes， including RGS5， PECAM1， VEGFB， and NOS3 （P<0.01）. ConclusionHuanglian Jiedutang exerts neuroprotective effects by regulating the metabolic reprogramming state of microglia and modulating their inflammatory levels， thereby inhibiting neuroinflammatory injury.

BACKGROUND: Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. RESULTS: A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis. CONCLUSIONS: For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; ErbB Receptors/genetics* ; Lung Neoplasms/drug therapy* ; Mutation/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Chemoradiotherapy ; Antibodies, Monoclonal/therapeutic use*

Objective To explore the accumulated effects of physical activity,sedentary behavior,and sleep on cardiorespiratory fitness(CRF)among college students and provide effective measures for enhancing their CRF. Methods From May to June in 2023,223 college students aged 18 to 24 years old were recruited from Tianjin University of Science and Technology for a 24 hours activity behavior survey and CRF testing.Compositional analysis was employed to investigate the relationships of physical activity,sedentary behavior,and sleep with CRF.Isotemporal substitution models were established to predict the effects of substituting various activity behaviors on CRF.Results The proportion of time spent on moderate-to-vigorous physical activity(MVPA)was positively correlated with CRF of college students(β=6.40,P=0.002),while the proportion of time spent on sedentary behavior was negatively correlated with CRF(β=-3.02,P=0.004).Light physical activity(LPA)and sleep were not correlated with CRF(β=-1.06,P=0.504).Isotemporal substitution results for 15-min increments showed that replacing other activity behaviors with MVPA significantly increased the CRF of college students[SB:1.72 mL/(kg·min),95% CI=0.94-2.51;LPA:1.82 mL/(kg·min),95% CI=0.95-2.68;sleep:1.64 mL/(kg·min),95% CI=0.84-2.45].In the dose-response relationship from -30 min to 30 min,reallocating time from other behaviors to MVPA had greater adverse effect on CRF than reallocating time from MVPA to other behaviors.Among all the substitutions,replacing LPA with MVPA had the most beneficial effect on improving CRF.Additionally,a 5-min increment was considered the optimal tipping point for MVPA replacing other activities.Conclusions This study underscores the importance of participating in MVPA for improving the CRF of college students.The isotemporal substitution model provides clear goals for the allocation of time for these behaviors,aiding in future intervention measure development and policy-making.
Humans ; Sedentary Behavior ; Sleep ; Students ; Cardiorespiratory Fitness ; Exercise ; Young Adult ; Adolescent ; Universities ; Male ; Female

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

OBJECTIVE: To investigate the efficacy and safety of oblique lateral interbody fusion(OLIF) channel technique combined with pedicle screw internal fixation in the treatment of single-segment lumbar intervertebral space/vertebral body infection. METHODS: A retrospective analysis was conducted on 23 patients who underwent surgical treatment for lumbar infection from January 2021 to December 2022. The patients were divided into the OLIF channel group and the traditional open surgery group according to the surgical methods. There were 16 cases in the OLIF channel group, including 9 males and 7 females, with an average age of (68.5±12.1) years old;there were 7 cases in the traditional open surgery group, including 4 males and 3 females, with an average age of (75.0±3.2) years old. The operation time, intraoperative blood loss, hospital stay, incision length, visual analogue scale(VAS), activities of daily living (ADL) score, Oswestry disability index (ODI), erythrocyte sedimentation rate(ESR), C-reactive protein(CRP) before and 1 week and 3 months after the operation, and the intervertebral fusion status on the last follow-up CT were compared between the two groups. RESULTS: Compared with the open surgery group, the OLIF channel group had shorter operation time (209.87±31.5) min vs. (246.0±42.7) min, less intraoperative blood loss (225.625±91.1) ml vs. (364.2±74.8) ml, and shorter incision length (6.1±1.2) vs. (14.0±1.4) cm, and the differences were statistically significant(P<0.05). Before and 1 week and 3 months after the operation, the lumbar VAS in the OLIF group were (6.3±0.6), (2.8±0.7), (1.1±0.5), and those in the traditional open surgery group were (6.4±0.6), (3.4±0.5), (1.2±0.3);the ADL scores in the OLIF group were (45.0±4.5), (60.3±4.3), (94.1±4.2), and those in the open group were (46.4±5.6), (60.7±4.5), (92.9±4.9); the ODI scores in the OLIF group were (86.3±2.9)%, (69.5±4.1)%, (23.0±3.2)%, and those in the open group were (87.3±3.8)%, (69.8±4.2)%, (23.8±3.6)%, all of which showed significant improvement(P<0.05). Three months after the operation, CRP, PCT, and ESR were significantly lower than those before the operation, and CRP and PCT returned to normal, while ESR was still slightly elevated in some patients. The last follow-up CT showed that continuous trabecular bone formation was observed between the upper and lower endplates of the surgical segments in all patients, and the fusion time was (8.7±4.5) months. CONCLUSION The OLIF channel technique combined with posterior internal fixation is a minimally invasive and effective treatment method, which can effectively control infection, relieve pain, and improve the quality of life of patients. Compared with traditional open surgery, it has the advantages of minimally invasive, shorter operation time, and less intraoperative blood loss.
Humans ; Male ; Female ; Spinal Fusion/methods* ; Lumbar Vertebrae/microbiology* ; Aged ; Middle Aged ; Retrospective Studies ; Aged, 80 and over ; Pedicle Screws ; Infections/surgery*

In recent decades,the incidence of human papillomavirus(HPV)-associated oropharyngeal squamous cell carcinoma(OPSCC)has shown a marked increase.Significant changes have also occurred in the OPSCC diagnosis and treatment paradigm.Deter-mining HPV status prior to treatment is now essential,and radiotherapy/chemotherapy,immunotherapy,and minimally invasive surgical techniques have progressively emerged as key modalities for managing OPSCC.However,alongside these paradigm shifts,a comprehen-sive technical consensus guiding the entire diagnostic and therapeutic process for OPSCC patients is currently lacking.Given China's large population base and the rising incidence of OPSCC,an expert panel convened to develop a clinical technical consensus on OPSCC diagno-sis and management tailored to China's specific context.This consensus aims to further enhance and standardize understanding of OPSCC management techniques among relevant healthcare professionals.