The rapid formation of a glial/fibrotic scar is one of the main factors hampering axon growth after spinal cord injury. The bidirectional Eph B2/ephrin-B2 signaling of the fibroblast-astrocyte contact-dependent intera...The rapid formation of a glial/fibrotic scar is one of the main factors hampering axon growth after spinal cord injury. The bidirectional Eph B2/ephrin-B2 signaling of the fibroblast-astrocyte contact-dependent interaction is a trigger for glial/fibrotic scar formation. In the present study, a new in vitro model was produced by coculture of fibroblasts and astrocytes wounded by scratching to mimic glial/fibrotic scar-like structures using an improved slide system. After treatment with RNAi to downregulate Eph B2, changes in glial/fibrotic scar formation and the growth of VSC4.1 motoneuron axons were examined. Following RNAi treatment, fibroblasts and astrocytes dispersed without forming a glial/fibrotic scar-like structure. Furthermore, the expression levels of neurocan, NG2 and collagen I in the coculture were reduced, and the growth of VSC4.1 motoneuron axons was enhanced. These findings suggest that suppression of Eph B2 expression by RNAi attenuates the formation of a glial/fibrotic scar and promotes axon growth. This study was approved by the Laboratory Animal Ethics Committee of Jiangsu Province, China(approval No. 2019-0506-002) on May 6, 2019.展开更多
In the central nervous system, the formation of fibrotic scar after injury inhibits axon regeneration and promotes repair. However, the mechanism underlying fibrotic scar formation and regulation remains poorly unders...In the central nervous system, the formation of fibrotic scar after injury inhibits axon regeneration and promotes repair. However, the mechanism underlying fibrotic scar formation and regulation remains poorly understood. M2 macrophages regulate fibrotic scar formation after injury to the heart, lung, kidney, and central nervous system. However, it remains to be clarified whether and how M2 macrophages regulate fibrotic scar formation after cerebral ischemia injury. In this study, we found that, in a rat model of cerebral ischemia induced by middle cerebral artery occlusion/reperfusion, fibrosis and macrophage infiltration were apparent in the ischemic core in the early stage of injury(within 14 days of injury). The number of infiltrated macrophages was positively correlated with fibronectin expression. Depletion of circulating monocyte-derived macrophages attenuated fibrotic scar formation. Interleukin 4(IL4) expression was strongly enhanced in the ischemic cerebral tissues, and IL4-induced M2 macrophage polarization promoted fibrotic scar formation in the ischemic core. In addition, macrophage-conditioned medium directly promoted fibroblast proliferation and the production of extracellular matrix proteins in vitro. Further pharmacological and genetic analyses showed that sonic hedgehog secreted by M2 macrophages promoted fibrogenesis in vitro and in vivo, and that this process was mediated by secretion of the key fibrosis-associated regulatory proteins transforming growth factor beta 1 and matrix metalloproteinase 9. Furthermore, IL4-afforded functional restoration on angiogenesis, cell apoptosis, and infarct volume in the ischemic core of cerebral ischemia rats were markedly impaired by treatment with an sonic hedgehog signaling inhibitor, paralleling the extent of fibrosis. Taken together, our findings show that IL4/sonic hedgehog/transforming growth factor beta 1 signaling targeting macrophages regulates the formation of fibrotic scar and is a potential therapeutic target for ischemic stroke.展开更多
Background: Liver diseases including chronic hepatitis, steatosis, fibrosis, cirrhosis and liver cancer are now a public health problem. In 2002, cirrhosis accounted for 27.63% of hepatobiliary diseases in Burkina Fas...Background: Liver diseases including chronic hepatitis, steatosis, fibrosis, cirrhosis and liver cancer are now a public health problem. In 2002, cirrhosis accounted for 27.63% of hepatobiliary diseases in Burkina Faso. In Africa and more particularly in Burkina Faso, the majority of the population (about 80%) uses medicinal plants for their primary health care. Calotropis procera (Ait.) R.Br (Apocynaceae) is a medicinal plant used in Burkina Faso in the treatment of liver problems. This work aims to evaluate the anti-fibrotic properties of Calotropis procera roots barks. Methods: The anti-fibrotic activity of the ethanolic extract of Calotropis procera roots barks was evaluated using diethylnitrosamine (DEN) to induce liver fibrosis in male Wistar rats. Serum biomarkers, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), Total protein, Albumin, Υ-Glutamyl transferase (GGT) were evaluated and the activities of antioxidant enzymes (Superoxide dismutase and catalase) as well as the level of malonedialdehyde (MDA) and that of nitric oxide (NO) were determined in the liver homogenate. Results: The treatment of rats suffering from hepatic fibrosis with the ethanolic extract leads to a significant restoration of the biomarkers of the hepatic function in particular, AST, ALP, GGT, Albumin. The extract also causes a reduction in oxidative stress in the liver through a significant increase in the activity rate of the antioxidant enzymes Superoxide dismutase (SOD) and catalase accompanied by a significant drop in the rate of MDA and NO suggesting the anti-oxidant effect of extract. Conclusion: The results of the study show that the ethanolic extract of the roots barks of Calotropis procera has anti-fibrotic properties.展开更多
Satellite glial cells are unique glial cells that surround the cell body of primary sensory neurons.An increasing body of evidence suggests that in the presence of inflammation and nerve damage,a significant number of...Satellite glial cells are unique glial cells that surround the cell body of primary sensory neurons.An increasing body of evidence suggests that in the presence of inflammation and nerve damage,a significant number of satellite glial cells become activated,thus triggering a series of functional changes.This suggests that satellite glial cells are closely related to the occurrence of chronic pain.In this review,we first summarize the morphological structure,molecular markers,and physiological functions of satellite glial cells.Then,we clarify the multiple key roles of satellite glial cells in chronic pain,including gap junction hemichannel Cx43,membrane channel Pannexin1,K channel subunit 4.1,ATP,purinergic P2 receptors,and a series of additional factors and their receptors,including tumor necrosis factor,glutamate,endothelin,and bradykinin.Finally,we propose that future research should focus on the specific sorting of satellite glial cells,and identify genomic differences between physiological and pathological conditions.This review provides an important perspective for clarifying mechanisms underlying the peripheral regulation of chronic pain and will facilitate the formulation of new treatment plans for chronic pain.展开更多
AIM: To investigate tumor necrosis factor-α (TNF-α), syndecan 1 and basic fibroblast growth factor (bFGF) balance in Crohn's disease (CD) strictures. METHODS: Our study was performed on 24 surgical specimens of ...AIM: To investigate tumor necrosis factor-α (TNF-α), syndecan 1 and basic fibroblast growth factor (bFGF) balance in Crohn's disease (CD) strictures. METHODS: Our study was performed on 24 surgical specimens of CD fibrotic stenosis. Ten histological normal surgical samples were retrieved for both the large and small bowel from patients with benign conditions and healthy tissue represented control collection. Sex and age in controls did not differ from CD group. Three endoscopic biopsy specimens taken after informed consent in subjects with normal colon were also used as negative controls. TNF-α, syndecan 1 and bFGF were detected by both reverse transcriptase reverse transcriptase polymerase chain reaction after mRNA extraction (results expressed as fold-change) and immunohistochemistry.RESULTS: TNF-α did not show any significant difference between CD and control specimens (1.54 ± 1.19; P > 0.05). Very high levels of bFGF were observed in CD (11.76 ± 4.65; P < 0.001) unlike syndecan 1 which showed a moderate increase (5.53 ± 2.18; P < 0.005). analysis of variance (ANOVA) plus Student-NeumannKeuls showed: bFGF > syndecan 1 > TNF-α = control. Immunoreactivity for bFGF was observed in epithelial, stromal, endothelial cells and even in the muscular layer, whilst in normal tissue it was almost unexpressed. Syndecan 1 and TNF-α staining was confined to mucosal epithelial and stromal cells, while in controls syndecan 1 was found in its normal site, i.e. , basolateral area of the crypts and TNF-α very poorly expressed. CONCLUSION: Fibrotic stenosis of CD may be the final result of an irreversible transformation of different cells into fibrogenic phenotype no longer inhibited by posttranscriptional regulation.展开更多
AIM: Hydrodynamics based transfection (HBT), the injection of a large volume of naked plasmid DNA in a short time is a relatively simple, efficient and safe method for in vivo transfection of liver cells. Though used ...AIM: Hydrodynamics based transfection (HBT), the injection of a large volume of naked plasmid DNA in a short time is a relatively simple, efficient and safe method for in vivo transfection of liver cells. Though used for quite some time, the mechanism of gene transfection has not yet been elucidated. METHODS: A luciferase encoding plasmid was injected using the hydrodynamics based procedure into normal and thioacetamide-induced fibrotic Sprague Dawley rats. Scanning and transmission electron microscopy images were taken. The consequence of a dual injection of Ringer solution and luciferase pDNA was followed. Halofuginone, an anti collagen type I inhibitor was used to reduce ECM load in fibrotic rats prior to the hydrodynamic injection. RESULTS: Large endothelial gaps formed as soon as 10’ following hydrodynamic injection; these gradually returned to normal 10 d post injection. Hydrodynamic administration of Ringer 10 or 30 m prior to moderate injection of plasmid did not result in efficient transfection suggesting that endothelial gaps by themselves are not sufficient for gene expression. Gene transfection following hydrodynamic injection in thioacetamide induced fibrotic rats was diminished coinciding with the level of fibrosis. Halofuginone, a specific collagen typeⅠ inhibitor, alleviated this effect. CONCLUSION: The hydrodynamic pressure formedfollowing HBT results in the formation of large endothelial gaps. These gaps, though important in the transfer of DNA molecules from the blood to the space of Disse are not enough to provide the appropriate conditions for hepatocyte transfection. Hydrodynamics based injection is applicable in fibrotic rats provided that ECM load is reduced.展开更多
AIM: To compare the outcome of an Ex-Press implant and subscleral trabeculectomy(SST) in the management of glaucoma after previous trabeculectomy on a fibrotic bleb.METHODS: This randomized prospective study included ...AIM: To compare the outcome of an Ex-Press implant and subscleral trabeculectomy(SST) in the management of glaucoma after previous trabeculectomy on a fibrotic bleb.METHODS: This randomized prospective study included 28 eyes from 28 patients(age range: 42-55 y) with primary open angle glaucoma(POAG) presented with elevated intraocular pressure(IOP) with fibrotic bleb despite previous SST for more than 4 mo. The eyes enrolled in the study were divided into two groups: group I(subjected to Ex-Press implant surgery) and group II [subjected to SST with mitomycin C(MMC)]. The follow-up continued one year after surgery to evaluate IOP, visual acuity(VA), visual field(VF), and postoperative complications. RESULTS: A significant decrease in IOP was found in both groups with a higher reduction in Ex-Press implant surgery with the mean IOP of 14.50 mm Hg(P=0.001), while the SST group recorded the mean IOP of 16.50 mm Hg(P=0.001) after one year. However, the difference between the two groups in terms of the decrease in IOP was insignificant. Fewer postoperative complications were recorded in the Ex-Press implant surgery and more cases requiring further anti-glaucomatous medications were seen in the SST group. Both groups showed stability in terms of VA and VF.CONCLUSION: Ex-Press implant surgery and SST with MMC are two surgical alternatives for controlling IOP in late failure that occurs more than 4 mo after previous SST with a fibrotic bleb. However, Ex-Press shunt is a safer surgery with fewer complications.展开更多
Background: Complete hypopharyngo-oesophageal occlusion is a rare complication of head and neck radiotherapy and a range of other conditions. Absolute dysphagia is accompanied by aspiration and dependence on gastrosto...Background: Complete hypopharyngo-oesophageal occlusion is a rare complication of head and neck radiotherapy and a range of other conditions. Absolute dysphagia is accompanied by aspiration and dependence on gastrostomy feeding. The condition presents a substantial management challenge. Surgical approaches to re-establish pharyngo-oesophageal continuity are varied, highly invasive and are associated with unpredictable outcomes. Minimally invasive techniques employing endoscopic and radiological techniques are emerging. This report describes a multidisciplinary approach which translates two interventional radiology techniques used in the management of central venous occlusions and biliary strictures to the management of three cases of complete hypopharyngo-oesophageal occlusion. Methods: Three cases with different underlying aetiologies had treatment initiated between 2009 and 2011. Antegrade pharyngoscopic access to the occlusions was accompanied by retrograde endoscopic access via a small gastrostomy. Luminal continuity was re-established by the interventional radiology technique of “sharp recanalisation” followed by passage of a wide bore nasogastric tube which was maintained in situ for 4-6 months, a duration of treatment analogous to that applied in the radiological management of fibrotic biliary strictures. After treatment a radiological contrast swallows examination was performed to gauge the calibre of the re-established lumen, assess functionality and to rule out aspiration. Results: Pharyngo-oesophageal continuity was re-established in all three cases on the first attempt. No complications occurred as a result of the procedures. In two cases, the excellent swallowing function was re-established, although one of these required prolonged post-treatment adjuvant interventions. In one case no swallowing function resulted, despite apparently successful re-establishment of luminal continuity. Conclusions: Complete fibrotic occlusion of the hypopharyngo-oesophageal lumen is rare and presents a substantial management challenge. A minimally invasive treatment combining antegrade radiological and retrograde endoscopic approaches resulted in successful re-establishment of luminal continuity in three cases of complete fibrotic occlusion of the hypopharyngo-oesophageal lumen. However variable responses to treatment suggest that both the underlying aetiology and the chronicity of the occlusion may influence the likelihood of a successful functional outcome. Until definitive management guidelines are established, we suggest that such cases are managed only by motivated multidisciplinary teams keen to develop their expertise in this area.展开更多
BACKGROUND Fibrotic hypersensitivity pneumonitis(FHP)is an allergic and diffuse pneumonia caused by repeated inhalation of antigenic substances,and sometimes developed in people working in specific environments.While ...BACKGROUND Fibrotic hypersensitivity pneumonitis(FHP)is an allergic and diffuse pneumonia caused by repeated inhalation of antigenic substances,and sometimes developed in people working in specific environments.While novel antigens and exposures continued to be described,physicians should maintain a high suspicion of potential exposures.A detailed assessment of the patient's occupational exposures as well as living environment is necessary and complete allergen avoidance is the first and most important step in the management of FHP once the allergens are determined.CASE SUMMARY A 35-year-old female was admitted to the hospital with a cough and breathing difficulties for more than one year.She was a nonsmoker and a manufacturer of halogen dishes,which are characteristic Chinese foods,for 15 years without any protection.High resolution computed tomography of the chest demonstrated an interstitial pneumonia pattern.Pulmonary function examination showed restricted ventilation dysfunction and a significant reduction in dispersion ability.Cell differentiation in bronchoalveolar lavage fluid demonstrated lymphocytosis(70.4%)with an increased lymphocyte CD4/CD8 ratio(0.94).Transbronchial lung biopsy combined with lung puncture pathology showed diffuse uniform alveolar interval thickening,chronic inflammatory cell infiltration,a proliferation of tissue in the bronchial wall fiber and alveolar epithelial follicle degeneration,resulting in fibrosis.CONCLUSION Exposure to spices used for the production of halogen dishes may cause FHP.展开更多
The trigeminal root entry zone is the zone at which the myelination switches from peripheral Schwann cells to central oligodendrocytes.Its special anatomical and physiological structure renders it susceptible to nerve...The trigeminal root entry zone is the zone at which the myelination switches from peripheral Schwann cells to central oligodendrocytes.Its special anatomical and physiological structure renders it susceptible to nerve injury.The etiology of most primary trigeminal neuralgia is closely related to microvascular compression of the trigeminal root entry zone.This study aimed to develop an efficient in vitro model mimicking the glial environment of trigeminal root entry zone as a tool to investigate the effects of glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor on the structural and functional integrity of trigeminal root entry zone and modulation of cellular interactions.Primary astrocytes and Schwann cells isolated from trigeminal root entry zone of postnatal rats were inoculated into a two-well silicon culture insert to mimic the trigeminal root entry zone microenvironment and treated with glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor.In monoculture,glial cell line-derived neurotrophic factor promoted the migration of Schwann cells,but it did not have effects on the migration of astrocytes.In the co-culture system,glial cell line-derived neurotrophic factor promoted the bidirectional migration of astrocytes and Schwann cells.Brain-derived neurotrophic factor markedly promoted the activation and migration of astrocytes.However,in the co-culture system,brain-derived neurotrophic factor inhibited the migration of astrocytes and Schwann cells to a certain degree.These findings suggest that glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor are involved in the regulation of the astrocyte-Schwann cell interaction in the co-culture system derived from the trigeminal root entry zone.This system can be used as a cell model to study the mechanism of glial dysregulation associated with trigeminal nerve injury and possible therapeutic interventions.展开更多
The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to investigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial...The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to investigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial scar.We used a pharmacologic approach to induce microglial depletion during different ICH stages and examine how ablating microglia affects astrocytic scar formation.Spatial transcriptomics(ST)analysis was performed to explore the potential ligand-receptor pair in the modulation of microglia-astrocyte interaction and to verify the functional changes of astrocytic scars at different periods.During the early stage,sustained microglial depletion induced disorganized astrocytic scar,enhanced neutrophil infiltration,and impaired tissue repair.ST analysis indicated that microglia-derived insulin like growth factor 1(IGF1)modulated astrocytic scar formation via mechanistic target of rapamycin(mTOR)signaling activation.Moreover,repopulating microglia(RM)more strongly activated mTOR signaling,facilitating a more protective scar formation.The combination of IGF1 and osteopontin(OPN)was necessary and sufficient for RM function,rather than IGF1 or OPN alone.At the chronic stage of ICH,the overall net effect of astrocytic scar changed from protective to destructive and delayed microglial depletion could partly reverse this.The vital insight gleaned from our data is that sustained microglial depletion may not be a reasonable treatment strategy for early-stage ICH.Inversely,early-stage IGF1/OPN treatment combined with late-stage PLX3397 treatment is a promising therapeutic strategy.This prompts us to consider the complex temporal dynamics and overall net effect of microglia and astrocytes,and develop elaborate treatment strategies at precise time points after ICH.展开更多
BACKGROUND Brain gliomas are malignant tumors with high postoperative recurrence rates.Early prediction of prognosis using specific indicators is of great significance.AIM To assess changes in ubiquitin carboxy-termin...BACKGROUND Brain gliomas are malignant tumors with high postoperative recurrence rates.Early prediction of prognosis using specific indicators is of great significance.AIM To assess changes in ubiquitin carboxy-terminal hydrolase L1(UCH-L1)and glial fibrillary acidic protein(GFAP)levels in patients with glioma pre-and postoperatively.METHODS Between June 2018 and June 2021,91 patients with gliomas who underwent surgery at our hospital were enrolled in the glioma group.Sixty healthy volunteers were included in the control group.Serum UCH-L1 and GFAP levels were measured in peripheral blood collected from patients with glioma before and 3 d after surgery.UCH-L1 and GFAP levels in patients with glioma with different clinicopathological characteristics were compared before and after surgery.The patients were followed-up until February 2022.Postoperative glioma recurrence was recorded to determine the serum UCH-L1 and GFAP levels,which could assist in predicting postoperative glioma recurrence.RESULTS UCH-L1 and GFAP levels in patients with glioma decreased significantly 3 d after surgery compared to those before therapy(P<0.05).However,UCH-L1 and GFAP levels in the glioma group were significantly higher than those in the control group before and after surgery(P<0.05).There were no statistically significant differences in preoperative serum UCH-L1 and GFAP levels among patients with glioma according to sex,age,pathological type,tumor location,or number of lesions(P>0.05).Serum UCH-L1 and GFAP levels were significantly lower in the patients with WHO grade I-II tumors than in those with gradeⅢ-IV tumors(P<0.05).Serum UCH-L1 and GFAP levels were lower in the patients with tumor diameter≤5 cm than in those with diameter>5 cm,in which the differences were statistically significant(P<0.05).Glioma recurred in 22 patients.The preoperative and 3-d postoperative serum UCH-L1 and GFAP levels were significantly higher in the recurrence group than these in the non-recurrence group(P<0.05).Receiver operating characteristic curves were plotted.The areas under the curves of preoperative serum UCH-L1 and GFAP levels for predicting postoperative glioma recurrence were 0.785 and 0.775,respectively.However,the efficacy of serum UCH-L1 and GFAP levels 3 d after surgery in predicting postoperative glioma recurrence was slightly lower compared with their preoperative levels.CONCLUSION UCH-L1 and GFAP efficiently reflected the development and recurrence of gliomas and could be used as potential indicators for the recurrence and prognosis of glioma.展开更多
目的 基于循证医学,构建一套适用于进行性纤维化间质性肺病患者的规范化肺康复训练方案,丰富肺康复指导的系统教育方案内涵,为临床康复护理提供科学指导。方法 计算机检索中国WanFang数据库、中国知网数据库(CNKI)、维普数据库(VIP)、...目的 基于循证医学,构建一套适用于进行性纤维化间质性肺病患者的规范化肺康复训练方案,丰富肺康复指导的系统教育方案内涵,为临床康复护理提供科学指导。方法 计算机检索中国WanFang数据库、中国知网数据库(CNKI)、维普数据库(VIP)、中国生物医学文献数据库(CBM)、PubMed、Embase、Cochrane Library、Web of Science数据库文献及指南网站,以循证医学为指导,通过文献回顾分析,采用《临床指南研究与评价系统》(Appraisal of Guidelines for Research and Evaluation,AGREEⅡ)评价指南质量及澳大利亚JBI(Joanna Briggs Institute)循证卫生保健中心开发的文献质量评价工具对随机对照试验、系统评价、类实验文献进行质量评价,对纳入的文献进行全文阅读及等级划分,以汇总最佳证据,拟定进行性纤维化间质性肺病患者肺康复训练方案初稿,最后结合专家会议和专家咨询结果,对方案初稿进行可用性评鉴,最终修订完善方案。结果 经文献质量评价及筛选后,共纳入30篇文献,其中指南与专家共识3篇,随机对照试验文献16篇,系统评价文献6篇,类实验文献5篇。方案内容包括训练评估、呼吸训练、运动训练、健康教育、社会心理干预、营养支持6个一级指标。结论 该研究构建的方案结果可靠,其规范性、科学性和安全性高,能够为进行性纤维化间质性肺病患者临床康复护理工作提供参考。展开更多
目的探讨血清低氧诱导因子-1α(HIF-1α)、神经元特异性烯醇化酶(NSE)、胶质纤维酸性蛋白(GFAP)及相关临床特征与新生儿缺氧缺血性脑病(HIE)发生风险的关系。方法选取2020年1月—2023年1月苏州大学附属儿童医院收治的85例HIE患儿作为HIE...目的探讨血清低氧诱导因子-1α(HIF-1α)、神经元特异性烯醇化酶(NSE)、胶质纤维酸性蛋白(GFAP)及相关临床特征与新生儿缺氧缺血性脑病(HIE)发生风险的关系。方法选取2020年1月—2023年1月苏州大学附属儿童医院收治的85例HIE患儿作为HIE组,另选取同期在该院出生的120例健康新生儿作为对照组,分析两组的临床资料并检测新生儿出生后3 d血清HIF-1α、NSE、GFAP水平。绘制受试者工作特征(ROC)曲线分析血清HIF-1α、NSE、GFAP水平预测新生儿HIE发病的价值;多因素逐步Logistic回归模型分析新生儿HIE发病的影响因素。结果与对照组相比,HIE组宫内窘迫、脐带异常、羊水污染、1 min Apgar评分≤7分的患儿比例较高(P<0.05),并且血清HIF-1α、NSE、GFAP水平较高(P<0.05);两组孕妇年龄、孕妇文化程度、胎龄、新生儿性别、出生体重、产次、剖宫产、胎膜早破比较,差异均无统计学意义(P>0.05)。ROC曲线分析结果显示,HIF-1α、NSE、GFAP及三者联合预测新生儿HIE发病的敏感性分别为82.7%(95%CI:0.795,0.862)、78.7%(95%CI:0.705,0.849)、84.0%(95%CI:0.803,0.891)、85.3%(95%CI:0.788,0.922),特异性分别为85.3%(95%CI:0.816,0.907)、74.7%(95%CI:0.715,0.796)、72.0%(95%CI:0.692,0.771)、90.5%(95%CI:0.825,0.956),AUC分别为0.907(95%CI:0.884,0.930)、0.850(95%CI:0.816,0.884)、0.893(95%CI:0.827,0.959)、0.936(95%CI:0.905,0.967);多因素逐步Logistic回归分析显示,宫内窘迫[O^R=3.592(95%CI:2.017,6.397)]、脐带异常[O^R=4.905(95%CI:2.862,8.406)]、羊水污染[O^R=7.262(95%CI:3.603,14.637)]、1 min Apgar评分≤7分[O^R=3.139(95%CI:1.954,5.043)]、HIF-1α≥0.463 ng/mL[O^R=2.916(95%CI:1.422,5.980)]、NSE≥12.395μg/L[O^R=3.714(95%CI:1.955,7.056)]、GFAP≥3.962 ng/mL[O^R=3.556(95%CI:2.039,6.202)]均是新生儿HIE发病的危险因素(P<0.05)。结论宫内窘迫、脐带异常、羊水污染、出生后1 min Apgar评分低及血清HIF-1α、NSE、GFAP水平高是新生儿HIE发病的危险因素,临床通过检测血清HIF-1α、NSE、GFAP水平可为临床筛查HIE提供帮助,3项指标联合检测可进一步提高诊断价值。展开更多
基金supported by the Priority Academic Program Development of Jiangsu Higher Education Institutes of China(PAPD)the Science and Technology Plan Project of Nantong of China,No.JC2020026(to JW)the National Science Research of Jiangsu Higher Education Institutions of China,No.19KJB310012(to RYY)。
文摘The rapid formation of a glial/fibrotic scar is one of the main factors hampering axon growth after spinal cord injury. The bidirectional Eph B2/ephrin-B2 signaling of the fibroblast-astrocyte contact-dependent interaction is a trigger for glial/fibrotic scar formation. In the present study, a new in vitro model was produced by coculture of fibroblasts and astrocytes wounded by scratching to mimic glial/fibrotic scar-like structures using an improved slide system. After treatment with RNAi to downregulate Eph B2, changes in glial/fibrotic scar formation and the growth of VSC4.1 motoneuron axons were examined. Following RNAi treatment, fibroblasts and astrocytes dispersed without forming a glial/fibrotic scar-like structure. Furthermore, the expression levels of neurocan, NG2 and collagen I in the coculture were reduced, and the growth of VSC4.1 motoneuron axons was enhanced. These findings suggest that suppression of Eph B2 expression by RNAi attenuates the formation of a glial/fibrotic scar and promotes axon growth. This study was approved by the Laboratory Animal Ethics Committee of Jiangsu Province, China(approval No. 2019-0506-002) on May 6, 2019.
基金supported by the National Natural Science Foundation of China,Nos.82171456 (to QY),81971229 (to QY)the Natural Science Foundation of Chongqing,No.cstc2021jcyj-msxmX0263 (to QY)the Postgraduate Research and Innovation Project of Chongqing,Nos.CYB20151 (to QY),CYS19182 (to YC)。
文摘In the central nervous system, the formation of fibrotic scar after injury inhibits axon regeneration and promotes repair. However, the mechanism underlying fibrotic scar formation and regulation remains poorly understood. M2 macrophages regulate fibrotic scar formation after injury to the heart, lung, kidney, and central nervous system. However, it remains to be clarified whether and how M2 macrophages regulate fibrotic scar formation after cerebral ischemia injury. In this study, we found that, in a rat model of cerebral ischemia induced by middle cerebral artery occlusion/reperfusion, fibrosis and macrophage infiltration were apparent in the ischemic core in the early stage of injury(within 14 days of injury). The number of infiltrated macrophages was positively correlated with fibronectin expression. Depletion of circulating monocyte-derived macrophages attenuated fibrotic scar formation. Interleukin 4(IL4) expression was strongly enhanced in the ischemic cerebral tissues, and IL4-induced M2 macrophage polarization promoted fibrotic scar formation in the ischemic core. In addition, macrophage-conditioned medium directly promoted fibroblast proliferation and the production of extracellular matrix proteins in vitro. Further pharmacological and genetic analyses showed that sonic hedgehog secreted by M2 macrophages promoted fibrogenesis in vitro and in vivo, and that this process was mediated by secretion of the key fibrosis-associated regulatory proteins transforming growth factor beta 1 and matrix metalloproteinase 9. Furthermore, IL4-afforded functional restoration on angiogenesis, cell apoptosis, and infarct volume in the ischemic core of cerebral ischemia rats were markedly impaired by treatment with an sonic hedgehog signaling inhibitor, paralleling the extent of fibrosis. Taken together, our findings show that IL4/sonic hedgehog/transforming growth factor beta 1 signaling targeting macrophages regulates the formation of fibrotic scar and is a potential therapeutic target for ischemic stroke.
文摘Background: Liver diseases including chronic hepatitis, steatosis, fibrosis, cirrhosis and liver cancer are now a public health problem. In 2002, cirrhosis accounted for 27.63% of hepatobiliary diseases in Burkina Faso. In Africa and more particularly in Burkina Faso, the majority of the population (about 80%) uses medicinal plants for their primary health care. Calotropis procera (Ait.) R.Br (Apocynaceae) is a medicinal plant used in Burkina Faso in the treatment of liver problems. This work aims to evaluate the anti-fibrotic properties of Calotropis procera roots barks. Methods: The anti-fibrotic activity of the ethanolic extract of Calotropis procera roots barks was evaluated using diethylnitrosamine (DEN) to induce liver fibrosis in male Wistar rats. Serum biomarkers, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), Total protein, Albumin, Υ-Glutamyl transferase (GGT) were evaluated and the activities of antioxidant enzymes (Superoxide dismutase and catalase) as well as the level of malonedialdehyde (MDA) and that of nitric oxide (NO) were determined in the liver homogenate. Results: The treatment of rats suffering from hepatic fibrosis with the ethanolic extract leads to a significant restoration of the biomarkers of the hepatic function in particular, AST, ALP, GGT, Albumin. The extract also causes a reduction in oxidative stress in the liver through a significant increase in the activity rate of the antioxidant enzymes Superoxide dismutase (SOD) and catalase accompanied by a significant drop in the rate of MDA and NO suggesting the anti-oxidant effect of extract. Conclusion: The results of the study show that the ethanolic extract of the roots barks of Calotropis procera has anti-fibrotic properties.
基金supported by the National Natural Science Foundation of China,No.82173796(to CX)the Research Project of Zhejiang Chinese Medical University,No.2022JKJNTZ13(to XQ).
文摘Satellite glial cells are unique glial cells that surround the cell body of primary sensory neurons.An increasing body of evidence suggests that in the presence of inflammation and nerve damage,a significant number of satellite glial cells become activated,thus triggering a series of functional changes.This suggests that satellite glial cells are closely related to the occurrence of chronic pain.In this review,we first summarize the morphological structure,molecular markers,and physiological functions of satellite glial cells.Then,we clarify the multiple key roles of satellite glial cells in chronic pain,including gap junction hemichannel Cx43,membrane channel Pannexin1,K channel subunit 4.1,ATP,purinergic P2 receptors,and a series of additional factors and their receptors,including tumor necrosis factor,glutamate,endothelin,and bradykinin.Finally,we propose that future research should focus on the specific sorting of satellite glial cells,and identify genomic differences between physiological and pathological conditions.This review provides an important perspective for clarifying mechanisms underlying the peripheral regulation of chronic pain and will facilitate the formulation of new treatment plans for chronic pain.
文摘AIM: To investigate tumor necrosis factor-α (TNF-α), syndecan 1 and basic fibroblast growth factor (bFGF) balance in Crohn's disease (CD) strictures. METHODS: Our study was performed on 24 surgical specimens of CD fibrotic stenosis. Ten histological normal surgical samples were retrieved for both the large and small bowel from patients with benign conditions and healthy tissue represented control collection. Sex and age in controls did not differ from CD group. Three endoscopic biopsy specimens taken after informed consent in subjects with normal colon were also used as negative controls. TNF-α, syndecan 1 and bFGF were detected by both reverse transcriptase reverse transcriptase polymerase chain reaction after mRNA extraction (results expressed as fold-change) and immunohistochemistry.RESULTS: TNF-α did not show any significant difference between CD and control specimens (1.54 ± 1.19; P > 0.05). Very high levels of bFGF were observed in CD (11.76 ± 4.65; P < 0.001) unlike syndecan 1 which showed a moderate increase (5.53 ± 2.18; P < 0.005). analysis of variance (ANOVA) plus Student-NeumannKeuls showed: bFGF > syndecan 1 > TNF-α = control. Immunoreactivity for bFGF was observed in epithelial, stromal, endothelial cells and even in the muscular layer, whilst in normal tissue it was almost unexpressed. Syndecan 1 and TNF-α staining was confined to mucosal epithelial and stromal cells, while in controls syndecan 1 was found in its normal site, i.e. , basolateral area of the crypts and TNF-α very poorly expressed. CONCLUSION: Fibrotic stenosis of CD may be the final result of an irreversible transformation of different cells into fibrogenic phenotype no longer inhibited by posttranscriptional regulation.
基金Supported by the Israel Science Foundation, No. 537/01, the C. Rosenblantt Cancer Research Fund and the Rappaport Institute Fund
文摘AIM: Hydrodynamics based transfection (HBT), the injection of a large volume of naked plasmid DNA in a short time is a relatively simple, efficient and safe method for in vivo transfection of liver cells. Though used for quite some time, the mechanism of gene transfection has not yet been elucidated. METHODS: A luciferase encoding plasmid was injected using the hydrodynamics based procedure into normal and thioacetamide-induced fibrotic Sprague Dawley rats. Scanning and transmission electron microscopy images were taken. The consequence of a dual injection of Ringer solution and luciferase pDNA was followed. Halofuginone, an anti collagen type I inhibitor was used to reduce ECM load in fibrotic rats prior to the hydrodynamic injection. RESULTS: Large endothelial gaps formed as soon as 10’ following hydrodynamic injection; these gradually returned to normal 10 d post injection. Hydrodynamic administration of Ringer 10 or 30 m prior to moderate injection of plasmid did not result in efficient transfection suggesting that endothelial gaps by themselves are not sufficient for gene expression. Gene transfection following hydrodynamic injection in thioacetamide induced fibrotic rats was diminished coinciding with the level of fibrosis. Halofuginone, a specific collagen typeⅠ inhibitor, alleviated this effect. CONCLUSION: The hydrodynamic pressure formedfollowing HBT results in the formation of large endothelial gaps. These gaps, though important in the transfer of DNA molecules from the blood to the space of Disse are not enough to provide the appropriate conditions for hepatocyte transfection. Hydrodynamics based injection is applicable in fibrotic rats provided that ECM load is reduced.
文摘AIM: To compare the outcome of an Ex-Press implant and subscleral trabeculectomy(SST) in the management of glaucoma after previous trabeculectomy on a fibrotic bleb.METHODS: This randomized prospective study included 28 eyes from 28 patients(age range: 42-55 y) with primary open angle glaucoma(POAG) presented with elevated intraocular pressure(IOP) with fibrotic bleb despite previous SST for more than 4 mo. The eyes enrolled in the study were divided into two groups: group I(subjected to Ex-Press implant surgery) and group II [subjected to SST with mitomycin C(MMC)]. The follow-up continued one year after surgery to evaluate IOP, visual acuity(VA), visual field(VF), and postoperative complications. RESULTS: A significant decrease in IOP was found in both groups with a higher reduction in Ex-Press implant surgery with the mean IOP of 14.50 mm Hg(P=0.001), while the SST group recorded the mean IOP of 16.50 mm Hg(P=0.001) after one year. However, the difference between the two groups in terms of the decrease in IOP was insignificant. Fewer postoperative complications were recorded in the Ex-Press implant surgery and more cases requiring further anti-glaucomatous medications were seen in the SST group. Both groups showed stability in terms of VA and VF.CONCLUSION: Ex-Press implant surgery and SST with MMC are two surgical alternatives for controlling IOP in late failure that occurs more than 4 mo after previous SST with a fibrotic bleb. However, Ex-Press shunt is a safer surgery with fewer complications.
文摘Background: Complete hypopharyngo-oesophageal occlusion is a rare complication of head and neck radiotherapy and a range of other conditions. Absolute dysphagia is accompanied by aspiration and dependence on gastrostomy feeding. The condition presents a substantial management challenge. Surgical approaches to re-establish pharyngo-oesophageal continuity are varied, highly invasive and are associated with unpredictable outcomes. Minimally invasive techniques employing endoscopic and radiological techniques are emerging. This report describes a multidisciplinary approach which translates two interventional radiology techniques used in the management of central venous occlusions and biliary strictures to the management of three cases of complete hypopharyngo-oesophageal occlusion. Methods: Three cases with different underlying aetiologies had treatment initiated between 2009 and 2011. Antegrade pharyngoscopic access to the occlusions was accompanied by retrograde endoscopic access via a small gastrostomy. Luminal continuity was re-established by the interventional radiology technique of “sharp recanalisation” followed by passage of a wide bore nasogastric tube which was maintained in situ for 4-6 months, a duration of treatment analogous to that applied in the radiological management of fibrotic biliary strictures. After treatment a radiological contrast swallows examination was performed to gauge the calibre of the re-established lumen, assess functionality and to rule out aspiration. Results: Pharyngo-oesophageal continuity was re-established in all three cases on the first attempt. No complications occurred as a result of the procedures. In two cases, the excellent swallowing function was re-established, although one of these required prolonged post-treatment adjuvant interventions. In one case no swallowing function resulted, despite apparently successful re-establishment of luminal continuity. Conclusions: Complete fibrotic occlusion of the hypopharyngo-oesophageal lumen is rare and presents a substantial management challenge. A minimally invasive treatment combining antegrade radiological and retrograde endoscopic approaches resulted in successful re-establishment of luminal continuity in three cases of complete fibrotic occlusion of the hypopharyngo-oesophageal lumen. However variable responses to treatment suggest that both the underlying aetiology and the chronicity of the occlusion may influence the likelihood of a successful functional outcome. Until definitive management guidelines are established, we suggest that such cases are managed only by motivated multidisciplinary teams keen to develop their expertise in this area.
文摘BACKGROUND Fibrotic hypersensitivity pneumonitis(FHP)is an allergic and diffuse pneumonia caused by repeated inhalation of antigenic substances,and sometimes developed in people working in specific environments.While novel antigens and exposures continued to be described,physicians should maintain a high suspicion of potential exposures.A detailed assessment of the patient's occupational exposures as well as living environment is necessary and complete allergen avoidance is the first and most important step in the management of FHP once the allergens are determined.CASE SUMMARY A 35-year-old female was admitted to the hospital with a cough and breathing difficulties for more than one year.She was a nonsmoker and a manufacturer of halogen dishes,which are characteristic Chinese foods,for 15 years without any protection.High resolution computed tomography of the chest demonstrated an interstitial pneumonia pattern.Pulmonary function examination showed restricted ventilation dysfunction and a significant reduction in dispersion ability.Cell differentiation in bronchoalveolar lavage fluid demonstrated lymphocytosis(70.4%)with an increased lymphocyte CD4/CD8 ratio(0.94).Transbronchial lung biopsy combined with lung puncture pathology showed diffuse uniform alveolar interval thickening,chronic inflammatory cell infiltration,a proliferation of tissue in the bronchial wall fiber and alveolar epithelial follicle degeneration,resulting in fibrosis.CONCLUSION Exposure to spices used for the production of halogen dishes may cause FHP.
基金supported by the National Natural Sclence Foundation of China in 2021No.82171213+1 种基金the Natural Science Foundation of Fujian Province in 2019No.2019J01289 (both to DSL)
文摘The trigeminal root entry zone is the zone at which the myelination switches from peripheral Schwann cells to central oligodendrocytes.Its special anatomical and physiological structure renders it susceptible to nerve injury.The etiology of most primary trigeminal neuralgia is closely related to microvascular compression of the trigeminal root entry zone.This study aimed to develop an efficient in vitro model mimicking the glial environment of trigeminal root entry zone as a tool to investigate the effects of glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor on the structural and functional integrity of trigeminal root entry zone and modulation of cellular interactions.Primary astrocytes and Schwann cells isolated from trigeminal root entry zone of postnatal rats were inoculated into a two-well silicon culture insert to mimic the trigeminal root entry zone microenvironment and treated with glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor.In monoculture,glial cell line-derived neurotrophic factor promoted the migration of Schwann cells,but it did not have effects on the migration of astrocytes.In the co-culture system,glial cell line-derived neurotrophic factor promoted the bidirectional migration of astrocytes and Schwann cells.Brain-derived neurotrophic factor markedly promoted the activation and migration of astrocytes.However,in the co-culture system,brain-derived neurotrophic factor inhibited the migration of astrocytes and Schwann cells to a certain degree.These findings suggest that glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor are involved in the regulation of the astrocyte-Schwann cell interaction in the co-culture system derived from the trigeminal root entry zone.This system can be used as a cell model to study the mechanism of glial dysregulation associated with trigeminal nerve injury and possible therapeutic interventions.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82071287,81870916)the National Natural Science Foundation of China(Grant No.:81971097)+3 种基金the Basic Public Interests Research Plan of Zhejiang Province,China(Grant No.:GF18H090006)the National Natural Science Foundation of China(Grant No.:81701214)the National Natural Science Foundation of China(Grant No.:82001299)the Natural Science Foundation of Zhejiang Province,China(Grant No.:TGD23C040017).
文摘The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to investigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial scar.We used a pharmacologic approach to induce microglial depletion during different ICH stages and examine how ablating microglia affects astrocytic scar formation.Spatial transcriptomics(ST)analysis was performed to explore the potential ligand-receptor pair in the modulation of microglia-astrocyte interaction and to verify the functional changes of astrocytic scars at different periods.During the early stage,sustained microglial depletion induced disorganized astrocytic scar,enhanced neutrophil infiltration,and impaired tissue repair.ST analysis indicated that microglia-derived insulin like growth factor 1(IGF1)modulated astrocytic scar formation via mechanistic target of rapamycin(mTOR)signaling activation.Moreover,repopulating microglia(RM)more strongly activated mTOR signaling,facilitating a more protective scar formation.The combination of IGF1 and osteopontin(OPN)was necessary and sufficient for RM function,rather than IGF1 or OPN alone.At the chronic stage of ICH,the overall net effect of astrocytic scar changed from protective to destructive and delayed microglial depletion could partly reverse this.The vital insight gleaned from our data is that sustained microglial depletion may not be a reasonable treatment strategy for early-stage ICH.Inversely,early-stage IGF1/OPN treatment combined with late-stage PLX3397 treatment is a promising therapeutic strategy.This prompts us to consider the complex temporal dynamics and overall net effect of microglia and astrocytes,and develop elaborate treatment strategies at precise time points after ICH.
基金Supported by Hebei Medical Science Research Project,No.20220648。
文摘BACKGROUND Brain gliomas are malignant tumors with high postoperative recurrence rates.Early prediction of prognosis using specific indicators is of great significance.AIM To assess changes in ubiquitin carboxy-terminal hydrolase L1(UCH-L1)and glial fibrillary acidic protein(GFAP)levels in patients with glioma pre-and postoperatively.METHODS Between June 2018 and June 2021,91 patients with gliomas who underwent surgery at our hospital were enrolled in the glioma group.Sixty healthy volunteers were included in the control group.Serum UCH-L1 and GFAP levels were measured in peripheral blood collected from patients with glioma before and 3 d after surgery.UCH-L1 and GFAP levels in patients with glioma with different clinicopathological characteristics were compared before and after surgery.The patients were followed-up until February 2022.Postoperative glioma recurrence was recorded to determine the serum UCH-L1 and GFAP levels,which could assist in predicting postoperative glioma recurrence.RESULTS UCH-L1 and GFAP levels in patients with glioma decreased significantly 3 d after surgery compared to those before therapy(P<0.05).However,UCH-L1 and GFAP levels in the glioma group were significantly higher than those in the control group before and after surgery(P<0.05).There were no statistically significant differences in preoperative serum UCH-L1 and GFAP levels among patients with glioma according to sex,age,pathological type,tumor location,or number of lesions(P>0.05).Serum UCH-L1 and GFAP levels were significantly lower in the patients with WHO grade I-II tumors than in those with gradeⅢ-IV tumors(P<0.05).Serum UCH-L1 and GFAP levels were lower in the patients with tumor diameter≤5 cm than in those with diameter>5 cm,in which the differences were statistically significant(P<0.05).Glioma recurred in 22 patients.The preoperative and 3-d postoperative serum UCH-L1 and GFAP levels were significantly higher in the recurrence group than these in the non-recurrence group(P<0.05).Receiver operating characteristic curves were plotted.The areas under the curves of preoperative serum UCH-L1 and GFAP levels for predicting postoperative glioma recurrence were 0.785 and 0.775,respectively.However,the efficacy of serum UCH-L1 and GFAP levels 3 d after surgery in predicting postoperative glioma recurrence was slightly lower compared with their preoperative levels.CONCLUSION UCH-L1 and GFAP efficiently reflected the development and recurrence of gliomas and could be used as potential indicators for the recurrence and prognosis of glioma.
文摘目的 基于循证医学,构建一套适用于进行性纤维化间质性肺病患者的规范化肺康复训练方案,丰富肺康复指导的系统教育方案内涵,为临床康复护理提供科学指导。方法 计算机检索中国WanFang数据库、中国知网数据库(CNKI)、维普数据库(VIP)、中国生物医学文献数据库(CBM)、PubMed、Embase、Cochrane Library、Web of Science数据库文献及指南网站,以循证医学为指导,通过文献回顾分析,采用《临床指南研究与评价系统》(Appraisal of Guidelines for Research and Evaluation,AGREEⅡ)评价指南质量及澳大利亚JBI(Joanna Briggs Institute)循证卫生保健中心开发的文献质量评价工具对随机对照试验、系统评价、类实验文献进行质量评价,对纳入的文献进行全文阅读及等级划分,以汇总最佳证据,拟定进行性纤维化间质性肺病患者肺康复训练方案初稿,最后结合专家会议和专家咨询结果,对方案初稿进行可用性评鉴,最终修订完善方案。结果 经文献质量评价及筛选后,共纳入30篇文献,其中指南与专家共识3篇,随机对照试验文献16篇,系统评价文献6篇,类实验文献5篇。方案内容包括训练评估、呼吸训练、运动训练、健康教育、社会心理干预、营养支持6个一级指标。结论 该研究构建的方案结果可靠,其规范性、科学性和安全性高,能够为进行性纤维化间质性肺病患者临床康复护理工作提供参考。
文摘目的探讨血清低氧诱导因子-1α(HIF-1α)、神经元特异性烯醇化酶(NSE)、胶质纤维酸性蛋白(GFAP)及相关临床特征与新生儿缺氧缺血性脑病(HIE)发生风险的关系。方法选取2020年1月—2023年1月苏州大学附属儿童医院收治的85例HIE患儿作为HIE组,另选取同期在该院出生的120例健康新生儿作为对照组,分析两组的临床资料并检测新生儿出生后3 d血清HIF-1α、NSE、GFAP水平。绘制受试者工作特征(ROC)曲线分析血清HIF-1α、NSE、GFAP水平预测新生儿HIE发病的价值;多因素逐步Logistic回归模型分析新生儿HIE发病的影响因素。结果与对照组相比,HIE组宫内窘迫、脐带异常、羊水污染、1 min Apgar评分≤7分的患儿比例较高(P<0.05),并且血清HIF-1α、NSE、GFAP水平较高(P<0.05);两组孕妇年龄、孕妇文化程度、胎龄、新生儿性别、出生体重、产次、剖宫产、胎膜早破比较,差异均无统计学意义(P>0.05)。ROC曲线分析结果显示,HIF-1α、NSE、GFAP及三者联合预测新生儿HIE发病的敏感性分别为82.7%(95%CI:0.795,0.862)、78.7%(95%CI:0.705,0.849)、84.0%(95%CI:0.803,0.891)、85.3%(95%CI:0.788,0.922),特异性分别为85.3%(95%CI:0.816,0.907)、74.7%(95%CI:0.715,0.796)、72.0%(95%CI:0.692,0.771)、90.5%(95%CI:0.825,0.956),AUC分别为0.907(95%CI:0.884,0.930)、0.850(95%CI:0.816,0.884)、0.893(95%CI:0.827,0.959)、0.936(95%CI:0.905,0.967);多因素逐步Logistic回归分析显示,宫内窘迫[O^R=3.592(95%CI:2.017,6.397)]、脐带异常[O^R=4.905(95%CI:2.862,8.406)]、羊水污染[O^R=7.262(95%CI:3.603,14.637)]、1 min Apgar评分≤7分[O^R=3.139(95%CI:1.954,5.043)]、HIF-1α≥0.463 ng/mL[O^R=2.916(95%CI:1.422,5.980)]、NSE≥12.395μg/L[O^R=3.714(95%CI:1.955,7.056)]、GFAP≥3.962 ng/mL[O^R=3.556(95%CI:2.039,6.202)]均是新生儿HIE发病的危险因素(P<0.05)。结论宫内窘迫、脐带异常、羊水污染、出生后1 min Apgar评分低及血清HIF-1α、NSE、GFAP水平高是新生儿HIE发病的危险因素,临床通过检测血清HIF-1α、NSE、GFAP水平可为临床筛查HIE提供帮助,3项指标联合检测可进一步提高诊断价值。