Objective To investigate the differences in clinical characteristics,surgical outcomes,and prognosis between sporadic intracranial hemangioblastoma(IC-HB)and von Hippel-Lindau(VHL)syndrome-associated IC-HB.Methods A retrospective consecutive series of patients who underwent microsurgical resection at the Department of Neurosurgery,Xuanwu Hospital,Capital Medical University,between April 2014 and January 2024,with postoperative pathological confirmation of IC-HB,was included.Clinical and imaging data were collected,including demographics(sex,age),preoperative clinical manifestations(asymptomatic,headache,dizziness,vertigo or imbalance,blurred vision or papilledema,nausea or vomiting,other symptoms),number of symptoms,lesion type(solid or solid-cystic),lesion size(volume,longest diameter,anteroposterior diameter,superoinferior diameter,transverse diameter),lesion location(cerebellar region:hemisphere,vermis;brainstem region:medulla oblongata,fourth ventricle;skull base region:cerebellopontine angle,jugular foramen,petroclival region),Karnofsky performance status(KPS)score(preoperative,postoperative;KPS score＞70 and 70),surgical information,and follow-up data.Based on past medical history,family history,and VHL gene test results,patients were classified into sporadic IC-HB and VHL syndrome-associated IC-HB groups.Differences in clinical characteristics,surgical outcomes,and follow-up status were compared between the groups.Improved outcomes were defined as increases in KPS scores over 0 at 6-month follow-ups in comparison with preoperative KPS,while non-improved outcomes were defined by unchanged or decreased(＞0 point)KPS scores.Survival outcomes,including postoperative recurrence(newly occurring abnormally enhancing nodules at the surgical site or periphery with continuous development during follow-ups.Recurrence could be verified through the combination of imaging enhancement features,clinical manifestations and post-operative pathological examinations),postoperative KPS improvement,and death of any cause during follow-up.The outcomes of postoperative KPS improvement versus non-improvement(unchanged or worsened)were analyzed through univariate analysis with the Firth penalized maximum likelihood Logistic regression model.Variables meeting the criteria(P＜0.05 in univariate analysis,clinical importance,statistical model feasibility)were included in a multivariate Logistic regression model to identify independent factors influencing functional outcomes.Survival outcomes were analyzed using Cox proportional hazards regression models.Kaplan-Meier survival analysis was used to assess recurrence-free survival rates between groups with the Log-rank test.Furthermore,univariate and multivariate Logistic regression analyses were performed separately for the sporadic IC-HB and VHL syndrome-associated IC-HB subgroups to explore independent factors for postoperative KPS improvement.Results A total of 82 IC-HB patients(41 male,41 female),aged 11-73 years(mean[42±15]years),were included.Among which,68 had sporadic IC-HB and 14 had VHL syndrome-associated IC-HB.39 patients had improved postoperative KPS and 43 patients showed no improvements in KPS scores.(1)For clinical characteristics,the age of onset was younger in the VHL syndrome-associated IC-HB group([35±14]years vs.[44±15]years,P=0.044).Lesions in VHL syndrome-associated IC-HB patients were more likely to involve the brainstem and adjacent critical structures(8/14 of which involved medulla oblongata),while sporadic IC-HB was more common in the cerebellar hemispheres(70.6％[48/68]).The distribution of lesion location across cerebellar,skull base,and brainstem regions differed significantly between groups(P=0.015),while other characteristics showed no significant differences(all P＞0.05).(2)For treatment and follow-ups,all patients underwent gross total microsurgical resection.Preoperative angiography via femoral artery was performed in 22 patients,with partial preoperative embolization in 4 patients.Postoperatively,KPS improved in 39 patients,remained unchanged in 33 patients,and worsened in 10 patients.The change in KPS scores pre-to post-operatively did not differ significantly between groups(P=0.707).The recurrence rate was higher in the VHL syndrome-associated IC-HB group(4/14 vs.5.9％[4/68],P=0.026),but there was no significant difference in mortality(P=0.999).(3)For analysis of factors influencing postoperative KPS improvement,univariate Logistic regression showed preoperative asymptomatic(OR,0.05,95％CI0.00-0.39,P=0.002),preoperative dizziness(OR,2.62,95％CI 1.09-6.47,P=0.031),vertigo/imbalance(OR,3.60,95％CI 1.04-15.45,P=0.043),nausea/vomiting(OR,4.49,95％CI 1.65-13.53,P=0.003),preoperative symptoms(OR,2.27,95％CI 1.46-3.86,P＜0.01)and preoperative KPS ≤70(OR,7.65,95％CI 1.60-74.47,P=0.009)were strongly associated with KPS improvement.Multivariate Logistic regression only identified the number of preoperative symptoms as an independent predictor of postoperative KPS improvement(OR,2.44,95％CI 1.04-6.32,P=0.049).(4)For survival outcome analysis,no significant differences in the risk of postoperative recurrence,KPS improvement,or death were observed between the VHL syndrome-associated and sporadic IC-HB patients(recurrence:HR,4.88,95％CI 0.97-24.69,P=0.055;KPS improvement:HR,0.60,95％CI 0.25-1.43,P=0.246;mortality:P=0.999).Kaplan-Meier curves showed no statistically significant difference in recurrence-free survival rate between groups(P=0.053).(5)In the subgroup analysis,in sporadic IC-HB patients,multivariate Logistic regression identified the number of preoperative symptoms as an independent predictor of postoperative KPS improvement(OR,1.97,95％CI 1.14-3.68,P=0.021).Due to the small sample size,reliable parameter estimation was not possible for the VHL syndrome-associated IC-HB subgroup due to the small sample size.Conclusions VHL syndrome-associated IC-HB patients have a higher risk of recurrence in comparison with sporadic IC-HB patients.The number of preoperative symptoms can guide survival ending assessment.

The intestine in a hypoxic state is an essential physiological organ,and its primary func-tions include digestion,absorption,excretion,hormone secretion,and providing barrier and immune protec-tion.Hypoxia-inducible factor-2α(HIF-2α)represents one of the important physiologicalregulators for the intestine,partaking in the regulation of iron homeostasis,oxygen homeostasis and energy metabo-lism in the intestinal environment.Recent studies have shown that HIF-2α is closely associated with the onset and progression of various intestinal-related diseases,including iron-relatedblood diseases,inflam-matory bowel disease(IBD),colorectal cancer(CRC),and obesity-related metabolic diseases.Thus,HIF-2α may be a novel target for the treatment.HIF-2α is currently a hot topic in drug development,and numerous studies have revealed that it has therapeutic potential for intestinal-related diseases.HIF-2α is a key transcription factor that regulates intestinal iron absorption and systemic iron homeostasis.Aberrant expression of HIF-2α has been closely linked to various hematological disorders associated with iron metabolism dysregulation.In the pathological hypoxic microenvironment of the intestine,sustained activation of HIF-2α induces inflammatory response and impairs epithelial barrier function,thereby exacerbating the progression of IBD.Within the tumor microenvironment,HIF-2α contributes to CRC progression through multiple mechanisms,including metabolic reprogramming,angiogenesis,enhanced prolifera-tion,migration,and invasion of tumor cells,as well as inflammation,iron accumulation,and immune evasion.Moreover,HIF-2α is involved in the regulation of obesity,insulin resistance,and glucose-lipid metabolism via the gut-liver axis.Although seven HIF-2α modulators have been approved for clinical use,adverse effects such as anemia and thrombosis remain concerns.Therefore,developing next-generation HIF-2α-targeted strategies with improved specificity and safety profiles is critical to future research.This article is an overview of the recent advancements in understanding the role and mecha-nisms of HIF-2α in intestinal health and associated diseases while analyzing the challenges to develop-ment and application of HIF-2α modulators in the future,in hopes of offering novel therapeutic avenues for intestinal-related ailments.

Objective:To construct a prediction model for postoperative poor in-hospital prognosis in patients with traumatic brain injury (TBI) and evaluate its predictive performance.Methods:A retrospective case control study was conducted to analyze the clinical data of 1 120 TBI patients admitted to Changde Hospital Affiliated to Xiangya Medical College of Central South University from May 2019 to December 2024. The patients were divided into the training set ( n=784) and verification set ( n=336) at a ratio of 7∶3. Based on the Glasgow outcome scale-extended (GOS-E) at discharge, the training set was stratified into favorable prognosis group ( n=335, GOS-E 5-8 points) and poor prognosis group ( n=449, GOS-E 1-4 points). The two groups in the training set were compared in terms of general baseline indicators, TBI-related clinical indicators, and admission laboratory blood test results. Univariate analysis and Lasso regression analysis were employed to screen risk factors associated with postoperative poor in-hospital prognosis in TBI patients. Multivariate Logistic regression analysis was used to determine independent risk factors and construct a regression equation. The regression equation was presented using R language to create a visual nomogram for predicting postoperative poor in-hospital prognosis in TBI patients. In both the training set and verification set, the predictive performance of the model was evaluated by calculating the area under the receiver operating characteristic (ROC) curve (AUC), plotting calibration curves, and performing decision curve analysis (DCA). Results:The results of the univariate analysis indicated that the age, Charlson complication index (CCI), time from trauma to admission, time from trauma to operation, cause of injury, abbreviated injury scale (AIS) (head and neck), injury severity score (ISS), admission Glasgow coma scale (GCS), admission pupil responsiveness, multiple craniocerebral injuries, subdural hematoma, intracerebral hematoma, intraventricular hemorrhage, subarachnoid hemorrhage, decompressive craniotomy, intraoperative blood loss, intraoperative blood transfusion, traumatic cerebral infarction, postoperative delayed bleeding, epilepsy seizures, as well as the following admission tested results including red blood cell count, white blood cell count, platelet count, neutrophil percentage, percentage of lymphocytes, albumin, total bilirubin, urea nitrogen, thrombin time (TT), prothrombin time (PT), international standardized ratio (INR), glutamic aminotransferase, alanine aminotransferase, creatinine, and blood glucose were statistically different between the two groups in the training set ( P<0.05). Lasso regression analysis suggested 14 risk factors of age, CCI, cause of injury, head and neck AIS, ISS, admission GCS, admission pupil responsiveness, multiple craniocerebral injuries, subdural hematoma, intracerebral hematoma, intraoperative blood loss, admission platelet count, admission albumin, admission blood glucose for postoperative poor in-hospital prognosis. The results of the multivariate Logistic regression analysis showed that age ( OR=1.02, 95% CI 1.00, 1.03, P<0.01), CCI ( OR=1.46, 95% CI 1.02, 2.09, P<0.05), head and neck AIS ( OR=1.43, 95% CI 1.11, 1.85, P<0.01), ISS ( OR=2.16, 95% CI 1.39, 3.35, P<0.01), admission GCS ( OR=1.59, 95% CI 1.19, 2.13, P<0.01), intracerebral hematoma ( OR=4.41, 95% CI 2.15, 9.44, P<0.01), intraoperative blood loss ( OR=1.05, 95% CI 1.00, 1.09, P<0.05), admission platelet count ( OR=0.98, 95% CI 0.97, 0.99, P<0.01), admission blood glucose ( OR=1.08, 95% CI 1.02, 1.15, P<0.05) could be the main risk factors to construct a prediction model for postoperative poor in-hospital prognosis in TBI patients. Meanwhile, a regression equation was constructed: Logit[ P/(1- P)]=-2.4+ 0.02×"age"+0.38×"CCI"+0.36×"head and neck AIS"+0.77×"ISS"+0.47×"admission GCS"+1.48×"intracerebral hematoma"+0.05×intraoperative blood loss-0.02×admission platelet count+0.08×admission blood glucose. In the training set, the predictive model for poor postoperative in-hospital prognosis in TBI patients achieved an AUC of 0.87 (95% CI 0.84, 0.89), with a Youden′s index of 0.57, sensitivity of 73.70%, and specificity of 83.00%. In the verification set, the model showed an AUC of 0.80 (95% CI 0.76, 0.85), with a Youden′s index of 0.63, sensitivity of 65.20%, and specificity of 77.90%. In the training set, the Brier score for the calibration curve was 0.14 (95% CI 0.13, 0.16). In the verification set, the Brier score for the calibration curve was 0.18 (95% CI 0.15, 0.20). The DCA diagram indicated that the nomogram prediction model provided high clinical net benefit for predicting postoperative poor in-hospital prognosis in TBI patients. Conclusion:The prediction model for postoperative poor in-hospital prognosis in TBI patients, constructed based on age, CCI, head and neck AIS, ISS, admission GCS, intracerebral hematoma, intraoperative blood loss, admission platelet count, and admission blood glucose, exhibits good predictive performance.

Objective:To construct a prediction model for postoperative poor in-hospital prognosis in patients with traumatic brain injury (TBI) and evaluate its predictive performance.Methods:A retrospective case control study was conducted to analyze the clinical data of 1 120 TBI patients admitted to Changde Hospital Affiliated to Xiangya Medical College of Central South University from May 2019 to December 2024. The patients were divided into the training set ( n=784) and verification set ( n=336) at a ratio of 7∶3. Based on the Glasgow outcome scale-extended (GOS-E) at discharge, the training set was stratified into favorable prognosis group ( n=335, GOS-E 5-8 points) and poor prognosis group ( n=449, GOS-E 1-4 points). The two groups in the training set were compared in terms of general baseline indicators, TBI-related clinical indicators, and admission laboratory blood test results. Univariate analysis and Lasso regression analysis were employed to screen risk factors associated with postoperative poor in-hospital prognosis in TBI patients. Multivariate Logistic regression analysis was used to determine independent risk factors and construct a regression equation. The regression equation was presented using R language to create a visual nomogram for predicting postoperative poor in-hospital prognosis in TBI patients. In both the training set and verification set, the predictive performance of the model was evaluated by calculating the area under the receiver operating characteristic (ROC) curve (AUC), plotting calibration curves, and performing decision curve analysis (DCA). Results:The results of the univariate analysis indicated that the age, Charlson complication index (CCI), time from trauma to admission, time from trauma to operation, cause of injury, abbreviated injury scale (AIS) (head and neck), injury severity score (ISS), admission Glasgow coma scale (GCS), admission pupil responsiveness, multiple craniocerebral injuries, subdural hematoma, intracerebral hematoma, intraventricular hemorrhage, subarachnoid hemorrhage, decompressive craniotomy, intraoperative blood loss, intraoperative blood transfusion, traumatic cerebral infarction, postoperative delayed bleeding, epilepsy seizures, as well as the following admission tested results including red blood cell count, white blood cell count, platelet count, neutrophil percentage, percentage of lymphocytes, albumin, total bilirubin, urea nitrogen, thrombin time (TT), prothrombin time (PT), international standardized ratio (INR), glutamic aminotransferase, alanine aminotransferase, creatinine, and blood glucose were statistically different between the two groups in the training set ( P<0.05). Lasso regression analysis suggested 14 risk factors of age, CCI, cause of injury, head and neck AIS, ISS, admission GCS, admission pupil responsiveness, multiple craniocerebral injuries, subdural hematoma, intracerebral hematoma, intraoperative blood loss, admission platelet count, admission albumin, admission blood glucose for postoperative poor in-hospital prognosis. The results of the multivariate Logistic regression analysis showed that age ( OR=1.02, 95% CI 1.00, 1.03, P<0.01), CCI ( OR=1.46, 95% CI 1.02, 2.09, P<0.05), head and neck AIS ( OR=1.43, 95% CI 1.11, 1.85, P<0.01), ISS ( OR=2.16, 95% CI 1.39, 3.35, P<0.01), admission GCS ( OR=1.59, 95% CI 1.19, 2.13, P<0.01), intracerebral hematoma ( OR=4.41, 95% CI 2.15, 9.44, P<0.01), intraoperative blood loss ( OR=1.05, 95% CI 1.00, 1.09, P<0.05), admission platelet count ( OR=0.98, 95% CI 0.97, 0.99, P<0.01), admission blood glucose ( OR=1.08, 95% CI 1.02, 1.15, P<0.05) could be the main risk factors to construct a prediction model for postoperative poor in-hospital prognosis in TBI patients. Meanwhile, a regression equation was constructed: Logit[ P/(1- P)]=-2.4+ 0.02×"age"+0.38×"CCI"+0.36×"head and neck AIS"+0.77×"ISS"+0.47×"admission GCS"+1.48×"intracerebral hematoma"+0.05×intraoperative blood loss-0.02×admission platelet count+0.08×admission blood glucose. In the training set, the predictive model for poor postoperative in-hospital prognosis in TBI patients achieved an AUC of 0.87 (95% CI 0.84, 0.89), with a Youden′s index of 0.57, sensitivity of 73.70%, and specificity of 83.00%. In the verification set, the model showed an AUC of 0.80 (95% CI 0.76, 0.85), with a Youden′s index of 0.63, sensitivity of 65.20%, and specificity of 77.90%. In the training set, the Brier score for the calibration curve was 0.14 (95% CI 0.13, 0.16). In the verification set, the Brier score for the calibration curve was 0.18 (95% CI 0.15, 0.20). The DCA diagram indicated that the nomogram prediction model provided high clinical net benefit for predicting postoperative poor in-hospital prognosis in TBI patients. Conclusion:The prediction model for postoperative poor in-hospital prognosis in TBI patients, constructed based on age, CCI, head and neck AIS, ISS, admission GCS, intracerebral hematoma, intraoperative blood loss, admission platelet count, and admission blood glucose, exhibits good predictive performance.

Objective To investigate the differences in clinical characteristics,surgical outcomes,and prognosis between sporadic intracranial hemangioblastoma(IC-HB)and von Hippel-Lindau(VHL)syndrome-associated IC-HB.Methods A retrospective consecutive series of patients who underwent microsurgical resection at the Department of Neurosurgery,Xuanwu Hospital,Capital Medical University,between April 2014 and January 2024,with postoperative pathological confirmation of IC-HB,was included.Clinical and imaging data were collected,including demographics(sex,age),preoperative clinical manifestations(asymptomatic,headache,dizziness,vertigo or imbalance,blurred vision or papilledema,nausea or vomiting,other symptoms),number of symptoms,lesion type(solid or solid-cystic),lesion size(volume,longest diameter,anteroposterior diameter,superoinferior diameter,transverse diameter),lesion location(cerebellar region:hemisphere,vermis;brainstem region:medulla oblongata,fourth ventricle;skull base region:cerebellopontine angle,jugular foramen,petroclival region),Karnofsky performance status(KPS)score(preoperative,postoperative;KPS score＞70 and 70),surgical information,and follow-up data.Based on past medical history,family history,and VHL gene test results,patients were classified into sporadic IC-HB and VHL syndrome-associated IC-HB groups.Differences in clinical characteristics,surgical outcomes,and follow-up status were compared between the groups.Improved outcomes were defined as increases in KPS scores over 0 at 6-month follow-ups in comparison with preoperative KPS,while non-improved outcomes were defined by unchanged or decreased(＞0 point)KPS scores.Survival outcomes,including postoperative recurrence(newly occurring abnormally enhancing nodules at the surgical site or periphery with continuous development during follow-ups.Recurrence could be verified through the combination of imaging enhancement features,clinical manifestations and post-operative pathological examinations),postoperative KPS improvement,and death of any cause during follow-up.The outcomes of postoperative KPS improvement versus non-improvement(unchanged or worsened)were analyzed through univariate analysis with the Firth penalized maximum likelihood Logistic regression model.Variables meeting the criteria(P＜0.05 in univariate analysis,clinical importance,statistical model feasibility)were included in a multivariate Logistic regression model to identify independent factors influencing functional outcomes.Survival outcomes were analyzed using Cox proportional hazards regression models.Kaplan-Meier survival analysis was used to assess recurrence-free survival rates between groups with the Log-rank test.Furthermore,univariate and multivariate Logistic regression analyses were performed separately for the sporadic IC-HB and VHL syndrome-associated IC-HB subgroups to explore independent factors for postoperative KPS improvement.Results A total of 82 IC-HB patients(41 male,41 female),aged 11-73 years(mean[42±15]years),were included.Among which,68 had sporadic IC-HB and 14 had VHL syndrome-associated IC-HB.39 patients had improved postoperative KPS and 43 patients showed no improvements in KPS scores.(1)For clinical characteristics,the age of onset was younger in the VHL syndrome-associated IC-HB group([35±14]years vs.[44±15]years,P=0.044).Lesions in VHL syndrome-associated IC-HB patients were more likely to involve the brainstem and adjacent critical structures(8/14 of which involved medulla oblongata),while sporadic IC-HB was more common in the cerebellar hemispheres(70.6％[48/68]).The distribution of lesion location across cerebellar,skull base,and brainstem regions differed significantly between groups(P=0.015),while other characteristics showed no significant differences(all P＞0.05).(2)For treatment and follow-ups,all patients underwent gross total microsurgical resection.Preoperative angiography via femoral artery was performed in 22 patients,with partial preoperative embolization in 4 patients.Postoperatively,KPS improved in 39 patients,remained unchanged in 33 patients,and worsened in 10 patients.The change in KPS scores pre-to post-operatively did not differ significantly between groups(P=0.707).The recurrence rate was higher in the VHL syndrome-associated IC-HB group(4/14 vs.5.9％[4/68],P=0.026),but there was no significant difference in mortality(P=0.999).(3)For analysis of factors influencing postoperative KPS improvement,univariate Logistic regression showed preoperative asymptomatic(OR,0.05,95％CI0.00-0.39,P=0.002),preoperative dizziness(OR,2.62,95％CI 1.09-6.47,P=0.031),vertigo/imbalance(OR,3.60,95％CI 1.04-15.45,P=0.043),nausea/vomiting(OR,4.49,95％CI 1.65-13.53,P=0.003),preoperative symptoms(OR,2.27,95％CI 1.46-3.86,P＜0.01)and preoperative KPS ≤70(OR,7.65,95％CI 1.60-74.47,P=0.009)were strongly associated with KPS improvement.Multivariate Logistic regression only identified the number of preoperative symptoms as an independent predictor of postoperative KPS improvement(OR,2.44,95％CI 1.04-6.32,P=0.049).(4)For survival outcome analysis,no significant differences in the risk of postoperative recurrence,KPS improvement,or death were observed between the VHL syndrome-associated and sporadic IC-HB patients(recurrence:HR,4.88,95％CI 0.97-24.69,P=0.055;KPS improvement:HR,0.60,95％CI 0.25-1.43,P=0.246;mortality:P=0.999).Kaplan-Meier curves showed no statistically significant difference in recurrence-free survival rate between groups(P=0.053).(5)In the subgroup analysis,in sporadic IC-HB patients,multivariate Logistic regression identified the number of preoperative symptoms as an independent predictor of postoperative KPS improvement(OR,1.97,95％CI 1.14-3.68,P=0.021).Due to the small sample size,reliable parameter estimation was not possible for the VHL syndrome-associated IC-HB subgroup due to the small sample size.Conclusions VHL syndrome-associated IC-HB patients have a higher risk of recurrence in comparison with sporadic IC-HB patients.The number of preoperative symptoms can guide survival ending assessment.

The intestine in a hypoxic state is an essential physiological organ,and its primary func-tions include digestion,absorption,excretion,hormone secretion,and providing barrier and immune protec-tion.Hypoxia-inducible factor-2α(HIF-2α)represents one of the important physiologicalregulators for the intestine,partaking in the regulation of iron homeostasis,oxygen homeostasis and energy metabo-lism in the intestinal environment.Recent studies have shown that HIF-2α is closely associated with the onset and progression of various intestinal-related diseases,including iron-relatedblood diseases,inflam-matory bowel disease(IBD),colorectal cancer(CRC),and obesity-related metabolic diseases.Thus,HIF-2α may be a novel target for the treatment.HIF-2α is currently a hot topic in drug development,and numerous studies have revealed that it has therapeutic potential for intestinal-related diseases.HIF-2α is a key transcription factor that regulates intestinal iron absorption and systemic iron homeostasis.Aberrant expression of HIF-2α has been closely linked to various hematological disorders associated with iron metabolism dysregulation.In the pathological hypoxic microenvironment of the intestine,sustained activation of HIF-2α induces inflammatory response and impairs epithelial barrier function,thereby exacerbating the progression of IBD.Within the tumor microenvironment,HIF-2α contributes to CRC progression through multiple mechanisms,including metabolic reprogramming,angiogenesis,enhanced prolifera-tion,migration,and invasion of tumor cells,as well as inflammation,iron accumulation,and immune evasion.Moreover,HIF-2α is involved in the regulation of obesity,insulin resistance,and glucose-lipid metabolism via the gut-liver axis.Although seven HIF-2α modulators have been approved for clinical use,adverse effects such as anemia and thrombosis remain concerns.Therefore,developing next-generation HIF-2α-targeted strategies with improved specificity and safety profiles is critical to future research.This article is an overview of the recent advancements in understanding the role and mecha-nisms of HIF-2α in intestinal health and associated diseases while analyzing the challenges to develop-ment and application of HIF-2α modulators in the future,in hopes of offering novel therapeutic avenues for intestinal-related ailments.

Objective To optimize the preparation process of hydroxysafflor yellow A(HSYA)nanoparticle and conduct in vitro release evaluation.Methods HSYA nanoparticles were prepared with PLGA as carrier by modified compound emulsion method.The optimal preparation process of the experiment was selected by Plackett-Burman and Box-Behnken response surface method.The nanoparticles were characterized by using particle size analyzer,TEM scanning electron microscope,Fourier transform infrared spectroscopy(FT-IR),X-ray diffraction(XRD).Frozen(4℃)storage stability,stability in physiological medium,lyophilized protective agent and in vitro release rate were investigated.Results The optimal process prescription of nanoparticle is as follow:pH value is 6.95,the dosage is 2.8 mg,and carrier dosage is 18.2 mg.The size of nanoparticles obtained at optimum condition is(176.4±1.29)nm,the polydiseperse index(PDI)is 0.152±0.014,the Zeta potential is(-17.6±0.46)mV,the encapsulation rate is(78.5±0.49)％,drug loading is(7.3±0.07)％.These nanoparticles showed round and good dispersion.Good stability in 4℃ storage environment and different physiological media of nanoparticles were observed.The best lyophilized protective agent was 1％glucose and the in vitro release rate of nanoparticles at 48 hours was 85％.Conclusion The optimization method is reasonable and reliable.The obtained nanoparticles have good stability and sustained-release effect.The in vitro release behavior conformed to first-order kinetic model.

Objective:To observe the regulatory effect of microRNA-10b(miR-10b)on the immune effect of glioma cells and explore its mechanism.Methods:Human glioma cell U251 was cultured to obtain cells in logarithmic growth stage.The cell suspen-sion was prepared according to the concentration of 1.0×105 cells/ml,and the control group,overexpression group,low expression group and blank group were set up,with 6 wells in each group.The negative control,miR-10b mimics and miR-10b inhibitor were transfected by liposome transfection in control group,overexpression group and low expression group,respectively.The blank group was given the same amount of sterile normal saline.Natural killer(NK)cells from peripheral blood of a healthy volunteer was isolated and cultured.The killing activity of NK cells was detected by MTT method.The expression of NK cell activated receptor(NKG2D)on the surface of NK cells in each group were detected by flow cytometry,and the expression of major histocompatibility complex class Ⅰ chain-related gene A(MICA),UL16 binding protein 2(ULBP2)and UL16 binding protein 3(ULBP3)on the surface of U251 hu-man glioma cells in each group were detected.Results:The transfection efficiency of control group,overexpression group and low ex-pression group were(93.55±2.05)％,(95.67±3.14)％,(94.18±3.26)％,respectively.Compared with control group and blank group,the expression of miR-10b increased in overexpression group and decreased in low expression group,and the difference were statisti-cally significant(P<0.05).There was no significant difference in the expression of miR-10b between control group and blank group(P>0.05).Compared with control group and blank group,the killing activity of NK cells with different effect target ratios in overex-pression group decreased,the expression of NKG2D decreased,the killing activity of NK cells with different effect target ratios in low expression group increased,and the expression of NKG2D increased,and the difference were statistically significant(P<0.05).The killing activity of NK cells in each group increased with the increase of effect target ratio,and the difference were statistically signifi-cant(P<0.05),and there was no significant difference in NK cell killing activity and NKG2D expression between control group and blank group(P>0.05).Compared with control group and blank group,the expression of MICA,ULBP2 and ULBP3 on the surface of human glioma cell U251 in overexpression group decreased,and the expression of MICA,ULBP2 and ULBP3 on the surface of human glioma cell U251 in low expression group increased,the difference were statistically significant(P<0.05),and there was no signifi-cant difference in the expression of MICA,ULBP2 and ULBP3 on the surface of U251 glioma cells between control group and blank group(P>0.05).Conclusion:Inhibiting the expression of miR-10b can increase the expression of NKG2D on the surface of NK cells and MICA,ULBP2 and ULBP3 on the surface of human glioma cell U251,and enhance the killing activity of NK cells against human glioma cell U251.

Objective:To evaluate the role of Z-DNA-binding protein 1 (ZBP1)/receptor-interacting protein kinase 1 (RIPK1) signaling pathway in lipopolysaccharide (LPS)-adenosine triphosphate (ATP)-induced pyroptosis in macrophages of mice.Methods:The RAW264.7 macrophages from mice were routinely cultured and divided into 6 groups ( n=9 each) using a random number table method: control group (group C), LPS-ATP group, LPS-ATP+ transfection negative control scRNA group (group LPS-ATP+ scRNA), LPS-ATP+ ZBP1 small interference RNA group (group LPS-ATP+ siRNA), LPS-ATP+ dimethyl sulfoxide group (group LPS-ATP+ DSMO), and LPS-ATP+ RIPK1 inhibitor nec-1 group (group LPS-ATP+ nec-1). The siRNA technique was used to inhibit the expression of ZBP1 in group LPS-ATP+ siRNA. The RIPK1 inhibitor nec-1 was given to inhibit the expression of RIPK1 protein in group LPS-ATP+ nec-1. Group C was routinely cultured. Cells were incubated with 10 μg/ml LPS for 24 h, then 5 mmol/L ATP was added, and the cells were incubated for 30 min to develop the cell pyroptosis model in the remaining 5 groups. The cell survival was detected by the CCK-8 assay. The concentrations of interleukin-1beta (IL-1β), IL-6, IL-18 and tumor necrosis factor-alpha (TNF-α) in cell supernatant were determined by enzyme-linked immunosorbent assay. The pyroptosis was determined by propidium iodide fluorescence staining. Western blot was used to detect the expression of ZBP1, RIPK1, caspase-1 and GSDMD. Results:Compared with group C, the cell survival rate was significantly decreased, the cell pyroptosis rate and concentrations of IL-1β, IL-6, IL-18 and TNF-α in the supernatant were increased, and the expression of ZBP1, RIPK1, caspase-1 and GSDMD was up-regulated in group LPS-ATP ( P<0.05). Compared with group LPS-ATP, no significant change was found in the parameters mentioned above in group LPS-ATP+ scRNA and group LPS-ATP+ DSMO ( P>0.05). Compared with group LPS-ATP+ scRNA, the cell survival rate was significantly increased, the cell pyroptosis rate and concentrations of IL-1β, IL-6, IL-18 and TNF-α in the supernatant were decreased, and the expression of ZBP1, RIPK1, caspase-1 and GSDMD was down-regulated in group LPS-ATP+ siRNA ( P<0.05). Compared with group LPS-ATP+ DMSO, the cell survival rate was significantly increased, the cell pyroptosis rate and concentrations of IL-1β, IL-6, IL-18 and TNF-α in the supernatant were decreased, the expression of ZBP1, caspase-1 and GSDMD was down-regulated ( P<0.05), and no significant change was found in the expression of ZBP1 in group LPS-ATP+ nec-1 ( P>0.05). Conclusions:Activation of ZBP1/RIPK1 signaling pathway is involved in LPS-ATP-induced pyroptosis in macrophages of mice.

Arteriovenous malformations(AVMs)are a kind of high-flow vascular malformation.AVMs can be classified in many ways,including histo-embryological classification,hemodynamic classification,etc.At present,the two mainstream classification systems used to guide the embolization treatment of peripheral AVMs are proposed by Cho and Yakes respectively based on the angiographic morphology of the lesions.Interventional embolization is the first-line treatment for AVMs.Among the many embolization agents,absolute ethanol is a permanent liquid embolization agent.Absolute ethanol can directly destroy the vascular endothelial cells to achieve a good curative efficacy,therefore,it has been wildly used in the treatment of peripheral AVMs.Yakes classification combines the angiographic classification with absolute ethanol embolization therapy.During absolute ethanol treatment,close attention should be paid to the occurrence of complications such as elevated pulmonary artery pressure.Although there are challenges remaining in the treatment of AVMs,the rapid development of molecular genetics has made targeted drug adjunctive treatment for AVMs possible.Perhaps,the novel therapeutic mode of combination use of traditional therapy targeted drug may be able to make a breakthrough in the treatment of AVMs.