Depression is a widespread psychiatric disorder with complex pathogenesis and unsatisfactory therapeutic effects. As a native flavonoid, Isorhamnetin (ISO) has been deemed to exert neuroprotective effects by antioxidation and regulation of immunity. However, no reports of anti-depressed effect of ISO have yet been found. The present study was conducted to clarify the mechanism basis of anti-depressed effect of ISO utilizing behavioral, biochemical, molecular approaches in vitro and in vivo and bio-informatics analysis. The effects of ISO on depressed mice was investigated through the SPT and FST, and the lesions were examined by H&E staining. Besides, the inflammatory factor and indicator in kynurenine pathway were assessed through detection kits, and the microbiota were checked by 16sRNA. Molecular docking study was performed to investigate the target of ISO. Additionally, Western blot was used to test the activation of PI3K/AKT signaling pathway. The results indicated that ISO could enhance the sugar water preference of mice in SPT and reduce immobility time in FST. Further more, ISO suppressed peripheral and central inflammation, regulated the changes in kynurenine pathway and gut microbiota, inhibited activation of PI3K/AKT pathway, and presented good binding patterns with target proteins on PI3K/AKT signaling pathway. Collectively, these findings demonstrate that ISO alleviated depression-like behaviour by normalizing inflammation-induced dysregulation of the crosstalk between KP and gut microbiota disorder through regulated PI3K/AKT/NF-κB pathway.

Depression is a widespread psychiatric disorder with complex pathogenesis and unsatisfactory therapeutic effects. As a native flavonoid, Isorhamnetin (ISO) has been deemed to exert neuroprotective effects by antioxidation and regulation of immunity. However, no reports of anti-depressed effect of ISO have yet been found. The present study was conducted to clarify the mechanism basis of anti-depressed effect of ISO utilizing behavioral, biochemical, molecular approaches in vitro and in vivo and bio-informatics analysis. The effects of ISO on depressed mice was investigated through the SPT and FST, and the lesions were examined by H&E staining. Besides, the inflammatory factor and indicator in kynurenine pathway were assessed through detection kits, and the microbiota were checked by 16sRNA. Molecular docking study was performed to investigate the target of ISO. Additionally, Western blot was used to test the activation of PI3K/AKT signaling pathway. The results indicated that ISO could enhance the sugar water preference of mice in SPT and reduce immobility time in FST. Further more, ISO suppressed peripheral and central inflammation, regulated the changes in kynurenine pathway and gut microbiota, inhibited activation of PI3K/AKT pathway, and presented good binding patterns with target proteins on PI3K/AKT signaling pathway. Collectively, these findings demonstrate that ISO alleviated depression-like behaviour by normalizing inflammation-induced dysregulation of the crosstalk between KP and gut microbiota disorder through regulated PI3K/AKT/NF-κB pathway.

Depression is a widespread psychiatric disorder with complex pathogenesis and unsatisfactory therapeutic effects. As a native flavonoid, Isorhamnetin (ISO) has been deemed to exert neuroprotective effects by antioxidation and regulation of immunity. However, no reports of anti-depressed effect of ISO have yet been found. The present study was conducted to clarify the mechanism basis of anti-depressed effect of ISO utilizing behavioral, biochemical, molecular approaches in vitro and in vivo and bio-informatics analysis. The effects of ISO on depressed mice was investigated through the SPT and FST, and the lesions were examined by H&E staining. Besides, the inflammatory factor and indicator in kynurenine pathway were assessed through detection kits, and the microbiota were checked by 16sRNA. Molecular docking study was performed to investigate the target of ISO. Additionally, Western blot was used to test the activation of PI3K/AKT signaling pathway. The results indicated that ISO could enhance the sugar water preference of mice in SPT and reduce immobility time in FST. Further more, ISO suppressed peripheral and central inflammation, regulated the changes in kynurenine pathway and gut microbiota, inhibited activation of PI3K/AKT pathway, and presented good binding patterns with target proteins on PI3K/AKT signaling pathway. Collectively, these findings demonstrate that ISO alleviated depression-like behaviour by normalizing inflammation-induced dysregulation of the crosstalk between KP and gut microbiota disorder through regulated PI3K/AKT/NF-κB pathway.

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.

Objective To evaluate the application of shear wave elastography(SWE)in the diagnosis of peripheral neuropathy in patients with diabetes.Methods Totally 85 patients with type 2 diabetes(T2DM)were selected from the Chengdu Office Hospital of People's Government of Tibetan Autonomous Region,including 46 patients with peripheral neuropathy(DPN)and 39 patients without peripheral neuropathy(NDPN).Compared for clinical data(gender,age,disease duration),cross-sectional area of the median nerve measured by high-frequency ultra-sound(CSA)and shear wave elastography(SWE)parameters(mean Young's modulus value,Emean)and shear wave velocity(SWV)between two groups of patients.Multifactor Logistic regression analysis was carried out on the indicators between the above groups to screen independent predictors in the diagnosis of peripheral neuropathy in diabetes patients,and a combined model was constructed.The area under the operating characteristic curve(AUC),sensitivity and specificity of the subjects were used to evaluate the diagnostic efficacy of the single model and com?bined model of the quantitative parameters(CSA,Emean,SWV)measured by clinical data,high?frequency ultra?sound and SWE in the diagnosis of peripheral neuropathy in diabetes patients.Results Age,course of disease,Emean,SWV and CSA were statistically significant in the diagnosis of peripheral neuropathy in diabetes patients(all P<0.05).AUC was 0.658,0.754,0.839,0.822 and 0.736,respectively.The combination model based on disease course,CSA and SWV showed the highest diagnostic efficiency,with AUC,sensitivity,and specificity of 0.887(0.800-0.946),80.43％,and 84.62％,respectively.Conclusions The combined model based on the course of disease,CSA and SWV have a high diagnostic efficiency in peripheral neuropathy of diabetes patients,and has good clinical application value.

Objective To investigate the clinical characteristics,imaging features,laboratory test results,and prognosis of children with acute lymphoblast leukemia(ALL)complicated by cerebral hemorrhage.Methods A retrospective analysis was conducted on the clinical data of 20 children with ALL complicated by cerebral hemor-rhage admitted to the Department of Hematology,Children's Hospital of Soochow University from June 20,2014 to June 20,2024.Results The clinical manifestation of the 20 children with ALL complicated by cerebral hemorrhage were complex and diverse,with disturbance of consciousness being the most common initial symptom.The prognosis varied depending on the size and location of the hematoma and whether it ruptured into the ventricle.Among the 20 cases,14(70％)demonstrated improvement in intracranial lesions,with 8(40％)cases exhibiting substantial lesion absorption and favorable prognosis.Six cases(30％)showed improvement in intracranial lesions but not complete resolution,three cases developed focal encephalomalacia,two cases had residual symptomatic epi-lepsy and one had residual right-sided hemiplegia.Furthermore,three(15％)cases suffered recurrent cerebral hemorrhages at distinct locations from the initial event following improvement of the primary hemorrhage,and 3(15％)cases led to mortality.Conclusions Neurological symptoms in children with acute lymphoblast leukemia(ALL)complicated by cerebral hemorrhage are diverse and often atypical.Timely cranial imaging and laboratory tests are necessary,while surgical intervention and platelet transfusion should be a prudential consideration.

Objective To observe the value of left atrial volume/mechanical coupling index(LACI)for predicting left atrial(LA)dysfunction in patients with chronic kidney disease(CKD).Methods Totally 213 CKD patients(CKD group)and 50 healthy controls(control group)were enrolled.Clinical data,laboratory indicators and echocardiographic parameters were compared between groups.According to quartile values of LACI,patients in CKD group were further divided into 4 subgroups,and their clinical,laboratory indicators and echocardiographic parameters were compared.The correlations between LACI and laboratory markers of myocardial injury as well as echocardiographic parameters were analyzed.Taken LAVI＞34 ml/m2 as LA dysfunction,the efficacy of LACI,LA strain and LA stiffness index(LASI)for predicting LA dysfunction in CKD patients were evaluated.Results Statistical differences of gender,blood pressure,creatinine,estimated glomerular filtration rate(eGFR),cardia troponinT(cTnT),creatine kinase isoenzymes(CK-MB)and N-terminal pro-B-type natriuretic peptide(NT-proBNP)were found between groups(all P＜0.05).In CKD group,with the increase of LACI,the prevalence of blood pressure and diabetes,the levels of cTnT and NT-proBNP in different subgroups showed increasing trend,while eGFR showed a decreasing trend.LACI was correlated with cTnT,CK-MB,NT-proBNP and multiple echocardiographic parameters(all P＜0.001).The AUC of LACI for predicting LA dysfunction in CKD patients was 0.884,higher than that of LA strain during reservoir phase,conduit phase,contraction phase and LASI(AUC=0.652,0.621,0.611,0.746,all P＜0.05).Conclusion LACI could be used to effectively predict LA dysfunction in CKD patients.

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.

Objective To observe the value of left atrial volume/mechanical coupling index(LACI)for predicting left atrial(LA)dysfunction in patients with chronic kidney disease(CKD).Methods Totally 213 CKD patients(CKD group)and 50 healthy controls(control group)were enrolled.Clinical data,laboratory indicators and echocardiographic parameters were compared between groups.According to quartile values of LACI,patients in CKD group were further divided into 4 subgroups,and their clinical,laboratory indicators and echocardiographic parameters were compared.The correlations between LACI and laboratory markers of myocardial injury as well as echocardiographic parameters were analyzed.Taken LAVI＞34 ml/m2 as LA dysfunction,the efficacy of LACI,LA strain and LA stiffness index(LASI)for predicting LA dysfunction in CKD patients were evaluated.Results Statistical differences of gender,blood pressure,creatinine,estimated glomerular filtration rate(eGFR),cardia troponinT(cTnT),creatine kinase isoenzymes(CK-MB)and N-terminal pro-B-type natriuretic peptide(NT-proBNP)were found between groups(all P＜0.05).In CKD group,with the increase of LACI,the prevalence of blood pressure and diabetes,the levels of cTnT and NT-proBNP in different subgroups showed increasing trend,while eGFR showed a decreasing trend.LACI was correlated with cTnT,CK-MB,NT-proBNP and multiple echocardiographic parameters(all P＜0.001).The AUC of LACI for predicting LA dysfunction in CKD patients was 0.884,higher than that of LA strain during reservoir phase,conduit phase,contraction phase and LASI(AUC=0.652,0.621,0.611,0.746,all P＜0.05).Conclusion LACI could be used to effectively predict LA dysfunction in CKD patients.

Diabetic cognitive dysfunction （DCD） is one of the complications of diabetes， which is characterized by impaired brain structure and progressively decreased learning and memory ability. With the increasing incidence of diabetes worldwide， DCD has become a serious medical and social problem. However， its pathophysiological mechanisms are not well understood. The occurrence and development of DCD involve multiple pathological links and mechanisms， and the prevention and treatment require multi-link and multi-target therapeutic measures. At present， there is no specific drug to prevent or improve DCD. Hypoglycemic drugs such as metformin and vigagliptin or anti-dementia drug including Donepezil are commonly used in clinical treatment to delay the occurrence and progression of cognitive dysfunction， but these drugs have a single target and obvious side effects. Traditional Chinese medicine has a long history in the prevention and treatment of diabetes and central cognitive diseases， and it has many unique advantages such as multiple components， multiple targets， side effects， and low price. A large number of studies have confirmed that traditional Chinese medicine has a significant prevention and treatment effect on DCD， which can improve insulin resistance， synaptic dysfunction， inflammation， oxidative stress， endoplasmic reticulum stress， and neuronal apoptosis by regulating phosphatidylin-ositol 3-kinase （PI3K）/protein kinase B （Akt）， advanced glycation end products （AGEs）/advanced glycation end products receptor （RAGE）/nuclear transcription factor-κB （NF-κB）， NOD-like receptor thermal protein domain associated protein 3 （NLRP3） inflammasome， and endoplasmic reticulum stress and nuclear factor E₂ related factor 2 （Nrf2）/antioxidant response element （ARE） signaling pathways. This article reviewed the effects and related mechanisms of traditional Chinese medicine on DCD in recent years， so as to provide a reference for the prevention and treatment of DCD by traditional Chinese medicine.