Objective:To separate and purify the polysaccharides from Polygonatum filipes,characterize their primary structure and investigate the immunomodulatory effects on RAW264.7 macrophages.Methods:Crude polysaccharides from Polygonatum filipes were extracted by ultrasound assisted method,then Polygonatum filipes polysaccharides(CSPFPs)were obtained after elimination of the proteins with combined papain-Sevag method.The total sugar content was determined by phenol-sulfuric acid method.Structures of CSPFPs were analyzed by fourier transform infrared spectroscopy(FT-IR),high performance gel permeation chromatography(HPGPC)and high performance liquid chromatography(HPLC).Effects of CSPFPs on cell viability,pinocytic activity,TNF-α secretion,MAPK and NF-κB signaling pathways of RAW264.7 cells were explored by MTT,Neutral red,ELISA and Western blot,respectively.Results:Extraction rate of CSPFPs by ultrasound-assisted method was 41.61%,which contained total sugar content of 94.00%.CSPFPs with Mw of 3 125 Da was composed of arabinose(1.85%),galactose(6.14%),glucose(56.41%)and mannose(35.60%).The in vitro experiments showed that CSPFPs were non-cytotoxic and enhanced the pinocytic activity,TNF-α secretion and phosphorylation levels of p38,ERK,JNK,p65,IκB and IKK,indicating the activation of MAPK and NF-κB signaling pathways under the concentra-tion of 2.5～200 μg/ml.Conclusion:The ultrasound-assisted method can efficiently isolate CSPFPs with immunomodulatory activity,which provides basic data for the development and application of CSPFPs as an immunostimulant.

Background and Aims:Abdominal aortic aneurysm(AAA)is a common arterial dilation disease in vascular surgery,with aneurysm rupture being its most serious complication,often leading to fatal hemorrhage and posing a severe threat to patients'lives.Endovascular aneurysm repair(EVAR),due to its minimally invasive nature,safety,and rapid recovery,has become the preferred treatment for AAA.However,endoleak,a complication unique to EVAR,remains a major clinical challenge.Persistent endoleak can lead to sustained high pressure within the aneurysm sac,increasing the risk of continued expansion and rupture.It is one of the main causes of the high reintervention rate following EVAR.In particular,the treatment strategy for type Ⅱ endoleaks remains controversial.This study was conducted to evaluate the clinical value of selective sac embolization via the iliac approach combined with standard EVAR in managing intraoperative immediate endoleaks.Methods:The clinical data of AAA patients with a risk of endoleak who underwent standard EVAR at the First Hospital of China Medical University between March 2023 and September 2024 were retrospectively collected.Patients were divided into an intervention group(n=42)and a non-intervention group(n=32)based on whether selective sac embolization via the iliac approach was performed during operation.General clinical data,preoperative anatomical characteristics of the AAA,surgical details,and postoperative follow-up results were compared between the two groups.Results:There were no statistically significant differences between the two groups in terms of age,sex,anatomical features,rupture rate,or off-label use(all P>0.05).The technical success rate during surgery was 100%in both groups.One patient in the intervention group experienced transient sigmoid colon ischemia after operation,which resolved with conservative treatment.The mean follow-up period was(6.49±4.68)months.The proportions of aneurysm sac shrinkage,stability,and enlargement in the intervention group were 40.5%,57.1%,and 2.4%,respectively,compared to 59.4%,40.6%,and 0.0%in the non-intervention group,with no statistically significant differences(all P>0.05).The incidence of endoleak during follow-up was also comparable between the two groups(P>0.05).Conclusion:For intraoperative endoleaks during standard EVAR,selective sac embolization via the iliac approach is a technically simple and safe method that provides short-term outcomes comparable to those in patients without intraoperative endoleaks.Its long-term efficacy warrants further investigation through extended follow-up.

Objective:To summarize the clinical and genetic characteristics of patients with neurodevelopmental disorder with or without variable brain abnormalities (NEDBA) caused by MAPK8IP3 gene variation. Methods:The clinical data and genetic testing results of 2 children with NEDBA treated in Henan Children′s Hospital from August 2019 to January 2022 were collected retrospectively. Literature was searched and reviewed from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, PubMed database and OMIM database (up to October 2024) with" MAPK8IP3 gene ""NEDBA ""neurodevelopmental disorders "as the search terms. The main clinical genetic characteristics of NEDBA caused by MAPK8IP3 gene variation were summarized. Results:The 2 children, a boy aged 1 year and 8 months and a girl aged 1 year and 4 months, both showed global developmental delay and the onset of the disease in infancy. The de novo heterozygous mutation c.1732C>T(p.Arg578Cys) of the MAPK8IP3 gene was detected by whole-exome sequencing. Case 1 was followed up to 3 years and 10 months old, who had severe developmental delay and was accompanied by hip subluxation and strephexopodia. Literature search retrieved 0 Chinese literature and 2 English literatures. A total of 18 patients including 2 cases reported in this study were identified as NEDBA caused by MAPK8IP3 gene variations, including 16 cases with missense mutations and 2 cases with truncation mutations. Among them, 7 patients carried c.1732C>T(p.Arg578Cys) and 5 patients carried c.3436C>T(p.Arg1146Cys). The main clinical manifestations of the 18 patients included developmental delay/intellectual disability (18 cases), poor or absent speech (11 cases), abnormal neurological examination (10 cases: 6 with spastic paraplegia, 2 with spasticity, 2 with ataxia, 1 with unstable gait), hypotonia (10 cases), skeletal malformations (10 cases: 4 with short stature, 3 with scoliosis, 1 with 5th finger clinodactyly and brachydactylky, 1 with flat-valgus feet, 1 with hip subluxation), seizures (3 cases), left hearing loss (1 case), myopic astigmatism and pseudostrabismus (1 case), abnormal brain magnetic resonance imaging (15 cases). Conclusions:Patients with NEDBA is usually characterized by global developmental delay apparent from infancy or early childhood, resulting in language and motor disorders. Additional features may include hypotonia, spasticity, skeletal malformations and abnormal brain magnetic resonance imaging. Currently, missense variations are frequent among the heterozygous MAPK8IP3 genotypes, among which c.1732C>T(p.Arg578Cys) and c.3436C>T(p.Arg1146Cys) are considered hot spot variations.

Objective:To summarize the clinical characteristics of 5 children with developmental epileptic encephalopathy type 17 (DEE17) caused by GNAO1 gene variants confirmed by whole-exome sequencing and analyze the features of their genetic variants. Methods:A retrospective analysis was conducted on the clinical data of 5 children diagnosed with GNAO1-related DEE17 in the Department of Neurology, Children′s Hospital of Soochow University from January 2019 to October 2024. Their clinical features, genetic testing results, neuroimaging findings, electroencephalogram (EEG) results, and treatment regimens were summarized. Follow-up was performed via telephone or outpatient visits. Results:Among the 5 diagnosed children (3 males, 2 females), the age of onset ranged from 2 days to 2 years, and the age at diagnosis ranged from 2 days to 6 years. Four children presented with seizures in the neonatal or infantile period, manifesting as hypotonia, developmental delay, and seizure types including generalized tonic-clonic, myoclonic, and epileptic spasms. One child had a later onset at 2 years, presenting with language delay, intellectual disability, and involuntary movements, followed by seizures at 6 years, including focal and generalized tonic-clonic seizures. Genetic testing revealed de novo heterozygous missense variants in GNAO1 in all 5 cases: c.119G>C (p.G40A), c.808A>C (p.N270H), c.808A>G (p.N270D), c.118G>C (p.G40R), and c.17G>T (p.S6I). Among these variants, c.119G>C and c.17G>T were previously unreported pathogenic variants. Neuroimaging showed nonspecific changes in 3 children (widened frontal-temporal subarachnoid space, delayed myelination) and abnormal white matter signals in 2 cases. Long-term video-EEG revealed abnormal discharges and background slowing in all cases: multifocal discharges in 4 cases and focal epileptiform discharges (left mid-temporal) in 1 case. Clinical seizures were captured in 3 cases: 1 with a burst-suppression pattern and 2 with hypsarrhythmia. All patients received 3 or more antiseizure medications. Four cases (cases 1-4) responded well to topiramate combination therapy, with 2 cases (cases 1, 2) achieving complete seizure freedom and 2 cases (cases 3, 4) experiencing more than a 50% reduction in seizures. One child (case 3) achieved seizure control with an adjunctive ketogenic diet. The late-onset case (case 5) required a combination of levetiracetam, oxcarbazepine, and valproate for seizure management. Conclusions:GNAO1 variants can lead to DEE17 with diverse seizure types, often requiring multiple antiseizure medications, among which topiramate is effective. Early-onset cases typically present with seizures and developmental delay, while late-onset cases may exhibit language delay, intellectual disability, movement disorders, and refractory epilepsy. Genetic testing should be performed early for timely diagnosis.

Objective:To separate and purify the polysaccharides from Polygonatum filipes,characterize their primary structure and investigate the immunomodulatory effects on RAW264.7 macrophages.Methods:Crude polysaccharides from Polygonatum filipes were extracted by ultrasound assisted method,then Polygonatum filipes polysaccharides(CSPFPs)were obtained after elimination of the proteins with combined papain-Sevag method.The total sugar content was determined by phenol-sulfuric acid method.Structures of CSPFPs were analyzed by fourier transform infrared spectroscopy(FT-IR),high performance gel permeation chromatography(HPGPC)and high performance liquid chromatography(HPLC).Effects of CSPFPs on cell viability,pinocytic activity,TNF-α secretion,MAPK and NF-κB signaling pathways of RAW264.7 cells were explored by MTT,Neutral red,ELISA and Western blot,respectively.Results:Extraction rate of CSPFPs by ultrasound-assisted method was 41.61%,which contained total sugar content of 94.00%.CSPFPs with Mw of 3 125 Da was composed of arabinose(1.85%),galactose(6.14%),glucose(56.41%)and mannose(35.60%).The in vitro experiments showed that CSPFPs were non-cytotoxic and enhanced the pinocytic activity,TNF-α secretion and phosphorylation levels of p38,ERK,JNK,p65,IκB and IKK,indicating the activation of MAPK and NF-κB signaling pathways under the concentra-tion of 2.5～200 μg/ml.Conclusion:The ultrasound-assisted method can efficiently isolate CSPFPs with immunomodulatory activity,which provides basic data for the development and application of CSPFPs as an immunostimulant.

Objective:To summarize the clinical and genetic characteristics of patients with neurodevelopmental disorder with or without variable brain abnormalities (NEDBA) caused by MAPK8IP3 gene variation. Methods:The clinical data and genetic testing results of 2 children with NEDBA treated in Henan Children′s Hospital from August 2019 to January 2022 were collected retrospectively. Literature was searched and reviewed from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, PubMed database and OMIM database (up to October 2024) with" MAPK8IP3 gene ""NEDBA ""neurodevelopmental disorders "as the search terms. The main clinical genetic characteristics of NEDBA caused by MAPK8IP3 gene variation were summarized. Results:The 2 children, a boy aged 1 year and 8 months and a girl aged 1 year and 4 months, both showed global developmental delay and the onset of the disease in infancy. The de novo heterozygous mutation c.1732C>T(p.Arg578Cys) of the MAPK8IP3 gene was detected by whole-exome sequencing. Case 1 was followed up to 3 years and 10 months old, who had severe developmental delay and was accompanied by hip subluxation and strephexopodia. Literature search retrieved 0 Chinese literature and 2 English literatures. A total of 18 patients including 2 cases reported in this study were identified as NEDBA caused by MAPK8IP3 gene variations, including 16 cases with missense mutations and 2 cases with truncation mutations. Among them, 7 patients carried c.1732C>T(p.Arg578Cys) and 5 patients carried c.3436C>T(p.Arg1146Cys). The main clinical manifestations of the 18 patients included developmental delay/intellectual disability (18 cases), poor or absent speech (11 cases), abnormal neurological examination (10 cases: 6 with spastic paraplegia, 2 with spasticity, 2 with ataxia, 1 with unstable gait), hypotonia (10 cases), skeletal malformations (10 cases: 4 with short stature, 3 with scoliosis, 1 with 5th finger clinodactyly and brachydactylky, 1 with flat-valgus feet, 1 with hip subluxation), seizures (3 cases), left hearing loss (1 case), myopic astigmatism and pseudostrabismus (1 case), abnormal brain magnetic resonance imaging (15 cases). Conclusions:Patients with NEDBA is usually characterized by global developmental delay apparent from infancy or early childhood, resulting in language and motor disorders. Additional features may include hypotonia, spasticity, skeletal malformations and abnormal brain magnetic resonance imaging. Currently, missense variations are frequent among the heterozygous MAPK8IP3 genotypes, among which c.1732C>T(p.Arg578Cys) and c.3436C>T(p.Arg1146Cys) are considered hot spot variations.

Objective:To summarize the clinical characteristics of 5 children with developmental epileptic encephalopathy type 17 (DEE17) caused by GNAO1 gene variants confirmed by whole-exome sequencing and analyze the features of their genetic variants. Methods:A retrospective analysis was conducted on the clinical data of 5 children diagnosed with GNAO1-related DEE17 in the Department of Neurology, Children′s Hospital of Soochow University from January 2019 to October 2024. Their clinical features, genetic testing results, neuroimaging findings, electroencephalogram (EEG) results, and treatment regimens were summarized. Follow-up was performed via telephone or outpatient visits. Results:Among the 5 diagnosed children (3 males, 2 females), the age of onset ranged from 2 days to 2 years, and the age at diagnosis ranged from 2 days to 6 years. Four children presented with seizures in the neonatal or infantile period, manifesting as hypotonia, developmental delay, and seizure types including generalized tonic-clonic, myoclonic, and epileptic spasms. One child had a later onset at 2 years, presenting with language delay, intellectual disability, and involuntary movements, followed by seizures at 6 years, including focal and generalized tonic-clonic seizures. Genetic testing revealed de novo heterozygous missense variants in GNAO1 in all 5 cases: c.119G>C (p.G40A), c.808A>C (p.N270H), c.808A>G (p.N270D), c.118G>C (p.G40R), and c.17G>T (p.S6I). Among these variants, c.119G>C and c.17G>T were previously unreported pathogenic variants. Neuroimaging showed nonspecific changes in 3 children (widened frontal-temporal subarachnoid space, delayed myelination) and abnormal white matter signals in 2 cases. Long-term video-EEG revealed abnormal discharges and background slowing in all cases: multifocal discharges in 4 cases and focal epileptiform discharges (left mid-temporal) in 1 case. Clinical seizures were captured in 3 cases: 1 with a burst-suppression pattern and 2 with hypsarrhythmia. All patients received 3 or more antiseizure medications. Four cases (cases 1-4) responded well to topiramate combination therapy, with 2 cases (cases 1, 2) achieving complete seizure freedom and 2 cases (cases 3, 4) experiencing more than a 50% reduction in seizures. One child (case 3) achieved seizure control with an adjunctive ketogenic diet. The late-onset case (case 5) required a combination of levetiracetam, oxcarbazepine, and valproate for seizure management. Conclusions:GNAO1 variants can lead to DEE17 with diverse seizure types, often requiring multiple antiseizure medications, among which topiramate is effective. Early-onset cases typically present with seizures and developmental delay, while late-onset cases may exhibit language delay, intellectual disability, movement disorders, and refractory epilepsy. Genetic testing should be performed early for timely diagnosis.

Objective To explore the relationship between of endothelial activation and stress index (EASIX) and the course and survival ending of sepsis. Methods A retrospective analysis of 197 patients meeting the definition of sepsis 3.0 were admitted to the Tongzhou Campus,Dongzhimeng Hospital of Beijing University of Chinese Medicine from March 2019 to March 2023,and grouped according to the course of disease and prognosis. The SOFA score and APACHE Ⅱ score were used to assess the severity of sepsis. The EASIX index consists of lactate dehydrogenase,creatinine,and platelets. Multivariate COX regression model analysis of factors affecting poor prognosis in sepsis. The receiver operator characteristic (ROC ) curve was drawn to investigate the predictive value of EASIX,SOFA and APACHE Ⅱ scores for the course and 30-day mortality in patients with sepsis. Patient subgroup analysis was performed according to the best cut-off value,and Kaplan-Meier survival curves were drawn. Results Compared with the sepsis group,the EASIX (2.55±0.54 vs 2.30±0.49),APACHE Ⅱ (16.47±4.10 vs 11.81±4.89),SOFA(8.66±3.00 vs 5.48±3.92) scores of the septic shock group were significantly in creased,and EASIX also increased significantly with the progression of the disease,with statistically significant differences(t=-3.293,-7.255,-6.431,all P<0.001). The 30-day mortality rates in the sepsis and septic shock groups were 11.96％ and 29.52％,respectively. EASIX was positively correlated with SOFA scores and APACHE Ⅱ scores (r=0.662,0.425,all P<0.05),and increased with the progression of the disease course(t=3.293,P=0.001). Multivariate COX regression analysis showed that elevated EASIX was an independent risk factor for 30-day death in septic shock[OR(95％CI):1.282(1.135～1.449),P=0.001]. The ROC curve analysis showed that the predictive performance of EASIX for 30-day mortality in septic patients compared with APACHE Ⅱ and SOFA scoring,with no statistically significant difference (Z=1.208,0.538,P=0.227,0.591). The Kaplan-Meier survival curve analysis showed that the 30-day mortality of sepsis patients in the EASIX>2.43 group was significantly higher than that in the EASIX≤ 2.43 group (Log-Rank x2=18.76,P<0.001). Conclusion EASIX is a potential biomarker for predicting poor short-term prognosis in sepsis.

Background and Aims:Abdominal aortic aneurysm(AAA)is a common arterial dilation disease in vascular surgery,with aneurysm rupture being its most serious complication,often leading to fatal hemorrhage and posing a severe threat to patients'lives.Endovascular aneurysm repair(EVAR),due to its minimally invasive nature,safety,and rapid recovery,has become the preferred treatment for AAA.However,endoleak,a complication unique to EVAR,remains a major clinical challenge.Persistent endoleak can lead to sustained high pressure within the aneurysm sac,increasing the risk of continued expansion and rupture.It is one of the main causes of the high reintervention rate following EVAR.In particular,the treatment strategy for type Ⅱ endoleaks remains controversial.This study was conducted to evaluate the clinical value of selective sac embolization via the iliac approach combined with standard EVAR in managing intraoperative immediate endoleaks.Methods:The clinical data of AAA patients with a risk of endoleak who underwent standard EVAR at the First Hospital of China Medical University between March 2023 and September 2024 were retrospectively collected.Patients were divided into an intervention group(n=42)and a non-intervention group(n=32)based on whether selective sac embolization via the iliac approach was performed during operation.General clinical data,preoperative anatomical characteristics of the AAA,surgical details,and postoperative follow-up results were compared between the two groups.Results:There were no statistically significant differences between the two groups in terms of age,sex,anatomical features,rupture rate,or off-label use(all P>0.05).The technical success rate during surgery was 100%in both groups.One patient in the intervention group experienced transient sigmoid colon ischemia after operation,which resolved with conservative treatment.The mean follow-up period was(6.49±4.68)months.The proportions of aneurysm sac shrinkage,stability,and enlargement in the intervention group were 40.5%,57.1%,and 2.4%,respectively,compared to 59.4%,40.6%,and 0.0%in the non-intervention group,with no statistically significant differences(all P>0.05).The incidence of endoleak during follow-up was also comparable between the two groups(P>0.05).Conclusion:For intraoperative endoleaks during standard EVAR,selective sac embolization via the iliac approach is a technically simple and safe method that provides short-term outcomes comparable to those in patients without intraoperative endoleaks.Its long-term efficacy warrants further investigation through extended follow-up.

Objective To explore the relationship between of endothelial activation and stress index (EASIX) and the course and survival ending of sepsis. Methods A retrospective analysis of 197 patients meeting the definition of sepsis 3.0 were admitted to the Tongzhou Campus,Dongzhimeng Hospital of Beijing University of Chinese Medicine from March 2019 to March 2023,and grouped according to the course of disease and prognosis. The SOFA score and APACHE Ⅱ score were used to assess the severity of sepsis. The EASIX index consists of lactate dehydrogenase,creatinine,and platelets. Multivariate COX regression model analysis of factors affecting poor prognosis in sepsis. The receiver operator characteristic (ROC ) curve was drawn to investigate the predictive value of EASIX,SOFA and APACHE Ⅱ scores for the course and 30-day mortality in patients with sepsis. Patient subgroup analysis was performed according to the best cut-off value,and Kaplan-Meier survival curves were drawn. Results Compared with the sepsis group,the EASIX (2.55±0.54 vs 2.30±0.49),APACHE Ⅱ (16.47±4.10 vs 11.81±4.89),SOFA(8.66±3.00 vs 5.48±3.92) scores of the septic shock group were significantly in creased,and EASIX also increased significantly with the progression of the disease,with statistically significant differences(t=-3.293,-7.255,-6.431,all P<0.001). The 30-day mortality rates in the sepsis and septic shock groups were 11.96％ and 29.52％,respectively. EASIX was positively correlated with SOFA scores and APACHE Ⅱ scores (r=0.662,0.425,all P<0.05),and increased with the progression of the disease course(t=3.293,P=0.001). Multivariate COX regression analysis showed that elevated EASIX was an independent risk factor for 30-day death in septic shock[OR(95％CI):1.282(1.135～1.449),P=0.001]. The ROC curve analysis showed that the predictive performance of EASIX for 30-day mortality in septic patients compared with APACHE Ⅱ and SOFA scoring,with no statistically significant difference (Z=1.208,0.538,P=0.227,0.591). The Kaplan-Meier survival curve analysis showed that the 30-day mortality of sepsis patients in the EASIX>2.43 group was significantly higher than that in the EASIX≤ 2.43 group (Log-Rank x2=18.76,P<0.001). Conclusion EASIX is a potential biomarker for predicting poor short-term prognosis in sepsis.