Objective:To explore the hemodynamic characteristics of the middle cerebral artery (MCA) in atherosclerotic stenosis using four-dimensional flow (4D Flow) MRI, and combining high-resolution magnetic resonance vessel wall imaging (HR VW-MRI) to analyze the relationship between hemodynamics and the degree of stenosis, as well as the morphological characteristics of plaques.Methods:The study was a cross-sectional study. A total of 24 patients with middle cerebral artery(MCA) M1 atherosclerotic stenosis and 10 age and sex matched healthy controls (HC group) were prospectively recruited from September 2018 to March 2021 at Beijing Tiantan Hospital, Capital Medical University. All subjects underwent MRI examination. The hemodynamic of MCA were collected by 4D Flow MRI, and the hemodynamic parameters of proximal and distal MCA stenosis were calculated by blood flow post-processing software, including average blood flow rate (FR avg), average blood flow velocity (V avg), peak blood flow velocity (V pk), time average wall shear stress (TAWSS), minimum wall shear stress (WSS min) and oscillatory shear index (OSI). The differences in hemodynamic parameters among the proximal and distal ends of MCA stenosis and the HC group were compared using one-way ANOVA or Kruskal-Wallis H test. The stenosis rate and characteristics of MCA plaque were analyzed by HR VW-MRI, including remodeling index (RI), normalized wall index (NWI) and plaque length. Pearson or Spearman correlation analysis was used to explore the correlation between stenosis rate and hemodynamic parameters. Taking the stenosis rate as the control variable, partial correlation analysis was used to explore the correlation between plaque morphological characteristics and hemodynamic parameters. Results:There were statistically significant differences in FR avg, V avg, V pk, TAWSS, OSI, WSS min among the proximal and distal stenosis of MCA and HC groups ( P<0.05). The proximal end of the MCA stenosis had significantly higher FR avg, V avg, TAWSS and WSS min than those of the distal end of the stenosis ( P<0.01). The FR avg, V avg, V pk, TAWSS, and WSS min in the distal end of MCA stenosis were lower than those in the HC group, while the OSI was higher than that in the HC group ( P<0.01). The correlation analysis results showed that the MCA proximal V pk ( r=-0.425, P=0.027) and distal V pk ( r=-0.538, P=0.004) were negatively correlated with the diameter stenosis rate. When the stenosis rate was taken as the control factor, in the MCA proximal stenosis, V avg ( r=0.553, P=0.003), TAWSS ( r=0.543, P=0.004) and WSS min ( r=0.547, P=0.004) were positively correlated with RI, proximal OSI was negatively correlated with RI ( r=-0.492, P=0.011), and was positively correlated with the plaque length ( r=0.437, P=0.026). At the distal end of the stenosis, V pk was negatively correlated with NWI ( r=-0.556, P=0.003), OSI was negatively correlated with RI ( r=-0.511, P=0.008), NWI ( r=-0.390, P=0.049). TAWSS was positively correlated with RI ( r=0.393, P=0.047). Conclusions:The 4D Flow MRI demonstrates characteristic hemodynamic changes in the proximal and distal ends of the stenotic MCA. The local hemodynamic characteristics of the stenotic MCA are correlated with plaque morphological parameters, including lumen stenosis, plaque load, and RI. It suggests an interaction between the occurrence and development of MCA plaque and local hemodynamic changes.

Objective:To explore the hemodynamic characteristics of the middle cerebral artery (MCA) in atherosclerotic stenosis using four-dimensional flow (4D Flow) MRI, and combining high-resolution magnetic resonance vessel wall imaging (HR VW-MRI) to analyze the relationship between hemodynamics and the degree of stenosis, as well as the morphological characteristics of plaques.Methods:The study was a cross-sectional study. A total of 24 patients with middle cerebral artery(MCA) M1 atherosclerotic stenosis and 10 age and sex matched healthy controls (HC group) were prospectively recruited from September 2018 to March 2021 at Beijing Tiantan Hospital, Capital Medical University. All subjects underwent MRI examination. The hemodynamic of MCA were collected by 4D Flow MRI, and the hemodynamic parameters of proximal and distal MCA stenosis were calculated by blood flow post-processing software, including average blood flow rate (FR avg), average blood flow velocity (V avg), peak blood flow velocity (V pk), time average wall shear stress (TAWSS), minimum wall shear stress (WSS min) and oscillatory shear index (OSI). The differences in hemodynamic parameters among the proximal and distal ends of MCA stenosis and the HC group were compared using one-way ANOVA or Kruskal-Wallis H test. The stenosis rate and characteristics of MCA plaque were analyzed by HR VW-MRI, including remodeling index (RI), normalized wall index (NWI) and plaque length. Pearson or Spearman correlation analysis was used to explore the correlation between stenosis rate and hemodynamic parameters. Taking the stenosis rate as the control variable, partial correlation analysis was used to explore the correlation between plaque morphological characteristics and hemodynamic parameters. Results:There were statistically significant differences in FR avg, V avg, V pk, TAWSS, OSI, WSS min among the proximal and distal stenosis of MCA and HC groups ( P<0.05). The proximal end of the MCA stenosis had significantly higher FR avg, V avg, TAWSS and WSS min than those of the distal end of the stenosis ( P<0.01). The FR avg, V avg, V pk, TAWSS, and WSS min in the distal end of MCA stenosis were lower than those in the HC group, while the OSI was higher than that in the HC group ( P<0.01). The correlation analysis results showed that the MCA proximal V pk ( r=-0.425, P=0.027) and distal V pk ( r=-0.538, P=0.004) were negatively correlated with the diameter stenosis rate. When the stenosis rate was taken as the control factor, in the MCA proximal stenosis, V avg ( r=0.553, P=0.003), TAWSS ( r=0.543, P=0.004) and WSS min ( r=0.547, P=0.004) were positively correlated with RI, proximal OSI was negatively correlated with RI ( r=-0.492, P=0.011), and was positively correlated with the plaque length ( r=0.437, P=0.026). At the distal end of the stenosis, V pk was negatively correlated with NWI ( r=-0.556, P=0.003), OSI was negatively correlated with RI ( r=-0.511, P=0.008), NWI ( r=-0.390, P=0.049). TAWSS was positively correlated with RI ( r=0.393, P=0.047). Conclusions:The 4D Flow MRI demonstrates characteristic hemodynamic changes in the proximal and distal ends of the stenotic MCA. The local hemodynamic characteristics of the stenotic MCA are correlated with plaque morphological parameters, including lumen stenosis, plaque load, and RI. It suggests an interaction between the occurrence and development of MCA plaque and local hemodynamic changes.

Objective:To establish a scientific and standardized evaluation index system of neonatal breastfeeding nursing quality under the state of mother-infant separation, in order to provide a tool for the detection and management of neonatal breastfeeding nursing quality under mother-infant separation, so as to promote the implementation of breastfeeding in China.Methods:A systematic and comprehensive search of Chinese and English databases was conducted to collect guidelines on neonatal breastfeeding in the state of mother-infant separation. Based on the "structure-process - result" three-dimensional quality structure model, the preliminary draft of evaluation indexes of neonatal breastfeeding nursing quality in the state of mother-infant separation was formed. The evaluation indexes of neonatal breastfeeding nursing quality in the state of mother-infant separation were constructed by Delphi expert correspondence method from July to October, 2023.Results:The effective recovery rates were 95.83% (23/24) and 91.30% (21/23), respectively. The expert authority coefficients were 0.895 and 0.870, respectively. The Kendall harmony coefficients of the whole index were 0.134 and 0.178 (both P<0.01), respectively. The final evaluation index system of neonatal breastfeeding nursing quality under the state of mother-infant separation includes 3 first-level indicators, 18 second-level indicators and 82 third-level indicators. Conclusions:The evaluation index system of neonatal breastfeeding nursing quality in the state of mother-infant separation established in this study is highly scientific and reliable, highlighting the characteristics of neonatal breastfeeding nursing work in the state of mother-infant separation, and can provide a reference for the evaluation of neonatal breastfeeding nursing quality in the state of mother-infant separation.

Carcinoma-associated fibroblasts (CAFs) are the main cellular components of the tumor microenvironment and promote cancer progression by modifying the extracellular matrix (ECM). The tumor-associated ECM is characterized by collagen crosslinking catalyzed by lysyl oxidase (LOX). Small extracellular vesicles (sEVs) mediate cell-cell communication. However, the interactions between sEVs and the ECM remain unclear. Here, we demonstrated that sEVs released from oral squamous cell carcinoma (OSCC)-derived CAFs induce collagen crosslinking, thereby promoting epithelial-mesenchymal transition (EMT). CAF sEVs preferably bound to the ECM rather than being taken up by fibroblasts and induced collagen crosslinking, and a LOX inhibitor or blocking antibody suppressed this effect. Active LOX (αLOX), but not the LOX precursor, was enriched in CAF sEVs and interacted with periostin, fibronectin, and bone morphogenetic protein-1 on the surface of sEVs. CAF sEV-associated integrin α2β1 mediated the binding of CAF sEVs to collagen I, and blocking integrin α2β1 inhibited collagen crosslinking by interfering with CAF sEV binding to collagen I. CAF sEV-induced collagen crosslinking promoted the EMT of OSCC through FAK/paxillin/YAP pathway. Taken together, these findings reveal a novel role of CAF sEVs in tumor ECM remodeling, suggesting a critical mechanism for CAF-induced EMT of cancer cells.
Humans ; Paxillin/metabolism* ; Protein-Lysine 6-Oxidase/metabolism* ; Carcinoma, Squamous Cell/pathology* ; Epithelial-Mesenchymal Transition ; Integrin alpha2beta1/metabolism* ; Mouth Neoplasms/pathology* ; Collagen/metabolism* ; Fibroblasts ; Extracellular Vesicles/metabolism* ; Cell Line, Tumor ; Tumor Microenvironment

Objective: To investigate the genotype and phenotype of children with KCNA2 gene related developmental and epileptic encephalopathy (DEE). Methods: Clinical data including the manifestations and electroencephalogram of 8 children with KCNA2 variants treated in the Department of Pediatrics, Peking University First Hospital from March 2017 to June 2019 were collected and analyzed retrospectively. Results: Among the 8 epileptic patients with KCNA2 variants, 5 were males and 3 were females. The age of onset was from 1 day to 11 months. The age at last follow-up ranged from 4 months to 86 months. Two variants including c.1214C>T (loss-of-function) and c.1120A>G (gain-and loss-of-function) were identified. The variant of c.1214C>T was found in six patients (case 1-6). For these patients, the age of onset was from 5 to 11 months and they were characterized by multiple seizure types. All had focal seizures and had normal development before seizure onset with developmental regression after seizure onset. The first electroencephalogram showed epileptic discharges in Rolandic region in two, epileptic discharges in Rolandic region combined with generalized discharge in one, generalized discharge with posterior predominance in two (combined with or transferred to Rolandic region during the course) and epileptic discharges in posterior region combined with generalized discharge in one. And in 5 of them the Rolandic discharges developed into epileptic electrical status (ESES) during sleep. All the six patients were still treated with a combination of multiple antiepileptic drugs. Two of them had seizure controlled at 80 months and 68 months, respectively. The variant of c.1120A>G were identified in two of eight patients (case 7 and 8) and they had seizure onset on the 1st day after birth. Their epileptic seizures were frequent and difficult to control. They had remarkably developmental delay and microcephaly since birth. One case (case 8) had a wide forehead. They had frequent seizures up to the last follow-up. In case 7, the early electroencephalogram showed epileptic discharges in temporal region, and interictal electroencephalogram at 3 months of age showed multifocal discharge with posterior and temporal region predominance. In case 8, the early electroencephalogram was normal and electroencephalogram showed burst suppression at 2 months of age, and it developed epileptiform discharge in posterior region at 1 year of age. Conclusions KCNA2 gene variants can lead to DEE with multiple seizures types. Among them, loss-of-function c.1214C>T is the most common, and these patients have seizure onset at infancy with Rolandic discharges tended to develop into to ESES pattern. The variant of c.1120A>G is a gain-of- and loss-of-function variant, patients with c.1120A>G have seizure onset in neonatal period, the phenotype overlaps with the former but is more severe.

Objective: To investigate the electroclinical findings in epilepsy children with epileptic negative myoclonus (ENM) restricted to the lower limb as the first seizure type. Methods: Each retrieved electroencephalogram record performed between March 2011 and March 2018 at the Department of Pediatrics of Peking University First Hospital was searched with "midline" . There were 302 records of 175 patients with "benign" or "functional" midline spikes. A retrospective review of each patient′s hospital record was performed. Thirteen patients had ENM restricted to the lower limb as the first seizure type. The clinical and electroencephalogram characteristics of them were analyzed. Results: Thirteen patients manifested ENM restricted to the lower limb as the first seizure type, diagnosed as benign childhood focal epilepsy with vertex spikes (BEVS). Six patients had ENM as the first and only seizure type during the short-time follow-up. Among them, there were 1 male and 5 females. The age at seizure onset was (2.5±0.7) years. One of them had electrical status epilepticus during sleep (ESES) identified on electroencephalogram at theage of 4 years and 8 months. The last follow-up age was (3.8±1.5) years. The remaining 7 patients developed nocturnal focal motor seizures. Among them, there were 4 males and 3 females. The age at seizure onset was (3.5±0.7) years. Two of them were diagnosed as BEVS evolving into benign childhood epilepsy with centrotemporal spikes (BECTS) and 5 were diagnosed as BEVS concurring with BECTS. The age at focal seizures was (4.1±0.6) years. The interval ranged from 1 month to 1 years. Six of 7 patients had electrical ESES with the age of (5.2±1.0) years. All had developmental regression, further diagnosed as atypical benign partial epilepsy (ABPE). The median age at last follow-up was 5.9 years. Five of 13 patients had repeated electroencephalogram records at our apartment, showing that epileptiform discharges in midline regions were significantly reduced either in frequency or amplitude with the improvement of ENM restricted to the lower limb and that independent epileptiform discharges in Rolandic regions from midline regions were noticed with the onset of nocturnal focal seizures. Conclusions ENM restricted to the lower limb has a close association with vertex (midline) epileptiform discharges. ENM restricted to the lower limb as the first seizure type is a peculiar phenomenon of BEVS. Some patients could evolve into BECTS or overlap with BECTS, and further into ABPE. The age of seizure onset in BEVS with ENM restricted to the lower limb as the first symptom is a little earlier than in BECTS. Ignorance of the close association between midline spikes and ENM restricted to the lower limb may lead to misdiagnosis of these patients.

Objective: To investigate the clinical and electroencephalogram (EEG) characteristics and treatment of ring chromosome 14 syndrome, and to improve its early recognition and accurate diagnosis. Methods: The cli-nical and EEG characteristics of 4 patients with ring chromosome 14 syndrome confirmed by genetic diagnosis were analyzed in the neurology outpatient department and ward of pediatrics in Peking University First Hospital from August 2012 to August 2018.The treatment and prognosis of the 4 patients were followed up. Results: Of the 4 patients, there were 2 males and 2 females.All the patients had developmental delay, abnormal facial features such as wide eye spacing, low nasal bridge and microcephaly.Seizures occurred in all the patients with varying onset ages from 8 months to 1 year.Seizure types included focal seizure, tonic seizure and generalized tonic-clonic seizure.EEG monitoring ages varied from 9 months to 4 years and 4 months.The characteristic EEG pattern manifested as slow activity of background, unilateral or bilateral anterior, posterior or diffuse slow activity, with or without interposed multifocal epileptiform discharges.Cranial magnetic resonance imaging (MRI) showed non-specific abnormality in 1 patient and normal in 3 patients.The ages at the last follow-up ranged from 1 year and 8 months to 7 years and 1 month with intervals from 9 months to 6 years and 5 months.Valproic acid combined with other antiepileptic drugs was used to treat seizures.Seizure reduction instead of control was observed in all the 4 cases.At the last follow-up, the development of movement and language were all delayed in the 4 patients.One case could walk independently, three could walk unsteadily alone; two could speak 2-3 simple words, one could call only " baba, mama" , and one had no language development. Conclusions The ring chromosome 14 syndrome is a rare disease caused by chromosome abnormality.Its main clinical manifestations included facial abnormalities, microcephaly, epilepsy, developmental delay especially for language and cognitive disability.The types of seizures included both focal and generalized.EEG showed non-specific features with slow background activity, with the migratory slow waves mixing multi-focal discharges as the main common pattern.The epilepsy of this disease was often drug resistant.Valproic acid combined with other antiepileptic drugs could reduce seizures.Seizures without control could further affect development outcome.

Objective To investigate the electroclinical findings in epilepsy children with epileptic negative myoclonus (ENM) restricted to the lower limb as the first seizure type. Methods Each retrieved electroencephalogram record performed between March 2011 and March 2018 at the Department of Pediatrics of Peking University First Hospital was searched with"midline". There were 302 records of 175 patients with "benign" or "functional" midline spikes. A retrospective review of each patient's hospital record was performed. Thirteen patients had ENM restricted to the lower limb as the first seizure type. The clinical and electroencephalogram characteristics of them were analyzed. Results Thirteen patients manifested ENM restricted to the lower limb as the first seizure type, diagnosed as benign childhood focal epilepsy with vertex spikes (BEVS). Six patients had ENM as the first and only seizure type during the short?time follow?up. Among them, there were 1 male and 5 females. The age at seizure onset was (2.5±0.7) years. One of them had electrical status epilepticus during sleep (ESES) identified on electroencephalogram at theage of 4 years and 8 months. The last follow?up age was (3.8 ± 1.5) years. The remaining 7 patients developed nocturnal focal motor seizures. Among them, there were 4 males and 3 females. The age at seizure onset was (3.5 ± 0.7) years. Two of them were diagnosed as BEVS evolving into benign childhood epilepsy with centrotemporal spikes (BECTS) and 5 were diagnosed as BEVS concurring with BECTS. The age at focal seizures was (4.1 ± 0.6) years. The interval ranged from 1 month to 1 years. Six of 7 patients had electrical ESES with the age of (5.2 ± 1.0) years. All had developmental regression, further diagnosed as atypical benign partial epilepsy (ABPE). The median age at last follow?up was 5.9 years. Five of 13 patients had repeated electroencephalogram records at our apartment, showing that epileptiform discharges in midline regions were significantly reduced either in frequency or amplitude with the improvement of ENM restricted to the lower limb and that independent epileptiform discharges in Rolandic regions from midline regions were noticed with the onset of nocturnal focal seizures. Conclusions ENM restricted to the lower limb has a close association with vertex (midline) epileptiform discharges. ENM restricted to the lower limb as the first seizure type is a peculiar phenomenon of BEVS. Some patients could evolve into BECTS or overlap with BECTS, and further into ABPE. The age of seizure onset in BEVS with ENM restricted to the lower limb as the first symptom is a little earlier than in BECTS. Ignorance of the close association between midline spikes and ENM restricted to the lower limb may lead to misdiagnosis of these patients.

Objective To explore the therapeutic effects and adverse reaction of high-dose Diazepam (DZP) in patients with electrical status epilepticus during sleep (ESES).Methods Nine patients in the Outpatient of the Department of Pediatrics,Peking University First Hospital from October 2016 to May 2017 with ESES were treated with high-dose DZP.Oral DZP was administered in a dose of 0.75-1.00 mg/kg(maximum:40 mg) during the first night followed by 0.5 mg/(kg · d) (maximum:20 mg) from the second night for 1-3 months and tapered over next 1-3 months.The seizures,electroencephalogram (EEG) changes and adverse reactions were observed before and after DZP treatment.Results Six of 9 patients were male and 3 were female.The age of onset was ranged from 1 year and 6 months to 10 years.Benign childhood epilepsy with central temporal spike was diagnosed in 5 cases,epileptic encephalopathy with continuous spike-and-wave during sleep in 1 case,and ESES related epilepsy in 3 cases.Age of onset DZP treatment ranged from 4 years and 4 months to 12 years,and the duration of DZP treatment was ranged from 1 to 5 months (1 case only for the first night).The follow-up interval was 6-12 months.The efficiency of DZP on seizures:intent effective in 5 patients,effective in 2 patients and ineffective in 2 patients,and the effective rate was 78％ (7/9 cases).The efficiency of DZP on EEG (1 month after DZP treatment):intent effective in 2 patients (EEG normalized),effect in 3 patients and no effect in 2 patients,and the effective rate was 71％ (5/7 cases),while 2 patients did not receive EEG examination.Four of 7 patients (57％) with intent effect and effective of DZP on seizures had seizures relapse during drug reduction and after drug withdrawal,and the EEG deteriorated simultaneously.Adverse reactions of DZP included 3 patients (33％) with adverse reactions,bed-wetting in 2 patients and snoring on the first night in 1 patient who withdrew DZP later.Conclusions The high-dose of DZP has a certain effect on seizures control and ESES suppression in patients with ESES,but also has a certain recurrence rate.The adverse reactions are mild and self-limiting.High-dose DZP treatment could be a choice for refractory patients with ESES to alleviate disease.

The study included 197 thyroid nodules which were confirmed by fine-needle aspiration cytology or histopathologic examination. All nodules were graded with malignancy risk stratification of thyroids nodule accordingto the 2015 American Thyroid Association(ATA)management guidelines. Both color Doppler flow imaging (CDFI) and superb microvascular imaging(SMI) were used to classify blood flows of thyroid nodules according to Adler's grading criteria. Morphologic and distribution features of blood flow were also observed by monochrome (mSMI). The optimal threshold drawing from ROC curve and diagnostic efficacy of single and combinative modality were calculated. The results showed that mSMI was more sensitive to detect blood flow of thyroid nodules than other Doppler techniques(P<0.01). Microvascular morphologic features between benign and malignant thyroid nodules were significantly different(P<0.01). The area under ROC curves of ATA,mSMI,and ATA+mSMI were 0.745, 0.740,and 0.834,respectively,suggesting that the diagnostic performance of ATA+mSMI is superior to that of ATA or mSMI alone. There was no significant deference in the sensitivity among ATA, mSMI, and ATA+mSMI (P>0.05). But the specficity and accuracy of combinative modality ATA+mSMI was significantly higher than that of ATA or mSMI alone(P<0.05).