Objective:To summarize the clinical features of epilepsy and (or) developmental delay associated with KCNB1 gene variants in children.Methods:A case series study was conducted on 24 children with KCNB1 gene variants associated with epilepsy and (or) developmental delay who were treated at the Children′s Medical Center of Peking University First Hospital and the Department of Neurology of Shenzhen Children′s Hospital from July 2015 to June 2024. The manifestations of seizures, electroencephalogram (EEG) and genetic test results of those children were analyzed.Results:All the KCNB1 gene variants were de novo, involving 20 different variation, including 15 missense variations, 3 frameshift variations and 2 nonsense variations. There were 7 novel variations. Among the 24 developmental and epileptic encephalopathy children, there were 14 boys and 10 girls. The last follow-up age ranged from 9 months to 13 years and 9 months. Seizures were present in 21 children (88%), with onset ranging from 1 month to 7 years, and 76% (16/21) began before 2 years of age. The seizure types included focal seizures in 15 children (71%), epileptic spasms, myoclonic seizures, and generalized tonic-clonic seizures in 6 children respectively, atypical absence seizures in 4 children, and myoclonic atonic seizures in 1 child. Seventeen children (81%) had a cluster of seizures and 5 had a history of focal status epilepticus with impaired consciousness. All 24 children had varying degrees of developmental delay, with 3 presenting solely developmental delay. EEG abnormalities were present in all the 21 children with seizures, including focal or multifocal discharges in 20 children, generalized discharges in 10 children, hypsarrhythmia in 2 children, and electrical status epilepticus during sleep in 3 children. Magnetic resonance imaging abnormalities were found in 5 of the 24 children. Among the 21 children with seizures, 57% (12/21) achieved seizure control.Conclusions:KCNB1 gene variants are predominantly de novo missense variation. Most affected children present with epilepsy, though some may exhibit only developmental delay. Epilepsy often begins before 2 years of age, with focal seizures being the most common type. About 80% of patients experience clustered seizures. Although most patients achieve seizure control, they still exhibit varying degrees of developmental delay, consistent with developmental epileptic encephalopathy.

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.

Objective:To evaluate the efficacy and safety of 308-nm excimer lamp and 308-nm excimer laser in the treatment of pediatric vitiligo.Methods:Clinical data were collected from children with stable vitiligo who received targeted phototherapy at the Department of Dermatology of Xijing Hospital from 2010 to 2015, and retrospectively analyzed. The patients were treated with either 308-nm excimer laser or 308-nm excimer lamp, and all were given topical drugs. The treatment lasted for at least 3 months, and follow-up for at least 6 months. The severity of vitiligo was assessed using the Vitiligo Area and Severity Index (VASI) score. The efficacy was evaluated after 3 months of treatment, and at least a 50% reduction in the VASI score (VASI50) was defined as "effectiveness". A logistic regression model was constructed using treatment efficacy as the dependent variable to screen factors related to the treatment outcome. The Wilcoxon signed-rank test was used to compare skewed data before and after treatment. Adverse reactions during treatment were recorded to evaluate the safety of targeted phototherapy.Results:A total of 194 children with stable vitiligo were included, comprising 103 males (53.1%) and 91 females (46.9%), with the age being 6 to 14 (10.2 ± 2.3) years. Among them, 138 (71.1%) received 308-nm excimer laser therapy, while 56 (28.9%) received 308-nm excimer lamp therapy. The VASI score ( M [ Q1, Q3]) was 0.12 (0.05, 0.40) at the baseline, significantly decreased to 0.06 (0.02, 0.19) after 3 months of treatment ( Z = 12.02, P < 0.001). After 3 months of treatment, 52 patients achieved VASI50, and 30 achieved VASI75, resulting in an overall response rate of 42.3% (82/194). Specifically, in the 308-nm excimer laser group, 38 patients achieved VASI50 and 26 achieved VASI75, with a response rate of 46.4% (64/138) ; in the 308-nm excimer lamp group, 14 patients achieved VASI50 and 4 achieved VASI75, yielding a response rate of 32.1% (18/56). Univariate logistic regression analysis indicated that lesions located on the head and neck or the trunk were more prone to repigmentation compared with those on the limbs ( OR = 3.56, 95% CI: 1.15 - 11.02, P = 0.027; OR = 6.58, 95% CI: 1.81 - 23.96, P = 0.004, respectively) ; additionally, facial lesions around the eyes were more prone to repigmentation compared with lesions on other facial areas ( OR = 4.58, 95% CI: 1.10 - 19.11, P = 0.037), and hair involvement in vitiligo lesions on the head and neck made repigmentation less likely to occur compared with lesions without hair involvement ( OR = 0.31, 95% CI: 0.13 - 0.75, P = 0.010). Multivariate logistic regression analysis revealed that the periorbital region was the most favorable site for repigmentation among facial areas ( OR = 5.37, 95% CI: 1.18 - 24.34, P = 0.029), and hair involvement in vitiligo lesions on the head and neck was an independent risk factor for phototherapy-induced repigmentation ( OR = 0.28, 95% CI: 0.08 - 0.96, P = 0.042). Among the 194 patients treated with targeted phototherapy for 3 months, 33 experienced short-term treatment-related adverse reactions, including erythema, blisters, desquamation, itching, and pain; most adverse reactions were mild, and no severe adverse reactions were observed. Conclusion:Targeted phototherapy using 308-nm excimer laser or 308-nm excimer lamp was safe and effective for the treatment of pediatric vitiligo.

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 safety and feasibility of the CHESS endoscpic ruler (CHESS ruler), and the consistency between the measured values and the interpretation values by endoscopic physician experience.Methods:From January 2021 to January 2022, a total of 105 liver cirrhosis patients with portal hypertension were prospectively enrolled from General Hospital, Xixia Branch Hospital, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region (29 cases), and the First People′s Hospital of Yinchuan (25 cases), General Hospital of Ningxia Medical University (18 cases), Wuzhong People′s Hospital (10 cases), the Fifth People′s Hospital of Ningxia Hui Autonomous Region (10 cases), Shizuishan Second People′s Hospital (6 cases), Yinchuan Second People′s Hospital (5 cases), and Zhongwei People′s Hospital (2 cases) 8 hospitals. The clinical characteristics of all the patients, including gender, age, nationality, etiolog of liver cirrhosis, and Child-Pugh classification of liver function were recorded. A big gastroesophageal varices was defined as diameter of varices ≥5 mm. Endoscopist (associated chief physician) performed gastroscopy according to the routine gastroscopy procedures, and the diameter of the biggest esophageal varices was measured by experience and images were collected, and then objective measurement was with the CHESS ruler and images were collected. The diameter of esophageal varices of 10 randomly selected patients (random number table method) was determined by 6 endoscopists (attending physician or associated chief physician) with experience or measured by CHESS ruler. Kappa test was used to test the consistency in the diameter of esophageal varices between measured values by CHESS ruler and the interpretation values by endoscopic physician experience.Results:Among 105 liver cirrhosis patients with portal hypertension, male 65 cases and female 40 cases, aged (54.8±12.2) years old, Han nationality 82 cases, Hui nationality 21 cases and Mongolian nationality 2 cases. The etiology of liver cirrhosis included chronic hepatitis B (79 cases), alcoholic liver disease (7 cases), autoimmune hepatitis (7 cases), chronic hepatitis C (2 cases), and other etiology (10 cases). Liver function of 32 cases was Child-Pugh A, Child-Pugh B 57 cases, and Child-Pugh C 16 cases. All 105 liver cirrhosis patients with cirrhotic portal hypertension were successfully measured the diameter of gastroesophageal varices by CHESS ruler, and the success rate of application of CHESS ruler was 100.0% (105/105). The procedure time from the CHESS ruler into the body to the exit of the body after measurement was (3.50±2.55) min. No complications happened in all the patients during measurement. Among 105 liver cirrhosis patients with cirrhotic portal hypertension, 96 cases (91.4%) were recognized as big gastroesophageal varices by the endoscopists. Totally 93 cases (88.6%) were considered as big gastroesophageal varices by CHESS ruler. Eight cases were recognized as big gastroesophageal varices by the endoscopist, however not by the CHESS ruler; 5 cases were recognized as big gastroesophageal varices by the CHESS ruler, but not by the endoscopists; 4 cases were not recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler; 88 cases were recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler. The missed diagnostic rate of big gastroesophageal varices by the endoscopists experience was 5.4% (5/93), and the Kappa value of consistency coefficient between the measurement by the CHESS ruler and the interpretation by endoscopists experience was 0.31 (95% confidence interval 0.03 to 0.60). The overall Kappa value of consistency coefficient by 6 endoscopists measured by CHESS ruler in big gastroesophageal varices diagnosis was 0.77 (95% confidence interval 0.61 to 0.93).Conclusion:As an objective measurement tool, CHESS ruler can make up for the deficiency of subjective judgment by endoscopists, accurately measure the diameter of gastroesophageal varices, and is highly feasible and safe.

Objective:To explore the effect of Qixian Tongluo Prescription fumigation on nerve function and rehabilitation effect in patients with hemiplegia after cerebral infarction of qi-deficiency blood stasis syndrome.Methods:Randomized controlled trial. Sixty-eight patients with hemiplegia after cerebral infarction of qi-deficiency blood stasis syndrome in the hospital were enrolled between October 2020 and December 2021. According to random odd-even numbering method, participants were divided into the control group (routine western medicine) and the observation group (Qixian Tongluo Prescription fumigation on basis of control group), 34 in each group. All were continuously treated for 8 weeks. TCM syndromes were scored before and after treatment. The severity of neurological impairment was evaluated by National Institutes of Health Stroke Scale (NIHSS). The severity of limb movement disorder was evaluated by Fugl-Meyer Assessment (FMA). The levels of central nervous specific protein (S-100β), neuron-specific enolase (NSE), endothelin (ET), nitric oxide (NO), C-reactive protein (CRP) and superoxide dismutase (SOD) were detected by ELISA. The clinical response rate was assessed.Results:There were significant differences in total response rate between the observation group and the control group [94.12% (32/34) vs. 76.47% (26/34); χ2=4.22, P=0.040]. After treatment, scores of hemiplegia, shortness of breath, palpitation and limbs swelling in observation group were significantly lower than those in the control group ( t=3.44, 2.37, 2.72, 3.89, P<0.05 or P<0.01), NIHSS score was significantly lower than that of the control group ( t=6.56, P<0.01), and FMA scores of upper and lower limbs were significantly higher than those in the control group ( t=2.17, 2.78, P<0.05). After treatment, levels of serum S-100β [(0.69±0.27) μg/L vs. (0.85±0.36) μg/L, t=2.07], NSE [(8.36±3.69) μg/L vs. (11.34±4.93) μg/L, t=2.82] and ET [(53.16±12.12) ng/L vs. (61.25±11.31) ng/L, t=2.85] in observation group were significantly lower than those in the control group ( P<0.05 or P<0.01), while NO [(82.26±14.53) μmol/L vs. (70.16±12.27) μmol/L, t=3.71] was significantly higher than that of the observation group ( P<0.01). The level of serum CRP in observation group was significantly lower than that of the control group ( t=2.74, P<0.01), and SOD activity was significantly higher than that of the control group ( t=2.49, P<0.05). Conclusion:Qixian Tongluo Prescription fumigation can promote the recovery of nerve function and vascular endothelial function in patients with hemiplegia after cerebral infarction, improve limb disorders and clinical effect.

Objective:To follow up and clarify the prognosis of 670 pediatric patients with Dravet syndrome (DS).Methods:The clinical data of DS pediatric patients treated in the Department of Pediatrics, Peking University First Hospital from February 2005 to August 2016 were recorded, and genetic testing was carried out.DS pediatric patients were followed up via subsequent visits at the outpatient and telephone interview.Results:Among 670 cases with DS, 556 cases (556/670 cases, 83.0%) carried SCN1A mutations.In the follow-up, 608 cases were contacted (608/670 cases, 90.7%) and 62 cases (62/670 cases, 9.3%) were lost.The last follow-up median age was 8 years 5 months.Eighty-two cases (82/608 cases, 13.5%) were seizure-free for more than 1 year, with a median age of 9 years and 2 months.Thirty-eight cases relapsed (38/82 cases, 46.3%), mainly induced by fever (34 cases) or mi-ssing antiepileptic drugs (2 cases). Analysis of the relative factors of patients that were seizure-free for more than 1 year showed that children with missense SCN1A mutations, inherited mutations and an older age had a relatively good outcome for seizure control.Twenty-five cases (25/608 cases, 4.1%) were deceased, with a median age of 4 years.The mortality factors included multiple organ dysfunction syndromes after prolonged status epilepticus (12 cases), possible sudden unexpected death in epilepsy (7 cases), asphyxiation after vomiting with or without a seizure (2 cases), and an accidental injury (1 case). The fatal causes in the remaining 3 cases were unknown. Conclusions:DS is an intractable epileptic syndrome, but few patients may have a seizure remission (seizure free for more than 1 year). Patients with mi-ssense SCN1A mutations, inherited mutations and an older age have a relatively good outcome for seizure control.The mortality rate is high in DS patients.The causes of mortality include multiple organ dysfunction syndromes after prolonged status epilepticus, possible sudden unexpected death in epilepsy, and so on.

Objective: To compare the visual quality after topography-guided customized femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and wavefront-optimized FS-LASIK treatment in myopic eyes. Methods: A non-randomized controlled clinical study was performed.Seventy-eight eyes of 39 myopic patients undergoing FS-LASIK in Beijing Tongren Hospital from October 2016 to February 2017 were enrolled in this study and divided into two groups according to each patient's opinion, with matched demography between the two groups.Topography-guided customized FS-LASIK was performed on 42 eyes of 21 myopia in the topography-guided group, and wavefront-optimized FS-LASIK was performed on 36 eyes of 18 patients in the wavefront-optimized group.Visual acuity, refractive error, higher order aberrations (HOAs) and contrast sensitivity(CS) were compared between the two groups before and 6 months after surgery.Written informed consent was obtained from each patient before the operation.This study protocol was approved by Ethic Committee of Beijing Tongren Hospital (No.TRECKY2014-026). Results: The postoperative uncorrected visual acuity (UCVA) levels were eaqual to or better than the preoperative best corrected visual acuity (BCVA) in 95.2% patients in the topography-guided group, and in 94.4% patients in the wavefront-optimized group 6 months after surgery, respectively.There were no significant differences in the spherical equivalent, sphere refraction and cylinder refraction between the two groups (all at P>0.05). The amount of induced coma was significantly lower in the topography-guided group than that in the wavefront-optimized group ([0.07±0.22]μm vs.[0.22±0.16]μm) at 6 mm pupil.LogCS improved under the 12.0 c/d in the background of mesopic in the topography-guided group and decreased under the 18.0 c/d both in the background of mesopic and mesopic + glare in the wavefront-optimized group 6 months after surgery, with signifcant differences between them (all at P<0.05). LogCS values under 6.0, 12.0 and 18.0 c/d in the background of mesopic and 18.0 c/d in the background of mesopic+ glare in the topography-guided group were significantly higher than those in the wavefront-optimized group 6 months after surgery, with significant differences between the two groups (all at P<0.05). Conclusions Topography-guided FS-LASIK has lower higher-order aberrations and better CS than wavefront-optimized FS-LASIK.

Objective: To summarize the clinical phenotype and genotype features of 3 children with progre-ssive myoclonic epilepsy (PME) caused by KCNC1 gene mutations, and to review the related literatures. Methods: The phenotype and genotype of 3 children with KCNC1 mutations in the Department of Pediatrics, Peking University First Hospital from October 2016 to January 2019 were analyzed.The 25 patients with KCNC1 mutations which had been reported internationally were also collected and analyzed. Results: Three children in this study were identified with KCNC1 de novo mutations, in which 2 children were identified with c. 959G>A (p.Arg320His) mutation, and 1 child with c. 1262C>T (p.Ala421Val) mutation.The clinical features of 3 children were consistent with PME, and the seizure onset ages were 3 months, 10 years and 11 years, respectively.Three children all had myoclonic seizures, among whom 1 child had generalized tonic-clonic seizure and 2 children had focal seizures.Three children all had intellectual and/or motor development delay.The electroencephalograph showed generalized spike and waves or polyspike and waves in 3 children, and focal discharge in 2 children.The brain imaging of 3 children was normal.The last follow-up ages were 3 years old, 13 years old and 12 years old, respectively.Until March 2019, there were 25 cases with KCNC1 gene mutations reported internationally.Including 3 patients in this study, there were 28 patients in total, of which 25 patients were diagnosed with PME.In these 25 patients, 24 patients were identified with p. Arg320His variant in the transmembrane area, 1 patient was identified with p. Ala421Val variant in the transmembrane area.The remaining 3 patients were only found with psychomotor developmental delay without seizures, and they were identified with p. Arg339X variant in the intracellular area.In the 28 patients, 16 cases received cranial imaging data, in which 12 patients had ce-rebellar atrophy and 4 cases were normal.Of the 28 patients, 18 cases were mentally retarded, 27 cases were development retardation or retrogression among whom 9 cases could not walk independently.Ten patients were over 30 years old when reported, and only 1 patient died of pneumonia and respiratory failure at 63 years old. Conclusions KCNC1 gene mutation mainly leads to PME phenotype, and a few patients can only show mental retardation.p.Arg320His is the most common variant of KCNC1 gene.The variants in different structural regions result in different clinical phenotypes, and variants in the transmembrane region can lead to severer clinical phenotypes.The 3 patients with KCNC1 gene mutations in this study are firstly reported cases in China.

Multiple Linear Regression (MLR) is a generalization of simple linear regression and is one of the commonly used models in multivariate statistical analysis. This article introduces the MLR model from the perspective of practical application. Four parts, including basic principle, application examples, the application condition and diagnosis, and the extension of the model, are sequentially illustrated in this article. Particularly, in the last part, alternative methods of the model are introduced when the application condition of the model is not met. We sincerely hope that this article could make our audiences have a better understanding of the MLR model in order to improve the efficiency of data utilization and statistical analysis by correctly performing this model in their research.