Objective:To explore the genetic and clinical characteristics of epilepsy related with ATP6V1A gene heterozygous variants.Methods:A case series study was conducted. The clinical data of 10 children of epilepsy associated with ATP6V1A gene variants who were admitted to the Children′s Medical Center, Peking University First Hospital from January 2019 to December 2024 was collected. The characteristics of children′ gene variation, clinical phenotype, auxiliary examination results, treatment and prognosis were analyzed.Results:Among the 10 children, there were 4 boys and 6 girls. All 10 children with ATP6V1A gene variants were de novo heterozygous variants, including 1 case of mosaic variant. A total of 9 different variants were identified and 7 variants have not been reported previously. The age at epilepsy onset was 28 (9, 48) months. Five children experienced their first seizure as a fever induction. The types of epileptic seizures included focal seizures in 6 children, epileptic spasms in 5 children, tonic spasms and atonic seizures in 1 child respectively. Three children had 2 seizure types. Global developmental delays were exhibited in 8 children, 2 of whom manifested autism spectrum disorder phenotypes. Two children showed normal development. Electroencephalography revealed slowed background activity in 5 children. Interictal epileptiform discharges were recorded in 9 cases, including hypsarrhythmia, focal, multifocal or generalized discharges. Clinical seizures were captured in 4 children. Brain magnetic resonance imaging abnormalities were found in 4 children, including frontotemporal cortical dysplasia, prominent sulci, delayed myelination of white matter, dysplasia of the corpus callosum, bilateral ventricular enlargement, and cerebral atrophy. Five children were diagnosed with developmental and epileptic encephalopathy (DEE), and 4 of them were diagnosed with infantile epileptic spasms syndrome. At the last follow-up, the age was 78 (25, 120) months. Seizures were controlled in 6 children, while 4 children had uncontrolled seizures despite treatment with ≥3 anti-seizure medications. Conclusions:All children with ATP6V1A gene related epilepsy harbored de novo heterozygous missense variants, with few showing mosaic variants. Seizure onset age ranged widely from the neonatal period to childhood. The predominant seizure types were focal seizures and epileptic spasms. The phenotypic spectrum may exhibit DEE, while a minority maintain normal development.

Therapeutic resistance in cancer is responsible for numerous cancer deaths in clinical practice. While target mutations are well recognized as the basis of genetic resistance to targeted therapy, nontarget mutation resistance (or nongenetic resistance) remains poorly characterized. Despite its complex and unintegrated mechanisms in the literature, nongenetic resistance is considered from our perspective to be a collective response of innate or acquired resistant subpopulations in heterogeneous tumors to therapy. These subpopulations, e.g., cancer stem-like cells, cancer cells with epithelial-to-mesenchymal transition, and drug-tolerant persisters, are protected by their resistance traits at cellular and molecular levels. This review summarizes recent advances in the research on resistant populations and their resistance traits. NOTCH signaling, as a central regulator of nongenetic resistance, is discussed with a special focus on its canonical maintenance of resistant cancer cells and noncanonical regulation of their resistance traits. This novel view of canonical and noncanonical NOTCH signaling pathways is translated into our proposal of reshaping therapeutic strategies targeting NOTCH signaling in resistant cancer cells. We hope that this review will lead researchers to study the canonical and noncanonical arms of NOTCH signaling as an integrated resistant mechanism, thus promoting the development of innovative therapeutic strategies.
Neoplasms/metabolism* ; Receptors, Notch/metabolism* ; Disease Resistance/physiology* ; Signal Transduction/physiology* ; Humans ; Drug Resistance, Neoplasm/physiology* ; Molecular Targeted Therapy/methods*

The gut microbiota is closely related to human health, and various gut microbiota health indices have been developed to assist in evaluating the health of the gut microbiota and even the overall health of the human body. Diets are one of the main factors that regulate the gut microbiota, while there is still no good method for evaluating the regulatory effects of dietary factors. To assess the regulatory effects of dietary factors on the gut microbiota of overweight individuals, we conducted an in vitro fermentation experiment based on 17 dietary factors, and developed an evaluation method for the regulatory effects of dietary factors based on the health index with principal component analysis (hiPCA). The results showed that most dietary factors had positive regulatory effects on the gut microbiota of overweight individuals. Galactooligosaccharides (GOS) and puerarin were the most significant dietary factors in regulating the gut microbiota of overweight individuals. The analysis of the contribution of species to the hiPCA indicated that GOS and puerarin might inhibit the activities of bacteria associated with overweight by regulating Eubacterium dolichum, Lactobacillus salivarius, Clostridium clostridioforme, Clostridium citroniae, and Lachnospiraceae bacterium 9_1_43BFAA. In addition, GOS may further enhance the inhibition of these activities by regulating Lachnospiraceae bacterium 6_1_63FAA, thereby reducing the gut health risks in overweight individuals. In summary, this study evaluated the health effects of dietary factors based on the hiPCA and specifically analyzed the role of different dietary factors in regulating the gut microbiota of overweight individuals. This provides new ideas and methods for improving gut microbiota health and has potential applications in the field of precision nutrition.
Humans ; Gastrointestinal Microbiome/physiology* ; Isoflavones/pharmacology* ; Overweight/microbiology* ; Diet ; Fermentation ; Oligosaccharides/pharmacology* ; Principal Component Analysis

Objective To introduce the application scene,operating steps and preliminary clinical effect of tibial bone mass preservation technique in medial unicompartmental knee arthroplasty(MUKA).Methods A total of 15 patients with antero-medial knee osteoarthritis(AMOA)treated in this hospital from May 2022 to May 2023 were selected as the study subjects.The tibial bone mass preservation technique was a-dopted to complete MUKA(fixed platform prosthesis).The operating time,intraoperative bleeding volume,hospitalization duration and operation complications were recorded.The VAS score before operation and in last follow up,range of motion(ROM)of knee joint,Knee Society Score(KSS),hip and knee stomping angle(HKA)of lower extremity in the operation side and image results were recorded to evaluate the clinical effect.Results The operations in 15 cases were successfully completed.The average operation time was(82.73±9.97)min,mean intraoperative bleeding volume was(21.00±9.49)mL and average hospital stay was(4.9±1.4)d.There was no intraoperative nerve,vascular and medial collateral ligament injury,no iatro-genic fracture,and no postoperative surgical site infection.All patients were followed up for average(5.87±2.77)months.The VAS score of knee joint,ROM,KSS and HKA angle of lower limb in the operated side were significantly improved compared with before operation(P<0.05).There was no prosthesis loosening,displacement or fragmentation,and no obvious degeneration aggravation of the lateral compartment of the knee joint.Conclusion The tibial bone mass preservation technique is a simple,effective and reliable method to deal with the slightly tight flexion space after tibial osteotomy during MUKA,and the postoperative clinical efficacy and imaging results are excellent.

Objective To explore the effect of dexmedetomidine nasal spray(DNS)on perioperative sleep quality,anxiety stress in patients undergoing hysterectomy.Methods A total of 75 patients who underwent laparoscopic hysterectomy at Taizhou First People's Hospital from May to December 2024 were selected and divided into control group(37 cases)and experimental group(38 cases)according to the random number table method.Patients in experimental group were respectively sprayed with 50μg or 75pg of DNS at 20:30 on the night before surgery and the night after surgery,patients in control group were respectively given an equal volume of normal saline nasal spray at 20:30 on the night before surgery and the night after surgery.Athens insomnia scale(AIS)scores and sleep quality on the first night of admission(T0),the first night before surgery(T1),the first night after surgery(T2),and the second night after surgery(T3),the scores of hospital anxiety and depression scale(HADS),salivary cortisol andα-amylase on the first day of admission,before entering the operating room,and on the first and second days after surgery,and incidence of adverse reactions 60 minutes after administration between two groups of patients were observed and compared.Results Compared with control group,the AIS scores in experimental group at T1,T2 and T3 were significantly lower,the latency to sleep was significantly shortened,the total sleep time and non-rapid eye movement sleep time were significantly prolonged,and rapid eye movement sleep time was significantly shortened(P＜0.05),number of awakenings at T1 and T2 decreased significantly(P＜0.05),and HADS score,salivary cortisol and α-amylase levels before entering the operating room,and on the first and second days after surgery were all significantly decreased(P＜0.05).There was no statistically significant difference in the incidence of adverse reactions within 60 minutes after administration between two groups of patients(P＞0.05).Conclusion Perioperative administration of DNS can significantly improve the sleep quality of patients undergoing laparoscopic hysterectomy,relieve anxiety,reduce stress levels,and has high safety.

Objective To explore the effect of dexmedetomidine nasal spray(DNS)on perioperative sleep quality,anxiety stress in patients undergoing hysterectomy.Methods A total of 75 patients who underwent laparoscopic hysterectomy at Taizhou First People's Hospital from May to December 2024 were selected and divided into control group(37 cases)and experimental group(38 cases)according to the random number table method.Patients in experimental group were respectively sprayed with 50μg or 75pg of DNS at 20:30 on the night before surgery and the night after surgery,patients in control group were respectively given an equal volume of normal saline nasal spray at 20:30 on the night before surgery and the night after surgery.Athens insomnia scale(AIS)scores and sleep quality on the first night of admission(T0),the first night before surgery(T1),the first night after surgery(T2),and the second night after surgery(T3),the scores of hospital anxiety and depression scale(HADS),salivary cortisol andα-amylase on the first day of admission,before entering the operating room,and on the first and second days after surgery,and incidence of adverse reactions 60 minutes after administration between two groups of patients were observed and compared.Results Compared with control group,the AIS scores in experimental group at T1,T2 and T3 were significantly lower,the latency to sleep was significantly shortened,the total sleep time and non-rapid eye movement sleep time were significantly prolonged,and rapid eye movement sleep time was significantly shortened(P＜0.05),number of awakenings at T1 and T2 decreased significantly(P＜0.05),and HADS score,salivary cortisol and α-amylase levels before entering the operating room,and on the first and second days after surgery were all significantly decreased(P＜0.05).There was no statistically significant difference in the incidence of adverse reactions within 60 minutes after administration between two groups of patients(P＞0.05).Conclusion Perioperative administration of DNS can significantly improve the sleep quality of patients undergoing laparoscopic hysterectomy,relieve anxiety,reduce stress levels,and has high safety.

Objective:To explore the genetic and clinical characteristics of epilepsy related with ATP6V1A gene heterozygous variants.Methods:A case series study was conducted. The clinical data of 10 children of epilepsy associated with ATP6V1A gene variants who were admitted to the Children′s Medical Center, Peking University First Hospital from January 2019 to December 2024 was collected. The characteristics of children′ gene variation, clinical phenotype, auxiliary examination results, treatment and prognosis were analyzed.Results:Among the 10 children, there were 4 boys and 6 girls. All 10 children with ATP6V1A gene variants were de novo heterozygous variants, including 1 case of mosaic variant. A total of 9 different variants were identified and 7 variants have not been reported previously. The age at epilepsy onset was 28 (9, 48) months. Five children experienced their first seizure as a fever induction. The types of epileptic seizures included focal seizures in 6 children, epileptic spasms in 5 children, tonic spasms and atonic seizures in 1 child respectively. Three children had 2 seizure types. Global developmental delays were exhibited in 8 children, 2 of whom manifested autism spectrum disorder phenotypes. Two children showed normal development. Electroencephalography revealed slowed background activity in 5 children. Interictal epileptiform discharges were recorded in 9 cases, including hypsarrhythmia, focal, multifocal or generalized discharges. Clinical seizures were captured in 4 children. Brain magnetic resonance imaging abnormalities were found in 4 children, including frontotemporal cortical dysplasia, prominent sulci, delayed myelination of white matter, dysplasia of the corpus callosum, bilateral ventricular enlargement, and cerebral atrophy. Five children were diagnosed with developmental and epileptic encephalopathy (DEE), and 4 of them were diagnosed with infantile epileptic spasms syndrome. At the last follow-up, the age was 78 (25, 120) months. Seizures were controlled in 6 children, while 4 children had uncontrolled seizures despite treatment with ≥3 anti-seizure medications. Conclusions:All children with ATP6V1A gene related epilepsy harbored de novo heterozygous missense variants, with few showing mosaic variants. Seizure onset age ranged widely from the neonatal period to childhood. The predominant seizure types were focal seizures and epileptic spasms. The phenotypic spectrum may exhibit DEE, while a minority maintain normal development.

The Xuming Decoction, which is recorded in the "Gu Jin Lu Yan" section of Zhang Zhongjing's Synopsis of the Golden Chamber, is a traditional Chinese medicine formula. Recent literature review and summary of the clinical application research progress have found that this formula is primarily used to treat diseases such as acute cerebral infarction, facial neuritis, multiple sclerosis, Guillain-Barre syndrome, and pulmonary distension. However, different medical practitioners and scholars hold diverse understandings of Xuming Decoction.

ObjectiveTo investigate the impact of acute respiratory infections in children under 12 years old in Pudong New Area， Shanghai from 2019 to 2023. MethodsAcute respiratory infection samples of children under 12 years old from three sentinel hospitals in Pudong New Area， Shanghai from 2019 to 2023 were collected， and 42 respiratory infection pathogens， including influenza virus， adenovirus， parainfluenza virus， respiratory syncytial virus， human enterovirus/rhinovirus， human pulmonary virus， human bokavirus， coronavirus （229E， HKU1， NL63 and OC43）， and novel coronavirus， were detected with microfluidic chips. The situation of acute respiratory infections among outpatient and inpatient children in this area was analyzed for the before the implementation of non pharmacological intervention measures （2019.12‒2020.1）， during the period of non pharmacological intervention measures （2020.2‒2022.12）， and after non pharmacological intervention measures （2023.1‒2023.6）. ResultsFrom 2019 to 2023， a total of 1 770 samples were collected， and 445 pathogens were detected， with a detection rate of 25.14% （445/1 770）. The main pathogens detected during the study period were influenza virus： 8.70% （154/1 770）， respiratory syncytial virus： 4.41% （78/1 770）， human enterovirus/rhinovirus： 2.66% （47/1 770）， human adenovirus： 2.49% （44/1 770）， and parainfluenza virus： 2.20% （39/1 770）. Before the implementation of non pharmacological intervention measures， outpatients were primarily infected with influenza， parainfluenza virus， and respiratory syncytial virus， with detection rates of 8.09%， 4.49%， and 4.04%， respectively； inpatients were mainly infected with influenza， respiratory syncytial virus， and parainfluenza virus， with detection rates of 4.49%， 3.82%， and 3.15%， respectively. During the period of non pharmacological intervention measures， influenza， rhinovirus and respiratory syncytial virus were the main viruses detected in the samples of outpatient children， with detection rates of 4.04%， 3.60%， and 2.47%， respectively； inpatient samples mainly detected respiratory syncytial virus， rhinovirus， and influenza virus， with detection rates of 3.60%， 2.02%， and 1.80%， respectively. After non pharmacological intervention measures， influenza， rhinovirus and respiratory syncytial virus were the main pathogens detected in the outpatients， with detection rates of 9.89%， 2.92% and 2.02%， respectively； influenza， respiratory syncytial virus， and rhinovirus were the main pathogens detected in inpatient children， with detection rates of 6.29%， 1.57%， and 1.35%， respectively. ConclusionThe prevalence of pathogens related to acute respiratory infections in children is influenced by non pharmacological preventive measures.

Objective:To summarize the genotype and clinical phenotype of children with WWOX gene related developmental and epileptic encephalopathy (DEE).Methods:Case series studies. The clinical data of 12 children with WWOX gene related DEE who were admitted to the Neurological Department of Children′s Medical Center, Peking University First Hospital from June 2019 to December 2023 were analyzed. The children′s characteristics of gene variation, clinical phenotype, auxiliary examination results, treatment and prognosis were analyzed.Results:Among 12 children with WWOX gene related DEE, there were 7 boys and 5 girls, the age of seizure onset ranged from 10 days to 6 months (median 1.8 months). Multiple seizure types were observed, including focal seizures in 10 cases, epileptic spasms in 9 cases, tonic seizures in 4 cases, myoclonic seizures in 1 case. Among 12 cases, 9 cases had multiple seizure types. All 12 cases showed microcephaly and global developmental delay. Video electroencephalography showed slowed background activity in 6 cases, hyperarrhythmia in 6 cases, multifocal discharges in 6 cases, and focal discharges in 1 case. Epileptic spasms were detected in 8 cases, tonic seizures in 4 cases and myoclonic seizures in 1 case. Brain magnetic resonance imaging showed bilateral frontotemporal subarachnoid space widening in 5 cases, deep sulci in 3 cases, bilateral ventricular enlargement in 2 cases, callosal hypoplasia in 5 cases, and delayed white matter myelination in 3 cases. The phenotypes of 12 cases were consistent with the diagnosis of DEE, and 8 of them were diagnosed with infantile epileptic spasm syndrome. All the WWOX gene variants in 12 cases were complex heterozygous variants, including 20 variants, 11 variants and 1 large intragenic WWOX gene deletion (p.Ala149Thr, p.Arg156Ser, p.R167Tfs*8, p.Leu186Val, c.605+5G>A, p.Trp218*, p.His263Arg, p.Leu275fs*19*1, p.N285Kfs*10, p.Ser304Tyr, p.Met326Arg, loss1 exon2-8) had not been reported previously. The age of last follow-up ranged from 11 months to 5 years and 3 months. During the follow-up, 1 case died at the age of 1 year and 10 months, 2 cases were seizure-free, and 9 cases still had seizures after multiple anti-seizure medications.Conclusions:The seizure onset age of children with WWOX gene related DEE is usually less than 6 months, and some of them in neonate. The common seizure types include focal seizures and epileptic spasms. Children usually have microcephaly and global developmental delay. WWOX gene related DEE usually has drug refractory epilepsy.