Objective:To summarize the clinical manifestations, genetic characteristics and diagnosis and treatment processes of ATP1A2 gene-related childhood neurological diseases presenting with hemiplegic migraine (HM) or epilepsy, and enhance the understanding of clinicians on the diseases related to this gene. Methods:A retrospective study was performed; data of 5 children with ATP1A2 gene variations admitted to Department of Neurology, Hunan Children's Hospital from April 2015 to June 2024 were collected, and their clinical characteristics were summarized. ATP1A2 gene variations were confirmed by whole exome sequencing on these 5 children's families using next-generation sequencing (NGS), and then, further validated by Sanger sequencing. A comprehensive literature search was performed through PubMed, CNKI, and Wanfang databases to summarize the disease spectrum associated with this gene. Results:Among the 5 pediatric patients, 3 exhibited HM phenotype (all presented with neurological symptoms of epilepsy/febrile seizures within the first year of life, followed by HM onset after intervals ranging from 3 years and 3 months to 7 years); 2 pediatric patients aligned with epilepsy phenotype, including one instance of drug-resistant focal-onset epileptic encephalopathy. These 5 pediatric patients carried de novo missense variants in the ATP1A2 gene, encompassing 5 distinct mutation sites. Notably, the c.1023C>G (p.Cys341Trp) and c.2458G>A (p.Ala820Thr) variants were not documented in ClinVar or HGMD databases, and were classified as likely pathogenic according to American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines. Literature review revealed that all reported ATP1A2 mutations in Chinese pediatric patients were missense variants, with c.2143G>C (p.Gly715Arg) being the most commonly prevalent (8/29, 27.6%). The predominant clinical manifestation was HM (22/29), characterized by hemiplegia, aphasia, fever, impaired consciousness, and convulsions (early transient neurological symptoms frequently manifested as febrile seizures [12/22, 54.4%]); additionally, alternating hemiplegia of childhood was noted in 4 pediatric patients and epilepsy in 3 pediatric patients. Conclusion:ATP1A2 gene variants can lead to neurological disorders such as HM and epilepsy, with varied severity at same phenotype; the missense variants c.1023C>G and c.2458G>A in the ATP1A2 gene expand the spectrum of ATP1A2 gene variants and may serve as genetic causes of epilepsy.

OBJECTIVE: To compare the effects of different chest compression rates (60-140 times/min) on hemodynamic parameters, return of spontaneous circulation (ROSC), resuscitation success, and survival in a porcine model of cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR). METHODS: Forty healthy male domestic pigs were randomly divided into five groups based on chest compression rate: 60, 80, 100, 120, and 140 times/min (n = 8). All animals underwent standard anesthesia and tracheal intubation. A catheter was inserted via the left femoral artery into the thoracic aorta to monitor aortic pressure (AOP), and another via the right external jugular vein into the right atrium to monitor right atrial pressure (RAP). In each group, animals were implanted with a stimulating electrode via the right external jugular vein to the endocardium, and ventricular fibrillation (VF) was induced by delivering alternating current stimulation, resulting in CA. After a 1-minute, manual chest compressions were performed at the assigned rate with a compression depth of 5 cm. The first defibrillation was delivered after 2 minutes of CPR. No epinephrine or other pharmacologic agents were administered during the entire resuscitation process. From 1 minute before VF induction to 10 minutes after ROSC, dynamic monitoring of AOP, coronary perfusion pressure (CPP), and partial pressure of end-tidal carbon dioxide (P_ETCO₂). Cortical ultrastructure was examined 24 hours post-ROSC using transmission electron microscopy. RESULTS: With increasing compression rates, both the total number of defibrillations and cumulative defibrillation energy significantly decreased, reaching their lowest levels in the 120 times/min group. The number of defibrillations decreased from (4.88±0.83) times in the 60 times/min group to (2.25±0.71) times in the 120 compressions/min group, and energy from (975.00±166.90)J to (450.00±141.42)J. However, both parameters increased again in the 140 times/min group [(4.75±1.04)times, (950.00±207.02)J], the differences among the groups were statistically significant (both P < 0.01). As compression frequency increased, P_ETCO₂, pre-defibrillation AOP and CPP significantly improved, peaking in the 120 times/min group [compared with the 60 times/min group, P_ETCO₂ (mmHg, 1 mmHg≈0.133 kPa): 18.69±1.98 vs. 8.67±1.30, AOP (mmHg): 95.13±7.06 vs. 71.00±6.41, CPP (mmHg): 14.88±6.92 vs. 8.57±3.42]. However, in the 140 times/min group, these values declined significantly again [P_ETCO₂, AOP, and CPP were (10.59±1.40), (72.38±11.49), and (10.36±4.57) mmHg, respectively], the differences among the groups were statistically significant (all P < 0.01). The number of animals achieving ROSC, successful resuscitation, and 24-hour survival increased with higher compression rates, reaching a peak in the 120 times/min group (compared with the 60 times/min group, ROSC: 7 vs. 2, successful resuscitation: 7 vs. 2, 24-hour survival: 7 vs.1), then decreased again in the 140 times/min group (the animals that ROSC, successfully recovered and survived for 24 hours were 3, 3, and 2, respectively). Transmission electron microscopy revealed that in the 60, 80, and 140 times/min groups, nuclear membranes in cerebral tissue were irregular and incomplete, nucleoli were indistinct, and mitochondria were swollen with reduced cristae and abnormal morphology. In contrast, the 100 times/min and 120 times/min groups exhibited significantly attenuated ultrastructural damage. CONCLUSIONS Among the tested chest compression rates of 60-140 times/min, a chest compressions frequency of 120 times/min is the most favorable hemodynamic profile and outcomes during CPR in a porcine CA model. However, due to the wide spacing between groups, further investigation is needed to determine the optimal compression rate range more precisely.
Animals ; Cardiopulmonary Resuscitation/methods* ; Swine ; Male ; Heart Arrest/therapy* ; Heart Massage/methods* ; Hemodynamics

Objective:To summarize the clinical manifestations, genetic characteristics and diagnosis and treatment processes of ATP1A2 gene-related childhood neurological diseases presenting with hemiplegic migraine (HM) or epilepsy, and enhance the understanding of clinicians on the diseases related to this gene. Methods:A retrospective study was performed; data of 5 children with ATP1A2 gene variations admitted to Department of Neurology, Hunan Children's Hospital from April 2015 to June 2024 were collected, and their clinical characteristics were summarized. ATP1A2 gene variations were confirmed by whole exome sequencing on these 5 children's families using next-generation sequencing (NGS), and then, further validated by Sanger sequencing. A comprehensive literature search was performed through PubMed, CNKI, and Wanfang databases to summarize the disease spectrum associated with this gene. Results:Among the 5 pediatric patients, 3 exhibited HM phenotype (all presented with neurological symptoms of epilepsy/febrile seizures within the first year of life, followed by HM onset after intervals ranging from 3 years and 3 months to 7 years); 2 pediatric patients aligned with epilepsy phenotype, including one instance of drug-resistant focal-onset epileptic encephalopathy. These 5 pediatric patients carried de novo missense variants in the ATP1A2 gene, encompassing 5 distinct mutation sites. Notably, the c.1023C>G (p.Cys341Trp) and c.2458G>A (p.Ala820Thr) variants were not documented in ClinVar or HGMD databases, and were classified as likely pathogenic according to American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines. Literature review revealed that all reported ATP1A2 mutations in Chinese pediatric patients were missense variants, with c.2143G>C (p.Gly715Arg) being the most commonly prevalent (8/29, 27.6%). The predominant clinical manifestation was HM (22/29), characterized by hemiplegia, aphasia, fever, impaired consciousness, and convulsions (early transient neurological symptoms frequently manifested as febrile seizures [12/22, 54.4%]); additionally, alternating hemiplegia of childhood was noted in 4 pediatric patients and epilepsy in 3 pediatric patients. Conclusion:ATP1A2 gene variants can lead to neurological disorders such as HM and epilepsy, with varied severity at same phenotype; the missense variants c.1023C>G and c.2458G>A in the ATP1A2 gene expand the spectrum of ATP1A2 gene variants and may serve as genetic causes of epilepsy.

Objective:To explore the clinical characteristics and genetic etiology of a child with Spondyloocular syndrome (SOS) in order to enhance the awareness and understanding of this disease.Methods:A 3.5-year-old boy with SOS who had presented at the Department of Medical Genetics of Hunan Children′s Hospital on August 10, 2023 due to the repeated fractures for over 2 years and after binocular cataract surgery was selected as the study subject. Clinical data of his pedigree were collected, and peripheral venous blood samples were collected for the extraction of genomic DNA and subjected to trio-whole exome sequencing. Candidate variants were verified by Sanger sequencing and analyzed with bioinformatic software. This study was approved by the Medical Ethics Committee of Hunan Children′s Hospital (No. KYSQ2022-263).Results:The child had manifested repeated fractures, bilateral bowed femur, osteoporosis, cataract, atrial septal defect, and developmental delay. Ultrasonography has revealed fetal edema, peritoneal effusion, pleural effusion and polyhydramnios. Trio-whole exome sequencing and Sanger sequencing revealed that he has harbored compound heterozygous variants of the XYLT2 gene, namely c. 1103_1104delAG (p.Gln368Argfs*8) and c. 1238_1253delinsA (p.Val413_Pro418delinsGlu), which were inherited from his phenotypically normal father and mother, respectively. Neither variant was reported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and recommendations from the Clinical Genome Resource (ClinGen), the c. 1103_1104delAG was predicted as a pathogenic variant (PVS1+ PM2_Supporting+ PP4), whilst the c.1238_1253delinsA was predicted as a likely pathogenic variant (PM4+ PM3+ PM2_Supporting+ PP4). Conclusion:The c. 1103_1104delAG and c. 1238_1253delinsA compound heterozygous variants of the XYLT2 gene probably underlay the pathogenesis in this child. Above finding has enriched the phenotypic and mutational spectrum of SOS, and provided a basis for the clinical diagnosis, treatment, prognosis assessment and genetic counseling for this pedigree.

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with Spondyloocular syndrome (SOS) in order to enhance the awareness and understanding of this disease. METHODS: A 3.5-year-old boy with SOS who had presented at the Department of Medical Genetics of Hunan Children's Hospital on August 10, 2023 due to the repeated fractures for over 2 years and after binocular cataract surgery was selected as the study subject. Clinical data of his pedigree were collected, and peripheral venous blood samples were collected for the extraction of genomic DNA and subjected to trio-whole exome sequencing. Candidate variants were verified by Sanger sequencing and analyzed with bioinformatic software. This study was approved by the Medical Ethics Committee of Hunan Children's Hospital (Ethics No. KYAQ2022-263). RESULTS: The child had manifested repeated fractures, bilateral bowed femur, osteoporosis, cataract, atrial septal defect, and developmental delay. Ultrasonography has revealed fetal edema, peritoneal effusion, pleural effusion and polyhydramnios. Trio-whole exome sequencing and Sanger sequencing revealed that he has harbored compound heterozygous variants of the XYLT2 gene, namely c.1103_1104delAG (p.Gln368Argfs*8) and c.1238_1253delinsA (p.Val413_Pro418delinsGlu), which were inherited from his phenotypically normal father and mother, respectively. Neither variant was reported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and recommendations from the Clinical Genome Resource (ClinGen), the c.1103_1104delAG was predicted as a pathogenic variant (PVS1+PM2_Supporting+PP4), whilst the c.1238_1253delinsA was predicted as a likely pathogenic variant (PM4+PM3+PM2_Supporting+PP4). CONCLUSION The c.1103_1104delAG and c.1238_1253delinsA compound heterozygous variants of the XYLT2 gene probably underlay the pathogenesis in this child. Above finding has enriched the phenotypic and mutational spectrum of SOS, and provided a basis for the clinical diagnosis, treatment, prognosis assessment and genetic counseling for this pedigree.
Humans ; Male ; Child, Preschool ; Heterozygote ; Pentosyltransferases/genetics* ; Pedigree ; UDP Xylose-Protein Xylosyltransferase ; Mutation ; Exome Sequencing ; Genetic Testing

A 13-year and 6-month-old girl attended the Hunan Children's Hospital due to delayed menarche. The laboratory test results indicated increased follicle-stimulating hormone and luteinizing hormone, decreased anti-Mullerian hormone, and pelvic ultrasound showed a cord-like uterus and absence of bilateral ovaries. Her 11-year and 5-month-old younger sister had the same laboratory and imaging findings, and both girls were diagnosed with primary ovarian insufficiency. Whole exome sequencing and Sanger sequencing confirmed that the proband and her sister carried heterozygous variants of HROB gene c.718C>T (p.Arg240*) and c.1351C>T (p.Arg451*), which were inherited from their parents respectively and consistent with autosomal recessive inheritance. Oral estradiol valerate at an initial dose of 0.125 mg/d was given to the proband, and the secondary sexual characteristics began to develop after 6 months.
Humans ; Female ; Child ; Infant ; Primary Ovarian Insufficiency/genetics* ; Luteinizing Hormone ; Estradiol

Objective:To observe the therapeutic effect of echinacoside (ECH) on liver injury and glucose metabolism disorder in sepsis rats induced by cecal ligation and puncture (CLP), and to explore its possible mechanism.Methods:Forty eight male Sprague Dawley (SD) rats were randomly divided into four groups: sham group (sham), model group (CLP), treatment group (CLP+ ECH) and inhibitor group (CLP+ ECH+ EX527). The sham group only received laparotomy, and the model group underwent CLP. The treatment group was intragastric administration of echinacea (30 mg/kg) every day after CLP modeling. The inhibitor group was injected with silence information regulator 1 (SIRT1) inhibitor EX527 (5 mg/kg) one hour before CLP, and then treated the same as the treatment group. Fasting blood glucose, insulin and serum biochemical indexes were detected in virous groups. The serum levels of interleukin (IL)-1 β, IL-6 and tumor necrosis factor-α(TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). 2′, 7′- dichlorofluorescein diacetate (DCFH-DA) staining was used to observe the production of reactive oxygen species (ROS) in liver tissue of rats in each group; hematoxylin-eosin (HE) staining was used to observe the pathological changes of liver tissue in each group; The expressions of SIRT1, glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), phosphorylated signal transducers and activators of transcription 3 (p-STAT3) and phosphorylated protein ki-nase B(p-AKT) were detected by Western blot.Results:Compared with sham group, the levels of serum glucose, serum insulin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), ROS, IL-1β, IL-6 and TNF-α in model group increased, while the liver glycogen and survival rate decreased (all P<0.05). After echinacoside treatment, the serum glucose, serum insulin, ALT, AST, ROS , IL-1β, IL-6 and TNF-α levels decreased, and the liver glycogen and survival rate increased (all P<0.05); After SIRT1 inhibitor intervention, the levels of serum insulin, ALT, AST, IL-6 and ROS in the inhibitor group increased ( P<0.05). HE staining showed that there were infiltration and necrosis of inflammatory cells in the liver tissue of model group, and echinacoside could significantly reduce the focal and massive necrosis; Western blot showed that compared with the sham group, the expression levels of SIRT1, p-STAT3 and p-AKT protein in the model group decreased, while the expression levels of G6Pase and PEPCK protein increased ( P<0.05); After echinacoside treatment, the expression levels of SIRT1, p-STAT3 and p-AKT increased, while the expression levels of G6Pase and PEPCK decreased ( P<0.05). After SIRT1 inhibitor intervention, the expression of SIRT1, p-STAT3 and p-AKT protein decreased, and the expression of G6Pase and PEPCK protein increased in the inhibitor group ( P<0.05). Conclusions:Echinacoside is a potential therapeutic agent for sepsis associated liver injury and glucose metabolism disorders, which may play a role by targeting SIRT1 to activate STAT3 and AKT in the liver.

Objective:To investigate the current Kangaroo Mother Care(KMC) knowledge among registered nurses working in neonatal intensive care unit (NICU) in China.Methods:A convenience sample of 607 registered nurses participated in this descriptive, cross sectional exploratory study. An online self-designed questionnaire was used to collect the data, including 12 items, 3 sections (Basic knowledge, Emergency handling, Breast feeding).Results:The total score was 6.52±2.29 (the total score was 12). The 5 items, accuracy below 50%, were ①In your opinion, the optimal duration of KMC was (10.2%,62/607); ②What to do if the baby had respiratory arrest or became blue during KMC (18.8%,114/607); ③Who should implement KMC (42.5%, 258/607); ④what could we do if the baby was not gaining weight (47.3%, 287/607); ⑤How to feed the baby during KMC (47.8%, 290/607). Registered nurses with more than 10 years of working experience in NICU scored higher; junior registered nurses scored lower; registered nurses learned by individuals scored lower ( F values were 9.413, 9.862, 5.368, all P<0.01). Conclusions:The insufficiency of KMC knowledge is common among NICU registered nurses. The understanding of basic concepts of KMC should be strengthened. Stratified training should be conducted for nurses′ ability to deal with emergencies, assess the changes in infants' conditions, and knowledge of breast feeding. All registered nurses′ KMC operation should be standardized to improve the level of implementation of KMC by NICU registered nurses.

Objective To explore the value of ultrasonic guidance-fine needle aspiration biopsy (UG-FNAB) and contrast-enhanced ultrasound (CEUS) in the differential diagnosis of benign and malignant thyroid nodules. Methods The clinical data of 160 patients (186 nodules) with conventional ultrasound suspected malignant thyroid nodules from January to December 2016 in Central Hospital of Enshi Autonomous Prefecture were retrospectively analyzed. The pathological results were used as the diagnostic gold standard to compare the value of UG-FNAB and CEUS in the differential diagnosis of benign and malignant thyroid nodules. Results Malignant thyroid nodules were characterized by low enhancement, uneven enhancement, unclear boundary and slow enhancement. The incidences in malignant thyroid nodules were significantly higher than those in benign thyroid nodules, and there were statistical differences (P＜0.01); there was no statistical difference in recession speed between benign thyroid nodules and malignant thyroid nodules (P＞0.05). The sensitivity of CEUS in the diagnosis of benign and malignant thyroid nodules was 75.56% (98/128), the specificity was 72.41% (42/58), the missed diagnosis rate was 23.44% (30/128), the misdiagnosis rate was 27.59% (16/58), the positive predictive value was 85.96% (98/114), and the negative predictive value was 58.33% (42/72); the sensitivity of UG-FNAB in the diagnosis of benign and malignant thyroid nodules was 93.75% (120/128), the specificity was 93.10% (54/58), the missed diagnosis rate was 6.25% (8/128), the misdiagnosis rate was 6.90% (4/58), the positive predictive value was 96.77% (120/124), and the negative predictive value was 87.10% (54/62). The sensitivity and specificity of UG-FNAB in the diagnosis of benign and malignant thyroid nodules were significantly higher than those in CEUS, and there were statistical differences (χ2=14.957 and 8.700, P<0.01). Conclusions Malignant thyroid nodules has unique CEUS characteristics. UG-FNAB has higher sensitivity and specificity in the differential diagnosis of benign and malignant thyroid nodules, compared with CEUS.

Objective To assess the efficacy and safety of propofol sedation for gastrointestinal endoscopy,we conducted a Meta-analysis of randomized controlled trials (RCT) comparing propofol with traditional sedative agents.Methods Referring Cochrane Collaboration search strategy to develop retrieval in Medline,Web of Science,Wanfang and CNKI database to retrieve the anesthetic propofol and traditional agents in the literature for randomized controlled trials of gastrointestinal endoscopy,surgery and assess their recovery effect.Results Twenty-one original RCTs investigating a total of 1 765 patients,of whom 894 received propofol only and 871 received traditional sedative agents only,met the inclusion criteria.Research showed that compared with traditional anesthetics,no significant differences existed in anesthetic effects of propofol on gastrointestinal endoscopy surgery time.However,surgery can significantly shorten recovery time and the average discharge time; and higher recovery rates.The result of racial subgroup analysis showed:the anesthetic propofol can significantly shorten the time of gastrointestinal endoscopy surgery for Asian populations,but had little effect on the European population.Contrast method for subgroup analysis showed:anesthetic propofol could significantly shorten the ERCP angiography in gastrointestinal endoscopy surgery time,but has little effect on the UGE and colonscopy angiography.Conclusions Propofol is safe and effective for gastrointestinal endoscopy procedures and is associated with shorter endoscopy recovery and discharge time,higher post-anesthesia recovery scores.Care should be taken when extrapolating our results to specific practice settings and high-risk patient subgroups.