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.

PURPOSE: This study aims to investigate the efficacy of novel distraction support (DS) in intramedullary nailing treatment for tibial shaft fracture. METHODS: The random controlled trial included adult patients with tibial shaft fractures who were treated with intramedullary nailing at the trauma center between July 2013 and December 2018. Participants were randomly assigned to either control group (n=43) or DS group (n=42) based on whether DS was used during the operation. All surgical procedures were conducted by a single, experienced surgeon. Parameters such as hospital stay, blood loss, operative time, infection, delayed union, and malalignment were recorded for assessment. Shapiro-Wilk test was used to assess normality, and the F test was adopted to measure variance homogeneity. Continuous variables were presented as mean±standard deviation and compared via independent samples t-tests. Categorical variables are expressed as percentages. The Pearson's Chi-squared or Fisher's exact test was used for categorical variables n (%). Two-sided p<0.05 indicated statistical significance. RESULTS: A total of 85 participants were enrolled in the study. All cases achieved acceptable reduction. The operative time was significantly shorter in the DS group than in control group ((75.3±10.5) min vs. (90.4±15.5) min, p<0.001). Additionally, the DS group showed lesser blood loss ((60.1±27.2) mL vs. (85.4±25.4) mL, p<0.001). No significant differences were observed between the 2 groups in terms of hospital stay ((9.4±2.7) days vs. (10.2±3.1) days, p=0.370), infection (3 (7.1%) vs. 2 (4.7%), p=0.978), delayed union (2 (4.8%) vs. 5 (11.6%), p=0.450), and malalignment (3 (7.1%) vs. 5 (11.6%), p=0.713). CONCLUSION The use of DS in intramedullary nailing surgery is effective. The application of this DS system may represent a valuable addition to future clinical practice.
Humans ; Fracture Fixation, Intramedullary/methods* ; Tibial Fractures/surgery* ; Male ; Female ; Adult ; Middle Aged ; Operative Time ; Length of Stay ; Young Adult ; Osteogenesis, Distraction/methods*

Objective To explore the clinical value of high-frequency ultrasound combined with minimally invasive plate osteosynthesis(MIPO)in preserving the supraclavicular nerve in clavicle fractures.Methods Sixty patients with mid-clavicle fractures who were treated at the First Affiliated Hospital of Ningbo University from September 2022 to May 2024 were selected.Patients were divided into minimally invasive incision group(n=30)treated with high-frequency ultrasound combined with MIPO and traditional incision group(n=30)treated with open reduction and locked plate fixation.The perioperative indicators,visual analogue scale scores for pain,Constant-Murley shoulder scoring scale(CMS),and incidence of complications were compared between two groups.Results All patients completed the surgery and were followed up for 6 months.The bone call formation time and incision length in minimally invasive incision group were lower than those in traditional incision group(P＜0.05);The CMS at 3 months and 6 months after surgery in minimally invasive incision group were higher than those in traditional incision group(P＜0.05).The incidence of skin sensory abnormalities in minimally invasive incision group at 2 weeks,1 month,and 3 months after surgery was lower than that in traditional incision group(P＜0.05).Conclusion Compared with traditional open reduction and plate internal fixation,the high-frequency ultrasound combined with MIPO technique can effectively reduce the iatrogenic injury of the supraclavicular nerve during surgery,reduce the incidence of postoperative skin sensory abnormalities,and also have significant advantages in terms of shoulder aesthetics,shoulder joint function,and fracture healing.

Objective To explore the clinical value of high-frequency ultrasound combined with minimally invasive plate osteosynthesis(MIPO)in preserving the supraclavicular nerve in clavicle fractures.Methods Sixty patients with mid-clavicle fractures who were treated at the First Affiliated Hospital of Ningbo University from September 2022 to May 2024 were selected.Patients were divided into minimally invasive incision group(n=30)treated with high-frequency ultrasound combined with MIPO and traditional incision group(n=30)treated with open reduction and locked plate fixation.The perioperative indicators,visual analogue scale scores for pain,Constant-Murley shoulder scoring scale(CMS),and incidence of complications were compared between two groups.Results All patients completed the surgery and were followed up for 6 months.The bone call formation time and incision length in minimally invasive incision group were lower than those in traditional incision group(P＜0.05);The CMS at 3 months and 6 months after surgery in minimally invasive incision group were higher than those in traditional incision group(P＜0.05).The incidence of skin sensory abnormalities in minimally invasive incision group at 2 weeks,1 month,and 3 months after surgery was lower than that in traditional incision group(P＜0.05).Conclusion Compared with traditional open reduction and plate internal fixation,the high-frequency ultrasound combined with MIPO technique can effectively reduce the iatrogenic injury of the supraclavicular nerve during surgery,reduce the incidence of postoperative skin sensory abnormalities,and also have significant advantages in terms of shoulder aesthetics,shoulder joint function,and fracture healing.

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.

Cabozantinib, mainly targeting cMet and vascular endothelial growth factor receptor 2, is the second-line treatment for patients with advanced hepatocellular carcinoma (HCC). However, the lower response rate and resistance limit its enduring clinical benefit. In this study, we found that cMet-low HCC cells showed primary resistance to cMet inhibitors, and the combination of cabozantinib and mammalian target of rapamycin (mTOR) inhibitor, rapamycin, exhibited a synergistic inhibitory effect on the in vitro cell proliferation and in vivo tumor growth of these cells. Mechanically, the combination of rapamycin with cabozantinib resulted in the remarkable inhibition of AKT, extracellular signal-regulated protein kinases, mTOR, and common downstream signal molecules of receptor tyrosine kinases; decreased cyclin D1 expression; and induced cell cycle arrest. Meanwhile, rapamycin enhanced the inhibitory effects of cabozantinib on the migration and tubule formation of human umbilical vascular endothelial cells and human growth factor-induced invasion of cMet inhibitor-resistant HCC cells under hypoxia condition. These effects were further validated in xenograft models. In conclusion, our findings uncover a potential combination therapy of cabozantinib and rapamycin to combat cabozantinib-resistant HCC.
Anilides/pharmacology* ; Animals ; Carcinoma, Hepatocellular/drug therapy* ; Cell Line, Tumor ; Cell Proliferation ; Endothelial Cells/metabolism* ; Humans ; Liver Neoplasms/drug therapy* ; Pyridines/pharmacology* ; Sirolimus/pharmacology* ; Xenograft Model Antitumor Assays

Objective:To analyze the clinical characteristics of adult Chinese patients with syncope.Methods:This is a cross-sectional survey study. Patients with preliminary diagnosis of syncope in the Emergency Department, Geriatrics and Cardiology Outpatient Department, or Syncope Unit of 37 hospitals in 19 provinces, autonomous regions and the Hong Kong Special Administrative Region from June 2018 to March 2021 were included in this study. The clinical features of these patients with syncope were analyzed.Results:A total of 4 950 consecutive patients with syncope were included in this study. The age was (56.3±16.8)years, and 2 604 cases (52.6%) were male. The most common type of syncope was neurally mediated syncope (2 345 (47.4%)), followed by cardiac syncope (1 085 (21.9%)), orthostatic hypotensive syncope (311 (6.3%)), and unexplained syncope accounted for nearly one third (1 155 (23.3%)). Predisposing syncope was more common in patients under 65 years of age(2 066(72.4%) vs. 786(27.6%),χ 2=136.5, P<0.001). Presyncope was more common in patients with neurally mediated syncope (1 972(79.0%) vs.1 908(73.9%), χ 2=17.756, P<0.001). Premonitory symptoms were more common in women(1 837(80.0%) vs. 1 863(73.0%),χ 2=33.432, P<0.001). Presyncope syndrome was more common in patients under 65 years of age (2 482(77.8%) vs. 1 218(73.4%),χ 2=17.523, P=0.001). Cyanosis was more common in ≥65 years old patients (271(18.2%) vs. 369(12.7%), χ 2=23.235, P<0.001). Urinary incontinence was more common in old patients aged ≥65 years(252(15.2%) vs. 345(10.8%), χ 2=19.313, P<0.001). Family history was more common in patients with cardiogenic syncope compared with other types of syncope (264(24.3%) vs. 754(19.5%), χ 2=11.899, P=0.001). Hypertention(1 480(30.5%)), coronary heart disease(1 057(21.4%)), atrial flutter and atrial fibrillation(359(7.2%)), second degree atrioventricular block(236(4.8%)) were common complications of syncope. The proportion of patients with coronary heart disease was significantly higher in cardiac syncope than that of other types of syncope(417(38.4%) vs. 640(16.6%), χ 2=241.376, P<0.001). Other common complications included cerebrovascular diseases (551 (11.1%)) and diabetes mellitus (632(12.8%)). Conclusions:Neurally mediated syncope is the most common syncope in adult Chinese population. Patients with predisposing conditions and premonitory conditions are younger. Presyncope is more common in women. The proportion of family history and coronary heart disease is higher in patients with cardiogenic syncope.

Objective:To introduce a new operative technique of mini-invasive plating of midshaft clavicle fractures with lateral clavicle anatomic locking plate and evaluate its clinical outcomes.Methods:From August 2017 to March 2019, 30 midshaft clavicular fracture patients were included in this study and retrospectively analyzed. There were 22 males and eight females with an average of 44.63±13.22 years (range 14-65 years). According to Robinson classification nine patients were classified as Type 2A2, 17 patients were classified as Type 2B1 and four patients were classified as Type 2B2. Before operation no symptoms of neurovascular injury was observed in this group. Operations were performed on an average of 2.33±1.75 d (range 0-7 d) after the injury. By comparing the injured clavicle lengths with the opposite healthy side pre and postoperatively on anteroposterior chest x-ray to evaluate the effect of indirect reduction. Shoulder function was evaluated using the Constant-Murley score at 6th month after the operation. Meanwhile, 32 patients with midshaft clavicular fracture treated with open reduction and internal fixation using clavicle reconstruction locking plate treated by the same group surgerons were compared in incision length, surgical duration, intraoperative fluoroscopy times, blood loss, fracture reduction, fracture healing time, Constant-Murley score and other complications. There were 25 males and seven females with an average of 42.63±14.18 years (range 16-70 years). According to Robinson classification six patients were classified as Type 2A2, 19 patients were classified as Type 2B1 and seven patients were classified as Type 2B2.Results:In mini-invasive group all patients were treated successfully with minimally invasive percutaneous osteosynthesis (MIPO) technique using lateral clavicle anatomic locking plate. The mean surgical duration was 63.40±7.82 minutes (range 48-92 min), The mean intraoperative fluoroscopy was 4.83±1.58 times (range 3-8 times). The mean blood lose was 15.67±4.13ml (range 10-30 ml). In open reduction group the mean surgical duration was 56.22±10.11 min (range 42-80 min), the mean intraoperative fluoroscopy was 3.91±1.49 times (range 2-5 times). The mean blood lose was 56.88±13.93 ml (range 40-100 ml). There was a significant difference in statistic by comparing surgical duration, intraoperative fluoroscopy times, blood loss ( P<0.05). In mini-invasive group the average proportional difference of the clavicular length was 12.15%±2.69% (range 5.2%-15.1%) preoperative and 0.45%±0.44% (range -0.2%-1.6%) postoperative comparing with the opposite healthy side, in open reduction group the average proportional difference of the clavicular length was 11.58%±2.67% (range 4.5%-16.1%) preoperative and 0.62%±0.41% (range -0.2%-1.2%) postoperative comparing with the opposite healthy side. There was no difference in statistic by comparing the fracture reduction in these two groups ( P>0.05). The mean follow-up period was 11.3±2.8 months (range 10-18 months) in mini-invasive group. Radiographic healing of the fracture was achieved at a mean time of 3.57±0.90 months (range 3-5 months). In open reduction group the mean follow-up period was 11.8±2.2 months (range 10-18 months), fracture healing time was 4.27±1.12 months (range 3-6 months), and there was significant difference in fracture union ( P<0.05). In mini-invasive group the mean total incision length was 2.8±0.48 cm (range 2.5-4.0 cm), no patient complained of numbness or paresthesia on subclavicular region or anterior chest wall, and all patients were satisfied with the cosmesis of the wounds and showed excellent shoulder joint function with a mean Constant-Murley score of 94.83±2.55 (range 89-97) at sixth month after the operation. In open reduction group the mean incision length was 11.0±1.08 cm (range 10-14 cm), 9 patients complained of numbness or paresthesia on subclavicular region or anterior chest wall, and only 5 patients were satisfied with the cosmesis of the wounds with a mean Constant-Murley score of 90.59±4.23 (range 78-97). There was a significant difference in statistic by comparing incision length, satisfactory cosmesis results, Constant-Murley score and paresthesia on subclavicular region ( P<0.05). Conclusion:Mini-invasive percutaneous plating of midshaft clavicle fractures with lateral clavicle anatomic locking plate is a good option for the treatment of midshaft clavicle fractures with satisfactory cosmesis results and excellent return to function.

Objective: To introduce the surgical method of lateral dorsalis pedis chain-linked artery based flap for repairing foot, ankle, and posterior heel wounds, and to evaluate its clinical outcome. Methods: From June 2013 to February 2016, 11 cases with skin defects of foot, ankle, and posterior heel wounds were reviewed. The defects were repaired using the lateral dorsalis pedis chain-linked artery based flap.The wounds in 7 cases were repaired using the island flap based on the descending branch of the anterior lateral malleolar artery. The wounds in 3 cases were repaired using the island flap based on the lateral calcaneal branch of the posterior lateral malleolar artery. The reversed flap based on the forth metatarsal artery was used in one patient. The wound defects ranged from 1.5 cm×2.0 cm to 6.0 cm×13.0 cm.The area of the flap ranged from 2 cm×3 cm to 7 cm×15 cm were used to repair the wound.The donor site was skin grafted with split-thickness skin harvested from the abdomen. Results: Circulations of the all 11 cases were stable, with good wound healing after 2 weeks.10 patients had clinical follow-up. The patients were followed up from 2 months to 18 months, average of 8 months.All flap grafts survived with no bloated menifestion in pedical or "cat′s ear" deformity.Flaps were soft. Color was consistent with normal skin.Skin graft donor sites had no obvious scars.Patients were extremely satisfied with the result of repair. Conclusions The use of the lateral dorsalis pedis chain-linked artery based flap has many advantages, such as no sacrifice of the main vessels, extended coverage area and thin flap. It is a simple and effective method to repair wounds of the foot, ankle, and posterior heel.

Objective To systematically evaluate the short-term outcomes of laparoscopic splenectomy and azygoportal disconnection (LSD) with open splenectomy and azygoportal disconnection (OSD) in the prevention and treatment of portal hypertension (PHT) hemorrhage.Methods A meta-analysis was conducted to evaluate the short-term outcomes published in randomized controlled studies and high quality casecontrolled studies on patients who underwent LSD or OSD from January 2006 to January 2016.Results 1 359 patients from 18 Chinese and English articles which met the inclusion criteria were included into this study.LSD and OSD were performed in 685 patients (the LSD group) and 674 patients (the OSD group),respectively.Meta-analysis showed that there was no significant difference in operation time between the LSD and OSD groups [MD=17.66,95％CI=(-2.46 ～37.78),P＞0.05].When compared with the OSD group,the LSD group had a shorter postoperative hospitalization stay [MD =-3.99,95％ CI =(-4.82 ～ -3.16),P ＜ 0.05],earlier postoperatively first passing of flatus [MD =-1.09,95％ CI =(-1.41 ～ -0.78),P ＜ 0.05],less intraoperative bleeding [MD =-272.66,95％ CI =(-345.11 ～-200.21),P ＜ 0.05],a lower complication rate [OR =0.34,95％ CI =(0.25 ～ 0.47),P ＜ 0.05],less postoperative pain [MD =-2.54,95％ CI =(-2.79 ～-2.29),P ＜ 0.05],shorter postoperative ambulation time [MD =-3.16,95％ CI =(-3.53 ～-2.79),P ＜ 0.05],less amount of peritoneal drainage [MD =-180.28,95％ CI =(-293.06 ～-67.49),P ＜0.05] and earlier recovery from postoperative loss in appetite [MD =-1.42,95％ CI =(-1.70 ～-1.13),P ＜ 0.05].Conclusion Compared with the traditional OSD,LSD had the advantages of less invasiveness,quicker recovery and higher quality of life in the perioperative period.LSD is the preferred operation for the prevention and treatment of PHT massive hemorrhage.