Objective To investigate the early cognitive development characteristics of children with Williams syndrome(WS)at different age stages.Methods From September 2018 to June 2023,106 children diagnosed with WS at the Department of Pediatric Health Care,Children's Hospital,Zhejiang University School of Medicine,aged 1 to<5 years,were prospectively enrolled.All children underwent Gesell developmental diagnostic assessments to analyze the cognitive development characteristics of WS children across different age groups.Results The average age of the 106 WS children was(3.1±1.2)years;58 were male,and 48 were female.There were no significant differences in developmental levels between males and females in the five domains of gross motor skills,fine motor skills,language,personal-social skills,and adaptive behavior(P>0.05).The incidence rates of mild,moderate,severe,and profound developmental disabilities among children of different age groups showed no significant differences(P>0.05).Comparisons of developmental levels in gross motor skills,language,personal-social skills,and adaptive behavior among different age groups were also not statistically significant(P>0.05).With the increase of age,the developmental level of fine motor skills showed a decreasing trend(P<0.05).There were no significant differences in verbal IQ and non-verbal IQ within each age group of WS children(P>0.05).Conclusions The overall developmental level of WS children stabilizes with age,and their early language abilities do not significantly exceed their non-verbal abilities.

Limb preservation techniques of severed limbs play an important role in autologous replantation or allografting. At present, static cold storage (SCS) remains the gold standard for the in vitro preservation of severed limbs, which minimizes oxygen and energy metabolism. However, with a relatively short time window of 4-6 hours, SCS is insufficient for clinical transfer, injury management and other medical resources. To address this issue, researchers have initiated investigations into alternative methods of supplying oxygen and nutrients to severed limbs, leading to the development of mechanical perfusion technology and per-sufflation technology. Mechanical perfusion technology aims to clear metabolic waste and provide essential nutrients by mimicking a physiological state, thereby prolonging the preservation time and improving the outcome of the repair. Per-sufflation technology aims to deliver oxygen directly to the tissue using a vascular system to maintain tissue integrity. With these emerging technologies showing great promise, further exploration and refinement are needed to address their time constraints and complexity in clinical work. Furthermore, for severed limbs that are not suitable for immediate reimplantation, autologous heterotopic parasitism techniques and temporary endovascular shunts offer promising avenues for preservation. Autologous heterotopic parasitism techniques maintain tissue viability by constructing a temporary parasitic environment, while temporary endovascular shunts establish a temporary vascular access at the damaged site to deliver donor blood, thereby maintaining blood flow and promoting repair. Xenogeneic cross-circulation techniques combine recent advances from multiple disciplines and demonstrate remarkable potential; however, they currently face challenges such as ethics, immune rejection, and technical complexity. The combination of these novel techniques has led to a significant advancement in the field of limb preservation and repair. This article aims to provide an overview of the current research status and development of static cold storage, pre-sufflation, mechanical perfusion preservation and temporary ectopic parasitic preservation techniques in limb preservation over recent years, providing information for clinical work, promoting the development of limb reimplantation and transplantation techniques in China and further consolidating China's leadership in the field of amputation reimplantation and allograft transplantation.

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

Objective To investigate the brain age differences between Alzheimer's disease(AD)and mild cognitive impairment(MCI)patients,and further explore the correlations between brain age gap(BAG)and clinical features.Methods The clinical data and radiologic findings of 132 probable AD and AD-derived MCI patients diagnosed at Beijing Tiantan Hospital,Capital Medical University from December 2018 to July 2021 were retrospectively analyzed.According to the diagnostic criteria for AD and MCI,the patients were assigned into AD and MCI groups.In addition,156 volunteers without neurological diseases and other severe diseases were recruited as the control group.The general data,Montreal cognitive assessment(MoCA)score,and mini-mental state examination(MMSE)score were compared among the three groups.The deep learning-based brain age prediction model was employed to calculate the BAGs of the three groups.Spearman correlation analysis was conducted to explore the correlations between BAG and clinical features.Results The 132 patients included 106 patients in the AD group and 26 patients in the MCI group.The MoCA and MMSE scores followed an ascending trend of AD groupP<0.001).The predicted brain age and BAG in the AD group were higher than those in the MCI group(P=0.040,P=0.003)and control group(P=0.001,P<0.001).There was no significant difference in predicted brain age or BAG between MCI and control groups(P=0.352,P=0.224).BAG was negatively correlated with MoCA score(r=-0.341,P<0.001)and MMSE score(r=-0.324,P=0.001)in the AD group.Conclusion BAG can be used as an imaging biomarker to evaluate the degree of brain structural variation and the severity of brain injury in the patients with cognitive impairment.
Humans ; Alzheimer Disease ; Retrospective Studies ; Cognitive Dysfunction ; Brain/diagnostic imaging*

Objective:To analyze the clinical manifestations, gene mutation characteristics and treatment effects of patients with GATOR1 complex-related epilepsy, and to explore the diagnosis and treatment of this disease.Methods:The medical history, electroencephalogram, brain imaging, genetic test results, treatment and follow-up data of patients with GATOR1 complex-related epilepsy who attended the Children′s Hospital Affiliated to Capital Institute of Pediatrics, Beijing Tsinghua Changgung Hospital, and Shanghai Deji Hospital from May 2017 to July 2022 were retrospectively analyzed.Results:A total of 16 patients with GATOR1 complex-related epilepsy were collected, including 7 males and 9 females. The age of onset of epilepsy was from 2 months to 14 years. Ten cases had focal seizures only, 2 cases had generalized seizures only, and 4 cases had coexistence of focal seizures and generalized seizures, of which generalized seizures included generalized tonic-clonic seizure, spastic seizure, and myoclonic seizure. Among the 16 patients, 2 had infantile spasms, 3 had familial focal epilepsy with variable focus, and 1 had sleep related hyperkinetic epilepsy. Electroencephalogram intervals suggested multiple brain areas discharge or diffuse discharge. A total of 13 DEPDC5 gene mutation sites, 1 NPRL2 gene mutation site, and 2 NPRL3 gene mutation sites were found; 4 sites of DEPDC5 gene were reported sites, the rest were unreported; all mutations had pathogenic significance; 8 cases had nonsense mutation, 1 case had large fragment deletion, 4 cases had frameshift mutation, 1 case had integer mutation, 2 cases had splicing mutation; 13 cases′ mutation was inherited from parents, 2 cases had new mutation, and 1 case had unverified mutation. Magnetic resonance imaging (MRI) showed 5 of the 16 patients were normal, and 11 had abnormal cerebral cortex structure, manifested as bottom-of-sulcus focal cortical dysplasia (FCD), abnormal formation of sulci and (or) gyri with or without ill-defined gray-white matter and malformation of cortical dysplasia of the bilateral brain. Seven patients underwent stereotactic electroencephalogram (SEEG) monitoring, and the SEEG showed low-amplitude fast rhythm at the beginning in 6 patients, of whom 5 cases started from the frontal lobe, and 1 case started from the parietal lobe. Eight patients were only treated with drugs, 1 with single-drug therapy and the rest with multi-drug combination therapy. Eight patients underwent surgery. Among them, 5 patients with DEPDC5 gene mutation underwent epileptogenic cortex excising after SEEG monitoring, and postoperative pathological examinations showed FCDⅡ, FCDⅢ or non-specific changes; 1 patient was waiting for surgery. One patient with NPRL3 gene mutation underwent epileptogenic foci resection and postoperative pathological examinations showed FCDⅡa; the other patient with NPRL3 gene mutation underwent radiofrequency thermocoagulation after SEEG monitoring. Follow-up showed that 3 patients were seizure-free with drug treatment, and 4 patients had fewer seizures after drug treatment. Six cases underwent epileptic foci resection. Five of them were assisted by SEEG to locate the epileptic foci before surgery and were seizure-free after the operation, but the range of surgical resection was wider than the abnormal range shown by MRI; whereas 1 case who was not assisted by SEEG showed no improvement. There was still 1 case who underwent SEEG-guided radiofrequency thermocoagulation and had no improvement after operation. Conclusions:GATOR1 complex-related epilepsy mostly manifests as focal seizures. SEEG shows that seizures originate from the frontal lobe more often, and cortical developmental abnormalities are often found. DEPDC5 gene mutations are the most common ones, mostly inherited from parents, with high incomplete penetrance rate. Therefore, genetic testing is recommended for non-acquired brain structural abnormalities. For those who are refractory to drugs, a radical cure can be obtained by resection of the epileptogenic foci after preoperative evaluation.

An increasing number of studies have recently indicated the important effects of gut microbes on various functions of the central nervous system.However, the underlying mechanisms by which gut microbiota regulate brain functions and behavioral phenotypes remain largely unknown. We therefore used isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic analysis to obtain proteomic profiles of the hippocampus in germ-free (GF), colonized GF, and specific pathogen-free (SPF) mice. We then integrated the resulting proteomic data with previously reported mRNA microarray data, to further explore the effects of gut microbes on host brain functions. We identified that 61 proteins were upregulated and 242 proteins were downregulated in GF mice compared with SPF mice. Of these, 124 proteins were significantly restored following gut microbiota colonization. Bioinformatic analysis of these significant proteins indicated that the glucocorticoid receptor signaling pathway and inflammation-related pathways were the most enriched disrupted pathways. This study provides new insights into the pathological mechanisms of gut microbiota-regulated diseases.

Objective: To compare the efficacy between laparoscopic and open proximal gastrectomy with double-tract reconstruction for Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). Methods: A retrospective cohort study was conducted. Inclusion criteria: (1) 18 to 80 years old; (2) Siewert II and III AEG was confirmed by preoperative gastroscopy and biopsy, which could not be resected by endoscopy; patients undergoing radical proximal gastrectomy with double-tract reconstruction; (3) contrast-enhanced abdominal CT staging was cT1-2N0M0; (4) Eastern Cooperative Oncology Group (ECOG) physical status score <2 points, American Association of Anesthesiologists (ASA) grade 1 to 2; (5) patients agreed to perform proximal gastrectomy and signed an informed consent. Those who had undergone neoadjuvant radiochemotherapy, suffered from serious mental diseases and had incomplete data were excluded. According to the above criteria, clinical data of 84 consecutive patients with Siewert II and III AEG undergoing surgery at General Surgery Department of The Affiliated Tumor Hospital of Zhengzhou University from October 2010 to December 2018 were collected and analyzed. Of 84 patients, 61 underwent open proximal gastrectomy with double-tract reconstruction (OPG group), while 23 underwent laparoscopic proximal gastrectomy with double-tract reconstruction (LPG group). The perioperative complications and postoperative reflux esophagitis of two groups were compared. A P-value of <0.05 was considered to be statistically significant. Results: Among 84 cases, 74 were male and 10 were female. There were 43 cases of Siewert type II and 41 cases of Siewert type III. There were no significant differences in age, gender, body mass index, comorbidities, Siewert type, and tumor staging between the two groups (all P>0.05). As compared to the OPG group, the LPG group had longer operation duration [(223±21) minutes vs. (161±14) minutes, t=15.352, P<0.001], less intraoperative blood loss [195 (150, 215) ml vs. 208 (192, 230) ml, Z=2.143, P=0.032], and shorter time to flatus [(2.8±0.7) days vs. (3.3±0.9) days, t=2.477, P=0.015]. There were no significant differences in the number of harvested lymph nodes, time to the first meal and postoperative hospital stay between the two groups (all P>0.05). Postoperative complications developed in 2 cases (8.7%, 1 case each for anastomotic leakage and intestinal obstruction) in the LPG group and 5 cases (8.2%, 1 case each for anastomotic leakage, anastomotic bleeding, and anastomotic stenosis, 2 cases of incision infection) in the OPG group (χ(2)=5.603, P=0.231). The median follow-up was 41.2 (12.8-110.5) months. One patient (1.6%,1/61) had obvious reflux symptoms in the OPG group, compared with none in the LPG group (χ(2)=0.644, P=0.422). Esophagitis occurred in 1 case (4.8%, 1/21) in LPG group, compared with 4 patients (7.1%, 4/56) in the OPG group, without significant difference between the two groups (χ(2)=0.505, P=0.477). Conclusion: Laparoscopic proximal gastrectomy with double-tract reconstruction is safe and feasible without increasing the risk of postoperative complication and reflux esophagitis.
Adenocarcinoma/surgery* ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Esophagogastric Junction/surgery* ; Female ; Gastrectomy ; Humans ; Laparoscopy ; Male ; Middle Aged ; Retrospective Studies ; Stomach Neoplasms/surgery* ; Treatment Outcome ; Young Adult

OBJECTIVE: To evaluate the efficacy of autogenous bone marrow injection and elastic intramedullary injection in the treatment of bone cyst in children. METHODS: From January 2012 to December 2016, 56 children with simple bone cyst were divided into two groups: autogenous bone marrow blood injection group and elastic intramedullary needle group. There were 28 cases in the autogenous bone marrow blood injection group, 16 boys and 12 girls, aged (7.7±1.9) years old, 10 cases of proximal humerus, 8 cases of proximal femur, 6 cases of proximal tibia and 4 cases of femoral shaft. In the elastic intramedullary needle group, there were 28 cases, 18 boys and 10 girls, aged(7.5±2.2) years old, 11 cases of proximal humerus, 7 cases of proximal femur, 5 cases of proximal tibia, 4 cases of femoral shaft and 1 case of distal femur. The treatment effect was evaluated by Capanna standard. RESULTS: All the patients were followed up, including 17 to 35(25.6±4.2) months in the elastic intramedullary needle group and 19 to 35(27.4±4.8) months in the autogenous marrow blood injection group. According to Capanna's evaluation standard of bone cyst, 27 patients in the elastic intramedullary needle group were treated effectively(25 patients cured, 2 patients healed but some remained lesions), 1 patients recurred, 0 patient had no response to treatment; 18 patients in the autogenous bone marrow blood injection group were treated effectively(13 patients cured, 5 patients healed but some remained lesions), 8 patients of cyst recurred, 2 patients had no response to treatment; the difference between the two groups was statistically significant(<0.01). The overall cure time was calculated by the follow-up of 25 cases in the elastic intramedullary injection group and 13 cases in the autogenous marrow blood injection group. The cure time was(20.2±3.5) months in the elastic intramedullary injection group and(27.7±4.9) months in the autogenous marrow blood injection group. The difference was statistically significant(<0.05). CONCLUSIONS For the treatment of bone cyst in children, the therapeutic effect of elastic intramedullary needle is better than that of autogenous bone marrow blood injection, and the cure time is shorter.
Bone Cysts ; Bone Marrow ; Child ; Child, Preschool ; Female ; Fracture Fixation, Intramedullary ; Humans ; Male ; Neoplasm Recurrence, Local ; Treatment Outcome

Objective To compare the effectiveness of two kinds of limb length measurement in total hip arthroplasty (THA) with modified Hardinge approaches on equal length of lower extremities. Methods Clinical records of 151 patients who had been through one-side THAwith modified Hardinge approaches for the first time in our hospital from January 2015 to May 2017 were retrospectively analyzed. Two limb length measurements were applied: 84 patients were measured using X-ray normal side control (group A) and 67 patients were measured using location method of Kirschner pin (group B). The operation duration, blood loss during operation, length difference of lower limbs, the incidence of unequal length of lower limbs, hospitalization time and Harris scores of hip function were compared between two groups. Results All of 151 patients completed the follow-up visit. The duration of operation in group Awas statistically longer than that in group B[(107. 32±12. 01) min vs (94. 56±15. 39) min)] (P＜0. 05). The length difference of lower limbs in group Awas significantly smaller than that in group B[(1. 08±0. 52) mm vs (3. 79±1. 54) mm)] (P＜0. 05). The blood loss during operation, the incidence of unequal length of lower limbs, hospitalization time and Harris score of hip function in two groups were not statistically different. Conclusion Between two methods mentioned above, X-ray normal side control (group A) was more accurate than the location method of Kirschner pin(group B) in length control of lower limbs, but it took longer duration of operation than group B.