Objective: To analyze the clinical and genetic characteristics of pediatric patients with dual genetic diagnoses (DGD). Methods: Clinical and genetic data of pediatric patients with DGD from January 2021 to February 2022 in Peking University First Hospital were collected and analyzed retrospectively. Results: Among the 9 children, 6 were boys and 3 were girls. The age of last visit or follow-up was 5.0 (2.7,6.8) years. The main clinical manifestations included motor retardation, mental retardation, multiple malformations, and skeletal deformity. Cases 1-4 were all all boys, showed myopathic gait, poor running and jumping, and significantly increased level of serum creatine kinase. Disease-causing variations in Duchenne muscular dystrophy (DMD) gene were confirmed by genetic testing. The 4 children were diagnosed with DMD or Becker muscular dystrophy combined with a second genetic disease, including hypertrophic osteoarthropathy, spinal muscular atrophy, fragile X syndrome, and cerebral cavernous malformations type 3, respectively. Cases 5-9 were clinically and genetically diagnosed as COL9A1 gene-related multiple epiphyseal dysplasia type 6 combined with NF1 gene-related neurofibromatosis type 1, COL6A3 gene-related Bethlem myopathy with WNT1 gene-related osteogenesis imperfecta type XV, Turner syndrome (45, X0/46, XX chimera) with TH gene-related Segawa syndrome, Chromosome 22q11.2 microduplication syndrome with DYNC1H1 gene-related autosomal dominant lower extremity-predominant spinal muscular atrophy-1, and ANKRD11 gene-related KBG syndrome combined with IRF2BPL gene-related neurodevelopmental disorder with regression, abnormal movement, language loss and epilepsy. DMD was the most common, and there were 6 autosomal dominant diseases caused by de novo heterozygous pathogenic variations. Conclusions: Pediatric patients with coexistence of double genetic diagnoses show complex phenotypes. When the clinical manifestations and progression are not fully consistent with the diagnosed rare genetic disease, a second rare genetic disease should be considered, and autosomal dominant diseases caused by de novo heterozygous pathogenic variation should be paid attention to. Trio-based whole-exome sequencing combining a variety of molecular genetic tests would be helpful for precise diagnosis.
Humans ; Abnormalities, Multiple ; Retrospective Studies ; Intellectual Disability/genetics* ; Bone Diseases, Developmental/complications* ; Tooth Abnormalities/complications* ; Facies ; Muscular Dystrophy, Duchenne/complications* ; Muscular Atrophy, Spinal/complications* ; Carrier Proteins ; Nuclear Proteins

The normal function of vascular endothelial cells is an important foundation for maintaining vascular permeability， restricting inflammatory activities of the vascular wall， and balancing the coagulation and fibrinolytic system. Endothelial dysfunction caused by persistent damage from pathological factors is considered as an early and prominent event of diabetic macroangiopathy. In traditional Chinese medicine， the classical theory of "restraining excessiveness to acquire harmony" was originally a condensed generalization of the rule of generation， restriction， replacement and evolution in the natural world， revealing the internal regulation mechanism of the stable operation of things. Then it gradually evolved into an important rule to explain the physiological phenomena and pathological mechanism of human body and guide the treatment. Corresponding to the nature， the body homeostasis also requires to achieve a state of strong viscera function and inexhaustible Qi and blood generation under the rule of restriction and generation. The pathogenesis of diabetic macroangiopathy is the process of "the predominant one failing to restrict and the hyperactive one becoming harmful". The loss of restriction and generation of the five organs leads to powerless Qi transformation and， as a result， the Qi， blood and body fluid cannot be dispersed. Therefore， the Qi， blood and body fluid turn into phlegm and blood stasis， such as glucose and lipid metabolism disorder， oxidative stress， inflammatory response and high blood viscosity， and finally block the veins. Excessive phlegm and blood stasis cannot be resolved， instead they become harmful and invade the blood vessel， causing endothelial dysfunction and further resulting in diabetic macroangiopathy. Under the guidance of the theory of "restraining excessiveness to acquire harmony"， the method of "harmonizing viscera， eliminating pathogen and removing turbidity" can effectively regulate the function of vascular endothelial cells， thus playing a positive role in preventing and treating diabetic macroangiopathy. The mechanism may be related to reducing oxidative stress， inhibiting inflammation， limiting vascular smooth muscle proliferation， and reducing platelet adhesion.

OBJECTIVE: To study the clinical characteristics of epileptic patients with synchronous occipital and frontopolar spikes phenomenon. METHODS: The clinical data,EEG features of patients with synchronous occipital and frontopolar spikes phenomenon were retrospectively reviewed. RESULTS: Totally 34 male and 21 female patients had synchronous occipital and frontopolar spikes. Ages at the time of recording the synchronous occipital and frontopolar spikes phenomenon ranged from 2 years 6 months to 14 years with the median age of 6 years 6 months. In the total 55 patients,12 patients had contralateral synchronous discharges,12 patients had ipsilateral synchronous,17 patients had bilateral synchronous discharges,7 patients had bilateral synchronous discharges tending to contralateral synchronously,and 7 patients had bilateral synchronous discharges tending to ipsilateral synchronously. Occipital preceded frontopolar discharges in 42 patients. Frontopolar preceded occipital discharges in 3 patients. The phase difference between the occipital and frontopolar spikes could not be distinguished in 10 patients. Based on the etiology and diagnoses,there was Panayiotopoulos syndrome in 33 patients,epilepsy with structural abnormality in 13 patients,secondary epilepsy due to immune encephalitis in 1 patient,epilepsy accompanied by inborn error of metabolism in 2 patients and epilepsy with unknown etiology in 6 patients. CONCLUSION: The synchronous occipital and frontopolar spikes phenomenon usually appears during childhood or develops from other discharge patterns in infancy stage. The synchronous occipital and frontopolar spikes phenomenon can be ipsilateral synchronous or contralateral synchronous discharges. The occipital spikes preceded frontopolar spikes in most patients. The synchronous occipital and frontopolar spikes phenomenon is mostly found in Panayiotopoulos syndrome,but it is also found in epilepsy with different etiologies.

OBJECTIVE: To investigate whether the tonic-clonic seizure (TCS) induced by intermittent photic stimulation (IPS)was generalized tonic-clonic seizure (GTCS)or partial secondarily tonic-clonic seizure (PGTCS),and to analyze the relationship between them. METHODS: Video-electroencephalogram (VEEG)database of Peking University First Hospital from March 2010 to October 2018 were reviewed. Fifteen cases with idiopathic epilepsy who had TCS induced by IPS were included in this study, and their clinical and electroencephalogram (EEG)characteristics were retrospectively analyzed. RESULTS: In this study, 4 of the 15 cases were boys and 11 were girls. The age of seizure onset ranged from 1 to 13 years. According to the medical records: 12 cases were considered as GTCS,while the remaining 3 cases were considered as PGTCS. The age at VEEG monitoring ranged from 2.5 to 16.0 years. All backgrounds of the VEEG were normal. Interictal discharges:generalized discharges in 11 cases, of which 4 cases coexisted with posterior discharges, 2 cases coexisted with Rolandic discharges, the other 5 cases merely had generalized discharges; merely focal discharges in two cases, one in the Rolandic area and the other in the posterior area; no interictal discharge in the remaining 2 cases. IPS induced photoparoxysmal response (PPR)results: 2 cases without PPR,the remaining 13 cases with PPR of generalized discharges, and 6 of the 13 cases coexisted with posterior discharges. IPS induced photoconvulsive response (PCR)results: GTCS in one case (contradictory to medical history),PGTCS in 11 cases (consistent with medical history),and GTCS and PGTCS hardly to distinguish in the remaining 3 cases. Of the three conditions above, there were generalized myoclonic seizures induced by IPS before TCS in 7 cases. CONCLUSION The medical history was unreliable in determining whether TCS was generalized or focal. Myoclonic seizures can coexist with PGTCS, and sometimes GTCS was indistinguishable from PGTCS, indicating that the dichotomy of seizure types need to be improved. Photosensitive TCS should be regarded as a continuum between focal and generalized seizures.
Electroencephalography ; Epilepsy, Generalized ; Epilepsy, Tonic-Clonic ; Female ; Humans ; Male ; Retrospective Studies ; Seizures

PURPOSETo evaluate the effect of retention sutures on abdominal pressure and postoperative prognosis in abdominal surgery patients.

METHODSThis prospective cohort study included patients who were admitted to Daping Hospital from May 15, 2014 to October 11, 2014. A total of 57 patients were enrolled, including 18 patients in the "U" type retention suture group, 17 patients in the intermittent retention suture group, and 22 patients in non-retention suture group. The demographic data, clinical data and risk factors for abdominal wound dehiscence were recorded. The bladder pressure (IVP) was monitored preoperatively, intraoperatively, and four days postoperatively. Additionally, the incidence of abdominal wound dehiscence and infection 14 days after the operation was recorded.

RESULTSDuring the operation, the IVP decreased and then increased; it was at its lowest 1 h after the start of the operation (5.3 mmHg ± 3.2 mmHg) and peaked after tension-reducing (8.8 mmHg ± 4.0 mmHg). The IVP values in the "U" type retention suture group and intermittent retention suture group were higher than in the non-retention suture group 4 days after operation (p < 0.005). The Visual Analogue Scale (VAS) pain scores were 3.9 ± 2.2, 3.8 ± 2.0, and 3.0 ± 1.0 in the retention suture group, intermittent retention suture group and non-retention suture group, respectively. The VAS pain scores in the "U" type tension-reducing group and intermittent tension-reducing group were higher than in the non-tension-reducing group (p < 0.005).

CONCLUSIONAlthough retention sutures may reduce the incidence of postoperative wound dehiscence in abdominal surgery patients, they can increase the IVP and postoperative pain.

OBJECTIVE: To investigate the clinical significance of high-frequency oscillations (HFOs) on scalp electroencephalography (EEG) in patients with epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS). METHODS: Twenty-one CSWS patients treated for epilepsy from January 2006 to December 2016 in Pediatric Department of Peking University First Hospital were enrolled into the study. Selected clinical variables including gender, age parameters, seizure frequencies and antiepileptic drugs were compared between (a). HFO-positive group and HFO-negative group before methylprednisolone treatment and (b). excellent seizure outcome group and not-excellent seizure outcome group after methylprednisolone treatment. Interictal HFOs and spikes in pre- and post-methylprednisolone scalp EEG were measured and analyzed. RESULTS: Before methylprednisolone treatment, there were 12 of 21 (57%) CSWS patients had HFOs, with a mean value 43.17 per 60 s per patient. The 12 patients with HFOs tended to have more frequent epileptic negative myoclonus/atonic/myoclonus/atypical absences than those without HFOs in a month before methylprednisolone treatment. A total of 518 HFOs and 22 592 spikes were found in the pre-methylprednisolone EEG data of 21 patients, and 441 HFOs (86%) were associated with spikes. The highest amplitudes of HFOs were significantly positively correlated with that of spikes (r=0.279, P<0.001). Rates reduced by methylprednisolone treatment were statistically significant for both HFOs (P=0.002) and spikes (P=0.006). The percentage of reduction was 91% (473/518) and 39% (8 905/22 592) for spikes and HFOs, respectively. The percentage of spike and HFOs changes was respectively 100% decrease and 47% decrease in the excellent seizure outcome group, and they were 79% decrease and 18% increase in the not-excellent seizure outcome group. CONCLUSION Prevalence of HFOs might reflect some aspect of epileptic activity. HFOs were more sensitive to methylprednisolone treatment than spikes and had a good correlation with the prognosis of seizures, and HFOs could be applied to assess epilepsy severity and antiepileptic therapy.
Anticonvulsants/therapeutic use* ; Child ; Electroencephalography/methods* ; Epilepsy/physiopathology* ; Epilepsy, Absence ; Humans ; Methylprednisolone ; Scalp ; Seizures ; Sleep

Objective To analyze the clinical characteristics,muscle pathological features and pathogenic gene mutation of a family with autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD).Methods Clinical data of the proband and her family members,a Chinese family of AD-EDMD,were collected.Skeletal muscle specimens were collected from the proband for pathological analysis.Genomic DNA from the proband and her parents was extracted using standard procedures from the peripheral blood leukocytes.PCR and DNA direct sequencing were employed to analyze all of the 12 exons of the LMNA gene to determine the gene mutation,and the case was summarized along with related literature review.Results The proband,female,4 years and 5 months old now,presented with muscle weakness during her early childhood,the proximally was more prominent,mild pectus excavatum.Her CK level was elevated,her electromyogram showed myogenic injuries,the muscle biopsy showed myopathy changes.Her father had the same symptom,with disease progressed,showed elbow contractures in early stage,stiff neck,tight achilles tendon,slowly progressive muscle weakness of the limbs,sinus bradycardia.A heterozygous missense mutation c.1580G ＞ C (p.Arg527Pro) was identified in exon 9 of the LMNA gene in the proband and her father,but not in her mother.This heterozygous missense mutation had been reported as a pathogenic gene mutation.Conclusions The patient who has elbow contractures in early stage,limited neck flexion,spine stiffness,muscle weakness with the proximal upper limbs and distal lower limbs,and arrhythmia,should have an analysis of the LMNA gene.It's important for the early diagnosis of EDMD,assessment of the prognosis,timely and effectively monitoring the changes of arrhythmia,then taking interventions to improve the quality of life and prolong life.So genetic analysis is most reliable method to diagnose EDMD.

Objective To analyze the clinical characteristics,muscle pathological features and pathogenic gene mutation in 4 cases with LMNA-related congenital muscular dystrophy (L-CMD).Methods Clinical data of the probands and the parents were collected.Skeletal muscle specimens were biopsied from the probands for pathological analysis.Genomic DNA and RNA were extracted from peripheral blood leukocytes,and PCR,reverse transcription(RT)-PCR and DNA direct sequencing were employed to analyze the LMNA gene to determine the gene mutation and confirm the pathogenicity.Results Four patients had symptoms from fetal period to several months after birth.They presented with motor retardation,muscle weakness with prominent the proximal upper limbs,distal lower limbs and neck extensor,hypotonia,contractures,with mild to moderate elevation of CK level.The muscle biopsies showed muscular dystrophic and with inflammatory changes,and the abnormal nuclear morphology was observed with transmission electron microscopy.Genetic analysis of them detected 4 dominant de novo mutations.Three of them had unreported pathogenic mutations.The same sites of the LMNA gene were wild type in their parents.Conclusions Four cases of L-CMD are genetically identified.Genetic counseling of the family can be possible.The patients should be considered LMNA gene mutation of they present themselves with muscle weakness with the proximal upper limbs,distal lower limbs and neck extensor,hypotonia,contractures,mild to moderate elevation of CK level,and if the biopsies show muscular dystrophic changes but also with inflammatory changes should be considered LMNA gene mutation.Genetic analysis is the most reliable method for diagnosing L-CMD.

OBJECTIVETo study the effect of skin-derived progenitor cell (SKP) combined with hyaluronic acid( HA) on the wound healing in diabetic rats.

METHODSSKP of Spraque-Dawley (SD) neonate rats were isolated and cultured and mixed with HA. The differentiation characteristics of SKP in the culture were observed. Sixty SD rats were injected intraperitoneally with 65 mg/kg streptozotocin( STZ) to induce diabetes. Two symmetrical full-thickness cutaneous wounds( 1.0 cm in diameter) were made on the back of each SD rat and randomly divided into A (n = 20, with treatment of 100 mircol SKP-HA) , B (n = 20, with treatment of 100 mirol HA) , and C ( n = 20, with treatment of DMEM/F12 culture medium) groups. Tissue samples from wound in each group were harvested on 1, 2, 3, 4 weeks after the treatment. Wound healing rate, changes in histomorphology, the content of hydroxyproline ( HYP) , and immigration of labelled SKP were determined and analyzed.

RESULTSSKP grew well when cultured with HA. The characteristics of SKP to differentiate into lipocyte, neuron, and neurogliocyte remained in the culture. Compared with that in C group, epithelization in the wounds of A and B groups appeared earlier. The wound healing rate in A group [ (72.1 +/- 2. 8)% ] and B group [ (53.7 +/- 2. 9)% ] were obviously higher at 2 post-treatment weeks(PTW) than that in group C [(42. 5 +/- 1.5)% ( P <0.05) , and that in A group was obviously higher compared with B and C groups at 3 PTW ( P < 0. 05 or 0. 01). The wound healing rates in A and B groups were (100. 00 +/- 0.00) % at 4 PIW, which were obviously higher than that of group C( P <0.01) . There was no obvious difference in the HYP content among the 3 groups at 1 PIW ( P > 0. 05) , but it was obviously higher in A and B groups than that in C group at 2,3,4 PTW( P <0.01) , and that in A group was significantly higher than that in B group at 3 and 4 PTW( P <0. 01). SKP survived well on the wound, and migrated towards the dermis as time elapses.

CONCLUSIONSKP-HA composition can promote wound healing in diabetic rats.

Animals ; Diabetes Mellitus, Experimental ; pathology ; Hyaluronic Acid ; pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Skin ; cytology ; Stem Cells ; chemistry ; cytology ; Wound Healing ; drug effects