Objective To explore the impact of peptidylarginine deiminase 2(Padi2)-knockout on depressive-like behaviors in socially isolated mice.Methods Using CRISPR/Cas9 technology,a Padi2-knockout(Padi2-/-)mouse model with a C57BL/6J background was established,and the effect of Padi2 knockout was identified by genotyping and RT-qPCR detection.Six-week-old male Padi2-/- mice and wild-type C57BL/6J mice were selected and divided into normal rearing and social isolation groups,with 15 mice per group.The normal rearing group mice were housed with 5 mice per cage,and the social isolation group was housed with 1 mouse per cage,and weighed once a week.After 4 weeks,forced swimming and open field tests were conducted.After the behavioral experiments,brain tissues were taken from mice in each group,and changes in microglia in the brains were detected by immunofluorescence.Results We successfully established Padi2-/- mice.There was no difference in behavior between Padi2-/- mice and C57BL/6J mice in the normal rearing group.After social isolation,compared with C57BL/6J mice,Padi2-/- mice showed a significant increase in depressive symptoms,obvious weight gain,and a significant increase in the number of microglia in brain tissue.Conclusions Padi2 knockout exacerbated depressive-like behaviors and obesity in socially isolated mice,indicating that Padi2 is involved in the progression of depression and may be an effective target for the prevention and treatment of depression.

Objective To explore the impact of peptidylarginine deiminase 2(Padi2)-knockout on depressive-like behaviors in socially isolated mice.Methods Using CRISPR/Cas9 technology,a Padi2-knockout(Padi2-/-)mouse model with a C57BL/6J background was established,and the effect of Padi2 knockout was identified by genotyping and RT-qPCR detection.Six-week-old male Padi2-/- mice and wild-type C57BL/6J mice were selected and divided into normal rearing and social isolation groups,with 15 mice per group.The normal rearing group mice were housed with 5 mice per cage,and the social isolation group was housed with 1 mouse per cage,and weighed once a week.After 4 weeks,forced swimming and open field tests were conducted.After the behavioral experiments,brain tissues were taken from mice in each group,and changes in microglia in the brains were detected by immunofluorescence.Results We successfully established Padi2-/- mice.There was no difference in behavior between Padi2-/- mice and C57BL/6J mice in the normal rearing group.After social isolation,compared with C57BL/6J mice,Padi2-/- mice showed a significant increase in depressive symptoms,obvious weight gain,and a significant increase in the number of microglia in brain tissue.Conclusions Padi2 knockout exacerbated depressive-like behaviors and obesity in socially isolated mice,indicating that Padi2 is involved in the progression of depression and may be an effective target for the prevention and treatment of depression.

Objective:To summarize the clinical characteristics and genetic features of tyrosine hydroxylase deficiency(THD) caused by TH gene variants for the improvement of the understanding of the disease. Methods:The clinical and genetic data of 33 children with THD caused by TH gene variants were diagnosed in the Department of Neurology of Beijing Children′s Hospital, Capital Medical University from May 2011 to January 2020 and their data were retrospectively collected and analyzed. Results:There were 19 females and 14 males.The age at onset was ranged from 0 to 6.3 years.13 patients developed diseases, accompanied with fever after infection, and 1 patient suffered from hypoxia, 19 patients suffered from no predisposing factors.There were 7 mild TH-deficient dopa-responsive dystonia cases, 16 severe TH-deficient infantile parkinsonism with motor delay cases and 10 very severe TH-deficient progressive infantile encephalopathy cases.Clinical symptoms were fluctuating, including 26 cases of diurnal fluctuation, 22 cases of infection aggravation, and 30 cases of fatigue aggravation.The initial symptoms included tiptoeing and numbness in the limbs(7 cases), motor development retardation or degression (26 cases), fremitus (8 cases), ptosis (2 cases), and status dystonicus (3 cases). Other clinical features had hypermyotonia (23 cases), hypomyotonia (27 cases), decreased movement (27 cases), decreased facial expression (24 cases), fremitus (18 cases), tiptoeing (20 cases), talipes equinovarus (7 cases), ptosis (8 cases), oculogyric crisis (10 cases), salivation (21 cases), dysphagia (12 cases), dysarthria (16 cases), dyspnea (3 cases), increased sleep (10 cases), decreased sleep (5 cases), irritable mood (15 cases), apathetic mood (2 cases), profuse sweating (8 cases), and status dystonicus (6 cases). A total of 6 patients′ right limbs were more severe, and 14 patients′ lower limbs were more severe.Eight patients had family history, and Levodopa treatment was effective for all patients.Ten patients suffered side effects, including dyskinesia and irritability.Four patients were lost follow-up, and 29 patients were followed up between 0.8 and 13.2 years old until Ja-nuary 2020.Totally, 22 patients almost had no such symptoms.Twenty-five TH gene pathogenic variants were discovered in 33 patients.There were 13 novel variants (c.1160T>C, c.1303T>C, c.887G>A, c.1084G>A, c.1097A>T, c.734G>T, c.907C>G, c.588G>T, c.992T>G, c.755G>A, c.184-6C>T, c.1510C>T, c.910G>A) and 2 patients had c. 910G>A variant.Meanwhile, there were 5 hot variants [c.698G>A(13 cases), c.457C>T(9 cases), c.739G>A(6 cases), c.1481C>T(4 cases), c.694C>T(3 cases)]. c.910G>A(2 cases) may be the foun-der variant of Chinese population. Conclusions:THD caused by TH gene variant mostly onsets from infant, with complex clinical features.Most of these patients were severe, and only a few were very severe and mild.Very severe and mild symptoms were easily misdiagnosed.Levodopa treatment was obviously effective.A possible founder variant of Chinese population (c.910G>A) was found.c.698G>A and c. 457C>T mutations mainly appeared in patients with severe and extremely severe THD, while c. 739G>A mainly appeared in patients with mild THD.

Objective:To evaluate the efficacy of sugammadex for the reversal of residual neuromuscular blockade after laparoscopic radical gastrectomy in elderly patients.Methods:Sixty patients of both sexes, aged 65-85 yr, with body mass index of 20-26 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ-Ⅲ, undergoing elective laparoscopic radical gastrectomy under general anesthesia, were divided into 2 groups ( n=30 each) by a random number table method: sugammadex group (S group) and neostigmine group (N group). Rocuronium 0.3-0.6 mg·kg -1·h -1 was intravenously infused during operation, and the muscle relaxation was monitored by a Veryark-TOF monitor, maintaining TOF ratio=0 and counting 1 or 2 after tonic stimulation.Rocuronium was discontinued when the peritoneum was closed.The patients were admitted to the PACU after operation.When the muscle relaxation monitoring T 2 appeared, sugammadex 2 mg/kg was intravenously injected in S group, and neostigmine 0.03 mg/kg plus atropine 0.015 mg/kg was intravenously injected in N group.The tracheal tube was removed after the patient′s consciousness and spontaneous breathing recovered.Before anesthesia (T 1) and 5 and 30 min after tracheal extubation (T 2, 3), arterial blood samples were collected for blood gas analysis, PaO 2 and PaCO 2 were recorded, and ultrasound was used to measure the diaphragm end-inspiratory thickness, end-expiratory thickness and mobility of diaphragm muscle at the above time points.The diaphragm thickening fraction was calculated.The time of T 2 appeared, time of extubation, time of postanesthesia care unit (PACU) stay, postoperative hospital stay, and residual neuromuscular blockade (TOF ratio <0.9) and hypoxemia occurred within 30 min after extubation were recorded.The pulmonary complications within 7 days after operation were recorded. Results:Compared with group N, PaO 2 was significantly increased and PaCO 2 was decreased at T 2, 3, the mobility of diaphragm muscle and diaphragm thickening fraction were increased at T 2, the tracheal extubation time, time of PACU stay and postoperative hospital stay were shortened, the residual neuromuscular blockade and hypoxemia occurred after extubation and incidence of pulmonary complications after operation were decreased ( P<0.05), and no significant change was found in the time of T 2 appeared in group S ( P>0.05). Conclusion:Sugammadex can quickly and effectively reverse the residual neuromuscular blockade after laparoscopic radical gastrectomy, which is helpful for early postoperative recovery in elderly patients.

Objective:To summarize the clinical characteristics of SYNGAP1-related epilepsy in children.Methods:Data of 13 patients with SYNGAP1 gene variants diagnosed with epilepsy at Department of Neurology, Beijing Children's Hospital were collected retrospectively from March 2017 to October 2020 and the patients were followed up. The clinical features, electroencephalogram(EEG), brain imaging, gene results and treatment were summarized.Results:Twelve patients were followed up successfully among the 13 patients with SYNGAP1 variants. The last follow-up age was 5 years and 7 months (3 years and 1 month to 9 years).The onset age of seizures was 2 years (4 months to 3 years). Seizure types included eyelid myoclonia with or without absence (9 cases), myoclonic seizure (5 cases), atypical absence (4 cases), suspicious atonic seizures(4 cases),unclassified fall attack (6 cases), and the frequency of seizures varied from several times to more than 100 times per day. Four cases had the mimic phenotype of myoclonic astatic epilepsy. The seizures of 10 cases could be triggered by eating (5 cases), emotion (5 cases), fever (3 cases), voice (2 cases), fatigue (2 cases), etc. Electroencephalography (10 cases) showed interictal generalized or focal epileptiform discharges (9 cases), and atypical aphasia (4 cases), myoclonic seizure (2 cases) and eyelid myoclonic seizure (1 case) were monitored. Of the 12 cases, 9 were added with valproate, all of which were effective (the frequency of seizures reduced>50%). Five cases received combined levetiracetam, in 3 the treatments were effective. To last follow-up, 3 cases were seizure free from 6 months to 1 year and 1 month, but the remaining 7 cases still had seizures, one or several times per day. All 13 cases had developmental retardation (speech ability impaired mostly), 2 cases were severe, 10 cases were moderate, 1 case was mild. The SYNGAP1 gene variants of 13 patients were all de novo, including 12 variants. Among them, 4 were frameshift variants, 4 were nonsense variants, 2 were missense variants and 2 were splice site variants.Conclusions:Patients with SYNGAP1-related epilepsy have an early onset age and many seizure types. The main seizure type is eyelid myoclonia with or without absence, and other seizure types include myoclonic seizure, atypical absence, unclassified fall attack, etc. Valproate is effective in most patients, but seizures in some patients might be intractable. Most patients have developmental delay (mainly moderate and severe), speech ability impaired mostly.

Objective:To investigate the effect of early and full course of hyperbaric oxygen (HBO) therapy on neuroelectrophysiology in patients with acute incomplete spinal cord injury (iSCI).Methods:A total of 65 patients with acute iSCI admitted to the Department of Orthopedics of Yantai Mountain Hospital and the Department of Spine Injury of Yuhuangding Hospital from February 2017 to February 2020 were selected as the research objects. According to the treatment, they were divided into observation group ( n=42) and control group ( n=23). The patients in the control group were treated with conventional drugs or surgery, while the patients in the observation group were treated with full course of HBO at early stage (<48 h) on the basis of the treatment in the control group. The scores of Frankel scale and American Spinal Injury Association (ASIA) impairment scale were collected before treatment, and 14 and 28 days after treatment; and the clinical efficacy was evaluated. The motor nerve conduction velocity (MCV), sensory nerve conduction velocity (SCV), amplitude of sensory action potential (SAP), motor evoked potential (MEP), and somatosensory evoked potential (SEP) of lower limbs were measured and calculated by electromyography and evoked potential meter before treatment, 14 days and 28 days after treatment. Results:After four courses of treatment, the total effective rate of the observation group (85.71%) was significantly higher than that of the control group (69.57%) with a statistically significant difference ( χ 2=6.994, P<0.05). Compared with those before treatment, the scores of neurological and motor functions (ASIA scale and Frankel scale) of the two groups after 14 days of treatment were significantly increased; compared with the scores after 14 days of treatment, the scores of neurological and motor functions after 28 days of treatment were significantly increased; compared with the scores of the control group, the scores of neurological and motor functions of the treatment group were significantly increased; and all of these were statistically significant( P<0.05). Compared with those before treatment, the peak amplitudes of SEP and MEP of tibial nerve and common peroneal nerve in the two groups were increased and the latencies were shortened after 14 days of treatment; compared with those after 14 days of treatment, the peak amplitudes of SEP and MEP of anterior tibial nerve and common peroneal nerve were increased and the latencies were shortened after 28 days of treatment; compared with those in the control group after treatment, the peak amplitudes of SEP and MEP of anterior tibial nerve and common peroneal nerve in the observation group after treatment were increased and the latencies were shortened; and all of these were statistically significant( P<0.05). Compared with those before treatment, the SCV and MCV of tibial nerve and common peroneal nerve in the two groups were significantly increased after 14 days of treatment; compared with those after 14 days of treatment, the SCV and MCV of anterior tibial nerve and common peroneal nerve were significantly increased after 28 days of treatment; compared with those in the control group after treatment, the SCV and MCV of anterior tibial nerve and common peroneal nerve in the observation group after treatment were significantly increased ( P<0.05); and all of these were statistically significant( P<0.05). Conclusion:For patients with acute iSCI, early and full course of HBO therapy can significantly improve their neuro-bioelectricity such as motor, sensory, and other evoked potentials, improve the clinical efficacy, and facilitate the recovery of spinal nerve function.

Objective:To investigate the effect of early and full course of hyperbaric oxygen (HBO) therapy on neuroelectrophysiology in patients with acute incomplete spinal cord injury (iSCI).Methods:A total of 65 patients with acute iSCI admitted to the Department of Orthopedics of Yantai Mountain Hospital and the Department of Spine Injury of Yuhuangding Hospital from February 2017 to February 2020 were selected as the research objects. According to the treatment, they were divided into observation group ( n=42) and control group ( n=23). The patients in the control group were treated with conventional drugs or surgery, while the patients in the observation group were treated with full course of HBO at early stage (<48 h) on the basis of the treatment in the control group. The scores of Frankel scale and American Spinal Injury Association (ASIA) impairment scale were collected before treatment, and 14 and 28 days after treatment; and the clinical efficacy was evaluated. The motor nerve conduction velocity (MCV), sensory nerve conduction velocity (SCV), amplitude of sensory action potential (SAP), motor evoked potential (MEP), and somatosensory evoked potential (SEP) of lower limbs were measured and calculated by electromyography and evoked potential meter before treatment, 14 days and 28 days after treatment. Results:After four courses of treatment, the total effective rate of the observation group (85.71%) was significantly higher than that of the control group (69.57%) with a statistically significant difference ( χ 2=6.994, P<0.05). Compared with those before treatment, the scores of neurological and motor functions (ASIA scale and Frankel scale) of the two groups after 14 days of treatment were significantly increased; compared with the scores after 14 days of treatment, the scores of neurological and motor functions after 28 days of treatment were significantly increased; compared with the scores of the control group, the scores of neurological and motor functions of the treatment group were significantly increased; and all of these were statistically significant( P<0.05). Compared with those before treatment, the peak amplitudes of SEP and MEP of tibial nerve and common peroneal nerve in the two groups were increased and the latencies were shortened after 14 days of treatment; compared with those after 14 days of treatment, the peak amplitudes of SEP and MEP of anterior tibial nerve and common peroneal nerve were increased and the latencies were shortened after 28 days of treatment; compared with those in the control group after treatment, the peak amplitudes of SEP and MEP of anterior tibial nerve and common peroneal nerve in the observation group after treatment were increased and the latencies were shortened; and all of these were statistically significant( P<0.05). Compared with those before treatment, the SCV and MCV of tibial nerve and common peroneal nerve in the two groups were significantly increased after 14 days of treatment; compared with those after 14 days of treatment, the SCV and MCV of anterior tibial nerve and common peroneal nerve were significantly increased after 28 days of treatment; compared with those in the control group after treatment, the SCV and MCV of anterior tibial nerve and common peroneal nerve in the observation group after treatment were significantly increased ( P<0.05); and all of these were statistically significant( P<0.05). Conclusion:For patients with acute iSCI, early and full course of HBO therapy can significantly improve their neuro-bioelectricity such as motor, sensory, and other evoked potentials, improve the clinical efficacy, and facilitate the recovery of spinal nerve function.

Objective:To summarize the clinical data of patients with acute pandysautonomia (APD) and discuss the treatment and prognosis of them.Methods:A total of 13 patients with APD in the Department of Neurology, Beijing Children′s Hospital, Capital Medical University, from January 2010 to December 2019, were investigated retrospectively.The general data, clinical symptoms, autonomic nerve examination and function test, laboratory examination, treatment and follow-up were collected and analyzed.Results:There were 4 males and 9 females in 13 patients with APD, with an average age was 8 years and 5 months (3 years and 8 months to 12 years and 5 months ). The average course of disease was 94.5 d (14-410 d). The common initial symptoms were gastrointestinal motility disorder (11 cases), dysuria (3 cases), and upright syncope/vertigo (3 cases). During the course of the disease, all the patients manifested with gastrointestinal motility disfunction and dyshidrosis, glands involvement and orthostatic hypotension in 12 cases, abnormal pupil in 9 case and urinary retention in 7 case.Other symptoms included fatigue in 9 cases, emotional disorder in 4 cases, limb weakness in 2 cases, and sensory disturbance in 2 cases.All the patients were treated with intravenous immunoglobulin (IVIG), and 3 cases combined with glucocorticoid.Six patients with severe gastrointestinal symptoms were treated with intravenous nutrition; 4 patients were fed with jejunum, 3 cases of whom returned to normal diet within 1-12 months, and 1 patient was followed up for 5 years and 2 months.Hyponatremia was found in 7 cases, which recovered in 2-30 d. Nine cases were followed up for 1 month to 9 years.Seven cases were normal in daily work and study, with satisfactory nutritional status, stable mood and no relapse.Conclusions:The clinical manifestations of APD are varied.The initial symptoms are gastrointestinal motility disorders, orthostatic hypotension, urinary retention and hyponatremia.Individualized multi-disciplinary comprehensive management for symptoms, especially the comprehensive treatment of gastrointestinal motility disorders, management of postural hypotension, and the urinary system diagnosis and individualized treatment of can shorten the length of hospital stay and improve the prognosis effectively.

Objective:To evaluate the modified efficacy of thoracic paravertebral block (TPVB) combined with general anesthesia in the patients undergoing laparoscopic radical nephrectomy.Methods:Eighty patients, aged 38-64 yr, with body mass index of 18-24 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, scheduled for elective laparoscopic radical nephrectomy, were selected and randomly divided into 2 groups ( n=40 each) using a random number table method: general anesthesia group (group GA) and TPVB combined with general anesthesia group (group TPVB+ GA). A paravertebral catheter was placed at T 8 and T 10 under ultrasound guidance before induction of anesthesia, and 0.5% ropivacaine 10 ml was administered via the catheter in group TPVB+ GA.Anesthesia was induced with propofol, sufentanil, etomidate and rocuronium and maintained by intravenous infusion of propofol and remifentanil.Patient-controlled intravenous analgesia was performed with sufentanil, ketorolac tromethamine and tropisetron at the end of surgery.When postoperative visual analog scale score≥4, tramadol 50 mg was intravenously injected as rescue analgesic.Immediately before anesthesia induction (T 0), at 5 min after establishing pneumoperitoneum (T 1), at 2 h of pneumoperitoneum (T 2), and immediately after the end of pneumoperitoneum (T 3), and at 24 h after operation (T 4), venous blood samples were collected for determination of plasma norepinephrine concentrations (by enzyme-linked immunosorbent assay), plasma cortisol level (using radioimmunoassay), and blood glucose concentrations were measured.The intraoperative consumption of sufentanil and remifentanil was recorded.The intraoperative hypertension, hypotension, and bradycardia were recorded, and the nausea and vomiting, pruritus, and requirement for rescue analgesia occurred within 24 h after surgery were recorded. Results:Compared with group GA, the plasma concentrations of norepinephrine, cortisol and blood glucose were significantly decreased at T 1-4, the intraoperative consumption of sufentanil and remifentanil was reduced, and the postoperative requirement for rescue analgesia was decreased in group TPVB+ GA ( P<0.05). There was no significant difference in the incidence of intraoperative and postoperative adverse reactions between the two groups ( P>0.05). Conclusion:TPVB combined with general anesthesia is helpful in carrying out the anesthetic model of low-consumption opioids and is more helpful in inhibiting intraoperative and postoperative stress responses and postoperative pain responses than general anesthesia alone when used for laparoscopic radical nephrectomy.

Objective:To investigate the clinical features, imaging findings and prognosis of children with overlapping syndrome of myelin oligodendrocyte glycoprotein (MOG) antibody disease and anti-N-methyl-D aspartate receptor (NMDAR) encephalitis (MNOS).Methods:The clinical manifestations, immunological antibodies in blood and cerebrospinal fluid, cranial image, treatment and follow-up of 11 patients diagnosed as MNOS in the Department of Neurology, Beijing Children′s Hospital from January 2011 to April 2019 were analyzed retrospectively.Results:A total of 11 patients, including 4 males and 7 females were analyzed, the age of onset was (10.4±2.3) years. A total of 29 episodes occurred in 11 children. At the last follow-up, 8 cases showed relapsed remission course, the interval of recurrence was 3 to 60 months. The onset symptoms of 11 patients included convulsions (10 cases), lethargy (6 cases), psychosis (6 cases). Among 29 episodes, the common symptoms were convulsions (16 episodes), psychosis (13 episodes),and lethargy (10 episodes). According to the diagnostic criteria of anti-NMDAR encephalitis and MOG-antibody disease, 29 episodes were divided into three phenotypes, including anti-NMDAR encephalitis(4 episodes), MOG-antibody diseases (10 episodes) and overlapping types (15 episodes).Twenty-seven times of acute stage cranial magnetic resonance imaging (MRI) were available, common lesions included cortical focus (22 times), subcortical white matter (7 times), brainstem (9 times). All patients were sensitive to first-line immunotherapy. Eight patients had recurrence during glucocorticoid reduction, 6 of them were treated with additional second-line immunosuppressive therapy, including cyclophosphamide (1 case) and mycophenolate mofetil (5 cases). The follow-up time of patients were 5-99 months. At the last follow-up, all patients were in remission, the pediatric cerebral performance category (PCPC) score was 1 (10 cases) and 2 (1 cases).Conclusions:MNOS mainly affects older children. In the period of acute episodes, convulsions and psychosis are common. The cranial MRI showed extensive brain involvement and mainly in the cortex. The recurrence rates of MNOS are relatively high, patients are sensitive to first-line immunotherapy. No significant neurological dysfunction was left in the remission stage.