Objective To clarify the effect of unilateral activation of the dopamine type I receptor medium-sized multi-spiny neurons(D1-MSN)in the dorsal striatum of mice on speed.Methods The transgenic animals were combined with optogenetic experiments to specifically activate the D1-MSN in the dorsal striatum of mice at different frequencies and to analyze the rotational behavior and speed of mice when stimulating the D1-MSN.Results Unilateral activation of D1-MSN induces contralateral rotational behavior in mice and either increases or decreases speed.The mechanisms by which different frequencies affect the speed of mice differently.As the frequency of stimulus increased,the contralateral rotational behavior of the mice increased.Unilateral stimulus of D1-MSN increased speed and induced contralateral rotational behavior,and the rotational behavior increased with increasing stimulus frequency.In the experiment where D1-MSN stimulus did not induce rotational behavior,it was found that 5 Hz stimulus still induced an increase in speed,but 15 Hz and 25 Hz stimulus did not induce an increase in speed.Further analysis of the pre-stimulus locomotor state of the mice showed that 5 Hz,15 Hz and 25 Hz stimulus increased speed when the average speed before stimulus was less than 5 cm/s.However,15 Hz stimulus decreased the speed when the average speed before stimulus was greater than 5 cm/s.Conclusion Unilateral activation of D1-MSN in the dorsal striatum modulates speed and induces contralateral rotational behavior in mice,and is related to the frequency of stimulus and the locomotor state of the mice before stimulus.

Objective To clarify the effect of unilateral activation of the dopamine type I receptor medium-sized multi-spiny neurons(D1-MSN)in the dorsal striatum of mice on speed.Methods The transgenic animals were combined with optogenetic experiments to specifically activate the D1-MSN in the dorsal striatum of mice at different frequencies and to analyze the rotational behavior and speed of mice when stimulating the D1-MSN.Results Unilateral activation of D1-MSN induces contralateral rotational behavior in mice and either increases or decreases speed.The mechanisms by which different frequencies affect the speed of mice differently.As the frequency of stimulus increased,the contralateral rotational behavior of the mice increased.Unilateral stimulus of D1-MSN increased speed and induced contralateral rotational behavior,and the rotational behavior increased with increasing stimulus frequency.In the experiment where D1-MSN stimulus did not induce rotational behavior,it was found that 5 Hz stimulus still induced an increase in speed,but 15 Hz and 25 Hz stimulus did not induce an increase in speed.Further analysis of the pre-stimulus locomotor state of the mice showed that 5 Hz,15 Hz and 25 Hz stimulus increased speed when the average speed before stimulus was less than 5 cm/s.However,15 Hz stimulus decreased the speed when the average speed before stimulus was greater than 5 cm/s.Conclusion Unilateral activation of D1-MSN in the dorsal striatum modulates speed and induces contralateral rotational behavior in mice,and is related to the frequency of stimulus and the locomotor state of the mice before stimulus.

Objective    To summarize the results of surgical treatment for 79 patients with coarctation of the aorta (CoA) combined with complex anomalies (CA) in recent years. Methods    The data from 79 patients with CoA combined with CA admitted to Guangzhou Women and Children's Medical Center between January 19, 2010 and September 7, 2017 were collected and analyzed. There were 52 males and 27 females. The median age was 71 days, and the median weight was 4.3 kg. There were 26 patients combined with tracheostenosis and 7 patients with preoperative tracheal intubation. Extended end-to-side anastomosis was used to correct the CoA, and the associated cardiac abnormalities were treated simultaneously by an incision through median sternotomy. All operations were performed by the same group of surgeons. Results    The median deep hypothermic circulatory arrest was 18 (13-28) minutes, the median aorta cross-clamp time was 62 (15-199) minutes, the median cardiopulmonary bypass time was 145 (71-674) minutes, the median ventilation time was 72 (9-960) hours, the median length of ICU stay was 144 (12-1 944) hours, and the median length of hospital stay was 24 (2-93) days. Early death occurred in 9 patients and late death occurred in 5 patients. Reoperation occurred in 28 patients and recoarctation developed in 10 patients. After operation, transcoarctation gradient was reduced, and the transcutaneous oxygen saturation, C-reactive protein (CRP), lactate and creatinine were increased. Compared to the survival group, both preoperative and postoperative transcutaneous oxygen saturation were worse and the postoperative levels of plasma brain natriuretic peptide (BNP) and CRP were higher in the death group. Conclusion    Correcting the CoA and the associated CA simultaneously with extended end-to-side anastomosis by an incision through median sternotomy is effective and safe, and the outcomes of immediate and medial-term are satisfactory. Improving oxygenation and limiting elevation of BNP and CRP levels may reduce the death rate.

Objective:To explore the clinical characteristics, therapeutic effect and prognosis of movement disorders in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.Methods:The prospectively collected data of hospitalized 163 patients with anti-NMDAR encephalitis admitted to Xuanwu Hospital, Capital Medical University from June 2012 to October 2019 were analyzed. According to the presence of movement disorders, the patients were divided into movement disorders group (75 cases, 46.0%) and non-movement disorders group (88 cases, 54.0%). Patients were followed up for six months and 12 months after immunotherapy. The clinical manifestations, auxiliary examinations, treatment and prognosis of the two groups were compared.Results:Among 163 patients with anti-NMDAR encephalitis, 91 patients (55.8%) were male and 72 patients (44.2%) were female, with an age of 26(19, 34) years. In the 75 patients of the movement disorders group, 50 patients (66.7%) presented with orofacial dyskinesia, 45 patients (60%) with limb stereotypies, 28 patients (37.3%) with choreoathetosis, nine patients (12.0%) with ballism, seven patients (9.3%) with bradykinesia, five patients (6.7%) with tremor, and 13 patients (17.3%) with status dystonicus. Compared with the non-movement disorders group, the movement disorders group had a higher proportion of ovarian teratoma (14.7% vs 3.4%), modified Rankin Scale score of 3-5 before immunotherapy (76.0% vs 33.0%), abnormal electroencephalogram (89.3% vs 77.3%), increased lumbar puncture pressure (53.3% vs 34.1%), cerebrospinal fluid (CSF) pleocytosis (73.3% vs 51.1%), strong positive NMDAR antibody of CSF (44.0% vs 25.0%), admitting to intensive care unit (60.0% vs 9.1%), treated with intravenous immunoglobulin (80.0% vs 40.9%), plasma exchange (36.0% vs 3.4%), and immunosuppressive therapy (37.2% vs 17.0%); had shorter days from the onset to the beginning of immunotherapy [20(10, 33) d vs 35(15, 77) d]; had longer days from the beginning of immunotherapy to the improvement [34(20, 60) d vs 20(15, 35) d]; and there were significant differences of above items between the two groups ( P<0.05). There was no significant difference in the prognosis and relaps between the two groups at six and 12 months after immunotherapy. Conclusions:Nearly a half of patients with anti-NMDAR encephalitis had movement disorders with multiple phenotypes. The severity of movement disorders was related to the severity of the disease. After active immunotherapy and symptomatic treatment, movement disorders improved with the improvement of primary disease in majority of patients.

The TEA domain (TEAD) family proteins (TEAD1‒4) are essential transcription factors that control cell differentiation and organ size in the Hippo pathway. Although the sequences and structures of TEAD family proteins are highly conserved, each TEAD isoform has unique physiological and pathological functions. Therefore, the development and discovery of subtype selective inhibitors for TEAD protein will provide important chemical probes for the TEAD-related function studies in development and diseases. Here, we identified a novel TEAD1/3 covalent inhibitor (DC-TEADin1072) with biochemical IC

Objective:To investigate the blocking effect of non-competitive N-methyl-D-aspartic acid(NMDA) receptor antagonist Memantine on glutamate abnormal signal transmission in immature white matter induced by ischemia in vitro and in vivo. Methods:The oligodendrocyte (OL) precursor oxygen glucose deprivation (OGD) cell models of 2-day-old newborn rats were prepared and divided into the normal control group, the OGD group and the Memantine group.The extracellular glutamate level of the OL precursor was measured by high performance liquid chromatography, while the concentration of intracellular calcium and the apoptosis rate of OL precursor were detected by flow cytometry.The animal models of ischemic periventricular leukomalacia (PVL) were established and divided into the sham group, the PVL group and the Memantine group.The pathological evaluation of white matter was performed under light microscope.The positive OL expression rate of myelin basic protein(MBP) was detected by immunohistoche-mistry.The myelination of white matter was evaluated under electron microscope.Results:Compared with the normal control group in vitro, the OGD group had a higher extracellular glutamate level of the OL precursor [(24.60±2.42) μmol/L vs.(9.49±1.08) μmol/L, t=9.28, P<0.01], a higher intracellular calcium concentration [(32.9±6.9)% vs.(6.9±3.5)%, t=4.41, P<0.01], a higher apoptosis rate of the OL precursor [(24.77±2.05)% vs.(6.65±1.39)%, t=15.01, P<0.01]. After treatment with Memantine, the extracellular glutamate level [(14.70±1.70) μmol/L, t=5.68, P<0.01], the intracellular calcium concentration [(23.1±2.0)%, t=6.13, P<0.01], and the apoptosis rate of the OL precursor [(11.80±2.06)%, t=5.18, P<0.01] decreased significantly.Compared with the sham group in vivo, the white matter of the PVL group showed mild or severe pathological changes, and the PVL group had a lower MBP-positive OL expression rate in the white matter [(5.94±1.37)% vs.(15.40±3.22)%, t=4.63, P<0.01]less myelin sheaths (4.00±1.00 vs.14.67±2.70, t=6.11, P<0.01) and thinner myelin sheaths [(33.83±3.21) nm vs.(79.67±6.45) nm , t=10.43, P<0.01]. After the treatment with Memantine, the number of myelin sheaths (10.30±1.50, t=6.01, P<0.01), the thickness of myelin sheaths [(57.21±4.05) nm, t=7.47, P<0.01], and the pathological changes in the white matter of newborn rats ( Z=88.479, P<0.01) all improved markedly, and the MBP positive OL expression rate in the cerebral white matter [(11.02±1.35)%, t=4.40, P<0.05] also increased significantly. Conclusions:Ischemia-induced abnormal signal transmission of glutamate in immature white matter is the important pathway leading to ischemic PVL.Memantine can effectively block the abnormal signal transmission and thus may probably provide a new approach for the effective prevention and treatment of PVL in premature infants.

Objective:To describe the long-term outcomes of intensive care unit (ICU) survivors of mechanical ventilation, and investigate the views of survivors on ICU rehabilitation clinics.Methods:A single-center cross-sectional descriptive study was designed. ICU survivors of mechanical ventilation admitted to the First Affiliated Hospital of Guangzhou Medical University from January to December 2016 were enrolled. Data were collected from August 2017 to March 2018. The general information questionnaire, Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) and ICU rehabilitation clinics questionnaire were used to evaluate ICU survivors social-demographic factors, social and economic outcomes, clinical data, quality of life and the views on ICU rehabilitation clinics.Results:A total of 248 ICU survivors of mechanical ventilation were included in the study, 130 (52.4%) of them were followed up successfully. The mean time from ICU discharge to follow-up day was (19.64±3.20) months. The average age of the survivors was (60.09±15.42) years old, and 55.4% of them were over 60 years old. Among 130 ICU survivors, severe pneumonia was the dominant ICU admission diagnosis (23.1%), followed by surgical operations (cardiac surgery 16.9%, other surgical operations 20.8%), lung transplantation (13.1%), and acute exacerbation of chronic obstructive pulmonary disease (AECOPD, 12.3%), etc. The first APACHEⅡ score after ICU admission was 16.88±7.37, the mechanical ventilation time was (12.52±12.34) days, and the length of ICU stay was (16.71±15.11) days. In terms of social and economic outcomes, the proportion of having full-time or part-time jobs decreased from 32.3% (42/130) before ICU admission to 25.4% (33/130) by the date of follow-up, while the unemployed rate increased from 6.9% (9/130) to 18.5% (24/130). Only 45.1% (23/51) of the ICU survivors returned to the post before ICU admission. 36.2% (47/130) of the ICU survivors reported that they needed care from others, and 86.9% (113/130) reported that their treatment experiences in ICU had an impact on their lives. In terms of quality of life, physiological function dimension, which was 34.62±33.15, scored the lowest and suffered the most. The physical pain dimension and mental health dimension suffered the least, and the scores were 90.19±16.98 and 75.28±15.15, respectively. Furthermore, physical component summary (PCS) score was 61.12±17.09, and mental component summary (MCS) score was 65.97±21.85. In terms of the views of ICU rehabilitation clinics, 68.5% (89/130) of the subjects believed that the establishment of ICU rehabilitation clinics was very helpful or helpful.Conclusions:The long-term outcomes of ICU survivors of mechanical ventilation are not optimistic. Their quality of life is lower than that of general people. It is necessary to set up ICU rehabilitation clinics.

Objective:To observe the efficacy and safety of vitrectomy combined with submacular injection of tissue-type plasminogen activator (t-PA), gas filling and anti-VEGF drugs (multiple therapy) for thick submacular hemorrhage.Methods:A retrospective case study. From January 2014 to June 2018, 24 patients (24 eyes) with thick submacular hemorrhage who received multiple therapy at the Department of Ophthalmology of Peking University Third Hospital were included in the study. Among them, there were 15 males and 9 females with the average age of 69.05±8.86 years. The average submacular bleeding time was 17.15±10.30 days, the average bleeding area was 13.85±8.63 DD. Seventeen eyes showed hemorrhagic RPE detachment. The international standard visual acuity chart was used to BCVA examination, which was converted to logMAR visual acuity in statistics. The frequency domain OCT was used to measure the height of the foveal elevation. The average logMAR BCVA of the affected eye was 1.37±0.38. The average height of the macular fovea was 824.94±294.38 μm. All eyes underwent 23G or 25G vitrectomy. During the operation, 0.1-0.5 ml t-PA (10 μg/0.1 ml) was injected under the macula. The vitreous cavity was filled with 15% C 3F 8 after gas-liquid exchange in 13 eyes, and 11 eyes were filled with sterilized air. Eleven eyes were injected with anti-VEGF drugs at the end of the operation, and anti-VEGF drugs were given PRN treatment according to the activity of the lesion. The average follow-up time after treatment was 27.90±22.21 months. The absorption of bleeding under the macula, the improvement of vision, the occurrence of rebleeding and treatment-related complications were observed and recorded. The Wilcoxon rank sum test was performed to compare the BCVA and the height of foveal elevation before and after treatment. Results:One month after the treatment, the blood in the fovea of all affected eyes was cleared. At the last follow-up, the logMAR BCVA and macular foveal elevation were 0.82±0.28 and 253.88±71.75 μm, respectively. Compared with those before treatment, the difference was statistically significant ( Z=-3.727, -3.234; P<0.001, <0.001). The average intravitreal injection of anti-VEGF drugs was 1.08 times. During the operation, a tiny hole was formed in the center of the macula when t-PA was injected under the retina. Two eyes showed mild vitreous hemorrhage early after the operation. During the follow-up period, bleeding recurred in 2 eyes. Conclusions:Vitrectomy combined with submacular injection of t-PA, gas filling, and anti-VEGF drugs is an optimal combination for the treatment of thick submacular hemorrhage. It can effectively remove submacular hemorrhage, improve vision, reduce foveal elevation with good safety.

OBJECTIVETo analyze clinical manifestations and genetic mutation in a child with severe short stature and other malformations.

METHODSThe child has undergone history taking and physical examination. Genome DNA was extracted from peripheral blood samples of the proband and her family members. Candidate genes were captured with Agilent SureSelect and sequenced on an Illumina platform. Suspected mutation was verified by Sanger sequencing.

RESULTSThe patient, a six-year-and-10-month old girl, presented with non-symmetrical short stature, dysmorphism, abnormalities of limbs and spine, amblyopia of left eye, and cataract of right eye, in addition with frequent respiratory infection and micturition. Laboratory testing suggested 25-hydroxy vitamin D deficiency (18.9 ng/mL). Spine X-ray showed multiple malformations with centrums. Her mother also featured short stature (138 cm). Her aunt had short stature (130 cm) and limb-length discrepancy. Her little brother was 2.5 years old, and his height was 81 cm (-3.4 SD). Exome sequencing revealed a heterozygous mutation c.184C to T (p.Arg62Trp) in the proband and her mother. The same mutation was not found in her father and brother.

CONCLUSIONThe patient was diagnosed with X-linked chondrodysplasia punctata 2. Mutation of the EBP gene probably underlied the disease in this family.

ObjectiveTo investigate the relationship between the serum concentration of IL-6,S100β,NT-3 and the cognitive functions in first-episode schizophrenia characterized by positive or negative symptoms.Methods44 first-episode schizophrenic patients characterized by positive symptoms (positive group),36 first-episode schizophrenic patients characterized by negative symptoms (negative group) and 50 healthy controls (controls) were collected.The serum levels of IL-6,S100β and NT-3 were measured by enzyme-linked immunosorbent assay (ELISA).The systematic evaluation tool-MCCB was applied to assess cognitive function in patients and controls.ResultsNT-3 serum levels in positive or negative groups were lower than those in controls and the differences were significant((118.39±37.50) ng/L,(112.55±32.29) ng/L vs (141.18±29.67) ng/L) (P<0.01).IL-6 and S100β serum levels in positive or negative groups were higher than those in controls and the differences were statistically significant((5.74±1.00)ng/L,(5.07±1.17)ng/L vs (4.23±0.91)ng/L),((132.98±46.71)ng/L,(124.99±43.14)ng/L vs (103.63±31.57)ng/L)(P<0.01).IL-6 serum levels in the positive group ((5.07±1.17)ng/L) were lower than those in the negative group ((5.74±0.99)ng/L) and the difference was statistically significant (P<0.05).In MCCB test,the TMT scores in patients characterize by positive symptoms or patients characterize by negative symptoms were higher than those in healthy control group (P<0.01).BACS SC,HVLT-R WMS-Ⅲ,SS,NAB,BVMT-R,CF in patients characterize by positive symptoms or by negative symptoms were lower than those in healthy control group(P<0.01).There were no statistical difference in the MCCB scores between the patients with positive symptoms and negative symptoms.In positive group,there was a positive correlation between the IL-6 serum concentration and the general symptom scores in PANSS (P<0.05).In positive group,NT-3 serum concentration was positively correlated with the general symptom scores or total scores of PANSS (P<0.05).BVMT-R scores in MCCB were also positively correlated with IL-6 or NT-3 serum concentration in positive group (P<0.05).ConclusionThe impairment of part of cognitive functions for schizophrenic patients may be related to the serum protein factors.There may be different in pathophysiology between the first-episode schizophrenic patients characterized by positive symptoms and those characterized by negative symptoms.