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Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABAA receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.
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Animals , Humans , Mice , Disease Models, Animal , Fragile X Mental Retardation Protein/metabolism , Fragile X Syndrome/metabolism , Mice, Knockout , Neurons/metabolismABSTRACT
Objective:To study the clinical features of children with pertussis and the risk factors of severe pertussis.Methods:A retrospective analysis was performed based on clinical data and laboratory examination results of hospitalized children with pertussis who admitted to the intensive care unit, respiratory department, and emergency general department at Hunan Children′s Hospital from January 2019 to March 2020.According to the age, the patients were divided into age ≤3 months group( n=58)and age >3 months group( n=64). According to sputum culture, 63 cases were divided into negative sputum culture group and 59 cases were positive sputum culture group.The patients were also divided into vaccinated group( n=19)and unvaccinated group( n=103). Severe disease was seen in 28 cases, and the other 94 cases had the modest disease.The clinical characteristics between two groups were compared, and the risk factors of severe pertussis pneumonia were analyzed. Results:The hospitalization days in age ≤3 months group was higher than that in age >3 months group.It was also found that shortness of breath, apnea, cyanosis after coughing, heart rate decline were more common in age ≤3 months group than those in age >3 months group( P<0.05). The incidences of respiratory failure and heart failure in positive sputum culture group were higher than those in negative sputum culture group.Clinical characteristics such as hospitalization days, hospitalization expenses, peak white blood cell count, peak lymphocyte count, and incidence of bacterial infection were higher in severe pertussis group than those in non-severe pertussis group( P<0.05). Four patients were treated with exchange blood transfusion, and one patient died.Logistic regression analysis revealed that fever, wheezing, cyanosis after coughing and white blood cell count>20×10 9/L were risk factors for severe pertussis.White blood cell count of 20×10 9/L and lymphocyte count of 14×10 9/L had the highest sensitivity and specificity in predicting severe pertussis(0.71, 0.78; 0.54, 0.79). Conclusion:The younger the children are, the more likely they have shortness of breath, apnea, cyanosis, heart rate falls, and the longer the hospital stay.Bacterial infection will aggravate pertussis.Patients with fever, wheezing, cyanosis after coughing, and white blood cell count>20×10 9/L are more likely to develop severe pertussis.The white blood cell count >20×10 9/L and the lymphocyte count >14×10 9/L are associated with severe pertussis.
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Objective:To summary the mixed infection as well as clinical characteristics and analyze the risk factors for mixed infection of severe adenovirus pneumonia(SAP) in children.Methods:The clinical data of 114 children with SAP were retrospectively analyzed.Multivariate Logistic regression analysis was performed to assess the risk factors for mixed infection.Results:The incidence age was from 6 months to 2 years(62.5%). High fever(94.7%), cough(98.2%), dyspnea(86.8%) and lethargy(95.6%) were the main symptoms.Laboratory examination showed that children with SAP were prone to increased white blood cell count, C-reactive protein, procalcitonin, aspartate aminotransferase, alanine aminotransferase and CK-MB, as well as decreased proportion of CD3 + , CD4 + , CD8 + , CD4 + /CD8 + and NK cells.The main complications intrapulmonary organ were respiratory failure(80.7%). The main complications extrapulmonary organ were circulatory complications (55.3%). SAP was easily combined with other pathogenic infections.Streptococcus pneumoniae(22.9%)was the most common bacterial pathogen.Respiratory syncytial virus(10.0%)were the most common virus, in addition, mycoplasma pneumoniae(17.1%) was also common.Multivariable Logistic regression analysis showed that the decreasing ratio of CD4 + /CD8 + and NK cells, congenital heart disease and congenital airway dysplasia were the independent risk factors for mixed infection of SAP in children( P<0.05). Conclusion:The SAP patients could easily suffer from mixed infection and high fatality rate.Immune dysregulation is the important risk factors for mixed infection of SAP in children.So immunoregulatory treatment is very important.
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Objective:To retrospectively analyze the clinical application of extracorporeal membrane oxygenation (ECMO) in severe adenovirus pneumonia, and to evaluate the application value of ECMO in children with severe adenovirus pneumonia.Methods:Children diagnosed with severe adenovirus pneumonia and intervened with ECMO in the Hunan Children′s Hospital from January 1, 2018 to December 31, 2019 were recruited in this study for analyzing.The gender, age, clinical manifestations, mechanical ventilation duration, ECMO duration, the length of hospital stay, complications and prognosis were collected and analyzed.Results:A total of 4 children were included in the study, involving 2 cases were successfully evacuated from ECMO.Finally, 3 children died, and 1 case survived.Three death cases had a longer than 18 days of duration from the onset to the start with ECMO.Their ventilator assist time before star-ting ECMO was 3-5 days, and ECMO intervention time was longer, with the maximum of 27.5 days.The survived case had an 11-day duration from the onset to the start with ECMO, and the ventilator assisted time and ECMO intervention time were 5 days, and less than 10 days, respectively.Conclusions:ECMO treatment for children with severe adenovirus pneumonia has a low success rate, but it is still the most important way to save children.Early application of ECMO can improve the prognosis of children with severe adenovirus pneumonia.
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In recent years, the number of patients who have lost their mobility due to neurological diseases such as stroke and spinal cord injury has been increasing. Guidelines state that early and scientific rehabilitation training is essential to improve prognosis and quality of life. However, existing rehabilitation methods rely on therapists to train one-on-one or many-to-one, which is not sufficient to meet clinical needs. As a new technology, the exoskeleton robot provides a unique rehabilitation program for patients with lower limb movement disorders, which has become a hot research topic at home and abroad, and related clinical research is also being carried out rapidly. This review summarizes the clinical research progress of exoskeleton robots in patients with lower limb movement disorders caused by nervous system damage in the past ten years, and the prospect of research, development, and clinical promotion about exoskeleton robots.
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Objective:To investigate the relationships between different doses of vancomycin with blood drug trough concentration and renal dysfunction in children with severe infection in intensive care unit (ICU).Methods:100 children with severe infection treated with vancomycin from January 2018 to November 2018 in the Ⅱ Department of Critical Care Medicine of Hunan Children's Hospital were studied, according to the dosage, they were divided into high-dose group [15 mg/(kg·time), 57 cases] and low-dose group [15 mg/(kg·time), 43 cases]. At the same time, according to the condition of renal dysfunction, children were divided into normal renal function group (42 cases), mild injury group (43 cases), moderate injury group (15 cases). The blood drug trough concentration was measured, and its relationship with serum creatinine (Scr), serum urea nitrogen (BUN), and renal dysfunction was analyzed. At the same time, the therapeutic effects of different doses of vancomycin were evaluated.Results:The cure rate and blood drug trough concentration of children with severe infection in high-dose group were significantly higher than those in low-dose group ( P<0.05), and the time to reach effective blood drug trough concentration was significantly shorter than that in low-dose group ( P<0.05); the levels of serum Scr and BUN in low-dose group and high-dose group were significantly lower than those before treatment ( P< 0.05); the blood drug trough concentration and the proportion of reaching the target trough concentration in mild injury group were significantly higher than those in normal group and moderate injury group ( P<0.05); the dose of vancomycin in mild injury group and moderate injury group was significantly higher than that in normal group ( P<0.05), and the course of treatment in mild injury group and moderate injury group was lower than that in normal group ( P<0.05). Conclusions:The high dose of vancomycin 15 mg/(kg/time) is effective in the treatment of ICU children with severe infection. the blood drug trough concentration and renal dysfunction should be monitored and individualized treatment plan should be formulated.
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Objective To compare the clinical efficacy of different blood purification methods in children with acute liver failure,and to explore the clinical application mode,time and prognosis of blood pur-ification in children with acute liver failure. Methods The clinical data of 85 children with acute liver failure admitted to PICU of Hunan Children′s Hospital from January 2010 to October 2016 were retrospectively ana-lyzed. Sixteen patients were treated with general integrated medical treatment(conservative group). Twenty-seven patients were treated with continuous venovenous hemodiafiltration ( CVVHDF) model non-biological artificial liver on the basis of general integrated medical treatment(CBP group). Sixteen cases were treated with plasma exchange ( PE group). Twenty-six cases were treated with plasma exchange combined with CVVHDF mode (combination group). The main biochemical indexes,coagulation function,model for end-stage liver disease(MELD) score and delta MELD before and after treatment among groups were compared. Results Compared with those before treatment,the improvement of liver function and prognosis in the con- servative was not significant after treatment. There were significant differences in the improvement of liver function and prognosis among the other three groups treated with non-biological artificial liver. Comparing the biochemical indexes and prognosis of three groups of children treated with different modes of non-biological artificial liver,there was no significant difference in the total effective rate between PE group and CBP group [56. 3% (9/16) vs 55. 6% (15/27),P>0. 05]. The total effective rate of combined group[84. 6% (22/26)] was significantly higher than those of PE group and CBP group. There was no significant difference in the improvement of liver function between PE group and CBP group (all P>0. 05),but the indexes of liver function in combined group were significantly lower than those in PE group and CBP group ( P<0. 05). It significantly increased prothrombin activity,albumin and alpha-fetoprotein levels(all P<0. 05). At the same time,procalcitonin, sequential organ failure assessment scores, pediatric end-stage liver disease scores and MELD scores in the death group were significantly higher than those in the survival group,and there were significant differences between the two groups. However,the effect of non-biological artificial liver was not good in the subgroups of MELD<25 and MELD>40. Conclusion PE and CBP have a good effect on chil-dren with acute liver failure,and if combined with the two methods can improve the therapeutic effect. At the same time,MELD score should be monitored in children with acute liver failure,and non-biological artificial liver therapy should not be recommended for children with MELD<25 and MELD>40.
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Objective To investigate the clinical efficacy and safety of continuous blood purification (CBP) in the treatment of severe sepsis in infants. Methods A retrospective analysis of 40 infants with severe sepsis treated with CBP was performed at PICU of Hunan Children's Hospital from January 2014 to July 2017,and 50 infants with severe sepsis who were not treated with CBP at the same period were enrolled as control group. The indicators included blood gas analysis,lactic acid (Lac),blood glucose,electrolytes, blood routine,C-reaction protein ( CRP) and procalcitonin ( PCT),alanine aminotransferase ( ALT) and aspartate aminotransferase (AST),total bilirubin(TB),urea nitrogen (BUN),serum creatinine (Scr) and creatine kinase isoenzyme MB (CK-MB),pediatric critical illness score (PCIS). Results (1) After 3 days of treatment,the recovery of body temperature,heart rate,respiratory rate and blood pressure in CBP group were better than those in the control group,and the differences between two groups were statistically signifi-cant(P < 0. 05). (2) After treatment,the levels of base excess(BE),Lac,white blood cell (WBC),PCT, CRP,ALT,AST,TB and BUN of CBP group recovered better than those of the control group,the differences were statistically significant (P < 0. 05). (3) The ΔPCIS (D3-D1) of CBP group was higher than that of the control group,and the difference between two groups was statistically significant (P < 0. 05). (4) The fatali-ty rate of CBP group was lower than that of the control group,and there was no significant difference between two groups (P > 0. 05). (5) Two cases of thrombocytopenia,2 cases of femoral vein thrombosis,2 cases of hypovolemic shock,and 1 case of blood coagulation in filter happened in CBP gruop,all cases had no punc-ture site infection. Conclusion CBP can improve the vital signs,internal environment,inflammatory reaction and organ function of infants with severe sepsis,and the effect is better than that of traditional methods. The complications of CBP in infants with severe sepsis are relatively large,so we should strictly master the indica-tions of CBP in the treatment of severe sepsis in children.
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Objective To explore the association between the cholesterol level and disease relapse in patients with Neuromyelitis Optica Spectrum Disorders (NMOSD). Methods Clinical and biochemical data of 96 patients with NMOSD were retrospectively analyzed. According to disease relapses, NMOSD patients were divided into primary and relapse groups.Their clinical characteristics and cholesterol level were compared between the two groups.The correlation between cholesterol level and disease recurrence was analyzed by partial correlation adjusted for sex. Results Between the primary group and relapse group,there were statistically significant differences in gender(48.8% vs. 80%, P<0.05), cholesterol (CHO)(4.27±0.85 vs. 5.18±1.26)and low density lipoprotein cholesterol (LDL-C)level[2.37(0.90)vs. 3.00 (1.21)](P<0.001). There were no significant difference in age, upper respiratory infection, gastrointestinal tract, rate of higher cerebrospinal fluid protein, triglyceride (TG)and high density lipoprotein cholesterol(HDL-C)(P>0.05). The percentage of recurrent patients in CHO normal and higher groups were 43.55% and 82.35% respectively, which was statistically significant difference between the two groups ( x2=13.51, P<0.01); The rate of relapse of LDL-C normal and higher groups were 47.69% and 75% respectively, which was statistically significant difference between the two groups ( x2=7.58,P<0.01).After adjusting for sex,CHO level was positively correlated with disease relapse(r=0.346,P<0.01),and LDL-C level also was positively correlated with disease relapse(r=0.380,P<0.01). Conclusion High CHO and LDL-C level may be associated with disease relapse, which has some clinical guiding significance for controlling CHO level in NMOSD patients.
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Objective·To eliminate the effects of intraperitoneal injection of transmembrane activator and calcium modulator and cyclophilin ligand interactor-Ig (TACI-Ig) on the opitc neuritis and the integrity of myelin sheath in mice.Methods·Twenty-four C57BL/6J mice were randomly divided into 4 groups,which were blank control group,saline control group,low-dose (0.4 mg/kg) TACI-Ig group and high-dose (4 mg/kg) TACI-Ig group,with 6 mice in each group.All groups were received intraperitoneal injection every other day.The saline control group received 0.2 mL saline injection in the same way,and the blank control group was not given any intervention.After 20 d of treatment,the eyeballs and optic nerve tissues were collected from each mouse under anaesthesia,embedded in paraffin and stained with hematoxylin-eosin (H-E) and Luxol fast blue (LFB),respectively.Results·H-E staining indicated that optic nerve fibers arranged closely both in blank and saline control groups and the staining of tissues was uniform.The optic nerve structure of low-dose TACI-Ig group was similar to blank and saline control groups,while in high-dose of TACI-Ig group,the infiltration of inflammatory cells was observed.The inflammatory cell infiltration scores were not significantly different in all groups (P=0.610 3).The retinal structures of all groups were clear and distinct to observe,and single ganglion cells arranged tightly with complete cell shape,visible nucleus and uniform distribution.There was no difference in the retina structure among 4 groups.LFB staining indicated that there was no significant loss of the optic nerve myelin in 4 groups by microscope observation (P=0.473 6).Conclusion·Low-dose (0.4 mg/kg) TACI-Ig injection wouldn't damage the normal structure of optic nerves and retinal ganglion cells,meanwhile high-dose (4 mg/kg) of TACI-Ig injection might cause minor infiltration of inflammatory cells into retina.
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Objectives To explore the correlation between the cerebrospinal fluid protein and facial paralysis in pa?tients with Guillain-Barre syndrome (GBS). Methods Clinical and biochemical data of 111 patients with GBS in depart?ment of neurology from January 2005 to September 2015 were retrospectively analyzed. According to facial paralysis, GBS patients were divided into the facial normal and paralysis groups. Their clinical and biochemical characteristics were compared between the two groups. According to level of cerebrospinal fluid protein, GBS patients were divided into cerebrospinal fluid protein normal, mild high and severe high groups. Incidences of facial paralysis were compared among these three groups. The correlation between the cerebrospinal fluid protein and facial paralysis was analyzed. Results There was no significant difference in gender, age, respiratory infection and other clinical symptoms (P>0.05), whereas there were statistically significant differences in cerebrospinal fluid protein, immunoglobulin G, and cerebrospinal fluid albumin/serum albumin ratio between the facial normal and paralysis groups (P<0.05). Among the three groups by differ?ent levels of cerebrospinal fluid protein, there were statistically significant differences in the incidence of facial paralysis (F=3.48,P=0.03). Cerebrospinal fluid protein was positively correlated with facial paralysis (r=0.288,P<0.01). Conclu? sions The incidence of facial paralysis is associated with the levels of cerebrospinal fluid protein. Thus, cerebrospinal flu?id protein may be helpful in monitoring of GBS patients with facial paralysis.
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siRNA drug research and development is becoming one of the main objectives in the future. However, due to the in-stability of siRNA and the complex environment in vivo, the safe and effective delivery of siRNA is limited in vivo. Thus, special vectors are used to assist siRNA to express biological effects. This paper reviews the advances in non-viral vector for delivery of siRNA in vivo.
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Objective The aim of this study is production of organ specific animal model for studying reproductive toxicity in mice.Methods F1 generation was gotten by mating the Ddx4 -cre transgenic male mice with the Rosa26mT/mG transgenic female mice.F1 offspring and its parents phenotype was screened by molecular biological, histopathological and in vivo imaging technology.Results At molecular level, specific DNA fragment was only found in testis of F1 offspring; At the organ level, the expression of green fluorescent protein could only be observed in testis of F1 offspring; Testicular frozen sections and sperm fluorescence observation showed that green fluorescent protein were mainly expressed in the germ cell lineage such as secondary spermatocyte and spermatocyte and spermatozoon.Conclusions The production of the mice with specific germ cell expressed green fluorescent protein by Cre/loxP recombination system were built successfully.
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Objective To observe the change of lipid metabolism during adaptive heart failure.Method The transverse aorta constriction mouse models established by minimal invasive surgery technique were evaluated for early small changes of body composition by EchoMRITM whole body composition analysis,and the different gene expression was analyzed by whole genome expression microarray.Results Three weeks after the surgery,the fat composition,in the mouse models were (0.49 ± 0.13) g,which was significantly lower than that in the sham surgery group [(0.81-±0.14) g] (P =0.002).The expression of the natriuretic peptide type A significantly increased over time (R2 =0.939,P =0.005).In addition,the levels of fatty acid desaturase,long-chain fatty acid elongase 5,and N-acylsphingosine amidohydrolase increased,and the levels of acyl-coenzyme A dehydrogenase,muscle glycogen phosphorylase,and pyruvate dehydrogenase kinase decreased,showing increased fat mobilization and decreased carbohydrate utilization.Conclusions Surgery for transverse aorta constriction can cause complex metablic changes in heart.The activated lipid mobilization maybe lead to the low body fat composition.
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Objective To discuss the signiifcance of serum albumin level in assessing severity, progress and prognosis of sepsis in children. Methods The clinical data of 212 patients diagnosed with sepsis admitted to PICU from February 2010 to July 2010 were retrospectively analyzed, and 52 patients had severe sepsis and 31 patients had septic shock. Meanwhile, 110 non-sepsis patients were selected as controls. The relationships of hypoalbuminemia with pediatric critical illness score (PCIS), pediatric risk of mortality III (PRISM III) and prognosis were evaluated, and the change of albumin level in patients with dif-ferent severity of sepsis was observed. Relative factors analysis of albumin level ≤25 g/L was performed. Results As the serum albumin level was decreased, the PCIS was signiifcantly decreased while the PRISM III was increased (P<0.01). The se-rum albumin level was signiifcantly different among children with septic shock, severe sepsis and sepsis and controls (F=13.938, P=0.000). The results of relative factors analysis showed that sepsis children with an albumin level≤25 g/L had more organ failures, higher mortality, longer hospital and PICU stay and more likelihood for ventilator support (P<0.01). Lower albumin levels were accompanied with lower rates of recovery and improvement but higher mortality (rs=-0.161, P=0.000). Conclusions Hypoalbuminemia can be used as indirect indicator for severity of infection. The albumin level≤25 g/L indicated the severity of illness and prognosis in children with sepsis.
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Objective To discuss the clinical value of procalcitonin (PCT) in guiding antibiotics use in children with severe diseases. Methods The clinical data of patients admitted to intensive care unit from January 2012 to July 2012 were retrospectively analyzed. The patients without antibiotics use before admission and with procalcitonin level less than 0.5 ng/ml on admission were selected. The body temperature, infection indicators and prognosis were compared between patients with and without antibiotics use during hospitalization. Results There was no difference in body temperature, PCT, C-reactive pro-tein (CRP), erythrocyte sedimentation rate (ESR) and white blood cell count (WBC) on admission between patients with and without antibiotics use during hospitalization. The PCT level was increased signiifcantly (P<0.05) on the day of starting the an-tibiotics when compared with that on admission in 60 patients while there was no change in the levels of WBC and CRP. Com-pared with the day of starting the antibiotics, body temperature declined (P<0.05) and PCT level in 56 patients reexamined was decreased (P<0.05) at 3 days after antibiotics use. Two hundred and eleven patients (98.14%) had favorable prognosis. Conclu-sions Monitoring PCT can guiding the clinical use of antibiotics.
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Objective To confirm that rat bone marrow mesenchymal stem cells (MSC) transfected with nerve growth factor (NGF) gene in the bladder tissue of diabetic rats bladder tissues can survive and stably express NGF. Methods A diabetic rat model was constructed. The BrdU-labelled MSC transfected with NGF gene were transplanted into the diabetic rats bladder tissues. BrdUlabelled immunohistochemistry was used to observe the growth of MSC transfected with NGF gene in the diabetic rats bladder tissues. The expression of NGF mRNA and protein were checked by RT-PCR and ELISA. Results A diabetic rat model was successfully built by a single intraperitoneal injectionof STZ. The blood glucose was still high after 8 weeks. NGF gene modified MSC could be detected in the bladder of diabetic rats by BrdU-labelled immunohistochemistry. The concentration of NGF in the control group, disease group and treatment group were ( 114 ± 3), ( 70 ± 2), ( 110 ± 2) pg/ml by ELISA and mRNA quantity by RT-PCR were 0. 183±0. 004, 0. 032±0. 139, 0. 130±0. 165, respectively. Compared with the control group, the expression of NGF gene was decreased (P＜0. 05) in the incidence group. The expression of NGF gene was increased (P＜0. 05) in the treatment group compared with the disease group. Conclusions The NGF gene-modified MSC could survive in diabetic rats bladder tissues. The NGF gene in MSC could stably express in diabetic rats bladder tissues.