Objective:To summarize the clinical manifestations, diagnosis, treatment and prognosis of acute flaccid myelitis (AFM) in children.Methods:Clinical characteristics of 4 AFM cases from Department of Neurology, Children′s Hospital Affiliated to Capital Institute of Pediatrics, from September 2018 to November 2022, were analyzed retrospectively.Results:The age of 4 children with AFM was 7 years, 4 years and 3 months, 7 years and 1 month, 6 years and 5 months, respectively. There were 2 boys and 2 girls. Prodromal infection status showed 3 children of respiratory tract infection and 1 child of digestive tract infection. The main manifestation was asymmetrical limb weakness after infection, and the affected limb range was from monoplegia to quadriplegia. Cranial nerve injury was involved in 1 child, no encephalopathy. Magnetic resonance imaging in the spinal cord of all 4 children showed long T1 and T2 signals, mainly involving gray matter. Cerebrospinal fluid cell-protein separation was observed in 2 children. Pathogen detected in 1 child pharyngeal swab was enterovirus D68. Antibody IgM to adenovirus was positive in the blood of 1 child. Antibody IgG against Echo and Coxsackie B virus were positive in the blood of another child. After glucocorticoid, human immunoglobulin or simple symptomatic treatment and at the same time under later rehabilitation training, muscle strength recovered to different degrees, but there were disabilities left in 3 children.Conclusions:AFM should be considered in children with acute and asymmetrical flaccid paralysis accompanied by abnormal magnetic resonance imaging signal in the central region of spinal cord, especially post-infection. The effective treatment is limited and the prognosis is poor.

More than 85% of patients with uveal melanoma (UM) carry a GNAQ or GNA11 mutation at a hotspot codon (Q209) that encodes G protein α subunit q/11 polypeptides (Gα_q/11). GNAQ/11 relies on palmitoylation for membrane association and signal transduction. Despite the palmitoylation of GNAQ/11 was discovered long before, its implication in UM remains unclear. Here, results of palmitoylation-targeted mutagenesis and chemical interference approaches revealed that the loss of GNAQ/11 palmitoylation substantially affected tumor cell proliferation and survival in UM cells. Palmitoylation inhibition through the mutation of palmitoylation sites suppressed GNAQ/11^Q209L-induced malignant transformation in NIH3T3 cells. Importantly, the palmitoylation-deficient oncogenic GNAQ/11 failed to rescue the cell death initiated by the knock down of endogenous GNAQ/11 oncogenes in UM cells, which are much more dependent on Gα_q/11 signaling for cell survival and proliferation than other melanoma cells without GNAQ/11 mutations. Furthermore, the palmitoylation inhibitor, 2-bromopalmitate, also specifically disrupted Gα_q/11 downstream signaling by interfering with the MAPK pathway and BCL2 survival pathway in GNAQ/11-mutant UM cells and showed a notable synergistic effect when applied in combination with the BCL2 inhibitor, ABT-199, in vitro. The findings validate that GNAQ/11 palmitoylation plays a critical role in UM and may serve as a promising therapeutic target for GNAQ/11-driven UM.
Humans ; Mice ; Animals ; Lipoylation ; NIH 3T3 Cells ; Uveal Neoplasms/genetics* ; Melanoma/genetics* ; Cell Proliferation ; Proto-Oncogene Proteins c-bcl-2 ; GTP-Binding Protein alpha Subunits, Gq-G11/genetics*

Objective To investigate the prevalence of pertussis in infants and children with persistent cough in Beijing during 2011-2016.Methods The eligible infants and children from over ten hospitals who were suspected to have pertussis from 2011 to 2016 were enrolled for detection.Nasopharyngeal secretions and blood samples were collected.Multiplex-PCR was performed for Bordetella pertussis and real-time PCR was performed for nucleic acid of Bordetella pertussis.Results A total of 1 318 eligible cases were enrolled,including 820 males and 498 females.Pertussis was detected positive in 534 cases,including 81.3％ (434/534) of B.pertussis positive cases and 31.8％ (170/534) of IgG positive cases.There were 13.1 ％ (70/534) had double positive for bacteria and antibodies.From 2011 to 2016,the enrolled patients were increased from 103 cases per year to 460 cases per year,and the test positive patients were increased from 29 cases to 194 cases.Among the pertussis patients,466 (87.3 ％) cases were younger than one year old.From the first quarter to the fourth quarter of the year,There were 65 cases,151 cases,205 cases,and 113 cases,respectively.In further analysis of the 268 cases from Children's Hospital affiliated to Capital Institute of Pediatrics,90.7％ of the patients who had whooping cough were scattered children;185 cases (69.0％) of the patients had not begun programmed immunization,71 cases (26.5％) did not complete programmed immunization and 12 cases (4.5％)completed the programmed immunization.Of all the inpatients,21.6％ were critical ill,0.8％ (2 cases) dead,and the remaining patients were recovered and discharged.Conclusions The prevalence of pertussis is increasing,especially in summer.Infants are the most susceptible population.Bordetella pertussis is one of the most important pathogen that can induce persistent and chronic cough.

Objective To study the epidemiological and clinical characteristics ofpertussis in infants younger than three months.Methods Infants younger than three months were enrolled from January 1,2011 to December 31,2015 with one or more of the following symptoms:persistent cough,spasmic cough,cyanosis of unknown causes,asphyxia and apnea.Multiplex polymerase chain reaction(PCR) assay was performed to identify Bordetella pertussis and enzyme-linked immunosorbent assay was used to detect antibody to pertussis toxin.Clinical features,complications,treatments and prognosis of the infants confirmed with pertussis were analyzed.Results Altogether 202 cases were enrolled in the five years,and 59 (29.2％) of which were positive for pertussis confirmed by multiplex PCR.Among the 59 cases,37 were boys and 22 were girls.The youngest baby was 13 days and the oldest one was 85 days.Length of stay ranged from 7 to 21 days.Twelve cases had a contact history with family members having chronic cough.Symptoms occurred in spring or summer in 46 cases (78.0％),and in autumn or winter in 13 (22.0％) cases.Symptoms of spasmic cough,cyanosis after coughing,vomiting after coughing and conjunctival hemorrhage were respectively found in 41 (69.5％),36 (61.0％),39 (66.1％)and 33 (55.9％) cases,while only six (10.2％) presented with inspiratory whooping sound on coughing.Fortynine cases (83.1％) showed increased lymphocyte count (≥ 10 × 109/L).Twenty-eight cases (47.5％) developed severe pertussis.Complications including apnea and bradycardia after coughing,respiratory failure and heart failure,pertussis encephalopathy as well as highly increased leucocyte count (≥ 60× 109/L) occurred in 23 (39.0％),18 (30.5％),five (8.5％) and four (6.8％) cases,respectively.Twenty-four cases with severe pertussis required respiratory support,of which six received invasive ventilation and 18 received non-invasive ventilation.Fifty-eight infants were recovered and discharged,while one baby died.Conclusions Bordetella pertussis infection is an important cause of persistent cough in unimmunized infants under three months of age.The symptoms of pertussis in infants are untypical,but the incidence of severe pertussis is high.Thus early diagnosis and timely treatment are necessary.

Alcohols ; metabolism ; Bioreactors ; microbiology ; History, 20th Century ; Microbiology ; history ; Molasses ; microbiology

Objective To explore the mechanism of severe intermittent hypoxia on oognitive function by evaluatig the effect of chronic intermittent hypoxia on cognitive function,neurons structure,damage,p38MAPK protein expression and neuronal apoptosis in rats hippocampal CA1.Methods Ninety-six mature and male Wistar rats were randomly divided into two groups:control group (UC) and 5％ chronic intermittent hypoxia group (5％CIH).Rats in IH groups were suffered 8 hours intermittent hypoxia everyday,and the duration of experiment was respectively 2,4,6 and 8 weeks.After exposed for 2,4,6,and 8 weeks,the cognitive function of rats was assessed with the Morris water maze (MWM) ; the changes in the morphology of nerve cells in hippocampus CA1 region were observed; the expression of phosphorylated p38MAPK protein in hippocampus was detected by the methods of immunohistochemistry and western blot; the apoptosis of nerve cells was detected by the method of TUNEL.Results Compared with control group,with prolonged hypoxia,the time of escape latency obviously prolonged and the time of across the target quadrant shortened significantly in rats of 5％ CIH group.The time of escape latency at the 8th week was the longest ((71.71 ± 5.49)s,P＜ 0.05) in 5％ CIH group,and the time of across the target quadrant at the 8th week was the shortest ((26.82 ± 4.30) s,P ＜ 0.05) in 5％ CIH group.There appeared neuronal degeneration and necrosis in hippocampus CA1 in 5％ CIH group.Compared with the control group,the density of the nerve cells survival in the region of hippocampal CA1 reduced dramatically at the 2nd,4th,6th and 8th week and was the lowest at the 8th week(14.16 ± 2.07,P ＜ 0.05).By Immunohistochemical method,the expression of phosphorylated p38 MAPK of 5％ CIH group in hippocampal CA1 was more than UC group at the 2nd,4th,6th and 8th week.By western blot,the expression of phosphorylated p38MAPK of 5％ CIH group was more than UC group at the 2nd,4th,6th and 8th week and was the most at the 6th week (2.45 ± 0.14,P＜ 0.05) ;the index of neuronal apoptosis in hippocampal CA1 was increased significantly at the 2nd,4th,6th and 8th week than UC group and reached to the peak at the 6th week (0.608 ± 0.069,P ＜ 0.05) in the 5 ％ CIH group.Conclusion Chronic intermittent hypoxia could cause the activation of p38MAPK/pathway of neuronal apoptosis and was important mechanism of cognitive dysfunction at the early and middle stage.

This study focused on prevention and treatment of acute and chronic asthma by oligonucleotides containing unmethylated CpG motifs (CpG-ODNs). Acute and chronic asthma models of mice were made by sensitizing and inhaling ovalbumin (OVA); The number of white blood cells (WBC) and eosnophils (EOS) in bronchoalveolar lavage fluid (BALF) was counted and the concentration of cytokines and vascular endothelial growth factor (VEGF) was examined in BALF by ELISA kit. After that, TLR-9 mRNA was detected in mice spleen cells by reverse transcription polymerase chain reaction (RT-PCR) and TLR-9 protein was determined in mice lung tissues by Western blotting. Compared with acute asthma models of mice, WBC in BALF decreased obviously in the groups of Bordetella pertussis, CpG-ODNs and seq A to seq I which were administrated by both of intragastric (ig) and intraperitoneal (ip) injection group, EOS decreased obviously in Bordetella pertussis, CpG+ and seq A to seq D ig groups, and in all ip administrating groups, although it was not effective in the groups of seq E to seq I. In chronic asthma models of mice, IFN-gamma increased ((1) control: 176.45 +/- 23.46 pg x mL(-1); (2) model: 174.11 +/- 22.71 pg x mL(-1); (3) CpG+ ip: 220.56 +/- 15.42 pg x mL(-1); (4) seq A ip: 225.23 +/- 21.60 pg x mL(-1)) and IL-4 decreased obviously (1) control: 66.91 +/- 5.81 pg x mL(-1); (2) model: 81.02 +/- 11.24 pg x mL(-1); (3) CpG+ ip: 63.99 +/- 6.09 pg x mL(-1); (4) seq A ip: 62.75 +/- 10.03 pg x mL(-1)) in the BALF of CpG+ and seq A ip group, although VEGF was not changed in this research. And also, TLR-9 mRNA in spleen cells (TLR-9/GAPDH: (1) control: 0.62 +/- 0.13; (2) model: 0.66 +/- 0.17; (3) CpG+ ip: 1.46 +/- 0.26; (4) seq A ip: 1.42 +/- 0.34) and TLR-9 protein in lung tissues (TLR-9/beta-actin: (1) control: 0.63 +/- 0.16; (2) model: 0.61 +/- 0.07; (3) CpG+ ip: 1.15 +/- 0.25; (4) seq A ip: 1.03 +/- 0.29) both increased in ip groups, but the change was not significant in ig group. The study confirms that CpG-ODNs and seq A could inhibit airway inflammation remarkably, this mechanism might be related with regulating Th1/Th2 balance and controlling the expression of TLR-9.

Academies and Institutes ; Biochemistry ; history ; Chemistry ; China ; History, 20th Century ; History, 21st Century ; Humans

Biochemistry ; history ; standards ; China ; Ethics, Research ; history ; History, 20th Century ; History, 21st Century