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 (Fmr1^KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1^KO 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 GABA_A 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 Fmr1^KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.
Animals ; Disease Models, Animal ; Fragile X Mental Retardation Protein/metabolism* ; Fragile X Syndrome/metabolism* ; Humans ; Mice ; Mice, Knockout ; Neurons/metabolism*

Objective:To analyze the clinical characteristics of children with Kawasaki disease complicated by hypoproteinemia.Methods:The clinical data of 105 children patients with Kawasaki disease who received treatment in Ji'an Central People's Hospital, China between January 2015 and December 2019 were retrospectively analyzed. These patients were divided into normal-level albumin (ALB) group (≥ 35 g/L, n = 54) and low-level ALB group (< 35 g/L, n = 51). White blood cell count, hemoglobin, C-reactive protein, erythrocyte sedimentation rate, alanine aminotransferase, aspartate aminotransferase, total bile acid, and coronary artery B-ultrasound examination results were compared between the two groups. Results:The incidence of hypoproteinemia was similar among all age groups. There was significant difference in coronary artery dilatation rate between the two groups (χ 2 = 5.49, P < 0.05). There were no significant differences in the percentage of patients with hand and foot scleredema and urinary protein-positive rate between the two groups (χ 2 = 0.40, 0.39, both P > 0.05). White blood cell count, erythrocyte sedimentation rate, C-reactive protein level in the low-level ALB group were 15.2 × 10 9/L, (82.1 ± 26.1) mm/h, 94.7 mg/L, respectively, which were significantly higher than those in the normal-level ALB group [11.5 × 10 9/L, (54.5 ± 26.2) mm/h, 43.65 mg/L, Z = -2.94, t = 5.40, Z = -6.01, all P < 0.01]. There were no significant differences in alanine aminotransferase, aspartate aminotransferase, and total bile acid levels between the two groups (all P > 0.05). Conclusion:The incidence of Kawasaki disease complicated by hypoproteinemia is unrelated to age and it is related to inflammatory reaction. Hypoproteinemia is a risk factor of coronary artery dilatation. This study is of great science.

Bone regeneration remains a great clinical challenge. Low intensity near-infrared (NIR) light showed strong potential to promote tissue regeneration, offering a promising strategy for bone defect regeneration. However, the effect and underlying mechanism of NIR on bone regeneration remain unclear. We demonstrated that bone regeneration in the rat skull defect model was significantly accelerated with low-intensity NIR stimulation. In vitro studies showed that NIR stimulation could promote the osteoblast differentiation in bone mesenchymal stem cells (BMSCs) and MC3T3-E1 cells, which was associated with increased ubiquitination of the core circadian clock protein Cryptochrome 1 (CRY1) in the nucleus. We found that the reduction of CRY1 induced by NIR light activated the bone morphogenetic protein (BMP) signaling pathways, promoting SMAD1/5/9 phosphorylation and increasing the expression levels of Runx2 and Osterix. NIR light treatment may act through sodium voltage-gated channel Scn4a, which may be a potential responder of NIR light to accelerate bone regeneration. Together, these findings suggest that low-intensity NIR light may promote in situ bone regeneration in a CRY1-dependent manner, providing a novel, efficient and non-invasive strategy to promote bone regeneration for clinical bone defects.
Animals ; Rats ; Bone Morphogenetic Protein 2/metabolism* ; Bone Regeneration ; Cell Differentiation ; Circadian Clocks ; Cryptochromes/metabolism* ; Osteoblasts/metabolism* ; Osteogenesis ; Transcription Factors/metabolism*

Plexiform fibromyxoma (PF) of the stomach is a very rare mesenchymal tumor of the gastrointestinal tract. We report the first case of PF with 2 different growth patterns pathologically confirmed after surgical resection. The tumor was characterized microscopically as infiltrative; it demonstrated diffuse growth into the smooth muscle bundles of the muscularis propria and was also multinodular and plexiform within the myxoid stroma.Immunohistochemical analysis revealed that the tumor cells were positive or weakly positive for smooth muscle actin, vimentin, and H-caldesmon and negative for desmin, CD117, CD34, CK-20, Pan-CK, Dog1, S100, ER, PR, and CD10. No mutations of C-kit and platelet-derived growth factor receptor alpha were detected. No genetic disruption of glioma-associated oncogene homolog 1 was detected by fluorescence in situ hybridization. The final diagnosis of PF was mainly based on the morphological and immunohistochemical findings.

OBJECTIVE: To explore the genotype-phenotype correlation of Cardio-facio-cutaneous syndrome (CFCS) caused by MAP2K1 gene variants. METHODS: Genomic DNA was extracted from peripheral blood sample from a child patient and his parents. Whole exome sequencing (WES) was carried out for the patient. Suspected variant was verified by Sanger sequencing. RESULTS: The patient was a 1-year-8-month old Chinese male who manifested short stature, psychomotor retardation, relative macrocephaly, distinctive facial features, and congenital heart disease. WES test revealed a heterozygous missense c.389A>G (p.Tyr130Cys) variant in the MAP2K1 gene. Sanger sequencing has confirmed the variant as de novo. According to ACMG/AMP guidelines, the variant was classified as pathogenic. CONCLUSION Compared with previously reported CFCS cases due to MAP2K1 variants. The patient showed obvious behavioral problems, good appetite and tricuspid regurgitation, which may to be novel features for CFCS.
China ; Ectodermal Dysplasia ; genetics ; Facies ; Failure to Thrive ; genetics ; Genetic Association Studies ; Genetic Variation ; Heart Defects, Congenital ; genetics ; Heterozygote ; Humans ; Infant ; MAP Kinase Kinase 1 ; genetics ; Male ; Mutation ; Whole Exome Sequencing

Objective: To screen, diagnose and follow up the abnormal mutation in the gene screening of neonatal deafness. Methods: A total of 24161 newborns born in Zhuhai Maternal and Child Health Hospital from February 1, 2015 to January 31, 2008 were screened for hearing and deafness genes, and audiological screening, diagnosis and 1-3 years follow-up were carried out for the newborns with positive gene screening. Results: There were 991 cases of deafness gene mutation (533 males and 458 females), and the rate of abnormal mutation was 4.10%(991/24 161). Among them, 921 cases were single heterozygous mutation, 130 cases were failed in primary hearing screening, 11 cases were failed in secondary hearing screening, 8 cases were abnormal in audiological diagnosis finally. In these 8 cases, 3 were diagnosed as otitis media and passed audiological follow-up after cure, 2 cases of single ear sensorineural injury caused by high-risk factors, passed after close audiological follow-up, and the other 3 cases were closely audiological follow-up while none of them were successfully sequenced. All of them were moderate to severe sensorineural deafness, 1 case was heterozygous mutation at 3 loci of GJB2(c.235delC,c.408C>A,c.134G>A), 1 case was heterozygous mutation at 2 loci of GJB2(c.235delC, c.109G>A), and 1 case was single heterozygous mutation of GJB2(c.235delC). The remaining 913 cases who passed the primary screening, secondary screening or hearing diagnosis were followed up for 1 to 3 years. Three cases of multiple heterozygous mutation were found in gene screening(2 cases were SLC26A4 2168A>G, IVS7-2A>G, 1 case was GJB2 c.176_191del 16bp, c.299_300del AT), all of them passed both primary and secondary hearing screening. In these 3 cases, the final audiological diagnosis was moderate sensorineural deafness in both ears, with no improvement in the follow-up of 1-3 years. There were 9 monogenic homozygous mutations, 7 failed in primary hearing screening, 3 failed in secondary hearing screening and also failed in audiological diagnosis and 1-3 years′ audiological follow-up, all of whom were GJB2 c.235 del C homozygous mutations, and one of whom had a definite family history of deafness. The remaining 6 cases of homozygous mutation diagnosed by primary screening, secondary screening or hearing diagnosis were GJB2 c109G>A homozygous mutation, and passed the 1-3 years′ hearing follow-up. 58 children with mtDNA mutations, including 2 with 12S rRNA 1494C>T homozygous mutation, 47 with 1555A>G homozygous mutation, and 9 with 1555A>G heterozygous mutation, all passed the primary or secondary hearing screening, and were instructed to ban ototoxic drugs for the whole life, and passed the 1-3 years′ hearing follow-up. Conclusions The audiological follow-up of children with monogenic heterozygous mutations in deafness gene screening is generally normal. In case of abnormality, the influencing factors such as otitis media should be excluded at first. In case of unexplained moderate to severe sensorineural deafness, the whole-gene sequencing should be performed to find possible pathogenic factors. The children with homozygous mutation or compound heterozygous mutation in gene screening, most of whom show different degrees of hearing loss, should be followed up for a long time, and provide parents with scientific and reasonable genetic counseling according to the mutation genes and loci,. The hearing of drug-induced deafness gene carriers is normal after birth. Parents should be advised to strengthen prevention and follow-up is generally enough.

Objective: To systematically evaluate the effects of hyperbaric oxygen on the hemodynamics and intracranial pressure of patients with severe craniocerebral injury (STBI). Methods: Reports of randomized and controlled trials applying hyperbaric oxygen in the treatment of STBI were retrieved from the Pubmed, Cochrane Library, Embase, CBM, CNKI, VIP and Wan Fang databases. Each report found was evaluated by two researchers independently applying pre-defined inclusion and exclusion criteria. The data were extracted and combined and a meta-analysis was performed. Results: Eight trials involving 725 patients were included in the meta-analysis. They combined to demonstrate that intracranial pressure, oxygen uptake and scores on the Glasgow coma scale improved significantly more in the hyperbaric oxygen group than in the control group after between 3 and 10 days of treatment. Conclusion Hyperbaric oxygen therapy is effective in treating severe craniocerebral injury and it is worthy of clinical application.

Objective To observe the effect of hyperbaric oxygen (HBO) therapy on neurological functioning in rats modelling cerebral hemorrhage (ICH).Methods Sixty Sprague-Dawley rats had intracerebral hemorrhage induced by injecting autologous blood.They were then randomly divided into an HBO-free group and an HBO group,each of 30 according to a random number table.The HBO group was further divided into HBO 3 h,HBO 6 h,HBO 1 d,HBO 2 d and HBO 7 d groups which received HBO therapy for 3 hours,6 hours,1 day,2 days and 7 days respectively.Each had 6 members.The HBO-free rats were also divided into analogous HBO-free 3 h,HBO-free 6 h,HBO-free 1 d,HBO-free 2 d and HBO-free 7 d groups,and give no HBO intervention.All of the rats were evaluated for neurological impairment using the Longa scoring method before the treatment and 10 days,20 days and 30 days afterward.Results After 10,20 and 30 days of HBO treatment,there were significant differences in neurological functioning between each pair of HBO-free and HBO-treated groups.After 10 and 20 days of HBO treatment the average neurological function score of the HBO 3 h group was significantly different from that of the HBO 2 d group.The average score in the HBO 7 d group was also significantly different from that of the HBO 3 h,HBO 6 h,HBO 1 d and HBO 2 d groups after 10,20 and 30 days of HBO treatment.The average scores of the HBO 3 h,HBO 6 h,HBO 1 d and HBO 2 d groups improved significantly between 10 and 20 days after the treatment.The average score of the rats which received 30 days of treatment was also significantly different from those after 10 and 20 days.Conclusion HBO treatment can improve neurological function after cerebral hemorrhage,at least in rats.The best time to start HBO treatment is no later than 24 hours after the hemorrhage.The curative effect increases with extension of the treatment's duration.

Objective To observe the effect of electroacupuncture of Siguan on contents of hippocampal monoamine neurotransmitter NE, DA and 5-HT in post-stroke depression rats, and throught it to probe the possible mechanism of anti-depressive.Methods 60 rats were divided into five groups randomly, as the normal group, MCAO group, PSD group, Siguan group, and fluoxetine group. Except the normal group, the rats of other groups were used to establish left side of the MCAO models by modified Longa filament method. PSD model was prepared by living alone in combination with mild stimulation by chronic unpredictable after stroke model success 7 days. The Siguan group was received electroacupuncture at Siguan point, and the fluoxetine group was gastrically perfused with fluoxetine, and all rats were received sugar consumption experiment in different period of treatment. After continuous treatment for 21 days, contents of NE, DA and 5-HT in hippocampal tissue were measured with RP-HPLC-fluorescent method. Results At the seventh day, compared with PSD group, the ratio of sugar water consumption(51.09%± 3.68%vs. 38.97%± 4.07%)has a significant increase in the Siguan group(P<0.01), while no significant changes in the fluoxetine group. At the fourteenth day, the ratio of sugar water consumption(68.25%± 4.69%vs. 39.64%± 4.49%)continued to rise in the Siguan group, the fluoxetine group also had significantly increased compared with the PSD group, the two groups were significantly higher than those in the PSD group (P<0.01), but the Siguan group was higher than that of the fluoxetine group(P<0.01).At the twenty-first day, the ratio of sugar water consumption (41.56%± 2.12%vs. 41.56%± 2.12%)increased further in the Siguan group and the fluoxetine group, which was significantly higher than those in the PSD group (P<0.01), but the Siguan group and fluoxetine group had no obvious difference(P>0.05). Compared with the PSD group,the contents of NE(244.93 ± 44.57 ng/g vs. 129.27 ± 11.68 ng/g), DA(86.80 ± 14.64 ng/g vs.44.22 ± 7.60 ng/g), 5-HT(526.31 ± 54.41 ng/g vs.221.56 ± 39.57 ng/g) in the hippocampus tissues were significantly higher than many in the Siguan group and fluoxetine group(P<0.01), but the difference between the two groups was not obvious(P>0.05). Conclusion The symptoms of PSD rats pleasure disappeared can be improved by electroacupuncture atSiguan. Its mechanism may be related with the increased contents of monoamine neurotransmitters in the hippocampus of rats.

OBJECTIVETo observe the clinical efficacy and side effects of brentuximab vedotin (BV) plus chlormethine hydrochloride (CH) in patients with relapsed and refractory Hodgkin lymphoma (HL) after failure with BV alone.

METHODSFrom March, 2014 to December, 2014, 6 patients who failed with BV monotherapy were enrolled in this study. The chemotherapy regimen consisted of BV (1.2-1.8 mg/kg, iv. gtt, d1) and CH (6 mg/m2, iv. gtt, d1) was given for 3 weeks as one course, and all patients received about 3-8 courses of chemotherapy, with an median of 4 courses. Clinical efficacy and adverse events were assessed and observed by radiographic examination and serological detection.

RESULTSAmong 6 patients, the overall response rate was 100% with 2 complete remission and 4 partial remission. The main adverse events were grade I (2 patients) and IV (2 patients) bone marrow depression, grade II (2 patients)gastrointestinal reaction, grade I (1 patient) increase of transaminase and myocardial enzyme and grade I (1 patient) mouth ulcers.

CONCLUSIONThe combination of BV and CH in the treatment of relapsed and refractory HL after failure with BV alone was high effective and the toxicities were well tolerable.