Objective To identify the key genes differentially expressed in Wilms tumor and analyze their potential impacts on prognosis and immune responses of the patients. Methods High-throughput RNA sequencing was used to identify the differentially expressed mRNAs in clinical samples of Wilms tumor and paired normal tissues, and their biological functions were analyzed using GO, KEGG and GSEA enrichment analyses. The hub genes were identified using STRING database, based on which a prognostic model was constructed using LASSO regression. The mutations of the key hub genes were analyzed and their impacts on immunotherapy efficacy was predicted using the cBioPortal platform. RT-qPCR was used to verify the differential expressions of the key hub genes in Wilms tumor. Results Of the 1612 differentially expressed genes identified in Wilms tumor, 1030 were up-regulated and 582 were down-regulated, involving mainly cell cycle processes and immune responses. Ten hub genes were identified, among which 4 genes (TP53, MED1, CCNB1 and EGF) were closely related to the survival of children with Wilms tumor. A 3-gene prognostic signature was constructed through LASSO regression analysis, and the patients stratified into with high- and low-risk groups based on this signature had significantly different survival outcomes (HR=1.814, log-rank P=0.002). The AUCs of the 3-, 5-and 7-year survival ROC curves of this model were all greater than 0.7. The overall mutations in the key hub genes or the individual mutations in TP53/CCNB1 were strongly correlated with a lower survival rates, and a high TP53 expression was correlated with a poor immunotherapy efficacy. RT-qPCR confirmed that the key hub genes had significant differential expressions in Wilms tumor tissues and cells. Conclusion TP53 gene plays an important role in the Wilms tumor and may potentially serve as a new immunotherapeutic biomarker as well as a therapeutic target.

Objective Neuromuscular electrical stimulation(NMES)-evoked kinesthetic information in muscle spindle can be purely extracted from the mixed motor and sensory afferents using Ischemic nerve block(INB).This study aims to investigate the somatosensory cortical response evoked by NMES activating muscle spindle afferents in forearm.Methods All subjects performed four experimental tasks designed according to a 2×2 factors,including one factor of the INB state(without INB and within INB)and the other of the stimulation intensity(above and below motor threshold).During the experiment,we recorded EEG data with 64 channels and then beta event-related desynchronization(Beta ERD)were utilized quantize somatosensory cortical excitability evoked by the tasks.The subjective perception about the sensation and movement of the right hand were evaluated by a psychophysical test after the right wrist was performed by INB.Results INB significantly reduced beta ERD on the contralateral somatosensory cortex evoked by NMES above the motor threshold,and there was significant difference of NMES-evoked beta ERD values on the contralateral somatosensory cortex between above and below motor threshold.Meanwhile,contralateral dominance of NMES-evoked beta ERD on the somatosensory cortex was transferred to ipsilateral hemisphere under INB.Conclusion INB can significantly reduce NMES-evoked somatosensory cortical response above motor threshold and decrease cortical perception on the stimulus intensity,which may be due to INB resulting in rapid functional reorganization of somatosensory cortex.

Objective To identify the key genes differentially expressed in Wilms tumor and analyze their potential impacts on prognosis and immune responses of the patients. Methods High-throughput RNA sequencing was used to identify the differentially expressed mRNAs in clinical samples of Wilms tumor and paired normal tissues, and their biological functions were analyzed using GO, KEGG and GSEA enrichment analyses. The hub genes were identified using STRING database, based on which a prognostic model was constructed using LASSO regression. The mutations of the key hub genes were analyzed and their impacts on immunotherapy efficacy was predicted using the cBioPortal platform. RT-qPCR was used to verify the differential expressions of the key hub genes in Wilms tumor. Results Of the 1612 differentially expressed genes identified in Wilms tumor, 1030 were up-regulated and 582 were down-regulated, involving mainly cell cycle processes and immune responses. Ten hub genes were identified, among which 4 genes (TP53, MED1, CCNB1 and EGF) were closely related to the survival of children with Wilms tumor. A 3-gene prognostic signature was constructed through LASSO regression analysis, and the patients stratified into with high- and low-risk groups based on this signature had significantly different survival outcomes (HR=1.814, log-rank P=0.002). The AUCs of the 3-, 5-and 7-year survival ROC curves of this model were all greater than 0.7. The overall mutations in the key hub genes or the individual mutations in TP53/CCNB1 were strongly correlated with a lower survival rates, and a high TP53 expression was correlated with a poor immunotherapy efficacy. RT-qPCR confirmed that the key hub genes had significant differential expressions in Wilms tumor tissues and cells. Conclusion TP53 gene plays an important role in the Wilms tumor and may potentially serve as a new immunotherapeutic biomarker as well as a therapeutic target.

OBJECTIVE: To explore the clinical phenotype and genetic basis of a neonate with Au-Kline syndrome (AKS). METHODS: Clinical data and result of genetic testing of a neonate with AKS who was admitted to the Affiliated Provincial Children's Hospital of Anhui Medical University in January 2021 were retrospectively analyzed. Relevant literature was searched from the Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure and PubMed databases using key words "Au Kline syndrome", "Au-Kline syndrome", "HNRNPK" and "AKS". The research period was set as from January 1, 2000 to December 31, 2020. RESULTS: The male newborn has manifested feeding difficulties, hypotonia, absence of the upper jaw to the uvula and facial dysmorphism. Trio-whole exome sequencing revealed that he has harbored a frameshift c.478dupA (p.Ile160AsnfsTer7) variant of the HNRNPK gene, which was varified by Sanger sequencing to have a de novo origin. The variant has not been included in the databases. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was rated as pathogenic (PVS1+PS2+PM2_Supporting). Literature retrieval has identified 14 children with AKS and de novo mutations of the HNRNPK gene. Their clinical manifestations have included growth and motor retardation, various degree of mental retardation, facial dysmorphism and a high frequency of congenital heart malformations. CONCLUSION The AKS in this child may be attributed to the c478dupA frameshifting variant of the HNRNPK gene. Diagnosis of AKS should be suspected for children with mental retardation and multiple congenital malformation syndromes including Kabuki syndrome.
Humans ; Male ; Abnormalities, Multiple/genetics* ; Genetic Testing ; Heterogeneous-Nuclear Ribonucleoprotein K/genetics* ; Intellectual Disability/genetics* ; Mutation ; Retrospective Studies ; Infant, Newborn

Objective:To investigate the value of the 8-channel eye surface phased array coil in improving image quality and demonstrating ocular masses on 3.0 T MR scanner.Methods:From July 2018 to January 2020, the data of orbital MRI in 692 patients with ocular masses on 6 medical centers were prospectively collected. The patients were simple randomly assigned into 8-channel eye surface phased array coil group (413 patients) or 8-channel head phased array coil group (279 patients), with the same MRI sequences. The signal to noise ratio (SNR) and contrast to noise ratio (CNR) were calculated in orbital anatomy structures and masses (eyelid mass, intraocular mass, lacrimal mass and orbital mass). The image quality scores including motion artifact, mass margin, the relationship between the mass and adjacent structures, and overall image quality were recorded. The differences of image quality between the two groups were compared by two independent sample t-test or Wilcoxon rank test. Results:The SNR and CNR were higher in eye surface coil group than those in head coil group ( P<0.05). The scores of ocular movement artifacts were higher in head coil group than those in surface coil group ( P<0.05). The scores of intraocular mass margin, the relationship between the mass and adjacent structures, and overall image quality were higher in surface coil group than those in head coil group ( P<0.001). There were no significant differences in mass margin, the relationship between the mass and adjacent structures, and overall image quality scores of eyelid, lacrimal gland, and orbital mass between the two groups ( P>0.05). Conclusion:3.0 T MR scanner combined with the 8-channel eye surface phased array coil can improve the SNR and CNR of orbital MR images, the demonstration of the intraocular mass margin and the relationship between the mass and adjacent structures.

Objective:To investigate the value of periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) in improving ability of demonstrating ocular masses on 3.0 T MR scanner.Methods:This study was a multi-center prospective study involving 6 centers. From July 2018 to January 2020, totally 413 patients with ocular masses from 6 centers were prospectively enrolled, and all of them underwent T 1WI and T 2WI, PROPELLER T 1 FLAIR and T 2WI, and contrast-enhanced scans. The signal intensity of eyelid, vitreous body, lacrimal gland, intraorbital segment of optic nerve, and orbital masses of eyelid, intraocular, lacrimal gland and retrobulbar were measured by two radiologists, and the signal to noise ratio (SNR) and contrast noise ratio (CNR) were calculated. The 5-point scoring method was used to evaluate the motion artefacts, tumor edges and the relationship between the tumor and adjacent structures, and the overall score of image quality was calculated. Paired t-test or Wilcoxon signed rank test was used to compare the image quality between PROPELLER and non-PROPELLER images. Results:The SNR and CNR of PROPELLER T 2WI were higher than those of non-PROPELLER T 2WI (all P<0.001). The SNR and CNR of PROPELLER T 1 FLAIR were lower than those of non-PROPELLER T 1WI (all P<0.05). The scores of artefacts and overall image quality in PROPELLER images were higher than those in non-PROPELLER images (all P<0.001). The tumor edge and the relationship between the tumor and adjacent structures scores of eyelid, intraocular, and lacrimal gland masses in PROPELLER images were higher than those in non-PROPELLER images (all P<0.001),while compared to non-PROPELLER images, retro-global masses in PROPELLER images showed no significant differences (all P>0.05). Conclusion:PROPELLER can reduce ocular motion artefacts, effectively improve image quality and ability of demonstrating anterior (eyelid, intraocular, and lacrimal gland) masses.

Cow′s milk protein allergy (CMPA) is one of the most common presentations of food allergy seen in early childhood.It is an abnormal immune response caused by cow′s milk protein.CMPA can be clinically subdivided into either immediate-onset IgE mediated or delayed onset non-IgE mediated, or both.At present, concerns regarding the early and timely diagnosis of CMPA have been high-lighted over the years and there are many expert consensus on CMPA in China, but these consensus did not distinguish IgE mediated or non-IgE mediated CMPA.In view of the obvious clinical differences between the two type of CMPA and non-IgE mediated CMPA is more common in infancy, experts focus on pediatric gastroenterology, allergy/immunology, dermatology, nutrition and child healthcare convened by the Allergy Prevention and Control Professional Committee of Chinese Preventive Medicine Association present this guideline to help practitioners in primary care settings to early recognize and make suitable management of non-IgE mediated CMPA in China.The guideline incorporates the cutting-edge international guidance and the actual situation of Chinese children describing in detail the types, clinical features, diagnosis and nutritional intervention of non-IgE mediated CMPA.There are 42 recommendations in 7 categories in total referring to the common questions related to non-IgE mediated CMPA.

OBJECTIVE: To explore the clinical features and genetic etiology for a neonate with Smith-Magenis syndrome (SMS). METHODS: Copy number variation sequencing (CNV-seq) was applied to the neonate and his parents, and the genotype-phenotype correlation was analyzed. RESULTS: On the second day after birth, the neonate had presented with pathological jaundice and immunodeficiency. Cranial MRI revealed ventricular enlargement and enlargement of cisterna magna. At 3 months, the infant has presented with square face, prominent forehead, deep-set eyes, hypertelorism, palpebral fissure upward and button noses. Genetic testing showed that he had carried a 2.9 Mb deletion in 17p11.2 region, seq[GRCh37] del(17)(p11.2)(chr17:16 836 379-19 880 992). The same deletion was not found in either parent. CONCLUSION SMS is mostly diagnosed in child and adulthood, but rarely in neonates. For neonates with SMS, the neurological and behavioral abnormalities have not been shown, but pathological jaundice, CNS abnormalities and immune deficiency may be the characteristics, which require attention of neonatal physicians.
Adult ; Chromosome Deletion ; Chromosomes, Human, Pair 17 ; DNA Copy Number Variations ; Genetic Testing ; Humans ; Infant, Newborn ; Intellectual Disability/genetics* ; Male ; Phenotype ; Smith-Magenis Syndrome/genetics*

After brachial plexus avulsion (BPA), microglia induce inflammation, initiating and maintaining neuropathic pain. EZH2 (enhancer of zeste homolog 2) has been implicated in inflammation and neuropathic pain, but the mechanisms by which it regulates neuropathic pain remain unclear. Here, we found that EZH2 levels were markedly upregulated during BPA-induced neuropathic pain in vivo and in vitro, stimulating pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) secretion in vivo. In rats with BPA-induced neuropathic pain, mechanical and cold hypersensitivities were induced by EZH2 upregulation and inhibited by EZH2 downregulation in the anterior cingulate cortex. Microglial autophagy was also significantly inhibited, with EZH2 inhibition activating autophagy and reducing neuroinflammation in vivo. However, this effect was impaired by inhibiting autophagy with 3-methyladenine, suggesting that the MTOR signaling pathway is a functional target of EZH2. These data suggest that EZH2 regulates neuroinflammation and neuropathic pain via a novel MTOR-mediated autophagy signaling pathway, providing a promising approach for managing neuropathic pain.

Objective:To investigate the safety and efficacy of sacral neuromodulation(SNM)therapy for the treatment of lower urinary tract dysfunction(LUTD)in elderly patients.Methods:Clinical data of 91 elderly patients with LUTD from multiple medical institutions who received SNM during the period from January 2012 to December 2016 were retrospectively analyzed.Patients were divided into four groups: the interstitial cystitis(IC)group(n=28), the neurogenic bladder(NB)group(n=36), the overactive bladder syndrome(OAB)group(n=13)and the idiopathic dysuria(ID)group(n=14). Different sets of evaluation parameters were used for different diseases.Patients’ baseline data and data in stage I(test phase)and stage Ⅱ(permanent SNM)were recorded, statistically analyzed and compared.Results:Ninety-one people underwent SNM treatment.Of them, 53 patients received permanent implants(stage Ⅱ), and the total conversion rate of stage I to stage Ⅱ was 58.2%(53/91). Patients receiving permanent implants(stage Ⅱ)had a preoperative period ranging from 3 months to 30 years, and were followed up for 2 to 58 months after treatment, with an average follow-up of 19.6 months.The improvement rates in stage I for urinary urgency, daily urination frequency, daily nocturnal urination frequency, maximum urine volume, daily average urine volume, daily urine leakage frequency, and quality of life score were 35.4%, 31.6%, 33.7%, 32.6%, 49.2%, 43.2% and 13.2%, respectively.The improvement rates in stage Ⅱ for urinary urgency, daily urination frequency, daily nocturnal urination frequency, maximum urine volume, daily average urine volume, daily urine leakage frequency, and quality of life score were 43.2%, 40.0%, 37.8%, 50.5%, 70.5%, 70.4% and 43.2%, respectively.Three adverse events occurred, including 1 case of recurrent symptoms, 1 case of moderate infection, and 1 case of electrical lead dislocation.Conclusions:Sacral nerve stimulation has definitive and consistent curative effects on LUTD in elderly people.The follow-up time should be extended to further study the safety of sacral nerve stimulation.