Objective:By analyzing the clinical phenotypic characteristics and gene sequences of two patients with Treacher Collins syndrome（TCS）, the biological causes of the disease were determined. Then discuss the therapeutic effect of hearing intervention after bone bridge implantation. Methods:All clinical data of the two family members were collected, and the patients signed the informed consent. The peripheral blood of the proband and family members was extracted, DNA was extracted for whole exome sequencing, and Sanger sequencing was performed on the family members for the mutation site.TCOF1genetic mutations analysis was performed on the paitents. Then, the hearing threshold and speech recognition rate of family 2 proband were evaluated and compared under the sound field between bare ear and wearing bone bridge. Results:In the two pedigrees, the probands of both families presented with auricle deformity, zygomatic and mandibular hypoplasia, micrognathia, hypotropia of the eye fissure, and hypoplasia of the medial eyelashes. The proband of Family 1 also presents with specific features including right-sided narrow anterior nasal aperture and dental hypoplasia, which were consistent with the clinical diagnosis of Treacher Collins syndrome. Genetic testing was conducted on both families, and two heterozygous mutations were identified in the TCOF1 gene: c. 1350_1351dupGG（p. A451Gfs*43） and c. 4362_4366del（p. K1457Efs*12）, resulting in frameshift mutations in the amino acid sequence. Sanger sequencing validation of the TCOF1 gene in the parents of the proband in Family 1 did not detect any mutations. Proband 1 TCOF1 c. 1350_1351dupGG heterozygous variants have not been reported previously. The postoperative monosyllabic speech recognition rate of family 2 proband was 76%, the Categories of Auditory Performance（CAP） score was 6, and the Speech Intelligibility Rating（SIR） score was 4. Assessment using the Meaningful Auditory Integration Scale（MAIS） showed notable improvement in the patient's auditory perception, comprehension, and usage of hearing aids. Evaluation using the Glasgow Children's Benefit Inventory and quality of life assessment revealed significant improvements in the child's self care abilities, daily living and learning, social interactions, and psychological well being, as perceived by the parents. Conclusion:This study has elucidated the biological cause of Treacher Collins syndrome, enriched the spectrum of TCOF1 gene mutations in the Chinese population, and demonstrated that bone bridge implantation can improve the auditory and speech recognition rates in TCS patients.
Child ; Humans ; Mandibulofacial Dysostosis/genetics* ; Quality of Life ; Speech ; Parents ; Mutation ; Nuclear Proteins/genetics* ; Phosphoproteins/genetics*

Objective:To study the frequency of SLC26A4 gene mutation sites in children with enlarged vestibular aqueduct deafness in Yunnan, report the new mutation sites of SLC26A4 gene, further clarify the mutation spectrum of SLC26A4gene, and explore the association between biallelic and monoallelic mutations of SLC26A4 gene and CT phenotype of inner ear, so as to provide basis for clinical and genetic diagnosis of deafness. Methods:Review the results of temporal bone CT examination of 390 children after cochlear implantation in the Department of Otolaryngology, Kunming Children's Hospital from August 2016 to September 2021. Sanger sequencing of SLC26A4 gene was performed in 59 children with enlarged vestibular aqueduct. According to the genetic test results, the children who underwent temporal bone CT examination were divided into two groups: SLC26A4 biallelic mutation group（homozygous mutation and compound heterozygous mutation）, monoallelic mutation group, and the association with inner ear CT phenotype was analyzed, and the new sites were summarized and analyzed. Results:The c.919-2a>g mutation was the most common mutation in children with enlarged vestibular aqueduct with SLC26A4 gene mutation. Three new variants of SLC26A4 gene were found; CT examination combined with genetic testing found that a part of children with enlarged vestibular aqueduct was associated with SLC26A4 monoallelic mutation or no SLC26A4 gene mutation was detected. Further research is needed to investigate the involvement of other pathogenic factors in the pathogenesis of EVA.
Child ; Humans ; Mutation Rate ; Membrane Transport Proteins/genetics* ; China ; Hearing Loss, Sensorineural/diagnosis* ; Mutation ; Vestibular Aqueduct ; Vestibular Diseases/pathology* ; Deafness/genetics*

Humans ; Hospital Rapid Response Team ; Attitude of Health Personnel ; Perception

OBJECTIVE: To study the effects of total ginsenosides (TG) extract from Panax ginseng on neural stem cell (NSC) proliferation and differentiation and their underlying mechanisms. METHODS: The migration of NSCs after treatment with various concentrations of TG extract (50, 100, or 200 µ g/mL) were monitored. The proliferation of NSCs was examined by a combination of cell counting kit-8 and neurosphere assays. NSC differentiation mediated by TG extract was evaluated by Western blotting and immunofluorescence staining to monitor the expression of nestin and microtubule associated protein 2 (MAP2). The GSK-3β/β-catenin pathway in TG-treated NSCs was examined by Western blot assay. The NSCs with constitutively active GSK-3β mutant were made by adenovirus-mediated gene transfection, then the proliferation and differentiation of NSCs mediated by TG were further verified. RESULTS: TG treatment significantly enhanced NSC migration (P<0.01 or P<0.05) and increased the proliferation of NSCs (P<0.01 or P<0.05). TG mediation also significantly upregulated MAP2 expression but downregulated nestin expression (P<0.01 or P<0.05). TG extract also significantly induced GSK-3β phosphorylation at Ser9, leading to GSK-3β inactivation and, consequently, the activation of the GSK-3β/β-catenin pathway (P<0.01 or P<0.05). In addition, constitutive activation of GSK-3β in NSCs by the transfection of GSK-3β S9A mutant was found to significantly suppress TG-mediated NSC proliferation and differentiation (P<0.01 or P<0.05). CONCLUSION TG promoted NSC proliferation and neuronal differentiation by inactivating GSK-3β.
Animals ; Cell Differentiation ; Cell Proliferation ; Ginsenosides/pharmacology* ; Glycogen Synthase Kinase 3 beta/metabolism* ; Neural Stem Cells/metabolism* ; Panax ; Plant Extracts/pharmacology* ; Rats ; beta Catenin/metabolism*

Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin's lymphoma. A total of 10%‒15% of DLBCL cases are associated with myelocytomatosis viral oncogene homolog(MYC) and/or B-cell lymphoma-2 (BCL2) translocation or amplification. BCL2 inhibitors have potent anti-tumor effects in DLBCL; however, resistance can be acquired through up-regulation of alternative anti-apoptotic proteins. The histone deacetylase (HDAC) inhibitor chidamide can induce BIM expression, leading to apoptosis of lymphoma cells with good efficacy in refractory recurrent DLBCL. In this study, the synergistic mechanism of chidamide and venetoclax in DLBCL was determined through in vitro and in vivo models. We found that combination therapy significantly reduced the protein levels of MYC, TP53, and BCL2 in activated apoptotic-related pathways in DLBCL cells by increasing BIM levels and inducing cell apoptosis. Moreover, combination therapy regulated expression of multiple transcriptomes in DLBCL cells, involving apoptosis, cell cycle, phosphorylation, and other biological processes, and significantly inhibited tumor growth in DLBCL-bearing xenograft mice. Taken together, these findings verify the in vivo therapeutic potential of chidamide and venetoclax combination therapy in DLBCL, warranting pre-clinical trials for patients with DLBCL.
Aminopyridines ; Animals ; Benzamides ; Biological Phenomena ; Bridged Bicyclo Compounds, Heterocyclic ; Down-Regulation ; Histone Deacetylase Inhibitors/therapeutic use* ; Humans ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Mice ; Neoplasm Recurrence, Local ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Proto-Oncogene Proteins c-myc/therapeutic use* ; Sulfonamides ; Tumor Suppressor Protein p53/metabolism*

Objective To obtain the physical anthropological characteristics of head and face of Tajik adults in Aketao, and to explore their ethnic origin through cluster analysis with other populations. Methods According to Anthropometric Method, 286 Tajik adults (male 121, female 165) in Aketao, Xinjiang were recruited and analyzed. The survey included 12 observation indicators of head and face, 19 measuring indicators of head and face, 12 indexes of head and face and its classification. Results The indicators of head length, head breadth, head height, minimum frontal breadth, face breadth, bigonial breadth, nose breadth, mouth breadth, auricular height, physiognomic facial height, morphological facial height, nasal length, nasal height, physiognomic ear length, physiognomic ear breadth, zygomatic protection, nasal root height, nasal profile, nasal base of Tajik adults in Aketao had gender differences (P < 0. 05). Compared with the Tajik adults in Aketao and Taxkorgan, the type indicators of head and face of zygomatic protection, direction of eyeslits, nasal root height, nasal base, maximal diameter of nostrils, lobe types, nreadth-height index of head type, morphological facial index type, nasal index type had regional differences (P<0. 05). The cluster analysis showed that Tajik adults have unique characteristics of head and face, which were grouped separately and were more similar to Iranians. Conclusion Tajik adults in Aketao have the characteristics of head and face of the West Eurasian. The characteristics of head and face of Tajik adults in Aketao and Taxkorgan are somewhat different. From characteristics of head and face, they may be related to the Eastern Iranian tribe.

COVID-19 ; Critical Care ; Humans ; Intensive Care Units ; SARS-CoV-2

Objective: To screen and analyze the mutations of MITF gene in two children of type Ⅱ Waardenburg syndrome (WS2) from different families in Yunnan,China,and to explore the possible molecular pathogenesis. Methods: With informed consent, medical history collection, physical examinations, audiological evaluation, and high resolution computer tomography (HRCT) scan of temporal bone were performed on the two WS2 probands and their family members. Genomic DNA was extracted from peripheral blood of all individuals. The coding regions including all exons, part of introns and promoters of MITF, PAX3, SOX10, SNAI2, END3, ENDRB, and KITLG genes were sequenced by high-throughput sequencing. According to the results of high-throughput sequencing, pathogenic mutations detected in the probands and their parents were verified by Sanger sequencing. Results: The proband 1 carried c.641_643delGAA mutation in the 7th exon of MITF gene, which was a frame-shift mutation resulting in an amino acid change of p.214delR. It was a de novo mutation as the parents of proband 1 showed no variation on this site. The proband 2 carried heterozygous loss of the large fragment ranging from exon 1 to exon 9 of MITF gene, which defected the function of MITF protein. Conclusion: Genetic examinations provide important evidence for diagnosis of Waardenburg syndrome. Heterozygous mutation c.641_643delGAA and heterozygous loss of the large fragment ranging from exon 1 to exon 9 of MITF gene might be the molecular pathogenesis of the two WS2 probands in this study.
Asians/genetics* ; Child ; China ; Humans ; Mutation ; Pedigree ; SOXE Transcription Factors/genetics* ; Waardenburg Syndrome/genetics*

INTRODUCTION: A second-tier rapid response team (RRT) is activated for patients who do not respond to first-tier measures. The premise of a tiered response is that first-tier responses by a ward team may identify and correct early states of deterioration or establish goals of care, thereby reducing unnecessary escalation of care to the RRT. Currently, utilisation and outcomes of tiered RRTs remain poorly described. METHODS: A prospective observational study of adult patients (age ≥18 years) who required RRT activations was conducted from February 2018 to December 2019. RESULTS: There were 951 consecutive RRT activations from 869 patients and 76.0% patients had a National Early Warning Score (NEWS) ≥5 at the time of RRT activation. The majority (79.8%) of patients required RRT interventions that included endotracheal intubation (12.7%), point-of-care ultrasound (17.0%), discussing goals of care (14.7%) and intensive care unit (ICU) admission (24.2%). Approximately 1 in 3 (36.6%) patients died during hospitalisation or within 30 days of RRT activation. In multivariate analysis, age ≥65 years, NEWS ≥7, ICU admission, longer hospitalisation days at RRT activation, Eastern Cooperative Oncology Group performance scores ≥3 (OR [odds ratio] 2.24, 95% CI [confidence interval] 1.45-3.46), metastatic cancer (OR 2.64, 95% CI 1.71-4.08) and haematological cancer (OR 2.78, 95% CI 1.84-4.19) were independently associated with mortality. CONCLUSION Critical care interventions and escalation of care are common with second-tier RRTs. This supports the need for dedicated teams with specialised critical care services. Poor functional status, metastatic and haematological cancer are significantly associated with mortality, independent of age, NEWS and ICU admission. These factors should be considered during triage and goals of care discussion.
Adolescent ; Adult ; Aged ; Critical Care ; Hospital Mortality ; Hospital Rapid Response Team ; Humans ; Prospective Studies ; Tertiary Care Centers

Objective:To analyze the research hotspot and frontier of severe coronavirus disease 2019 (COVID-19) in China and abroad.Methods:The CiteSpace software was used to visually analyze the relevant research of severe COVID-19 published by CNKI and Web of Science databases from January 30th to April 20th in 2020. The analysis content included the author of the literature, the publishing institutions, and high-frequency keywords.Results:There were 389 Chinese literatures and 59 English literatures included. Analysis using CiteSpace software showed that there were four large teams in China currently concerning about the research on severe COVID-19. The co-authoring of each team was relatively close, but the teams were lack of cooperation. The main issuing institutions were affiliated hospitals of colleges and universities, but colleges and enterprises had less participation. The authors of English-language publications mainly had five research teams, some of whom had co-authored relationships. The country with the most enormous volume of English-language publications was China, followed by the United States and Canada. The Chinese keyword co-occurrence, clustering and highlighted words analysis showed that the main research areas of severe COVID-19 included clinical features, traditional Chinese medicine treatment, medical imaging, integrated traditional Chinese and Western medicine treatment and so on; nucleic acid detection, clinical features and diagnosis, plague theory and etiology mechanism, traditional Chinese medicine and integrated Chinese and Western medicine treatment, severe COVID-19 combined with diabetes and prognosis research will become future research trends; keyword cluster analysis showed that severe COVID-19, combined chronic underlying diseases, CT imaging characteristics will also become new trends in the field of research. Co-occurrence analysis of keywords in English literatures showed that the main research areas of severe COVID-19 included the names of novel coronavirus, pandemic diseases, infectious diseases, medical supplies distribution, and indicators related to myocardial damage.Conclusions:Researchers in China and abroad have different concerns about severe COVID-19. Domestic research focuses on the diagnosis and treatment of severe cases, while foreign countries attach importance to epidemic response and prevention.