Objectives: . Branchio-oto syndrome (BOS) primarily manifests as hearing loss, preauricular pits, and branchial defects. EYA1 is the most common pathogenic gene, and splicing mutations account for a substantial proportion of cases. However, few studies have addressed the structural changes in the protein caused by splicing mutations and potential pathogenic factors, and several studies have shown that middle-ear surgery has limited effectiveness in improving hearing in these patients. BOS has also been relatively infrequently reported in the Chinese population. This study explored the genetic etiology in the family of a proband with BOS and provided clinical treatment to improve the patient’s hearing. Methods: . We collected detailed clinical features and peripheral blood samples from the patients and unaffected individuals within the family. Pathogenic mutations were identified by whole-exome sequencing and cosegregation analysis and classified according to the American College of Medical Genetics and Genomics guidelines. Alternative splicing was verified through a minigene assay. The predicted three-dimensional protein structure and biochemical experiments were used to investigate the pathogenicity of the mutation. The proband underwent middle-ear surgery and was followed up at 1 month and 6 months postoperatively to monitor auditory improvement. Results: . A novel heterozygous EYA1 splicing variant (c.1050+4 A>C) was identified and classified as pathogenic (PVS1(RNA), PM2, PP1). Skipping of exon 11 of the EYA1 pre-mRNA was confirmed using a minigene assay. This mutation may impair EYA1-SIX1 interactions, as shown by an immunoprecipitation assay. The EYA1-Mut protein exhibited cellular mislocalization and decreased protein expression in cytological experiments. Middle-ear surgery significantly improved hearing loss caused by bone-conduction abnormalities in the proband. Conclusion . We reported a novel splicing variant of EYA1 in a Chinese family with BOS and revealed the potential molecular pathogenic mechanism. The significant hearing improvement observed in the proband after middle-ear surgery provides a reference for auditory rehabilitation in similar patients.

Data mining technology was adopted to analyze the rules of acupoint selection in treatment of erectile dysfunction with acupuncture and moxibustion. All of the articles for acupuncture and moxibustion in treatment of erectile dysfunction were searched from the databases, i.e. Chinese national knowledge infrastructure (CNKI), Wanfang database, VIP, Chinese biomedical literature database (SinoMed) and PubMed, and the clinical trials on erectile dysfunction treated with acupuncture and moxibustion were screened. The database was set up by using Excel 2019 and input into R 4.0.3, and then, the therapeutic method, use frequency of acupoint, meridian tropism, collection visualization analysis, cluster analysis and association rule analysis were summarized. A total of 240 articles were included, with 516 prescriptions and 145 acupoints involved. The methods for treatment of erectile dysfunction included acupuncture and moxibustion therapy, acupuncture, acupoint injection, electroacupuncture, etc. The acupoints with high use frequency were Guanyuan (CV 4), Shenshu (BL 23), Sanyinjiao (SP 6), Mingmen (GV 4), Zusanli (ST 36), Zhongji (CV 3), Ciliao (BL 32), Qihai (CV 6), Taixi (KI 3) and Taichong (LR 3). The meridians involved with high frequency were the bladder meridian of foot-taiyang, the conception vessel, the spleen meridian of foot-taiyin, etc. The common acupoint combination was Shangliao (BL 31), Zhongliao (BL 33), Ciliao (BL 32), Xialiao (BL 34) and Sanyinjiao (SP 6), Shenshu (BL 23), Guanyuan (CV 4). In association rule analysis (confidence ≥ 90%, support ≥ 20%), there were 27 association rules in total. The acupoint combination with the highest support referred to "Shenshu (BL 23), Sanyinjiao (SP 6)→Guanyuan (CV 4)" (support 46.7%) and the acupoint combination with the highest confidence was "Sanyinjiao (SP 6), Qihai (CV 6)→Guanyuan (CV 4)" (confidence 98.0%). The acupoints could be divided into 5 effective clusters. Acupuncture and moxibustion therapy has a certain of rules of acupoint selection in treatment of erectile dysfunction, which provides the evidences for modern clinical trial and treatment.
Acupuncture Points ; Acupuncture Therapy ; Data Mining ; Erectile Dysfunction/therapy* ; Humans ; Male ; Meridians ; Moxibustion ; Technology

Objective:To investigate the pathogenic distribution of benign infantile convulsions with mild gastroenteritis(BICE)and explore the relevance of serum cytokines and BICE.Methods:Eighty BICE infants admitted in Inner Mongolia Maternal and Child Health Hospital from January 2017 to December 2019 were selected as BICE group, and 80 mild gastroenteritis infants without convulsion attack were selected as control group during the same period.Fluorometric real-time PCR was used to detect the pathogen of enterovirus.Serum cytokines including interleukin(IL)-6, tumor necrosis factor(TNF)-α, IL-8 and soluble interleukin-2 receptor(SIL-2R)were detected by using chemiluminescence method.The relevance of frequency and duration of convulsion in infants with BICE and the indicators above were analyzed.Results:Rotavirus infection was the main cause of BICE during the study period in this region.Among 80 cases in the BICE group, rotavirus positive infants accounted for 38.8%(31/80) and norovirus positive infants accounted for 10.0%(8/80). The levels of IL-6, IL-8 and SIL-2R in the BICE group were prominently higher than those in the control group( P<0.05); the difference of TNF-α level between two groups had no statistical significance( P>0.05). The levels of IL-6, TNF -α, IL-8, SIL-2R in the group with convulsion attack times ≥ 2 and convulsion duration ≥5 min were higher than those in the group with convulsion attack times<2 and convulsion duration<5 min( P<0.05). The frequency and duration of convulsions were positively correlated with the levels of IL-6, TNF -α, IL-8 and SIL-2R( P<0.05). Conclusion:Rotavirus is the main pathogen of BICE in this region.There is immunologic imbalance in children with BICE, especially the changes of IL-6 and SIL-2R levels, which may provide effective cytological and experimental data evidence for judging progression and prognosis of the disease.

Objective:To explore the performance of the commonly used whole blood C-reactive protein (CRP) detection systems and give related recommendation on the performance requirements of detection systems.Methods:A total of 7 540 venous blood samples from 26 maternal, child and children′s hospitals were collected to conduct this multi-center study on the analytical performance of 5 commonly used whole blood CRP detection systems from March to April in 2019. The blank check, carryover, repeatability, intermediate precision, linearity, sample stability, influence of hematocrit/triglyceride/bilirubin, comparison with SIEMENS specific protein analyzer and trueness were evaluated. The 5 systems included BC-5390CRP autohematology analyzer, AstepPLUS specific protein analyzer, Ottoman-1000 Automated Specific Protein POCT Workstation, i-CHROMA Immunofluorometer equipment Reader and Orion QuikRead go detecting instrument. The 5 systems were labeled as a, b, c, d and e randomly.Results:Within the 5 systems, all values of blank check were less than 1.00 mg/L, the carryovers were lower than 1.00%. The repeatability of different ranges of CRP concentrations including 3.00-10.00, 10.00-30.00 and>30.00 mg/L were less than 10.00%, 6.00% and 5.00%, respectively, and the intermediate precision was less than 10.00%. The linearity correlation coefficients of the 5 systems were all above 0.975, while the slope was within 0.950-1.050. Whole blood samples were stable within 72 hours both at room temperature (18-25 ℃) and refrigerated temperature (2-8 ℃). The CRP results were rarely influenced by high triglyceride or bilirubin, except for the immmunoturbidimetric test based on microparticles coated with anti-human CRP F(ab) 2 fragments. When triglyceride was less than 15.46 mmol/L, the deviation of CRP was less than 10.00%. When bilirubin was less than 345.47 μmol/L, the deviation of CRP was less than 10.00%. CRP was more susceptible to Hct on the systems without Hct correction. The deviation of CRP between different Hct dilution concentration and 40% dilution concentration can reach as high as 67.48%. The correlation coefficients ( r) of 5 systems were all more than 0.975 in the range of 0-300.00 mg/L compared with Siemens specific protein analyzer. All systems passed the trueness verification using the samples with specified values of 12.89 and 30.60 mg/L. Conclusion:The performance of 5 systems can basically meet the clinical needs, but it is suggested that the whole blood CRP detection system without automatic Hct correction should be modified manually.

As the progress of population aging in China, the proportion of elderly population is increasing. Both chronic diseases and infectious diseases can threaten the health of the elderly. There are many kinds of infectious diseases, including vaccine preventable infectious diseases affecting the health of adults, such as influenza, pneumococcal diseases and herpes zoster. In addition, the newly emerged COVID-19 has caused a pandemic in the world, resulting the highest proportion of deaths occurred in the elderly and posing a serious threat to the health of the elderly. This paper mainly summarizes the prevention and control of vaccine preventable diseases and COVID-19 to which the elderly are susceptible, analyzes the infectious disease problems affecting the health of elderly population, and recommends countermeasures for the prevention and control of these diseases in elderly population.

OBJECTIVE: To investigate the effect of Aurora kinase B (AURKB) silencing-induced autophagy on apoptosis of osteosarcoma 143B cells and the underlying molecular mechanisms. METHODS: Human osteosarcoma 143B cells were transfected with Lv/shAURKB or the negative control vector Lv/shScrambled followed by treatment with chloroquine (CQ) for 24 h. Western blotting was performed to detect the protein expression levels of AURKB, P62, LC3, cleaved caspase-3, Bcl-2, and P-ULK1. Transmission electron microscopy and LC3 dual-label fluorescence method were used to trace the autophagosomes in 143B cells to assess cell autophagy, and the cell apoptosis was detected using flow cytometry and TUNEL assay. Co-immunoprecipitation assay was used to detect the interaction between AURKB and ULK1. RESULTS: The ratio of autophagy-related proteins LC3 II/I and the number of autophagosomes were significantly increased in 143B cells after transfection with Lv/shAURKB ( < 0.05), which significantly increased the expression of cleaved caspase-3 and reduced the expression of Bcl-2 ( < 0.05). Combined treatment of the cells with Lv/shAURKB and the autophagy inhibitor chloroquine obviously restored the expressions of caspase-3 and Bcl-2 ( < 0.05). Transfection with Lv/shAURKB significantly increased the apoptosis rate of 143B cells ( < 0.05), and this effect was significantly antagonized by combined treatment with chloroquine ( < 0.05). AURKB silencing strongly activated the phosphorylation of the autophagy-initiating protein ULK1 in 143B cells ( < 0.05). The results of co-immunoprecipitation assay confirmed when AURKB was immunoprecipitated, ULK1 also precipitated. CONCLUSIONS Silencing AURKB can induce autophagy by activating ULK1 phosphorylation to promote apoptosis in 143B cells.

Objective To investigate the diagnosis and treatment of adult Hirschsprung disease. Methods The clinical data of 10 patients with adult Hirschsprung disease from August 2011 to August 2017 in the Department of General Surgery of the First Affiliated Hospital of Soochow University were retrospectively analyzed. Results Among the 10 patients, 4 cases were male, and 6 cases were female, with age 21 to 65 years old, and body mass index 16.77 to 25.73 kg/m2. The patients were diagnosed with Hirschsprung disease by postoperative pathological examination. All patients had difficult defecation medical history. Barium enema examination in 3 patients before operation showed obvious narrow segment, migrating segment and dilatation segment. Four cases received emergency surgical operation, and 6 cases received selective surgical operation. Complications included intestinal obstruction in 3 cases, incisions infection in 2 cases, and incision rupture in 1 case. Conclusions Adult Hirschsprung disease is difficult to be diagnosed, and the aspect of medical history, barium enema examination, surgical findings and pathological examination has to be combined. The surgery way of AHD is diverse and ought to be individual. Laparoscopic surgery with small trauma and quick recovery has great development space.

In the original publication the Supplementary Material and Fig. 2 are incorrect. The correct version is provided in this correction article. The text HBG2 appearing in the article should be read as HBG1.

Bacterial Proteins ; genetics ; CRISPR-Cas Systems ; genetics ; Endonucleases ; genetics ; Gene Editing ; HEK293 Cells ; Humans ; Transcriptional Activation ; genetics ; p300-CBP Transcription Factors ; genetics