Objective:To explore the genetic and clinical characteristics of Guizhou patients with enlarged vestibular aqueduct（EVA） syndrome through combined SLC26A4 variant analysis and clinical phenotype analysis. Methods:Seventy-two EVA patients underwent comprehensive genetic testing using a multiplex PCR-based deafness gene panel and next-generation sequencing（NGS）. The audiological and temporal bone imaging characteristics were compared across mutation subtypes. Results:A total of 27 pathogenic loci of SLC26A4 were detected in 72 patients, including c.919-2A>G in 79.2%（57/72）. A novel deletion（c.1703_1707+6del） was discovered. Among 65 cases, truncated mutations were 89.2%（58/65）, 52.3%（34/65）, 28（43.1%） and 7（10.8%）. No significant differences were observed in the midpoint diameter of the vestibular aqueduct and the incidence of incomplete partitioning typeⅡ（IP-Ⅱ） of the cochlea among the three groups of patients. Moreover, there was no difference in the midpoint diameter of different vestibular pipes or the combination with IP-Ⅱ. Conclusion:The most common mutation site of SLC26A4 in EVA patients in Guizhou is c.919-2A>G, though genotype-phenotype correlations remain elusive. The detection of 27 mutation sites and the discovery of new mutation sites suggested the precise diagnostic significance of NGS technology in EVA patients in Guizhou.
Humans ; Sulfate Transporters ; Vestibular Aqueduct/abnormalities* ; Mutation ; Membrane Transport Proteins/genetics* ; Hearing Loss, Sensorineural/genetics* ; Male ; Female ; Child ; Adolescent ; Child, Preschool ; Adult ; Young Adult ; Phenotype ; High-Throughput Nucleotide Sequencing

Objective:To review and summarize the best evidence of prevention and control measures of carbapenem-resistant Enterobacteriaceae (CRE) hospital infection, and provide evidence-based reference for health care workers to prevent and control CRE infection. Methods:A literature search strategy was developed to systematically search BMJ Best Clinical Practice, UpToDate, the World Health Organization, the Centers for Disease Control and Prevention website, the European Centers for Disease Control and Prevention website, the International Guidelines Collaboration website, the National Practice Technical Guidelines Library of the United States, the National Institute of Health and Clinical Optimization in the United Kingdom, the Ontario Medical Association of Canada, Maimai Tong, Cochrane Library, Australian Joanna Briggs Institute Evidence-Based Health Care Center database, PubMed, Web of Science, China National Knowledge Network, Wanfang database, VIP database, Chinese Biomedical Literature database of evidence related to the prevention and control of CRE hospital infection. The search period was from January 1, 2018 to October 1, 2023. The literature quality was evaluated independently by two research members, and evidence extraction and synthesis were carried out for the included literature.Results:A total of 10 articles were included, including 6 guidelines, 3 expert consensus articles, and 1 systematic review. 29 best evidences were formed from 6 aspects: preventive monitoring, active screening, contact isolation, environmental cleaning and disinfection, bacterial colonization, and hand hygiene measures.Conclusions:This study summarized the best evidence on the prevention and control measures of CRE infection in hospitals. Clinical staff and management departments should take active and effective prevention and control measures based on the local CRE epidemiological situation and resource requirements to reduce the risk of CRE infection.

Objective:To analyze ultrasonographic manifestations and genetic etiology of nine fetuses with 7q11.23 duplication syndrome.Methods:Ultrasonographic finding, pregnancy outcome and follow-up of nine fetuses detected at the Prenatal Diagnosis Center of the Third Affiliated Hospital of Zhengzhou University from January 2017 to December 2021 were retrospectively analyzed.Results:The fetuses were found to harbor a duplication in the 7q11.23 region by chromosomal microarray analysis (CMA). Among these, five had shown ventriculomegaly, including four syndromic and one non-syndromic. For the remainders, one had ventricular septal defect and mild tricuspid regurgitation, one had echogenic intracardiac focus, whilst another two were normal. Five couples had accepted parental verification, and the results confirmed that the 7q11.23 duplication carried by their fetuses were de novo in origin. Following genetic counseling, seven couples had opted to terminate their pregnancies. Two fetuses were delivered at full term, and follow-up had found no abnormalities. Conclusion:Prenatal ultrasonographic manifestations of fetuses with 7q11.23 duplication syndrome are variable. CMA can provide assistance for their diagnosis and genetic counseling.

Objective:To explore the clinical characteristics and variant of CREBBP gene in a fetus with Rubinstein-Taybi syndrome (RSTS). Methods:A fetus with RSTS diagnosed at the Third Affiliated Hospital of Zhengzhou University in August 2022 was selected as the study subject. Clinical data, amniotic fluid sample of the fetus and peripheral blood samples of its parents were collected for whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Results:Foot malformation, cerebellar vermis agenesis, brain agenesis, polysyndactyly of the big toes and other phenotypes were found by prenatal ultrasound. WES revealed that the fetus has harbored a heterozygous c. 4684G>T (p.E1562*) variant in exon 28 of the CREBBP gene (NM_004380.3), which was de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic (PVS1+ PS2_Moderate+ PM2_Supporting). After genetic counseling, the couple had opted to terminate the pregnancy and refused autopsy for the fetus. Conclusion:The c. 4684G>T (p.E1562*) variant of the CREBBP gene probably underlay the RSTS in this fetus. The newly discovered variant has enriched the mutational spectrum of the CREBBP gene and illustrated that WES is an efficient tool for the prenatal diagnosis of RSTS.

Objective:To evaluate the feasibility of 8E5 cells and CD19-CAR-Jurkat cells used as reference cells in the detection of lentiviral vector integration sites with different methods.Methods:Single clones of 8E5 cells and CD19-CAR-Jurkat cells were selected using limiting dilution method. Digital PCR was established to detect the copy number of HIV-1 in 8E5 cells and the copy number of CAR in CD19-CAR-Jurkat cells. High-throughput sequencing techniques (whole-genome resequencing, modified genome sequencing and probe hybridization capture) were used to detect integration sites in 8E5 cells and CD19-CAR-Jurkat cells, and optical genome mapping (OGM) technology was used for further confirmation.Results:Three clones of 8E5-D8 cells and six clones of CD19-CAR-Jurkat 2-6 cells were selected using the limiting dilution method. 8E5-D8 and CD19-CAR-Jurkat 2-6 were chosen as candidate cells based on their gene copy numbers detected by digital PCR and flow cytometry. These cells were then expanded and cryopreserved. Digital PCR showed that 8E5-D8 cells contained approximately 1 copy per cell, while CD19-CAR-Jurkat 2-6 cells contained approximately 13 copies per cell. High-throughput sequencing revealed one integration site in 8E5 cells and 13 integration sites in CD19-CAR-Jurkat cells, which matched the copy number detection results. All these integration sites were further confirmed at the submicroscopic level of chromosomes using OGM.Conclusions:Based on the insertion copy numbers and integration sites, 8E5-D8 cells and CD19-CAR-Jurkat 2-6 cells could be used as reference cells in further development of methods for detecting integration sites in CAR-T cell lentiviral vectors.

With the recent ongoing autumn/winter 2022 COVID-19 wave and the adjustment of public health control measures, there have been widespread SARS-CoV-2 infections in Chinese mainland. Here we have analyzed 369 viral genomes from recently diagnosed COVID-19 patients in Shanghai, identifying a large number of sublineages of the SARS-CoV-2 Omicron family. Phylogenetic analysis, coupled with contact history tracing, revealed simultaneous community transmission of two Omicron sublineages dominating the infections in some areas of China (BA.5.2 mainly in Guangzhou and Shanghai, and BF.7 mainly in Beijing) and two highly infectious sublineages recently imported from abroad (XBB and BQ.1). Publicly available data from August 31 to November 29, 2022 indicated an overall severe/critical case rate of 0.035% nationwide, while analysis of 5706 symptomatic patients treated at the Shanghai Public Health Center between September 1 and December 26, 2022 showed that 20 cases (0.35%) without comorbidities progressed into severe/critical conditions and 153 cases (2.68%) with COVID-19-exacerbated comorbidities progressed into severe/critical conditions. These observations shall alert healthcare providers to place more resources for the treatment of severe/critical cases. Furthermore, mathematical modeling predicts this autumn/winter wave might pass through major cities in China by the end of the year, whereas some middle and western provinces and rural areas would be hit by the upcoming infection wave in mid-to-late January 2023, and the duration and magnitude of upcoming outbreak could be dramatically enhanced by the extensive travels during the Spring Festival (January 21, 2023). Altogether, these preliminary data highlight the needs to allocate resources to early diagnosis and effective treatment of severe cases and the protection of vulnerable population, especially in the rural areas, to ensure the country's smooth exit from the ongoing pandemic and accelerate socio-economic recovery.

OBJECTIVE To analyze the si tuation and hot spots of gabapentinoid drugs in the treatment of pain. METHODS Related researches about gabapentinoid drugs in the treatment of pain were retrieved from Web of Science core collection database during Jan. 1st，2011-Dec. 31st，2020. VOSviewer 1.6.17，CiteSpace 5.8.R1 and Excel 2018 software were used to statistically analyze the key characteristics of relevant literature ，such as the annual publications ，countries/regions，institutions，authors， journals and research hot spots. RESULTS & CONCLUSIONS A total of 3 519 literatures were retrieved ，and the annual publication outputs showed an upward trend generally. Totally 86 countries/regions had conducted relevant studies ，of which the United States ranked first （up to 1 219），and had close cooperation with the United Kingdom ，Canada，China，Germany，Japan， etc；a total of 3 996 institutions had published relevant literatures ，and the Pfizer Inc. issued the most publications ；the most studies were devoted by Professor Parsons from the University of California San Diego ，and the highest co-citations author was Professor Gilron from the Queen ’s University. Among 1 185 journals，Pain ranked first not only in the high-productive journal ，but also in the co-cited journal. The main hot topics include abuse and misuse of gabapentinoid ，off-label use of gabapentinoid ，clinical application of gabapentinoid as a component of multimodal analgesia ，and the update of guidelines for pain based on systematic evaluation and meta-analysis.

Objective:To investigate the clinical value of modified acute aortic dissection risk score in the early diagnosis of acute aortic dissection (AAD).Methods:The general, clinical, and imaging data of 162 patients who complained of chest and back pain who received treatment between January 2019 and January 2021 in the Department of Emergency, The Second Hospital of Jiaxing, China were collected for this study. The included patients were divided into control (non-AAD, n = 120) and observation (AAD, n = 42) groups according to whether they were diagnosed with AAD. The indexes with statistical significance between the two groups were analyzed using multivariate logistic regression analysis. A score table was established according to the size of OR value. The modified AAD risk score was predicted using the receiver operating curve. Results:Multivariate logistic regression analysis showed that male sex, family history, sudden severe chest and back pain, bilateral blood pressure asymmetry, hypertension, abnormal ultrasound, and D-dimer level were independent risk factors for the diagnosis of AAD (statistical values = 7.84, 6.96, 7.04, 11.38, 7.12, 8.15, 15.07, 9.11, all P < 0.05). Taking the total score of 5 as the prediction standard, the specificity and sensitivity in the prediction of the occurrence of AAD were 84.94% and 95.43%, respectively. The area under the receiver operating curve regarding the modified AAD risk score was 0.909. Conclusion:The modified AAD risk score can be used to conveniently and quickly predict the occurrence of AAD and has a high predictive value. This study is highly innovative and scientific.

Objective:To understand the current status of the compliance of immunosuppressive drugs in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to explore the influencing factors of their compliance.Methods:This study was a cross-sectional study. Using the convenient sampling method, a total of 238 allo-HSCT patients who were followed up in the Transplant Center of Taizhou Hospital of Zhejiang Province, Zhejiang Provincial Hospital of Traditional Chinese Medicine and the First Affiliated Hospital of Wenzhou Medical University from March 2020 to February 2021 were selected as the research objects. The self-designed general information questionnaire, Basel Assessment Scale for Immunosuppressive Drug Compliance, Chinese version of Medication Belief-Specific Scale, General Self-Efficacy Scale, Perceived Social Support Scale and Family Care Index Scale were used for on-site investigation of patients. Pearson correlation analysis was used to analyze the correlation between medication compliance and medication belief, self-efficacy, social support and family care of allo-HSCT patients. Multiple linear regression analysis was used to investigate the influencing factors of immunosuppressive medication compliance in allo-HSCT patients.Results:A total of 238 questionnaires were distributed in this study, and 228 valid questionnaires were finally recovered. The medication compliance score of allo-HSCT patients was (4.80±1.18) points. And 111 patients (48.68%, 111/228) had poor medication compliance, among which the incidence of not taking medication on time was the highest, accounting for 44.30% (101/238) . Multiple linear regression analysis showed that average monthly family income, rejection, medication belief, social support and family care were the influencing factors of medication compliance ( P< 0.05) . Conclusions:The immunosuppressant medication compliance of allo-HSCT patients is at a medium and low level. Average monthly family income, rejection reaction, medication belief, social support and family care are the main factors affecting the immunosuppressant medication compliance of allo-HSCT patients. Medical staff should formulate targeted intervention measures according to the influencing factors of medication compliance to improve the immunosuppressive medication compliance of allo-HSCT patients.

Objective:To explore the effect of nursing management model based on the man, machine, material, method, measurement and environment (5M1E) analysis on nosocomial infection of multidrug-resistant organism (MDRO) in Intensive Care Unit (ICU) .Methods:From January 2019 to December 2020, convenience sampling was used to select ICU patients in the Second Hospital of Shanxi Medical University as the research objects. Patients admitted to the hospital from January to December 2019 were taken as the control group ( n=1 224) to implement routine nursing management. Patients admitted to the hospital from January to December 2020 were taken as the observation group ( n=1 134) , and the nursing management model based on 5M1E analysis was implemented. The differences in the use rate of antibacterial drugs, the intensity of antibacterial drug use, the separation amount of newly MDRO per thousand hospitalization days, the length of ICU stay, the total length of stay, and the cost of treatment were compared between the two groups. Results:The use rate of antibacterial drugs, the intensity of antibacterial drug use, and the separation amount of newly MDRO per thousand hospitalization days in the observation group were lower than those in the control group, and the differences were statistically significant ( P<0.01) . The length of ICU stay, total length of stay, and treatment costs of the observation group were less than those of the control group, and the differences were statistically significant ( P<0.01) . Conclusions:The nursing management model based on the 5M1E analysis can reduce the use rate of antibacterial drugs in ICU patients, the intensity of antibacterial drug use, the separation amount of newly MDRO per thousand hospitalization days, shorten the length of ICU stay, total length of stay, and reduce treatment costs, which is worthy of clinical promotion.