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

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

ObjectiveTo analyze the distribution, drug resistance characteristics, and changing trends of Acinetobacter baumannii (AB) isolated from environmental surfaces and healthcare workers’ hands in a grade Ⅱ level A general hospital in Xuhui District of Shanghai from 2018 to 2023, and to provide reference for infection control in the hospital. MethodsEnvironmental samples were collected quarterly from critical surfaces and healthcare workers’ hands in the intensive care unit (ICU), geriatrics, and respiratory departments from 2018 to 2023. Clinical isolates were obtained from all patients with AB infections in ICU, geriatrics, respiratory department, rehabilitation department, infectious diseases department, emergency department, cardiology department, and orthopedics of the hospital from 2018 to 2023. Retrospective analyses were performed on AB detection rates, strain origins, resistance rates to commonly used antimicrobial agents, and resistance gene features, comparing the antimicrobial resistance between clinically isolated strains and environmentally isolated strains. ResultsFrom 2018 to 2023, a total of 1 416 samples were collected from the hospital and a total of 272 strains of AB were detected, with a positive detection rate of 19.21%. The detection rate gradually decreased year-on-year (χ²_trend=45.290, P<0.001). The majority of samples originated from patient-contacted items (34.56%, 94/272), followed by shared items (26.84%, 73/272) and healthcare worker-contacted items (15.07%, 41/272). From 2018 to 2023, the resistance rate of AB on environmental surfaces and healthcare workers’ hands to commonly tested antibiotics in the hospital ranged from 10% to 40%. The resistance rates to cefotaxime (42.52%) and piperacillin (38.58%) were relative high, while the resistance to polymyxin E (1.57%), polymyxin B (2.36%), and doxycycline (3.94%) maintained low. The annual fluctuations in resistance to cefotaxime, piperacillin, ceftriaxone, tobramycin, doxycycline, minocycline and cotrimoxazole were statistically significant (all P<0.05). There were statistically significant differences in the resistance of clinical and environmental isolates to ampicillin/sulbactam, cefepime, ceftazidime, subamphetamine, meropenem, piperacillin, aztreonam, gentamicin, tobramycin, minocycline, ciprofloxacin, levofloxacin, and cotrimoxazole in the hospital from 2018 to 2023 (all P<0.05). The resistance rate of clinical isolates was generally high, especially to β-lactam and quinolone drugs, which were mostly above 80% [such as cefepime (93.86%), cefotaxime (97.37%), imipenem (98.25%), and ciprofloxacin (99.12%)]. The resistance rate of environmental isolated strains to similar antibiotics was relatively lower, mostly concentrated at 10%‒30%. The whole-genome sequencing of 34 carbapenem-resistant Acinetobacter baumannii (CRAB) strains isolated from the hospital environment in 2023 revealed that the main resistance mechanism was overexpression of efflux pumps (51.97%), followed by changes in target sites (32.46%). Among the 34 CRAB strains, carbapenem resistance genes OXA-23 and OXA-51 were detected in 6 strains (17.65%), while genes such as KPC, IMP, VIM, and SIM were not detected. ConclusionFrom 2018 to 2023, AB in the hospital environment exhibited high resistance rates to certain antimicrobial agents and carried multiple resistance genes, indicating a potential transmission risk. It is necessary to further strengthen bacterial resistance monitoring and hospital infection control, and use antibiotics reasonably.

Objective To analyze the correlation between the expression of soluble glycoprotein A(GPA)in plasma of healthy blood donors and anti-M and anti-"Mia"antibodies.Methods Plasma from healthy donors from February 9,2022 to February 15,2023 was collected:irregular antibody-negative NN type(group Ⅰ,n=118)and MM type(group Ⅱ,n=51),anti-M antibody positive NN type(group Ⅲ,n=145)and anti-"Mia"antibody positive companion type(group Ⅳ,n= 87),the GPA content in plasma of different individuals in 4 groups was detected,and the difference in GPA expression was analyzed by t-test.Results The average plasma GPA contents in groupsⅠ,Ⅱ,Ⅲ and Ⅳ were 9.941±0.252,10.97±0.256,5.139±0.129 and 4.28±0.139ng/ml,respectively.The average GPA content of groups Ⅰ and Ⅱ was higher,and the average GPA content of groups Ⅲ and Ⅳ was lower,and the differences were statistically significant(all P＜0.01).Conclusion The GPA content in plasma of healthy donors with anti-M and anti-"Mia"antibodies was significantly lower than that of the antibody-negative group.The results of this study lay a foundation for further investigation of whether GPA in plasma has the ability to neutralize anti-M and anti-"Mia"antibodies,improve disease diagnosis and safe blood transfusion.

Objective:To evaluate the anesthetic effect of transcutaneous electrical acupoint stimulation (TEAS)-erector spinal plane block (ESPB)-general anesthesia in elderly patients undergoing lumbar spine surgery.Methods:A total of 100 American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ elderly patients, aged 65-75 yr, with a body mass index of 19-27 kg/m 2, undergoing elective lumbar fusion internal fixation within two levels in the First Affiliated Hospital of Guangzhou University of Chinese Medicine from October 2023 to March 2024, were selected and divided into 2 groups ( n=50 each) using a random number table method: TEAS group (T group) and control group (C group). In T group, TEAS was performed at 30 min before anesthesia induction until the end of operation, then transcutaneous electrical stimulation of bilateral Hegu, Neiguan and Zusanli was performed for 2 consecutive days after surgery, once a day, 30 min per time. Electrodes were applied to the same acupoints without electrical stimulation in group C. After induction of general anesthesia, bilateral ESPB was performed under ultrasound guidance, and 0.375% ropivacaine 20 ml was injected on each side in both groups. Patient-controlled intravenous analgesia was carried out with sufentanil citrate from the end of surgery until 48 h after surgery. When VAS score≥4, tramadol was intravenously injected as rescue analgesic. The consumption of remifentanil and propofol, the total number of successfully delivered doses (D1) and the number of attempts (D2) within 48 h after operation, and the D1/D2 ratio and rescue analgesia were recorded. The concentrations of interleukin-6, interleukin-10, tumor necrosis factor-α and T-lymphocyte subsets (CD3 +, CD4 +, CD8 + ) were determined before stimulation of acupoints and at 24 and 48 h after surgery. The CD4 + /CD8 + ratio was calculated. Results:Compared with group C, the consumption of intraoperative remifentanil was significantly decreased, D1 and D2 were reduced, the D1/D2 ratio was increased, the rate of rescue analgesia was decreased, the serum concentrations of interleukin-6, interleukin-10 and tumor necrosis factor-α were decreased at each time point after operation, and the serum concentrations of CD3 + and CD4 + and CD4 + /CD8 + ratio were increased in group T ( P<0.05). Conclusions:Compared with combination of ESPB and general anesthesia, TEAS-ESPB-general anesthesia can provide better analgesic effect, reduce postoperative inflammatory responses and improve the immune function in elderly patients undergoing lumbar spine surgery.

Objective To explore the effect of transcutaneous electrical acupoint stimulation(TEAS)on perioperative analgesia in elderly patients undergoing lumbar fusion internal fixation.Methods Eighty-two elderly patients undergoing lumbar fusion internal fixation within two levels,57 males and 25 fe-males,aged 65-74 years,BMI 18.5-24.0 kg/m2,ASA physical status Ⅰ-Ⅲ,were randomly divided into two groups:TEAS group and control group,41 patients in each group.Both groups were given tracheal intubation intravenous general anesthesia.TEAS group was treated with TEAS from 30 minutes before anes-thesia induction to the end of the operation,and continued TEAS for 2 days after surgery,once a day,30 minutes once time,and the stimulation sites were bilateral Hegu,Neiguan,and Zusanli.In the control group,the electrodes were only connected at the same time point without electrical stimulation.Both groups were treated with bilateral erector spinae plane block(ESPB)under ultrasound guidance after anesthesia in-duction.PCIA was performed by connecting the analgesic pump after operation.HR and MAP before stimu-lation and at the time of skin incision were recorded.The dosage of propofol and remifentanil and the number of sufentanil additions during operation were recorded.The addition rate of sufentanil was calculated.The resting and activity VAS pain scores 2,4,8,12,24,and 48 hours after operation were recorded.First compression time of analgesic pump,the consumption of sufentanil 48 hours after operation,the ratio of ef-fective pressing times of analgesic pump to actual pressing times(D1/D2),rescue analgesia rate and ad-verse reactions were recorded.Results Compared with control group,HR was slowed down significantly and MAP was decreased significantly at the time of skin incision in TEAS group,the rate of sufentanil addi-tions,the activity VAS scores 2,4,8,12,24,and 48 hours after operation,the resting VAS pain scores 12,24,and 48 hours after operation in TEAS group were significantly decreased,the first compression time of analgesic pump was significantly prolonged,the consumption of sufentanil 48 hours after operation was significantly decreased,D1/D2 was significantly increased,the rate of rescue analgesia,nausea and vomi-ting,dizziness were significantly decreased(P＜0.05).Conclusion TEAS can provide better analgesia for elderly patients undergoing lumbar fusion internal fixation,reduce the use of opioids,prolong the postop-erative analgesia time and reduce the incidence of postoperative adverse reactions.

Objectives: . The annual prevalence of chronic rhinosinusitis (CRS) is increasing, and the lack of effective treatments imposes a substantial burden on both patients and society. The formation of nasal polyps in patients with CRS is closely related to tissue remodeling, which is largely driven by the epithelial-mesenchymal transition (EMT). MicroRNA (miRNA) plays a pivotal role in the pathogenesis of numerous diseases through the miRNA-mRNA regulatory network; however, the specific mechanism of the miRNAs involved in the formation of nasal polyps remains unclear. Methods: . The expression of EMT markers and Smad3 were detected using western blots, quantitative real-time polymerase chain reaction, and immunohistochemical and immunofluorescence staining. Differentially expressed genes in nasal polyps and normal tissues were screened through the Gene Expression Omnibus database. To predict the target genes of miR-145-5p, three different miRNA target prediction databases were used. The migratory ability of cells was evaluated using cell migration assay and wound healing assays. Results: . miR-145-5p was associated with the EMT process and was significantly downregulated in nasal polyp tissues. In vitro experiments revealed that the downregulation of miR-145-5p promoted EMT. Conversely, increasing miR-145-5p levels reversed the EMT induced by transforming growth factor-β1. Bioinformatics analysis suggested that miR-145-5p targets Smad3. Subsequent experiments confirmed that miR-145-5p inhibits Smad3 expression. Conclusion . Overall, miR-145-5p is a promising target to inhibit nasal polyp formation, and the findings of this study provide a theoretical basis for nanoparticle-mediated miR-145-5p delivery for the treatment of nasal polyps.

Objective This study seeks to conduct a comprehensive visual analysis of the current research status and de-velopmental trends concerning party building in Chinese hospitals.The goal is to map the research landscape,pinpoint existing trends,and predict upcoming focal points in the future.Methods We searched the full-text database of Utilizing the China Na-tional Knowledge Infrastructure(CNKI)employing"hospital"and"Party building philosophy"as the search terms,retrieving the articles published between 1993 and 2023.After reviewing and screening the retrieved literature,we extracted key data and conducted a bibliometric analysis using CNKI's visualization tool,VOS viewer and Cite Space.Results A total of 1 831 publi-cations were included.A significant surge in publication volume was observed since 2017.Notable journals such as"Chinese Hospital"and"Chinese Hospital Management"were prominent in this domain.Equally,research institutions like Guangdong Provincial People's Hospital and the First Affiliated Hospital of Hunan University of Chinese Medicine emerged as substantial contributors.The research team at Xuanwu Hospital of Capital Medical University was identified as a leading force in this field.Keywords like"public hospitals,""deep integration,""guidance with Party building philosophy,""high-quality development,"and"Healthy China"increased in number in recent years.Conclusion The research in hospital Party building has been experi-encing sustained and vigorous growth since 2017.With the strategic"Healthy China"initiative,studies focus on"public hospi-tals"are expected to become emerging research hotspots,indicating a vibrant future for this area of study.

The human oral microbiome harbors one of the most diverse microbial communities in the human body,playing critical roles in oral and systemic health.Recent technological innovations are propelling the characterization and manipulation of oral microbiota.High-throughput sequencing enables comprehensive taxonomic and functional profiling of oral microbiomes.New long-read platforms improve genome assembly from complex samples.Single-cell genomics provides insights into uncultured taxa.Advanced imaging modalities including fluorescence,mass spectrometry,and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing resolution.Fluorescence techniques link phylogenetic identity with localization.Mass spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for classification.Culturomics facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput approaches.Ongoing integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly,gene expression,metabolites,microenvironments,virulence mechanisms,and microbe-host interfaces in the context of health and disease.However,significant knowledge gaps persist regarding community origins,developmental trajectories,homeostasis versus dysbiosis triggers,functional biomarkers,and strategies to deliberately reshape the oral microbiome for therapeutic benefit.The convergence of sequencing,imaging,cultureomics,synthetic systems,and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict,prevent,diagnose,and treat associated oral diseases.

The human oral microbiome harbors one of the most diverse microbial communities in the human body,playing critical roles in oral and systemic health.Recent technological innovations are propelling the characterization and manipulation of oral microbiota.High-throughput sequencing enables comprehensive taxonomic and functional profiling of oral microbiomes.New long-read platforms improve genome assembly from complex samples.Single-cell genomics provides insights into uncultured taxa.Advanced imaging modalities including fluorescence,mass spectrometry,and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing resolution.Fluorescence techniques link phylogenetic identity with localization.Mass spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for classification.Culturomics facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput approaches.Ongoing integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly,gene expression,metabolites,microenvironments,virulence mechanisms,and microbe-host interfaces in the context of health and disease.However,significant knowledge gaps persist regarding community origins,developmental trajectories,homeostasis versus dysbiosis triggers,functional biomarkers,and strategies to deliberately reshape the oral microbiome for therapeutic benefit.The convergence of sequencing,imaging,cultureomics,synthetic systems,and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict,prevent,diagnose,and treat associated oral diseases.