Objectives: . This study aimed to explore the role of the Pcdh15 gene in hearing maintenance and to examine the effects of its deficiency on cochlear structure, cochlear function, and hearing loss in mice. Methods: . CRISPR/Cas9 technology was used to generate Pcdh15 knockout (KO) mice. Auditory function was evaluated using hearing tests, while histological approaches were employed to assess morphological changes in cochlear hair cells and spiral ganglion neurons (SGNs). RNA sequencing (RNA-seq) was performed on cochlear tissue from postnatal day 18 (P18) wild-type (WT) and Pcdh15 KO mice to identify differentially expressed genes (DEGs). These DEGs were subjected to functional annotation and pathway analysis, with particular emphasis on oxidative phosphorylation (OXPHOS). Reactive oxygen species (ROS) levels were quantified using flow cytometry and DCFH-DA assays. Results: . Pcdh15 KO mice exhibited progressive sensorineural hearing loss, which worsened to profound deafness by P18. Notably, cochlear hair cells and SGNs showed substantial loss and pronounced morphological abnormalities, particularly within the basal high-frequency region. RNA-seq analysis identified 1,359 DEGs, including 1,024 downregulated and 335 upregulated genes. Pathway analysis indicated that Pcdh15 deficiency was associated with inhibition of the OXPHOS pathway, potentially disrupting mitochondrial respiratory chain complexes I, III, IV, and V and thereby impairing energy production and ATP metabolism. In addition, early-stage cochleae from KO mice demonstrated elevated ROS levels and increased oxidative stress, suggesting that redox imbalance may contribute to hearing damage. Conclusion . Pcdh15 plays a critical role in hearing maintenance. Its deficiency is associated with severe hearing loss and marked cochlear abnormalities, which are linked to inhibition of OXPHOS, disruption of energy metabolism, and exacerbation of oxidative stress. Together, these findings provide new insights into the mechanisms underlying hearing loss and suggest potential targets for therapeutic intervention.

Objective To develop a novel protective ventilator circuit component and to verify its performance by water seal and anti-splash experiments.Methods A novel protective ventilator circuit component had a design scheme with the multifunctional joint,and consisted of a tee connection tube,an isolation sleeve and a stop sleeve,of which,the tee connection tube was made of polyethylene polymer material and the others were made of silicone material.The tee connection tube had a T-shaped structure with two standard connection ports,which was composed of an adapter,a sealing cap,a plug and a sealing ring;the isolation sleeve was in the shape of a cylinder with a raised bottom,which was inserted into the adapter;the stop sleeve was located in the isolation sleeve,with an inverted frustum of a cone at the bottom and a rounded hole in the middle of the inverted frustum.An open ventilator circuit tube was involved in the performance verification of the circuit component developed.In the water seal experiment,sputum aspiration was simulated and the heights of the liquid level drop in the L-shaped tubes were compared after sputum aspiration.In the anti-splash experiment,the infection rates on the surfaces of the sterile hole towels and gloves were calculated.Results Water seal experiment showed after sputum aspiration the open ventilator circuit tube had the liquid level at the L-shaped tube higher significantly than that of the circuit component;the anti-splash experiment indicated sputum aspiration resulted in the occurance of the splashing out of the secretion and 77.5%infection rate by the open ventilator circuit tube,while no splashing out and 0%infection rate by the circuit component developed.Conclusion The novel protective ventilator circuit component behaves well in sealing and anti-splashing,and thus is worthy of clinical application for sputum aspiration.[Chinese Medical Equipment Journal,2025,46(4):113-117]

Purpose To investigate the relationship between FN1 expression and clinical and pathologic features of laryngeal squamous cell carcinoma(LSCC)and the expression of tumor-associated macrophages(TAMs).Methods LSCC datasets GSE33232 and GSE84957 were analyzed and screened the differentially expressed gene FN1,and draw the receiver operating characteristic(ROC)curve.Bioinformatics analysis of FN1 expression,and prognosis in LSCC was performed.To investigate the effect of down-regulating FN1 expression in TU177 cells on the malignant bio-logical behavior of LSCC,we performed a scratch wound healing assay and a Transwell chamber assay to assess the effect of FN1 on cell proliferation,migration,and invasion in vitro.Immunohistochemical(IHC)staining was per-formed to detect the expression of FN1 and CD 163 in LSCC tissues.Results Analysis of the GSE33232 and GSE84957 datasets and online databases showed that FN1 was significantly overexpressed in LSCC tissues(P＜0.05),and patients with high FN1 expression had a significantly lower recurrence-free survival rate(HR=1.6,P=0.017).After transfection with si-FN1,the expression of FN1 in TU177 cells was significantly reduced(0.34±0.02 vs 1.00±0.03,P＜0.01).Compared with the control group,the down-regulation of FN1 expression inhibited the in vitro migra-tion(56.1±3.1 vs 19.23±1.0)and invasion(480±23 vs 288±20)ability of TU177 cells(both P＜0.01).Im-munohistochemistry findings showed that FN1 was highly expressed in both the tumor parenchyma(nest)and stromal cells of LSCC tissue,with a statistically significant difference[52.1％(24/46)vs 71.7％(33/46),P＜0.001].It was found that high expression of N-FN1 was associated with patients' pathological grade and lymph node metastasis(P＜0.05),while high expression of S-FN1 was associated with patients' age,lymph node metastasis,and TNM stage(P＜0.05).In addition,the co-expression of FN1 and CD163 was correlated with patients' pathological grad-ing,lymph node metastasis,and TNM stage(all P＜0.05).Conclusion FN1 and CD163 exhibit high expression levels in LSCC patients,which are closely associated with malignant progression,including invasion and metastasis.Notably,during LSCC progression,there may be a potential synergistic interaction between FN1 and CD 163-positive macrophages in the tumor microenvironment.

[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].

[This corrects the article DOI: 10.1016/j.apsb.2019.01.013.].

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

OBJECTIVE: To explore the implementation effect of hour-1 bundle for sepsis patients based on crisis resource management (CRM) system. METHODS: A historical control study was conducted. The hour-1 bundle for sepsis based on CRM was used to train 24 nurses in the emergency department from October 2022 to March 2023. Clinical data of sepsis patients admitted to the emergency department of the First People's Hospital of Zunyi from April 2022 to September 2023 were collected. The patients were divided into three groups based on different stages of CRM system construction: control group (before construction, from April to September in 2022), improvement group (during construction, from October 2022 to March 2023) and observation group (after construction, from April to September in 2023). The baseline data, implementation rate of hour-1 bundle [including blood culture, antibiotic usage, blood lactic acid (Lac) detection, fluid resuscitation, hypertensors usage], identification and diagnosis time, and prognosis parameters [including correction rate of hypoxemia, intensive care unit (ICU) occupancy rate, and 28-day survival rate]. Sepsis cognition survey and non-technical skill (NTS) evaluation of nurses in emergency department were conducted before and after training. RESULTS: Finally 43 cases were enrolled in the control group, improvement group and observation group, respectively. There was no statistically significant difference in baseline data including the gender, age, primary site, heart rate, systolic blood pressure, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, mechanical ventilation ratio among the three groups with comparability. With the gradual improvement of the CRM system, the implementation rate of 1-hour bundle was gradually increased, and the implementation rate in the control group, improvement group and observation group were 65.12% (28/43), 74.42% (32/43) and 88.37% (38/43), respectively, with statistically significant difference (P < 0.05). It was mainly reflected in the completion rate of blood culture, antibiotic usage rate, Lac detection rate and hypertensors usage rate within 1 hour, which were significantly higher in the observation group than those in the control group [completion rate of blood culture: 90.70% (39/43) vs. 62.79% (27/43), antibiotic usage rate: 88.37% (38/43) vs. 60.47% (26/43), Lac detection rate: 93.02% (40/43) vs. 72.09% (31/43), hypertensors usage rate: 88.37% (38/43) vs. 60.47% (26/43), all P < 0.05]. The fluid resuscitation rates within 1 hour in the three groups were all over 90%, with no statistically significant difference among the three groups. The recognition and diagnosis time in the observation group was significantly shorter than that in the control group and the improvement group (hours: 0.41±0.15 vs. 0.61±0.21, 0.51±0.18, both P < 0.05), the correction rate of hypoxemia and 28-day survival rate were significantly higher than those in the control group [correction rate of hypoxemia: 95.35% (41/43) vs. 74.42% (32/43), 28-day survival rate: 83.72% (36/43) vs. 60.47% (26/43), both P < 0.05], and ICU occupancy rate was significantly lower than that in the control group [72.09% (31/43) vs. 93.02% (40/43), P < 0.05]. After training in the CRM system, the score of the sepsis awareness survey questionnaire for emergency department nurses was significantly increased as compared with before training (60.42±5.29 vs. 44.17±9.21, P < 0.01), and NTS also showed significant improvement. CONCLUSION CRM plays a significant role in promoting the implementation of sepsis hour-1 bundle, which can improve the implementation rate of hour-1 bundle and NTS of medical staff, effectively improve patients' hypoxemia, reduce patients' ICU occupancy rate and 28-day risk of death.
Humans ; Sepsis/therapy* ; Emergency Service, Hospital ; Patient Care Bundles ; Intensive Care Units ; Female ; Male ; Middle Aged

The medulla oblongata,situated at the caudal portion of the brainstem,serves as a critical regulatory center responsible for maintaining fundamental vital functions including respiratory and cardiovascular homeostasis.As a pivotal hub within the autonomic nervous system,it orchestrates the coordinated control of afferent and efferent neural pathways.Dysfunction of this region may precipitate life-threatening cardiorespiratory arrest,associated with substantial mortality rates.This case report presents a patient who developed acute extensive anterior myocardial infarction during treatment with dual antiplatelet therapy and moderate-intensity statins following acute medullary infarction.It is hypothesized that the pathogenesis may involve the acceleration of plaque erosion by the stroke-heart syndrome.This clinical case provides valuable insights into the complex neurocardiac interplay,particularly highlighting the imperative for enhanced recognition of brain-heart axis interactions in cerebrovascular pathology.

Objective To explore the impact of preoperative fibrinogen levels on the 1-year adverse outcomes after endovascular revascularization in patients with diabetes complicated with lower extremity arteriosclerosis obliterans(LEASO).Methods We collected the baseline clinical data of 289 patients with diabetes complicated with LEASO,who were admitted to The First Affiliated Hospital of Xi'an Jiaotong University from May 2020 to December 2022 for endovascular revascularization.All patients were followed up for 13 to 24 months after interventional therapy,with the follow-up information including major adverse cardiovascular events(MACEs)such as all-cause death,acute myocardial infarction and acute stroke,as well as major adverse lower extremity events(MALEs)such as rest pain in the lower extremities,ulcers or skin defects,gangrene,reocclusion and amputation.A multivariable Cox regression model was used to analyze the related risk factors for adverse outcomes 1 year after endovascular revascularization in patients with diabetes complicated with LEASO,and receiver operating characteristic(ROC)curves were constructed to evaluate the predictive efficacy and optimal cutoff value of fibrinogen levels for endpoint events,and Kaplan-Meier survival curves were drawn.Sensitivity analysis was made to assess the differences in the impact of fibrinogen on endpoint events across various subgroups.Results We recruited a total of 289 patients(55 patients in MACEs and 234 in non-MACEs;68 patients in MALEs and 221 in non-MALEs),with a mean age of 67.6±9.3 years,including 215 males.Multivariate Cox regression analysis showed that elevated plasma fibrinogen was an independent risk factor for MACEs(HR=1.250,95％CI:1.053-1.484,P=0.011)and all-cause death(HR=1.297,95％CI:1.030-1.633,P=0.027)in the cohort followed up 1 year after interventional therapy,but had no significant impact on the occurrence of MALEs(P=0.625).Baseline plasma fibrinogen level 4.32 g/L was the optimal cutoff value for predicting MACEs(sensitivity=0.673,95％CI:0.582-0.767;specificity=0.688,95％CI:0.562-0.775)and all-cause death(sensitivity=0.679,95％CI:0.483-0.880;specificity=0.651,95％CI:0.465-0.755).The AUC for predicting MACEs and all-cause death after interventional therapy was 0.652(95％CI:0.564 2-0.739 1)and 0.619(95％CI:0.507-0.733),respectively.After a median follow-up of 14.03 months,patients with preoperative fibrinogen level ≥ 4.32 g/L had a significantly higher risk of MACEs and all-cause death compared to patients with preoperative fibrinogen＜4.32 g/L(P＜0.001),and there were no significant differences in different subgroups,including gender(male/female,interaction P=0.836),age(＜65 years/≥65 years,interaction P=0.211),smoking status(never smoked/current or former smoker,interaction P=0.779),chronic kidney disease(yes/no,interaction P=0.360),and heart failure(yes/no,interaction P=0.114).Conclusion Preoperative plasma fibrinogen≥4.32 g/L is an effective indicator for predicting MACEs and all-cause mortality following endovascular revascularization in patients with diabetes and LEASO.