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 comparatively analyze the clinical characteristics of primary bilateral macronodular adrenal hyperplasia(PBMAH)and adrenal cortisol-producing Adenoma(CPA),and enhance the understanding of two diseases.Methods The clinical data of 85 PBMAH patients(PBMAH group)and 195 CPA patients(CPA group)diagnosed at Department of Endocrinology,the First Medical Center of Chinese PLA General Hospital,from September 2014 to August 2024 were retrospectively analyzed.The demographic characteristics,comorbidities,biochemical indicators,adrenocorticotropic hormone-cortisol(ACTH-F)levels,and adrenal imaging features and treatment conditions were compared between the two groups.Results(1)General characteristics:Compared with CPA group,PBMAH group had older age at diagnosis and a higher proportion of male patients.(2)Clinical characteristics:Compared with CPA group,PBMAH group had a longer disease duration,a higher proportion of subclinical Cushing's syndrome(CS),and a higher proportion of hypertension,impaired glucose tolerance/diabetes,bone mass reduction or osteoporosis,with higher serum potassium levels,and the differences were statistically significant(P<0.01).(3)Hormone levels:Both PBMAH and CPA groups showed ACTH-F rhythm disorder,significantly increased cortisol levels and suppressed ACTH.Compared with PBMAH group,CPA group had stronger autonomous cortisol secretion ability,manifested by increased midnight serum cortisol(F0:00),16:00 serum cortisol(F16:00),24-hour urinary free cortisol(24 h UFC)levels and lower 8:00 serum ACTH(ACTH8:00)and 16:00 serum ACTH(ACTH16:00)(P<0.01).After low-dose dexamethasone suppression test(LDDST),CPA group showed lower suppression rates of ACTH and cortisol,and higher proportions of paradoxical elevation in serum cortisol and 24 h UFC compared with PBMAH(P<0.01).Conclusions PBMAH has a longer disease course and higher proportions of comorbid metabolic disorders than CPA,mostly manifested as subclinical Cushing's syndrome.CPA has stronger autonomous cortisol secretion ability,with cortisol less likely to be suppressed after LDDST and more obvious paradoxical elevation of cortisol and 24 h UFC.

Objective To characterize multimodal metabolic disorders in subclinical Cushing's syndrome(SCS)patients with different cortisol levels,providing a reference for clinical diagnosis and treatment.Methods A retrospective analysis was conducted on the clinical data of 165 SCS patients diagnosed at the First Medical Center of Chinese PLA General Hospital due to adrenal masses from January 2014 to October 2024.Using the serum cortisol levels after the midnight 1 mg dexamethasone suppression test(1 mg DST)as the cut-off point,SCS patients were divided into high-level group(1 mg DST-F>138 nmol/L,n=96)and low-level group(50 nmol/L<1 mg DST-F≤138 nmol/L,n=69).The differences in age,gender,body mass index(BMI),blood pressure,glucolipid metabolism indices,electrolytes,hormone levels,and imaging features of adrenal adenoma(such as CT values)were compared between the two groups.Multivariate linear regression was used to analyze the correlation between CT values and metabolic indices.Results Compared with low-level group,patients in high-level group were younger(54.0±11.3 vs.57.7±10.3,P=0.034),while there were no statistically significant differences in gender ratio or BMI between the two groups(P>0.05).Both groups exhibited decreased adrenocorticotropic hormone(ACTH)levels and disrupted circadian rhythm.Compared with low-level group,high-level group showed significantly higher F0:00 levels[250.00(170.07,422.53)nmol/L vs.110.00(82.74,133.90)nmol/L]and 24-hour urinary free cortisol(24 h UFC)[568.40(377.80,875.45)nmol/24 h vs.369.40(265.40,494.69)nmol/24 h](P<0.001),with no significant differences in serum F8:00,or 1 mg DST ACTH0:00 levels(P>0.05).Except for the fasting C-peptide level in the high-level group being higher than that in low-level group[(2.88±1.01)ng/ml vs.(2.46±0.78)ng/ml,P=0.024],there were no significant differences in blood pressure,blood lipids,glycated hemoglobin(HbA1c),fasting blood glucose,fasting insulin,serum electrolytes,uric acid,and other indices between the two groups(P>0.05).The CT value of adrenal adenoma during contrast-enhanced scanning was higher in high-level group[80.00(17.80,93.00)Hu vs.52.00(35.50,75.00)Hu,P=0.006]compared with low-level group.Multivariate linear regression analysis revealed that diastolic blood pressure was positively correlated with CT values of adrenal adenomas in both plain scanning(β=0.49,95%CI 0.09-0.90)and contrast-enhanced scanning(β=2.08,95%CI 0.76-3.39),while triglyceride levels were negatively correlated with plain scanning CT values(β=-5.77,95%CI-10.88--0.66).Conclusion Patients with SCS at different cortisol levels differ in age,fasting C-peptide levels,and CT values.CT values may serve as potential imaging markers to assess metabolic risk in SCS patients.

Objective To construct a prediction model for in-hospital mortality in the elderly(≥65 years)patients undergoing unsynchronous cardioversion in ICU and to evaluate its effectiveness.Methods A retrospective study was conducted on 276 elderly eligible patients in the ICU of the Ninth and the First Medical Centers of Chinese PLA General Hospital between June 2022 and August 2024.According to their clinical outcomes,they were divided into a non-in-hospital dead group(111 cases)and an in-hospital dead group(165 cases).Clinical data were collected,and pre-dictive factors for in-hospital mortality were screened.And then a nomogram prediction model was developed based on the obtained predictive factors,which was evaluated with ROC curve and deci-sion curve analyses.Results When compared to the non-in-hospital dead group,the in-hospital dead group had significantly higher heart rate,ratio of hemodialysis,and levels of alanine amin-otransferase,aspartate aminotransferase,lactate dehydrogenase,alkaline phosphatase,serum cre-atinine,blood glucose,lactate,low base excess,sequential organ failure assessment(SOFA)score,model for end-stage liver disease score,and larger proportions of ventricular fibrillation/flutter and structural heart disease induced by pulseless ventricular tachycardia,and had significantly lower Glasgow Coma Scale(GCS)(P＜0.05).Multivariate logistic regression analysis identified body temperature＞37℃(OR=0.426,95％CI:0.198-0.915,P=0.029),chronic obstructive pulmonary disease(OR=2.333,95％CI:1.217-4.473,P=0.011),GCS score(OR=0.622,95％CI:0.410-0.944,P=0.026),hemoglobin(OR=0.817,95％CI:0.715-0.934,P=0.003),lactate(OR=1.365,95％CI:1.174-1.587,P=0.000),heart rate＞100 bpm(OR=2.757,95％CI:1.397-5.441,P=0.003),and SOFA score(OR=1.112,95％CI:1.032-1.198,P=0.005)as pre-dictors of in-hospital mortality.ROC curve analysis showed an AUC value of above indicators combined together in the prediction was 0.797,with a sensitivity of 76.97％and a specificity of 65.77％.Calibration curve analysis demonstrated good consistency between predicted and observed outcomes.Decision curve analysis indicated favorable clinical utility of the model.Conclusion This study identifies independent risk factors for in-hospital mortality among elderly patients in the ICU who underwent asynchronous cardioversion.Based on these factors,a nomo-gram model is established,demonstrating good discrimination,calibration,and model fit,with high clinical applicability.

Objective To propose a brain electrical phase prediction method based on long short-term memory network(LSTM)to improve the accuracy and robustness of phase synchronization prediction in transcranial magnetic stimulation(TMS).Methods First,an LSTM consisting of an input layer,an LSTM layer,an ReLU activation layer,a fully connected layer and a regression layer was constructed to capture the EEG signal features through the synergistic action of input gates,forgetting gates and output gates.Second,eye-open resting-state EEG data from 30 healthy subjects were trained using the LSTM to obtain a predictive model for EEG signal and EEG phase prediction.Finally,the LSTM method and the traditional autoregressive(AR)method were compared in terms of the phase prediction errors at the overall and individual levels and the prediction performance for peaks and troughs.A regression model was used to explore the relationships between instantaneous EEG amplitude,signal-to-noise ratio and phase prediction error with the LSTM method.Results The LSTM method achieved a total phase prediction error of 0.04°±5.69°,which was lower than that of the traditional AR method(-3.36°±51.13°).For each subject,the LSTM method demonstrated superior phase prediction accuracy compared to the traditional AR method(P＜0.001).The accuracy for predicting peaks(troughs)by the LSTM method(about 89％)was higher than that by the traditional AR method(about 10％).Unlike the traditional AR method,the LSTM method didnot result in linear relationships between instantaneous EEG amplitude,signal-to-noise ratio and phase prediction error,with Pvalues being 0.58 and 0.18,respectively.Conclusion The LSTM-based brain electrical phase prediction method shows high accuracy and robustness when used for EEG phase-synchronized TMS.[Chinese Medical Equipment Journal,2025,46(3):1-8]

Objective:To evaluate the applicability of a new anti-G capability assessment trainer (AG-CAT) in high-performance (HP) anti-G maneuver training and positive pressure breathing for high-G (PHP) training for pilots.Methods:A total of 142 fighter pilots who were subjected to anti-G maneuver training at Dujiangyan Special Crew Sanatorium of PLA Air Force between January and November 2023 were enrolled. According to the Guidelines for Aviation Physiological Training, 123 pilots underwent both HP anti-G maneuver training and PHP positive pressure breathing training, 15 received only HP training, and 4 received only PHP training. Based on the training devices used, these pilots were divided into AG-CAT group and an anti-G and anti-hypoxia capability detection instrument (GHyCDI) group. The 2 groups were compared regarding the pedal force of lower limbs, blood pressure, and improvement of +G z tolerance during training. Results:Of the 138 pilots undergoing HP training, 88 used AG-CAT and 50 used GHyCDI. One hundred and twenty-seven pilots participated in PHP training, with 73 in the AG-CAT group and 54 in the GHyCDI group. During HP training, the pedal force of left lower limbs in the AG-CAT group was greater than that of the right limbs and of the GHyCDI group ( t=4.38, 2.64, P<0.001, =0.009). In PHP training, the AG-CAT group exhibited greater pedal force in left limbs than in right ones, while the GHyCDI group showed an opposite trend ( t=2.25, 3.37, P=0.029, 0.002). Systolic and diastolic blood pressures during HP training (with or without anti-G suits) were higher in the AG-CAT group than in the GHyCDI group ( t=3.50, 3.72, 2.55, 4.21, P=0.001,<0.001,=0.012,<0.001). Similarly, during PHP training, both systolic and diastolic pressures were higher in the AG-CAT group ( t=2.03, 3.81, P=0.045,<0.001). The AG-CAT group demonstrated superior improvements in +G z tolerance during HP training (without/with anti-G suits: Z=2.14, 3.21, P=0.049, 0.001) and PHP training ( Z=2.56, P=0.010) compared with the GHyCDI group. Conclusions:AG-CAT shows excellent applicability in aviation physiological training of pilots. Its ergonomic design, practical functionalities and enhanced compatibility with personnel protective equipment can better meet training requirements compared to conventional devices.

Objective::To report a fetus with ARCN1-related syndrome caused by a novel de novo heterozygous variant, highlighting the importance of early genetic diagnosis in prenatal care. Methods::The clinical and genetic data of a fetus with a complex combination of clinical signs and a novel de novo heterozygous variant were collected and have been summarized in this study. The potential pathogenic variant was identified throughout the whole exome sequencing and the effects of candidate variants were further validated by a minigene splicing assay. Results::Prenatal systematic ultrasound detected fetal growth restriction. Genetic analysis identified a novel de novo heterozygous variant within the ARCN1 gene—c.1241 +5G>A-located in intron 8. In vitro minigene splicing assays demonstrated that the variant led to two abnormal transcripts. The longer transcript retained 189 base pairs of intron 8, resulting in a truncated protein of 414 amino acids (p.Ser415*). The shorter transcript involved exon 8 skippings, producing a truncated protein of 407 amino acids (p.Ile378Serfs*31). Conclusion::A novel de novo heterozygous variant of the ARCN1 gene, namely NM_001655.5: c.1241 +5G>A, was discovered and identified in a fetus with rhizomelic short stature, microretrognathia, and developmental delays.

Objective::To evaluate the diagnostic efficacy and clinical application of the Obstetrical Chinese Disseminated Intravascular Coagulation (DIC) Scoring System (OCDSS).Methods::This study is a retrospective study that collected 1063 cases from Wuhan Union Hospital, Yichang Central People’s Hospital, and the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture between July 2017 and June 2024. These cases were divided into DIC and non-DIC groups based on score standard. Diagnosis of DIC, the rate of hysterectomy, neonatal mortality, and severe asphyxia are the main outcome measures. All the laboratory indicators are all determined by clinical laboratory department of the hospital. Data were expressed as mean ± standard deviation or median (interquartile range) and frequencies. Independent sample t-test or non-parametric test were used to compare measurement data, while the chi-square test was used for count data. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to test the predictive accuracy. Using univariate and multivariate logistic regression analysis to study the high-risk factors. P < 0.050 indicates a statistical significance. Results::Of 1063 participants in this study, 29 participants (2.73%) were diagnosed with obstetrical DIC by OCDSS score standard, and all the participants were diagnosed as DIC with underlying disease. When the Takao, Clark, and Erez score standard is the "gold standard", the OCDSS score standard always shows good sensitivity and specificity, with all the AUC over 0.75. OCDSS score standard also has better predictive of hysterectomy (68.18%, 91.07%, 0.872), severe neonatal asphyxia and death (79.17%, 75.07%, 0.842) than the other three score standards. All the indicators included in the OCDSS score standard contributed to the DIC diagnosis (all the P < 0.001). The indicators in the DIC group were more abnormal than the non-DIC group (all the P < 0.001). Conclusion::OCDSS is a first score standard, especially for pregnancies, it considers the underlying disease, clinical symptoms, and laboratory results. This score system shared a good diagnosis performance for DIC in the Chinese population and may help clinicians make timely decisions.

Objective::To report a fetus with ARCN1-related syndrome caused by a novel de novo heterozygous variant, highlighting the importance of early genetic diagnosis in prenatal care. Methods::The clinical and genetic data of a fetus with a complex combination of clinical signs and a novel de novo heterozygous variant were collected and have been summarized in this study. The potential pathogenic variant was identified throughout the whole exome sequencing and the effects of candidate variants were further validated by a minigene splicing assay. Results::Prenatal systematic ultrasound detected fetal growth restriction. Genetic analysis identified a novel de novo heterozygous variant within the ARCN1 gene—c.1241 +5G>A-located in intron 8. In vitro minigene splicing assays demonstrated that the variant led to two abnormal transcripts. The longer transcript retained 189 base pairs of intron 8, resulting in a truncated protein of 414 amino acids (p.Ser415*). The shorter transcript involved exon 8 skippings, producing a truncated protein of 407 amino acids (p.Ile378Serfs*31). Conclusion::A novel de novo heterozygous variant of the ARCN1 gene, namely NM_001655.5: c.1241 +5G>A, was discovered and identified in a fetus with rhizomelic short stature, microretrognathia, and developmental delays.

Objective::To evaluate the diagnostic efficacy and clinical application of the Obstetrical Chinese Disseminated Intravascular Coagulation (DIC) Scoring System (OCDSS).Methods::This study is a retrospective study that collected 1063 cases from Wuhan Union Hospital, Yichang Central People’s Hospital, and the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture between July 2017 and June 2024. These cases were divided into DIC and non-DIC groups based on score standard. Diagnosis of DIC, the rate of hysterectomy, neonatal mortality, and severe asphyxia are the main outcome measures. All the laboratory indicators are all determined by clinical laboratory department of the hospital. Data were expressed as mean ± standard deviation or median (interquartile range) and frequencies. Independent sample t-test or non-parametric test were used to compare measurement data, while the chi-square test was used for count data. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to test the predictive accuracy. Using univariate and multivariate logistic regression analysis to study the high-risk factors. P < 0.050 indicates a statistical significance. Results::Of 1063 participants in this study, 29 participants (2.73%) were diagnosed with obstetrical DIC by OCDSS score standard, and all the participants were diagnosed as DIC with underlying disease. When the Takao, Clark, and Erez score standard is the "gold standard", the OCDSS score standard always shows good sensitivity and specificity, with all the AUC over 0.75. OCDSS score standard also has better predictive of hysterectomy (68.18%, 91.07%, 0.872), severe neonatal asphyxia and death (79.17%, 75.07%, 0.842) than the other three score standards. All the indicators included in the OCDSS score standard contributed to the DIC diagnosis (all the P < 0.001). The indicators in the DIC group were more abnormal than the non-DIC group (all the P < 0.001). Conclusion::OCDSS is a first score standard, especially for pregnancies, it considers the underlying disease, clinical symptoms, and laboratory results. This score system shared a good diagnosis performance for DIC in the Chinese population and may help clinicians make timely decisions.