Background: Hearing loss (HL) is one of the most common sensory disorders, affecting over 5-8% of the world's population. Approximately half of HL cases are attributed to genetic factors. In hereditary deafness, about 75-80% is inherited through autosomal recessive inheritance, and common pathogenic genes include GJB2 and SLC26A4. Pathogenic variants in the SLC26A4gene are the leading cause of hereditary hearing loss in humans, second only to the GJB2 gene. Variants in the SLC26A4gene cause hearing loss, which can be non-syndromic autosomal recessive deafness (DFNB4, OMIM #600791) associated with enlarged vestibular aqueduct (EVA) or Pendred syndrome (Pendred, OMIM #605646). DFNB4 is characterized by sensorineural hearing loss combined with EVA or less common cochlear malformation defect. Pendred syndrome is characterized by bilateral sensorineural hearing loss with EVA and an iodine defect that can lead to thyroid goiter. Currently, it is known that EVA is associated with variants in the SLC26A4 gene and is a penetrant feature of SLC26A4-related HL. Predominant mutations in these genes differ significantly across populations. For instance, predominant SLC26A4 mutations differ among populations, including p.T416P and c.1001G>A in Caucasians, p.H723R in Japanese and Koreans, and c.919-2A>G in Han Taiwanese and Han Chinese. On the other hand, there has been no study of hearing loss related to SLC26A4 gene variants among Mongolians, which is the basis of our research. Aim: We aimed to identify the characteristics of the SLC26A4 gene variants in Mongolian people with Enlarged vestibular aqueduct and Mondini malformation. Materials and Methods: In 2022-2024, We included 13 people with hearing loss and enlarged vestibular aqueduct, incomplete cochlea (1.5 turns of the cochlea with cystic apex- incomplete partition type II- Mondini malformation) were examined by CT scan of the temporal bone in our study. WES (Whole exome sequencing) analysis was performed in the Genetics genetic-laboratory of the National Taiwan University Hospital. Results: Genetic analysis revealed 26 confirmed pathogenic variants of bi-allelic SLC26A4 gene of 8 different types in 13 cases, and c.919-2A>G variant was dominant with 46% (12/26) in allele frequency, and c.2027T>A (p.L676Q) variant 19% (5/26), c.1318A>T(p.K440X) variant 11% (3/26), c.1229C>T (p.T410M) variant 8% (2/26) ) , c.716T>A (p.V239D), c.281C>T (p.T94I), c.1546dupC, and c.1975G>C (p.V659L) variants were each 4% (1/26)- revealed. Two male children, 11 years old (SLC26A4: c.919-2A>G) and 7 years old (SLC26A4: c.919-2A>G:, SLC26A4: c.2027T>A (p.L676Q))had history of born normal hearing and progressive hearing loss. Conclusions 1. 26 variants of bi-allelic SLC26A4 gene mutation were detected in Mongolian people with EVA and Mondini malformation, and c.919-2A>G was the most dominant allele variant, and rare variants such as c.1546dupC, c.716T>A (p.V239D) were detected. 2. Our study shows that whole-exome sequencing (WES) can identify gene mutations that are not detected by polymerase chain reaction (PCR) or NGS analysis.

BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

OBJECTIVE: To assess the efficacy and safety of Erzhu Jiedu Decoction (EZJDD) Granules in treating mid-advanced hepatitis B virus-associated primary liver cancer (HBV-PLC) patients with Pi (Spleen)-deficiency and dampness-heat syndrome. METHODS: From January 2021 to June 2023, a cohort of 132 patients were enrolled and randomly assigned to a control group or a EZJDD group according to the random numbers, with 66 patients in each group. The patients in the control group received conventional treatment for 3 months, followed by a 3-month follow-up. In addition to the conventional treatment, patients in the EZJDD group were administered EZJDD Granules (10.9 g/pack, 2 packs twice per day) orally for same duration. Progression-free survival (PFS) as primary outcome was evaluated by Kaplan Meier method. Karnofsky performance status (KPS) scores were used to assess the quality of life in two groups before and after treatment, and survival rates were determined as well. The efficacy of Chinese medicine syndrome was calculated with Nimodipine method. Liver function, tumor indicators and T lymphocyte subsets were measured, respectively. Safety indicators were recorded and assessed. RESULTS: Of the 116 patients who completed the study, 57 were in the control group and 59 in the EZJDD group. The median PFS was 3.53 months (106 days) in the EZJDD group compared to 2.33 months (70 days) in the control group (P=0.005). Six-month survival rate was 52.63% (30/57) in the control group and 69.49% (41/59) in the EZJDD group (P=0.039). The median KPS score in the EZJDD group [70(63, 90)] was higher than that in the control group [70(60, 80)] (P=0.013). The total effective rate of CM syndrome was 52.63% (30/57) in the control group and 77.97% (46/59) in the EZJDD group (P=0.005). The levels of alpha fetoprotein, alpha fetoprotein-L3, alpha-L-fucosidase and protein induced by Vitamin K absence or antagonist- II in the EZJDD group increased less than the control group (P>0.05). CD8⁺ levels were decreased, while CD3⁺ and CD4⁺ levels, as well as CD4⁺/CD8⁺ ratio were significantly increased in the EZZJD group (P<0.05). No treatment-related adverse reactions were observed during the study. CONCLUSION EZJDD Granules significantly prolonged the median PFS and improved 6-month survival rate in patients with mid-advanced HBV-PLC (Registration No. ChiCTR2200056922).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Liver Neoplasms/complications* ; Hepatitis B virus/physiology* ; Hepatitis B/complications* ; Treatment Outcome ; Adult ; Spleen/drug effects* ; Quality of Life ; Medicine, Chinese Traditional ; Aged ; Syndrome

Objective:To investigate the impact of different etiologies on the spatial distribution pattern of infarcts and the mapping pattern of focal symptoms in acute ischemic stroke (AIS) using a population-based standardized spatial analysis of MRI.Methods:This was a cross-sectional study. Clinical [age, sex distribution, admission National Institutes of Health Stroke Scale (NIHSS) score and 90-day modified Rankin Scale (mRS) score at discharge, etc.] and imaging data of 2 610 patients with AIS attending 9 Medical Centers from January 2015 to December 2021 were retrospectively analyzed. All patients were categorized into 1 718 cases of large artery atherosclerosis (LAA) type, 335 cases of cardioembolism (CE) type, and 557 cases of small artery occlusion (SAO) type according to TOAST typing. All patients underwent diffusion-weighted imaging, and the detected infarct lesions were segmented and aligned to the standardized space using artificial intelligence-assisted methods, and the spatial distribution frequency heatmaps of lesion locations in patients with different TOAST subtypes were plotted and compared with each other by χ2 test. Lesion-symptom image brain maps with different clinical symptoms were further plotted, and differences of lesion-symptom image relationships among different TOAST subtypes were observed and compared with each other by interaction effect. Results:In all patients, the favored sites of infarct lesions were the bilateral middle cerebral artery region in the anterior circulation and the occipital and brainstem regions in the posterior circulation. Compared with the LAA type, the CE type lesions were more likely to occur in the anterior cerebral artery region, the occipital lobe, and the cerebellum posterior, while the SAO type lesions were more likely to occur in the perforator artery supply area. The lesion-symptom mapping results showed that AIS patients with infarct lesions in the frontoparieto-temporal region in the presence of a left middle cerebral artery supply had higher admission NIHSS scores and higher discharge 90-day mRS scores for the LAA type than for the CE type( P<0.05); AIS patients with infarcted lesions in the brainstem region and some cerebellar regions in the presence of vertebrobasilar artery supply had higher admission NIHSS scores and higher discharge 90-day mRS scores for the CE type than for the LAA type( P<0.05). Conclusion:At the population level, brain mapping reveals specific infarct distribution patterns and differences in lesion-symptom mapping patterns of different etiologies AIS patients, providing imaging evidence for the understanding of AIS pathogenetic mechanisms and clinical management.

Objective:To assess the safety and efficacy of thiotepa, busulfan, and etoposide (TBE) conditioning followed by autologous hematopoietic stem-cell transplantation (TBE auto-HSCT) in primary central nervous system lymphoma (PCNSL) patients.Methods:Clinical data from 27 PCNSL patients who received TBE auto-HSCT at the Fifth Medical Center of PLA General Hospital between November 1, 2021, and April 30, 2024, were retrospectively analyzed.Results:Twenty-seven patients [16 males, 11 females; median age 57 (23–72) years] were included, with 12 (44.4%, 12/27) over 60. Twenty-five had newly diagnosed PCNSL and 2 were relapsed. Median time from diagnosis to transplantation was 6.9 (5.0–10.0) months. TBE auto-HSCT increased complete remission (CR) rate from 63.0 to 96.3% ( P= 0.005), and 9 of 10 patients in partial remission achieving CR post-transplant. Median follow-up was 24.5 months (range 2.0–36.0). Two-year progress-free and OS rates were (87.2±6.9) % and (88.6±6.2) %, respectively. Common grade 3 nonhematologic adverse events were diarrhea (18.5%, 5/27) and bacterial infections (14.8%, 4/27). One patient (64 years old) died from carbapenem-resistant Enterobacteriaceae infection within 2 months post-transplant, yielding a 100-day treatment-related mortality of 3.7% (1/27) . Conclusion:TBE-conditioned high-dose chemotherapy with auto-HSCT is effective, safe, and well-tolerated in PCNSL patients, including the elderly.

Objective: To understand the association of physical exercise willingness and insomnia with depressive symptoms among college students, so as to provide reference for improving depressive symptoms of college students. Methods: From October 2022 to April 2023, cluster sampling was used to recruit 11 101 college students from four colleges in Anhui Province. The questionnaire survey was conducted to investigate the willingness to engage in physical exercise, insomnia and depressive symptoms of college students. The multivariate Logistic regression model was used to analyze the association of physical exercise willingness and insomnia with depressive symptoms of college students. Results: The prevalence of depressive symptoms among college students was 9.24%. Multivariate Logistic regression analysis showed that college students who were passive participants/non participants in physical activity, or who experienced insomnia, had a higher likelihood of depressive symptoms compared to those who were active participants or did not experience insomnia ( OR =1.84, 2.07, 4.02, all P <0.01). College students who were passive participants or non participants in physical activity and concurrently experienced insomnia had a higher risk of depressive symptoms compared with those who were active participants or did not experience insomnia ( OR =1.87-8.39, all P <0.01). Gender stratified analysis showed that the combined effect of passive physical exercise and insomnia increased the risk of depressive symptoms in both male ( OR = 1.81 -9.87) and female college students ( OR =1.67-7.39) (all P <0.05). Conclusions Both physical exercise willingness and insomnia are associated with depressive symptoms in college students. In order to improve the depressive symptoms of college students, it is necessary to improve the enthusiasm of physical exercise and strengthen the education of sleep health awareness.

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 investigate the influence and threshold effect of preoperative intraocular pressure(IOP)on secondary glaucoma(SG)after pars plana vitrectomy(PPV).Methods A retrospective analysis was conducted on 88 patients with retinal detachment who developed SG after PPV(SG group)treatment at Hebei Eye Hospital from January 2020 to January 2024.Meanwhile,88 patients with retinal detachment who underwent PPV at the same hospital during the same period but did not develop SG postoperatively were selected as non-SG group in a 1:1 ratio.Univariate analysis was used to compare the differences in clinical data between the two groups.A stratified regression model was applied to analyze the correlation between postoperative characteristics and preoperative IOP.Multivariate logistic regression analysis was used to identify the factors affecting the occurrence of SG after PPV,with multicollinearity diagnosis and sensitivity analysis performed for the parameters.Additionally,the threshold effect of preoperative IOP on the risk of postoperative SG was analyzed.A predictive model was constructed based on the results of multivariate logistic regression.The receiver operating characteristic(ROC)curve was employed to evaluate the efficacy and accuracy of the predictive model,while the calibration curve and clinical decision curve were utilized to assess the consistency between the predictive model and actual conditions as well as the clinical practicality of the model.Results Compared with non-SG group,SG group had a higher proportion of patients with a history of diabetes,family history of glaucoma,a higher preoperative IOP,higher proportion of postoperative closed anterior chamber angle status,longer silicone oil tamponade duration(≥6 months),higher incidence of silicone oil emulsification(P<0.05).Postoperative anterior chamber angle status(closed)was significantly positively correlated with preoperative IOP levels(P<0.05).Multivariate logistic regression analysis showed that history of diabetes,family history of glaucoma,silicone oil emulsification,postoperative anterior chamber angle closure,silicone oil tamponade duration≥6 months,and preoperative IOP≥21 mmHg were independent risk factors for SG after PPV(P<0.05).Multicollinearity diagnosis indicated no significant collinearity among the above variables.Sensitivity analysis showed that the association tended to be null when E=5.014.With the increase of preoperative IOP,the probability of SG after PPV in patients showed an upward trend.The threshold effect analysis revealed that when preoperative IOP≥19 mmHg,the probability of SG after PPV increased significantly with the elevation of preoperative IOP(OR=2.942,95%CI 1.794-4.826,P<0.001).After adjusting for covariates,preoperative IOP remained an independent influencing factor for different degrees of SG after PPV(OR=7.392,95%CI 1.379-12.510,P=0.001).Before and after validation,the area under the ROC curves(AUCs)of the model for predicting SG after PPV were 0.987(95%CI 0.974-1.000,P<0.001)and 0.989(95%CI 0.969-1.000,P<0.001),with sensitivities of 0.9332 and 0.9545,and specificities of 0.9981 and 0.9773,respectively.Both the calibration curve and decision curve analysis demonstrated that the predictive model had good discrimination and accuracy.Conclusion Preoperative IOP is an influencing factor and a sensitive indicator for the development of SG after PPV in patients with retinal detachment.

Objective:To investigate the impact of different etiologies on the spatial distribution pattern of infarcts and the mapping pattern of focal symptoms in acute ischemic stroke (AIS) using a population-based standardized spatial analysis of MRI.Methods:This was a cross-sectional study. Clinical [age, sex distribution, admission National Institutes of Health Stroke Scale (NIHSS) score and 90-day modified Rankin Scale (mRS) score at discharge, etc.] and imaging data of 2 610 patients with AIS attending 9 Medical Centers from January 2015 to December 2021 were retrospectively analyzed. All patients were categorized into 1 718 cases of large artery atherosclerosis (LAA) type, 335 cases of cardioembolism (CE) type, and 557 cases of small artery occlusion (SAO) type according to TOAST typing. All patients underwent diffusion-weighted imaging, and the detected infarct lesions were segmented and aligned to the standardized space using artificial intelligence-assisted methods, and the spatial distribution frequency heatmaps of lesion locations in patients with different TOAST subtypes were plotted and compared with each other by χ2 test. Lesion-symptom image brain maps with different clinical symptoms were further plotted, and differences of lesion-symptom image relationships among different TOAST subtypes were observed and compared with each other by interaction effect. Results:In all patients, the favored sites of infarct lesions were the bilateral middle cerebral artery region in the anterior circulation and the occipital and brainstem regions in the posterior circulation. Compared with the LAA type, the CE type lesions were more likely to occur in the anterior cerebral artery region, the occipital lobe, and the cerebellum posterior, while the SAO type lesions were more likely to occur in the perforator artery supply area. The lesion-symptom mapping results showed that AIS patients with infarct lesions in the frontoparieto-temporal region in the presence of a left middle cerebral artery supply had higher admission NIHSS scores and higher discharge 90-day mRS scores for the LAA type than for the CE type( P<0.05); AIS patients with infarcted lesions in the brainstem region and some cerebellar regions in the presence of vertebrobasilar artery supply had higher admission NIHSS scores and higher discharge 90-day mRS scores for the CE type than for the LAA type( P<0.05). Conclusion:At the population level, brain mapping reveals specific infarct distribution patterns and differences in lesion-symptom mapping patterns of different etiologies AIS patients, providing imaging evidence for the understanding of AIS pathogenetic mechanisms and clinical management.