OBJECTIVE: Previous studies have shown that insomnia is closely related to erectile dysfunction（ED）. However, the causal relationship between them is still unclear. Mendelian randomization (MR) provides a new method for studying the relationship between the two, and the theory of heart-kidney interaction in TCM provides a new idea for exploring the causal relationship between them. METHODS: Based on the statistical data collected by genome-wide association studies (GWAS), the causal relationship between insomnia and ED was discussed by MR. Inverse variance weighted (IVW) is the main analysis method, and weighted median (WME), simple mode (SM), weighted mode (WM) and MR Egger method were the supplementary analysis to evaluate the causal effect. MR-Egger intercept test, Cochran Q test and leave-one-out method were used in sensitivity analysis to verify the reliability of MR results. RESULTS: Thirty-nine SNPs significantly related to insomnia were finally included for MR analysis. The results of IVW method in MR analysis showed that insomnia had a significant causal relationship with the increased risk of ED (OR = 3.111，95% CI= 1.566－6.181，P=1.193×10－3). The results obtained by MR-Egger method, WME method, WM method and SM method were consistent with IVW method in the direction of effect. The sensitivity results suggested that the results of this study were robust. CONCLUSION Our study reveals the causal relationship between insomnia and ED, which provides a new basis for future clinical practice and prevention and treatment of ED.
Causality ; Sleep Initiation and Maintenance Disorders/genetics* ; Erectile Dysfunction/genetics* ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Humans ; Male ; Heart/physiology* ; Kidney/physiology* ; Polymorphism, Single Nucleotide ; Data Interpretation, Statistical

In 2040, neurodegenerative diseases (NDD) will overtake cancer as the second leading cause of death after cardiovascular and cerebrovascular diseases. Therefore, the search for effective intervention measures has become the top priority to deal with this difficult burden. Hyperbaric oxygen therapy (HBOT) has been used for the past 50 years to treat conditions such as decompression sickness, carbon monoxide poisoning and radiation damage. In recent years, studies have confirmed that HBOT has good effects in improving cognitive impairment after brain injury and stroke, and alleviating neurodegeneration and dysfunction related to NDD. Here we reviewed the pathogenesis and treatment state of NDD, introduced the application of HBOT in animal models and clinical studies of NDD, and expounded the application potential of HBOT in the treatment of NDD from the perspective of mitochondrial function, neuroinflammation, neurogenesis and angiogenesis, oxidative stress, apoptosis, microcirculation and epigenetics.
Hyperbaric Oxygenation ; Humans ; Neurodegenerative Diseases/physiopathology* ; Animals ; Oxidative Stress ; Apoptosis ; Mitochondria/physiology* ; Neurogenesis ; Epigenesis, Genetic

This study aims to integrate data mining techniques of single cell transcriptomics and spatial transcriptomics, along with animal experiment validation, so as to systematically characterize the protective effects of Jianpi Tongluo Formula(JTF) on the cartilage in knee osteoarthritis(KOA) and elucidate the underlying molecular mechanisms. Single cell transcriptomics and spatial transcriptomics datasets(GSE254844 and GSE255460) of the cartilage tissue obtained from KOA patients were analyzed to map the single cell-spatial heterogeneity and identify key pathogenic factors. After that, a KOA rat model was established via knee joint injection of papain. The intervention effects of JTF on the expression features of these key factors were assessed through real-time quantitative polymerase chain reaction(PCR), Western blot, and immunohistochemical staining. As a result, the integrated single cell and spatial transcriptomics data identified distinct cell subsets with different pathological changes in different regions of the inflamed cartilage tissue in KOA, and their differentiation trajectories were closely related to the inflammatory fibrosis-like pathological changes of chondrocytes. Accordingly, the expression levels of the two key effect targets, namely nuclear receptor coactivator 4(NCOA4) and high mobility group box 1(HMGB1) were significantly reduced in the articular surface and superficial zone of the inflamed joints when JTF effectively alleviated various pathological changes in KOA rats, thus reversing the abnormal chondrocyte autophagy level, relieving the inflammatory responses and fibrosis-like pathological changes, and promoting the repair of chondrocyte function. Collectively, this study revealed the heterogeneous characteristics and dynamic changes of inflamed cartilage tissue in different regions and different cell subsets in KOA patients. It is worth noting that NCOA4 and HMGB1 were crucial in regulating chondrocyte autophagy and inflammatory reaction, while JTF could reverse the regulation of NCOA4 and HMGB1 and correct the abnormal molecular signal axis in the target cells of the inflamed joints. The research can provide a new research idea and scientific basis for developing a personalized therapeutic schedule targeting the spatiotemporal heterogeneity characteristics of KOA.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Osteoarthritis, Knee/pathology* ; Humans ; Male ; Cartilage, Articular/metabolism* ; Chondrocytes/metabolism* ; Rats, Sprague-Dawley ; Female ; Protective Agents/administration & dosage* ; Single-Cell Analysis ; Middle Aged ; HMGB1 Protein/metabolism*

Objective:To analyze the clinical characteristics of malignant lymphoma of the head and neck in children, and to improve the understanding and diagnosis and treatment of this type of disease by otolaryngologists. Methods:Clinical data of 49 children with malignant lymphoma of the head and neck hospitalized in the Department of Otorhinolaryngology, Head and Neck Surgery of Kunming Children's Hospital from 2013-2021 were retrospectively analyzed and statistically analyzed according to gender, age distribution, duration of the disease, site of onset, type of pathology and survival status. Results:A total of 49 cases of malignant lymphoma of the head and neck in children were collected, of which, 39 were male and 10 female. The minimum age was 3 years, the maximum was 14 years and 4 months, the median age of onset was 7 years, and the largest percentage （51.02%） of children was in the school age（6-12 years）. The duration of the disease ranged from 5 days to 2 years, with a median of 1 month, and the site of the lesion was located in the neck in the majority of cases, 41（83.67%）. The pathologic types of hodgkin lymphoma（HL） were 25 cases（51.02%） and non-hodgkin lymphoma（NHL） were 24 cases（48.98%）, and among hodgkin lymphomas, mixed-cell classical hodgkin lymphoma was the most common, with 9 cases（18.37%）; among non-hodgkin lymphomas,originated from B-cells in 16 cases （32.65%） and from T-cells in 7 cases （14.29%）, with Burkitt's lymphoma being the most numerous of B-cell origin in 13 cases （26.53%）, and T-cell lymphoblastoid lymphoma being the most common of T-cell origin in 4 cases （8.16%）. The follow-up period was from 22 days to 6 years and 10 months, with 3 cases losing, 43 cases surviving, 3 cases dying, with a survival rate of 93 5%, and 3 cases relapsing, with a relapse rate of 6 5%. Conclusion:Children's head and neck malignant lymphoma has its own characteristics in terms of age of onset, gender distribution, site of onset, pathological type and treatment prognosis, which should be comprehensively assessed, diagnosed as early as possible, and multidisciplinary joint treatment actively carried out to propose personalized treatment plans.
Humans ; Male ; Female ; Child ; Head and Neck Neoplasms/therapy* ; Child, Preschool ; Retrospective Studies ; Adolescent ; Lymphoma/therapy* ; Survival Rate ; Hodgkin Disease ; Prognosis ; Infant ; Lymphoma, Non-Hodgkin

Objective:To investigate the molecular characteristics and clinical heterogeneity of Usher syndrome（USH） -related gene variants in patients with hereditary hearing loss in southwest China, providing a basis for early diagnosis and clinical management. Methods:Thirteen patients from twelve families with hearing loss who attended the Affiliated Children's Hospital of Kunming Medical University between January 2017 and March 2021 were enrolled. All patients were identified as carrying USH-related gene variants through next-generation sequencing. Sanger sequencing was performed for all patients and their parents to validate the pathogenic variants. Comprehensive clinical evaluations, including medical history collection, otologic and ophthalmologic examinations, and vestibular function assessments, were conducted. Results:Among the 13 patients, 4 were diagnosed with USH type 1 and 2 with USH type 2. A total of 19 pathogenic or likely pathogenic variants were detected in USH-related genes, including MYO7A,CDH23,USH1C, and USH2A. The causative gene was MYO7A in 3 probands, CDH23 in 5, USH1C in 3, and USH2Ain 2. All patients exhibited an autosomal recessive inheritance pattern. Vestibular dysfunction was observed in 4 patients, and retinitis pigmentosa（RP） in 3 patients. Based on the genotype-phenotype correlation, 6 patients were initially diagnosed with USH, while 7 were classified as having non-syndromic hearing loss（NSHL）. Conclusion:This study revealed the clinical heterogeneity of USH-related gene variants in patients with hereditary deafness in southwest China. Although the clinical manifestations of USH are complex and there are overlapping characteristics between different subtypes, genetic testing provides an important basis for early diagnosis and precise clinical management. Especially for those with typical hearing loss, early genetic diagnosis can provide a window of time for early detection and intervention of retinitis pigmentosa.
Humans ; Usher Syndromes/genetics* ; Myosin VIIa ; Phenotype ; Male ; Female ; Myosins/genetics* ; Mutation ; Cadherins/genetics* ; Child ; Extracellular Matrix Proteins/genetics* ; Adolescent ; Pedigree ; High-Throughput Nucleotide Sequencing ; Cadherin Related Proteins ; Cytoskeletal Proteins ; Cell Cycle Proteins

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Transcranial electrical stimulation (tES) is a non-invasive neural modulation technique known for its high safety, patient compliance, and portability. It holds promise as a potential non-pharmacological method for analgesia. However, challenges persist in utilizing tES for pain management, including inconsistent research findings and limited understanding of its analgesic mechanisms. Therefore, by summarizing the advances in the analgesic researches employing the 3 primary tES techniques, transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial random noise stimulation (tRNS), we reviewed the analgesic effects on both acute and chronic pain, as well as the neural mechanisms underlying the analgesic effect of each technique. Accumulating evidence suggests that the analgesic effects of tDCS are significant, but studies on analgesic effects of tACS and tRNS remain limited. And the exact mechanisms of pain relief through tES turned out to be not yet well established. Furthermore, we systematically discussed the limitations of analgesia-related studies employing tES techniques across various aspects, involving research design, stimulation protocol formulation, neural response observation, analgesic effect assessment, and safety considerations. To address these limitations and advance clinical translation, we emphasized utilizing promising stimulation techniques and offered practical suggestions for future research endeavors. Specifically, employing numerical simulation of electric field guided by magnetic resonance imaging (MRI) would reduce variability of outcomes due to individual differences in head anatomy. For this purpose, it is advisable to establish standardized head models based on MRI data from the Chinese populations and validate simulated electric field results in tES research to diminish confounding factors concerning anatomy. Meanwhile, novel techniques like multi-site brain stimulation and interferential stimulation (IFS) could broaden the range of stimulation sites in both scope and depth. Multi-site brain stimulation facilitates modulation of entire neural networks, enabling more sophisticated investigations into the complexity of pain. IFS can reach deep brain tissues without invasive surgical procedures, achieving more comprehensive modulation. Regarding neural response observations, establishing a tES-neuroimaging synchronized platform would enable revealing its mechanisms and personalizing protocols based on inter-subject neural response variability detected through recordings. By integrating tES with various neuroimaging techniques, such as functional MRI, electroencephalography (EEG) and magnetoencephalography, into one unified platform, researchers could examine brain activities in baseline before stimulation, dynamic changes in brain activities during stimulation, and sustained brain responses after stimulation. Additionally, collecting finer-grained data on participant characteristics and pain intensity would enhance the sensitivity of future studies. In designing clinical trials to evaluate chronic pain treatments and reporting the results, adopting the six core outcome domain measures recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) could prove beneficial. Lastly, safety considerations can never be overemphasized in future tES studies especially when combining tES with MRI and EEG techniques. These efforts may help to broaden the research scope, reconcile inconsistencies in findings and elucidate the analgesic mechanisms of tES, thus facilitating the development of pragmatic pain management strategies such as combination therapies and home therapies. Ultimately, these suggestions will maximize the clinical application value of tES in pain treatment to achieve pain relief for patients.