Background Hypertension is one of the chronic diseases with the highest prevalence in China, and a history of hypertension may potentially exacerbate hearing loss. Investigating the association between long-term blood pressure trends and hearing thresholds could contribute to hearing protection efforts for occupationally noise-exposed populations. Objective By investigating hearing thresholds and blood pressure levels among occupationally noise-exposed workers in an urban rail transit enterprise, and conducting a comprehensive analysis of the association between long-term blood pressure changes and hearing thresholds, to provide data references for health management strategies targeting occupationally noise-exposed workers. Methods Workers exposed to occupational noise at a rail transit enterprise were enrolled as study subjects and underwent pure-tone audiometry. Group-based trajectory modeling was employed to identify blood pressure trajectories. Categorical data were compared using chi-square tests, while normally distributed continuous variables were analyzed via t-tests and analysis of variance (ANOVA). Generalized linear mixed models (GLMMs) were subsequently applied toexamine associations between these trajectory groups and high-frequency hearing thresholds. Results Among 2 002 occupationally noise-exposed workers, the median (P₂₅, P₇₅) age was 32 (28, 35) years, with a median (P₂₅, P₇₅) working tenure of 7 (3, 10) years. In 2019, the positive hypertension rate was 9.04%, with a mean systolic blood pressure (SBP) of (122.97±11.60) mmHg and a mean diastolic blood pressure (DBP) of (76.37±9.02) mmHg. The hearing loss prevalence was 10.1%, showing bilateral high-frequency average hearing thresholds of (17.18±8.71) dB and speech-frequency average thresholds of (13.79±3.46) dB. Three distinct trajectory groups were identified for both SBP and DBP. Compared with other trajectory groups, the high-stable DBP group exhibited significantly higher hearing loss prevalence (χ²=6.34, P=0.042) and elevated high-frequency hearing thresholds (all Ps<0.05). Specifically, within the 30-39 age subgroup, the moderate-stable DBP group demonstrated 1.96 dB lower high-frequency thresholds than the high-stable group [β(95%CI): −1.96 (−3.61, −0.32), P=0.020]. Conclusion Among occupationally noise-exposed workers in a municipal rail transit enterprise, DBP trajectories demonstrated a positive association with high-frequency hearing thresholds. Notably, in young and middle-aged occupationally noise-exposed populations, DBP may exert a more critical influence than SBP on the progression of hearing loss.

Objective To evaluate the surgical efficacy of unilateral pneumonectomy for the treatment of tuberculous destroyed lung, analyze the causes of severe postoperative complications, and explore clinical management strategies. Methods A retrospective analysis was conducted on the clinical data of patients with tuberculous destroyed lung who underwent unilateral pneumonectomy at the Public Health Clinical Center of Chengdu from 2017 to 2023. Postoperative severe complications were statistically analyzed. Patients were divided into a non-severe complication group and a severe-complication group, and the causes, management, and outcomes of complications were analyzed. Results A total of 134 patients were included, comprising 69 males and 65 females, with a mean age of 17-73 (40.43±12.69) years. There were 93 patients undergoing left pneumonectomy and 41 patients undergoing right pneumonectomy. Preoperative sputum smear was positive in 35 patients, all of which converted to negative postoperatively. There were 58 patients with hemoptysis preoperatively, and none experienced hemoptysis postoperatively. Postoperative incisional infection occurred in 8 (5.97%) patients, and postoperative pulmonary infection in 26 (19.40%) patients. Severe postoperative complications occurred in 17 (12.69%) patients, including empyema in 9 (6.72%) patients, bronchopleural fistula with empyema in 1 (0.75%) patient, severe pneumonia in 3 (2.24%) patients, postpneumonectomy syndrome in 1 (0.75%) patient, chylothorax in 1 (0.75%) patient, ketoacidosis in 1 (0.75%) patient, and heart failure with severe pneumonia in 1 (0.75%) patient. Perioperative mortality occurred in 2 (1.49%) patients, both of whom underwent right pneumonectomy. Multivariate logistic regression analysis revealed that a history of ipsilateral thoracic surgery, concomitant Aspergillus infection, and greater blood loss were independent risk factors for severe complications following unilateral pneumonectomy for tuberculous destroyed lung (P<0.05). Conclusion Unilateral pneumonectomy for patients with tuberculous destroyed lung can significantly improve the clinical cure rate, sputum conversion rate, and hemoptysis cessation rate. However, there is a certain risk of severe perioperative complications and mortality, requiring thorough perioperative management and appropriate management of postoperative complications.

Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the "therapeutic module" of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

OBJECTIVE: To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation. METHODS: Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing. RESULTS: APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ _1-42, and Aβ _1-40, were decreased in SV2A-overexpressed cells. CONCLUSION These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Amyloid beta-Protein Precursor/genetics* ; Membrane Glycoproteins/genetics* ; Animals ; Protein Transport ; Nerve Tissue Proteins/genetics* ; Humans ; Mice ; Endosomes/metabolism* ; trans-Golgi Network/metabolism*

Persistent atrial fibrillation and other factors can cause mitral and tricuspid annular dilation and leaflet regurgitation,leading to severe functional mitral and tricuspid regurgitation.Patients often experience significant heart failure symptoms and poor prognosis.For patients with severe mitral or tricuspid regurgitation who are at high risk or contraindicated for surgical procedures,transbronchial repair(TEER)is an important alternative therapy that can effectively reduce valve regurgitation and improve cardiac function;Although there is a lack of large-scale data on atrial functional reflux,existing experience still shows that TEER can significantly reduce reflux and improve patients'quality of life.However,double valve intervention therapy poses challenges,especially when combined with TEER repair,which is technically more complex,time-consuming,and carries higher risks.Foreign data shows that simultaneous or staged double valve intervention can safely improve cardiac function and increase survival rates,but the optimal intervention strategy still needs further research.Due to the fact that tricuspid TEER devices have not yet been launched in China,only staged treatment can be adopted at present.This case report shows a patient with severe atrial functional mitral and tricuspid regurgitation who underwent staged transcatheter edge to edge repair surgery successfully.During a 1-year follow-up,bilateral valve regurgitation continued to improve,indicating that staged repair of bilateral atrioventricular valve regurgitation through the catheter margin is a feasible and effective treatment option.

Objective:To explore the effect of remote motor imagery therapy on rehabilitation of patients with severe coronary heart disease(CHD)after percutaneous coronary intervention(PCI).Methods:This randomized con-trolled study enrolled 164 patients with severe CHD undergoing PCI who admitted in the First Affiliated Hospital of Hebei North University between January 2022 and January 2024.Patients were divided into control group(n=82)and intervention group(n=82).Patients in the control group was given conventional home nursing intervention comparing to those in the intervention group receiving additional remote motor imagery therapy.Both groups were intervened for 8 weeks.Indexes of pain,psychological emotion,ability of daily living,motor function and fall were compared between two groups.Results:Compared to those in control group after intervention,patients in interven-tion group had significant lower scores of visual analogue scale(VAS)[(2.03±0.81)points vs.(5.14±0.84)points],the Hospital anxiety and depression scale(HADS)anxiety subscale(HADS-A)[(4.89±0.84)points vs.(9.05±0.78)points],HADS depression subscale(H ADS-D)[(5.31±1.10)points vs.(10.13±0.82)points],HADS total score[(10.20±1.39)points vs.(19.18±1.18)points](P＜0.001 all),and significant higher 6-min walking distance(6MWD)[(439.31±16.51)m vs.(364.94±12.76)m],peak oxygen uptake(VO2 peak)[(20.28±2.40)ml·kg-1·min-1 vs.(17.26±1.35)ml·kg-1·min-1],anaerobic threshold oxygen consumption(VO2AT)[(17.04±1.18)ml·kg-1·min-1 vs.(13.62±1.16)ml·kg-1·min-1],scores of Chinese modified Fall Efficacy Scale(MFES)[(107.28±4.84)points vs.(87.41±4.73)points],ability of daily living(ADL)scale[(78.95±3.92)points vs.(68.00±4.10)points]and Barthel index[(85.83±2.50)points vs.(69.79±3.42)points](P＜0.001 all).We detected significant lower incidence of falling(7.50％vs.21.25％)in the intervention group compared to control group(P=0.013).Conclusion:Remote motor imagery therapy may strengthen motor function and ability of daily living,and relieve pain and negative emotions in patients with severe CHD after PCI.

Persistent atrial fibrillation and other factors can cause mitral and tricuspid annular dilation and leaflet regurgitation,leading to severe functional mitral and tricuspid regurgitation.Patients often experience significant heart failure symptoms and poor prognosis.For patients with severe mitral or tricuspid regurgitation who are at high risk or contraindicated for surgical procedures,transbronchial repair(TEER)is an important alternative therapy that can effectively reduce valve regurgitation and improve cardiac function;Although there is a lack of large-scale data on atrial functional reflux,existing experience still shows that TEER can significantly reduce reflux and improve patients'quality of life.However,double valve intervention therapy poses challenges,especially when combined with TEER repair,which is technically more complex,time-consuming,and carries higher risks.Foreign data shows that simultaneous or staged double valve intervention can safely improve cardiac function and increase survival rates,but the optimal intervention strategy still needs further research.Due to the fact that tricuspid TEER devices have not yet been launched in China,only staged treatment can be adopted at present.This case report shows a patient with severe atrial functional mitral and tricuspid regurgitation who underwent staged transcatheter edge to edge repair surgery successfully.During a 1-year follow-up,bilateral valve regurgitation continued to improve,indicating that staged repair of bilateral atrioventricular valve regurgitation through the catheter margin is a feasible and effective treatment option.

The development of traditional Chinese medicine (TCM) diagnosis and treatment has undergone multiple paradigms, evolving from sporadic experiential practices to systematic approaches in syndrome differentiation and treatment and further integration of disease and syndrome frameworks. TCM is a vital component of the medical system, valued alongside Western medicine. Treatment based on syndrome differentiation embodies both personalized treatment and holistic approaches; however, the inconsistency and lack of stability in syndrome differentiation limit clinical efficacy. The existing integration of diseases and syndromes primarily relies on patchwork and embedded systems, where the full advantages of synergy between Chinese and Western medicine are not fully realized. Recently, driven by the development of diagnosis and treatment concepts and advances in analytical technology, Western medicine has been rapidly transforming from a traditional biological model to a precision medicine model. TCM faces a similar need to progress beyond traditional syndrome differentiation and disease-syndrome integration toward a more precise diagnosis and treatment paradigm. Unlike the micro-level precision trend of Western medicine, precision diagnosis and treatment in TCM is primarily reflected in data-driven applications that incorporate information at various levels, including precise syndrome differentiation, medication, disease management, and efficacy evaluation. The current priority is to accelerate the development of TCM precision diagnosis and treatment technology platforms and advance discipline construction in this area.

Objective:To investigate the therapeutic effect of platelet-rich plasma(PRP)combined with Xianling Gubao Capsule on rats with osteoarthritis(OA)and the changes in the levels of related factors.Methods:Anterior cruciate ligament transection was performed to establish a rat model of OA,and after modeling,the rats were randomly divided into control group,model group,Xianling Gubao Capsule group,PRP group,and Xianling Gubao Capsule+PRP group,with 10 rats in each group.After intervention,ELISA was used to measure the serum levels of IL-1β and TNF-α;knee articular cartilage was collected,and qPCR and Western blot were used to measure the mRNA and protein expression levels of MMP3,MMP13,Col2,Aggrecan,and p-p38;Micro-CT was used to assess the changes in bones around the knee joint;HE staining and SF staining were used to observe the changes in knee articular cartilage.Results:ELISA showed that PRP combined with Xianling Gubao Capsule significantly reduced the serum levels of the inflammatory factors such as IL-1β and TNF-α(P<0.05).The results of qPCR and Western blot showed that PRP combined with Xianling Gubao Capsule significantly reduced the expression levels of MMP3,MMP13,and p-p38 and increased the expression levels of Col2 and Ag-grecan in knee articular cartilage(P<0.05).Micro-CT,HE staining,and SF staining showed a certain degree of improvement in knee articular cartilage degeneration in the Xianling Gubao Capsule+PRP group(P<0.05).Conclusion:PRP combined with Xianling Gubao Capsule exerts a therapeutic effect on rats with OA,possibly by regulating the p38MAPK signaling pathway.