Objectives: . This study aimed to investigate the regulatory functions of gamma-aminobutyric acid (GABA)ergic neural circuits from the inferior colliculus (IC) to the medial geniculate body (MGB) in salicylate-induced tinnitus. Methods: . Mice were treated with salicylate to induce tinnitus, and tinnitus-like behaviors were evaluated via gap prepulse inhibition of acoustic startle. Using combined viral tracing methodologies, we identified and mapped the pathways and connections from the IC to the MGB. Furthermore, we employed Gq-coupled human M3 designer receptors exclusively activated by designer drugs (DREADDs) and Gi-coupled human M4 DREADDs to achieve targeted excitation or suppression of GABAergic neurons in the IC and MGB. Following the administration of clozapine N-oxide, which binds to these receptors, we modulated these neural circuits to assess their impact on tinnitus severity in a mouse model. Results: . Our findings demonstrated that mice exposed to salicylate exhibited tinnitus-like behaviors. GABAergic neurons projecting retrogradely from the MGB to the IC were primarily concentrated in the external nucleus of the IC. After clozapine N-oxide administration, chemogenetic activation of IC-MGB GABAergic neurons aggravated salicylate-induced tinnitus. Additionally, activation of GABAergic neurons between the IC and MGB induced the perception of tinnitus even without salicylate. However, chemogenetic inhibition of the IC-MGB GABAergic circuit did not reverse salicylate-induced tinnitus. Conclusion . These findings suggest that activation of the IC-MGB GABAergic neural circuit may contribute to tinnitus generation through a mechanism distinct from that of salicylate-induced tinnitus. This study provides novel insights into the mechanisms underlying tinnitus.

Objective To compare the performance of 7 Chinese-developed GenAI models (DeepSeek, Wenxin Yiyan, Tongyi, Doubao, Kimi, Hunyuan, and iFLYTEK Spark) in responding to common diseases of the pediatric genitourinary system and to explore their potential applications.Methods A total of 80 questions covering basic disease information, diagnosis, treatment, and prognosis related to “hypospadias, hydronephrosis, and cryptorchidism” were developed as prompts.The models were tested under 3 modes:“quick thinking, ”“deep thinking, ” and “deep thinking + internet access.” The results were evaluated in a blinded review by two pediatric urologists.The responses were graded into 4 levels—A, B, C, and D—based on accuracy, completeness, and relevance.The proportions of responses rated as A and A+B were statistically analyzed and compared across the different models/modes.Results The “deep thinking” mode of DeepSeek demonstrated the best performance, with 88% of responses rated as A and 96% rated as A+B.DeepSeek (deep thinking + internet access), Doubao (quick thinking), Hunyuan (deep thinking), and Doubao (deep thinking + internet access) followed closely, also showing excellent response capabilities.Among the top 5 models/modes, significant differences were observed in the proportion of Alevel responses (P＜0.05), while differences in the proportion of A+B-level responses were not statistically significant (P＞0.05).Conclusion Certain Chinese-developed GenAI models, represented by DeepSeek (deep thinking), demonstrate significant application potential.However, they still cannot consistently provide recommendations rated at the A+B level (recommended grade or higher) with 100% accuracy.In clinical practice, both doctors and patients should view GenAI as an auxiliary tool for education and information acquisition rather than as a final decision-making authority.All information must be reviewed and confirmed by professional physicians.

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

The chemical constituents from Cephalotaxus lanceolata were isolated and purified by using multiple chromatographic techniques, including octadecylsilane(ODS), silica gel, Sephadex LH-20 column chromatography, and semi-preparative high-performance liquid chromatography(HPLC). A total of 17 compounds obtained were identified by using spectroscopic methods such as nuclear magnetic resonance(NMR), mass spectrometry(MS), and ultraviolet(UV) combined with literature data. Compound 1 was a new alkaloid dimer, named cephalancetine E. The known compounds were determined as cephalancetine A(2), 11-hydroxycephalotaxine(3), 4-hydroxycephalotaxine(4), cephalotaxine(5), epicephalotaxine(6), cephalotaxine β-N-oxide(7), acetylcephalotaxine(8), cephalotine A(9), cephalotine B(10), 11-hydroxycephalotaxine hemiketal(11), 3-deoxy-3,11-epoxy-cephalotaxine(12), cephalotaxinone(13), isocephalotaxinone(14), 2,11-epoxy-1,2-dihydro-8-oxo-cephalotaxine(15), cephalotaxamide(16), and drupacine(17), respectively. Compounds 11, 12, and 15 were isolated from the Cephalotaxus genus for the first time. The biological activity was tested for compounds 1-17. The results reveal that compound 17 displays potent inhibitory activities against three human cancer cell lines(HepG-2, MCF-7, and SH-SY5Y).
Cephalotaxus/chemistry* ; Humans ; Cell Line, Tumor ; Drugs, Chinese Herbal/pharmacology* ; Harringtonines/pharmacology* ; Molecular Structure ; Dimerization ; Alkaloids/isolation & purification* ; Magnetic Resonance Spectroscopy

OBJECTIVE: To explore clinical effective and safety of subarachnoid block (SA), adductor canal block (ACB), and femoral nerve block (FNB) for early analgesia in anterior cruciate ligament (ACL) reconstruction. METHODS: From September 2022 to October 2023, 90 patients with ACL rupture who received unilateral knee arthroscopic ACL reconstruction were selected and divided into ACB group, FNB group and SA group according to different anesthesia methods, with 30 patients in each group. There were 12 males and 18 females in ACB group, aged from 18 to 60 years old with an average of (33.3±13.8) years old;14 patients with gradeⅠand 16 patients with gradeⅡaccording to American Society of Aneshesiologists (ASA);13 patients on the left side and 17 patients on the right side. There were 15 males and 15 females in FNB group, aged from 18 to 60 years old with an average of (33.5±12.9) years old;15 patients with gradeⅠand 15 patients with gradeⅡ;16 patients on the left side and 14 patients on the right side. There were 16 males and 14 females in SA group, aged from 18 to 60 years old with an average of (31.0±12.6) years old;18 patients with grade I and 12 patients with gradeⅡ;17 patients on the left side and 13 patients on the right side. In ACB and FNB groups, the nerve block of ACB and FNB were performed under ultrasound guidance before SA anesthesia with 15 ml of 0.3% ropivacaine. Visual analogue scale (VAS) and quadriceps muscle strength at rest and passive movement were recorded and compared among 3 groups at 4, 8, 12, 16, 24 and 48 h after operation, as well as the dosage of tramadol injection analgesics, incidence of nausea and vomiting, nerve block time and other complications within 48 h after operation were compared. RESULTS: All patients were followed up for 11 to 20 (15.8±2.4) months. VAS at 4, 8, 12, 16, 24 and 48 h after operation of SA group was significantly higher than that of ACB and FNB groups, with statistical significance (P<0.05). There were no significant difference in VAS of rest and passive movement at 4, 8, 12, 16, 24 and 48 h after operation between ACB group and FNB group(P>0.05). At 4, 8, 12 and 16 h after operation, the quadriceps muscle strength in SA and ACB groups was higher than that in FNB group, with statistical significance (P<0.05);but there was no statistical significance in quadriceps muscle strength among three groups at 24 and 48 h after operation(P>0.05). One patient occurred nausea and vomiting in ACB group, 2 patients in FNB group and 5 patients in SA group, and no significant difference among three groups (χ²=0.352, P=0.171). The dosage of tramadol in SA group was (300.00±136.50) mg, which was higher than that in FNB group (168.33±73.70) mg and ACB(163.33±70.70) mg, and the difference was statistically significant (P<0.05). There was no significant difference in nerve block time between ACB group and FNB group (t=1.964, P=0.054). There was no puncture site bleeding, local anesthesia drug poisoning and hematoma formation among three groups. CONCLUSION Both FNB and ACB could provide good early analgesia after ACL reconstruction, but ACB group has little effect on quadriceps muscle strength. Patients could have early postoperative functional training without pain, which is more beneficial to the recovery of knee joint function, and could reduce the use of analgesic drugs, without serious complications, which is safe and reliable method.
Humans ; Male ; Female ; Nerve Block/methods* ; Adult ; Anterior Cruciate Ligament Reconstruction ; Adolescent ; Middle Aged ; Young Adult ; Analgesia/methods* ; Pain, Postoperative/drug therapy* ; Femoral Nerve

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that is often accompanied by mental health disorders. However, the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain. This study analyzed widely targeted metabolomic data of expressed prostatic secretions (EPS) and plasma to reveal the underlying pathological mechanisms of CP/CPPS. A total of 24 CP/CPPS patients from The Second Nanning People's Hospital (Nanning, China), and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University (Nanning, China) were enrolled. The indicators related to CP/CPPS and psychiatric symptoms were recorded. Differential analysis, coexpression network analysis, and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS. The crucial links between EPS and plasma were further investigated. The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals. Pathway analysis revealed dysregulation of amino acid metabolism, lipid metabolism, and the citrate cycle in EPS. The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes. Moreover, the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS. Overall, metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage, energy metabolism abnormalities, neurological impairment, and immune dysregulation. These alterations may be associated with chronic pain, voiding symptoms, reduced fertility, and depression in CP/CPPS. This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.
Humans ; Male ; Prostatitis/blood* ; Adult ; Pelvic Pain/blood* ; Metabolomics ; Prostate/metabolism* ; Middle Aged ; Chronic Pain/blood* ; Metabolome ; Case-Control Studies ; Tryptophan/blood* ; Depression/blood* ; Oxidative Stress/physiology* ; Chronic Disease ; Lipid Metabolism/physiology*

OBJECTIVE: To investigate the clinical features and prognosis of central nervous system (CNS) invasion in peripheral T-cell lymphoma (PTCL) and construct a risk prediction model for CNS invasion. METHODS: Clinical data of 395 patients with PTCL diagnosed and treated in the First Affiliated Hospital of Zhengzhou University from 1st January 2013 to 31st December 2022 were analyzed retrospectively. RESULTS: The median follow-up time of 395 PTCL patients was 24(1-143) months. There were 13 patients diagnosed CNS invasion, and the incidence was 3.3%. The risk of CNS invasion varied according to pathological subtype. The incidence of CNS invasion in patients with anaplastic large cell lymphoma (ALCL) was significantly higher than in patients with angioimmunoblastic T-cell lymphoma (AITL) (P <0.05). The median overall survival was significantly shorter in patients with CNS invasion than in those without CNS involvement, with a median survival time of 2.4(0.6-127) months after diagnosis of CNS invasion. The results of univariate and multivariate analysis showed that more than 1 extranodal involvement (HR=4.486, 95%CI : 1.166-17.264, P =0.029), ALCL subtype (HR=9.022, 95%CI : 2.289-35.557, P =0.002) and ECOG PS >1 (HR=15.890, 95%CI : 4.409-57.262, P <0.001) were independent risk factors for CNS invasion in PTCL patients. Each of these risk factors was assigned a value of 1 point and a new prediction model was constructed. It could stratify the patients into three distinct groups: low-risk group (0-1 point), intermediate-risk group (2 points) and high-risk group (3 points). The 1-year cumulative incidence of CNS invasion in the high-risk group was as high as 50.0%. Further evaluation of the model showed good discrimination and accuracy, and the consistency index was 0.913 (95%CI : 0.843-0.984). CONCLUSION The new model shows a precise risk assessment for CNS invasion prediction, while its specificity and sensitivity need further data validation.
Humans ; Lymphoma, T-Cell, Peripheral/pathology* ; Prognosis ; Retrospective Studies ; Central Nervous System Neoplasms/pathology* ; Neoplasm Invasiveness ; Male ; Female ; Central Nervous System/pathology* ; Middle Aged ; Adult

BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*