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.

ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

Background: En bloc resection is recommended for the treatment of malignant and aggressive benign spinal tumors; however, it often requires a combined anterior-posterior approach, which is usually accompanied by longer surgical duration, increased blood loss, larger trauma, and surgical complexity. The present study describes a novel rotation-reversion technique for en bloc resection of the thoracic and upper lumbar spinal tumors using a posterior-only approach and evaluate its safety and efficacy. Methods: Thirteen patients with thoracic and upper lumbar (L1-L3) spinal tumors were treated with en bloc resection using the rotation-reversion technique through a posterior-only approach at our institution between 2015 and 2023. The clinical characteristics and surgical results of the patients were reviewed and analyzed. Results: Posterior-only en bloc resection was performed successfully in all 13 patients using the rotation-reversion technique, with a median follow-up of 30.4 months (range, 6–74 months). The average maximum size of these 13 tumors was 5.7 × 5.8 × 4.8 cm.The mean operation time and blood loss were 458.5 minutes (range, 220–880 minutes) and 3,146.2 mL (range, 1,000–6,000 mL), respectively, with 4 of the 13 patients (30.8%) experiencing perioperative complications. Negative margins were achieved in all the 13 patients (100%). One patient experienced local recurrence (7.7%) and 1 patient experienced instrumentation failures. Interbody fusion was confirmed in 11 of the 13 patients (84.6%), with a median fusion time of 6.9 months. All of the 13 patients experienced varying degrees of mild postoperative neurological deficits owing to resection of the nerve roots affected by tumor invasion of the vertebrae. No vessel injury or postoperative neurological paralysis occurred, except 1 patient who had been completely paralyzed before surgery. Conclusions The rotation-reversion technique is an effective procedure for en bloc resection of selected thoracic and upper lumbar spinal tumors through the posterior-only approach.

[Objective] To evaluate the efficacy and safety of sacral neuromodulation (SNM) in the treatment of patients with benign prostatic hyperplasia (BPH) complicated with underactive bladder (UAB) who respond poorly to transurethral resection of the prostate (TURP). [Methods] A retrospective analysis was performed on 10 patients with BPH and UAB treated with TURP by the same surgeon in Zhongda Hospital Southeast University during Jan.2018 and Jan.2023.The residual urine volume was not significantly relieved after operation, and the maximum urine flow rate and urine volume per discharge were not significantly improved.All patients underwent phase I SNM, and urinary diaries were recorded before and after surgery to observe the average daily frequency of urination, volume per urination, maximum urine flow rate, and residual urine volume. [Results] The operation time was (97.6±11.2) min.During the postoperative test of 2-4 weeks, if the residual urine volume reduction by more than 50% was deemed as effective, SNM was effective in 6 patients (60.0%). Compared with preoperative results, the daily frequency of urination [(20.2±3.8) times vs. (13.2±3.2) times], volume per urination [(119.2±56.7) mL vs. (246.5±59.2) mL], maximum urine flow rate [(8.7±1.5) mL/s vs. (16.5±2.6) mL/s], and residual urine volume [(222.5±55.0) mL vs. (80.8±16.0) mL] were significantly improved, with statistical significance (P<0.05). There were no complications such as bleeding, infection, fever or pain.The 6 patients who had effective outcomes successfully completed phase II surgery, and the fistula was removed.During the follow-up of 1 year, the curative effect was stable, and there were no complications such as electrode displacement, incision infection, or pain in the irritation sites.The residual urine volume of the other 4 unsuccessful patients did not improve significantly, and the electrodes were removed and the vesicostomy tube was retained. [Conclusion] SNM is safe and effective in the treatment of BPH with UAB patients with poor curative effects after TURP.

Objective To investigate the role and mechanism of paeoniflorin(PF)in sepsis-associated acute kidney injury(SA-AKI)in mice.Methods Mouse SA-AKI model was constructed by intraperitoneal injection of 15 mg/kg LPS.Twenty-four male C57BL/6J mice(6～8 weeks old,weighing 20～25 g)were randomly divided into Control group,model group,PF group(intraperitoneally injected with 50 mg/kg PF 30 min before LPS administration),and β-catenin specific agonist BML284 group(10 mg/kg BML284 by intraperitoneal injection after 50 mg/kg PF administration).The renal histopathological changes were observed by HE staining and Paller scoring.ELISA was used to determine the contents of serum creatinine(Scr),neutrophil gelatinase-associated lipocalin(NGAL)and lactate,and renal contents of hexokinase 2(HK2),lactate dehydrogenase A(LDHA),IL-1β and IL-18.Western blotting was performed to detect the expression of total β-catenin,p-β-cateninY654,nucleus β-catenin and c-Myc.Results Compared with the Control group,the LPS group showed obviously damaged renal tissue,higher Paller score(P＜0.05),increased serum Scr and NGAL levels(P＜0.05),elevated renal contents of aerobic glycolytic indexes such as HK2,LDHA and serum lactate,as well as contents of IL-1β and IL-18(P＜0.05),and enhanced expression of total β-catenin,p-β-cateninY654,nucleus β-catenin and c-Myc in the renal tissue(P＜0.05).PF treatment attenuated the renal tissue damage,decreased Paller score(P＜0.05),reduced serum Scr and NGAL levels(P＜0.05),HK2,LDHA and serum lactate levels,and contents of IL-1 β and IL-18 in renal tissues(P＜0.05),and down-regulated the renal expression of total β-catenin,p-β-cateninY654,nucleusβ-catenin and c-Myc when compared with the levels in the model group(P＜0.05).While,addition of BML284 reversed above effects of PF treatment with significant differences(P＜0.05).Conclusion PF can alleviate SA-AKI,and its mechanism may be through its inhibiting the β-catenin/c-Myc pathway,thus reducing the aerobic glycolysis level and inflammatory response in renal tissue.

Catechol(CC)is a highly toxic phenolic pollutant,and its sensitive detection holds significant importance for environmental monitoring.Herein,graphene was used as a template to prepare graphdiyne/graphene(GDY/GR)heterogeneous materials,serving as high-performance electrochemical sensing materials for CC determination.GR played the role of an epitaxial template during the growth of GDY.The electrochemical experiment results demonstrated that the glassy carbon electrode(GCE)modified with GDY/GR showed excellent electrochemical response to CC,with a wide linear detection range(1-900 μmol/L)and a low detection limit(0.11 μmol/L).Meanwhile,GDY/GR/GCE also exhibited good anti-interference ability,stability and reproducibility.More importantly,the practicality of GDY/GR/GCE was evaluated and satisfactory results were obtained in actual water samples,which showed significant potential for practical applications in environmental monitoring.

Objective To explore a deep learning-based automatic bone age estimation model for elbow joint X-ray images of Chinese Han adolescents and children and evaluate its performance.Methods A total of 943(517 males and 426 females)elbow joint frontal view X-ray images of Chinese Han ado-lescents and children aged 6.00 to<16.00 years were collected from East,South,Central and North-west China.Three experimental schemes were adopted for bone age estimation.Scheme 1:Directly in-put preprocessed images into the regression model;Scheme 2:Train a segmentation network using"key elbow joint bone annotations"as labels,then input segmented images into the regression model;Scheme 3:Train a segmentation network using"full elbow joint bone annotations"as labels,then in-put segmented images into the regression model.For segmentation,the optimal model was selected from U-Net,UNet++and TransUNet.For regression,VGG16,VGG19,InceptionV2,InceptionV3,ResNet34,ResNet50,ResNet101 and DenseNet121 models were selected for bone age estimation.The dataset was randomly split into 80%(754 samples)for training and validation for model fitting and hyperparameter tuning,and 20%(189 samples)as an internal test set to test the performance of the trained model.An additional 104 elbow joint X-ray images from the same demographic and age group were col-lected and used as an external test set.Model performance was evaluated by comparing the mean ab-solute error(MAE),root mean square error(RMSE),accuracies within±0.7 years(P±0.7 years)and±1.0 years(P±1.0 years)between the estimated age and the actual age,and by drawing radar charts,scat-ter plots,and heatmaps.Results When segmented with Scheme 3,the UNet++model achieved good segmentation performance with a segmentation loss of 0.000 4 and an accuracy of 93.8%at a learning rate of 0.000 1.In the internal test set,the DenseNet121 model with Scheme 3 yielded the best results with MAE,P±0.7 years and P±1.0 years being 0.83 years,70.03%,and 84.30%,respectively.In the external test set,the DenseNet121 model with Scheme 3 also performed best,with an average MAE of 0.89 years and an average RMSE of 1.00 years.Conclusion When performing automatic bone age estima-tion using elbow joint X-ray images in Chinese Han adolescents and children,it is recommended to use the UNet++model for segmentation.The DenseNet121 model with Scheme 3 achieves optimal per-formance.Using segmentation networks,especially that trained with annotation areas encompassing the full elbow joint including the distal humerus,proximal radius,and proximal ulna,can improve the ac-curacy of bone age estimation based on elbow joint X-ray images.

Objective To explore a deep learning network model suitable for bone age estimation using shoulder joint X-ray images in Chinese Han adolescents.Methods A retrospective collection of 1 286 shoulder joint X-ray images of Chinese Han adolescents aged 12.0 to<18.0 years(708 males and 578 females)was conducted.Using random sampling,approximately 80%of the samples(1 032 cases)were selected as the training and validation sets for model learning,selection and optimization,and the other 20%samples(254 cases)were used as the test set to evaluate the model's generalization ability.The original single-channel shoulder joint X-ray images and dual-channel inputs combining original images with segmentation labels(manually annotated shoulder joint regions multiplied pixel-by-pixel with original images,followed by segmentation via the U-Net++network to retain only key shoulder joint region information)were respectively input into four network models,namely VGG16,ResNet18,ResNet50 and DenseNet121 for bone age estimation.Additionally,manual bone age estimation was con-ducted on the test set data,and the results were compared with the four network models.The mean absolute error(MAE),root mean square error(RMSE),coefficient of determination(R2),and Pear-son correlation coefficient(PCC)were used as main evaluation indicators.Results In the test set,the bone age estimation results of the four models with dual-channel input of shoulder joint X-ray images outperformed those with single-channel input in all four evaluation indicators.Among them,DenseNet121 with dual-channel input achieved best results with MAE of 0.54 years,RMSE of 0.82 years,R2 of 0.76,and PCC(r)of 0.88.Manual estimation yielded an MAE of 0.82 years,ranking second only to dual-channel DenseNet121.Conclusion The DenseNet121 model with dual-channel input combined with original images and segmentation labels is superior to manual evaluation results,and can effectively estimate the bone age of Chinese Han adolescents.

Objective To investigate the characteristics and differences of congenital endowment in senile dementia population based on the theory of five circuits and six qi.Methods Based on the cross-sectional data of China Health and Retirement Longitudinal Survey(CHARLS)in 2018,the dementia status of the population aged 60 and above in China was evaluated by using the Mini-Mental State Examination(MMSE),and the five-circuit and six-qi features at birth in the senile dementia population were analyzed by descriptive statistics and Chi-square goodness-of-fit test.Results A total of 854 patients with senile dementia were included.The five-circuit and six-qi features at birth in the senile dementia population were as follows:most of them were born at the heavenly stem of Bing while the least at the heavenly stem of Ji and Geng(P＜0.001),most of them were born at the earthly branch of Wei while the least at the earthly branch of Zi(P＜0.001),most of them were born at the yearly circuit of excessive water circuit while the least at the yearly circuit of excessive gold circuit and deficient earth circuit(P＜0.001),and most of the patients were born at sitan of taiyin damp-earth and zaiquan of taiyang cold-water while the least at sitan of jueyin wind-wood and zaiquan of shaoyang ministerial fire;no statistically significant differences were found in the dominant qi and guest qi(P＞0.05);most of the patients were born in the year of combination of circuit and qi being Shunhua while the least in the year of combination of circuit and qi being same celestial correspondence(P＜0.001),and the patients born in the year of Shunhua usually were frequently distributed in heavenly-stem and earthly-branch year of Jiawu(P＜0.001).Conclusion There is a certain relationship between the congenital endowment at birth and the incidence of senile dementia in the population of senile dementia.The circuit-qi features at birth for the prevalence of senile dementia are the yearly circuit of excessive water circuit,sitan of taiyin damp-earth and zaiquan of taiyang cold-water,and the year of the combination of circuit and qi being Shunhua.The population born at the time with the above circuit-qi features are prone to suffer the injury of the kidneys,the heart,and the spleen,and then result into illness.