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 construct and validate a clinical model combining CYP11B2 gene polymorphisms with clinical parameters to predict complete postoperative hypertension remission in primary aldosteronism patients.Methods:The clinical data of a total of 116 patients with primary aldosteronism who underwent unilateral adrenalectomy from April 2018 to August 2024 were retrospectively included. There were 63 males and 53 females，with a body mass index（BMI）of（25.50 ± 2.03）kg/m 2. Genomic DNA was extracted from venous blood leukocytes before surgery，and polymerase chain reaction-restriction fragment length polymorphisms（PCR-RFLP）were used to detect CYP11B2（rs1799998）promoter region 344（C > T）base substitution. The follow-up duration was more than 6 months，with the following parameters recorded at the last follow-up：plasma aldosterone，renin，serum potassium，and sodium levels. Blood pressure progression and antihypertensive medication usage were also assessed. The postoperative outcome was determined according to the Primary Aldosteronism Surgical Outcome score（PASO）for primary aldosteronism，and the specific criteria were as follows. ① Clinical complete remission：the patient's blood pressure returned to normal（< 140/90 mmHg，1 mmHg = 0.133 kPa）and all antihypertensive drugs were discontinued；②Partial clinical remission：blood pressure returns to normal，and the number or dose of antihypertensive drugs is reduced compared with before；③Clinical non-remission：blood pressure does not drop and antihypertensive drugs do not change or increase compared with before surgery. Patients were divided into complete and incomplete remission groups. The chi-square test was used for univariate analysis，followed by binary logistic forward conditional regression for multivariate analysis，and a variety of machine learning algorithms such as random forest，logistic regression，support vector machine and gradient lifter were integrated，and the results of multivariate analysis were included to construct a postoperative blood pressure outcome model，and the predictive performance of the model was evaluated by using receiver operating characteristic（ROC）curve，calibration curve and clinical decision curve. Results:The PCR-RFLP detection results of 116 cases showed the genotype distribution of CYP11B2（344C > T）（rs1799998）as follows：CC type in 50 cases（43.1%），CT type in 46 cases（39.7%），and TT type in 20 cases（17.3%）. There were 74 cases in the complete remission group and 42 cases in the incomplete remission group，and the rate of complete remission with hypertension at the end of the operation was 63.8%. Univariate analysis showed that the the differences between complete remission group and incomplete remission group in body mass index［（24.27 ± 2.90）kg/m 2 vs.（26.98 ± 3.17）kg/m 2， P<0.001］，preoperative hypertension grade（grade 1/2/3：29/29/16 cases vs. 9/13/20 cases， P = 0.012），preoperative antihypertensive drugs（0/1/≥ 2：25/32/17 cases vs. 7/15/20 cases， P = 0.016），and CYP11B2（344C > T）（CC/TT + CT：39/35 cases vs. 11/31 cases， P = 0.006）were statistically significant. Multivariate analysis showed that the type of preoperative antihypertensive drugs［≥ 2： OR = 5.26（95% CI 1.12?24.61， P = 0.016；1： OR = 4.55（95% CI 1.23?22.47）， P = 0.025］was the strongest independent predictor，followed by CYP11B2（344C > T）［ OR = 4.02（95% CI 1.16?13.82）， P = 0.028］and BMI［ OR = 3.96（95% CI 2.26?6.92）， P < 0.001］. Comparing the receiver operating feature（ROC）curves of the four types of machine learning models，the best model was the support vector machine model with an area under the curve（AUC）of 0.88（95% CI 0.82?0.95），followed by the gradient elevator model of 0.83（95% CI 0.76?0.91），the logistic regression model of 0.78（95% CI 0.68?0.88），and the random forest model of 0.77（95% CI 0.68?0.86）. The optimal threshold of the Yoden index of the support vector machine model was 0.588，with a sensitivity of 78.5% and a specificity of 86.5%. The clinical decision curve and calibration curve show that the support vector machine model has a higher net benefit and acceptable stability and reliability. Conclusions:The support vector machine model incorporating CYP11B2 gene polymorphisms，BMI，and types of preoperative antihypertensive medications could effectively predict postoperative hypertension remission in primary aldosteronism patients，providing new evidence for personalized treatment strategies

Objective:To investigate the predictive value of endothelial activation and stress index(EASIX)for the prognosis of patients with mantle cell lymphoma(MCL).Methods:A retrospective analysis was conducted to assess prognosis and compare the clinical features of patients diagnosed with MCL who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to June 2023,had therapeutic indications and received standard treatment.Results:A total of 66 patients were included and divided into high EASIX group and low EASIX group,according to a cutoff value of 0.97 determined by the receiver operating characteristic(ROC)curve.Multivariate Cox regression analysis showed that prealbumin＜0.2 g/L,high EASIX,and ECOG PS score ≥2 were independent risk factors influencing overall survival(OS)in MCL patients.The median OS of patients in the high and low EASIX group was 13.0 and 37.5 months,and the median progression-free survival was 8.8 and 26.0 months,respectively.The proportions of patients with ECOG PS score ≥2 and prealbumin＜0.2 g/L at onset significantly increased in the high EASIX group compared to those in the low EASIX group.Conclusion:At the time of initial diagnosis,EASIX can serve as an independent prognostic indicator impacting OS in patients with MCL.Furthermore,patients in the high EASIX group experience a poorer prognosis and shorter survival duration compared with those in the low EASIX group.

Objective:To construct and validate a clinical model combining CYP11B2 gene polymorphisms with clinical parameters to predict complete postoperative hypertension remission in primary aldosteronism patients.Methods:The clinical data of a total of 116 patients with primary aldosteronism who underwent unilateral adrenalectomy from April 2018 to August 2024 were retrospectively included. There were 63 males and 53 females，with a body mass index（BMI）of（25.50 ± 2.03）kg/m 2. Genomic DNA was extracted from venous blood leukocytes before surgery，and polymerase chain reaction-restriction fragment length polymorphisms（PCR-RFLP）were used to detect CYP11B2（rs1799998）promoter region 344（C > T）base substitution. The follow-up duration was more than 6 months，with the following parameters recorded at the last follow-up：plasma aldosterone，renin，serum potassium，and sodium levels. Blood pressure progression and antihypertensive medication usage were also assessed. The postoperative outcome was determined according to the Primary Aldosteronism Surgical Outcome score（PASO）for primary aldosteronism，and the specific criteria were as follows. ① Clinical complete remission：the patient's blood pressure returned to normal（< 140/90 mmHg，1 mmHg = 0.133 kPa）and all antihypertensive drugs were discontinued；②Partial clinical remission：blood pressure returns to normal，and the number or dose of antihypertensive drugs is reduced compared with before；③Clinical non-remission：blood pressure does not drop and antihypertensive drugs do not change or increase compared with before surgery. Patients were divided into complete and incomplete remission groups. The chi-square test was used for univariate analysis，followed by binary logistic forward conditional regression for multivariate analysis，and a variety of machine learning algorithms such as random forest，logistic regression，support vector machine and gradient lifter were integrated，and the results of multivariate analysis were included to construct a postoperative blood pressure outcome model，and the predictive performance of the model was evaluated by using receiver operating characteristic（ROC）curve，calibration curve and clinical decision curve. Results:The PCR-RFLP detection results of 116 cases showed the genotype distribution of CYP11B2（344C > T）（rs1799998）as follows：CC type in 50 cases（43.1%），CT type in 46 cases（39.7%），and TT type in 20 cases（17.3%）. There were 74 cases in the complete remission group and 42 cases in the incomplete remission group，and the rate of complete remission with hypertension at the end of the operation was 63.8%. Univariate analysis showed that the the differences between complete remission group and incomplete remission group in body mass index［（24.27 ± 2.90）kg/m 2 vs.（26.98 ± 3.17）kg/m 2， P<0.001］，preoperative hypertension grade（grade 1/2/3：29/29/16 cases vs. 9/13/20 cases， P = 0.012），preoperative antihypertensive drugs（0/1/≥ 2：25/32/17 cases vs. 7/15/20 cases， P = 0.016），and CYP11B2（344C > T）（CC/TT + CT：39/35 cases vs. 11/31 cases， P = 0.006）were statistically significant. Multivariate analysis showed that the type of preoperative antihypertensive drugs［≥ 2： OR = 5.26（95% CI 1.12?24.61， P = 0.016；1： OR = 4.55（95% CI 1.23?22.47）， P = 0.025］was the strongest independent predictor，followed by CYP11B2（344C > T）［ OR = 4.02（95% CI 1.16?13.82）， P = 0.028］and BMI［ OR = 3.96（95% CI 2.26?6.92）， P < 0.001］. Comparing the receiver operating feature（ROC）curves of the four types of machine learning models，the best model was the support vector machine model with an area under the curve（AUC）of 0.88（95% CI 0.82?0.95），followed by the gradient elevator model of 0.83（95% CI 0.76?0.91），the logistic regression model of 0.78（95% CI 0.68?0.88），and the random forest model of 0.77（95% CI 0.68?0.86）. The optimal threshold of the Yoden index of the support vector machine model was 0.588，with a sensitivity of 78.5% and a specificity of 86.5%. The clinical decision curve and calibration curve show that the support vector machine model has a higher net benefit and acceptable stability and reliability. Conclusions:The support vector machine model incorporating CYP11B2 gene polymorphisms，BMI，and types of preoperative antihypertensive medications could effectively predict postoperative hypertension remission in primary aldosteronism patients，providing new evidence for personalized treatment strategies

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Objective To explore the optimization strategy of Qishen Granules in treating coronary heart disease with heart failure(CHD-HF)based on data mining and the pathogenic"toxin"theory,and to predict its active components and mechanisms using network pharmacology.Methods Literature on traditional Chinese medicine(TCM)for treating CHD-HF was collected from relevant databases,and prescriptions were screened and established into a database according to inclusion and exclusion criteria.Frequency,association rules,and hierarchical clustering analyses were performed using the Ancient and Modern Medical Case Cloud Platform.Network pharmacology techniques were applied to screen potential targets of the optimized combination for treating CHD-HF,and carry out the targets and pathways enrichment analysis.Results A total of 336 articles and 339 prescriptions involving 191 herbs were included,with 12 herbs used more than 100 times.The core drug combinations for treating CHD-HF included Astragali Radix,Poria,Salviae Miltiorrhizae Radix et Rhizoma,Glycyrrhizae Radix et Rhizoma,Chuanxiong Rhizoma,etc,while commonly used detoxifying herbs included Leonuri Herb,Coptidis Rhizoma,etc.Association rule analysis yielded 10 two-item associations and 17 three-item associations;clustering analysis grouped the data into 5 categories.Based on data mining and the pathogenic"toxin"theory,the combination for treating CHD-HF was optimized to include Astragali Radix,Salviae Miltiorrhizae Radix et Rhizoma,Aconiti Lateralis Radix Praeparata,Glycyrrhizae Radix et Rhizoma,Coptidis Rhizoma,and Taraxaci Herba.Network pharmacology analysis identified 366 common targets between the optimized combination and CHD-HF,with 16 core targets screened out.Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis revealed significant enrichment in pathways such as cancer pathways,lipid and atherosclerosis,Rap1 signaling pathway,hypoxia-inducible factor 1(HIF-1)signaling pathway,phosphatidylinositol-3-kinase/protein kinase B(PI3K/Akt)signaling pathway,Ras signaling pathway,and mitogen-activated protein kinase(MAPK)signaling pathway.Conclusion TCM treatment for CHD-HF primarily focuses on replenishing qi and warming yang,activating blood circulation and resolving fluid retention.Based on data mining results and the pathogenic"toxin"theory,the formulation strategy of Qishen Granules for treating CHD-HF was optimized,potentially exerting therapeutic effects through anti-inflammatory,anti-apoptotic,and anti-hypoxia physiological processes.

Traditional mass measurement methods are not applicable in microgravity environments,and the main challenge for in-orbit body mass measurement technology based on inertial principles is to address the random errors brought about by the weightless environment.These include additional torques due to shifts in the center of mass,nonlinear accelerations due to non-rigid human bodies,mechanical energy consumption due to organ vibrations,and random vibrations of the measurement device itself.To address the above difficulties,the project proposes a technical scheme based on the principle of linear acceleration,designs and constructs a ground-specific air-floating experimental and simulation platform,studies key data such as motion trajectory,acceleration change,and vibration frequency amplitude during the mass measurement process,and simulates the changes in the center of mass and random vibrations of the human body in a weightless environment.The project has designed an adjustable posture bracket to adapt to changes in the center of mass,enhance body restraint,and greatly reduce shaking;it has also developed an integrated four-bar linkage motion guidance mechanism,high-precision integrated photoelectric distance measurement,and modular motion constant force measurement device to ensure the accurate measurement of acceleration and constant force data.The product has undergone simulation calculations,ground human applicability tests,and in-orbit applicability verification in the space station.Ground test results show that the device achieves a body mass measurement accuracy better than 0.5%,and the dispersion is better than 0.38%;after flight mission verification and evaluation,the in-orbit body mass measurement dispersion is less than 0.4%,which is superior to the SLAMMD,a mass measurement device of the same principle on the International Space Station,and is at the forefront internationally,achieving accurate body mass measurement.

As a comprehensive high technology,robotics has gained extensive attention from numerous researchers.Intelligent soft robots,representing a new direction in robotics research,are shining brightly in fields such as fragile objects manipulating,medical assistance,and environment exploration due to their unique advantages.In the field of specialized medicine,intelligent soft robots can adapt to the complex and extreme space working environment due to their small stiffness,strong variability and high flexibility,and have broad application prospects in specialized medicine like aerospace,navigation and diving.In this paper,the research status of intelligent soft robots is reviewed from four aspects:materials,structure,actuation modalities,modeling and simulation.Furthermore,the application of intelligent soft robots in the field of specialized medicine is summarized and prospected in this paper.

OBJECTIVE: To investigate the predictive role of the modified Endothelial Activation and Stress Index (mEASIX) in the efficacy of chimeric antigen receptor T-cell (CAR-T) therapy and cytokine release syndrome (CRS). METHODS: The clinical data of 70 relapsed and refractory (R/R) B-cell tumor patients who were treated with CAR-T therapy from September 1, 2018 to February 28, 2023 in the Department of Hematology, Affiliated Hospital of Xuzhou Medical University, were retrospectively analyzed. The value of log-2 mEASIX before conditioning (-7 d) was calculated, and the patients were divided into a low-mEASIX group (42 patients) and a high-mEASIX group (28 patients) based on the cut-off value of 5.443 determined by the receiver operating characteristic (ROC) curve. Eventually, the predictive role of mEASIX before conditioning on the efficacy of CAR-T cell therapy and CRS was analyzed. RESULTS: The high-mEASIX group exhibited significantly worse median overall survival (OS) and median progression-free survival (PFS) in comparison to the low mEASIX group (OS: 3.2 months vs not reached, P < 0.01; PFS: 1.3 months vs 6.0 months, P =0.009). The incidence of grade ≥2 CRS in the high-mEASIX group was substantially higher than that in the low-mEASIX group (57.1% vs 19.0%, P =0.007). The degree of remission after CAR-T therapy (P =0.001), whether CRS occurs or not (P =0.041), the lactate dehydrogenase (LDH) level before conditioning (P =0.046), and the mEASIX score before conditioning (P =0.047) were independent influencing factors for the OS of patients receiving CAR-T cell therapy. CONCLUSION The mEASIX score before conditioning can predict OS and the incidence of grade ≥2 CRS in patients with relapsed and refractory B-cell tumors who receive CAR-T cell therapy.
Cytokine Release Syndrome/therapy* ; Immunotherapy, Adoptive/methods* ; Humans ; Lymphoma, B-Cell/therapy* ; Retrospective Studies ; Hematology ; China ; Receptors, Chimeric Antigen/blood* ; Predictive Value of Tests

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*