ObjectiveTo investigate the protective effect of genistein （Gen） on etoposide-induced chondrocyte senescence and its underlying mechanism. MethodsThe C28/I2 cell line was treated with different concentrations of Gen and etoposide， and the cell viability was detected by the CCK-8 assay. The senescence model of C28/I2 chondrocytes was induced by etoposide， with Gen intervention. Senescence-associated β-galactosidase （SA-β-gal） staining was performed to detect the senescence-positive rate and staining characteristics of chondrocytes. The expressions of peroxiredoxin 6 （Prdx6）， cyclin-dependent kinaseto clarify the functional necessity of Prdx6. ResultsCompared with the etoposide group， the C28/I2 chondrocyte viability significantly increased （P<0.01）， the expression ofsenescence-associated proteins p21 and p16 decreased （P<0.01， P<0.05）， the expression of senescence-associated genes p21 and p16 reduced （both P<0.01）， the fluorescence intensity of senescence-associated proteins p21 and p16 was diminished （P<0.05， P<0.01）， and the proportion of SA-β-gal-positive cells decreased （P<0.01） in the Gen+etoposide group. Compared with the Control group， the expression of Prdx6 was downregulated in the etoposide group （P<0.05）. Compared with the etoposide group， the expression of Prdx6 was upregulated in the Gen+etoposide group （P<0.01）. Compared with the Control group， the GPx activity significantly decreased in the si-Prdx6 group （P<0.01）. Furthermore， compared with the si-Prdx6 group， the GPx activity increased in the si-Prdx6+Gen group （P<0.05）. Molecular docking results revealed that Gen formed hydrogen bond interactions with the active site of Prdx6. After Prdx6 knockdown， the expression of senescence-associated genes p21 and p16 and the fluorescence intensity of senescence-associated proteins p21 and p16 both increased in the Gen+etoposide+si-Prdx6 group （both P<0.01）. ConclusionGen can inhibit etoposide-induced senescence of C28/I2 chondrocytes by upregulating the expression of Prdx6. This study provides potential drug targets and experimental basis for the prevention and treatment of chondrocyte senescence-related diseases.

BACKGROUND:Ca2+expression in astrocytes has been found to be closely related to cognitive function,and the Ca2+signaling pathway regulated by inositol 1,4,5-trisphosphate receptors(IP3R2)and ryanodine receptor(RYR)2 receptors has become a hot spot in the study of cognitive disorder-related diseases. OBJECTIVE:To investigate the expression of Ca2+signals mediated by IP3R2 and RYR2 in hippocampal astrocytes in animal models of delayed encephalopathy after acute carbon monoxide poisoning,and to explore the possible pathogenesis of delayed encephalopathy after acute carbon monoxide poisoning. METHODS:C57BL mice with qualified cognitive function were selected by Morris water maze experiment and randomly divided into control group and experimental group.An animal model of delayed encephalopathy after acute carbon monoxide poisoning was established by static carbon monoxide inhalation in the experimental group,and the same amount of air was inhaled in the control group.Behavioral and neuronal changes,astrocyte specific marker glial fibrillary acidic protein,IP3R2,RYR2 receptor and Ca2+concentration in astrocytes of the two groups were detected using Morris water maze,hematoxylin-eosin staining,western blot,immunofluorescence double labeling and Ca2+fluorescence probe at 21 days after modeling. RESULTS AND CONCLUSION:In the Morris water maze,the escape latency of the experimental group was significantly longer than that of the control group(P<0.05).Hematoxylin-eosin staining results showed that in the experimental group,the number of hippocampal pyramidal cells decreased,the cell structure was disordered,and the nucleus was broken and dissolved.Immunofluorescence results showed that IP3R2 and RYR2 were co-expressed with glial fibrillary acidic protein in the hippocampus,and the expressions of IP3R2,RYR2 and glial fibrillary acidic protein were up-regulated in the hippocampus of the experimental group(P<0.05).Western blot analysis showed that the expressions of IP3R2,RYR2,and glial fibrillary acidic protein in the hippocampus of the experimental group were increased(P<0.05).Ca2+concentration in hippocampal astrocytes increased significantly in the experimental group(P<0.05).To conclude,astrocytes may affect Ca2+signals by mediating IP3R2 and RYR2 receptors,then impair the cognitive function of mice with carbon monoxide poisoning,and eventually lead to delayed encephalopathy after acute carbon monoxide poisoning.

Objective : To explore the effects and mechanisms of Kobophenol A ( KPA) on lipopolysaccharide ( LPS) -induced M1 macrophage polarization，and to provide a theoretical basis for the treatment of inflammatory immune diseases and the development of new drugs． Methods: The M1 macrophage polarization model of RAW264. 7 was established by LPS induction，and the peroxiredoxin 6 ( Prdx6) knockdown model was constructed using the Prdx6 inhibitor MJ33 and Prdx6-siRNA．RAW264. 7 cells，a mouse macrophage cell line，were treated with various concentrations of KPA． Cell viability was assessed using the CCK-8 assay．The expression levels of Prdx6 and M1 macrophage polarization-related proteins，including inducible nitric oxide synthase ( iNOS) and cyclooxygenase-2 ( COX-2) ，were detected by Western blot and immunofluorescence staining．The expression levels of Prdx6 and M1 macrophage polarization-related genes iNOS，interleukin-6 ( IL-6) ，and tumor necrosis factor α ( TNF-α) ，were measured by RT-qPCR. Flow cytometry was employed to detect the expression of cluster of differentiation 86 ( CD86) ，a marker of M1 macrophages． Results: Compared with the LPS-induced M1 macrophage polarization model ， KPA significantly reversed the morphological changes of M1 macrophage polarization in RAW264. 7 macrophages and decreased the expression of M1 macrophage polarization-related proteins iNOS，COX- 2，CD86 and related genes iNOS，IL-6，TNF-α ( all P＜0. 05) ．In addition，LPS significantly downregulated the expression of Prdx6 in RAW264. 7 macrophages，while KPA upregulated the expression of Prdx6．Moreover，treatment with the Prdx6 inhibitor MJ33 significantly upregulated the expression of iNOS，a marker of M1 macrophage polarization，in RAW264. 7 macrophages，whereas treatment with KPA significantly downregulated the expression of iNOS ( all P＜0. 05) ． Conclusion KPA inhibits LPS-induced M1 polarization of RAW264. 7 macrophages by upregulating the expression of Prdx6．

Objective To summarize the medicinal properties of new foreign introducing Chinese materia medica Drimia maritima(L.)Stearn based on literature research;To further verify its five flavors by applying intelligent sense;To provide new ideas for the medicinal properties research of new foreign introducing Chinese materia medica.Methods Literature about Drimia maritima(L.)Stearn was retrieved from CNKI,VIP,Wanfang Data,PubMed,Web of Science,and combined with the TCM theories medicinal properties of Drimia maritima(L.)Stearn was summarized.PEN3 electronic nose and SA402B electronic tongue were used to obtain intelligent sensory information of Drimia maritima(L.)Stearn,and the principal component analysis(PCA)was used to identify its five flavors.Results Literature research summarize Drimia maritima(L.)Stearn with antioxidant,anti-tumor,strengthening cardiac functions and diuresis,reducing cough and asthma and other pharmacological effects.Combined with the theories,it explored that its property was mainly slightly warm,the tastes were mainly bitter,pungent,sweet,and slightly toxic,belonging to the lung,spleen,stomach and heart meridians.Based on intelligent sense,identification results of five tastes of Drimia maritima(L.)Stearn were bitter,slightly pungent,slightly sweet,salty,non-acid,basically consistent with the literature research.Conclusion Literature research combined with intelligent sense can better summarize and recognize the medicinal properties of Drimia maritima(L.)Stearn.This study can provide a certain reference for a more objective and adequate medicinal properties analysis of new foreign introducing Chinese materia medica.

Both the androgen receptor pathway and PI3K/AKT pathway play pivotal roles in the progression of prostate cancer.There are intricate interactions between these two pathways,showing a negative regulatory relationship of mutual restriction between them.In view of the above,a combined inhibition strategy targeting these two pathways is expected to become a significant therapeutic approach for prostate cancer.This article aims to comprehensively review the molecular mechanisms underlying the interactions between the androgen receptor and PI3K/AKT pathways,to provide new perspectives and insights for research in the fields.

Objective: To evaluate the clinical value of combining low-dose energy spectrum CT with virtual un-enhanced(VUE) scanning and deep-learning image reconstruction(DLIR) in aortic CT angiography(CTA). Methods : In a prospective study, 94 patients scheduled for aortic CTA were randomized into two groups: a low-dose energy spectrum group and a standard 100 kVp enhancement group, with 47 patients in each. All patients initially underwent a true un-enhanced(TUE) scan at 120 kVp using adaptive statistical iterative reconstruction-V(ASIR-V) at 40% for image reconstruction. The low-dose group received enhanced scans using gemstone spectral imaging(GSI) mode with DLIR-H, producing 60 keV virtual monoenergetic images(VMIs) and VUE images. The standard group was scanned at 100 kVp, with images reconstructed using ASIR-V at 50%. Parameters were measured including CT values, noise(SD), signal-to-noise ratio(SNR), and contrast-to-noise ratio(CNR) for key vascular and muscular areas, alongside the effective radiation dose(ED). Two radiologists evaluated the image quality using a 5-point scale. Results : The low-dose group exhibited significantly higher SNR and CNR values in the ascending aorta, descending aorta, abdominal aorta, and common iliac artery compared to the standard group(P<0.05), with comparable subjective quality scores. The VUE images also demonstrated superior SNR values in the abdominal aorta, common iliac artery, and psoas major muscle, and CNR value in the ascending aorta compared to TUE images, with similar subjective quality. Importantly, the ED in the low-dose group was about 40% lower than that of the standard group. Conclusion Low-dose energy spectrum CT with DLIR in aortic CTA can significantly enhance SNR and CNR, while approximating the image quality of traditional TUE scans, thereby substantially reducing radiation exposure.

Objective:To evaluate the safety, efficacy, advantages and disadvantages of the modified double-orifice valve plasty via total thoracoscopy for partial atrioventricular septal defect(PAVSD) through a retrospective analysis of early postoperative results.Methods:Patients diagnosed with PAVSD who underwent the standardized modified double-orifice valve plasty via total thoracoscopy between September 2023 and August 2024 were retrospectively enrolled. Baseline characteristics, surgical parameters, and follow-up outcomes were systematically analyzed.Results:A total of 14 patients(6 males, 8 females) were included, with a mean age of(32.9±15.5) years old and body weight of(55.1±11.6) kg. All procedures were successfully completed. The mean operative time, cardiopulmonary bypass time, and aortic cross-clamp time were(266.6±67.2) min, (160.7±34.2) min, and(97.0±31.1) min, respectively. Postoperative ICU stay, hospital stay, and total hospitalization duration were(1.7±1.1) days, (6.4±4.2) days, and(12.6±4.5) days, respectively. The mean follow-up duration was(7.9±3.6) months. Preoperatively, left atrioventricular valve regurgitation(LAVVR) was graded as mild, moderate, or severe in 5, 4, and 5 patients. Postoperatively, 13 patients exhibited mild or less LAVVR, with 1 case of moderate regurgitation. By 3 months, all patients demonstrated LAVVR of mild or lower severity, which remained stable through follow-up. Peak LAVV gradients were(4.6±2.7) mmHg(1 mmHg=0.133 kPa)(range: 1.8-10.2 mmHg) postoperatively, improving to(3.6±0.6) mmHg(3.2-4.0) mmHg at 1 year. Right atrioventricular valve regurgitation improved from preoperative moderate-severe(50.0%) to LAVVR of mild or lower severity in all patients by 3 months. No mortality, residual shunts, or high-grade atrioventricular block occurred through follow-up. By 1 month, NYHA functional class improved to Ⅰ in all patients, which remained stable through follow-up.Conclusion:Standardized modified double-orifice valve plasty via total thoracoscopy for PAVSD demonstrates safety, minimal invasiveness, and rapid recovery, with favorable early outcomes.

Objective:To evaluate the left atrial structure and function in patients with non-obstructive hypertrophic cardiomyopathy（NOHCM）and atrial fibrillation（AF）using four-dimensional automatic left atrial quantification（4D Auto LAQ）technology，and to explore the correlation between left atrial remodeling and AF.Methods:Ninety patients with NOHCM treated in the First Affiliated Hospital of Zhengzhou University from May 2023 to September 2024 were prospectively selected and divided into AF group（ n=27）and non-AF group（ n=63）according to whether they had AF. Clinical data of all enrolled patients were collected，and two-dimensional，color Doppler，and tissue Doppler ultrasound parameters were measured. 4D Auto LAQ technology was used to obtain left atrial volume and strain parameters. Inter-group comparison，univariate and multivariate Logistic regression analysis，and repeatability test were used to analyze the data. Results:Compared with non-AF group，left atrial maximum volume index（LAVImax），left atrial minimum volume index（LAVImin）and left atrial pre-systolic volume index（LAVIpreA）were increased in the AF group，but left atrial total ejection fraction（LAEF），left atrial passive ejection fraction（LApEF），left atrial active ejection fraction（LAaEF）and the absolute values of left atrial reservoir longitudinal and circumferential strains（LASr，LASr-c），left atrial conduit longitudinal and circumferential strains（LAScd，LAScd-c）and left atrial contraction longitudinal and circumferential strains（LASct，LASct-c）were decreased（all P<0.05）. Multivariate Logistic regression analysis showed that LAVImin was independently associated with AF（ OR=0.837， P<0.001）. Conclusions:4D Auto LAQ can quantitatively evaluate the left atrial structure and function in patients with NOHCM and AF，and LAVImin is independently associated with the presence of AF.

Objective:To observe the high-frequency ultrasound characteristics of the median nerve（MN）in patients with acromegaly，and to investigate the clinical value of multiparameter quantitative ultrasound for noninvasive assessment of carpal tunnel syndrome（CTS）in acromegalic patients.Methods:A total of 132 acromegalic patients due to pituitary growth hormone tumors in Huashan Hospital during July 2023 to September 2024 including initial patients and postoperative revisions were prospectivly collected. The patients were divided into no neurological symptoms group（ n=51）and clinical CTS group（ n=81）based on the Boston Carpal Tunnel Questionnaire. All patients underwent bilateral MN ultrasonography，the ultrasound parameters included the cross-sectional area（CSA）of MN at the entrance of carpal tunnel，the maximum CSA of MN in carpal tunnel，the maximum and minimum thickness of MN in carpal tunnel，CSA of MN at forearm 1/3，soft tissue thickness at the wrist，CSA of MN at elbow transverse stripe，blood flow signals within the MN at the carpal tunnel，ratio of the CSA（CSA of MN at the entrance of carpal tunnel/ CSA of MN at forearm 1/3），ratio of thickness（maximum / minimum thickness of MN in carpal tunnel）. Differences in general information，clinical indicators and ultrasound parameters were analyzed between the two groups. The diagnostic model was established with ultrasound parameters and clinical indicators using univariate and multivariate logistic analyses in a training cohort of 106 patients，to predict CTS within acromegaly. And ROC curve was used to evaluate the efficacy of the model in a test cohort of 26 patients with neurophysiological examination data. Results:Patients in clinical CTS group were older，with longer disease duration，higher levels of growth hormone 25-hydroxyvitamin D 3 and insulin-like growth factor-1 and were more likely to have impaired glucose tolerance relative to the no neurologic symptoms group（all P < 0.05）. Comparison between the two groups revealed significant differences in all ultrasound parameters：the CSA at the entrance of the MN carpal tunnel，the 1/3 of the forearm and the elbow were larger than the no neurological symptoms group（all P < 0.001），and the MN thickness ratio was greater observably in the clinical CTS group（ P < 0.001）. Greater thickness of the soft tissue at wrist and more blood flow signals in MN in carpal tunnel were revealed in clinical CTS group patients（ P < 0.001）.Combining the results of multifactorial logistic analysis，the multiparametric ultrasound combined with clinical index diagnosing model based on the predicted disease duration，CSA of MN at the entrance of carpal tunnel，MN thickness ratio and soft tissue thickness at the carpal tunnel was established to diagnose CTS combined with acromegaly. The ROC curve was plotted in the test cohort and the area under the curve for this model was 0.894. Conclusions:High-frequency ultrasound is sensitive to observe MN changes in acromegalic patients and the combination of multiparametric ultrasound and clinical index is useful for the non-invasive diagnosis of acromegalic patients with CTS.

Objective:To evaluate the left atrial function in patients with hypertrophic cardiomyopathy（HCM）combined with heart failure with preserved ejection fraction（HFpEF）using four-dimensional automated left atrial quantification（4D Auto LAQ）technology，and to investigate the independent factors affecting patients with HCM combined with HFpEF.Methods:One hundred HCM patients with left ventricular ejection fraction（LVEF）≥ 50% who were admitted to the First Affiliated Hospital of Zhengzhou University from September 2023 to March 2025 were prospectively selected. There were 50 cases in the HFpEF group and 50 cases in the non-HF group. The clinical data and conventional ultrasound parameters of HCM patients were collected. The 4D Auto LAQ technology was applied to obtain the four-dimensional volume and strain parameters of the left atrium，including the minimum left atrial volume（LAVmin），the maximum left atrial volume（LAVmax），the maximum left atrial volume index（LAVImax），the pre-atrial contraction volume（LAVpreA），the left atrial emptying volume（LAEV），the left atrial ejection fraction（LAEF），the longitudinal and circumferential strains in the left atrial reservoir period（LASr，LASr-c），the longitudinal and circumferential strains in the left atrial conduit period（LAScd，LAScd-c），the longitudinal and circumferential strains in the left atrial contraction period（LASct，LASct-c），and the minimum left atrial volume index（LAVImin）. The differences in the above parameters between the two groups were compared. Univariate and multivariate Logistic regression analyses were used to analyze the independent influencing factors in HCM patients with HFpEF. The intraclass correlation coefficient was used to test the repeatability of the 4D Auto LAQ parameters.Results:Compared with the non-HF group，LAVmin，LAVmax，LAVpreA，LAVImin，and LAVImax increased，while LAEF，LASr，LAScd，LASct，LASr-c，LAScd-c，and LASct-c decreased in the HFpEF group（all P<0.05）. Multivariate Logistic regression analysis showed that LASr was the strongest independent influencing factor in patients with HCM combined with HFpEF（ OR=0.255， P=0.003）. The consistency test showed that the intraclass correlation coefficients of each parameters of 4D Auto LAQ were all>0.7，the consistency was good. Conclusions:4D Auto LAQ technology can be used to evaluate left atrial function in patients with HCM combined with HFpEF，and LASr is the strongest independent influence factor in patients with HCM combined with HFpEF.