Objective:To investigate the effect of saikosaponin A on depressive-like behaviors and hippocampal cyclic adenosine monophosphate response element-binding(CREB) protein expression in olfactory bulbectomized mice.Methods:Totally thirty male SPF-grade C57BL/6J mice, six weeks old, were randomly divided into 3 groups ( n=10 in each group): the control group, the olfactory bulbectomy group, and the saikosaponin A group.Olfactory bulbectomy was performed to damage the olfactory bulbs in the mice of bulbectomy group and saikosaponin A group, while the mice of control group only had a cranial drill hole at the same coordinates without damaging the olfactory bulbs. Mice in saikosaponin A group were administered saikosaponin A solution (dose: 5 mg/kg) via gavage, while mice in the control and olfactory bulbectomy groups were given the same volume of 0.9% NaCl solution once a day for 21 days. The depressive-related behavioral changes of mice in each group were evaluated by open field test, tail suspension test, forced swimming test, and weight measurement. The expression of CREB in the hippocampus of mice were detected by Western blot. Graphpad prism 5 software was used for data analysis.The data comparison among the multiple groups was conducted by one-way ANOVA and further pairwise comparisons were conducted by Tukey test. Results:(1) The results of weight measurement showed that there was no significant difference in body weight among the three groups( F=0.468, P=0.631) on the day of the olfactory bulbectomy surgery, but there was a statistically significant difference in body weight among the three groups ( F=37.340, P<0.001) on the 28th day after the olfactory bulbectomy.The body weight of mice in the olfactory bulbectomy group was lower than that of the control group ((24.09±1.01) g, (27.22±0.58)g)( P<0.05). The body weight of mice in the saikosaponin A group((26.23±0.83)g) was higher than that of the olfactory bulbectomy group( P<0.05). There was a statistically significant difference in body weight differences among the three groups of mice ( F=48.180, P<0.001). The body weight difference of mice in the olfactory bulbectomy group was lower than that of the control group ((2.34±0.96) g, (5.57±0.72) g) ( P<0.05). The body weight difference of mice in the saikosaponin A group was higher than that of the olfactory bulbectomy group ((4.74±0.56) g, (2.34±0.96) g) ( P<0.05).(2) The results of the open field test showed that there were statistically significant differences in the central area residence time and total activity distance in mice among the three groups ( F=27.03, 10.98, both P<0.001). The central area residence time ((13.87±4.59) s) and total activity distance ((35.67±4.88) m) of mice in the olfactory bulbectomy group were both less than those of the control group ((27.44±2.76) s, (59.02±16.21) m) (both P<0.05).The central area residence time ((21.77±4.78) s) and total activity distance ((52.33±10.41) m) of mice in the saikosaponin A group were both higher than those of the olfactory bulbectomy group(both P<0.05).(3) The results of tail suspension test showed that there was a statistically significant difference in immobility time among the three groups ( F=74.57, P<0.001). The immobility time of mice in the olfactory bulbectomy group was longer than that of the control group ((148.20±8.84)s, (97.89±8.64)s) ( P<0.05). The immobility time of mice in the saikosaponin A group((135.70±11.09)s) was less than that of the olfactory bulbectomy group( P<0.05). (4) The results of forced swimming test showed that there was a significant difference in immobility time among the three groups ( F=51.73, P<0.001). The immobility time of mice in the olfactory bulbectomy group was longer than that of the control group ((61.39±5.20) s, (40.80±4.30) s) ( P<0.05).The immobility time of mice in the saikosaponin A group((53.52±4.13)s) was less than that of the olfactory bulbectomy group( P<0.05). (5) The results of Western blot showed that there was a significant difference in hippocampal CREB protein expression among the three groups ( F=13.32, P<0.001).Compared with the control group, hippocampal CREB protein expression of mice in the olfactory bulbectomy group was significantly down-regulated(0.51±0.15, 1.45±0.61) ( P<0.05).Compared with the olfactory bulbectomy group, hippocampal CREB protein expression in the saikosaponin A group(0.97±0.09) was up-regulated( P<0.05). Conclusion:Saikosaponin A can significantly alleviate the depressive-like behaviors in olfactory bulbectomized mice, and its mechanism may be related to the up-regulation of CREB protein expression in the hippocampus.

Objective:To investigate the combined application of cytology, cell block histology and immunohistochemistry to improve the diagnostic accuracy of solid pancreatic lesions in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) samples.Methods:The pathological data of EUS-FNA in 311 cases of solid pancreatic lesions submitted to the Second Hospital of Hebei Medical University, Shijiazhuang, China from May 2019 to September 2023 were retrospectively analyzed. The cases included pancreatic ductal adenocarcinoma (PDAC, 172 cases), solid pseudopapillary neoplasm (SPN, 12 cases), neuroendocrine tumors (PNET, 14 cases) and chronic pancreatitis (113 cases). The cytological features of smears, the histology of cell block sections and the diagnostic markers in PDAC, SPN and PNET were analyzed. The diagnostic accuracies of cytology, cell block histology/immunohistochemistry and combination of the two methods for classifying these pancreatic solid lesions were evaluated.Results:Irregular arrangement of atypical (cancer) cells, anisonucleosis and nuclear atypia were the typical cytological features of PDAC, while presence of pseudopapillae with a myxoid/hyalinized fibrovascular core and low adhesion/salt-and-pepper chromatin were diagnostic features of SPN and NET, respectively. Immunohistochemical results showed that CK7 and CK19 were the most sensitive markers of pancreatic ductal epithelia, and the diffuse strong expression of S-100P (102/111, 91.9%) and aberrant expression of p53 (80/111, 72.1%) were important immunophenotypic markers of PDAC. Various degrees of CDX2 expression could be found in 66.4% PDAC. The expression of CD10, PR, vimentin, CD99 and cyclinD1 and the aberrant expression of β-catenin were the immunophenotypic features of SPN, while the expression of CgA, Syn and CD56 were indispensable immunemarkers for the diagnosis of PNET. Overall, cytology had higher sensitivity than cell block histology (93.9% versus 82.8%) and lower specificity (92.9% versus 99.1%), while the combination of the two methods significantly improved the sensitivity to 96.9% in solid pancreatic lesions. The combination of cytology and cell block histology could significantly improve the diagnostic efficacy of EUS-FNA in PDAC.Conclusions:Integrated diagnosis based on cytology (including rapid on-site evaluation), cell block histology and immunohistochemical findings could significantly improve the diagnostic yield of EUS-FNA in classifying solid pancreatic lesions.

Objective:To explore the clinical value of autologous umbilical cord whole blood(UCB) priming of the cardiopulmonary bypass(CPB) circuit in neonatal cardiac surgery for congenital heart disease(CHD).Methods:This prospective non-randomized controlled trial included neonates undergoing CHD surgery at Guangdong Provincial People’s Hospital from August 2024 to January 2025. The experimental group used autologous UCB for CPB circuit priming, while the control group used adult allogeneic blood(AAB) priming when UCB was unavailable. Preoperative characteristics, intraoperative CPB and aortic cross-clamping(ACC) times, postoperative ICU stay duration, mechanical ventilation time, and hospitalization length were compared.Results:There were no significant differences in preoperative baseline characteristics between the two groups( P>0.05). At the end of surgery, red blood cell count(RBC), hemoglobin level(Hb), and creatine kinase(CK) showed no significant differences between the groups( P> 0.05). Additionally, perioperative left ventricular ejection fraction(LVEF) demonstrated no statistically significant variations( P>0.05). At surgery completion, the UCB group exhibited lower hematocrit(HCT) and higher blood lactic acid(Lac) levels but these differences resolved by 6 hours postoperatively( P>0.05). The UCB group had higher maximum vasoactive-inotropic scores(VISmax) within 48 hours and longer ICU stays, though total hospitalization and mechanical ventilation durations showed no significant differences( P>0.05). Conclusion:Autologous UCB priming reduces AAB requirements and has minimal impact on postoperative cardiac and pulmonary function recovery, or homeostasis., which is safe and feasible. This study provides evidence supporting the clinical application of UCB priming in CPB circuits.

Objective To explore the effects of physical activity(PA)on carotid intima-media thickness(CIMT)thickening in patients with type 2 diabetes mellitus(T2DM)with poor HbA1c control.Methods A total of 2505 T2DM inpatients with poor HbA1c control who visited the Endocrinology Department of the Integrated Traditional Chinese and Western Medicine Hospital Affiliated with Nanjing University of Traditional Chinese Medicine and Changzhou Second People's Hospital Affiliated with Nanjing Medical University from January 2019 to February 2022 were enrolled in this study.The patients were categorized into the mild-intensity PA(1～599 MET-min/w,n=795),moderate-intensity PA(600～1499 MET-min/w,n=1107)and high-intensity PA(≥1500 MET-min/w,n=603)based on the metabolic equivalence level(MET).Logistic regression was performed to analyze the relationship between PA and CIMT thickening.Statified analysis was used to investigate the effects of blood pressure(BP)and low-density lipoprotein cholesterol(LDL-C)target status on CIMT thickness in different PA groups.Results Restricted cubic spline plots showed a nonlinear relationship between PA levels and the risk of CIMT thickening(P<0.05).Logistic regression showed that with moderate-intensity PA as the control,while high-intensity PA was the influence factor of CIMT thickening(OR 1.581,95%CI 1.244～2.010,P<0.05).Statified analyses showed that under mild-intensity PA,using neither BP nor LDL-C on target as reference,achievement of either index and both were the influence factor of CIMT thickening.Using BP on target as reference,achievements of both indexes,achievements of neither of both indexes,and achievement of LDL-C only were the influence factor of CIMT thickening.Using LDL-C on target as reference,achievement of neither of them and achievement of BP only were the influence factor of CIMT thickening.Under high-intensity PA,achievement of both indexes was negatively associated with CIMT thickening.Conclusions Moderate-intensity PA is the recommended scheme to prevent CIMT thickening in T2DM patients whose HbA1c is not up to standard.Mild-intensity PA is not related to the risk of CIMT thickening,while high-intensity PA is positively related to the risk of CIMT thickening,and focusing on LDL-C compliance is particularly important to avoid CIMT thickening.

Cerebral small vessel disease represents a group of common vascular disorders involving pathological changes in arterioles,capillaries and venules,with microvascular investigation remaining a key challenge in stroke.With high signal-to-noise ratio and high contrast enabled by enhanced field strength,7T MRI can surpass the resolution limits of 3T MRI,revealing structural and functional abnormalities in cerebral small vessels below 400 μm,as well as detecting subtle lesions in brain tissue.This paper reviews the research progress of multimodal high-resolution imaging techniques based on 7T MRI,such as time-of-flight angiography,phase contrast imaging and susceptibility imaging,in the study of cerebral small vessel disease.Utilizing these technologies,7T MRI can clearly display the structure of cerebral small vessels,such as the lenticulostriate arteries and deep medullary veins,and measure functional parameters like flow velocity and susceptibility.Additionally,it can sensitively detect cerebral microbleeds and cortical cerebral microinfarct.These imaging data provide valuable information for detecting early features of cerebral small vessel disease and assessing its progression,offering new insights into its pathogenesis.Combined with artificial intelligence-based image analysis methods,7T MRI holds great promise for early diagnosis and progression evaluation in cerebral small vessel disease.

Objective To explore the mediating effect of empowerment ability between type D personality and self-management behavior of patients with diabetes mellitus(DM).Methods A total of 738 patients with type 2 diabetes mellitus(T2DM)hospitalized in the Department of Endocrinology of three tertiary hospitals in Hainan Province from December 2022 to May 2023 were selected and divided into Type D personality(Type D,n=104)group and T2DM group(n=634).The general data,biochemical indexes,scores of negative emotion(NA),social inhibition(SI),empowerment ability,and scale of DM self-management activities(SDSCA)were compared between the two groups,and the correlation between type D personality,empowerment ability and self-management ability was analyzed.The mediating effect model was used to analyze the mediating effect of empowerment ability on the four self-management behaviors of patients with type D personality,and the chain mediating effect model was used to analyze the relationship between type D personality,empowerment ability,self-management behaviors and HbA1c.Results Compared with the T2DM group,HbA1c,proportion of rural residence,proportion of complications≥3,proportion of education level of junior high school or above,proportion of monthly income<3000 yuan,and NA and SI scores were significantly higher in the Type D group(P<0.05).The empowerment ability and scores of healthy diet,regular exercise,blood glucose monitoring and medication compliance were lower in the Type D group than in the T2DM group(P<0.05).Spearman correlation analysis showed that the empowerment ability score was positively correlated with the scores of healthy diet,regular exercise,blood glucose monitoring and medication compliance(P<0.05).NA and SI scores were negatively correlated with empowerment ability score,healthy diet,regular exercise,blood glucose monitoring and medication compliance(P<0.05).The results of model analysis with empowerment ability as the mediating variable showed that type D personality had direct,indirect and total effects on regular exercise,blood glucose monitoring,medication compliance and SDSCA total score(P<0.05),and indirect and total effects on regular diet score(P<0.05).The mediating effect of empowerment ability was significant(Bootstrap CI did not include 0).The chain mediating effect analysis showed that type D personality could indirectly affect HbA1c through empowerment ability,healthy diet(γ=0.389,95%CI 0.206～0.591),and medication compliance(γ=0.149,95%CI 0.040～0.265),and the effect proportion was 39.4%and 14.1%,respectively.Conclusions Type D personality can indirectly influence self-management behavior through the mediating effect of empowerment,and simultaneously affecting HbA1c through the chain effect of empowerment,diet,and medication behavior.

Objective:To explore the interrelationship between brain functional networks and features in functional magnetic resonance imaging(fMRI)of patients with Alzheimer's disease(AD),and to construct mixed-function networks(MFN),and apply them in machine learning classification models to improve the accuracy of AD classification.Methods:102 AD patients and 227 healthy subjects in the Alzheimer's Neuroimaging Initiative(ADNI)dataset were retrospectively analyzed.The partial correlation brain network of the blood oxygen level dependent(BOLD)signal was calculated and fused with low-frequency wave amplitude(ALFF),fractional low-frequency wave amplitude(fALFF)and local consistency(ReHo)features to construct MFN.Network topology parameters were extracted,and a variety of machine learning classification models were constructed based on MFN topological parameters,accuracy,precision,recall and area under the curve(AUC)were used to evaluate the predictive efficiency of the models.Results:By constructed MFN and calculated intra group to inter group ratio(IIGR),35 features could be obtained from ALFF,fALFF and ReHo feature topological parameter analysis,after rank sum test and FDR correction,there were statistical differences among 28 features(P＜0.05).The classification results show that,all the five classifiers have high classification performance on the test data set.The accuracy,precision and recall rates of random forest(RF),adaptive lifting algorithm(AdaBoost),guided aggregation algorithm(Bagging)and support vector machine(SVM)were all 99.7％,and the AUC values were up to 100％,99.5％,99.1％and 99.5％,respectively.The accuracy(98.5％),precision(98.5％),recall(98.5％),and AUC(99.1％)of the multi-layer perceptron(MLP)were slightly lower than other models,but remained excellent.It was worth noting that RF has the highest AUC value of all models at 100.0％,while Bagging has the lowest AUC value(99.1％)in the integrated approach.The results of performance comparison show that,MFN classification model can significantly improve the recognition and classification of AD disease,and greatly improve the performance of various indicators of the classifier.The results showed that,MFN classification model was superior to intelligent classification based fusion,DBN-based multitask learning,PVT-TSVM,unsupervised learning and clustering,SVM and SVM of degree 3 polynomial kernel function in key indicators such as accuracy(99.13％),AUC(99.42％),recall rate(99.46％)and specificity(99.42％)with plasma proteins,machine learning algorithms.It was further proved that MFN classification model has good generalization ability and robustness in AD disease classification.Conclusion:The AD classification model constructed based on brain mixed function network topology parameters and machine learning can improve the accuracy of AD classification.

Aim To systematically investigate the ac-tive components,targets,and regulatory pathways of Po-lygonum capitatum in intervening atherosclerosis(AS)through network pharmacology,molecular docking and animal experiments.Methods Active components of Polygonum capitatum and AS-related targets were screened and identified through database searches.Protein-protein interaction(PPI)network analysis was performed using the STRING database,followed by GO and KEGG enrichment analyses via the David plat-form.Molecular docking validation was conducted with AutoDock.An AS model was established in Syrian golden hamsters fed a high-fat diet.Predicted pathways and targets were validated using qPCR,ELISA,and histopathological assessment of aortic and hepatic tis-sues via HE staining.Results Network pharmacology identified 27 potential active components of Polygonum capitatum(primarily flavonoids such as quercetin and luteolin)and 110 drug-disease intersection targets,in-cluding core targets MMP-9,ALB,and AKT1.GO and KEGG analyses enriched 593 and 125 pathways,re-spectively,with the NF-κB inflammatory pathway,TNF signaling pathway and lipid metabolism/atherosclerosis pathways highlighted as key mechanisms.Animal ex-periments demonstrated that Polygonum capitatum im-proved serum lipid profiles(reduced TC,TG,LDL-C)in AS hamsters,suppressed the MMP-9/NF-κB signa-ling pathway(downregulated MMP-9,p65 phosphoryla-tion,TNF-α,and IL-6),and inhibited VSMC synthetic phenotypic transformation(upregulated α-SMA and myocardin)by downregulating MCPIP1.Additionally,Polygonum capitatum ameliorated aortic lesions and he-patic lipid deposition in AS hamsters.Conclusions Polygonum capitatum alleviates AS by synergistically regulating the MMP-9/NF-κB/MCPIP1 axis through flavonoid components,suppressing vascular inflammato-ry cascades and maintaining VSMC contractile pheno-types.This reflects Polygonum capitatum's multi-com-ponent,multi-pathway,and multi-target characteristics in combating AS.

Experimental teaching is an important component of the course Medical Immunology,which requires the use of experimental animals and the execution of experimental animals by medical students.By applying the carbon dioxide euthanasia system,it can effectively reduce the pain of experimental animals,ensure their welfare,and meet ethical requirements.It can also improve the efficiency of experimental teaching in Medical Immunology,reduce environmental pollution,and promote medical students to estab-lish scientific values and worldviews that pay attention to experimental animals and respect life,which is conducive to becoming future medical service talents.In the experimental teaching of Medical Immunology,the appropriate application of carbon dioxide euthanasia system combined with effective ideological and political construction of the curriculum can further implement the Party's educational policy of cultivating morality and talents,and lay a good foundation for cultivating medical talents with comprehensive knowledge,high skills and excellent quality.

Objective:To investigate the effect of saikosaponin A on depressive-like behaviors and hippocampal cyclic adenosine monophosphate response element-binding(CREB) protein expression in olfactory bulbectomized mice.Methods:Totally thirty male SPF-grade C57BL/6J mice, six weeks old, were randomly divided into 3 groups ( n=10 in each group): the control group, the olfactory bulbectomy group, and the saikosaponin A group.Olfactory bulbectomy was performed to damage the olfactory bulbs in the mice of bulbectomy group and saikosaponin A group, while the mice of control group only had a cranial drill hole at the same coordinates without damaging the olfactory bulbs. Mice in saikosaponin A group were administered saikosaponin A solution (dose: 5 mg/kg) via gavage, while mice in the control and olfactory bulbectomy groups were given the same volume of 0.9% NaCl solution once a day for 21 days. The depressive-related behavioral changes of mice in each group were evaluated by open field test, tail suspension test, forced swimming test, and weight measurement. The expression of CREB in the hippocampus of mice were detected by Western blot. Graphpad prism 5 software was used for data analysis.The data comparison among the multiple groups was conducted by one-way ANOVA and further pairwise comparisons were conducted by Tukey test. Results:(1) The results of weight measurement showed that there was no significant difference in body weight among the three groups( F=0.468, P=0.631) on the day of the olfactory bulbectomy surgery, but there was a statistically significant difference in body weight among the three groups ( F=37.340, P<0.001) on the 28th day after the olfactory bulbectomy.The body weight of mice in the olfactory bulbectomy group was lower than that of the control group ((24.09±1.01) g, (27.22±0.58)g)( P<0.05). The body weight of mice in the saikosaponin A group((26.23±0.83)g) was higher than that of the olfactory bulbectomy group( P<0.05). There was a statistically significant difference in body weight differences among the three groups of mice ( F=48.180, P<0.001). The body weight difference of mice in the olfactory bulbectomy group was lower than that of the control group ((2.34±0.96) g, (5.57±0.72) g) ( P<0.05). The body weight difference of mice in the saikosaponin A group was higher than that of the olfactory bulbectomy group ((4.74±0.56) g, (2.34±0.96) g) ( P<0.05).(2) The results of the open field test showed that there were statistically significant differences in the central area residence time and total activity distance in mice among the three groups ( F=27.03, 10.98, both P<0.001). The central area residence time ((13.87±4.59) s) and total activity distance ((35.67±4.88) m) of mice in the olfactory bulbectomy group were both less than those of the control group ((27.44±2.76) s, (59.02±16.21) m) (both P<0.05).The central area residence time ((21.77±4.78) s) and total activity distance ((52.33±10.41) m) of mice in the saikosaponin A group were both higher than those of the olfactory bulbectomy group(both P<0.05).(3) The results of tail suspension test showed that there was a statistically significant difference in immobility time among the three groups ( F=74.57, P<0.001). The immobility time of mice in the olfactory bulbectomy group was longer than that of the control group ((148.20±8.84)s, (97.89±8.64)s) ( P<0.05). The immobility time of mice in the saikosaponin A group((135.70±11.09)s) was less than that of the olfactory bulbectomy group( P<0.05). (4) The results of forced swimming test showed that there was a significant difference in immobility time among the three groups ( F=51.73, P<0.001). The immobility time of mice in the olfactory bulbectomy group was longer than that of the control group ((61.39±5.20) s, (40.80±4.30) s) ( P<0.05).The immobility time of mice in the saikosaponin A group((53.52±4.13)s) was less than that of the olfactory bulbectomy group( P<0.05). (5) The results of Western blot showed that there was a significant difference in hippocampal CREB protein expression among the three groups ( F=13.32, P<0.001).Compared with the control group, hippocampal CREB protein expression of mice in the olfactory bulbectomy group was significantly down-regulated(0.51±0.15, 1.45±0.61) ( P<0.05).Compared with the olfactory bulbectomy group, hippocampal CREB protein expression in the saikosaponin A group(0.97±0.09) was up-regulated( P<0.05). Conclusion:Saikosaponin A can significantly alleviate the depressive-like behaviors in olfactory bulbectomized mice, and its mechanism may be related to the up-regulation of CREB protein expression in the hippocampus.