Objective:To investigate the clinical significance of CD105 and erythropoietin-producing hepatocellular receptor A2 (EPHA2) expressions in breast invasive ductal carcinoma and the effects of the combination of diabetes mellitus on CD105 and EPHA2 expressions.Methods:A retrospective case series study was conducted. A total of 74 patients with breast invasive ductal carcinoma in Affiliated Hospital of Jiangsu University from June 2019 to June 2024 were selected, and paraffin specimens from the patients after surgery were collected. Immunohistochemistry SP method was used to detect the expressions of CD105 and EPHA2 proteins in specimens. CD105 expression was expressed as the number of CD105 labeled microvessels, and EPHA2 expression was expressed as the proportion of EPHA2 positive expression area. The correlation of CD105 and EPHA2 expressions with the clinicopathological characteristics and diabetes mellitus of patients, as well as the relationship between the expressions of CD105 and EPHA2 were analyzed. Cox proportional hazards model was used to make univariate and multivariate analysis of the factors influencing overall survival of patients.Results:All 74 patients were female. The median age was 60 years old, 44 patients (59.46%) had tumor grade ≥ grade 3, 36 patients (48.65%) had tumor diameter ≥ 2 cm, 28 patients (37.84%) had lymph node metastasis, 30 patients (40.54%) had nerve vessel invasion, and 32 patients (43.24%) had diabetes mellitus. There were statistically significant differences in the proportion of patients with different age, tumor diameter, TNM stage, lymph node metastasis or not and nerve vessel invasion or not between diabetes mellitus group and non-diabetes mellitus group (all P < 0.05). The number of CD105 marking the microvessel was (32±9) and (24±8), respectively in diabetes mellitus group and non-diabetes mellitus group, and the difference was statistically significant ( t = 3.63, P < 0.010); the positive expression area proportion of EPHA2 was (19±5)% and (15±4)%, respectively, and the difference was statistically significant ( t = 3.85, P < 0.010). The expression of CD105 was related to the duration of diabetes mellitus, tumor diameter, TNM stage and lymph node metastasis or not (all P < 0.05), and the expression of EPHA2 was related to tumor diameter and TNM stage (all P < 0.05). Pearson correlation analysis showed a positive correlation between CD105 and EPHA2 expression ( r = 0.75, P < 0.001). The differences in overall survival of patients with or without diabetes mellitus and patients with different CD105 and EPHA2 expressions were statistically significant (all P < 0.05). Multivariate analysis showed that CD105 expression ( HR = 1.10, 95% CI: 1.04-1.16, P = 0.001) and EPHA2 expression ( HR = 1.35, 95% CI: 1.10-1.66, P = 0.005) were independent factors influencing the overall survival of patients with breast invasive ductal carcinoma. Conclusions:The expressions of CD105 and EPHA2 are independent prognostic factors in patients with breast invasive ductal carcinoma, and diabetes mellitus can promote the expressions of CD105 and EPHA2, which may increase the risk of poor prognosis.

The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

OBJECTIVE: To observe the clinical efficacy of auricular electroacupuncture for post-stroke dysphagia in the pharyngeal phase. METHODS: Eighty-two patients with post-stroke dysphagia in the pharyngeal phase were randomized into an auricular electroacupuncture group (41 cases) and a swallowing electrical stimulation group (41 cases, 1 case dropped out). In the auricular electroacupuncture group, electroacupuncture was applied at auricular points, i.e. Xin (CO₁₅) and Yanhou (TG₃), using disperse-dense wave, in frequency of 2 Hz/10 Hz, 30 min a time. In the swallowing electrical stimulation group, swallowing electrical stimulation was delivered for 30 min a time. Both groups were treated once daily for 4 weeks. The functional oral intake scale (FOIS) grade, as well as the hyolaryngeal complex displacement, the pharyngeal constriction rate (PCR) and the pharyngeal delay time (PDT) under video fluoroscopic study of swallowing (VFSS) were observed before and after treatment, and the clinical efficacy was evaluated in the two groups. RESULTS: Compared before treatment, the FOIS grade was improved (P<0.01), the forward and upward displacement amplitude of hyoid bone and thyroid cartilage was increased (P<0.05), and the PCR and PDT were decreased (P<0.05) after treatment in the two groups. After treatment, compared with the swallowing electrical stimulation group, the FOIS grade was superior (P<0.01), the upward displacement amplitude of hyoid bone and thyroid cartilage was larger (P<0.05) and the PCR and PDT were lower (P<0.05) in the auricular electroacupuncture group. The total effective rate was 85.4% (35/41) in the auricular electroacupuncture group, which was higher than 62.5% (25/40) in the swallowing electrical stimulation group (P<0.05). CONCLUSION Auricular electroacupuncture can effectively trigger pharyngeal initiation and improve post-stroke dysphagia in the pharyngeal phase.
Humans ; Electroacupuncture ; Male ; Deglutition Disorders/etiology* ; Female ; Middle Aged ; Aged ; Stroke/physiopathology* ; Pharynx/physiopathology* ; Acupuncture, Ear ; Acupuncture Points ; Deglutition ; Treatment Outcome ; Adult

Objective To evaluate the application of high-resolution magnetic resonance vessel wall imaging(HRMR-VWI)in identifying high-risk features of intracranial atherosclerotic plaques,and to analyze the correlation between plaque characteristics and stroke recurrence under varying degrees of stenosis.Methods The data from 368 patients with intracranial atherosclerotic stenosis(ICAS)across two centers were retrospectively analyzed.Based on the degree of stenosis,all patients were categorized into mild-to-moderate stenosis group(luminal stenosis<70%,n=155)and severe stenosis group(luminal stenosis≥70%,n=213).HRMR-VWI images and clinical information of the patients were collected and analyzed,and the culprit plaques were quantitatively analyzed.Univariate and multivariate logistic regression analyses were employed to identify the risk factors for stroke recurrence,and the predictive performance was evaluated using the area under the curve(AUC)of the receiver operating characteristic(ROC)curve.Results Higher normalized wall index(NWI)[odds ratio(OR)=1.082,95%confidence interval(CI)1.050-1.118,P<0.05]and the presence of intraplaque hemorrhage(IPH)(OR=1.843,95%CI 1.120-3.036,P<0.05)were risk factors for stroke recurrence in all patients.And these two factors were also significant in the mild-to-moderate stenosis group(NWI:OR=1.088,95%CI 1.009-1.186,P<0.05;IPH:OR=4.049,95%CI 1.227-16.065,P<0.05).A predictive model for stroke recurrence was constructed using the combination of IPH and NWI,with the best performance in the mild-to-moderate stenosis group(AUC=0.813,95%CI 0.723-0.906).Conclusion In patients with luminal stenosis<70%,the increase of NWI and the presence of IPH have been validated as significant and effective indicators for predicting stroke recurrence,demonstrating notable predictive performance.In contrast,among patients with luminal stenosis≥70%,the utility of plaque characteristics in predicting stroke recurrence is relatively lower,indicating that the correlation between plaque characteristics and stroke recurrence varies across different degrees of stenosis.

Objective To investigate the effectiveness and safety of electroconvulsive therapy(ECT)in reducing suicidal ideation and depressive symptoms of major depressive disorder patients,as well as its effect on cognitive function.Methods A total of 160 adolescent patients with major depressive disorder were recruited for this study.The ECT group(n=81)received conventional antidepressant medication combined with 8 sessions of electroconvulsive therapy,and the control group(n=79)received conventional antidepressant medication only.Depressive symptoms,suicidal ideation,and cognitive functioning were assessed using 17-item Hamilton rating scale for depression(HAMD-17)and self-rating idea of suicide scale(SIOSS),at baseline(before ECT),after ECT,and at 2 and 6 weeks after treatment.The Montreal cognitive assessment(MoCA)was used to evaluate the cognitive function of the patients,and the patients were followed up for side effects such as dizziness and nausea.Results Generalized estimating equation(GEE)analysis of HAMD-17 and SIOSS scores showed significant group×time interaction effects(P<0.01).Both groups exhibited a reduction in HAMD-17 scores before and after treatment(scores at four time points:ECT group 24.59±4.56 vs.13.25±4.32 vs.6.20±1.95 vs.3.62±2.04,control group 23.48±3.66 vs.15.42±3.11 vs.10.10±2.05 vs.4.68±2.01;P<0.01).The mean difference in HAMD-17 scores before and after treatment was-9.62±3.13 in the ECT group,and was-8.16±1.71 in the control group.Additionally,suicidal ideation reduced in both groups after treatment(SIOSS scores at four time points:ECT group 18.57±2.85 vs.10.93±3.52 vs.8.02±2.79 vs.3.70±1.96,control group 18.97±3.03 vs.15.51±2.98 vs.11.11±2.18 vs.6.44±1.78;P<0.01).For cognitive function scores,there was no interaction between group and time(P=0.21),the difference in the change in MoCA scores at different follow-up time points was significant(P<0.01),and the difference in the change in MoCA scores between the two groups was not significant(P=0.05),and the cognitive functions of the two groups could be restored to the baseline level at 6 weeks after treatment.No severe side effects were reported in either group of patients during the study.Conclusions Our findings confirm that ECT is effective and safe for improving suicidal ideation and depressive symptoms in adolescents with major depressive disorder.The impairment of cognitive function by ECT in adolescent patients with major depressive disorder is reversible.

Objective To investigate the effectiveness and safety of electroconvulsive therapy(ECT)in reducing suicidal ideation and depressive symptoms of major depressive disorder patients,as well as its effect on cognitive function.Methods A total of 160 adolescent patients with major depressive disorder were recruited for this study.The ECT group(n=81)received conventional antidepressant medication combined with 8 sessions of electroconvulsive therapy,and the control group(n=79)received conventional antidepressant medication only.Depressive symptoms,suicidal ideation,and cognitive functioning were assessed using 17-item Hamilton rating scale for depression(HAMD-17)and self-rating idea of suicide scale(SIOSS),at baseline(before ECT),after ECT,and at 2 and 6 weeks after treatment.The Montreal cognitive assessment(MoCA)was used to evaluate the cognitive function of the patients,and the patients were followed up for side effects such as dizziness and nausea.Results Generalized estimating equation(GEE)analysis of HAMD-17 and SIOSS scores showed significant group×time interaction effects(P<0.01).Both groups exhibited a reduction in HAMD-17 scores before and after treatment(scores at four time points:ECT group 24.59±4.56 vs.13.25±4.32 vs.6.20±1.95 vs.3.62±2.04,control group 23.48±3.66 vs.15.42±3.11 vs.10.10±2.05 vs.4.68±2.01;P<0.01).The mean difference in HAMD-17 scores before and after treatment was-9.62±3.13 in the ECT group,and was-8.16±1.71 in the control group.Additionally,suicidal ideation reduced in both groups after treatment(SIOSS scores at four time points:ECT group 18.57±2.85 vs.10.93±3.52 vs.8.02±2.79 vs.3.70±1.96,control group 18.97±3.03 vs.15.51±2.98 vs.11.11±2.18 vs.6.44±1.78;P<0.01).For cognitive function scores,there was no interaction between group and time(P=0.21),the difference in the change in MoCA scores at different follow-up time points was significant(P<0.01),and the difference in the change in MoCA scores between the two groups was not significant(P=0.05),and the cognitive functions of the two groups could be restored to the baseline level at 6 weeks after treatment.No severe side effects were reported in either group of patients during the study.Conclusions Our findings confirm that ECT is effective and safe for improving suicidal ideation and depressive symptoms in adolescents with major depressive disorder.The impairment of cognitive function by ECT in adolescent patients with major depressive disorder is reversible.

Objective To evaluate the application of high-resolution magnetic resonance vessel wall imaging(HRMR-VWI)in identifying high-risk features of intracranial atherosclerotic plaques,and to analyze the correlation between plaque characteristics and stroke recurrence under varying degrees of stenosis.Methods The data from 368 patients with intracranial atherosclerotic stenosis(ICAS)across two centers were retrospectively analyzed.Based on the degree of stenosis,all patients were categorized into mild-to-moderate stenosis group(luminal stenosis<70%,n=155)and severe stenosis group(luminal stenosis≥70%,n=213).HRMR-VWI images and clinical information of the patients were collected and analyzed,and the culprit plaques were quantitatively analyzed.Univariate and multivariate logistic regression analyses were employed to identify the risk factors for stroke recurrence,and the predictive performance was evaluated using the area under the curve(AUC)of the receiver operating characteristic(ROC)curve.Results Higher normalized wall index(NWI)[odds ratio(OR)=1.082,95%confidence interval(CI)1.050-1.118,P<0.05]and the presence of intraplaque hemorrhage(IPH)(OR=1.843,95%CI 1.120-3.036,P<0.05)were risk factors for stroke recurrence in all patients.And these two factors were also significant in the mild-to-moderate stenosis group(NWI:OR=1.088,95%CI 1.009-1.186,P<0.05;IPH:OR=4.049,95%CI 1.227-16.065,P<0.05).A predictive model for stroke recurrence was constructed using the combination of IPH and NWI,with the best performance in the mild-to-moderate stenosis group(AUC=0.813,95%CI 0.723-0.906).Conclusion In patients with luminal stenosis<70%,the increase of NWI and the presence of IPH have been validated as significant and effective indicators for predicting stroke recurrence,demonstrating notable predictive performance.In contrast,among patients with luminal stenosis≥70%,the utility of plaque characteristics in predicting stroke recurrence is relatively lower,indicating that the correlation between plaque characteristics and stroke recurrence varies across different degrees of stenosis.

Objective:To investigate the clinical significance of CD105 and erythropoietin-producing hepatocellular receptor A2 (EPHA2) expressions in breast invasive ductal carcinoma and the effects of the combination of diabetes mellitus on CD105 and EPHA2 expressions.Methods:A retrospective case series study was conducted. A total of 74 patients with breast invasive ductal carcinoma in Affiliated Hospital of Jiangsu University from June 2019 to June 2024 were selected, and paraffin specimens from the patients after surgery were collected. Immunohistochemistry SP method was used to detect the expressions of CD105 and EPHA2 proteins in specimens. CD105 expression was expressed as the number of CD105 labeled microvessels, and EPHA2 expression was expressed as the proportion of EPHA2 positive expression area. The correlation of CD105 and EPHA2 expressions with the clinicopathological characteristics and diabetes mellitus of patients, as well as the relationship between the expressions of CD105 and EPHA2 were analyzed. Cox proportional hazards model was used to make univariate and multivariate analysis of the factors influencing overall survival of patients.Results:All 74 patients were female. The median age was 60 years old, 44 patients (59.46%) had tumor grade ≥ grade 3, 36 patients (48.65%) had tumor diameter ≥ 2 cm, 28 patients (37.84%) had lymph node metastasis, 30 patients (40.54%) had nerve vessel invasion, and 32 patients (43.24%) had diabetes mellitus. There were statistically significant differences in the proportion of patients with different age, tumor diameter, TNM stage, lymph node metastasis or not and nerve vessel invasion or not between diabetes mellitus group and non-diabetes mellitus group (all P < 0.05). The number of CD105 marking the microvessel was (32±9) and (24±8), respectively in diabetes mellitus group and non-diabetes mellitus group, and the difference was statistically significant ( t = 3.63, P < 0.010); the positive expression area proportion of EPHA2 was (19±5)% and (15±4)%, respectively, and the difference was statistically significant ( t = 3.85, P < 0.010). The expression of CD105 was related to the duration of diabetes mellitus, tumor diameter, TNM stage and lymph node metastasis or not (all P < 0.05), and the expression of EPHA2 was related to tumor diameter and TNM stage (all P < 0.05). Pearson correlation analysis showed a positive correlation between CD105 and EPHA2 expression ( r = 0.75, P < 0.001). The differences in overall survival of patients with or without diabetes mellitus and patients with different CD105 and EPHA2 expressions were statistically significant (all P < 0.05). Multivariate analysis showed that CD105 expression ( HR = 1.10, 95% CI: 1.04-1.16, P = 0.001) and EPHA2 expression ( HR = 1.35, 95% CI: 1.10-1.66, P = 0.005) were independent factors influencing the overall survival of patients with breast invasive ductal carcinoma. Conclusions:The expressions of CD105 and EPHA2 are independent prognostic factors in patients with breast invasive ductal carcinoma, and diabetes mellitus can promote the expressions of CD105 and EPHA2, which may increase the risk of poor prognosis.

Objective To investigate the risk factors of femoral head necrosis after internal fixation of fem-oral neck fracture,and to clarify the predictive role of serological index plasminogen activator inhibitors-1(PAI-1)on femoral head necrosis.Methods A total of 95 patients undergoing internal fixation for femoral neck fracture were included in the study.Relevant clinical information of patients was obtained and the serum PAI-1 levels of the patients before surgery,1,2,and 3 days after surgery were detected.After 1-year follow-up,patients were divided into necrosis group and non-necrosis group according to the occurrence of femoral head necrosis.Visual Analog Scale(VAS),Western Ontario McMaster University Osteoarthritis Index(WOMAC),and Harris Hip Score(HHS)were conducted in all patients one year after the surgery.The differences of basic clinical information and serum PAI-1 levels before and after the surgery between necrosis group and non-necrosis group were compared,and Logistic regression analysis was performed to identify the relevant risk factors for femoral head necrosis.The relationships between the PAI-1 level after operation and the VAS,WOMAC,and HHS scores of patients were figured out.The receiver operating characteristic(ROC)curve of serum PAI-1 as a predictive indicator for femoral head necrosis was drawn to clarify its predictive val-ue.Results Garden classification and reduction quality between the necrosis group and the non-necrosis group were risk factors for femoral head necrosis(P＜0.05).The serum PAI-1 at 1 day and 2 days after surgery in the necrosis group were significantly higher than that in the non-necrosis group(P＜0.05).The level of PAI-1 at 1 day and 2 days after surgery was positively correlated with VAS and WOMAC(P＜0.05),and negative-ly correlated with HHS(P＜0.05).Logistic regression analysis showed that the increase of serum PAI-1 level at 1 day and 2 days after surgery were risk factors for femoral head necrosis(P＜0.05).The ROC curve showed that serum PAI-1 level at 2 days after surgery had higher predictive value than that at 1 day after sur-gery,and the cut-off value was 44.8 ng/L,the sensitivity was 68.49％,the specificity was 86.36％,and the ar-ea under the curve(AUC)was 0.807.Conclusion The serum PAI-1 level at 1 day and 2 days after internal fixation of femoral neck fracture could be used to predict the occurrence of femoral head necrosis,especially the serum PAI-1 levels at 2 days after surgery.

Enzymes are widely used in chemical and pharmaceutical industries because of their advantages of high efficiency and specificity. However， the shortcomings of the free enzymes， such as poor stability and difficulty in recycling， limit their application. Therefore， the immobilization and application of enzymes have become one of the research hotspots. The selection of the immobilization carriers is a critical step in the process of enzyme immobilization. Metal-organic frameworks（MOFs）， a kind of porous materials， are formed by the coordination of metal ions or metal clusters with organic ligands. As an emerging immobilization carrier， its advantages such as high porosity， strong stability， and surface modifiability make it ideal for immobilized enzyme carriers. By immobilizing the free enzyme on MOFs， the above mentioned deficiencies of the free enzymes can be effectively solved， which greatly broaden the applicable condition. Ligand fishing is a method to find receptor-specific ligands from complex components， which has the advantages of high efficiency， simple sample pretreatment and high specificity. The MOF-enzyme complex formed by enzyme immobilization can act as a "fishing rod" for ligand fishing， which can screen out the targets from the complex system of components. The complex chemical composition and various active ingredients of traditional Chinese medicine（TCM） make the ligand fishing technology to play a big role in the screening of enzyme inhibitors from TCM. And the screened enzyme inhibitors are expected to be further developed into the lead compounds with good efficacy and low adverse effects， so the immobilized enzymes of MOFs have a wide application in the screening of active ingredients from TCM. Based on this， this paper summarized the methods of immobilized enzymes of MOFs in recent years， analyzed the characteristics， advantages and disadvantages of each method， and summarized the laws of preparation conditions and mechanisms. Meanwhile， the application and future development of immobilized enzymes of MOFs in the field of enzyme inhibitor screening from TCM were also summarized and prospected， with a view to providing a reference for the development of natural ingredients and the modernization of TCM.