AIM: To detect the distribution and expression of vascular endothelial growth factor(VEGF)in radiation retinopathy(RR)through fluorescence targeted imaging.METHODS:Covalent binding of fluorescein FITC with VEGF antibody ranibizumab to prepare targeted fluorescent imaging probe ranibizumab-FITC. SD rats were randomly divided into three groups based on the principle of weight balance: a normal control group(Con group), a low-dose radiation group(10 Gy group), and a high-dose radiation group(30 Gy group). Medical linear accelerators and lead blocks were used to locally irradiate the rat eyeballs for modeling. Western blot and qRT-PCR were used to detect the expression levels of VEGF-A in each group and to screen for appropriate modeling dose. The inverted fluorescence microscope and the confocal microscope were used to observe the distribution of VEGF and imaging probes in the retinas of control and RR model group rats, and to verify the effectiveness of targeted probes.RESULTS:The expression level of VEGF-A in the retina of rats in the high-dose radiation group(30 Gy group)was higher than that in the normal control group(Con group). In early RR, VEGF expression was observed to be associated with microaneurysms and abnormal microvessels in the retina. VEGF accumulation was observed at the site of capillary wall damage. When retinal capillary endothelial damage occurred, targeted probes gathered on the outer surface of the vessel wall.CONCLUSION:The expression level of VEGF in the retina of RR model rats is elevated, and fluorescent targeted molecular imaging probes can detect the spatial distribution of VEGF at the microvascular lesions in the retina of RR rats.

Adenosine, a critical molecule regulating cellular function both inside and outside cells, is controlled by two human adenosine deaminases: ADA1 and ADA2. While ADA1 primarily resides in the cytoplasm, ADA2 can be transported to lysosomes within cells or secreted outside the cell. Patients with ADA2 deficiency (DADA2) often suffer from systemic vasculitis due to elevated levels of TNF-α in their blood. Monocytes from DADA2 patients exhibit excessive TNF-α secretion and differentiate into pro-inflammatory M1-type macrophages. Our findings demonstrate that ADA2 localizes to endolysosomes within macrophages, and its intracellular concentration decreases in cells secreting TNF-α. This suggests that ADA2 may function as a lysosomal adenosine deaminase, regulating TNF-α expression by the cells. Interestingly, pneumonia patients exhibit higher ADA2 concentrations in their bronchoalveolar lavage (BAL), correlating with elevated pro-inflammatory cytokine levels. Conversely, cord blood has low ADA2 levels, creating a more immunosuppressive environment. Additionally, secreted ADA2 can bind to apoptotic cells, activating immune cells by reducing extracellular adenosine levels. These findings imply that ADA2 release from monocytes during inflammation, triggered by growth factors, may be crucial for cell activation. Targeting intracellular and extracellular ADA2 activities could pave the way for novel therapies in inflammatory and autoimmune disorders.
Humans ; Adenosine Deaminase/deficiency* ; Monocytes/cytology* ; Cell Differentiation ; Intercellular Signaling Peptides and Proteins/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Biomarkers/metabolism* ; Macrophages/metabolism* ; Pneumonia/metabolism*

Objective:To explore the efficacy of intensive repetitive transcranial magnetic stimulation (irTMS) in treatment-resistant depression (TRD) and its impact on cognitive function and systemic immune-inflammation index (SII).Methods:Forty-eight TRD patients were divided into observation group and control group using random number table method, with 24 patients in each group. The observation group was treated with irTMS, and the stimulation site was the left dorsolateral prefrontal lobe. The stimulation intensity was 110% of the motor threshold, and the stimulation frequency was 15 Hz. The stimulation interval was 26 s, and 3 000 pulses were stimulated each time. Stimulating 5 times per day, with an interval of 50 min, and continuous treatment for 5 days. The total stimulation amount for 5 days was 75 000 pulses. The control group was treated with pseudo stimulation. Before treatment (T0), 5 days after treatment (T1), and 1 month after treatment (T2), 17-item Hamilton depression scale (HAMD-17) was used to assess depressive mood. Evaluating cognitive function using the Wisconsin card sorting test.A fully automated blood cell analyzer was used to detect platelet count (PLT), neutrophil count (NC), and lymphocyte count (LC), calculate the systemic immune inflammation index (SII), SII=PLT × NC/LC. Statistical analysis was conducted using SPSS 20.0 software. The comparison between two sets of repeated measurement data was performed using repeated measurement analysis of variance.Simple effect analysis was performed if the interaction effect was significant.Pearson analysis was used for correlation testing.Results:The interaction effect between the time and group of HAMD-17 scores was significant ( F=121.784, P<0.05). The results of simple effects analysis showed that the HAMD-17 scores of the observation group at T1 and T2 ((12.07±4.08) and (14.78±4.99), respectively) were lower than those of the control group ((23.78±5.87) and (24.67±7.00), P<0.05). The treatment response rate and remission rate of the observation group at T1 were higher than those of the control group ( χ2=4.090, 7.378, both P<0.05).The treatment response rate and remission rate of the observation group at T2 were higher than those of the control group ( χ2=4.463, 4.547, both P<0.05). The time and group interaction effects of the percentage of correct response and conceptualization level in the Wisconsin card sorting test were significant ( F=30.087, 20.004, P<0.05). The results of simple effects analysis showed that the percentage of correct response and conceptualization level in the observation group at T1 and T2 were higher than those in the control group (all P<0.05). The time and group interaction effect of SII was significant ( F=8.173, P<0.05). The results of simple effects analysis showed that there was no statistically significant difference in SII between the two groups at T0 ( P>0.05). The SII at T1 and T2 in the observation group was lower than that in the control group ( P<0.05). In the observation group, the changes in SII from T2 to T0 was positively correlated with the change in HAMD-17 scores ( r=0.527, P<0.05), and negatively correlated with the percentage of correct responses to the Wisconsin card sorting test ( r=-0.412, P<0.05) and the percentage of conceptualization level ( r=-0.411, P<0.05). Conclusion:irTMS is effective in treating TRD and can improve patients' cognitive function and immune inflammation damage.

Objective To investigate the effects of perioperative blood glucose(BG)levels on postoperative acute kidney injury(AKI)and rehabilitation in diabetic patients with coronary heart disease after coronary artery bypass grafting(CABG).Methods Randomly select data from 142 patients who underwent CABG treatment at The Fuwai Cardiovascular Hospital in Qingdao from January to December 2022,and compare the BG indicators,AKI incidence,cardiac function improvement and quality of life between good control group(n=57)and poor control group(n=85).Results The operation time,ventilator use time,postoperative ICU time,hospital stay time and various BG indexes in the good control group were significantly lower than those in the poor control group(P<0.05 or P<0.01).27 patients(19.01%)developed AKI after surgery,and the incidence of AKI in the good control group was significantly lower than that in the poor control group(10.53%vs 24.71%,P<0.05).After treatment,the cardiac function indexes in both groups were significantly improved compared with those before surgery,and the good control had significantly better cardiac function and quality of life than the poor control(P<0.05).Conclusions The incidence of AKI after CABG in patients with diabetes and coronary heart disease was 19.01%.Good perioperative BG level control can reduce the risk of postoperative AKI and help early postoperative recovery.

Objective:To investigate the difference in brain activity intensity between methamphetamine (MA) dependent patients (MA group) and healthy controls (control group) using fractional amplitude of low-frequency fluctuation (fALFF), and to establish a classification model between these two groups using support vector machine (SVM).Methods:From February 2014 to October 2019, a total of 46 male MA-dependent patients and 46 male healthy controls were recruited from the Affiliated Kangning Hospital of Ningbo University. The study collected resting-state functional magnetic resonance imaging (rs-fMRI) data and analyzed the differences in brain functional activity between the two groups. This analysis was conducted using both static and dynamic fractional amplitude of low-frequency fluctuations (d-fALFF). Additionally, the study examined the correlation between fALFF/d-fALFF values in specific brain regions and the total scores, as well as each factor score, of the Brief Psychiatric Rating Scale (BPRS). Furthermore, the relationship between fALFF/d-fALFF values and the age of first use and total dose of MA in the MA group was investigated. Finally, the fALFF map and d-fALFF map of brain regions with significant differences between groups were used as features for constructing classification.Results:Compared to the healthy control group, those dependent on MA showed significantly increased fALFF mainly in the nucleus accumbens, caudate nucleus, thalamus, and amygdala nucleus( t=-5.21--2.72, all P<0.05). The MA group exhibited decreased fALFF in the superior frontal gyrus, middle frontal gyrus, orbital gyrus, and cingulate gyrus( t=3.59-5.00, all P<0.05). Most of the brain regions with decreased d-fALFF overlapped with those exhibiting decreased fALFF( t=3.33-4.87, all P<0.05). The results of the correlation analysis showed that the fALFF value of the right nucleus accumbens was positively correlated with the age of first use of MA ( r=0.537, P<0.001). There is no significant relationship between the abnormal fALFF and d-fALFF values in the MA group and the total scores and each factor scores of BPRS, as well as the total dose of MA taken (after removing outliers). Based on fALFF and d-fALFF values, the SVM classifier achieved accuracies of 90.33%±6.89% and 71.56%±7.80%, respectively. Conclusions:There are significant abnormalities in the low-frequency fluctuation of the resting brain in patients dependent on MA. These abnormalities reflect the rigidity of prefrontal cortex activity, functional impairment, and dysfunction of the anti-reward system. These factors may be one of the causes for MA dependent behavior and repeated episodes. In addition, the fALFF values may be helpful for distinguishing MA dependent individuals from the control group.

Objective:To explore the efficacy of intensive repetitive transcranial magnetic stimulation (irTMS) in treatment-resistant depression (TRD) and its impact on cognitive function and systemic immune-inflammation index (SII).Methods:Forty-eight TRD patients were divided into observation group and control group using random number table method, with 24 patients in each group. The observation group was treated with irTMS, and the stimulation site was the left dorsolateral prefrontal lobe. The stimulation intensity was 110% of the motor threshold, and the stimulation frequency was 15 Hz. The stimulation interval was 26 s, and 3 000 pulses were stimulated each time. Stimulating 5 times per day, with an interval of 50 min, and continuous treatment for 5 days. The total stimulation amount for 5 days was 75 000 pulses. The control group was treated with pseudo stimulation. Before treatment (T0), 5 days after treatment (T1), and 1 month after treatment (T2), 17-item Hamilton depression scale (HAMD-17) was used to assess depressive mood. Evaluating cognitive function using the Wisconsin card sorting test.A fully automated blood cell analyzer was used to detect platelet count (PLT), neutrophil count (NC), and lymphocyte count (LC), calculate the systemic immune inflammation index (SII), SII=PLT × NC/LC. Statistical analysis was conducted using SPSS 20.0 software. The comparison between two sets of repeated measurement data was performed using repeated measurement analysis of variance.Simple effect analysis was performed if the interaction effect was significant.Pearson analysis was used for correlation testing.Results:The interaction effect between the time and group of HAMD-17 scores was significant ( F=121.784, P<0.05). The results of simple effects analysis showed that the HAMD-17 scores of the observation group at T1 and T2 ((12.07±4.08) and (14.78±4.99), respectively) were lower than those of the control group ((23.78±5.87) and (24.67±7.00), P<0.05). The treatment response rate and remission rate of the observation group at T1 were higher than those of the control group ( χ2=4.090, 7.378, both P<0.05).The treatment response rate and remission rate of the observation group at T2 were higher than those of the control group ( χ2=4.463, 4.547, both P<0.05). The time and group interaction effects of the percentage of correct response and conceptualization level in the Wisconsin card sorting test were significant ( F=30.087, 20.004, P<0.05). The results of simple effects analysis showed that the percentage of correct response and conceptualization level in the observation group at T1 and T2 were higher than those in the control group (all P<0.05). The time and group interaction effect of SII was significant ( F=8.173, P<0.05). The results of simple effects analysis showed that there was no statistically significant difference in SII between the two groups at T0 ( P>0.05). The SII at T1 and T2 in the observation group was lower than that in the control group ( P<0.05). In the observation group, the changes in SII from T2 to T0 was positively correlated with the change in HAMD-17 scores ( r=0.527, P<0.05), and negatively correlated with the percentage of correct responses to the Wisconsin card sorting test ( r=-0.412, P<0.05) and the percentage of conceptualization level ( r=-0.411, P<0.05). Conclusion:irTMS is effective in treating TRD and can improve patients' cognitive function and immune inflammation damage.

Objective To investigate the effects of perioperative blood glucose(BG)levels on postoperative acute kidney injury(AKI)and rehabilitation in diabetic patients with coronary heart disease after coronary artery bypass grafting(CABG).Methods Randomly select data from 142 patients who underwent CABG treatment at The Fuwai Cardiovascular Hospital in Qingdao from January to December 2022,and compare the BG indicators,AKI incidence,cardiac function improvement and quality of life between good control group(n=57)and poor control group(n=85).Results The operation time,ventilator use time,postoperative ICU time,hospital stay time and various BG indexes in the good control group were significantly lower than those in the poor control group(P<0.05 or P<0.01).27 patients(19.01%)developed AKI after surgery,and the incidence of AKI in the good control group was significantly lower than that in the poor control group(10.53%vs 24.71%,P<0.05).After treatment,the cardiac function indexes in both groups were significantly improved compared with those before surgery,and the good control had significantly better cardiac function and quality of life than the poor control(P<0.05).Conclusions The incidence of AKI after CABG in patients with diabetes and coronary heart disease was 19.01%.Good perioperative BG level control can reduce the risk of postoperative AKI and help early postoperative recovery.

Objective:To investigate the safety and efficacy of a modified radiofrequency ablation（RFA）treatment method for primary great saphenous vein varicose.Methods:Clinical data of 90 patients with primary great saphenous vein varicose treated with ultrasound-guided RFA from January 2021 to April 2024 in the Ultrasound Department of the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Among them，45 patients were treated with traditional RFA treatment method（traditional group）and 45 patients were treated with improved RFA treatment method（improved group）. Number of punctures，operation time，foam hardener dosage，intraoperative and postoperative complications were recorded in the two groups. The preoperative and postoperative venous clinical severity score（VCSS）and chronic venous insufficiency questionnaire（CIVIQ-14）were compared. The closure rate and recurrence rate of great saphenous vein varicose were followed up and the efficacy of the two methods were analyzed.Results:The success rate of the improved group and the traditional group was 100%.The number of punctures in the improved group was less than those of the traditional group［1（1，1） vs. 2（2，3）， Z = -7.431， P<0.001］，and the operation time of the modified group was shorter than that of the traditional group［（15.89 ± 3.63）min vs.（30.91 ± 5.58）min， t=-15.145， P<0.001］，the average volume of lauryl foam was lower than that of the traditional RFA group［（7.96 ± 2.36）ml vs.（15.69 ± 2.89）ml， t=-13.892， P<0.001］. The incidence of complications was similar between the two groups，with no statistical significance（all P>0.05）. Postoperative VCSS and CIVIQ-14 scores were significantly improved compared with before（all P<0.001），with no statistical significance between the two groups（all P>0.05）. At 12 months after the operation，there was no significant difference in the closure rate of the saphenous vein between the improved group and the traditional group（ P>0.05），and the recurrence rate of varicose veins in both groups was 0. Conclusions:This modified RFA treatment method for the treatment of lower extremity varicose veins is minimally invasive，safe，and has the same efficacy as the traditional RFA treatment method. Compared with the traditional RFA treatment method，the modified RFA treatment method has the advantages of convenient operation，less puncture times and shorter operation time，and is worthy of clinical promotion.

Objective To provide relevant suggestions for ethical considerations in clinical research by searching literature related to ethics in clinical research using the visualization analysis software CiteSpace,and to analyze and compare the current research status of clinical research ethics at home and abroad.Methods The papers on the application of medical ethics in clinical trials from the core collection of CNKI and Web of Science databases were collected and the bibliometric software CiteSpace was used to draw a knowledge map of domestic and foreign literature.The research hotspots and development trends of medical ethics in clinical trials were analyzed.Results In terms of the process of informed consent,risk minimization,fair selection,and protection on the rights and interests of vulnerable groups,the focus of medical ethics research in China were basically consistent with foreign literature.The difference was that foreign research focused more on ethical education,the quality of life of research participants,and ethical counseling.Otherwise,domestic research focused more on the quality management of clinical trials and the specificity of traditional Chinese medicine research,with research on vulnerable groups mostly focused on children.Conclusion Chinese researchers should strengthen multi-dimensional research on medical ethics in China,and gradually expand their view from ethical review points and management research to applied research solved clinical problems and the specificity of research participants,and increasing the number and dimensions of research.

Objective To provide relevant suggestions for ethical considerations in clinical research by searching literature related to ethics in clinical research using the visualization analysis software CiteSpace,and to analyze and compare the current research status of clinical research ethics at home and abroad.Methods The papers on the application of medical ethics in clinical trials from the core collection of CNKI and Web of Science databases were collected and the bibliometric software CiteSpace was used to draw a knowledge map of domestic and foreign literature.The research hotspots and development trends of medical ethics in clinical trials were analyzed.Results In terms of the process of informed consent,risk minimization,fair selection,and protection on the rights and interests of vulnerable groups,the focus of medical ethics research in China were basically consistent with foreign literature.The difference was that foreign research focused more on ethical education,the quality of life of research participants,and ethical counseling.Otherwise,domestic research focused more on the quality management of clinical trials and the specificity of traditional Chinese medicine research,with research on vulnerable groups mostly focused on children.Conclusion Chinese researchers should strengthen multi-dimensional research on medical ethics in China,and gradually expand their view from ethical review points and management research to applied research solved clinical problems and the specificity of research participants,and increasing the number and dimensions of research.