Background: Diabetes-induced testicular damage (DITD) is a common complication of diabetes. We investigated underlying mechanism of retinoblastoma-binding protein 6 (Rbbp6)-mediated brain and muscle ARNT-like 1 (Bmal1) ubiquitination in modulating ferroptosis in DITD. Methods: Spermatogenic cell apoptosis and viability were measured by flow cytometry and cell counting kit 8 (CCK-8), respectively. The impact of Rbbp6 and Bmal1 on ferroptosis was assessed by determining expression of ferroptosis markers glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), and levels of malondialdehyde (MDA), glutathione (GSH), iron, and lipid peroxidation. Co-immunoprecipitation was performed to determine the interaction between Rbbp6 and Bmal1, as well as the ubiquitination level of Bmal1. The expression levels of Rbbp6, Bmal1, Yes-associated protein 1 (YAP1), ferroptosis markers, and testicular steroidogenic enzymes were tested by Western blot. Results: Bmal1 protein expression was significantly downregulated, while Rbbp6 was upregulated in DITD mouse model and high glucose (HG)-induced GC-1 spg cells. Overexpression of Bmal1 improved testicular injury in diabetic mice, reduced 4-hydroxynonenal (4-HNE), MDA, iron levels, and increased expression levels of GPX4, SLC7A11, GSH, as well as testicular steroidogenic enzymes. Rbbp6 decreased Bmal1 level through promoting its ubiquitination. Meanwhile, Rbbp6 knockdown inhibited the ferroptosis of HG-induced GC-1 spg cells, which were abolished by silencing Bmal1. In addition, knockdown of YAP1 or treatment with ferroptosis inducer erastin blocked the above effects caused by Bmal1 overexpression. Conclusion Rbbp6-mediated Bmal1 ubiquitination suppressed YAP1 pathway, promoting ferroptosis in DITD. This study highlighted Rbbp6/Bmal1/YAP1 axis as a potential therapeutic target for mitigating DITD.

Background: Diabetes-induced testicular damage (DITD) is a common complication of diabetes. We investigated underlying mechanism of retinoblastoma-binding protein 6 (Rbbp6)-mediated brain and muscle ARNT-like 1 (Bmal1) ubiquitination in modulating ferroptosis in DITD. Methods: Spermatogenic cell apoptosis and viability were measured by flow cytometry and cell counting kit 8 (CCK-8), respectively. The impact of Rbbp6 and Bmal1 on ferroptosis was assessed by determining expression of ferroptosis markers glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), and levels of malondialdehyde (MDA), glutathione (GSH), iron, and lipid peroxidation. Co-immunoprecipitation was performed to determine the interaction between Rbbp6 and Bmal1, as well as the ubiquitination level of Bmal1. The expression levels of Rbbp6, Bmal1, Yes-associated protein 1 (YAP1), ferroptosis markers, and testicular steroidogenic enzymes were tested by Western blot. Results: Bmal1 protein expression was significantly downregulated, while Rbbp6 was upregulated in DITD mouse model and high glucose (HG)-induced GC-1 spg cells. Overexpression of Bmal1 improved testicular injury in diabetic mice, reduced 4-hydroxynonenal (4-HNE), MDA, iron levels, and increased expression levels of GPX4, SLC7A11, GSH, as well as testicular steroidogenic enzymes. Rbbp6 decreased Bmal1 level through promoting its ubiquitination. Meanwhile, Rbbp6 knockdown inhibited the ferroptosis of HG-induced GC-1 spg cells, which were abolished by silencing Bmal1. In addition, knockdown of YAP1 or treatment with ferroptosis inducer erastin blocked the above effects caused by Bmal1 overexpression. Conclusion Rbbp6-mediated Bmal1 ubiquitination suppressed YAP1 pathway, promoting ferroptosis in DITD. This study highlighted Rbbp6/Bmal1/YAP1 axis as a potential therapeutic target for mitigating DITD.

Background: Diabetes-induced testicular damage (DITD) is a common complication of diabetes. We investigated underlying mechanism of retinoblastoma-binding protein 6 (Rbbp6)-mediated brain and muscle ARNT-like 1 (Bmal1) ubiquitination in modulating ferroptosis in DITD. Methods: Spermatogenic cell apoptosis and viability were measured by flow cytometry and cell counting kit 8 (CCK-8), respectively. The impact of Rbbp6 and Bmal1 on ferroptosis was assessed by determining expression of ferroptosis markers glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), and levels of malondialdehyde (MDA), glutathione (GSH), iron, and lipid peroxidation. Co-immunoprecipitation was performed to determine the interaction between Rbbp6 and Bmal1, as well as the ubiquitination level of Bmal1. The expression levels of Rbbp6, Bmal1, Yes-associated protein 1 (YAP1), ferroptosis markers, and testicular steroidogenic enzymes were tested by Western blot. Results: Bmal1 protein expression was significantly downregulated, while Rbbp6 was upregulated in DITD mouse model and high glucose (HG)-induced GC-1 spg cells. Overexpression of Bmal1 improved testicular injury in diabetic mice, reduced 4-hydroxynonenal (4-HNE), MDA, iron levels, and increased expression levels of GPX4, SLC7A11, GSH, as well as testicular steroidogenic enzymes. Rbbp6 decreased Bmal1 level through promoting its ubiquitination. Meanwhile, Rbbp6 knockdown inhibited the ferroptosis of HG-induced GC-1 spg cells, which were abolished by silencing Bmal1. In addition, knockdown of YAP1 or treatment with ferroptosis inducer erastin blocked the above effects caused by Bmal1 overexpression. Conclusion Rbbp6-mediated Bmal1 ubiquitination suppressed YAP1 pathway, promoting ferroptosis in DITD. This study highlighted Rbbp6/Bmal1/YAP1 axis as a potential therapeutic target for mitigating DITD.

Background: Diabetes-induced testicular damage (DITD) is a common complication of diabetes. We investigated underlying mechanism of retinoblastoma-binding protein 6 (Rbbp6)-mediated brain and muscle ARNT-like 1 (Bmal1) ubiquitination in modulating ferroptosis in DITD. Methods: Spermatogenic cell apoptosis and viability were measured by flow cytometry and cell counting kit 8 (CCK-8), respectively. The impact of Rbbp6 and Bmal1 on ferroptosis was assessed by determining expression of ferroptosis markers glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), and levels of malondialdehyde (MDA), glutathione (GSH), iron, and lipid peroxidation. Co-immunoprecipitation was performed to determine the interaction between Rbbp6 and Bmal1, as well as the ubiquitination level of Bmal1. The expression levels of Rbbp6, Bmal1, Yes-associated protein 1 (YAP1), ferroptosis markers, and testicular steroidogenic enzymes were tested by Western blot. Results: Bmal1 protein expression was significantly downregulated, while Rbbp6 was upregulated in DITD mouse model and high glucose (HG)-induced GC-1 spg cells. Overexpression of Bmal1 improved testicular injury in diabetic mice, reduced 4-hydroxynonenal (4-HNE), MDA, iron levels, and increased expression levels of GPX4, SLC7A11, GSH, as well as testicular steroidogenic enzymes. Rbbp6 decreased Bmal1 level through promoting its ubiquitination. Meanwhile, Rbbp6 knockdown inhibited the ferroptosis of HG-induced GC-1 spg cells, which were abolished by silencing Bmal1. In addition, knockdown of YAP1 or treatment with ferroptosis inducer erastin blocked the above effects caused by Bmal1 overexpression. Conclusion Rbbp6-mediated Bmal1 ubiquitination suppressed YAP1 pathway, promoting ferroptosis in DITD. This study highlighted Rbbp6/Bmal1/YAP1 axis as a potential therapeutic target for mitigating DITD.

Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.

Objective To investigate the medication rules of tradition Chinese medicine for the treatment of ulcerative colitis(UC)at remission stage by data mining method,thus to provide reference for clinical prescription and medication.Methods The clinical research or medical case report of UC remission treated by Chinese medicine issued in CNKI,Wanfang Data and VIP from July 2000 to December 2022 were retrieved.Excel 2019 was used to analyze the frequency statistics,and the distribution of the nature,flavor and meridian tropism of the prescribed drugs in the included literature.Modeler 18.0 and SPSS Statistics 26.0 were used for association rules and cluster analysis,and Cytoscape 3.9.1 was used to construct the network diagram of the associated drugs.Results A total of 121 articles were included in the analysis,involving 167 drugs,of which 24 drugs were frequently used,mainly including Atractylodis Macrocephalae Rhizoma,Poria,Aucklandiae Radix,Coptidis Rhizoma,Codonopsis Radix,Paeoniae Radix Alba,Coicis Semen,Astragali Radix,Glycyrrhizae Radix et Rhizoma Praeparata cum Melle,Angelicae Sinensis Radix,Citri Reticulatae Pericarpium,and Dioscoreae Rhizoma.According to the therapeutic actions,the drugs were mainly classified into deficiency-supplementing drugs,heat-clearing drugs,qi-regulating drugs,urination-promoting and dampness-percolating drugs,blood-stanching drugs,exterior-relieving drugs,interior-warming drugs,astringent drugs,dampness-resolving drugs,and blood-activating and stasis-resolving drugs.The medicinals were mainly warm,mild and cold in nature,and were sweet,bitter and pungent in flavor.Most of the drugs had the meridian tropism of the spleen,stomach,lung and liver.A total of 25 drug association rules were mined out,and five prescriptions were obtained after cluster analysis.Conclusion The Chinese medicine prescriptions for the treatment of UC remission usually deprive from the classical formulas such as Shenling Baizhu San,Sishen Pills,and Tongxie Yaofang.The compatibility of drugs reflects the thoughts of treating UC remission from the perspective of spleen,and embodies the therapies of strengthening the spleen and removing dampness,promoting qi and regulating blood,and focusing on tonifying ministerial fire and supporting yang in the later stage,which has the characteristics of treating both symptoms and root causes simultaneously by using multiple drugs through multiple methods.

Objective:To observe the influence of dabigatran etexilate combined with aspirin+clopidogrel on coagulation function and ankle-brachial index(ABI)in patients with non-valvular atrial fibrillation(NVAF).Methods:A total of 108 NVAF patients who underwent percutaneous coronary intervention(PCI)in Huangshi Fourth Hospital Co.,Ltd be-tween January 2018 and October 2020 were selected,and divided into combined treatment group(n=54,dabigatran etexi-late+aspirin+clopidogrel)and control group(n=54,aspirin+clopidogrel)according to random number table meth-od.After 6-month treatment,coagulation function,toe-brachial index(TBI),ABI,thromboelastography,serum level of matrix metalloproteinase-9(MMP-9),incidence of embolic events,bleeding events and adverse reactions were com-pared between two groups.Results:After treatment,compared with control group,patients in combined treatment group had significant higher activated partial thromboplastin time(APTT)[(45.46±4.27)s vs.(52.38±5.03)s],prothrom-bin time(PT)[(13.14±1.33)svs.(15.32±1.57)s],thrombin time(TT)[(22.67±2.21)s vs.(27.05±3.15)s],TBI[(0.78±0.13)vs.(0.84±0.15)],ABI[(1.11±0.14)vs.(1.18±0.13)],R value[(11.43±3.42)s vs.(14.48±4.51)s],K value[(8.54±2.18)s vs.(10.78±3.26)s]and MA value[(46.06±15.11)mm vs.(55.49±18.26)mm],and significant lower serum MMP-9 level[(182.47±18.84)μg/mlvs.(165.52±14.17)μg/ml](P＜0.05 or＜0.01).Total incidence rates of embolic events(5.56％)and bleeding events(1.85％)in combined treatment group were significantly lower than those of control group(18.52％,14.81％)(P＜0.05 both).There was no significant difference in incidence rate of adverse reactions between two groups(P=0.687).Conclusion:Dabigatran etexilate combined with aspi-rin+clopidogrel can significantly improve coagulation function,reduce embolic events and bleeding events,and reduce ser-um MMP-9 level in NVAF patients without increasing adverse reactions.

Objective:To systematically evaluate the effect of cognitive behavioral therapy (CBT) in elderly patients with depression.Methods:The randomized controlled trials on the effect of CBT in elderly patients with depression, published until December 15, 2022, were searched in PubMed, CINHAL, Cochrane Library, China Biology Medicine, China National Knowledge Infrastructure, WanFang Data, and VIP. Two researchers independently screened the literature, extracted data, and used the revised Cochrane risk of bias tool for randomized trials (ROB 2.0) to evaluate the quality of the included studies. Statistical analysis was conducted using Stata 16.0, and the quality of evidence was rated using Appraisal of Guidelines for Research and Evaluation (GRADE) predictor software.Results:A total of 11 randomized controlled trials were included, with a total of 833 elderly patients with depression. Randomized effect models were used to analyze outcome indicators such as depression, anxiety, and quality of life by combining effect quantities. Meta-analysis and GRADE evidence quality showed that compared to the control group, medium quality evidence showed that CBT could relieve depression in elderly depression patients with a statistical difference [ SMD=-1.58, 95% CI (-2.16, -0.99), P<0.05]. Low quality evidence suggested that CBT could alleviate anxiety in elderly depression patients also with a statistical difference [ SMD=-2.25, 95% CI (-4.04, -0.47), P<0.05]. Very low quality evidence indicated that CBT did not significantly improve the quality of life in elderly depression patients compared to conventional or pharmacological treatment [ SMD=-0.09, 95% CI (-2.07, 1.88), P>0.05] . Conclusions:Existing evidence suggests that CBT can alleviate depression and anxiety in elderly depression patients, but its improvement in quality of life is not yet significant. Treatment feedback and forms of CBT may become a research focus in recent years on intervention for elderly depression patients.

Objective:To investigate the impact of neferine(NEF)on the blood-brain barrier in ischemic stroke(IS)rats by regulating the CC chemokine ligand 2(CCL2)-CC chemokine receptor 2(CCR2)signal pathway.Methods:SD rats were randomly divided into model group,low-dose NEF group(NEF-L group,25 mg/kg NEF),high-dose NEF group(NEF-H group,50 mg/kg NEF),and high-dose NEF+CCR2 antagonist group(NEF-H+RS102895 group,50 mg/kg NEF+10 mg/kg RS102895),sham opera-tion group(Sham group),with 15 rats in each group.The neurological function scores of rats in each group were compared.The perme-ability of blood-brain barrier of rats in each group was evaluated by Evans blue(EB)permeation method.The water content of brain tis-sue of rats in each group was determined by dry and wet weight method.The expression levels of CCL2 and CCR2 mRNA in rat brain tissue were measured by real-time fluorescence quantitative PCR(RT-qPCR).The expression levels of CCL2,CCR2,ZO-1 and Clau-din-5 proteins in rat brain tissue were detected by Western blot.Results:Compared with Sham group,the neural function score,EB content,water content,the expression levels of CCL2,CCR2 mRNA and protein in the right brain tissue of the model group were obvi-ously higher(P<0.05),the expression levels of ZO-1 and Claudin-5 were lower(P<0.05).Compared with the model group,the neuro-logical function score,water content,EB content,the expression levels of CCL2,CCR2 mRNA and protein in the right brain tissue of rats in the NEF-H group were obviously lower(P<0.05),the expression levels of ZO-1 and Claudin-5 were obviously higher(P<0.05).RS102895 enhanced the protective effect of NEF on the blood-brain barrier in IS rats.Conclusion:NEF may protect the blood-brain barrier of IS rats by inhibiting CCL2-CCR2 signal pathway.

Micro-computed tomography(Micro-CT)is a non-invasive technology that is widely used in animal experiments to assist in the detection of bone,lung,oral,metabolic,middle and inner ear diseases,as well as tumors,and in other animal disease models.The technique can provide diverse scientific and reliable imaging data for animal experiments and has accordingly become an indispensable experimental method in animal experiments.In this review,we introduce the imaging principles of Micro-CT,review its application in the study of animal disease models,summarize the limitations of Micro-CT technology,and consider its future prospects.