OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment of "biaoben acupoint combination" on cardiomyocyte mitochondrial fission in the rats with myocardial ischemia-reperfusion injury (MIRI) and explore its mechanism. METHODS: Fifty male SD rats were randomly divided into a sham-operation group, a model group, an EA pretreatment group, an EA pretreatment + Compound C group and an EA pretreatment+ML385 group, 10 rats in each group. In the EA pretreatment, the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, EA was delivered at bilateral "Neiguan" (PC6), "Zusanli" (ST36) and "Guanyuan" (CV4) for 20 min, with continuous wave and 2 Hz of frequency, 1 mA of current, once daily for consecutive 7 days. On day 8, in the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, 30 min before model preparation, the intraperitoneal injection with Compound C (0.3 mg/kg) and ML385 (30 mg/kg) was administered respectively. Except in the sham-operation group, the ligation of the left anterior descending coronary artery was performed to prepare MIRI rat model in the rest groups. In the sham-operation group, the thread was not ligated. After modeling, the content of reactive oxygen species (ROS) in the ischemic area was measured by flow cytometry, superoxide dismutase (SOD) was detected using xanthine oxidase method, and malondialdelyde (MDA) was detected using thiobarbituric acid (TBA) chromatometry. The morphology of myocardial tissue in the ischemic area was observed with HE staining, and the mitochondria ultrastructure of cardiomyocytes observed under transmission electron microscopy. Using immunofluorescence analysis, the positive expression of mitochondrial fission factor (MFF), mitochondrial fission 1 protein antibody (Fis1) and dynamin-related protein 1 (Drp1) was detected; and with immunohistochemical method used, the protein expression of adenosine monophosphate-activated protein kinase (AMPK), nuclear factor E2-associated factor2 (Nrf2) and Drp1 in the ischemic area was detected. RESULTS: Compared with the sham-operation group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 increased in the model group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 decreased (P<0.01), and the protein expression of Drp1 elevated (P<0.01). Compared with the model group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 were dropped in the EA pretreatment group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 rose (P<0.01), and the protein expression of Drp1 declined (P<0.01); and in the EA pretreatment+Compound C group and the EA pretreatment+ML385 group, the positive expression of MFF, Fis1 and Drp1, and the protein expression of Drp1 were all reduced (P<0.01). When compared with the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 were dropped in the EA pretreatment group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 rose (P<0.01, P<0.05), and the protein expression of Drp1 decreased (P<0.05). In comparison with the model group, the EA pretreatment+Compound C group and the EA pretreatment+ML385 group, the cardiac muscle fiber rupture, cell swelling and mitochondrial disorders were obviously alleviated in the EA pretreatment group. The morphological changes were similar among the model group, the EA pretreatment+Compound C group and the EA pretreatment+ML385 group. CONCLUSION Electroacupuncture pretreatment of "biaoben acupoint combination" attenuates myocardial injury in MIRI rats, probably through promoting the phosphorylation of AMPK and Nrf2, inhibiting the excessive mitochondrial fission induced by Drp1, and reducing mitochondrial dysfunction caused by mitochondrial fragmentation and vacuolation.
Animals ; Electroacupuncture ; Male ; Rats, Sprague-Dawley ; Myocardial Reperfusion Injury/physiopathology* ; Myocytes, Cardiac/cytology* ; Rats ; Acupuncture Points ; Mitochondrial Dynamics ; Humans ; Reactive Oxygen Species/metabolism* ; NF-E2-Related Factor 2/genetics* ; Superoxide Dismutase/metabolism*

The rich club, as a community of highly interconnected nodes, serves as the topological center of the network. However, the similarities and differences in how the rich club supports functional integration and segregation in the brain across different species remain unknown. In this study, we first detected and validated the rich club in the structural networks of mouse, monkey, and human brains using neuronal tracing or diffusion magnetic resonance imaging data. Further, we assessed the role of rich clubs in functional integration, segregation, and balance using quantitative metrics. Our results indicate that the presence of a rich club facilitates whole-brain functional integration in all three species, with the functional networks of higher species exhibiting greater integration. These findings are expected to help to understand the relationship between brain structure and function from the perspective of brain evolution.
Animals ; Humans ; Brain/diagnostic imaging* ; Mice ; Male ; Nerve Net/diagnostic imaging* ; Macaca ; Female ; Neural Pathways/diagnostic imaging* ; Magnetic Resonance Imaging ; Biological Evolution ; Adult ; Diffusion Magnetic Resonance Imaging ; Brain Mapping ; Species Specificity ; Mice, Inbred C57BL

Background and aims:Environmental pollutants,particularly organochlorine insecticides like endosulfan(ENDO),are increasingly linked to liver toxicity and related diseases.Despite its widespread historical use,the mechanisms underlying ENDO-induced liver damage remain poorly understood.This study aims to elucidate the cellular and molecular mechanisms of ENDO-induced hepatotoxicity.Methods:C57BL/6 mice were exposed to ENDO for two weeks.Single-cell RNA sequencing(scRNA-seq)was subsequently performed on mouse livers to explore ENDO-induced hepatotoxicity at the single-cell level.Differentially expressed genes(DEGs)across cell types and treatments were identified and then subjected to pathway enrichment to uncover key biological processes affected by ENDO.Transcription factor(TF)regulatory network,pseudotime trajectory,and cellular communication analysis were used to explore the molecular and cellular changes after ENDO exposure.Results:ENDO not only caused direct hepatocyte injury but also activated hepatic stellate cells and lymphocytes,triggering inflammatory responses with upregulation of multiple key chemokines and cytotoxic genes.Additionally,ENDO exposure led to the recruitment and activation of myeloid cells,contributing to the inflammatory milieu.An increase in intercellular communication and changes to the hepatic microenvironment,especially the interaction between activated hepatic stellate cells and CD8+T cells were observed,further implicating these processes in ENDO-induced liver damage.Conclusions:This study provides new insights into the cellular and molecular mechanisms underlying liver injury induced by organochlorine insecticides like ENDO.Key genes and pathways involved in ENDO-associated liver toxicity have been identified at a single-cell resolution.These findings suggest that altered cellular communications and inflammatory responses may play pivotal roles in the pathogenesis of ENDO-induced liver injury.

The incidence of cardiovascular diseases(CVD)has been increasing year by year,with atherosclerosis(As)being the leading cause in terms of both incidnce and mortality for CVD in China.Traditional theories suggest that the pathogenesis of atherosclerotic CVD is associated with endothelial dysfunction and inflammatory responses caused by the accumulation of oxidized low density lipoprotein(ox-LDL).However,recent studies have demonstrated that perivascular adipose tissue(PVAT)can positively influence the occurrence and development of CVD through the vascular adventitia pathway.This article reviews the connection between PVAT and CVD,effective pathways for promoting CVD improve-ment,and the regulatory role of AMP-activated protein kinase(AMPK)on PVAT,aiming to explore effective intervention targets for CVD.

Objective To explore the protective effects of pretreatment with the Mongolian medicine Jiruhen Gurigumu-7(JG-7)and Guangzao Sanwei Tang(GZ-3)on myocardial ischemia-reperfusion injury(MIRI)in mice.Methods 60 male C57BL/6J mice were randomly divided into sham operation(Sham)group,model(Model)group,compound danshen drip pill(CDDP)positive control group,JG-7 group,GZ-3 group,and 12 mice in each group to establish the MIRI model,and the H9C2 cells were randomly divided into Control(normoxic)group,H/R(hypoxia 6 h reoxygenation 14 h)group,H/R+JG-7 group,H/R+GZ-3 group.The mice in each group were tested for cardiac function indexes after 30 min of ischemia,24 h and 7 d of reperfusion,TTC staining to detect infarct area after 24 h of MIRI,HE staining to detect myocardial tissue structure and cellular morphology after 24 h of MIRI,TUNEL apoptosis kit to detect apoptosis of myocardial cells after 24 h of MIRI,Masson staining to detect myocardial fibrosis after 7 d of MIRI.Blood was taken from the abdominal aorta,serum was separated,and the indexes after oxidative stress of MIRI were detected in each group of mice,and the survival rate of H9C2 cells after H/R was detected in each group by CCK-8 method.Results The results of TTC showed that JG-7 and GZ-3 reduced the infarct area after 24 h of MIRI in mice.ELISA and kit assays proved that JG-7 and GZ-3 reduced creatine phosphokinase isoenzyme(Creatinekinase-MB,CK-MB),Lactic dehydrogenase(LDH),malondialdehyde(MDA)levels,and increased superoxide dismutase(SOD)levels.HE staining showed that JG-7 and GZ-3 improved myocardial pathology after MIRI 24 h.The results of TUNEL apoptosis assay showed that JG-7 and GZ-3 improved apoptosis in myocardial tissues 24 h after MIRI.Masson staining results showed that JG-7 and GZ-3 could reduce the area of myocardial tissue fibrosis after MIRI 7 d.CCK-8 assay results showed that JG-7 and GZ-3 could improve the cell survival rate after H/R in H9C2 cells.Conclusion Pre-treatment with Mongolian medicine Jiruhen Gurigumu-7 and Guangzao Sanwei Tang can reduce the damage caused after ischemia-reperfusion(I/R),decrease the area of myocardial infarction and fibrosis after I/R in mice,and protect the heart.

Objective:To investigate the application effect of BOPPPS+team-based learning (TBL) based on the concept of outcome-based education (OBE) in the teaching of infectious rash and fever illnesses in children.Methods:A total of 199 undergraduate students of the class 2019 in the five-year program of Department of Pediatrics in Chongqing Medical University were selected as subjects, and they were divided into experimental group with 99 students and control group with 100 students using a random number table. The students in the experimental group received BOPPPS+TBL teaching based on the OBE concept, while those in the control group received traditional teaching. After the end of the curriculum, scores were compared between the two groups, and a questionnaire survey was conducted for self-evaluation of teaching and learning effectiveness and the acceptance of teaching models. SPSS 22.0 was used to perform the t-test and the chi-square test. Results:The experimental group had a significantly higher score of the course than the control group [(88.08±5.31) vs. (85.62±8.44), P=0.014]. The questionnaire survey showed that compared with the control group, the experimental group had significantly higher scores of the self-evaluation of teaching effectiveness [(4.40±0.75) vs. (3.36±1.13), P<0.001] and learning effectiveness [(4.31±0.84) vs. (3.35±1.19), P<0.001]. In the experimental group, 96.96% (96/99) of the students believed that BOPPPS+TBL teaching based on the OBE concept could help students to master and understand the knowledge points, and 93.93% (93/99) of the students were willing to use this teaching model in future learning. Conclusions:BOPPPS+TBL teaching based on the OBE concept can help to achieve teaching objectives and significantly improve student satisfaction and learning outcomes.

Objective:To investigate the differences in protein profile expression in serum samples from children with corona virus disease 2019（COVID-19）related encephalopathy and to explore the underlying mechanisms.Methods:From December 1,2022 to January 31,2023,28 children with COVID-19 who were admitted to the Department of Pediatric Intensive Medicine at Shandong Provincial Hospital Affiliated to Shandong First Medical University were collected,including 21 patients with encephalopathy(COVID-19 with encephalopathy group) and seven patients without encephalopathy(COVID-19 without encephalopathy group).Three children from each group were selected for serum proteomic analysis using tandem mass spectrometry labeling proteomics technology.Proteins were considered significantly different if the fold change was >1.2 or <0.8，with P<0.05.Bioinformatics analysis，including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes Pathway Enrichment were performed on differentially expressed proteins.Protein-protein interaction networks were analyzed using the STRING database.Selected proteins were further validated by enzyme-linked immunosorbert assay. Results:A total of 41 differentially expressed proteins were identified between the two groups.Among these，14 proteins were upregulated and 27 proteins were downregulated in COVID-19 patients with encephalopathy compared to those without encephalopathy.Bioinformatics analysis revealed that these proteins were primarily enriched in critical signaling pathways，including complement and coagulation regulation，neutrophil degranulation and activation，and platelet degranulation.Enzyme-linked immunosorbert assay validation confirmed significant differences in key coagulation-regulating proteins(von willebrand factor upregulated，serpin family F member 2 downregulated in COVID-19 patients with encephalopatly）between the two groups.Conclusion:Coagulation dysfunction may play a role in the development of COVID-19 associated encephalopathy in children，providing valuable insights for future research.

The incidence of cardiovascular diseases(CVD)has been increasing year by year,with atherosclerosis(As)being the leading cause in terms of both incidnce and mortality for CVD in China.Traditional theories suggest that the pathogenesis of atherosclerotic CVD is associated with endothelial dysfunction and inflammatory responses caused by the accumulation of oxidized low density lipoprotein(ox-LDL).However,recent studies have demonstrated that perivascular adipose tissue(PVAT)can positively influence the occurrence and development of CVD through the vascular adventitia pathway.This article reviews the connection between PVAT and CVD,effective pathways for promoting CVD improve-ment,and the regulatory role of AMP-activated protein kinase(AMPK)on PVAT,aiming to explore effective intervention targets for CVD.

[Purpose]To analyze the incidence and mortality of thyroid cancer in Hefei of Anhui Province in 2021 and the trend from 2013 to 2021.[Methods]Using the data of Hefei Cancer Registry,the crude incidence/mortality rate,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)and world standard population(ASIRW/ASMRW)were cal-culated in 2021.The average annual percentage change(AAPC)of the crude incidence/mortality rate and age-standardized incidence/mortality rate were calculated using Joinpoint software to ana-lyze trends from 2013 to 2021.[Results]In 2021,the crude incidence rate of thyroid cancer in Hefei was 47.54/105,the ASIRC was 42.30/105,the ASIRW was 35.85/105.The crude mortality rate of thyroid cancer was 0.70/105,the ASMRC was 0.38/105,the ASMRW was 0.40/105.The in-cidence rate of thyroid cancer reached its peak in the 50～54 age group and the mortality rate reached its peak in the group over 85 years old.The incidence rate and mortality rate of women were higher than those of men,and the incidence and mortality rates in urban areas were higher than those in rural areas.The incidence and mortality of thyroid cancer showed a upward trend from 2013 to 2021 in Hefei City(AAPC were 38.23％and 9.68％,both P＜0.05).[Conclusion]The ASIRC/ASMRC of thyroid cancer showed a upward trend from 2013 to 2021 in Hefei City.It is necessary to strengthen prevention and control to reduce the exposure of risk factors.At the same time,diagnosis and treatment should be standardized to avoid over diagnosis.

Objective To explore the protective effects of pretreatment with the Mongolian medicine Jiruhen Gurigumu-7(JG-7)and Guangzao Sanwei Tang(GZ-3)on myocardial ischemia-reperfusion injury(MIRI)in mice.Methods 60 male C57BL/6J mice were randomly divided into sham operation(Sham)group,model(Model)group,compound danshen drip pill(CDDP)positive control group,JG-7 group,GZ-3 group,and 12 mice in each group to establish the MIRI model,and the H9C2 cells were randomly divided into Control(normoxic)group,H/R(hypoxia 6 h reoxygenation 14 h)group,H/R+JG-7 group,H/R+GZ-3 group.The mice in each group were tested for cardiac function indexes after 30 min of ischemia,24 h and 7 d of reperfusion,TTC staining to detect infarct area after 24 h of MIRI,HE staining to detect myocardial tissue structure and cellular morphology after 24 h of MIRI,TUNEL apoptosis kit to detect apoptosis of myocardial cells after 24 h of MIRI,Masson staining to detect myocardial fibrosis after 7 d of MIRI.Blood was taken from the abdominal aorta,serum was separated,and the indexes after oxidative stress of MIRI were detected in each group of mice,and the survival rate of H9C2 cells after H/R was detected in each group by CCK-8 method.Results The results of TTC showed that JG-7 and GZ-3 reduced the infarct area after 24 h of MIRI in mice.ELISA and kit assays proved that JG-7 and GZ-3 reduced creatine phosphokinase isoenzyme(Creatinekinase-MB,CK-MB),Lactic dehydrogenase(LDH),malondialdehyde(MDA)levels,and increased superoxide dismutase(SOD)levels.HE staining showed that JG-7 and GZ-3 improved myocardial pathology after MIRI 24 h.The results of TUNEL apoptosis assay showed that JG-7 and GZ-3 improved apoptosis in myocardial tissues 24 h after MIRI.Masson staining results showed that JG-7 and GZ-3 could reduce the area of myocardial tissue fibrosis after MIRI 7 d.CCK-8 assay results showed that JG-7 and GZ-3 could improve the cell survival rate after H/R in H9C2 cells.Conclusion Pre-treatment with Mongolian medicine Jiruhen Gurigumu-7 and Guangzao Sanwei Tang can reduce the damage caused after ischemia-reperfusion(I/R),decrease the area of myocardial infarction and fibrosis after I/R in mice,and protect the heart.