OBJECTIVE: To investigate the regulatory effect of electroacupuncture (EA) at "Neiguan" (PC6) on mitochondrial autophagy in rats with myocardial ischemia-reperfusion injury (MIRI) at different phases (ischemia and reperfusion phases), and to explore the bidirectional regulatory effects of EA at "Neiguan" (PC6) and its potential mechanism. METHODS: Forty-five male SD rats were randomly divided into 6 groups according to the random number table method, namely, sham-operation group (n=9), model-A group (n=6), model-B group (n=9), EA-A1 group (n=6), EA-B1 group (n=6), and EA-B2 group (n=9). Except the rats in the sham-operation group, the MIRI model was established in the other groups with the physical ligation and tube pushing method. In the model-A group, the samples were collected directly after ligation, and in the model-B group, the samples were collected after ligation and reperfusion. In the EA-A1 group, EA was delivered while the ligation was performed, and afterwards, the samples were collected. In the EA-B1 group, while the ligation was performed, EA was operated at the same time, and after reperfusion, the samples were collected. In the EA-B2 group, during ligation and the opening of the left anterior descending branch of the coronary artery, EA was delivered, and after reperfusion, the samples were collected. EA was performed at bilateral "Neiguan" (PC6), with a disperse-dense wave, a frequency of 2 Hz/100 Hz, a current of 1 mA, and a duration of 30 min. HE staining was employed to observe the morphology of cardiomyocytes, TUNEL was adopted to detect the apoptosis of cardiomyocytes, transcriptome sequencing was to detect the differentially expressed genes in the left ventricle, JC-1 flow cytometry was to detect the mitochondrial membrane potential (MMP) of cardiomyocytes, Western blot was to detect the protein expression of phosphatase and tensin homolog-induced kinase 1 (Pink1), Parkin and p62 in the left ventricle of rats, and ELISA was to detect the levels of serum creatine kinase isoenzyme (CK-MB) and cardiac troponin I (cTn-I) in the rats. RESULTS: Compared with the sham-operation group, the cardiomyocytes of rats in the model-B group were severely damaged, with disordered arrangement, unclear boundaries, broken muscle fibers, edema and loose distribution; and the cardiomyocytes in the EA-B2 group were slightly damaged, the cell structure was partially unclear, the cells were arranged more regularly, and the intact cardiomyocytes were visible. Compared with the sham-operation group, the apoptosis of cardiomyocytes increased in the model-B group (P<0.001); and when compared with the model-B group, the apoptosis alleviated in the EA-B2 group (P<0.001). The differentially expressed genes among the EA-B2 group, the sham-operation group and the model-B group were closely related to cell autophagy and mitochondrial autophagy. Compared with the sham-operation group, MMP of cardiomyocytes was reduced (P<0.001), the protein expression of Pink1, Parkin, and p62 of the left ventricle and the levels of serum CK-MB and cTn-I were elevated in the model B group (P<0.001). In comparison with model-A group, the MMP of cardiomyocytes and the levels of serum CK-MB and cTn-I were reduced (P<0.001, P<0.05), and the protein expression of Pink1 in the left ventricle rose in the EA-A1 group (P<0.01). Compared with the model-B group, MMP of cardiomyocytes increased (P<0.001), the protein expression of Pink1, Parkin, and p62 of the left ventricle, and the levels of serum CK-MB and cTn-I decreased (P<0.001) in the EA-B1 group and the EA-B2 group. When compared with the EA-A1 group, MMP of cardiomyocytes increased (P<0.001), and the protein expression of Pink1, Parkin, and p62 of the left ventricle, and the levels of serum CK-MB and cTn-I decreased in the EA-B1 group (P<0.01). CONCLUSION EA at "Neiguan" (PC6) can ameliorate MIRI in rats, which may be achieved through the Pink1/Parkin-mediated mitochondrial autophagy pathway. EA can alleviate myocardial injury by enhancing mitochondrial autophagy at the ischemia phase, and it can reduce reperfusion injury by weakening mitochondrial autophagy at the reperfusion phase.
Animals ; Electroacupuncture ; Male ; Myocardial Reperfusion Injury/metabolism* ; Rats, Sprague-Dawley ; Rats ; Acupuncture Points ; Autophagy ; Humans ; Mitochondria/genetics*

OBJECTIVE To investigate the damage effect and potential toxic mechanism of SARS-CoV-2 spike protein(S protein)on human neuroblastomacells(SH-SY5Y).METHODS SH-SY5Y were treated with S protein at concentrations of 25,50,75,and 100 mg·L-1 for 24 h.Cell viability of SH-SY5Y was detected using the CCK-8 assay.The cytotoxic lactate dehydrogenase(LDH)detection kit was used to measure the release rate of LDH,and the 5-ethynyl-2′-deoxyuridine(EdU)-488 cell prolifera-tion kit was used to assess cell proliferation.The ATP detection kit was used to measure intracellular ATP content.The JC-1 fluorescent probe method was employed to detect the mitochondrial membrane potential(MMP)of cells.Seahorse XF was used to measure mitochondrial respiratory and glycolytic capacity.RESULTS Compared with the cell control group,cell viability was significantly reduced in S protein 25,50,75 and 100 mg·L-1 groups(P<0.01),and the half-inhibition concentration(IC50)was 65.05 mg·L-1.The LDH release rate wassignificantly increased(P<0.01)and the proportion of EdU positive cellswas significantly reduced(P<0.01)in S protein 25,50,75 and 100 mg·L-1 groups.S protein signifi-cantly reduced intracellular ATP content(P<0.01)at the concentrations of 75 and 100 mg·L-1,while significantly reduced intracellular MMP(P<0.05,P<0.01)at the concentrations of 50 and 75 mg·L-1.S protein 50 mg·L-1 increased the maximum value of basal glycolysis levels and glycolytic capacity(P<0.05,P<0.01),and S protein 25 and 50 mg·L-1 increased the maximum value of respiration capacity(P<0.05,P<0.01).SH-SY5Y cell viability was positively correlated with the intracellular ATP content and the MMP level(r2=0.9209,P=0.001;r2=0.6170,P=0.0025),and negatively correlated with the maximum level of basal glycolysis and glycolytic capacity(r2=0.5194,P=0.0285;r2=0.6664,P=0.0073),and nega-tively correlated with ATP production capacity(r2=0.8204,P=0.0008).CONCLUSIONS protein decreases the viability of SH-SY5Y cells and inhibited cell proliferation.The mechanism may be closely related to the disorder of energy metabolism.

OBJECTIVE To investigate the damage effect and mechanisms of cyclophosphamide(CTX)and its active metabolite derivative 4-hydroperoxycyclophosphamide(4-HC)to human neuroblas-toma SH-SY5Y cells.METHODS SH-SY5Y cells were treated with CTX[0(cell control),0.01,0.1,1,5,10,20,40 and 80 mmol·L-1]and 4-HC[0(cell control),0.01,0.1,1,5,10,20,40 and 80 μmol·L-1]for 48 h.Cell confluence and morphology were observed by the IncuCyte ZOOM system.Cell viability was assessed by CCK-8 assay.Lactate dehydrogenase(LDH)release was measured by LDH assay kit.SH-SY5Y cells were treated with CTX(0,1,5,10 and 20 mmol·L-1)and 4-HC(0,1,5,10 and 20 μmol·L-1)for 48 h before cell proliferation was analyzed by 5-ethynyl-2′-deoxyuridine(EdU)staining assay.Immunofluorescence was employed to assess the levels of the DNA double-strand break marker γ-H2AX and to evaluate changes in mitochondrial membrane potential.SH-SY5Y cells were treated with CTX(0,1,5 and 10 mmol·L-1)and 4-HC(0,1,5 and 10 μmol·L-1)for 48 h,and the alterations in glycolysis and oxidative phosphorylation levels were analyzed using the Seahorse XFe96 Analyzer.RESULTS Compared with the cell control group,cell confluence and cell viability were significantly reduced in the CTX and 4-HC groups(P<0.01),and the half-maximal inhibitory concentrations(IC50)for CTX and 4-HC were 4.44 mmol·L-1 and 4.78 μmol·L-1,respectively.The release rate of LDH was signif-icantly increased while the percentage of EdU+cells was significantly reduced in the CTX and 4-HC groups(P<0.01).The percentage of γ-H2AX+cells was significantly increased and mitochondrial membrane potential significantly decreased in the CTX and 4-HC group(P<0.05).Treatment with CTX and 4-HC resulted in reduced levels of maximum glycolytic capacity,glycolytic reserve,maximal respi-ration,and ATP production(P<0.05).CONCLUSION CTX and 4-HC exert significant cytotoxic effects on SH-SY5Y cells by disrupting cell membrane structure,impeding cell proliferation,and reducing cell viability.The mechanisms underlying these effects may involve intracellular DNA damage,disturbance of energy metabolism and mitochondrial dysfunction.

Background::Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer’s disease (AD). This study aimed to develop and validate a novel genetic-clinical-radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism.Methods::This retrospective study included 165 patients with AD from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) cohort between June 1, 2021, and March 31, 2022. Data on demographics, neuropsychological assessments, single-nucleotide polymorphisms of AD risk genes, and regional brain volumes were collected. A multivariate logistic regression model identified BPSD-associated factors, for subsequently constructing a diagnostic nomogram. This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1, 2022, and February 1, 2023. Area under receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess the discrimination, calibration, and clinical applicability of the nomogram.Results::Factors independently associated with BPSD were: CETP rs1800775 (odds ratio [OR] = 4.137, 95% confidence interval [CI]: 1.276-13.415, P = 0.018), decreased Mini Nutritional Assessment score (OR = 0.187, 95% CI: 0.086-0.405, P <0.001), increased caregiver burden inventory score (OR = 8.993, 95% CI: 3.830-21.119, P <0.001), and decreased brain stem volume (OR = 0.006, 95% CI: 0.001-0.191, P = 0.004). These variables were incorporated into the nomogram. The area under the ROC curve was 0.925 (95% CI: 0.884-0.967, P <0.001) in the internal validation and 0.791 (95% CI: 0.686-0.895, P <0.001) in the external validation. The calibration plots showed favorable consistency between the prediction of nomogram and actual observations, and the DCA showed that the model was clinically useful in both validations. Conclusion::A novel nomogram was established and validated based on lipid metabolism-related genes, nutritional status, and brain stem volumes, which may allow patients with AD to benefit from early triage and more intensive monitoring of BPSD.Registration::Chictr.org.cn, ChiCTR2100049131.

Objective:To analyze the gender difference in behavioral and psychological symptoms of dementia (BPSD) of amnestic mild cognitive impairment (aMCI) and Alzheimer′s disease (AD).Methods:It was a cross-sectional study. The clinical data of 201 patients with aMCI and 146 patients with AD were continuously collected from the Chinese Imaging, Biomarkers and Lifestyle Study of Alzheimer′s Disease (CIBL) cohort between June 1, 2021 to February 1, 2023 in Beijing Tiantan Hospital, Capital Medical University. The BPSD subtypes were compared between different gender. The gender-different BPSD subtypes were divided into depression group (126 cases) and non-depression group (221 cases), anxiety group (140 cases) and non-anxiety group (207 cases), indifference group (131 cases) and non-indifference group (216 cases). The sociodemographic data (age, sex, education level, marital status), hypertension, diabetes, stroke, heart disease, hyperlipidemia, smoking history, drinking history, carrier status of apolipoprotein E epsilon4 allele (APOE ε4), and the scores of the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), Activity of Daily Living (ADL) were compared by using hypothesis testing. Multivariate logistic regression was used to analyze the gender differences of BPSD in aMCI and AD patients.Results:The incidence rates of depression and anxiety in female were both significantly higher than those in male (44.93% vs 23.57%, 44.93% vs 33.57%), and the incidence rate of apathy was significantly lower than that in male (32.37% vs 45.71%) (all P<0.05). The proportion of female and ADL scores in depression group were both significantly higher than those in non-depression group [73.81% vs 51.58%, 22.00 (20.00, 30.00) vs 20.00 (20.00, 26.00) points], and the proportion of smoking and drinking history and MoCA scores in depression group were all significantly lower than those in non-depression group [13.49% vs 25.79%, 19.84% vs 35.75%, 16.00 (10.00, 22.00) vs 19.00 (13.00, 24.00) points] (all P<0.05). The proportion of female and ADL scores in anxiety group were both significantly higher than those in non-anxiety group [66.43% vs 55.07%, 23.00 (20.00, 30.75) vs 20.00 (20.00, 25.00) points], and the MMSE and MoCA scores in anxiety group were both significantly lower than those in non-anxiety group [23.00 (16.00, 27.00) vs 24.00 (19.00, 28.00) points, 16.00 (10.00, 21.00) vs 20.00 (13.00, 13.00) points] (all P<0.05). The proportion of female and the MMSE and MoCA scores in apathy group were all significantly lower than those in non-apathy group [51.15% vs 64.81%, 19.00 (11.00, 25.00) vs 26.00 (22.00, 28.00) points, 14.00 (7.00, 19.00) vs 21.00 (15.25, 24.00) points], and the age, proportion of APOE ε4 carriers and ADL scores in apathy group were all significantly higher [67.0 (61.0, 76.0) vs 66.0 (60.0, 71.0) years, 42.74% vs 31.31%, 27.00 (22.00, 38.00) vs 20.00 (20.00, 22.00) points] (all P<0.05). Female ( OR=2.384, 95% CI: 1.274-4.459) and decrease in MoCA score ( OR=0.955, 95% CI: 0.914-0.998) were positively correlated with risk of depression. Female ( OR=1.704, 95% CI: 1.077-2.695) was positively correlated with risk of anxiety. Male ( OR=0.558, 95% CI: 0.333-0.936), decrease in MoCA scores ( OR=0.937, 95% CI: 0.894-0.983) and increase in ADL scores ( OR=1.070, 95% CI: 1.027-1.116) were positively correlated with risk of apathy (all P<0.05). Conclusions:There are significant gender differences in BPSD in aMCI and AD patients. Female is positively correlated with risk of depression and anxiety, while male is positively correlated with the occurrence of apathy. Clinical attention should be paid to hierarchical management of BPSD patients of different gender.

Objective·To analyze the anatomical and macroscopic characteristics of the pterygopalatine suture(PPS)in Chinese population using cone-beam computed tomography(CBCT)technology,and to preliminarily investigate its developmental pattern and its association with the correction of maxillary underdevelopment.Methods·A total of 134 CBCT images,taken from July to August 2023 at Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,were categorized into six age groups.The PPS landmarks were utilized to determine the overall transverse position(XPPS),sagittal position(YPPS),insertion angle(IAP),insertion width of the pyramidal process(IWP),and insertion depth of the pyramidal process(IDP).The pterygomaxillary junction was identified through multiplanar observations.Regression analysis was performed to assess the correlation of these parameters with age and gender,and pairwise comparisons were made to determine the stable age range for parameter changes.Paired t-tests and paired chi-squared tests were conducted to analyze the bilateral parameter differences.Results·Results showed that YPPS and IDP did not exhibit significant correlation with age,whereas XPPS,IAP,IWP,and the incidence of pterygomaxillary fusion were significantly positively correlated with age(P<0.01).Gender differences were only significant for XPPS,with males demonstrating greater values than females(P<0.01).Analysis of age-related trends indicated significant differences in XPPS between group 1(6 years≤age<9 years)and group 2(9 years≤age<12 years)(female:P=0.006,male:P=0.004);significant differences in IAP were observed between group 2 and group 3(12 years≤age<15 years)(P=0.042),with 98.5%of samples having an IAP greater than 45 degrees;IWP differences were significant between group 1 and group 3(P=0.016),and the pterygomaxillary fusion incidence was significantly different among group 1,2,and 3(group 1 vs.2:P<0.001,group 2 vs 3:P=0.037,group 1 vs 3:P<0.001),with an incidence rate exceeding 90%in adults.No significant bilateral differences were found for all parameters.Conclusion·No significant changes were observed in YPPS and IDP after the age of 6,indicating a trend towards fusion of the maxilla with the pterygoid process.The overall transverse position of the PPS tends to stabilize around 12 years of age,while the IAP and IWP continue to increase and reach stability around 15 years of age,with a sagittal insertion orientation of the pyramidal process into the pterygoid notch.

Background: In the Chinese coal industry, widespread blame avoidance behavior (BAB) greatly impacts coal mine accidents. Therefore, it is necessary to stop the BAB of coal mine managers and raise the management level of coal mine enterprises for the safe development of Chinese coal industry. Methods: Based on the semi-structured interviews and questionnaire surveys (20 middle-level managers in coal mines), this paper used the Grounded Theory and Nvivo Software qualitative research methodology to open, spindle, and selectively encode the interview data. Then, an index system of factors influencing BAB of coal mine managers was constructed. The influence degree, affected degree, centrality degree, cause degree of each influencing factor were calculated and the hierarchical model of influencing factors of BAB of coal mine managers was established by the DEMATEL-ISM method which is a decision support tool used to evaluate and analyze the interdependencies between influencing factors. Results: Index system of factors influencing BAB of coal mine managers included four levels and 12 influencing factors: individual, organizational, institutional environmental, and situational factors. The hierarchical model identified eight causal factors and four consequential factors, of which safety management (15.355), work attitude (14.380), and work group performance (14.281) in the top three of the centrality rankings are the key factors affecting the avoidance behavior of coal mine managers; A 3-level multilevel structure was constructed to reflect the interactions among the factors influencing the BAB of coal mine managers in terms of direct, indirect, and root causes, and corresponding improvement measures were proposed. Conclusion This study offers a theoretical complement and practical guidance for stopping BAB of coal mine managers.

Background: In the Chinese coal industry, widespread blame avoidance behavior (BAB) greatly impacts coal mine accidents. Therefore, it is necessary to stop the BAB of coal mine managers and raise the management level of coal mine enterprises for the safe development of Chinese coal industry. Methods: Based on the semi-structured interviews and questionnaire surveys (20 middle-level managers in coal mines), this paper used the Grounded Theory and Nvivo Software qualitative research methodology to open, spindle, and selectively encode the interview data. Then, an index system of factors influencing BAB of coal mine managers was constructed. The influence degree, affected degree, centrality degree, cause degree of each influencing factor were calculated and the hierarchical model of influencing factors of BAB of coal mine managers was established by the DEMATEL-ISM method which is a decision support tool used to evaluate and analyze the interdependencies between influencing factors. Results: Index system of factors influencing BAB of coal mine managers included four levels and 12 influencing factors: individual, organizational, institutional environmental, and situational factors. The hierarchical model identified eight causal factors and four consequential factors, of which safety management (15.355), work attitude (14.380), and work group performance (14.281) in the top three of the centrality rankings are the key factors affecting the avoidance behavior of coal mine managers; A 3-level multilevel structure was constructed to reflect the interactions among the factors influencing the BAB of coal mine managers in terms of direct, indirect, and root causes, and corresponding improvement measures were proposed. Conclusion This study offers a theoretical complement and practical guidance for stopping BAB of coal mine managers.

Background: In the Chinese coal industry, widespread blame avoidance behavior (BAB) greatly impacts coal mine accidents. Therefore, it is necessary to stop the BAB of coal mine managers and raise the management level of coal mine enterprises for the safe development of Chinese coal industry. Methods: Based on the semi-structured interviews and questionnaire surveys (20 middle-level managers in coal mines), this paper used the Grounded Theory and Nvivo Software qualitative research methodology to open, spindle, and selectively encode the interview data. Then, an index system of factors influencing BAB of coal mine managers was constructed. The influence degree, affected degree, centrality degree, cause degree of each influencing factor were calculated and the hierarchical model of influencing factors of BAB of coal mine managers was established by the DEMATEL-ISM method which is a decision support tool used to evaluate and analyze the interdependencies between influencing factors. Results: Index system of factors influencing BAB of coal mine managers included four levels and 12 influencing factors: individual, organizational, institutional environmental, and situational factors. The hierarchical model identified eight causal factors and four consequential factors, of which safety management (15.355), work attitude (14.380), and work group performance (14.281) in the top three of the centrality rankings are the key factors affecting the avoidance behavior of coal mine managers; A 3-level multilevel structure was constructed to reflect the interactions among the factors influencing the BAB of coal mine managers in terms of direct, indirect, and root causes, and corresponding improvement measures were proposed. Conclusion This study offers a theoretical complement and practical guidance for stopping BAB of coal mine managers.

Background: In the Chinese coal industry, widespread blame avoidance behavior (BAB) greatly impacts coal mine accidents. Therefore, it is necessary to stop the BAB of coal mine managers and raise the management level of coal mine enterprises for the safe development of Chinese coal industry. Methods: Based on the semi-structured interviews and questionnaire surveys (20 middle-level managers in coal mines), this paper used the Grounded Theory and Nvivo Software qualitative research methodology to open, spindle, and selectively encode the interview data. Then, an index system of factors influencing BAB of coal mine managers was constructed. The influence degree, affected degree, centrality degree, cause degree of each influencing factor were calculated and the hierarchical model of influencing factors of BAB of coal mine managers was established by the DEMATEL-ISM method which is a decision support tool used to evaluate and analyze the interdependencies between influencing factors. Results: Index system of factors influencing BAB of coal mine managers included four levels and 12 influencing factors: individual, organizational, institutional environmental, and situational factors. The hierarchical model identified eight causal factors and four consequential factors, of which safety management (15.355), work attitude (14.380), and work group performance (14.281) in the top three of the centrality rankings are the key factors affecting the avoidance behavior of coal mine managers; A 3-level multilevel structure was constructed to reflect the interactions among the factors influencing the BAB of coal mine managers in terms of direct, indirect, and root causes, and corresponding improvement measures were proposed. Conclusion This study offers a theoretical complement and practical guidance for stopping BAB of coal mine managers.