AIM:To explore the expression of calcium binding and coiled-coil domain 2(CALCOCO2)in ani-mal models of atrial fibrillation(AF)and its role and mechanism in reversing atrial remodeling in AF mice.METHODS:Twelve rats and 12 mice were randomly divided into the following 2 groups(n=6 each):saline control group(saline group)and angiotensin Ⅱ(Ang Ⅱ)-induced AF group(Ang Ⅱ group).Western blot and immunohistochemistry(IHC)were used to detect CALCOCO2 expression in rat and mouse atrial muscle tissues.Another 24 mice were randomly divided into 4 groups(n=6 each):saline-oeNC,Ang Ⅱ-oeNC,saline-oeCALCOCO2,and Ang Ⅱ-oeCALCOCO2.An adeno-asso-ciated virus was used to induce CALCOCO2 overexpression in mouse atrial myocardium.Subsequently,transthoracic echocardiography and intracardiac electrophysiological testing were used to compare mouse cardiac function among the 4 groups.Western blot and TUNEL staining were also used to evaluate the effect of CALCOCO2 on apoptosis of cardiomyo-cytes in AF models.Additionally,IHC was used to assess the effect of CALCOCO2 on the levels of oxidative stress-related proteins[NADPH oxidase 2(NOX2)and NOX4]and fibrosis-related proteins[collagen type Ⅰ(Col Ⅰ),connexin 40(Cx40)and α-smooth muscle actin(α-SMA)]in AF atrial myocardium.RESULTS:The CALCOCO2 protein level in the atrial myocardium of rats and mice was significantly decreased in Ang Ⅱ group compared with saline group,as detected by Western blot and IHC(0.19±0.01 vs 0.32±0.03 for rats,0.37±0.10 vs 1.00±0.10 for mice,P<0.01).Compared with Ang Ⅱ-oeNC group,the mice in Ang Ⅱ-oeCALCOCO2 group exhibited decreased left atrial inner diameter,shorter AF duration,and increased ejection fraction(P<0.05).Semi-quantitative analysis of TUNEL staining revealed a signifi-cantly decreased apoptosis rate of mouse atrial myocytes in Ang Ⅱ-oeCALCOCO2 group compared with Ang Ⅱ-oeNC group(0.30±0.06 vs 0.61±0.03,P<0.01),which was consistent with the Western blot trend of apoptosis-related proteins such as BAX(1.94±0.34 vs 3.14±0.34,P<0.05)and cleaved caspase-3(2.19±0.41 vs 3.52±0.55,P<0.05).The semi-quantitative results of IHC and immunofluorescence revealed significantly increased levels of oxidative stress-related pro-teins(NOX2 and NOX4)and fibrosis-related proteins(Col Ⅰ and α-SMA),as well as decreased Cx40 levels,in Ang Ⅱ-oeNC group compared with saline-oeNC group.However,the expression levels of these proteins were significantly re-versed after CALCOCO2 overexpression(all P<0.05).CONCLUSION:Overexpression of CALCOCO2 reverses AF-in-duced electrical and structural remodeling by inhibiting the oxidative stress,apoptosis and fibrosis in mouse atrial tissues.

Objectives:This study aims to explore the effects of pioglitazone on the attenuation of ventricular arrhythmias(VAs)induced by β1-adrenergic receptor autoantibodies(β1AAb)and its potential mechanisms. Methods:48 SD rats were uniformly randomly divided into four groups using number table:control group received vehicle injection,β1AAb group received back multi-point injection of β1AR-ECLⅡ antigen peptide with adjuvant,2 mg/(kg·time),pioglitazone group received pioglitazone gavage for 2 weeks after 8 weeks of immunization,4 mg/(kg·d),and GW9662 group received pioglitazone+GW9662 intraperitoneal injection for 2 weeks after 8 weeks of immunization,1 mg/(kg·d).Powerlab recorded electrocardiograms and blood collection every 2 weeks.Baseline and week 10 echocardiography were recorded,followed by electrophysiology,histopathology,immunohistochemical staining,and electron microscopy examination after 10 weeks. Results:Compared to control group,β1AAb group showed a higher incidence of ventricular arrhythmias,shorter ventricular effective refractory period(VERP),longer action-recovery interval(ARI),lower left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS),lower positive staining area ratio of glucose transporter 1(GLUT1)and carnitine palmitoyltransferase 1a(CPT1a),all P＜0.05.Mitochondrial morphology abnormalities and network damage were also significantly observed(P＜0.05).In contrast to β1AAb group,pioglitazone group showed a reduced incidence of ventricular arrhythmias,prolonged VERP,shortened ARI,recovered LVEF and LVFS,increased the positive staining area ratio of GLUT1 and CPT1a,all P＜0.05.Improvement was observed in mitochondrial morphology abnormalities and network damage(P＜0.05).Compared to pioglitazone group,GW9662 group exhibited a higher incidence of ventricular arrhythmias,shorter VERP,and longer ARI,lower LVEF and LVFS,lower positive staining area ratio of GLUT1 and CPT1a,all P＜0.05.Mitochondrial morphology abnormalities and network damage did not recover(P＜0.05). Conclusions:Pioglitazone can reduce VAs induced by β1AAb,improve ventricular electrical conduction and activation recovery time heterogeneity,and mitigate ventricular remodeling caused by β1AAb at the tissue pathology level,accompanied by upregulation of ventricular cardiomyocyte glucose and lipid transport channel proteins and repair of damaged mitochondrial networks.

Objective:To explore the association between cognitive function and the level of gamma-amino-butyric acid(GABA)in anterior cingulate cortex(ACC)before and after treatment in patients with major depres-sion disorder.Methods:Totally 31 medication-naive patients with major depression disorder meeting the criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)and 33 normal controls were col-lected.Each eligible patient received treatment with selective serotonin reuptake inhibitor agents for 8 weeks.The MATRICS Consensus Cognitive Battery(MCCB)was used to evaluate the cognitive function.By means of 1H magnetic resonance spectroscopy,anterior cingulate cortex GABA concentrations were measured.Results:At base-line,the concentration of ACC GABA relative to water(GABA+/W)was lower in the patient group than in the control group(P＜0.05)and increased after treatment(P＜0.05).ACC GABA+/W was negatively associated with verbal learning and visual memory score in patient group at baseline(correlation coefficient and P value were r=-0.40,P＜0.05;r=-0.42,P＜0.05,respectively).The ACC GABA+/W difference resulted of treatment in patient group was positively associated with the difference of working memory score and the difference of reasoning and problem-solving score(correlation coefficient and P value were r=0.58,P＜0.05;r=0.66,P＜0.05,respec-tively).Conclusion:The cognitive dysfunction of patients with major depression disorder may not be related to the degree of depression and anxiety.And improvement of cognitive function may be associated with increase of ACC GABA concentrations.

Bavachin is a dihydroflavonoid compound isolated from Psoralea corylifolia, and exhibits anti-bacterial, anti-inflammatory, anti-tumor and lipid-lowering activities. Recent attention has gradually drawn on bavachin-induced apoptosis in many human cancer cell lines. However, the anti-cancer effects and related mechanisms in colorectal cancer remain unknown. Here, we investigated the effects of bavachin on colorectal cancer in vivo and in vitro. The results showed that bavachin inhibited the proliferation of human colorectal cancer cells and induce apoptosis. These changes were mediated by activating the MAPK signaling pathway, which significantly up-regulated the expression of Gadd45a. Furthermore, Gadd45a silencing obviously attenuated bavachin-mediated cell apoptosis. Inhibition of the MAPK signaling pathway by JNK/ERK/p38 inhibitors also weakened the up-regulation of Gadd45a by bavachin. The anticancer effect of bavachin was also validated using a mouse xenograft model of human colorectal cancer. In conclusion, these findings suggest that bavachin induces the apoptosis of colorectal cancer cells through activating the MAPK signaling pathway.
Humans ; Signal Transduction ; Flavonoids/pharmacology* ; Proteins/pharmacology* ; MAP Kinase Signaling System ; Colorectal Neoplasms/metabolism* ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Cell Cycle Proteins/pharmacology*

Objective:To explore the possible correlation between allostatic load (AL) and clinical symptoms in patients with first-episode schizophrenia (FES) and AL influence upon the onset.Methods:Patients with FES (schizophrenia group, n=93) who received treatment at Beijing Huilongguan Hospital from October 2017 to July 2019 and the healthy controls (control group, n=111) recruited during the same period were enrolled in the research. Systolic blood pressure, diastolic blood pressure, resting heart rate, body mass index, waist-hip ratio, high-density lipoprotein cholesterol, total cholesterol, glycosylated hemoglobin, high-sensitivity C-reactive protein, 12-hour urine adrenaline, 12-hour urine norepinephrine, 12-hour urine cortisol, and serum dehydroepiandrosterone of all subjects were collected to calculate the AL index. The positive and negative symptom scale (PANSS) was used to assess the psychopathological symptoms of patients. Covariance analysis was used to compare the differences of AL index and the thirteen biological components between FES patients and controls. Pearson correlation analysis was used to explore the correlation between AL index and clinical symptoms, and the Logistic regression analysis was used to explore the risk factors of schizophrenia. Results:AL index among schizophrenic patients was higher than the controls (5.87±1.90 vs. 3.50±2.21, F=65.97, P<0.001). AL index was possitively correlated with PANSS positive symptoms ( r=0.25, P=0.019) and was a risk factor of schizophrenia ( OR=1.76, 95% CI: 1.47-2.11, P<0.01). Conclusions:The AL is possitively correlated with positive symptoms in the FES, and the higher AL may be one of important inducements to the schizophrenia onset.

Objective:To explore the possible correlation between allostatic load (AL) and clinical symptoms in patients with first-episode schizophrenia (FES) and AL influence upon the onset.Methods:Patients with FES (schizophrenia group, n=93) who received treatment at Beijing Huilongguan Hospital from October 2017 to July 2019 and the healthy controls (control group, n=111) recruited during the same period were enrolled in the research. Systolic blood pressure, diastolic blood pressure, resting heart rate, body mass index, waist-hip ratio, high-density lipoprotein cholesterol, total cholesterol, glycosylated hemoglobin, high-sensitivity C-reactive protein, 12-hour urine adrenaline, 12-hour urine norepinephrine, 12-hour urine cortisol, and serum dehydroepiandrosterone of all subjects were collected to calculate the AL index. The positive and negative symptom scale (PANSS) was used to assess the psychopathological symptoms of patients. Covariance analysis was used to compare the differences of AL index and the thirteen biological components between FES patients and controls. Pearson correlation analysis was used to explore the correlation between AL index and clinical symptoms, and the Logistic regression analysis was used to explore the risk factors of schizophrenia. Results:AL index among schizophrenic patients was higher than the controls (5.87±1.90 vs. 3.50±2.21, F=65.97, P<0.001). AL index was possitively correlated with PANSS positive symptoms ( r=0.25, P=0.019) and was a risk factor of schizophrenia ( OR=1.76, 95% CI: 1.47-2.11, P<0.01). Conclusions:The AL is possitively correlated with positive symptoms in the FES, and the higher AL may be one of important inducements to the schizophrenia onset.

Objective:To investigate the public psychosocial status and regional differences of Chinese residents during the outbreak of the novel coronavirus pneumonia epidemic.Methods:A convenience sampling method was used to distribute online self-assessment tools of mental health including the Self-Reporting Questionnaire (SRQ-20), 9-item Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7) through WeChat and other self media platforms from January 30 to February 13, 2020. A total of 14 592 people from all over the country were evaluated on mental health. The positive detection rate was regarded as the primary outcome measure.Results:The positive detection rate of SRQ-20 was 33.2% (4 840/14 592), and that of the PHQ-9 was 53.5% (7 503/14 037), with 29.3% (4 115/14 037) for mild, 14.0% (1 967/14 037) for moderate and 10.1% (1 421/14 037) for severe depression. The positive detection rate of GAD-7 was 44.6% (6 196/13 904), with 27.8% (3 862/13 904) for mild, 10.2% (1 413/13 904) for moderate and 6.6% (921/13 904) for severe anxiety. Except for a few areas, the positive rates of these three scales were almost the same all over the country, and the anxiety level of the inhabitants in Hubei province (GAD-7:54.7%) was significantly higher than that in other provinces ( P<0.05). Conclusion:As a Public Health Emergency of International COVID-19 has brought obvious psychological impact to the nationwide people, with more prominent in anxiety and depression. The public is in a general group crisis in the early stage of the outbreak, especially in areas with serious epidemic situation. It is suggested that great attention should be paid to public mental health while fighting against the epidemic situation aiming at ensuring their life safety, so as to implement effective psychological assistance and timely psychological crisis intervention.

Objective:To investigate the public psychosocial status and regional differences of Chinese residents during the outbreak of the novel coronavirus pneumonia epidemic.Methods:A convenience sampling method was used to distribute online self-assessment tools of mental health including the Self-Reporting Questionnaire (SRQ-20), 9-item Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7) through WeChat and other self media platforms from January 30 to February 13, 2020. A total of 14 592 people from all over the country were evaluated on mental health. The positive detection rate was regarded as the primary outcome measure.Results:The positive detection rate of SRQ-20 was 33.2% (4 840/14 592), and that of the PHQ-9 was 53.5% (7 503/14 037), with 29.3% (4 115/14 037) for mild, 14.0% (1 967/14 037) for moderate and 10.1% (1 421/14 037) for severe depression. The positive detection rate of GAD-7 was 44.6% (6 196/13 904), with 27.8% (3 862/13 904) for mild, 10.2% (1 413/13 904) for moderate and 6.6% (921/13 904) for severe anxiety. Except for a few areas, the positive rates of these three scales were almost the same all over the country, and the anxiety level of the inhabitants in Hubei province (GAD-7:54.7%) was significantly higher than that in other provinces ( P<0.05). Conclusion:As a Public Health Emergency of International COVID-19 has brought obvious psychological impact to the nationwide people, with more prominent in anxiety and depression. The public is in a general group crisis in the early stage of the outbreak, especially in areas with serious epidemic situation. It is suggested that great attention should be paid to public mental health while fighting against the epidemic situation aiming at ensuring their life safety, so as to implement effective psychological assistance and timely psychological crisis intervention.

Objective: To explore the relationship between the level of mental stimulation and the suicide attempts of rural residents in Shandong Province. Methods: A 1:1 matched case-control study was designed to collect 1 200 cases from a survey of three suicide attempts in rural areas of Shandong Province. Controls were selected according to the following matched factors: age difference within 3 years, same gender, same village or neighboring village, no blood relationship, no suicide history. The basic characteristics of all subjects were collected through the questionnaire, and the level of mental stimulation of life events was measured. Multivariate conditional logistic regression model was used to analyze the relationship between the level of mental stimulation of life events and suicide attempts. Results: The mean age of the case group and the control group was both (36.6±0.3) years old, and 35.8% (430/1 200) were males in each group. The low-medium level of mental stimulation of negative life events in the case group was 16.7% (200/1 200) and 61.7% (740/1 200), respectively, which was higher than that in the control group, about 2.5% (30/1 200) and 29.3% (352/1 200) (all P values <0.05), respectively. A total of 11.1% (133/1 200) of the case group had positive life events, which was lower than that of the control group [16.8% (201/1 200)] (all P values<0.05). Multivariate logistic regression model analysis showed that after the adjustment of gender, age, place of residence, education level, marital status, occupation, family income, somatic disease, mental disorders, family history of suicide, and opposite life events, the low-medium and high level of mental stimulation of negative life events were risk factors for suicide attempts, with OR (95%CI) as 5.88 (4.53-7.64) and 13.94 (8.15-23.86), respectively. Mental stimulation of positive life events was protective factor of suicide attempts, with OR (95%CI) as 0.58 (0.41-0.82). Conclusion Mental stimulation of negative and positive life events were risk and protective factors for suicide attempts.

Objective To explore the relationship between the level of mental stimulation and the suicide attempts of rural residents in Shandong Province. Methods A 1:1 matched case?control study was designed to collect 1 200 cases from a survey of three suicide attempts in rural areas of Shandong Province. Controls were selected according to the following matched factors: age difference within 3 years, same gender, same village or neighboring village, no blood relationship, no suicide history. The basic characteristics of all subjects were collected through the questionnaire, and the level of mental stimulation of life events was measured. Multivariate conditional logistic regression model was used to analyze the relationship between the level of mental stimulation of life events and suicide attempts. Results The mean age of the case group and the control group was both (36.6±0.3) years old, and 35.8% (430/1 200) were males in each group. The low?medium level of mental stimulation of negative life events in the case group was 16.7% (200/1 200) and 61.7% (740/1 200), respectively, which was higher than that in the control group, about 2.5% (30/1 200) and 29.3% (352/1 200) (all P values<0.05), respectively. A total of 11.1% (133/1 200) of the case group had positive life events, which was lower than that of the control group [16.8% (201/1 200)] (all P values<0.05). Multivariate logistic regression model analysis showed that after the adjustment of gender, age, place of residence, education level, marital status, occupation, family income, somatic disease, mental disorders, family history of suicide, and opposite life events, the low?medium and high level of mental stimulation of negative life events were risk factors for suicide attempts, with OR (95%CI) as 5.88 (4.53-7.64) and 13.94 (8.15-23.86), respectively. Mental stimulation of positive life events was protective factor of suicide attempts, with OR (95%CI) as 0.58 (0.41-0.82). Conclusion Mental stimulation of negative and positive life events were risk and protective factors for suicide attempts.