Objective To explore the mechanism of Huoxin pill(HXP)in the prevention and treatment of heart failure(HF)based on transcriptomics and network pharmacology.Methods The mice were randomly divided into the normal control group,model control group,positive control group treated with sacubitril/valsartan(60 mg·kg-1),low-dose group treated with HXP(31.2 mg·kg-1),and high-dose group treated with HXP(62.4 mg·kg-1).The model control group and each drug treat-ment group were subcutaneously injected with an equal volume of ISO(5 mg·kg-1)for modeling,while the normal control group was given an equal volume of sterile saline.Six hours later,each drug administration group was gavaged with the corresponding drug for intervention,and the normal control and model control groups were gavaged with an equal volume of sterile water.The modeling and drug administration were continued for 21 days.The cardiac function parameters of the mice were measured using color Doppler ultrasound imaging;ELISA was used to detect the levels of mouse serum cAMP,NT-proBNP,and BNP;HE staining and Masson's trichrome staining were used to evaluate the pathological morphology of cardiac tissue,and the CVF was calculated.Network pharmacology combined with transcriptomics was used to predict potential targets and signaling pathways of HXP in the prevention and treatment of HF,and molecular biology methods were used for validation.Results Compared with the normal control group,the model control group showed an increase in LVESd and LVEDd(P＜0.01),and a decrease in LVEF and LVFS(P＜0.01);BNP,NT-proBNP,and cAMP levels were increased(P＜0.01);myocardial collagen fibers increased and CVF in-creased(P＜0.01).Compared with the model control group,the HXP low-dose group,HXP high-dose group,and positive control groups showed a decrease in LVESd and LVEDd(P＜0.01),and an increase in LVEF and LVFS(P＜0.01);serum levels of BNP,NT-proBNP,and cAMP decreased(P＜0.05);the degree of myocardial fibrosis decreased and CVF decreased(P＜0.01).Network pharmacology combined with transcriptomics predicted 10 key targets for HXP in the prevention and treatment of HF:CACNA1H,SCN10A,FGF12,PVALB,ACAN,LGALS3,SERPINE1,MMP3,GSTM1,VDR.Western blot results showed that the protein activation levels of PKA and CREB in myocardial tissue were increased in the model control group compared with the nor-mal control group(P＜0.01).Compared with the model control group,HXP low-dose group、HXP high-dose group,and positive control groups showed a decrease in the protein activation levels of PKA and CREB in myocardial tissue(P＜0.05).Conclusion HXP has an improvement effect on ISO-induced HF in mice,which may involve numerous targets and the cAMP/PKA signaling pathway.

Objective:To investigate the prevalence and risk factors of the 4 most common functional gastrointestinal disorders (FGID) among school-aged children in Shanghai.Methods:A cross-sectional questionnaire survey was conducted from January to December 2019. Using stratified cluster sampling, 26 097 students in grades 1-12 from Huangpu and Jiading District, Shanghai were enrolled. The questionnaire of pediatric gastrointestinal symptoms-Rome Ⅳ (QPGS-Ⅳ) and the pediatric quality of life inventory (PedsQL) were used to assess the prevalence and health-related quality of life (HRQoL) of functional dyspepsia (FD), irritable bowel syndrome (IBS), functional abdominal pain-not otherwise specified (FAP-NOS), and functional constipation (FC). Multivariate Logistic regression analysis was performed to identify correlations between sociodemographic factors, lifestyle habits, comorbidities and 4 major FGID. A trend chi-square test was used to explore the relationship between HRQoL scores and FGID prevalence.Results:A total of 26 097 valid participants (26 097/27 036, 96.5%) were included in the study, with the age of (10.8±3.1) years and 12 441 cases (47.7%) were female. The prevalence of FC was found to be the highest (5 537 cases, 21.2%), followed by IBS (797 cases, 3.1%), FAP-NOS (267 cases, 1.0%) and FD (218 cases, 0.8%). Multivariate Logistic regression analysis revealed the following findings: junior high school (FD: OR=1.88 (95% CI 1.35-2.61); IBS: OR=1.42 (95% CI 1.18-1.71); FAP-NOS: OR=1.39 (95% CI 1.02-1.90)), senior high school (FD: OR=2.67 (95% CI 1.84-3.86);IBS: OR=2.36 (95% CI 1.93-2.89) ;FAP-NOS: OR=2.20 (95% CI 1.56-3.11)) and frequent respiratory infections (FD: OR=2.15 (95% CI 1.45-3.18); IBS: OR=2.59 (95% CI 2.12-3.16); FAP-NOS: OR=1.49 (95% CI 1.00-2.21)) were common risk factors for FD, IBS and FAP-NOS. Allergic symptoms (FD: OR=2.21 (95% CI 1.56-3.14); IBS: OR=2.30 (95% CI 1.04-1.51); FAP-NOS: OR=2.54 (95% CI 1.85-3.50); FC: OR=1.09 (95% CI 1.01-1.17)) was a common risk factor for FD, IBS, FAP-NOS and FC. Family history of allergy was a risk factor for IBS ( OR=1.41 (95% CI 1.20-1.65)) and FAP-NOS ( OR=1.33 (95% CI 1.01-1.74)). Female exhibited increased risks for FD ( OR=1.49 (95% CI 1.13-1.96)), IBS ( OR=1.50 (95% CI 1.30-1.74)) and FC ( OR=1.10 (95% CI 1.03-1.17)). The presence of dietary bias was associated with of IBS ( OR=1.46 (95% CI 1.26-1.69)) and FC ( OR=1.26 (95% CI 1.19-1.34)); late bedtime ( OR=1.32 (95% CI 1.06-1.64)) and allergen exposure ( OR=1.25 (95% CI 1.04-1.51)) were risk factors for IBS. Insufficient sleep ( OR=1.11 (95% CI 1.02-1.21)), insufficient outdoor time ( OR=1.20 (95% CI 1.01-1.43)) and severe lack of outdoor time ( OR=1.48 (95% CI 1.23-1.76)) were significant risk factors for FC. Pet ownership ( OR=1.39 (95% CI 1.07-1.81)) was a risk factor for FAP-NOS. HRQoL scores were significantly lower in children with FD, IBS, or FAP-NOS compared to non-FGID peers (all P<0.05). χ2 trend test analysis showed that the Pearson correlation coefficients between the prevalence of FD, IBS, FAP-NOS, FC and HRQoL scores were -0.93, -0.93, -0.97 and -0.84, respectively. Conclusions:The prevalence of FGID among school-aged children in Shanghai varies by sub-type. FC was the most prevalence. Junior and senior high school, female sex, allergic symptoms and frequent respiratory infections were major risk factors. Meanwhile, dietary bias, late bedtime, insufficient outdoor time and pet ownership were associated with specific subtypes. The HRQoL is significantly reduced in children with FD, IBS and FAP-NOS.

Environmental factors such as air pollutants,plastic micro-particles,ionizing radiation,and traffic noise promote the onset and progression of atherosclerotic cardiovascular disease(CVD)through mechanisms including inducing inflammatory responses,promoting oxidative stress,and accelerating lipid deposition.Notably,the modification of apoli-poprotein(Apo)by reactive oxygen species(ROS)accelerates this process.On one hand,ROS can oxidize key amino acid residues in Apo,altering its structure and thereby impairing its normal physiological function.On the other hand,ROS can induce lipid peroxidation of Apo,rendering the oxidized Apo more susceptible to recognition and uptake by macro-phages.This accelerates foam cell formation and drives the progression of atherosclerotic(As)plaques.This review summarizes recent research advances on the role of ROS-induced modification of Apo by environmental factors in atheroscle-rotic CVD.

Environmental factors such as air pollutants,plastic micro-particles,ionizing radiation,and traffic noise promote the onset and progression of atherosclerotic cardiovascular disease(CVD)through mechanisms including inducing inflammatory responses,promoting oxidative stress,and accelerating lipid deposition.Notably,the modification of apoli-poprotein(Apo)by reactive oxygen species(ROS)accelerates this process.On one hand,ROS can oxidize key amino acid residues in Apo,altering its structure and thereby impairing its normal physiological function.On the other hand,ROS can induce lipid peroxidation of Apo,rendering the oxidized Apo more susceptible to recognition and uptake by macro-phages.This accelerates foam cell formation and drives the progression of atherosclerotic(As)plaques.This review summarizes recent research advances on the role of ROS-induced modification of Apo by environmental factors in atheroscle-rotic CVD.

Objective:To investigate microstructural alterations in the optic chiasm and optic radiations of multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) based on diffusion kurtosis imaging (DKI).Methods:This study was a cross-sectional study. Retrospective analyses were conducted on the clinical and imaging data of 63 patients with relapsing-remitting MS (RRMS) and 62 patients with NMOSD diagnosed at First Affiliated Hospital of Chongqing Medical University from January 2019 to December 2023. According to the occurrence of optic neuritis (ON), they were categorized into ON-positive MS (ON+MS) group (40 cases), ON-negative MS (ON-MS) group (23 cases), ON-positive NMOSD (ON+NMOSD) group (40 cases) and ON-negative NMOSD (ON-NMOSD) group (22 cases). In addition, 40 healthy controls were enrolled during the same period. DKI data of all subjects were collected, and DKI post-processing was performed to obtain fractional anisotropy (FA), mean kurtosis (MK), axial kurtosis (AK), and radial kurtosis (RK) values of the optic chiasm and bilateral optic radiations. The scores of the mini-mental state examination (MMSE), montreal cognitive assessment (MoCA), and expanded disability status scale (EDSS) were obtained. The Kruskal-Wallis test was used to analyze the differences in DKI parameters of the optic chiasm and bilateral optic radiation among the 5 groups, and the Holm-Bonferroni method was employed for multiple comparison correction in pairwise comparisons.Results:There were statistically significant overall differences in the DKI parameters of the optic chiasm and bilateral optic radiations among healthy control group, ON+MS group, ON-MS group, ON+NMOSD group, and ON-NMOSD group (all P0.05). The FA value of the optic chiasm in ON+NMOSD group was significantly lower than that of healthy control group and ON-MS group, as well as ON-NMOSD group ( P0.05). The FA value of the left optic radiation in ON+NMOSD group was lower than that in healthy control group and the ON-MS group. The RK value of the optic chiasm in ON+MS group was lower than that in the healthy control group and ON-NMOSD group ( P0.05). The MK and RK values of the left optic radiation in ON-MS group were significantly lower than those in the ON+NMOSD group and ON-NMOSD group ( P0.05). Conclusions:NMOSD and RRMS patients demonstrate varying degrees of microstructural damage in the optic chiasm and optic radiations. Differences of DKI parameters suggest different pathological mechanisms of visual pathway damage between NMOSD and MS, which may be helpful for early detection of occult visual pathway lesions.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Image 1.

Objective To explore the mechanism of Huoxin pill(HXP)in the prevention and treatment of heart failure(HF)based on transcriptomics and network pharmacology.Methods The mice were randomly divided into the normal control group,model control group,positive control group treated with sacubitril/valsartan(60 mg·kg-1),low-dose group treated with HXP(31.2 mg·kg-1),and high-dose group treated with HXP(62.4 mg·kg-1).The model control group and each drug treat-ment group were subcutaneously injected with an equal volume of ISO(5 mg·kg-1)for modeling,while the normal control group was given an equal volume of sterile saline.Six hours later,each drug administration group was gavaged with the corresponding drug for intervention,and the normal control and model control groups were gavaged with an equal volume of sterile water.The modeling and drug administration were continued for 21 days.The cardiac function parameters of the mice were measured using color Doppler ultrasound imaging;ELISA was used to detect the levels of mouse serum cAMP,NT-proBNP,and BNP;HE staining and Masson's trichrome staining were used to evaluate the pathological morphology of cardiac tissue,and the CVF was calculated.Network pharmacology combined with transcriptomics was used to predict potential targets and signaling pathways of HXP in the prevention and treatment of HF,and molecular biology methods were used for validation.Results Compared with the normal control group,the model control group showed an increase in LVESd and LVEDd(P＜0.01),and a decrease in LVEF and LVFS(P＜0.01);BNP,NT-proBNP,and cAMP levels were increased(P＜0.01);myocardial collagen fibers increased and CVF in-creased(P＜0.01).Compared with the model control group,the HXP low-dose group,HXP high-dose group,and positive control groups showed a decrease in LVESd and LVEDd(P＜0.01),and an increase in LVEF and LVFS(P＜0.01);serum levels of BNP,NT-proBNP,and cAMP decreased(P＜0.05);the degree of myocardial fibrosis decreased and CVF decreased(P＜0.01).Network pharmacology combined with transcriptomics predicted 10 key targets for HXP in the prevention and treatment of HF:CACNA1H,SCN10A,FGF12,PVALB,ACAN,LGALS3,SERPINE1,MMP3,GSTM1,VDR.Western blot results showed that the protein activation levels of PKA and CREB in myocardial tissue were increased in the model control group compared with the nor-mal control group(P＜0.01).Compared with the model control group,HXP low-dose group、HXP high-dose group,and positive control groups showed a decrease in the protein activation levels of PKA and CREB in myocardial tissue(P＜0.05).Conclusion HXP has an improvement effect on ISO-induced HF in mice,which may involve numerous targets and the cAMP/PKA signaling pathway.

Objective:To investigate microstructural alterations in the optic chiasm and optic radiations of multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) based on diffusion kurtosis imaging (DKI).Methods:This study was a cross-sectional study. Retrospective analyses were conducted on the clinical and imaging data of 63 patients with relapsing-remitting MS (RRMS) and 62 patients with NMOSD diagnosed at First Affiliated Hospital of Chongqing Medical University from January 2019 to December 2023. According to the occurrence of optic neuritis (ON), they were categorized into ON-positive MS (ON+MS) group (40 cases), ON-negative MS (ON-MS) group (23 cases), ON-positive NMOSD (ON+NMOSD) group (40 cases) and ON-negative NMOSD (ON-NMOSD) group (22 cases). In addition, 40 healthy controls were enrolled during the same period. DKI data of all subjects were collected, and DKI post-processing was performed to obtain fractional anisotropy (FA), mean kurtosis (MK), axial kurtosis (AK), and radial kurtosis (RK) values of the optic chiasm and bilateral optic radiations. The scores of the mini-mental state examination (MMSE), montreal cognitive assessment (MoCA), and expanded disability status scale (EDSS) were obtained. The Kruskal-Wallis test was used to analyze the differences in DKI parameters of the optic chiasm and bilateral optic radiation among the 5 groups, and the Holm-Bonferroni method was employed for multiple comparison correction in pairwise comparisons.Results:There were statistically significant overall differences in the DKI parameters of the optic chiasm and bilateral optic radiations among healthy control group, ON+MS group, ON-MS group, ON+NMOSD group, and ON-NMOSD group (all P0.05). The FA value of the optic chiasm in ON+NMOSD group was significantly lower than that of healthy control group and ON-MS group, as well as ON-NMOSD group ( P0.05). The FA value of the left optic radiation in ON+NMOSD group was lower than that in healthy control group and the ON-MS group. The RK value of the optic chiasm in ON+MS group was lower than that in the healthy control group and ON-NMOSD group ( P0.05). The MK and RK values of the left optic radiation in ON-MS group were significantly lower than those in the ON+NMOSD group and ON-NMOSD group ( P0.05). Conclusions:NMOSD and RRMS patients demonstrate varying degrees of microstructural damage in the optic chiasm and optic radiations. Differences of DKI parameters suggest different pathological mechanisms of visual pathway damage between NMOSD and MS, which may be helpful for early detection of occult visual pathway lesions.

Objective:To investigate the prevalence and risk factors of the 4 most common functional gastrointestinal disorders (FGID) among school-aged children in Shanghai.Methods:A cross-sectional questionnaire survey was conducted from January to December 2019. Using stratified cluster sampling, 26 097 students in grades 1-12 from Huangpu and Jiading District, Shanghai were enrolled. The questionnaire of pediatric gastrointestinal symptoms-Rome Ⅳ (QPGS-Ⅳ) and the pediatric quality of life inventory (PedsQL) were used to assess the prevalence and health-related quality of life (HRQoL) of functional dyspepsia (FD), irritable bowel syndrome (IBS), functional abdominal pain-not otherwise specified (FAP-NOS), and functional constipation (FC). Multivariate Logistic regression analysis was performed to identify correlations between sociodemographic factors, lifestyle habits, comorbidities and 4 major FGID. A trend chi-square test was used to explore the relationship between HRQoL scores and FGID prevalence.Results:A total of 26 097 valid participants (26 097/27 036, 96.5%) were included in the study, with the age of (10.8±3.1) years and 12 441 cases (47.7%) were female. The prevalence of FC was found to be the highest (5 537 cases, 21.2%), followed by IBS (797 cases, 3.1%), FAP-NOS (267 cases, 1.0%) and FD (218 cases, 0.8%). Multivariate Logistic regression analysis revealed the following findings: junior high school (FD: OR=1.88 (95% CI 1.35-2.61); IBS: OR=1.42 (95% CI 1.18-1.71); FAP-NOS: OR=1.39 (95% CI 1.02-1.90)), senior high school (FD: OR=2.67 (95% CI 1.84-3.86);IBS: OR=2.36 (95% CI 1.93-2.89) ;FAP-NOS: OR=2.20 (95% CI 1.56-3.11)) and frequent respiratory infections (FD: OR=2.15 (95% CI 1.45-3.18); IBS: OR=2.59 (95% CI 2.12-3.16); FAP-NOS: OR=1.49 (95% CI 1.00-2.21)) were common risk factors for FD, IBS and FAP-NOS. Allergic symptoms (FD: OR=2.21 (95% CI 1.56-3.14); IBS: OR=2.30 (95% CI 1.04-1.51); FAP-NOS: OR=2.54 (95% CI 1.85-3.50); FC: OR=1.09 (95% CI 1.01-1.17)) was a common risk factor for FD, IBS, FAP-NOS and FC. Family history of allergy was a risk factor for IBS ( OR=1.41 (95% CI 1.20-1.65)) and FAP-NOS ( OR=1.33 (95% CI 1.01-1.74)). Female exhibited increased risks for FD ( OR=1.49 (95% CI 1.13-1.96)), IBS ( OR=1.50 (95% CI 1.30-1.74)) and FC ( OR=1.10 (95% CI 1.03-1.17)). The presence of dietary bias was associated with of IBS ( OR=1.46 (95% CI 1.26-1.69)) and FC ( OR=1.26 (95% CI 1.19-1.34)); late bedtime ( OR=1.32 (95% CI 1.06-1.64)) and allergen exposure ( OR=1.25 (95% CI 1.04-1.51)) were risk factors for IBS. Insufficient sleep ( OR=1.11 (95% CI 1.02-1.21)), insufficient outdoor time ( OR=1.20 (95% CI 1.01-1.43)) and severe lack of outdoor time ( OR=1.48 (95% CI 1.23-1.76)) were significant risk factors for FC. Pet ownership ( OR=1.39 (95% CI 1.07-1.81)) was a risk factor for FAP-NOS. HRQoL scores were significantly lower in children with FD, IBS, or FAP-NOS compared to non-FGID peers (all P<0.05). χ2 trend test analysis showed that the Pearson correlation coefficients between the prevalence of FD, IBS, FAP-NOS, FC and HRQoL scores were -0.93, -0.93, -0.97 and -0.84, respectively. Conclusions:The prevalence of FGID among school-aged children in Shanghai varies by sub-type. FC was the most prevalence. Junior and senior high school, female sex, allergic symptoms and frequent respiratory infections were major risk factors. Meanwhile, dietary bias, late bedtime, insufficient outdoor time and pet ownership were associated with specific subtypes. The HRQoL is significantly reduced in children with FD, IBS and FAP-NOS.