Objective:To investigate the influence of sulforaphane(SFN)on ventricular remodeling in myocardial infarction(MI)rat model by regulating extracellular regulated protein kinase(ERK)/nuclear respiratory factor 1(NRF1)signaling pathway.Methods:Among 48 SD male rats,12 were randomly selected as Sham group.The remaining rats were treated with ligation of left ante-rior descending coronary artery to establish myocardial infarction model.After modeling,36 rats were randomly divided into MI model group,SFN treatment group(10 mg/kg),SFN+SCH772984(ERK inhibitor)group(10 mg/kg+15 mg/kg),with 12 rats in each group.Animal ultrasound was performed to detect cardiac structure and function.Histological analysis was performed to evaluate myo-cardial fibrosis and cell apoptosis.ELISA was used to measure pro-inflammatory factor levels in serum,and Western blot assay was used to observe the expression of ERK/NRF1 pathway related proteins in myocardium of rats in each group.Results:Compared with rats in Sham group,rats in MI model group showed a loss of myocardial compliance and disarray of ventricular myocardial fibers,along with increased myocardial fibrosis and myocardial cell apoptosis.Moreover,rats in MI model group also exhibited overactive inflammatory response and inhibition of the ERK/NRF1 signaling pathway in cardiac tissues(P<0.05).Notably,SFN treatment signifi-cantly not only improved cardiac function,but also ameliorated myocardial fibrosis and cell apoptosis(P<0.05).SFN treatment inhib-ited inflammatory cytokine expression and activated the ERK/NRF1 pathway as well(P<0.05).However,SCH772984 significantly abrogated the protective effect of SFN against myocardial fibrosis and apoptosis in MI rats.Conclusion:SFN may protect against ventricular remodeling in MI rat by activating ERK/NRF1 pathway.

Objective:To compare the consistency of lymphoma multigene detection panels based on next-generation sequencing (NGS) with FISH detection of B-cell lymphoma gene rearrangement.Methods:From January 2019 to May 2023, fusion genes detected by lymphoma-related 413 genes that targeted capture sequencing of 489 B-cell lymphoma tissues embedded in paraffin were collected from Henan Cancer Hospital, and the results were compared with simultaneous FISH detection of four break/fusion genes: BCL2, BCL6, MYC, and CCND1. Consistency was defined as both methods yielding positive or negative results for the same sample. The relationship between fusion mutation abundance in NGS and the positivity rate of cells in FISH was also analyzed.Results:Kappa consistency analysis revealed high consistency between NGS and FISH in detecting the four B-cell lymphoma-related gene rearrangement ( P<0.001 for all) ; however, the detection rates of positive individuals differed for the four genes. Compared with FISH, NGS demonstrated a higher detection rate for BCL2 rearrangement, a lower detection rate for BCL6 and MYC rearrangement, and a similar detection rate for CCND1 rearrangement. No correlation was found between fusion mutation abundance in NGS and the positivity rate of cells in FISH. Conclusions:NGS and FISH detection of B-cell lymphoma gene rearrangement demonstrate overall good consistency. NGS is superior to FISH in detecting BCL2 rearrangement, inferior in detecting MYC rearrangement, and comparable in detecting CCND1 rearrangement.

Aim To study the effect of liraglutide on myocardial metabolites and related metabolic pathways in diabetic cardiomyopathy(DCM)rats.Methods Among 60 SPF male SD rats aged 3 weeks,10 rats were randomly selected as normal control group(n=10),and the remaining 50 rats were established by peritoneal injection of streptozoto-cin combined with high-sugar and high-fat diet for DCM rat model.A total of 36 rats were successfully modeled for DCM and randomly divided into DCM model group(DCM group,n=12),low-dose liraglutide treatment group(LL group,n=12)and high-dose liraglutide treatment group(HL group,n=12).Rats in LL group(100 μg/kg)and HL group(200μg/kg)were given intraperitoneal injection of liraglutide once a day.And after 12 weeks of intervention,the rats were killed under anesthesia after echocardiography to detect cardiac function,and the heart tissues were taken for metabolomics detection.The differential metabolites and related pathways that may be related to liraglutide improving myocardial metab-olism in DCM rats were screened and enriched.Results Compared with normal control group,left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)in DCM group were significantly decreased,and the ra-tio of early to late diastolic mitralflow velocities(E/A)was significantly increased(P＜0.05).Compared with DCM group,LVEF and LVFS in LL group and HL group were significantly increased,and E/A ratio was significantly decreased(P＜0.05),suggesting that the impairment of left ventricular systolic and diastolic function in LL group and HL group was significantly alleviated.395 metabolites were detected by metabolomics,among which 239,116 and 187 different metab-olites and 13,6 and 20 metabolic pathways were enriched in DCM group and normal control group,LL group and DCM group,HL group and DCM group.In the above three groups,29 key differential metabolites were identified related to 3 metabolic pathways including choline metabolic pathway,caffeine metabolic pathway and valine,leucine and isoleucine bi-osynthesis pathway,among which choline metabolic pathway had the most significant differences.Conclusion These results indicated that liraglutide can ameliorate cardiac dysfunction in DCM rats through improving myocardial metabolism in which choline metabolism pathway may play a key role.

Objective To explore the value of tissue Doppler imaging(TDI)corrected diaphragm ultrasonic parameters for evaluating diaphragmatic function in dyspnea patients who underwent non-invasive mechanical ventilation.Methods Thirty-one acute dyspnea patients who underwent non-invasive mechanical ventilation less than 1 h(non-invasive ventilation group)and 31 healthy subjects(control group)were prospectively enrolled,and ultrasound of diaphragm was performed.Routine diaphragmatic parameters,including diaphragm displacement(DD),diaphragm thickness of end-expiratory(DTee),diaphragm thickness of end-inspiratory(DTei)and diaphragm thickening fraction(DTF)were measured and calculated,while peak systolic velocity of diaphragm(DPSV)and peak diastolic velocity of diaphragm(DPDV)were measured using TDI mode.Based on DD and DTF after rapid shallow breathing index(RSBI),DD-RSBI and DTF-RSBI were corrected,DPSV-RSBI and DPDV-RSBI were obtained by calculating product of DPSV and DPDV with respiratory rate,respectively.The index of compensatory work of diaphragm during systole(DD/DPSV and DTF/DPSV)and diastole(DD/DPDV and DTF/DPDV)were obtained by corrected DD and DTF with DPSV and DPDV,respectively.The ultrasonic parameters of diaphragm were compared between groups.Receiver operating characteristic(ROC)curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficacy of ultrasonic parameters of diaphragm for assessing diaphragmatic function in dyspnea patients who underwent non-invasive mechanical ventilation.Results DPSV,DPDV,DD-RSBI,DTF-RSBI,DPSV-RSBI and DPDV-RSBI in non-invasive ventilation group were all higher,while DD/DPSV,DD/DPDV,DTF/DPSV and DTF/DPDV were all lower than those in control group(all P＜0.05).No significant difference of DD,DTee,DTei nor DTF was found between groups(all P＞0.05).DPSV-RSBI and DPDV-RSBI had excellent efficacy for assessing diaphragmatic function in dyspnea patients after non-invasive mechanical ventilation(AUC=0.974,0.919),DPSV,DD-RSBI,DTF-RSBI,DD/DPSV and DTF/DPSV had good efficacy(AUC 0.760-0.881),while DD,DPDV,DTee,DTei,DTF,DD/DPDV and DTF/DPDV had bad or general efficacy(AUC 0.467-0.698).Conclusion TDI corrected diaphragm ultrasonic parameters could effectively evaluate diaphragmatic function in dyspnea patients who underwent non-invasive mechanical ventilation.

Objective To compare the accuracy of bedside lung ultrasound in emergency(BLUE)and combined cardiac-lung and additional ultrasound(CLAUS)for diagnosing the causes of acute dyspnea.Methods Totally 1 016 patients with acute dyspnea were retrospectively enrolled and divided into cardiogenic pulmonary edema group(n=268),pneumonia group(n=574),pneumothorax group(n=33),pulmonary embolism group(n=67)and CAD(chronic obstructive pulmonary disease/asthma/diaphragmatic dysfunction)group(n=74)according to the causes of acute dyspnea.The findings of CLAUS protocol were compared among groups,and the accuracy of BLUE and CLAUS protocol for diagnosing the causes of acute dyspnea were also compared.Results CLAUS showed that B-B and B-C were the most common modes in cardiogenic pulmonary edema group,while A-B/A-C/B-A/B-B/B-C/C-C modes were common in pneumonia group,and A-A mode was the most common in pneumothorax group,pulmonary embolism group and CAD group.Significant differences of the manifestations of pulmonary ultrasound,pleural feature of anterior chest wall,left/right cardiac insufficiency and abnormal inferior vena cava diameter were found among groups(all P＜0.05).The accuracy of BLUE and CLAUS protocol for diagnosing the causes of acute dyspnea was 86.91%(883/1 016)and 94.49%(960/1 016),respectively,the latter was higher than the former(χ2=34.587,P＜0.05).Conclusion CLAUS protocol could be used to effectively diagnose the causes of acute dyspnea,with higher accuracy than BLUE protocol.

Objective: To investigate the causal relationship between antioxidant nutrients and pregnancy complications, so as to provide the reference for the prevention and treatment of pregnancy complications. Methods: Data of seven antioxidant nutrients including vitamin A, vitamin C, vitamin E, selenium, zinc, copper and iron were collected from genome-wide association study (GWAS) Catalog database, and data of four pregnancy complications including gestational diabetes mellitus, pre-eclampsia, spontaneous abortion and preterm birth were collected from the Finland database. Single nucleotide polymorphism (SNP) data were collected, and 27 SNPS strongly correlated with seven antioxidant nutrients were selected as instrumental variables. Mendelian randomization (MR) analyses were performed using the inverse-variance weighted (IVW) method with seven antioxidant nutrients as exposures factors and four pregnancy complications as outcome variables. The heterogeneity was assessed using the Cochran's Q test, the horizontal pleiotropy was assessed using the MR-PRESSO test and MR-Egger regression, and the robustness of the results was verified with the leave-one-out. Results: Cochran's Q test showed heterogeneity of MR results between vitamin C and gestational diabetes mellitus, preeclampsia and preterm birth, between vitamin E and iron and gestational diabetes (all P<0.05), and a random effect model was employed. There was no heterogeneity in other results (all P>0.05), and a fixed effect model was employed. MR analysis results showed that there was no causal association between seven antioxidant nutrients and the risk of four pregnancy complications (all P>0.05). MR-PRESSO test and the MR-Egger regression identified no horizontal pleiotropy of instrumental variables (both P>0.05). Conclusion This study did not find genetically predicted associations of antioxidant nutrients with pregnancy complications.

Objective:To investigate the independent and combined effects of maternal smoking during pregnancy and offspring genetic susceptibility on overall cancer mortality.Methods:Based on the United Kingdom Biobank ( n=419 228) data, the Cox proportional hazard regression model was used to estimate the effect of maternal smoking during pregnancy on offspring overall cancer (including 16 cancers in men and 18 in women) mortality and its combined effect and interaction with offspring genetic factors. Results:Maternal smoking during pregnancy was significantly associated with a 13% increased risk of overall cancer mortality in men [hazard ratio( HR)=1.13, 95% CI: 1.06-1.20] and 19% increased risk in women ( HR=1.19, 95% CI: 1.11-1.27). Participants with high genetic risk had the highest overall cancer mortality than those with low genetic risk (men: HR=1.42, 95% CI: 1.30-1.55; women: HR=1.38, 95% CI: 1.25-1.52). Compared with participants without maternal smoking during pregnancy and low genetic risk, those with maternal smoking during pregnancy and high genetic risk were associated with a 56% increased risk of overall cancer mortality in men ( HR=1.56, 95% CI: 1.37-1.77) and 59% in women ( HR=1.59, 95% CI: 1.39-1.83). Conclusion:Maternal smoking during pregnancy may increase offspring overall cancer mortality and more severe harm in individuals with high genetic risk.

Humans ; COVID-19/genetics* ; SARS-CoV-2/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; CRISPR-Cas Systems/genetics* ; RNA, Viral/genetics*

【Objective】 To investigate the effect of isoliquiritigenin on inflammatory response of vascular endothelial cells and whether the regulatory effect of isoliquiritigenin on inflammation is mediated by histone deacetylase 3 (HDAC3). 【Methods】 Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and treated with LPS, different concentrations of isoliquiritigenin and HDAC3 specific inhibitor, respectively. Real-time PCR and Western blotting were used to detect the mRNA and protein expressions of inflammatory cytokines and HDAC3. Male C57BL/6J mice were randomly divided into vehicle group and isoliquiritigenin treatment group. The vascular inflammation model of C57BL/6J mice was established by ligation of the left carotid arteries. The mRNA expressions of inflammatory cytokines and HDAC3 in the carotid arteries of mice were detected by Real-time PCR. A molecular docking study was performed to investigate the interaction between isoliquiritigenin and HDAC3. 【Results】 Compared with the vehicle group, isoliquiritigenin reduced the mRNA expressions of inflammatory cytokines NLRP3, IL-1β, IL-18, MCP-1 and ICAM-1 and decreased the expression of HDAC3 mRNA and protein in HUVECs stimulated with LPS. In addition, isoliquiritigenin also decreased the mRNA expressions of NLRP3, IL-1β and HDAC3 in carotid arteries of ligated C57BL/6J mice. The docking of isoliquiritigenin in the active site of HDAC3 showed that isoliquiritigenin might act through HDAC3. Furthermore, HDAC3 specific inhibitor RGFP966 further promoted the inhibitory effect of isoliquiritigenin on the expression of inflammatory cytokines in vascular endothelial cells. 【Conclusion】 These results suggest that isoliquiritigenin suppresses the inflammatory response of vascular endothelial cells via HDAC3.

Heart sound analysis is significant for early diagnosis of congenital heart disease. A novel method of heart sound classification was proposed in this paper, in which the traditional mel frequency cepstral coefficient (MFCC) method was improved by using the Fisher discriminant half raised-sine function (F-HRSF) and an integrated decision network was used as classifier. It does not rely on segmentation of the cardiac cycle. Firstly, the heart sound signals were framed and windowed. Then, the features of heart sounds were extracted by using improved MFCC, in which the F-HRSF was used to weight sub-band components of MFCC according to the Fisher discriminant ratio of each sub-band component and the raised half sine function. Three classification networks, convolutional neural network (CNN), long and short-term memory network (LSTM), and gated recurrent unit (GRU) were combined as integrated decision network. Finally, the two-category classification results were obtained through the majority voting algorithm. An accuracy of 92.15%, sensitivity of 91.43%, specificity of 92.83%, corrected accuracy of 92.01%, and F score of 92.13% were achieved using the novel signal processing techniques. It shows that the algorithm has great potential in early diagnosis of congenital heart disease.
Humans ; Heart Sounds ; Algorithms ; Neural Networks, Computer ; Heart Defects, Congenital/diagnosis* ; Signal Processing, Computer-Assisted