Immune-resistant colorectal cancer (irCRC), represented by microsatellite stable/proficient mismatch repair (MSS/pMMR) tumors, responds poorly to immune checkpoint blockade (ICB). Here, we developed an ultrasound-targeted nanodroplet destruction (UTND) strategy combined with surface anti-PD-L1-decorated nanodroplets (PPP@P@map) to enhance ICB responsiveness in MSS colorectal cancer. In CT26 and CMT93 murine subcutaneous MSS colorectal cancer models, PPP@P@map combined with UTND markedly suppressed tumor growth compared with control treatments. Single-cell RNA sequencing identified CAF_Pi16 as a candidate therapy-associated cancer-associated fibroblast subset that showed a treatment-related increase after PPP@P@map + UTND, which was further supported by flow cytometry and multiplex immunofluorescence validation. Mechanistically, UTND induced oxidative stress in tumor cells and promoted the generation of advanced glycation end products (AGEs), which activated the AGE-RAGE/PKCα/NF-κB pathway in CAF_Pi16 and increased CCL7 secretion. CAF_Pi16-derived CCL7 provided a CCR2-dependent functional cue to CD8+ T cells. In purified CD8+ T cells, CCL7 activated NF-κB-related signalling, enhanced activation and cytotoxic effector features, and promoted NKG2D expression; these effects were attenuated by CCR2 blockade or NF-κB inhibition. Functionally, CCL7 enhanced CD8+ T cell-mediated tumor-cell killing, whereas NKG2D blockade reduced this effect and weakened the antitumor efficacy of PPP@P@map + UTND in vivo. Together, these findings reveal a UTND-induced tumor cell-CAF_Pi16-CCL7-CD8+ T-cell signalling axis that enhances NKG2D-associated antitumor immunity and provides a mechanistic basis for further investigation of UTND-based strategies to improve ICB responsiveness in MSS/pMMR colorectal cancer.

The most severe side effect of chemotherapy is cardiotoxicity, frequently causing myocardial injury characterized by excessive oxidative stress and fibrosis for which effective treatments are lacking. To address this, a hydrogen delivery system, hydrogen nanobubbles (HNBs), was constructed, leveraging hydrogen's selective antioxidant and antifibrotic properties to counteract doxorubicin (Dox)-induced myocardial injury and explore its mechanism. HNBs were constructed via polymer self-assembly. Nanoparticle tracking analysis indicated a size of 265.1 ± 26 nm. The average hydrogen content of HNBs measured by chemical titration was about 1.9 mg/L. TEM revealed spherical HNBs with a dense outer lipid polymer layer encapsulating hydrogen. CCK-8 assays confirmed over 90% cell viability, demonstrating good biosafety. ROS fluorescence staining and flow cytometry showed that HNBs significantly reduced Dox-induced ROS increases. RT-qPCR revealed the upregulation of antioxidant genes (NRF2, SOD2, and GPX-1). Flow cytometry and JC-1 staining indicated that HNBs mitigated apoptosis and restored mitochondrial membrane potential. TEM displayed reduced mitochondrial damage and intracellular vacuolation. In a Dox-induced cardiomyopathy mouse model, HNBs improved cardiac function, normalized echocardiographic parameters (EF, FS, LVIDs, and LVIDd), and lowered myocardial ROS levels. Ultrasonic enhanced images showed that HNBs have good myocardial differential targeting. In vivo fluorescence imaging of mice showed that HNBs could accumulate in the myocardium in large quantities at 1 h. mRNA-seq and network pharmacology suggested that HNBs inhibit myocardial fibrosis. Masson staining results showed that HNBs could improve Dox-induced myocardial fibrosis. RT-qPCR and Western blotting confirmed the reduced expression of fibrosis markers (ACTA2, COL1, and FN1), preliminarily linking the mechanism to suppression of both PI3K/AKT and TGF-β/SMAD pathways. In summary, HNBs inhibit oxidative stress and myocardial fibrosis, reversing Dox-induced cardiac injury primarily through the dual suppression of the PI3K/AKT and TGF-β/SMAD pathways.

Pathological cardiac hypertrophy, often triggered by the excessive production and accumulation of reactive oxygen and nitrogen species (RONS), may ultimately lead to heart failure. The treatment of myocardial hypertrophy often involves antioxidant stress therapy. In this study, by coordinating curcumin with ferric ions during the synthesis of Prussian blue nanoparticles, a Prussian blue-curcumin (PB-Cur) nanozyme is successfully engineered with exceptional reactive oxygen and nitrogen species (RONS) elimination capabilities. Following PVP modification, the PB-Cur nanozyme exhibited favorable biocompatibility and stability in aqueous solutions. Furthermore, the PB-Cur nanozyme shows remarkable reversible treatment efficacy against myocardial hypertrophy in both in vitro and in vivo models. After one week of treatment, the PB-Cur group in the transverse aortic constriction (TAC)-induced cardiac hypertrophy models displayed a notable decrease in myocardial hypertrophy and fibrosis. Echocardiographic findings also revealed a substantial improvement in cardiac function among TAC mice following PB-Cur administration. Mechanistically, through reactive oxygen species (ROS) elimination, the PB-Cur effectively downregulated oxidative stress-related pathways, including MAPK and PI3K-Akt, which hold promise for treating oxidative stress-related cardiac diseases.

PurposeWe aim to establish an LPS-induced human aortic endothelial cells (HAECs) inflammatory injury model and explore the optimal conditions for inducing its injury. We expect to provide modeling references for the related experiments of vascular inflammatory diseases.MethodsHAECs were cultured in vitro and treated with different concentrations of lipopolysaccharide (LPS) (0.1, 1, 10, 50, 100 μg/mL) for 6, 12, and 24 h to establish the HAECs inflammatory injury model. The cell viability was determined by CCK-8 assay; the expression levels of inflammatory cytokines in the cells were detected by RT-PCR；the apoptosis rate of the cells was detected by flow cytometry.Results① Within 24 h of LPS treatment, the cell viability of the 0.1 and 1 μg/mL groups showed an overall increasing trend with time, while the cell viability of the 10, 50, and 100 μg/mL groups increased first and then decreased with time, and the cell viability of 50 and 100 μg/mL groups was significantly lower than the normal control group at 24 h (P<0.01). ② RT-PCR results showed that after 50 and 100 μg/mL LPS for 24 h, the inflammatory cytokines all showed an apparent upward trend compared with the normal control group (P<0.05), which was more significant in the 100 μg/mL group. ③ After 100 μg/mL LPS for 24 h, the apoptotic necrosis rate of HAECs was higher than the normal control group (P<0.01).ConclusionsThis experiment successfully established a HAECs injury model, indicating that the optimal conditions for inducing injury are an LPS concentration of 100 μg/mL and a treatment time of 24 h.

目的 应用血流向量成像技术检测慢性心力衰竭患者左心室能量损耗指标,探讨其评估左心室收缩及舒张功能的价值.方法 65例慢性心力衰竭患者,根据心力衰竭分类指南分为射血分数保留(heart failure with preserved ejection fraction,HFpEF)组 32 例,射血分数减低(heart failure with reduced ejection fraction,HFrEF)组 33 例;同期体检健康者32例为对照组.3组采用免疫分析法检测血清N末端脑钠肽前体(N-terminal pro-B-type natriuretic peptide,NT-proBNP)水平;行超声心动图测量左心室舒张末期内径(left ventricular end-diastolic dimension,LVEDD)、左心室收缩末期内径(left ventricular end-systolic dimension,LVESD)、左心室舒张末期容积(left ventricular end-diastolic volume,LVEDV)、左心室收缩末期容积(left ventricular end-systolic volume,LVESV)、左室射血分数(left ventricular ejection fraction,LVEF)及二尖瓣前向血流速度E峰、间隔壁及侧壁心肌运动速度e',计算E/e';应用血流向量成像技术在能量损耗模式下测量舒张期(等容舒张期、快速充盈期、心房收缩期)及收缩期(等容收缩期、快速射血期)左心室整体平均能量损耗(average energy loss,EL-ave);采用Pearson相关法分析慢性心力衰竭患者收缩期、舒张期EL-ave与E/e'的相关性.结果 HFrEF 组血清 NT-proBNP 水平[(6 785.56±1 254.34)ng/L]高于 HFpEF 组[(165.69±20.34)ng/L]和对照组[(27.46±17.42)ng/L](P＜0.05),左心房前后径[(52.45±5.05)mm]、LVEDD[(69.56±7.89)mm]、LVESD[(53.49±4.87)mm]、LVEDV[(235.67±7.89)mL]、LVESV[(142.45±7.01)mL]、E/e'(23.64±2.58)均大于 HFpEF组[(38.49±5.42)mm、(48.65±6.12)mm、(33.15±4.01)mm、(110.52±6.67)mL、(46.67±6.02)mL、15.43±2.03]和对照组[(33.68±6.21)mm、(48.32±6.21)mm、(29.47±3.34)mm、(98.67±7.33)mL、(45.45±5.98)mL、9.12±1.35](P＜0.05),LVEF[(32.71±6.02)％]低于 HFpEF 组[(63.35±5.89)％]和对照组[(65.54±5.43)％](P＜0.05);HFpEF组血清NT-proBNP水平高于对照组(P＜0.05),左心房前后径、E/e'均大于对照组(P＜0.05),LVEDD、LVEDV、LVESD、LVESV、LVEF与对照组比较差异无统计学意义(P＞0.05).HFpEF组快速充盈期(20.24±4.65)、心房收缩期(7.56±2.63)、等容收缩期(10.01±2.97)、快速射血期(5.82±1.78)EL-ave 均高于 HFrEF组(2.82±0.49、3.17±1.02、0.16±0.05、0.83±0.14)和对照组(13.12±3.69、3.34±0.97、4.00±1.47、2.27±1.68)(P＜0.05),等容舒张期 EL-ave(1.76±0.58)高于 HFrEF 组(0.36±0.08)(P＜0.05),与对照组(2.20±0.58)比较差异无统计学意义(P＞0.05);HFrEF组等容舒张期、快速充盈期、等容收缩期、快速射血期EL-ave均低于对照组(P＜0.05).慢性心力衰竭患者等容收缩期EL-ave与LVEF呈正相关(r=0.582,P=0.017),等容舒张期、快速充盈期EL-ave与E/e'呈负相关(r=-0.768,P=0.001;r=-0.605,P=0.021).结论 血流向量成像技术可定量慢性心力衰竭患者左心室EL-ave,EL-ave在反映HFpEF患者左心室收缩及舒张功能改变上较LVEF敏感.

Atherosclerosis (AS) is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease, stroke, and peripheral vascular disease. Despite the current treatments, mortality and disability still remain high. Sonodynamic therapy (SDT), a non-invasive and localized methodology, has been developed as a promising new treatment for inhibiting atherosclerotic progression and stabilizing plaques. Promising progress has been made through cell and animal assays, as well as clinical trials. For example, the effect of SDT on apoptosis and autophagy of cells in AS, especially macrophages, and the concept of non-lethal SDT has also been proposed. In this review, we summarize the ultrasonic parameters and known sonosensitizers utilized in SDT for AS; we elaborate on SDT's therapeutic effects and mechanisms in terms of macrophages, T lymphocytes, neovascularization, smooth muscle cells, lipid, extracellular matrix and efferocytosis within plaques; additionally, we discuss the safety of SDT. A comprehensive summary of the confirmed effects of SDT on AS is conducted to establish a framework for future researchers.

Background:Type 2 diabetes mellitus (T2DM) and hypertension (HT) often coexist and contribute to left atrial (LA) functional abnormalities. The aim of the present study was to explore whether there is a potential interaction effect between T2DM and HT on LA function.Methods:A total of 135 patients (45 with T2DM only, 45 with HT only, and 45 with both T2DM and HT) were enrolled and compared to 45 age- and sex-matched controls. LA volume fraction, including LA ejection fraction (LAEF), LA expansion index (LAEI), LA passive emptying fraction (LAPEF), and LA active emptying fraction (LAAEF), and strain parameters, including LA reservoir longitudinal strain (LASr), LA conduit longitudinal strain (LAScd), and LA contraction longitudinal strain (LASct), were obtained using three-dimensional echocardiography (3DE).Results:Patients with T2DM had significantly more impaired LA reservoir and conduit functions compared to those without T2DM (P<0.05), and patients with HT had a significantly more impaired LA reservoir function, conduit function, and booster pump function compared to those without HT (P<0.05). Two-way analysis of variance showed that there were significant additive interaction effects between T2DM and HT with respect to LASr (PT2DM + HT =0.002) and LAScd (PT2DM + HT =0.001). Generalized linear model demonstrated that T2DM + HT had a greater relative contribution than either T2DM or HT alone to the LA strain indexes, even after adjustment for other confounders (LASr, βT2DM + HT =-3.931, 95% CI: -6.237 to -1.624, P=0.001; LAScd, βT2DM + HT=-3.781, 95% CI: -5.653 to -1.908, P<0.001).Conclusions:Both T2DM and HT had an adverse effect on LA function. The coexistence of both conditions further impaired LA performance in an additive interaction fashion.

Objective:To evaluate the right ventricular function in patients with dilated cardiomyopathy (DCM) by four-dimensional automatic right ventricular quantitative analysis (4D Auto RVQ), and compare with the right ventricular ejection fraction measured by cardiac magnetic resonance (CMR-RVEF), and to explore the clinical application value of 4D Auto RVQ technique in evaluating the right ventricular function of patients with DCM.Methods:A prospective study was conducted to select 52 patients with DCM who were treated in Fuwai Central China Cardiovascular Hospital of Zhengzhou University from March to October 2022 as DCM group, and 52 healthy volunteers were selected as the control group during the same period. The four-dimensional right ventricular ejection fraction (4D-RVEF), right ventricular stroke volume index (RVSVI), right ventricular end-diastolic volume index (RVEDVI), right ventricular end-systolic volume index (RVESVI), four-dimensional right ventricular basal diameter (4D-RVDd-base), four-dimensional right ventricular middle diameter (4D-RVDd-mid), four-dimensional right ventricular long axis diameter (4D-RVLd), four-dimensional tricuspid annular plane systolic excursion (4D-TAPSE) and four-dimensional right ventricular fractional area change (4D-RVFAC) were obtained by 4D Auto RVQ technique. The differences of the above parameters between DCM group and control group were compared.Pearson linear correlation analysis was used to evaluate the correlation between echocardiographic parameters and CMR-RVEF. The ROC curve was used to find the most sensitive parameters for evaluating right ventricular function, and the area under the ROC curve ( AUC ) was calculated and compared.Results:Compared with the control group, RVEDVI, RVESVI, 4D-RVDd-base and 4D-RVDd-mid in the DCM group were increased, and the absolute values of 4D-RVEF, 4D-TAPSE, 4D-RVFAC, right ventricular global longitudinal strain(RVGLS) and right ventricular free wall longitudinal strain(RVFWLS) were decreased (all P<0.05). Correlation analysis showed that 4D-RVEF was positively correlated with CMR-RVEF ( r=0.711, P<0.05). ROC curve analysis showed that 4D-RVEF was superior to other parameters in evaluating right ventricular function in DCM patients (AUC: 0.916). Conclusions:4D Auto RVQ technique can quantitatively evaluate right ventricular function in DCM patients. 4D-RVEF has a significant correlation with CMR-RVEF, and 4D-RVEF has the best efficacy in evaluating right ventricular function in DCM patients.

In recent years, tumor immunotherapy has made significant progress. However, tumor immunotherapy, particularly immune checkpoint inhibitors (e.g., PD-1/PD-L1 inhibitors), benefits only a tiny proportion of patients in solid cancers. The tumor microenvironment (TME) acts a significant role in tumor immunotherapy. Studies reported that tumor-associated macrophages (TAMs), as one of the main components of TME, seriously affected the therapeutic effect of PD-1/PD-L1 inhibitors. In this review, we analyzed TAMs from epigenetic and single-cell perspectives and introduced the role and mechanisms of TAMs in anti-programmed death protein 1(anti-PD-1) therapy. In addition, we summarized combination regimens that enhance the efficacy of tumor PD-1/PD-L1 inhibitors and elaborated on the role of the TAMs in different solid cancers. Eventually, the clinical value of TAMs by influencing the therapeutic effect of tumor PD-1/PD-L1 inhibitors was discussed. These above are beneficial to elucidate poor therapeutic effect of PD-1/PD-L1 inhibitors in solid tumors from the point of view of TAMs and explore the strategies to improve its objective remission rate of solid cancers.

BackgroundCardiac-resident or -enriched microRNAs (miRNAs) could be released into the bloodstream becoming circulating cardiac miRNAs, which are increasingly recognized as non-invasive and accessible biomarkers of multiple heart diseases. However, dilated cardiomyopathy (DCM)-associated circulating miRNAs (DACMs) and their roles in DCM pathogenesis remain largely unexplored. MethodsTwo human cohorts, consisting of healthy individuals and DCM patients, were enrolled for serum miRNA sequencing (10 vs. 10) and quantitative polymerase chain reaction validation (46 vs. 54), respectively. Rigorous screening strategy was enacted to define DACMs and their potentials for diagnosis. DCM mouse model, different sources of cardiomyocytes, adeno-associated virus 9 (AAV9), gene knockout, RNAscope miRNA in situ hybridization, mRFP-GFP-LC3B reporter, echocardiography and transmission electron microscopy were adopted for mechanistic explorations. ResultsSerum miRNA sequencing revealed a unique expression pattern for DCM circulating miRNAs. DACMs miR-26a-5p, miR-30c-5p, miR-126-5p and miR-126-3p were found to be depleted in DCM circulation as well as heart tissues. Their expressions in circulation and heart tissues were proven to be correlated significantly, and a combination of these miRNAs was suggested potential values for DCM diagnosis. FOXO3, a predicted common target, was experimentally demonstrated to be co-repressed within cardiomyocytes by these DACMs except miR-26a-5p. Delivery of a combination of miR-30c-5p, miR-126-5p and miR-126-3p into the murine myocardium via AAV9 carrying an expression cassette driven by cTnT promoter, or cardiac-specific knockout of FOXO3 (Myh6-Cre(ERT2), FOXO3 flox(+/+)) dramatically attenuated cardiac apoptosis and autophagy involved in DCM progression. Moreover, competitively disrupting the interplay between DACMs and FOXO3 mRNA by specifically introducing their interacting regions into murine myocardium crippled the cardioprotection of DACMs against DCM. ConclusionsCirculating cardiac miRNA-FOXO3 axis plays a pivotal role in safeguarding against myocardial apoptosis and excessive autophagy in DCM development, which may provide serological cues for DCM non-invasive diagnosis and shed light on DCM pathogenesis and therapeutic targets.

Background Type 2 diabetes mellitus (T2DM) and hypertension (HT) often coexist and contribute to left atrial (LA) functional abnormalities. The aim of the present study was to explore whether there is a potential interaction effect between T2DM and HT on LA function. Methods A total of 135 patients (45 with T2DM only, 45 with HT only, and 45 with both T2DM and HT) were enrolled and compared to 45 age- and sex-matched controls. LA volume fraction, including LA ejection fraction (LAEF), LA expansion index (LAEI), LA passive emptying fraction (LAPEF), and LA active emptying fraction (LAAEF), and strain parameters, including LA reservoir longitudinal strain (LASr), LA conduit longitudinal strain (LAScd), and LA contraction longitudinal strain (LASct), were obtained using three-dimensional echocardiography (3DE). Results Patients with T2DM had significantly more impaired LA reservoir and conduit functions compared to those without T2DM (P<0.05), and patients with HT had a significantly more impaired LA reservoir function, conduit function, and booster pump function compared to those without HT (P<0.05). Two-way analysis of variance showed that there were significant additive interaction effects between T2DM and HT with respect to LASr (PT2DM + HT =0.002) and LAScd (PT2DM + HT =0.001). Generalized linear model demonstrated that T2DM + HT had a greater relative contribution than either T2DM or HT alone to the LA strain indexes, even after adjustment for other confounders (LASr, βT2DM + HT =−3.931, 95% CI: −6.237 to −1.624, P=0.001; LAScd, βT2DM + HT=−3.781, 95% CI: −5.653 to −1.908, P<0.001). Conclusions Both T2DM and HT had an adverse effect on LA function. The coexistence of both conditions further impaired LA performance in an additive interaction fashion.

According to reports, gut microbiota and metabolites regulate the intestinal immune microenvironment. In recent years, an increasing number of studies reported that bile acids (BAs) of intestinal flora origin affect T helper cells and regulatory T cells (Treg cells). Th17 cells play a pro-inflammatory role and Treg cells usually act in an immunosuppressive role. In this review, we emphatically summarised the influence and corresponding mechanism of different configurations of lithocholic acid (LCA) and deoxycholic acid (DCA) on intestinal Th17 cells, Treg cells and intestinal immune microenvironment. The regulation of BAs receptors G protein-coupled bile acid receptor 1 (GPBAR1/TGR5) and farnesoid X receptor (FXR) on immune cells and intestinal environment are elaborated. Furthermore, the potential clinical applications above were also concluded in three aspects. The above will help researchers better understand the effects of gut flora on the intestinal immune microenvironment via BAs and contribute to the development of new targeted drugs.

Abstract Pulmonary atresia (PA) is a severe cyanotic congenital heart disease. Although some genetic mutations have been described to be associated with PA, the knowledge of pathogenesis is insufficient. The aim of this research was to use whole-exome sequencing (WES) to determine novel rare genetic variants in PA patients. We performed WES in 33 patients (27 patient–parent trios and 6 single probands) and 300 healthy control individuals. By applying an enhanced analytical framework to incorporate de novo and case–control rare variation, we identified 176 risk genes (100 de novo variants and 87 rare variants). Protein‒protein interaction (PPI) analysis and Genotype-Tissue Expression analysis revealed that 35 putative candidate genes had PPIs with known PA genes with high expression in the human heart. Expression quantitative trait loci analysis revealed that 27 genes that were identified as novel PA genes that could be affected by the surrounding single nucleotide polymorphism were screened. Furthermore, we screened rare damaging variants with a threshold of minor allele frequency at 0.5% in the ExAC_EAS and GnomAD_exome_EAS databases, and the deleteriousness was predicted by bioinformatics tools. For the first time, 18 rare variants in 11 new candidate genes have been identified that may play a role in the pathogenesis of PA. Our research provides new insights into the pathogenesis of PA and helps to identify the critical genes for PA.

Quality of life profiles measured by the General Life Functioning (GLF) Scale were examined in elderly patients with recurrent major depression, before and during combined treatment with nortriptyline and interpersonal psychotherapy. The study group included 110 patients, 91 recovered and 19 nonrecovered, aged 60 to 80 years, suffering from at least their second lifetime episode of major depression. Repeated measures analysis of covariance (with Hamilton and Beck depression scores as time-dependent covariates) was used to compare the temporal course of overall GLF scores for the recovered and the nonrecovered groups. Factor analysis was used to examine whether the GLF Scale yielded an overall score and measured specific aspects of well-being and coping. There were significant differences in the overall GLF scores between recovered and nonrecovered patients, with the differences increasing from week 8 of treatment onward. Analysis revealed significant improvements in quality of life, as measured by overall GLF scores, over the course of treatment in both recovered and nonrecovered patients. Even when changes in Hamilton and Beck depression ratings were controlled for in the statistical analysis, improvements in GLF scores were found to be greater in recovered than in nonrecovered patients. Thus, the GLF measures more than change in level of depression. Its overall score also has high internal reliability.

目的:总结重度肺动脉瓣狭窄伴右心发育不良综合征(HRHS)胎儿的宫内介入治疗.方法 与结果:对郑州大学人民医院2例孕中晚期肺动脉瓣狭窄伴HRHS的胎儿,经多学科会诊、评估,分别于孕32周及孕28周实施超声引导下宫内胎儿肺动脉瓣成形术(FPV).2例FPV术后围术期恢复良好,右心系统发育及血流动力学指标较术前明显改善,右室流出道前向血流增加.病例1产后患儿出现肺动脉瓣再狭窄,通过经皮肺动脉瓣成形术及外科手术再干预最终实现双心室循环.病例2行FPV治疗2周后,孕妇选择终止妊娠.结论:宫内FPV可促进孕中晚期肺动脉瓣狭窄伴HRHS胎儿右心系统再发育,利于产后双心室矫治.

目的:研究血管紧张素受体脑啡肽酶抑制剂(ARNI)类药物LCZ696能否通过上调心房利钠肽(ANP)改善阿霉素心肌病心力衰竭大鼠心肌纤维化及心功能.方法:选取成年雄性Wistar大鼠并随机分为正常对照组(n=10)、模型组(n=12,注射用盐酸阿霉素2.5 mg/kg,腹腔注射,每周1次,连续6周)和LCZ696治疗组[n=12,阿霉素注射同模型组,在首次注射阿霉素前1周开始给予LCZ696治疗,按照60 mg/(kg·d)剂量灌胃,持续7周].给药完成后,第7周行超声心动图检测大鼠左心收缩功能.ELISA方法检测大鼠外周血中N端脑利钠肽前体(NT-proBNP)、ANP、环磷酸鸟苷(cGMP)的浓度;左室心肌组织行Masson染色检测心肌纤维化情况.RT-qPCR方法检测大鼠左室心肌中TGF-β的mRNA表达.结果:与模型组相比,LCZ696治疗组大鼠死亡率明显降低(16.7％ vs 41.7％,P＜0.05),左室收缩末期内径及舒张末期内径明显降低(P＜0.05),左室射血分数及左室短轴缩短率明显升高(P＜0.05);LCZ696治疗组大鼠心肌纤维化程度明显减轻,胶原容积分数明显下降(P＜0.05).LCZ696治疗组大鼠外周血中ANP、cGMP的水平较模型组进一步升高,外周血中NT-proBNP的浓度明显降低(P＜0.05);与模型组相比,LCZ696治疗组大鼠心肌组织TGF-β的mRNA表达明显降低(P＜0.05).结论:ARNI类药物LCZ696可改善阿霉素心肌病心力衰竭大鼠左室心肌纤维化及心功能,这一保护作用可能与ANP增加有关.

BackgroudNoninvasive myocardial work, estimated by left ventricular (LV) pressure-strain loop (PSL), has been introduced for assessing LV myocardial performance. Based on both blood pressure and speckle-tracking derived strain data, noninvasive myocardial work is considered to be less load-dependent than global longitudinal strain (GLS). In some conditions, such as hypertension or aortic coarctation, the increased afterload will affect strain measurements, and myocardial work can serve as a more robust metric.ObjectiveWe prospectively recruited healthy children to explore the relationship between myocardial work indices and body size parameters, and to determine the reference values of noninvasive myocardial work indices in healthy children.Methods183 healthy children (aged 1–18 years, males: 52.5%) were enrolled in the study. Global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE), were assessed by LVPSL and compared according to age and sex.ResultsThe mean for GWI was 1,448.7 ± 265.0 mm Hg%, 1,859.8 ± 290.7 mm Hg% for GCW, and the median (interquartile range) for GWW was 54.0 (33.0–82.0) mm Hg% and 97.0 (95.0–99.0) % for GWE. male had greater GWI and GCW) than female (1,572.5 ± 250.2 mm Hg% vs. 1,312.2 ± 208.7 mm Hg% and 1,944.3 ± 299.2 mm Hg% vs. 1,766.6 ± 251.5 mm Hg%, respectively, all P < 0.001). GWI and GCW were significantly correlated with baseline parameters, including age, height, weight, BSA, body mass index, heart rate, and blood pressure. After indexed to BSA, GWI (BSA), GCW (BSA) remained significantly negatively correlated with age (P < 0.001).Conclusionswe proposed the normal reference values and regression equations for GWI and GCW based on age and BSA in healthy children. This might provide a basis of reference for the evaluation of cardiac function in children with cardiopulmonary disease.

Objective:To evaluate the medium-term clinical and hemodynamic outcomes of percutaneous pulmonary valve implantation (PPVI) using a domestic Venus-P self-expanding valve in the treatment of severe pulmonary regurgitation after Tetralogy of Fallot (TOF).Methods:Retrospective study.From December 2017 to December 2020, 13 TOF patients with (17.8±4.7) years old and (50.2±12.3) kg underwent PPVI using the Venus-P self-expanding valve in the Department of Children′s Heart Center, Zhengzhou University People′s Hospital were recruited.The mean valve size was (31.9±3.1) mm.All patients received the transannular patch surgery and developed severe pulmonary regurgitation.After PPVI, 13 patients were followed up for at least 12 months.The operation-related complications, improvement of valve and heart function and the durability and reintervention of the Venus-P self-expanding valve were analyzed.The right ventricular end-diastolic volume index (RVEDVi) before and after operation was compared by the paired t-test, and the New York Heart Association (NYHA) class was compared by the paired Wilcoxon signed rank sum test. Results:PPVI was successfully performed in all 13 patients without death.At 6 months post-PPVI, cardiac magnetic resonance imaging findings showed that RVEDVi was significantly reduced[(145.7±9.6) mL/m 2vs.(100.2±12.2) mL/m 2, P<0.05], and the NYHA class was significantly improved ( P<0.05). One patient presented moderate pulmonary valve regurgitation at 12 months postoperatively.No vegetation was found on echocardiography, and blood culture was negative in this case.Six patients did not have postoperative pulmonary valve regurgitation, and the remaining presented mild or less pulmonary regurgitation.One patient had sudden ventricular tachycardia on the 6 th day postoperatively, which was converted to sinus rhythm after synchronous electrocardiography.Only one case underwent appendectomy 7 months after operation due to acute appendicitis, and the remaining did not require valve-related reintervention after implantation.During the follow-up for (22.8±8.0) months, no patients had perivalve leakage, stent migration and rupture.Complications like embolization and coronary artery compression were not reported. Conclusions:PPVI using the Venus-P self-expanding valve is safe and effective in patients with severe pulmonary valve regurgitation after TOF surgery, showing an acceptable medium-term follow-up outcome.Studies with a large sample size and long follow-up period are still needed to validate our findings.