The study proposes an innovative ECG-free algorithm for the automatic annotation of cardiac feature points in seismo-cardiogram (SCG) signals from valvular heart disease (VHD) patients. The algorithm is based on multi-modality signals, obviating the need for manual SCG annotation. It consists of self-supervised learning and pseudo-label generation from ECG signals. Initially, the algorithm employs self-supervised learning to analyze the pseudo-periodic nature of SCG signals. Subsequently, pseudo-labels are established using synchronized ECG signals for model training. Finally, labeling tests are conducted with SCG signals alone. The training and testing datasets consist of samples from 100 VHD patients. Experiments demonstrate that the proposed algorithm achieves a precision of 98.94% and a recall of 97.44% on the test set, suggesting the feasibility of the proposed method. The presented framework would be essential for further fiducial point detection and analysis of cardio-mechanical signals, which might provide out-of-clinic evaluations of VHD in the future.

In this paper, we investigated the effectiveness of entropy features in the classification of mitral regurgitation (MR), based on the cardio-mechanical signals. These entropy features were extracted from the original data and data after continuous wavelet transform (CWT) expansion. XGBoost was selected for the classifier. The performance of different entropy features and different training-test set classification methods were compared. The contribution of different entropy features to the classification results is compared by SHapley Additive exPlanations (SHAP) values. It is concluded that the entropy features extracted from the signal after CWT expansion perform better in classification results. Approximate entropy (ApEn), permutation entropy (PEn), and sample entropy (SampEn) demonstrated greater contributions to the classification outcomes. The entropy features extracted from the Y-axis (along the head-to-foot direction) channels are more important than those from other channels. However, the sensitivity decreases significantly when dividing the training-testing set in terms of subjects. These results provide valuable insights for future research on utilizing entropy measures for assessing MR.

Background The study aimed to assess the correlation between the monitoring frequency of PT-INR and the long-term prognosis in patients with mechanical heart valve (MHV) replacement after discharge. Methods This single-center, observational study enrolled patients who underwent MHV replacement and discharged from June 2015 to May 2018. Patients or their corresponding family members were followed with a telephone questionnaire survey in July-October 2020. Based on monitoring intervals, patients were divided into frequent monitoring (FM) group (≤ 1 month) and less frequent monitoring (LFM) group (> 1 month). The primary endpoint was the composite of thromboembolic event, major bleeding or all-cause death. The secondary endpoints were thromboembolic event, major bleeding or all-cause death, respectively. Results A total of 188 patients were included in the final analysis. The median follow-up duration was 3.6 years (Interquartile range: 2.6 to 4.4 years). 104 (55.3%) patients and 84 (44.7%) patients were classified into the FM group and the LFM group, respectively. The FM group had a significantly lower incidence of the primary endpoint than the LFM group (3.74 vs. 1.16 per 100 patient-years, adjusted HR: 3.31 [95% CI 1.05–10.42, P = 0.041]). Secondary analysis revealed that the risk of thromboembolic events and all-cause death were also reduced in the FM group. Conclusions The management of warfarin treatment in patients after MHV replacement remains challenging. Patients with less frequent monitoring of PT-INR might have worse clinical prognosis than those with frequent PT-INR monitoring.

目的 基于网络药理学预测三七治疗幽门螺杆菌(Hp)相关疾病机制,研究三七中有效活性成分人参皂苷Rb3对Hp造成的胃上皮细胞损伤的保护作用及机制.方法 使用Herb数据库收集"三七"的相关预测靶点,使用Gene Cards数据库收集Hp相关疾病的靶点;使用Draw Venn Diagram网站绘制Venn图,得到靶点交集;进行蛋白互作(PPI)网络分析、基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析.将GES-1细胞分为对照组、模型组及人参皂苷Rb3低、中和高浓度(1、5、10 μmol·L-1)组,人参皂苷Rb3组使用相应浓度的人参皂苷Rb3预处理,培养过夜12h至融合度为70％～80％.Hp悉尼株1(SS1)按感染复数(MOI)100加入细胞中制备损伤模型,人参皂苷Rb3继续给药,共培养48h.对照组不加SS1,对照组和模型组不加药.改良吉姆萨染色后通过光学显微镜观察细胞形态;结合Hoechst 33342荧光染色和Annexin V/PI双染流式细胞术检测细胞凋亡;试剂盒法检测活性氧(ROS)水平;采用实时荧光定量PCR(qRT-PCR)检测凋亡相关基因 TP53、Bax、Bcl-2 表达量;Western blotting法检测 P53、p-Akt、cleaved/pro-Caspase 9、Bcl-2、Bax、cleaved/pro-Caspase3的蛋白表达情况.结果 网络药理学结果表明三七治疗Hp相关疾病的靶点共16个,其PPI网络分析得到按度值大小排名前6位靶点为TP53、CASP3、PTGS2、IL6、TNF、IL1β.GO富集分析与KEGG富集分析结果均显示与凋亡相关.与模型组比较,经人参皂苷Rb3处理后,GES-1细胞的细胞核染色质致密深染,破裂的细胞逐渐减少;Hoechst 33342荧光染色细胞核强荧光数目明显减少;细胞凋亡率显著降低(P＜0.05);ROS水平显著降低(P＜0.05);TP53与Bax的mRNA水平显著降低,Bcl-2 mRNA水平显著升高(P＜0.05);p-Akt、Bcl-2蛋白表达显著升高(P＜0.05),P53、Bax、cleaved/pro-Caspase 9与cleaved/pro-Caspase 3蛋白表达显著降低(P＜0.05).结论 三七可能通过包括炎症及凋亡在内的多种途径治疗Hp相关疾病,人参皂苷Rb3对Hp诱导的胃上皮细胞凋亡发挥显著改善作用,其可能机制是降低氧化应激水平,并调节Akt的磷酸化和P53的表达.

目的 通过幽门螺杆菌(Hp)感染小鼠建立Hp相关胃炎模型,探讨猪苓多糖的保护作用及机制.方法 将C57BL/6小鼠随机分为4组:对照组、模型组、猪苓多糖(250mg,kg-1)组、核转录因子-κB(NF-κB)通路的抑制剂——吡咯烷二硫代甲酸铵(PDTC,阳性对照,100mg·kg-1)组.除对照组外,其余各组小鼠ig给予Hp悉尼株1(SS1)菌液(1×109CFU·mL-1),第1天每只0.4 mL,以后连续3 d每天igl次,每次0.2 mL.igHp完成4周后,猪苓多糖组和PDTC组给予相应剂量的药物,对照组和模型组小鼠给予无菌水,每只0.4 mL,每天1次持续14 d.将胃取出,沿胃大弯切开,肉眼观察胃黏膜变化;吉姆萨染色验证Hp在小鼠胃黏膜的定植;HE染色观察小鼠胃黏膜组织的炎症浸润状态;免疫组化检测核因子-κB(NF-κB)p65的表达;Western blotting法检测小鼠胃腺组织炎症因子白细胞介素-8(IL-8)蛋白表达;酶联免疫吸附法(ELISA)检测小鼠血清中IL-8的表达.结果 与模型组比较,猪苓多糖组小鼠胃黏膜褶皱整齐,出血点消失,黏膜光滑,胃黏膜颜色红润有光泽;炎症细胞浸润和其他组织损伤明显减少;细菌定植数量明显减少;胃上皮细胞中NF-κB p65的表达减弱;胃腺组织IL-8蛋白表达水平显著降低(P＜0.001);小鼠血清中IL-8表达水平显著降低(P＜0.001).结论 猪苓多糖可能通过抑制炎症信号通路NF-κB 相关分子的表达在 Hp 相关胃炎中发挥保护作用.

PRKAG2 cardiomyopathy is a rare progressive disease characterized by increased ventricular wall thickness and preexcitation. Dysfunction of the protein 5 '-AMP-activated protein kinase (AMPK) plays a decisive role in the progression of ventricular lesions. Although patients with the PRKAG2-R302Q mutation have a high incidence of atrial fibrillation (AF), the molecular mechanism contributing to the disease remains unclear. We carried out whole-genome sequencing with linkage analysis in three affected members of a family. Atrial samples were obtained from the proband via surgical intervention. Control atrium biopsies were obtained from patients with persistent AF. Pathological changes were analyzed using the hematoxylin and eosin (H&E), Masson, and periodic acid-Schiff (PAS) staining. The AMPK signaling pathway was investigated by western blot. A murine atrial cardiomyocyte cell line (HL-1) and human induced pluripotent stem derived atrial cardiomyocytes (hiPSC-ACMs) were transfected with an adenovirus carrying the same mutation. We used enzyme linked immunosorbent assay (ELISA) to determine the AMPK activity in HL-1 cells and hiPSC-ACMs overexpressing PRKAG2-R302Q. Pathological results showed a large quantity of glycogen accumulation and vacuolization in cardiomyocytes from the proband atrial tissue. Western blot analysis revealed that the AMPK activity was significantly downregulated compared with that of the controls. Furthermore, remarkable glycogen deposition and impairment of AMPK activity were reproduced in HL-1 cells overexpressing PRKAG2-R302Q. Taken together, PRKAG2-R302Q mutation directly impair atrial cardiomyocytes. PRKAG2-R302Q mutation lead to glycogen deposition and promote the growth of atrial lesions by disrupting the AMPK pathway.

目的 传统三明治技术可能会对夹层累及窦部患者造成假腔封闭不完全,甚至根部扩大,导致可能再次手术的可能.文中总结"改良三明治"技术在急性A型主动脉夹层(ATAAD)手术中的应用效果.方法 回顾性分析2020年1月至12月期间江苏省人民医院收治并采用"改良三明治"技术处理主动脉根部的91例ATAAD患者临床资料.所有患者均在深低温停循环(DHCA)下行急诊手术,术前完成食道超声心动图(TEE)以及CT血管造影(CTA)评估主动脉根部及主动脉瓣情况.结果 本组患者中,45例累及窦部,26例累及冠状动脉(Neri A型18例、Neri B型8例).18例患者重度主动脉瓣关闭不全(AI),29例中度AI,38例轻度AI,6例无AI.主动脉根部处理采用"改良三明治"技术,依据夹层累及范围,单纯行升主动脉替换4例,半弓或次全弓替换16例,全弓替换+支架象鼻技术71例.全组患者体外循环时间189(170～250)min,主动脉根部处理时间25(22～33)min,DHCA时间14(11～19)min,手术时间306(277～351)min.全组患者围术期死亡7例(7.6％).术后并发症包括血液透析14例(15.4％),神经系统并发症4例(4.4％),气管切开2例(2.1％);机械通气时间为64(22～98)h,术后住院时间为22(18～25)d.术后6个月复查CTA和二维超声心动图结果显示所有存活患者主动脉根部均无残留夹层,轻度AI 37例,无中度及以上AI病例,主动脉峰值跨瓣压差7.9(4.0～9.5)mmHg.结论 "改良三明治"技术在ATAAD手术中效果满意.其围术期死亡率及并发症发生率均较低.对于夹层累及窦部以及合并重度AI的患者可以有效封闭假腔,保留瓣膜;对于Neri A和Neri B型患者亦可有效保护冠脉.但其远期效果仍需进一步随访.

目的 目前有报导发现猪苓多糖可以降低炎性浸润的表达,但对Hp引起的胃黏膜上皮细胞炎症是否同样具有保护作用尚不得知.研究猪苓多糖(PPS)对幽门螺杆菌(Hp)诱导的人胃黏膜上皮细胞系(GES-1)的抗炎作用及相关机制.方法 细胞分组:①Hp与GES-1细胞共培养:分别设置对照组、M50组,M100组、M200组,对照组不做处理,其余各组分别按照MOI 50、100、200向人胃黏膜上皮细胞(GES-1)中加入Hp菌液,与之共培养;②加入猪苓多糖干预:分别设置空白组、模型组、Hp+猪苓多糖低、中、高浓度组,药物浓度分别为1.25、2.5、5 mg/mL,分别记作PPS-L组、PPS-M组、PPS-H组,以NF-κB通路抑制剂吡咯烷二硫代甲酸铵(Pyrrolidinedithiocarbamate ammonium,PDTC)作为阳性对照组,药物浓度为100μmol/L,记作PDTC组.运用RT-qPCR、Western blot检测白细胞介素8(IL-8)及核转录因子-κB(NF-κB)的基因及蛋白表达变化.结果 M50、M100、M200各组的炎症因子IL-6、IL-8在Hp感染的GES-1的表达明显高于对照组(P<0.05);与对照组相比,48 h后M50、M100、M200各组P65的表达升高(P<0.05).IκBα在48 h时表达量(1.246±0.279、1.118±0.123、1.102±0.076)较对照组(1.657±0.074)降低(P<0.05),各组的NF-κB及P65的mRNA表达量在共培养48 h时升高(P<0.05),且表达趋势呈浓度依赖性.加入猪苓多糖和PDTC干预后,与模型组对比,猪苓多糖各个浓度组及PDTC组的IL-6、IL-8及P65的表达明显降低(P<0.05),IκBα的表达量升高(P<0.05).细胞免疫荧光显示,与模型组相比,PPS-M和PDTC组P65入核的细胞个数明显减少(P<0.05).结论 PPS可能通过抑制NF-κB信号通路对Hp感染的GES-1细胞发挥炎症保护作用.

Complement factor properdin (CFP), encodes plasma glycoprotein, is a critical gene that regulates the complement pathway of the innate immune system. However, correlations of CFP in cancers remain unclear. In this study, the expression pattern and prognostic value of CFP in pan-cancer were analyzed via the Oncomine, PrognoScan, GEPIA and Kaplan-Meier plotters. In addition, we used immunohistochemical staining to validate CFP expression in clinical tissue samples. Finally, we evaluated the correlations between CFP and cancer immune infiltrates particularly in stomach adenocarcinoma (STAD) and lung adenocarcinoma (LUAD) by using GEPIA and TIMER databases. The results of database analysis and immunohistochemistry showed that the expression level of CFP in STAD and LUAD was lower than that in normal tissues. Low expression level of CFP was associated with poorer overall survival (OS), first progression (FP), post progression survival (PPS) and was detrimental to the prognosis of STAD and LUAD, specifically in stage 3, stage T3, stage N2 and N3 of STAD (P<0.05). Moreover, expression of CFP had significant positive correlations with the infiltration levels of CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells (DCs) in STAD and LUAD. Furthermore, gene markers of infiltrating immune cells exhibited different CFP-related immune infiltration patterns such as tumor-associated-macrophages (TAMs). These results suggest that CFP can serve as a prognostic biomarker for determining prognosis and immune infiltration in STAD and LUAD.

目的 观察化痰消瘀方对胃癌前病变的逆转效果及对患者胃液外泌体miR-133 a和miR-421表达水平的影响,探讨其作用机制.方法 选择2019年1月—2020年5月在南京医科大学第一附属医院就诊的62例萎缩性胃炎伴肠化生患者,采用随机数字表法将患者分为对照组和观察组各31例.对照组给予维酶素片治疗,观察组在对照组治疗基础上给予化痰消瘀方治疗,疗程3个月.观察2组患者治疗前后胃液外泌体miR-133 a和miR-421表达水平、中医症状积分和内镜检查结果变化.结果 治疗后2组患者胃液外泌体miR-133 a表达水平均较治疗前显著升高(P均<0.05),且观察组miR-133 a表达水平显著高于对照组(P<0.05);治疗后2组患者胃液外泌体miR-421表达水平、中医症状积分和胃黏膜萎缩严重程度分度、胃炎伴肠上皮化生、异型增生得分均较治疗前显著降低(P均<0.05),且观察组上述指标均显著低于对照组(P均<0.05).结论 化痰消瘀方可逆转胃癌前病变,减轻症状,调控miR-133 a和miR-421表达可能是其重要作用机制.

目的:探讨香砂六君合半夏泻心汤对糖尿病胃轻瘫大鼠尿液中内源性代谢产物的影响,利用尿液代谢组学分析其可能的作用机制.方法:采用腹腔注射80 mg/kg链脲佐菌素联合不规则饮食以制备糖尿病胃轻瘫模型,造模成功后,随机分为模型对照组、莫沙比利1.56 mg/kg组、香砂六君合半夏泻心汤9.3 g/kg组,每组6只;另设6只健康SD大鼠为正常对照组.灌胃给药干预8w后,测定各组大鼠胃排空率和小肠推进率,利用代谢笼收集24 h尿液,通过气相色谱与质谱联用(GS-MS)技术检测尿液样品,应用主成分分析(PCA)和偏最小二乘法-判另1别分析(PLS-DA)进行代谢轮廓的比较以及生物标志物的鉴定,利用MetPa数据库分析相关代谢通路.结果:与正常对照组比较,模型对照组胃排空率和小肠推进率显著降低(P＜0.01),其尿液代谢轮廓发生明显变化.与模型对照组比较,莫沙比利1.56 mg/kg、香砂六君合半夏泻心汤9.3 g/kg组胃排空率明显升高(P＜0.05),其尿液代谢轮廓能明显区分且趋近正常对照组.香砂六君合半夏泻心汤9.3 g/kg干预治疗后对β-丙氨酸、葡萄糖酸内酯、苯甲酸、3-(3-羟基苯基)-丙酸、糖二酸、异麦芽酮糖醇、核糖醇、苏氨酸、肌酸、丝氨酸、苯乙酸、对苯二酚、甲基乙内酰脲这13个代谢产物的含量具有一定的回调作用,并作用于3条代谢通路.结论:香砂六君合半夏泻心汤可促进糖尿病胃轻瘫大鼠的胃排空,其作用机制可能与改善尿液中代谢产物的含量异常有关.

Dabigatran is a widely used non-Vitamin K antagonist oral anticoagulant and has demonstrated a better efficacy and safety profile compared to Vitamin K antagonists. However, in some specific situations, the bleeding risk of dabigatran will be much increased. A 76-year-old female atrial fibrillation patient with concomitant nonrheumatic mitral valve regurgitation and chronic heart failure was described. She was on dabigatran 110 mg twice a day. On day 2 after admission, the patient presented with acute decompensated heart failure, the creatinine clearance level markedly decreased from 40.9 mL/min to 23.1 mL/min, and the trough-activated partial thromboplastin time exceeded the detection range. In this clinical context, renal and coagulation function should be monitored closely to avoid severe adverse events, especially major bleeding. Low-molecular-weight heparin might be considered to be applied temporarily, and rivaroxaban may be prescribed in this condition. The ethical approval was waived by the institutional review board of our hospital owing to the retrospective nature of the study.

目的 观察负压封闭引流(VSD)对心脏术后胸部正中切口愈合不良的治疗效果.方法 对心脏术后发生胸部正中切口愈合不良的17例患者使用VSD处理,并观察临床结局.结果 本组患者植入VSD时间为(19.6±10.7)d,术后更换VSD次数为(2.5±1.2)次.6例患者在VSD吸引7～10 d后切口肉芽组织新鲜,创面良好,无明显感染分泌物,予以Ⅱ期缝合切口.除1例主动脉夹层患者自动出院外,其余患者愈合良好,顺利出院.随访4～26个月,无感染再次复发或慢性窦道形成病例.结论 采用VSD治疗心脏术后胸部正中切口愈合不良患者的临床效果良好,安全性较高.

Background/Aims: Heart failure induced by tachycardia, the most common arrhythmia, is frequently observed in clinical practice. This study was designed to investigate the underlying mechanisms. Methods: Rapid electrical stimulation (RES) at a frequency of 3 Hz was applied on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for 7 days, with 8 h/day and 24 h/day set to represent short-term and long-term tachycardia, respectively. Age-matched hiPSC-CMs without electrical stimulation or with slow electrical stimulation (1 Hz) were set as no electrical stimulation (NES) control or low-frequency electrical stimulation (LES) control. Following stimulation, JC-1 staining flow cytometry analysis was performed to examine mitochondrial conditions. Apoptosis in hiPSC-CMs was evaluated using Hoechst staining and Annexin V/propidium iodide (AV/PI) staining flow cytometry analysis. Calcium transients and L-type calcium currents were recorded to evaluate calcium homeostasis. Western blotting and qPCR were performed to evaluate the protein and mRNA expression levels of apoptosis-related genes and calcium homeostasis-regulated genes. Results: Compared to the controls, hiPSC-CMs following RES presented mitochondrial dysfunction and an increased apoptotic percentage. Amplitudes of calcium transients and L-type calcium currents were significantly decreased in hiPSC-CMs with RES. Molecular analysis demonstrated upregulated expression of Caspase3 and increased Bax/Bcl-2 ratio. Genes related to calcium re-sequence were downregulated, while phosphorylated Ca2+/calmodulin-dependent protein kinase II (CaMKII) was significantly upregulated following RES. There was no significant difference between the NES control and LES control groups in these aspects. Inhibition of CaMKII with 1 µM KN93 partly reversed these adverse effects of RES. Conclusion: RES on hiPSC-CMs disturbed calcium homeostasis, which led to mitochondrial stress, promoted cell apoptosis and caused electrophysiological remodeling in a time-dependent manner. CaMKII played a central role in the damages induced by RES, pharmacological inhibition of CaMKII activity partly reversed the adverse effects of RES on both structural and electrophysiological properties of cells.

Background: Long-term ventricular pacing has deleterious effects and becomes more significant when cumulative percent ventricular pacing (Cum%VP) exceeds 40% of time. However, cellular disturbances and pathways by which pacing leads to myocardial disorders are not well understood. Attempts to resolve these questions have been hampered by difficulties in obtaining human cardiac tissue and the inability to build a longer-lasting (lasting longer than weeks) pacing model in vitro.Methods: Human induced pluripotent stem cell-derived ventricular cardiomyocytes (VCMs) were cultured in the presence of electrical stimulation for 2 weeks. Quantitative structural and electrophysiological analyses were used to define the functional disturbances of pacing.Results: Compared to controls, paced VCMs exhibited a remarkable reduction in the contractile protein expression, an increased apoptosis ratio and electrophysiological remodelling in a Cum% VP-dependent manner. Investigation of the protein expression levels revealed that long-term pacing universally activated both ER stress and downstream calpain. Moreover, the inhibition of calpain attenuated the adverse effects on the structural remodelling and increased the ICa, L in paced VCMs.Conclusions: The results demonstrated that pacing VCMs for 2 weeks in vitro led to a series of structural and electrophysiological dysfunctions. The increased ER stress and downstream calpain could be a central mechanism underlying the disease pathogenesis. This finding could represent a new therapeutic target in the management of long-term pacing patients.