Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

OBJECTIVE: To explore and verify that transient receptor potential vanilloid 4(TRPV4) affects chondrocyte degeneration. METHODS: Neonatal SD rats were selected, primary chondrocytes were extracted, and identified by toluidine blue staining and alcian blue staining;an in vitro chondrocyte inflammation model was constructed by IL-1β, and TRPV4 inhibitor was used to treat chondrocytes under inflammatory conditions, and the chondrocytes were treated by RT-PCR method was used to detect matrix metallopeptidase 13(MMP-13), a disintegrin and metalloproteinase with thrombospondin 5, (ADAMTS-5)、nitric oxide synthase 2(NOS2)、Collagen, type II alpha 1(Col2α1)and aggrecan (Acan) mRNA in chondrocytes; primary chondrocytes were treated with different concentrations of TRPV4 overexpression plasmid, and the optimal overexpression dose was screened. The mRNA expressions of TRPV4, MMP-13, ADAMTS-5, NOS2, Col2α1 and Acan in chondrocytes under the optimal TRPV4 overexpression dose were detected. RESULTS: Toluidine blue staining and Alcian blue staining identified the extracted cells as primary chondrocytes;RT-PCR showed that TRPV4, MMP-13, ADAMTS-5, NOS2 mRNA in chondrocytes treated with TRPV4 inhibitor under inflammatory conditions. The expression of Col2α1 mRNA was significantly decreased (P<0.05), and the expression of Col2α1 mRNA was increased (P<0.05). Although there was no significant difference in the expression of Acan mRNA, the overall trend was also increasing. The expression of Col2α1 and Acan mRNA in chondrocytes was significantly decreased (P<0.05), and the expression of NOS2 mRNA was increased(P<0.05), but there was no significant difference in MMP-13 and ADAMTS-5 (P>0.05). CONCLUSION Inhibiting the expression of TRPV4 can down-regulate the expression of genes related to chondrocyte degeneration.
Animals ; Rats ; Aggrecans/metabolism* ; Cartilage, Articular ; Cells, Cultured ; Chondrocytes ; Interleukin-1beta/metabolism* ; Matrix Metalloproteinase 13/metabolism* ; Rats, Sprague-Dawley ; RNA, Messenger/metabolism* ; TRPV Cation Channels/metabolism*

Objective: To investigate the representability and etiological diagnostic value of myocardium samples obtained from patients with hypertrophic cardiomyopathy (HCM) by transthoracic echocardiography-guided percutaneous intramyocardial septal biopsy (myocardial biopsy of Liwen procedure). Methods: This study was a retrospective case-series analysis. Patients with HCM, who underwent myocardial biopsy of Liwen procedure and radiofrequency ablation in Xijing Hospital, Air Force Military Medical University from July to December 2019, were included. Demographic data (age, sex), echocardiographic data and complications were collected through electronic medical record system. The histological and echocardiographic features, pathological characteristics of the biopsied myocardium of the patients were analyzed. Results: A total of 21 patients (aged (51.2±14.5) years and 13 males (61.9%)) were enrolled. The thickness of ventricular septum was (23.3±4.5)mm and the left ventricular outflow tract gradient was (78.8±42.6)mmHg (1 mmHg=0.133 kPa). Eight patients (38.1%) were complicated with hypertension, 1 patient (4.8%) had diabetes, and 2 patients (9.5%) had atrial fibrillation. Hematoxylin-eosin staining of myocardial samples of HCM patients before radiofrequency ablation evidenced myocytes hypertrophy, myocytes disarray, nuclear hyperchromatism, hypertrophy, atypia, coronary microvessel abnormalities, adipocyte infiltration, inflammatory cell infiltration, cytoplasmic vacuoles, lipofuscin deposition. Interstitial fibrosis and replacement fibrosis were detected in Masson stained biopsy samples. Hematoxylin-eosin staining of myocardial samples of HCM patients after radiofrequency ablation showed significantly reduced myocytes, cracked nuclear in myocytes, coagulative necrosis, border disappearance and nuclear fragmentation. Quantitative analysis of myocardial specimens of HCM patients before radiofrequency ablation showed that there were 9 cases (42.9%) with mild myocardial hypertrophy and 12 cases (57.1%) with severe myocardial hypertrophy. Mild, moderate and severe fibrosis were 5 (23.8%), 9 (42.9%) and 7 (33.3%), respectively. Six cases (28.6%) had myocytes disarray. There were 11 cases (52.4%) of coronary microvessel abnormalities, 4 cases (19.0%) of adipocyte infiltration, 2 cases (9.5%) of inflammatory cell infiltration,6 cases (28.5%) of cytoplasmic vacuole, 16 cases (76.2%) of lipofuscin deposition. The diameter of cardiac myocytes was (25.2±2.8)μm, and the percentage of collagen fiber area was 5.2%(3.0%, 14.6%). One patient had severe replacement fibrosis in the myocardium, with a fibrotic area of 67.0%. The rest of the patients had interstitial fibrosis. The myocardial specimens of 13 patients were examined by transmission electron microscopy. All showed increased myofibrils, and 9 cases had disorder of myofibrils. All patients had irregular shape of myocardial nucleus, partial depression, mild mitochondrial swelling, fracture and reduction of mitochondrial crest, and local aggregation of myofibrillary interfascicles. One patient had hypertrophy of cardiomyocytes, but the arrangement of muscle fibers was roughly normal. There were vacuoles in the cytoplasm, and Periodic acid-Schiff staining was positive. Transmission electron microscopy showed large range of glycogen deposition in the cytoplasm, with occasional double membrane surround, which was highly indicative of glycogen storage disease. No deposition of glycolipid substance in lysozyme was observed under transmission electron microscope in all myocardial specimens, which could basically eliminate Fabry disease. No apple green substance was found under polarized light after Congo red staining, which could basically exclude cardiac amyloidosis. Conclusion: Myocardium biopsied samples obtained by Liwen procedure of HCM patients are representative and helpful for the etiological diagnosis of HCM.
Biopsy/adverse effects* ; Cardiomegaly/pathology* ; Cardiomyopathy, Hypertrophic/diagnosis* ; Eosine Yellowish-(YS) ; Fibrosis ; Heart Defects, Congenital ; Hematoxylin ; Humans ; Lipofuscin ; Male ; Myocardium/pathology* ; Retrospective Studies

Objective:To investigate the safety and efficacy of echocardiography-guided trans-right-ventricular percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) in a healthy sheep model, and to observe the pathological changes of myocardium in ablation area one year later.Methods:Twelve sheep were divided into PIMSRA group ( n=6) and sham group ( n=6). In PIMSRA group, a radiofrequency (RF) electrode was inserted to the interventricular septum (IVS) with maximum power of 80 Watts for 5 minutes. In the sham group, RF electrode tip was positioned in IVS segment but without the RF power delivery. Electrocardiogram (ECG), echocardiography, myocardial contrast echocardiography(MCE) were performed to assess the efficacy of PIMSRA at postoperative immediately, 2-week, 1-month, 2-month, 3-month, 6-month and 12-month during the follow-up. The following parameters were recorded, including the thickness of ablation area, the systolic wall thickening rate and amplitude of movement of the ablated region, left ventricular outflow tract pressure gradient (LVOT PG), and left ventricular ejection fraction (LVEF), mitral valve early diastolic peak velocity(E), late diastolic peak velocity(A) and the E/A ratio, peak velocity of early diastolic mitral annular motion(E′), peak velocity of late diastolic mitral annular motion(A′), and the E′/A′ ratio.For both groups, the myocardial biomarkers of troponin I, myoglobin and isoenzymes of creatine kinase were tested before the ablation and 3 h after the ablation, and again after 2 weeks. Tissue pathology examinations were performed at the end of study. Results:None of the animals in both groups was observed to have pericardial tamponade during perioperative period.Immediately after the procedure, septal hypokinesis was seen in all PIMSRA group animals, the systolic wall thickening rate and amplitude of movement of the ablated region were significantly decreased ( P<0.001), which was sustained until 12 months.In Sham group, there were no significant differences in the wall thickening rate and amplitude of movement of the operated region(all P>0.05).The thickness of the ablation area in the PIMSRA group was significantly increased immediately after the procedure( P<0.001), decreased to baseline level at 1-week ( P=0.931), and significantly increased at 3-month ( P<0.001).In the Sham group, the IVS thickness was significantly increased immediately after the procedure( P=0.005), decreased to baseline level at 1-week ( P=0.027), then has no further significant changes.There were no significant differences in LVEF, E/A, E′/A′ between PIMSRA and Sham group(all P>0.05).MCE showed the thickness of the ablation area was significantly decreased in the PIMSRA group 12 months after the operation.In both groups, troponin I increased significantly 3 h after the operation(all P<0.005), which decreased to baseline level 2 weeks later(all P>0.05). ECG showed that all the sheep had normal sinus rhythm. Pathological examinations revealed the tissue in the ablation area was fibrotic, having clear boundary with the surrounding normal tissue and no carbonization was observed 1 year later. Conclusions:Echocardiography-guided trans-right-ventricular PIMSRA produced precisely ablated myocardial tissues, reduced the IVS thickness significantly, preserved the global left ventricular function. All the sheep had normal sinus rhythm and without pericardial tamponade in 1 year follow-ups. Echocardiography-guided trans-right-ventricular PIMSRA is a safe and effective minimally invasive treatment for septal reduction therapy.

Objective:To discuss the clinical value of cystatin C (Cys C), serum creatinine (Scr) and serum urea nitrogen (Urea) in the diagnosis of mycoplasma pneumoniae-associated nephritis (MPAN), thus to provide reference basis for MPAN diagnosis.Methods:From June 2015 to June 2017, 50 patients with MPAN who were treated in Women and Children Hospital of Guangdong Province were selected as observation group, and 50 healthy children who underwent physical examination in the hospital during the same period were selected as control group.The observation group was divided into group A, group B and group C according to the level of endogenous creatinine clearance rate.The serum levels of Cys C, Scr and Urea were compared between the control group and the observation group.The levels of Cys C, Scr and Urea and the abnormal rate in group A, group B and group C were compared.Results:In the observation group, the Cys C levels of groups A, B and C were (1.25±0.13)mg/L, (1.74±0.34)mg/L, (3.72±1.33)mg/L, respectively, the Scr levels were (150.46±21.09)μmol/L, (268.57±108.68)μmol/L, (476.66±91.25)μmol/L, respectively, the Urea levels were (8.75±1.09)mmol/L, (11.49±1.50)mmol/L and (17.68±2.92)mmol/L, respectively.In the control group, the Cys C, Scr and Urea levels were (0.74±0.23)mg/L, (56.86±42.36)mol/L, (3.43±1.33)mmol/L, respectively.Compared with the control group, the Cys C level of the observation group was higher, the differences were statistically significant ( t=20.379, 22.991, 13.128, all P<0.05). The Scr level of each group in the observation group were higher than those of the control group, the differences were statistically significant ( t=21.768, 21.423, 43.640, all P<0.05). The Urea level of each group in the observation group was higher than that of the control group, the differences were statistically significant ( t=37.501, 33.404, 46.661, all P<0.05). The levels of Cys C, Scr and Urea in group C were higher than those in group B, the differences were statistically significant ( t=9.737, 9.333, 12.389, all P<0.05). The Cys C, Scr and Urea levels in group C were higher than those in group A, the differences were statistically significant ( t=19.880, 35.753, 27.127, all P<0.05). The Cys C, Scr and Urea levels in group B were higher than those in group A, the differences were statistically significant ( t=13.207, 11.163, 11.177, all P<0.05). In the early stage of renal function injury, namely renal insufficiency compensation stage, the abnormal rate of Cys C(62.07%) was significantly higher than that of Scr and Urea(10.34%, 24.13%). Conclusion:The serum Cys C, Scr and Urea levels of MPAN patients are all higher than healthy people.The more severe the renal function damage is, the higher the serum Cys C, Scr and Urea levels are, which can provide clinical reference for the diagnosis, disease prediction and auxiliary diagnostic criteria of MPAN.In particular, Cys C is more important for the early diagnosis of MPAN.

BACKGROUND AND OBJECTIVES: The differences between electromagnetic-based mapping (EM) and impedance-based mapping (IM) in 3D anatomical reconstruction have not been fully clarified. We aimed to investigate the anatomical accuracy between EM (MediGuide™) and IM (EnSite Velocity™) systems. METHODS: We investigated 15 consecutive patients (10 males, mean age 58±9 years) who underwent pulmonary veins (PVs) isolation for paroxysmal atrial fibrillation (PAF). Contrast-enhanced computed tomography (CT) image of the left atrium (LA) was acquired before ablation and the 3D geometry of the LA was constructed using EM during ablation procedure. We measured the 4 PV angles between the main trunk of each PV and the posterior LA after field scaling. Additionally, the posterior LA surface area was measured. The variables were compared to those of CT-based geometry. A control group of 40 patients who underwent conventional PVs isolation using IM were also evaluated. RESULTS: The actual and relative changes of EM and CT-based geometry in all PV angles and posterior LA were significantly smaller compared to those of IM and CT-based geometry. Intraclass correlation coefficient (ICC) between EM and CT-based geometry were 0.871 (right superior pulmonary vein [RSPV]), 0.887 (right inferior pulmonary vein [RIPV]), 0.853 (left superior pulmonary vein [LSPV]), 0.911 (left inferior pulmonary vein [LIPV]), and 0.833 (posterior LA). On the other hand, ICC between IM and CT-based geometry were 0.548 (RSPV), 0.639 (RIPV), 0.691 (LSPV), 0.706 (LIPV), and 0.568 (posterior LA). CONCLUSIONS: Image integration with EM enables high accurate visualization of cardiac anatomy compared to IM in PAF ablation.
Atrial Fibrillation ; Atrial Flutter ; Catheters ; Fluoroscopy ; Hand ; Heart Atria ; Humans ; Magnets ; Male ; Pulmonary Veins

Objective This study aims to examine the association between leptin and postpartum depression symptoms. Methods Two hundred pregnant women were enrolled and their prenatal serum leptin levels were measured by using enzyme-linked immunosorbent assay (ELISA). The state of depression was first assessed on the third day after delivery and reassessed by a telephone follow up on the 42nd day using the Edinburg postnatal depression scale (EPDS) after delivery. Patients with postpartum depression symptoms with EPDS score ≥13 points after 3 days postpartum or 42 days postpartum were recruited as the depressive symptom group. Results The medians and lower and upper quartiles of the prenatal serum leptin levels in the depressive symptom group (the 3rd day) and the control group were 1.36 (1.15, 1.68) μg/L and 1.49 (1.28, 1.91) μg/L, respectively. After normal conversion, the serum leptin level was significantly lower in the depressive symptom group than in the control group (P=0.021). The medians and lower and upper quartiles of the prenatal serum leptin levels in the depressive symptom group (the 42nd day) and the control group were 1.17 (1.01, 1.36) μg/L and 1.50 (1.29, 1.90) μg/L, respectively. After normal conversion, the serum leptin level was significantly lower in the depressive symptom group than in the control group (P＜0.001). EPDS scores 3 days postpartum (r=-0.199, P=0.014) and 42 days postpartum (r=-0.254, P=0.002) were negatively correlated with prenatal serum leptin levels. Multiple logistic regression analysis showed that the prenatal leptin levels were associated with depressive symptoms at 42 days postpartum (OR=0.026, P=0.001). Conclusion Prenatal serum leptin levels may be associated with postpartum depressive symptoms, and high levels of leptin are protective factors for postpartum depression.

Objective To establish a predictive model for inpatients of cardio-cerebrovascular disease in rural areas of Wugang through time series analysis, and predict the changing trend of cardio-cerebrovascular disease, so as to offer guidance for the health care resources allocation and prevention and control of cardio-cerebrovascular disease. Methods The seasonal autoregressive integrated moving average model (SARIMA) was constructed based on the monthly number of cases of cardio-cerebrovascular disease in rural areas from January 2013 to December 2016 by Stata 14.0 software, and the predictive effect of the model was verified with the monthly number of inpatients of cardio-cerebrovascular disease in 2017. Results The final fitting model of inpatients of cardio-cerebrovascular disease was SARIMA (2, 1, 1)×(0, 1, 0)12. The residual sequence of the model was diagnosed. Results of Ljung-Box Q test showed that the residual sequence was white noise sequence (Q=11.12, P=0.68). In addition, the 2017 forecast was basically consistent with the observations, the overall relative error was around -1.2%. The results showed that the summer was the peak period of cardiovascular and cerebrovascular hospitalization. Conclusion SARIMA model can accurately predict the number of inpatients of cardio-cerebrovascular disease in Wugang, which can provide data support for the hospital administrator to rationally allocate medical resources in the cardiovascular according to the needs of cardio-cerebrovascular treatment in different months.

BACKGROUND AND OBJECTIVES: The differences between electromagnetic-based mapping (EM) and impedance-based mapping (IM) in 3D anatomical reconstruction have not been fully clarified. We aimed to investigate the anatomical accuracy between EM (MediGuide™) and IM (EnSite Velocity™) systems. METHODS: We investigated 15 consecutive patients (10 males, mean age 58±9 years) who underwent pulmonary veins (PVs) isolation for paroxysmal atrial fibrillation (PAF). Contrast-enhanced computed tomography (CT) image of the left atrium (LA) was acquired before ablation and the 3D geometry of the LA was constructed using EM during ablation procedure. We measured the 4 PV angles between the main trunk of each PV and the posterior LA after field scaling. Additionally, the posterior LA surface area was measured. The variables were compared to those of CT-based geometry. A control group of 40 patients who underwent conventional PVs isolation using IM were also evaluated. RESULTS: The actual and relative changes of EM and CT-based geometry in all PV angles and posterior LA were significantly smaller compared to those of IM and CT-based geometry. Intraclass correlation coefficient (ICC) between EM and CT-based geometry were 0.871 (right superior pulmonary vein [RSPV]), 0.887 (right inferior pulmonary vein [RIPV]), 0.853 (left superior pulmonary vein [LSPV]), 0.911 (left inferior pulmonary vein [LIPV]), and 0.833 (posterior LA). On the other hand, ICC between IM and CT-based geometry were 0.548 (RSPV), 0.639 (RIPV), 0.691 (LSPV), 0.706 (LIPV), and 0.568 (posterior LA). CONCLUSIONS Image integration with EM enables high accurate visualization of cardiac anatomy compared to IM in PAF ablation.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is predominantly an inherited cardiomyopathy with typical histopathological characteristics of fibro-fatty infiltration mainly involving the right ventricular (RV) inflow tract, RV outflow tract, and RV apex in the majority of patients. The above pathologic evolution frequently brings patients with ARVD/C to medical attention owing to the manifestation of syncope, sudden cardiac death (SCD), ventricular arrhythmogenesis, or heart failure. To prevent future or recurrent SCD, an implantable cardiac defibrillator (ICD) is highly desirable in patients with ARVD/C who had experienced unexplained syncope, hemodynamically intolerable ventricular tachycardia (VT), ventricular fibrillation, and/or aborted SCD. Notably, the management of frequent ventricular tachyarrhythmias in ARVD/C is challenging, and the use of antiarrhythmic drugs could be unsatisfactory or limited by the unfavorable side effects. Therefore, radiofrequency catheter ablation (RFCA) has been implemented to treat the drug-refractory VT in ARVD/C for decades. However, the initial understanding of the link between fibro-fatty pathogenesis and ventricular arrhythmogenesis in ARVD/C is scarce, the efficacy and prognosis of endocardial RFCA alone were limited and disappointing. The electrophysiologists had broken through this frontier after better illustration of epicardial substrates and broadly application of epicardial approaches in ARVD/C. In recent works of literature, the application of epicardial ablation also successfully results in higher procedural success and decreases VT recurrences in patients with ARVD/C who are refractory to the endocardial approach during long-term follow-up. In this article, we review the important evolution on the delineation of arrhythmogenic substrates, ablation strategies, and ablation outcome of VT in patients with ARVD/C.
Anti-Arrhythmia Agents ; Arrhythmogenic Right Ventricular Dysplasia ; Cardiomyopathies ; Catheter Ablation ; Catheters ; Death, Sudden, Cardiac ; Defibrillators ; Epicardial Mapping ; Follow-Up Studies ; Heart Failure ; Humans ; Prognosis ; Recurrence ; Syncope ; Tachycardia ; Tachycardia, Ventricular ; Ventricular Fibrillation