The clinical effectiveness of sivelestat in treating sepsis patients with both acute respiratory distress syndrome and septic cardiomyopathy.

BACKGROUND: We aimed to assess the efficacy of the neutrophil elastase inhibitor, sivelestat, in the treatment of sepsis-induced acute respiratory distress syndrome (ARDS) and septic cardiomyopathy (SCM). METHODS: Between January 2019 and December 2021, we conducted a randomized trial on patients who had been diagnosed with sepsis-induced acute respiratory distress syndrome (ARDS) and septic cardiomyopathy (SCM) at Wuhan Union Hospital. The patients were divided into two groups by random envelop method, the Sivelestat group and the Control group. We measured the serum concentrations of Interleukin (IL)-6, IL-8, Tumor necrosis factor-α (TNF-α), and High-mobility group box 1 (HMGB1) at five time points, which were the baseline, 12 h, 24 h, 48 h, and 72 h after admission to the ICU. We evaluated the cardiac function by sonography and the heart rate variability (HRV) with 24-hour Holter recording between the time of admission to the intensive care unit (ICU) and 72 h after Sivelestat treatment. RESULTS: From January 2019 to December 2021, a total of 70 patients were included in this study. The levels of IL-6, IL-8, and TNF-α were significantly lower in the Sivelestat group at different time points (12 h, 24 h, 48 h, and 72 h). HMGB1 levels were significantly lower at 72 h after Sivelestat treatment (19.46 ± 2.63pg/mL vs. 21.20 ± 2.03pg/mL, P = 0.003). The stroke volume (SV), tricuspid annular plane systolic excursion (TAPSE), early to late diastolic transmitral flow velocity (E/A), early (e') and late (a') diastoles were significantly low in the Control group compared with the Sivelestat group. Tei index was high in the Control group compared with the Sivelestat group (0.60 ± 0.08 vs. 0.56 ± 0.07, P = 0.029). The result of HRV showed significant differences in standard deviation of normal-to-normal intervals (SDNN), low frequency (LF), and LF/HF (high frequency) between the two groups. CONCLUSIONS: Sivelestat can significantly reduce the levels of serum inflammatory factors, improve cardiac function, and reduce heart rate variability in patients with Sepsis-induced ARDS and SCM.

Effects of Doxorubicin, Epirubicin, and Liposomal Doxorubicin (Anthracycline) on cardiac function in patients with osteosarcoma and their influencing factors.

OBJECTIVE: The objective of this study was to investigate the impact of Doxorubicin, Epirubicin, and Liposomal Doxorubicin (Anthracycline) on cardiac function in osteosarcoma patients and analyze the factors influencing this effect. METHODS: A retrospective study was conducted on 165 osteosarcoma patients admitted to our hospital from January 2020 to December 2022. Based on the chemotherapy regimen, the patients were divided into two groups: the control group (n = 62) treated with Cisplatin and cyclophosphamide, and the observation group (n = 103) treated with Doxorubicin, Epirubicin, and Liposomal Doxorubicin (Anthracycline). The general records of both groups were analyzed, and left ventricular ejection fraction (LVEF) was evaluated through echocardiography before and after chemotherapy. Blood cTnT and CK-MB levels were measured using immunoluminescence. The incidence of adverse reactions during chemotherapy was also analyzed. Univariate analysis was performed to identify patients with cardiotoxic events, and multiple logistic regression analysis was done to study the effects of Doxorubicin, Epirubicin, Liposomal Doxorubicin, and their dosages on cardiotoxicity in patients. RESULTS: The general records between the two groups showed no significant differences (P > 0.05). However, at the fourth cycle of chemotherapy, the observation group exhibited a lower LVEF (P < 0.05), and a higher percentage of LVEF decrease compared to the control group (P < 0.05). Moreover, the observation group had higher levels of blood cTnT and CK-MB (P < 0.05). The incidence of cardiotoxicity in the observation group was also higher (P < 0.05), but no significant differences were seen in other adverse reaction rates (P > 0.05). The occurrence of cardiotoxicity was found to be related to the choice and dosage of chemotherapy drugs (P < 0.05), but not significantly correlated with age, sex, and mediastinal irradiation in patients (P > 0.05). Furthermore, the use of Doxorubicin, Epirubicin, and Liposomal Doxorubicin in chemotherapy, as well as an increase in their dosages, was found to elevate the risk of cardiotoxicity in osteosarcoma patients (P < 0.05). However, age, sex, and mediastinal radiation were not significantly associated with cardiotoxicity in osteosarcoma patients (P > 0.05). CONCLUSION: We demonstrated that Doxorubicin, Epirubicin, Liposomal Doxorubicin (Anthracycline), and other drugs adversely affected cardiac function in osteosarcoma patients, increasing the risk of cardiac toxicity. Therefore, close monitoring of cardiac function during chemotherapy is crucial, and timely adjustments to the chemotherapy regimen are necessary. In addition, rational control of drug selection and dosage is essential to minimize the occurrence of cardiac toxicity.

Short-term study of atrial shunt and improvement of functional mitral regurgitation.

BACKGROUND: This study used an atrial septal shunt to compare the treatment progress and prognosis for patients with heart failure (HF) who have different ejection fractions. METHODS: Twenty HF patients with pulmonary hypertension, who required atrial septal shunt therapy, were included in this study. The patients underwent surgery between December 2012 and December 2020. They were divided into two groups based on their ejection fraction: a group with reduced ejection fraction (HFrEF) and a group with preserved ejection fraction(HFpEF) + mid-range ejection fraction (HfmrEF). Echocardiography was utilized to evaluate parameters such as left ventricular dimension (LVD), left ventricular ejection fraction (LVEF), and left ventricular end-diastolic volume (LVEDV). Hemodynamic parameters were measured using cardiac catheterization. The patient's cardiac function was assessed using the six-minute walking test (6MWT), KCCQ score, NYHA classification, and the degree of functional mitral regurgitation (FMR). Followed-up visits were conducted at 1, 3, and 6 months, and any adverse effects were recorded. RESULTS: The LVEF values were consistently higher in the HFpEF+HFmrEF group than HFrEF group at all periods (P < 0.05). Differences in LVD were observed between the two groups before the surgery. Statistically, significant differences were found at the preoperative stage, 1 month, and 3 months (P < 0.05, respectively). However, the LVEDV showed a significant difference between the two groups only at 3 months (P = 0.049). Notably, there were notable variations in LAPm, LAPs, and the pressure gradient between the LA-RA gradient at baeline, after implantation, and during the 6 months follow-up (all P < 0.05). CONCLUSION: Following treatment, the HFpEF+HFmrEF group exhibited more significant improvements in echocardiographic and cardiac catheterization indices than the HFrEF group. However, there was no statistically significant difference between the two groups regarding the 6MWT and KCCQ scores. It is important to note that the findings of this study still require further investigation in a large sample size of patients.

TranSDFNet: Transformer-Based Truncated Signed Distance Fields for the Shape Design of Removable Partial Denture Clasps.

The ever-growing aging population has led to an increasing need for removable partial dentures (RPDs) since they are typically the least expensive treatment options for partial edentulism. However, the digital design of RPDs remains challenging for dental technicians due to the variety of partially edentulous scenarios and complex combinations of denture components. To accelerate the design of RPDs, we propose a U-shape network incorporated with Transformer blocks to automatically generate RPD clasps, one of the most frequently used RPD components. Unlike existing dental restoration design algorithms, we introduce the voxel-based truncated signed distance field (TSDF) as an intermediate representation, which reduces the sensitivity of the network to resolution and contributes to more smooth reconstruction. Besides, a selective insertion scheme is proposed for solving the memory issue caused by Transformer blocks and enables the algorithm to work well in scenarios with insufficient data. We further design two weighted loss functions to filter out the noisy signals generated from the zero-gradient areas in TSDF. Ablation and comparison studies demonstrate that our algorithm outperforms state-of-the-art reconstruction methods by a large margin and can serve as an intelligent auxiliary in denture design.

The first clinical data of the SAPIEN 3 aortic valve in the treatment of aortic stenosis in China.

Background: Data on outcomes following transcatheter aortic valve replacement with SAPIEN 3 in China is limited as it was approved by the National Medical Products since 2020. The present study was designed to collect clinical data on the SAPIEN 3 aortic valve in Chinese patients with bicuspid aortic valve and tricuspid aortic valve stenosis. Methods: We analyzed the patient characteristics, procedural features and procedural outcomes of the first 438 patients (223 for bicuspid aortic valve and 215 tricuspid aortic valve) from 21 provinces in 74 sites treated with the SAPIEN 3 valve system for transcatheter aortic valve replacement between September 2020 and May 2022. Results: Procedural mortality was 0.7%. 5 cases during the operation were converted to surgery. Among 438 cases, permanent pacemaker implantation was performed in a total of 12 cases (2.7%). The patient had severe leaflet calcification of the aortic valve, with moderate and severe calcification reaching 39.7% and 35.2% respectively. The size of the implanted valves was predominantly 26 mm and 23 mm, reaching 42.5% and 39.5% respectively. The incidence of moderate or severe perivalvular leak in the postoperative period was 0.5%, with a predominance of 90/10 and 80/20 valve deployment height. There was a significant difference in the deployment height of the valve between bicuspid aortic valve and tricuspid aortic valve, with the bicuspid aortic valve having a more deployment height of 90/10. Annulus size in bicuspid aortic valve group was significantly larger than tricuspid aortic valve group. Valve sizing for oversized, within size, and undersized were different between bicuspid aortic valve and tricuspid aortic valve. Conclusions: Procedural success rates were high, with similar and good results for bicuspid aortic valve and tricuspid aortic valve, low perivalvular leak for both valve types, and low permanent pacemaker implantation rates for both valve types. Annulus size, valve sizing and coronary artery height were significantly different in the BAV and TAV group.

Enhancing Mechanical Properties of 3D Printing Metallic Lattice Structure Inspired by Bambusa Emeiensis.

Metallic additive manufacturing process parameters, such as inclination angle and minimum radius, impose constraints on the printable lattice cell configurations in complex components. As a result, their mechanical properties are usually lower than their design values. Meanwhile, due to unavoidable process constraints (e.g., additional support structure), engineering structures filled with various lattice cells usually fail to be printed or cannot achieve the designed mechanical performances. Optimizing the cell configuration and printing process are effective ways to solve these problems, but this is becoming more and more difficult and costly with the increasing demand for properties. Therefore, it is very important to redesign the existing printable lattice structures to improve their mechanical properties. In this paper, inspired by the macro- and meso-structures of bamboo, a bionic lattice structure was partitioned, and the cell rod had a radius gradient, similar to the macro-scale bamboo joint and meso-scale bamboo tube, respectively. Experimental and simulated results showed that this design can significantly enhance the mechanical properties without adding mass and changing the printable cell configuration. Finally, the compression and shear properties of the Bambusa-lattice structure were analyzed. Compared with the original scheme, the bamboo lattice structure design can improve the strength by 1.51 times (ß=1.5). This proposed strategy offers an effective pathway to manipulate the mechanical properties of lattice structures simultaneously, which is useful for practical applications.

ALP Inhibitors Inhibit Inflammatory Responses and Osteoblast Differentiation in hVIC via AKT-ERK Pathways.

Objective: The aim of this study was to explore the calcification process of aortic valve interstitial cells and its potential association with osteogenic differentiation and alkaline phosphatase (ALP) activity. Methods: The study patients were divided into 3 groups: the control group, the osteogenic induction medium (OM) group and the OM+ALP inhibitor group. Cell calcification was measured by alizarin red S staining and alizarin red S dye released by extracellular matrix (ECM) was quantified by spectrophotometry. Immunohistochemical staining was performed on valve tissues of patients harboring calcified and non-calcified aortic valve disease. Expression of bone morphogenetic protein (BMP), runt related transcription factor 2 (RUNX2), osteocalcin and osteopontin (OPN), was evaluated using immunohistochemistry¸and expression of osteogenic specific markers (BMP, RUNX2 and OPN) was detected using Wesern blot analysis. RNA sequencing was analyzed to further study the exact mechanism of ALP inhibitors in terms of inhibiting the osteogenic differentiation of valvular interstitial cells (VIC). The mRNA levels of tumor necrosis factor alpha (TNF-α), Toll-like receptor 4 (TLR4) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3), were detected using reverse-transcription quantitative polymerase chain reaction (RT-qPCR). In addition, Western blot analysis was performed to evaluate the expression of phosphorylated extracellular regulated protein kinases (ERK), nuclear factor κ B inhibitor α (IκBα) and protein kinase B (AKT) in protein. Results: Alizarin red staining was positive in the OM and OM+ALP inhibitor groups, and calcified nodules were formed in VIC, which showed a significant difference compared with the control group (P < .05). The semi-quantitative level of calcification in the OM group was higher than in the control group (P < .05), and the semi-quantitative level of calcification in the OM+ALP inhibitor group was lower than in the OM group (P < .05). ALP staining intensity, ALP activity and messenger RNA (mRNA) levels of BMP, RUNX2, osteocalcin, OPN, ERK, IκBα, AKT, TNF-α, Toll-like receptor 4 (TLR4) and NLRP3 inflammasome (NLRP3) in the OM group were higher than in the control group (P < .05). ALP staining intensity, ALP activity and mRNA expressions of BMP, RUNX2, osteocalcin, OPN, phosphorylated ERK, IκBα, AKT, TNF-α and NLRP3 in the OM+ALP inhibitor group were lower than in the OM group (P < .05). Compared with the control group, 723 genes were upregulated and 248 genes were downregulated in the OM group. Compared with the OM group, 352 genes were upregulated and 586 genes were downregulated in the OM+ALP inhibitor group. Conclusion: We suggest that ALP inhibitors have potential in terms of inhibiting the inflammatory response and osteoblast differentiation of human VIC (hVIC) via the TLR4, AKT, ERK and NLRP3 pathways.

The Clinical Trial Outcomes of Med-Zenith PT-Valve in the Treatment of Patients With Severe Pulmonary Regurgitation.

Objective: Nearly 2/3 of patients with dilated right ventricular outflow tract (RVOT) were excluded from pulmonary valves transplantation due to the lack of size-matched valves. Here, we explored the safety and efficacy of the Med-Zenith PT-Valve for the treatment of patients with severe pulmonary regurgitation. Methods: 22 Patients with severe PR (grade 3+,4+) were enrolled based on the anatomical features of native RVOT and the valve design. The immediate, 3-months and 1-year post-procedural follow-up data were analyzed. Results: The baseline mean systolic diameters in the distal main pulmonary artery (MPA), MPA sinus junction, MPA sinus, pulmonary annulus, RVOT aneurysm and muscular outlet measured with computed tomography were 33.6 ± 6.1, 34.0 ± 5.8, 37.9 ± 6.0, 32.4 ± 7.3, 41.9 ± 9.3, and 34.4 ± 8.0 mm, respectively. The PT-Valve landing zone was set within these levels. Successful valve implantations were achieved in all patients without noticeable device malposition, coronary artery compression, pulmonary branch obstruction or paravalvular leak during follow-ups. Post-procedural pulmonary artery diastolic pressure increased from 5.8 ± 3.1 to 11.3 ± 2.5 mmHg. In the 3-month and 1-year follow-up, the right ventricular end diastolic volume index reduced from the baseline 181.6 ± 29.0 to 143.7 ± 29.7 ml/m2 and 123.4 ± 31.2 ml/m2, and the trans-pulmonary valve gradient decreased from 25.6 ± 22.2 to 10.64 ± 3.54 mmHg and 11.16 ± 3.0 mmHg, respectively. The 6-min walk distance increased from 416.6 ± 97.9 to 455.9 ± 64.6 m and 467.8 ± 61.2 m, respectively. Conclusion: This clinical trial revealed favorable outcomes for the safety, efficacy and feasibility of the Med-Zenith PT-Valve in the treatment of severe PR with significantly enlarged RVOT.

Highly Potent, Selective, Biostable, and Cell-Permeable Cyclic d-Peptide for Dual-Targeting Therapy of Lung Cancer.

The application of peptide drugs in cancer therapy is impeded by their poor biostability and weak cell permeability. Therefore, it is imperative to find biostable and cell-permeable peptide drugs for cancer treatment. Here, we identified a potent, selective, biostable, and cell-permeable cyclic d-peptide, NKTP-3, that targets NRP1 and KRASG12D using structure-based virtual screening. NKTP-3 exhibited strong biostability and cellular uptake ability. Importantly, it significantly inhibited the growth of A427 cells with the KRASG12D mutation. Moreover, NKTP-3 showed strong antitumor activity against A427 cell-derived xenograft and KRASG12D-driven primary lung cancer models without obvious toxicity. This study demonstrates that the dual NRP1/KRASG12D-targeting cyclic d-peptide NKTP-3 may be used as a potential chemotherapeutic agent for KRASG12D-driven lung cancer treatment.

Haemodynamic changes of interatrial shunting devices for heart failure: a systematic review and meta-analysis.

AIMS: To assess the efficacy and safety, primarily in relation to the haemodynamic effects, of interatrial shunting devices (ISD) for the treatment of heart failure (HF), we conducted a systematic review and a meta-analysis. METHODS AND RESULTS: We used the MEDLINE, Cochrane Library, Embase, and PubMed databases to identify clinical studies (published to 4 August 2021) that evaluated the effect of ISD on HF. The primary endpoint was defined as changes in pulmonary capillary wedge pressure (PCWP). Secondary endpoints included (i) other haemodynamic indexes, including cardiac output (CO), right atrial pressure (RAP), and mean pulmonary artery pressure (mPAP) by right heart catheterization, and (ii) change from baseline in 6 min walk distance (6MWD). After a literature search and detailed evaluation, six trials enrolling a total of 203 individuals were included in the quantitative analysis. Pooled analyses showed that after ISD implantation, PCWP decreased by a mean 3.10 mmHg [95% confidence interval (CI) -4.56 to -1.64; I2  = 0%; P < 0.0001]. Overall, CO increased by 0.77 L/min (95% CI 0.02 to 1.52; P = 0.04; I2  = 82%), but there were no significant changes in RAP or mPAP. The mean 6MWD increased by 32.33 m (95% CI 10.74 to 53.92; P = 0.003; I2  = 0) after ISD implantation. CONCLUSIONS: Interatrial shunting device can effectively reduce PCWP, increase CO and 6MWD, and has no obvious adverse effects on the right heart and pulmonary pressure. Studies with larger sample size and longer follow-up time are needed for further verification.

Clinical study on the treatment of chronic heart failure with a novel D-shant atrium shunt device.

BACKGROUND: Atrial septal shunt devices might improve hospitalizations and also prognosis in heart failure with increased pulmonary pressures due to left heart diseases. In recent years, atrial shunt devices have been used for the treatment of chronic heart failure, but there remains a lack of clinical experience. This study aimed to analyse the therapeutic effect of a novel type of atrial shunt on chronic heart failure. METHODS AND RESULTS: From May 2020 to September 2020, six patients who were diagnosed with chronic heart failure and completed percutaneous D-shant atrium shunt device implantation in the Department of Cardiovascular Surgery, Union Hospital, were retrospectively included. The shunt location was evaluated by echocardiography and digital subtraction angiography. Heart function was evaluated by New York Heart Association functional class. Echocardiography was used to measure the diameter of the new chamber and ventricle, and to evaluate the degree of mitral and tricuspid regurgitation. Before operation and 6 months after operation, left atrial end-diastolic volume, right atrial end-diastolic volume, left ventricular end-diastolic volume, and right ventricular end-diastolic volume were measured by magnetic resonance imaging. Left ventricular ejection fractions and right ventricular ejection fractions were calculated. Haemodynamic indexes of right heart catheterization and clinical cardiac function indexes were collected and compared before and 6 months after shunt implantation. All six patients completed percutaneous shunt device implantation. Echocardiography and digital subtraction angiography showed that the shunt device was correctly positioned and unobstructed in all patients. Echocardiography revealed that the left ventricular diameter decreased significantly from 6.40 ± 0.57 mm to 5.03 ± 0.73 mm (P < 0.05). There was an obvious decrease in mitral regurgitation. Magnetic resonance imaging showed a reduction in the volume of the left ventricle (182.00 ± 27.02 mL vs. 125.75 ± 16.11 mL, P < 0.05). Cardiac catheter examination showed the mean left atrium pressure or pulmonary capillary wedge pressure decreased postoperatively (31.83 ± 11.55 vs. 18.00 ± 5.51 mmHg, P < 0.05). There was also obvious improvement in clinical indicators of cardiac function at 6 months after implantation. CONCLUSIONS: This novel D-shant atrium shunt device revealed maintained good function, no dislodgement and no paradoxical emboli. After implantation, functional mitral regurgitation in all patients with heart failure with reduced ejection fraction improved.

Mechanism of CircANKRD36 regulating cell heterogeneity and endothelial mesenchymal transition in aortic valve stromal cells by regulating miR-599 and TGF-ß signaling pathway.

OBJECTIVE: To explore the mechanism of CircANKRD36 regulating cell heterogeneity and endothelial mesenchymal transition in aortic valve stromal cells by regulating miR-599 and TGF-ß signaling pathway. METHODS: Human tissue specimens were divided into Control group (n = 25) and CAVD group (n = 25). The mRNA expressions of CircANKRD36 and miR-599 in tissue samples were analyzed by qRT-PCR. Western blot was used to analyze the protein expression of osteogenic differentiation related factors induced by OM.The expressions of ALP, osteocalcin, osteopontin, Runx2 and Cadherin11 were detected by Western blot. RESULTS: The expression of CircANKRD36mRNA in CAVD tissue was lower than that in Control tissue (P < 0.05), and the expression of miR-599mRNA in CAVD tissue was higher than that in Control tissue (P < 0.05). CircANKRD36 was negatively correlated with ALP, osteocalcin, osteopontin, Runx2, Cadherin11 expression level after OM induced osteogenic differentiation. The expression level of miR-599 was positively correlated with ALP, osteocalcin, osteopontin, Runx2 and Cadherin11 after OM induced osteogenic differentiation.The expression of ALP, osteocalcin, osteopontin, Runx2 and Cadherin11 protein in circ+miR-599 group was lower than that in circ+miR-NC group (P < 0.05). Compared with Vector+miR-NC group, the protein expressions of TGF-ß1, TGF-ß2 and SMAD4 in circ+miR-NC group decreased (P < 0.05), while the protein expressions of TGF-ß1, TGF-ß2 and SMAD4 in circ+miR-599 group increased (P < 0.05). CONCLUSION: CircANKRD36 can inhibit the expression of miR-599 and the activation of TGF-ß signaling pathway, thus inhibiting the expression of differentiation-related factors of VIC osteogenesis and the formation of calcified nodules. Therefore, circANKRD36-miR-599-TGF-ß axis can be a new theoretical basis for treating CAVD.

Design of a defined grain distribution brazed diamond grinding wheel for ultrasonic assisted grinding and experimental verification.

Ultrasonic assisted grinding (UAG) is a promising manufacturing technology in processing hard and brittle materials, mostly due to its excellent machining performance. In UAG, improvements in grain trajectory interactions and overlapping stemming from kinematic characteristics were identified as the main reasons for reduced grinding forces and improved processing quality. However, in existing studies, the grinding wheels with disordered abrasive grain distributions and irregular grain protrusion heights were generally used. Consequently, it is difficult to control both the interactions between grain trajectories and overlapping. Aiming to solve this problem, a brazed diamond grinding wheel with defined grain distribution was proposed in this study. The grinding wheel matrix was designed using finite element analysis, while abrasive grain distribution was obtained by kinematic analysis of UAG. Finally, the grinding wheel was prepared using brazing technology and to verify its grinding performance, an electroplated grinding wheel with the identic matrix and abrasive grain size was prepared. Morphology analysis of both grinding wheels has shown that compared to the electroplated grinding wheel, the brazed one has both higher and more uniform grain protrusion height. In the next step, UAG and CG experiments were carried out using the brazed and electroplated grinding wheel. The effects of grain distribution and grinding parameters on the grinding force, force ratio, surface profile wave, and surface roughness were studied. The results have shown that in similar operating conditions the brazed grinding wheel produced smaller grinding force, force ratio, smoother ground surface, and lower surface roughness compared to the electroplated grinding wheel. Additionally, for both grinding wheels, the UAG reduced grinding force, force ratio, surface roughness, and profile wave height. However, it also caused a more extensive ultrasonic vibration effect on grinding compared to the electroplated grinding wheel; its reduction percentage in grinding force was larger, while surface roughness and average height difference for UAG were higher compared to CG.

Evaluation of pulmonary arterial pressure in patients with connective tissue disease-associated pulmonary arterial hypertension by myocardial perfusion imaging.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a complex and severe complication of connective tissue disease (CTD). We aimed to evaluate the application value of myocardial perfusion imaging (MPI) in evaluating CTD-associated PAH (CTD-PAH). METHODS: We retrospectively included 88 patients who were diagnosed with CTD between January 2018 and December 2020 at our hospital. Fifty-eight patients had PAH and were included into the CTD-PAH group. Thirty patients without PAH were included in the control group. All patients received routine physical examination, biochemical tests and cardiac function evaluation, right heart catheterization (RHC), and 99m Tc-MIBI MPI. PAH patients were divided into the mild, moderate, and severe PAH group according to their mean pulmonary artery pressures by RHC. Pearson correlation analysis was used to calculate the correlation between the right ventricle target/background (T/B) and right ventricle stroke volume (RV-SV), total pulmonary resistance (TPR), pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), 6-minute walk distance (6-MWD), and N-terminal B-type natriuretic peptide (NT-proBNP). The ROC curves of T/B and pulmonary artery pressure classification were plotted and the sensitivity and specificity of T/B in diagnosing PAH of different severities were analyzed. RESULTS: The analysis of correlation revealed that T/B correlated negatively with 6-MWD and positively with NT-proBNP and exhibited good positive correlation with mPAP, TPR, and PVR by RHC and negative correlation with RV-SV. T/B was of the most diagnostic value for severe PAH, and its correlation with severe PAH was stronger than that with mild PAH and moderate PAH. CONCLUSIONS: Target/background is a noninvasive method that can simultaneously evaluate pulmonary arterial pressure and myocardial perfusion of CTD-CHD patients and is particularly of relatively high value for severe PAH patients.

Right ventricular contractility as a potential independent evaluation parameter in pulmonary hypertension.

BACKGROUND: Pulmonary artery hypertension (PAH) is a common disease with high disability and mortality rates, and can lead to right heart failure. We aimed to evaluate the capability of right ventricular pressure-volume coupling parameters, end-systolic elastance (Ees), right ventricular afterload (Ea), and arterial elastance (Ees/Ea) for assessing right ventricular performance during the chronic development of PAH. METHODS: Thirty-six PAH patients were enrolled in this study. We reported the cutoff values of the right ventricular pressure-volume coupling parameters in the progression of PAH and their relations with other pressure-volume loop measurements in both the right and left ventricles. RESULTS: Ees and normalised Ees (Ees/Ea) calculated from the pressure method performed better than ones from the volume method in correlation with mean pulmonary arterial pressure and mean right arterial pressure. The cutoff sets of Ees and Ees/Ea were capable of grouping pulmonary hypertension patients which were well supported by their significant correlation with several key right ventricular hemodynamic parameters. Additionally, the normalised Ees was able to reflect the changes in left ventricular function during the deterioration of PAH. CONCLUSION: Ees and Ees/Ea are promising independent reference parameters for assessing ventricular function in progressing PAH patients.

Multiple adsorption properties of aptamers on metal-organic frameworks for nucleic acid assay.

Enrichment and detection of circulating free nucleic acids in biological samples have gained great attention for disease diagnosis or prognostic evaluation. Nanoscale metal-organic frameworks (NMOFs) have been used for aptamer-based nucleic acid sensing. In this work, different NMOFs, including ZIF-8, MIL-88, MIL-100, MIL-101, as well as Eu-TDA and Tb-TDA [prepared by the coordination of 2,2'-thiodiacetic acid (TDA) and Eu3+ or Tb3+], were investigated in nucleic acid sensing by employing their aptamer adsorption ability and fluorescence quenching capacity for the labeled dyes. Two types of dye aptamer, FAM-labeled aptamer (FAM-Ap) and TexasRedaptamer (TexasRed-Ap) were designed, and their adsorption properties on NMOFs-were compared. It was found that the TexasRed-Ap can be well used for nucleic acid (miR-21) extraction and sensing by linking with a pH-responsive nucleotide chain (TexasRed-Ap-pH) or with an additional random chain ssDNA-1' (TexasRed-Ap-a). After interacted with the target miR-21 in biosamples, the TexasRed-dsDNA + NMOFs composites can be collected, and the formed TexasRed-dsDNA can be released by changing pH value or addition of ssDNA-1, which is matched with ssDNA-1'. A linear relationship from 0.1 to 200 pM for miR-21 detection was obtained. The results show that the NMOFs can be used as promising platforms for nucleic acid extraction and fluorescent sensing.

Colorable Zeolitic Imidazolate Frameworks for Colorimetric Detection of Biomolecules.

We report a series of colorable zeolitic imidazolate framework (ZIF)-based nanomaterials prepared by encapsulating starches (amylopectin, dextrin, or amylose) or tannic acid in the frameworks of ZIFs and first applied them in colorimetric assay of microRNA/DNA by adding I2/KI or FeCl3 solutions as chromogenic reagents. We found that iodine molecules can lead to rapid degradation of the ZIF-8 framework, while ZIF-90 remains stable. Therefore, ZIF-90 was selected for encapsulating the starches or tannic acid, and then assembled with polyethylenimine (PEI) and aptamers of microRNA/DNA. After interacting with the target microRNA/DNA, the aptamers (Ap) move away from the surface of the prepared Ap-starch@ZIF-90 or Ap-tan@ZIF-90, and the I2/KI or FeCl3 solution is added into the system to interact the starches (amylopectin, dextrin, or amylose) or tannic acid to generate different colors. According to the absorbance spectra, good linear correlations between the logarithm of absorbance intensity and the concentration of microRNA (1-180 nM) can be observed, and the naked eye can distinguish the change from ∼60 to ∼180 nM with a concentration gradient of 20 nM. A similar colorimetric assay ability for pathogenic bacteria can also be realized by detecting the gene fragments IS200 and eaeA. The detection limits can be potentially optimized by changing the amount of adsorbed PEI and aptamers on the surface of Ap-starch@ZIF-90 (or Ap-tan@ZIF-90) nanoparticles. This method could be a promising alternative for simple and cost-effective assay of microRNA/DNA.

An Infectious Pseudoaneurysm Caused by Ventricular Septal Defect Occluder in Patent Ductus Arteriosus Closure in a Two-Year-Old Child.

We present a case of an infectious pseudoaneurysm after patent ductus arteriosus (PDA) closure with a ventricular septal defect (VSD) occluder in a two-year-old child. The aneurysm grew rapidly but was successfully removed in time and the patient survived. To our knowledge, this is the first report of an infectious pseudoaneurysm caused by VSD occluder in PDA closure.