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Abstract Gliomas represent a highly aggressive class of tumors located in the brain. Despite the availability of multiple treatment modalities, the prognosis for patients diagnosed with glioma remains unfavorable. Therefore, further exploration of new biomarkers is crucial to enhance the prognostic assessment of glioma and to investigate more effective treatment options. In this research, we utilized multiple machine learning techniques to assess the significance of genes related to angiogenesis and epithelial-mesenchymal transition (EMT) in the context of prognosis and treatment for glioma patients. The random forest algorithm highlighted the significance of CALU, and further analysis indicated that the effect of CALU on glioma progression may be regulated by MYC. Different machine learning approaches were employed in our investigation to uncover crucial genes associated with angiogenesis and EMT in glioma. Our findings verify the connection between these genes and the prognosis of patients with glioma, as well as the results of immunotherapeutic interventions. Notably, through experimental verification, we identified CALU as a new prognostic marker for glioma, and inhibiting the expression of CALU can impede the progression of glioma.

Abstract Background Pulmonary arterial hypertension is a major cause of death in systemic lupus erythematosus, but there are no tools specialized for predicting survival in systemic lupus erythematosus-associated pulmonary arterial hypertension. Research question To develop a practical model for predicting long-term prognosis in patients with systemic lupus erythematosus-associated pulmonary arterial hypertension. Methods A prognostic model was developed from a multicenter, longitudinal national cohort of consecutively evaluated patients with systemic lupus erythematosus-associated pulmonary arterial hypertension. The study was conducted between November 2006 and February 2020. All-cause death was defined as the endpoint. Cox regression and least absolute shrinkage and selection operators were used to fit the model. Internal validation of the model was assessed by discrimination and calibration using bootstrapping. Results Of 310 patients included in the study, 81 (26.1%) died within a median follow-up of 5.94 years (interquartile range 4.67–7.46). The final prognostic model included eight variables: modified World Health Organization functional class, 6-min walking distance, pulmonary vascular resistance, estimated glomerular filtration rate, thrombocytopenia, mild interstitial lung disease, N-terminal pro-brain natriuretic peptide/brain natriuretic peptide level, and direct bilirubin level. A 5-year death probability predictive algorithm was established and validated using the C-index (0.77) and a satisfactory calibration curve. Risk stratification was performed based on the predicted probability to improve clinical decision-making. Conclusions This new risk stratification model for systemic lupus erythematosus-associated pulmonary arterial hypertension may provide individualized prognostic probability using readily obtained clinical risk factors. External validation is required to demonstrate the accuracy of this model's predictions in diverse patient populations.

A case of immune checkpoint inhibitors (ICIs)-associated myocarditis with reversible advanced atrioventricular block (AVB) was reported. We innovatively used active fixation lead connected to an external device for prolonged temporary pacing until atrioventricular conduction recovered. Invasive electrophysiology studies were performed to evaluate atrioventricular conduction in detail. Long-term follow-up for nearly 120-days and repeated long-term electrocardiography was conducted to ensure the conduction system was truly recovered.

IntroductionAmyloid light-chain cardiac amyloidosis is a progressive infiltrative disease characterized by the deposition of amyloid fibrils in the cardiac tissue, which can cause serious atrioventricular block requiring pacemaker implantation. Left bundle branch pacing has emerged as an alternative method for delivering physiological pacing to achieve electrical synchrony of the left ventricle. However, left bundle branch pacing in patients with amyloid light-chain cardiac amyloidosis has not been studied in detail. Therefore, in this study, we present a case of left bundle branch pacing in a patient with amyloid light-chain cardiac amyloidosis.Case summaryA 66-year-old male patient with amyloid light-chain cardiac amyloidosis presented with syncope for 1 month. Holter monitoring revealed intermittent third-degree atrioventricular block. Left bundle branch pacing was performed successfully. During the 1-year follow-up, it was observed that the left bundle branch capture threshold remained stable without any pacemaker-related complications or left ventricle systolic dysfunction, and there was no recurrence of syncope.ConclusionLeft bundle branch pacing appears to be a safe and feasible option for patients with amyloid light-chain cardiac amyloidosis experiencing atrioventricular block.

ObjectiveThe aim of this study is to identify risk factors of intra-cystic hemorrhage in microwave ablation of mixed solid and cystic microwave ablation s, and to design a preoperative nomogram to predict the risk value of intraoperative bleeding with the goal of individualizing the surgical approach toward different types of cystic and solid thyroid nodules.MethodsA total of 241 patients with cystic-solid thyroid nodules who underwent ultrasound-guided percutaneous microwave ablation were retrospectively divided into a bleeding group and a non-bleeding group to compare the diameter, cystic proportion, cystic fluid nature, color Doppler flow imaging, Contrast-enhanced ultrasound (CEUS) findings, and operative methods. Based on univariate and multivariate analysis, the important risk factors of nodular intracapsular hemorrhage in the ablation procedure were projected to a nomogram for predicting the possibility of intraoperative hemorrhage in the thyroid cystic solid nodules.ResultsIntra-cystic hemorrhage was developed in 37 cases during the ablation of mixed thyroid nodules with a total incidence of 15% (37/241). Significant differences were found statistically between the two groups on the diameter of the lesions, CEUS findings, the cystic fluid ratio, and operative methods (P = 0.000, P = 0.001, P = 0.024, P = 0.002). The possibility of intraoperative nodular intracapsular hemorrhage was predicted by the model based on the risk factors with the accuracy of 81% and prediction consistency index (C-index) of 0.78.ConclusionA new and efficient prediction model was developed based on the identified risk factors for intracapsular hemorrhage during microwave ablation of mixed thyroid nodules, which will aid in the development of targeted surgical planning for different types of cystic thyroid nodules, thus reducing the risk of hemorrhage during ablation.

Background: Low-voltage zones (LVZ) are surrogate markers for cardiac fibrosis, which contribute to the maintenance of atrial fibrillation (AF). The aim of this study was to investigate the effect of the distribution of left atrial (LA) LVZ on the outcome following catheter ablation. Methods: This retrospective study enrolled patients with AF who underwent initial catheter ablation. LVZ were defined as areas with bipolar voltage amplitude 30 s after the initial catheter ablation. Results: Altogether, 148 patients were included, with a mean age of 61 ± 11 years, of which 53 (35.8%) had persistent AF. During a mean follow-up of 14 ± 3 months post-ablation, AA recurrence occurred in 25 (16.9%) patients after the initial catheter ablation. Kaplan–Meier analysis showed that patients without roof LVZ had a higher AA-free survival rate than those with roof LVZ (P = 0.047). In the multivariate Cox regression analysis, the proportion of LA LVZ ≥6% [hazard ratio (HR) 2.315, 95% confidence interval (CI) 1.048–5.114; P = 0.038] and a longer AF duration (HR 1.008, 95% CI 1.002–1.014; P = 0.006) were independent predictors of AA recurrence. Conclusions: In patients with AF, LA roof LVZ may increase the risk of AA recurrence after initial catheter ablation.

Abstract Backgrounds The EmPHasis-10 questionnaire is a disease-specific quality of life (QoL) measurement in patients with pulmonary hypertension. We report the results of cross-cultural validation of the Chinese version of the EmPHasis-10 and its relationship with risk stratification in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH). Methods The Emphasis-10 was administered to 75 CTD-PAH patients along with the 36-item Medical Outcomes Study Short Form Survey (SF-36) and EuroQol five dimensions questionnaire (EQ-5D). The diagnosis of PAH was confirmed by right heart catheterization. Demographic and clinical data were obtained. Multivariable logistic regression was conducted based on the low risk profile assessed by a 4-strata risk assessment model (COMPERA 2.0) at follow-up. Results Date from 75 patients with CTD-PAH were analysed. The EmPHasis-10 demonstrated satisfactory reliability (Cronbach α = 0.95) and convergent validity showed by the significant relationship with WHO Functional Class (P = 0.003), SF-36 (P

BackgroundBy the end of 2022, more than 100 million people were infected with COVID-19 in the United States, and the cumulative death rate in rural areas (383.5/100,000) was much higher than in urban areas (280.1/100,000). As the pandemic spread, people used social media platforms to express their opinions and concerns about COVID-19–related topics. ObjectiveThis study aimed to (1) identify the primary COVID-19–related topics in the contiguous United States communicated over Twitter and (2) compare the sentiments urban and rural users expressed about these topics. MethodsWe collected tweets containing geolocation data from May 2020 to January 2022 in the contiguous United States. We relied on the tweets’ geolocations to determine if their authors were in an urban or rural setting. We trained multiple word2vec models with several corpora of tweets based on geospatial and timing information. Using a word2vec model built on all tweets, we identified hashtags relevant to COVID-19 and performed hashtag clustering to obtain related topics. We then ran an inference analysis for urban and rural sentiments with respect to the topics based on the similarity between topic hashtags and opinion adjectives in the corresponding urban and rural word2vec models. Finally, we analyzed the temporal trend in sentiments using monthly word2vec models. ResultsWe created a corpus of 407 million tweets, 350 million (86%) of which were posted by users in urban areas, while 18 million (4.4%) were posted by users in rural areas. There were 2666 hashtags related to COVID-19, which clustered into 20 topics. Rural users expressed stronger negative sentiments than urban users about COVID-19 prevention strategies and vaccination (P

Abstract Growth‐differentiation factor (GDF)‐15 is a member of transforming growth factor‐β‐related cytokine and may respond to right ventricular overload. The objective of this article was to assess the diagnosis and prognostic value of GDF‐15 in systemic lupus erythematosus‐associated pulmonary arterial hypertension (SLE‐PAH). Serum samples were obtained from 65 patients with SLE‐PAH, 51 sex and age matched patients of SLE without PAH (SLE‐non‐PAH), and 32 healthy controls. Serum GDF‐15 level was detected by enzyme‐linked immunosorbent assay and the optimal cut‐off point was determined by receiver operating characteristic curve. The primary end‐point was death from any cause and the secondary end‐point was target goal achievement (TGA). Cox regression analyses and Kaplan−Meier method were performed to identify the prognostic value of GDF‐15. Serum GDF‐15 levels were significantly higher in SLE‐PAH patients (1112.14 ± 781.80 pg/mL) than SLE‐non‐PAH patients (810 ± 408 pg/mL) and healthy controls (442 ± 139 pg/mL) at baseline. The optimal cut‐off value of GDF‐15 in the diagnosis of SLE‐PAH was 733 pg/mL (AUC = 0.84). In patients with SLE‐PAH, GDF‐15 level was associated with 6 min walking distance (ρ = −0.385, p = 0.017) and higher serum N terminal‐pro brain natriuretic peptide (NT‐proBNP) (ρ = 0.605, p 733 pg/mL were more likely to death (adjusted hazard ratio [HR] = 4.01, 95% confidence intervals [CI]: 1.23−6.27, p = 0.041) and less likely to achieve treatment goal (adjusted HR = 0.57, 95% CI: 0.23−0.79, p = 0.028). In addition, patients with simultaneous elevation of GDF‐15 and NT‐proBNP showed lower proportion of TGA (p = 0.046). In conclusion, GDF‐15 is a new and promising biomarker of development and prognosis in SLE‐PAH. The combination of GDF‐15 and NT‐proBNP may provide more accurate prognostic information.

BackgroundColorectal cancer is a common malignancy of the gastrointestinal tract, and its incidence and mortality rates have increased in recent years. RNF128 is an E3 ubiquitin ligase that plays an important role as a suppressor gene or oncogene in various cancers, but its mechanism in colorectal cancer is not yet clear. The aim of this study was to investigate the role and mechanism of RNF128 in colorectal cancer.MethodsThe expression of RNF128 in colorectal cancer tissues was assessed by immunohistochemistry and western blotting. The proliferation ability of colorectal cancer cells was measured by colony formation assay and CCK-8 assay, the migration and invasion ability of colorectal cancer cells was measured by wound healing assay and transwell assay, and the protein expression levels of the Hippo signaling pathway and its target gene were examined by western blotting. Immunoprecipitation was used to assess the interaction of RNF128 with MST. In vivo, a xenograft tumor model was used to detect the effect of RNF128 on tumor growth.ResultsAt the tissue level, the expression level of RNF128 was significantly higher in colorectal cancer tissues than in adjacent normal tissues. In LoVo cells and HCT116 cells, the proliferation, migration and invasion abilities were significantly reduced with RNF128 knockdown. At the protein level, knockdown of RNF128 resulted in significant activation of the Hippo signaling pathway. In vivo experiments, the volume and weight of xenograft tumors in nude mice were significantly decreased compared with those in the normal control group with RNF128 knockdown.ConclusionRNF128 promotes the malignant behaviors of colorectal cancer cells by inhibiting the Hippo signaling pathway, which may provide a new target for colorectal cancer prevention and treatment.

Background and objectivesOsteogenesis imperfecta (OI) is a rare disorder of abnormal production or modification of type I collagen, which is caused by mutations in COL1A1, COL1A2 or other genes. We investigate the cardiac abnormalities and its correlation with pathogenic mutations in OI children.MethodsA cross-sectional comparative study was completed in a relatively large sample of OI children, who were matched in body surface area (BSA) with healthy controls. All echocardiography was performed by experienced cardiologists using Vivid 7 equipment (GE Medical Systems, Horton, Norway). The resting standard 12-lead electrocardiogram (ECG) were obtained in OI patients by FX-8600 machine. Skeletal phenotypes of OI patients were evaluated, including information of bone fractures, deformities, motility, and bone mineral density (BMD). Pathogenic mutations of OI were detected by a next-generation sequencing panel and confirmed by Sanger sequencing.ResultsA total of 69 OI children and 42 healthy children matched in BSA were enrolled. Abnormalities of echocardiography were found in 6 OI children, including enlarged left atrium (n=5), increased internal diameter of the left ventricle (n=1), who all carried the COL1A1 mutation. Mild regurgitation of mitral or tricuspid valves was observed in 26 OI patients. Abnormal ECG manifestations were found in 8 OI children, including deep Q wave, T wave change, premature ventricular complexes, short P-R interval, incomplete bundle branch block and high voltage of left ventricular. Compared with healthy controls, OI children had significant larger values in the main pulmonary artery (1.84 vs 1.60 cm, P < 0.01), left atrial diameter (2.58 vs 2.11 cm, P < 0.001), left ventricular internal dimension at end-diastolic (LVEDd) (3.85 vs 3.50 cm, P < 0.05) and lower left ventricular ejection fraction (LVEF) (68.40% vs 71.74%, P < 0.01). Moreover, OI patients with COL1A1 mutation tended to have greater main pulmonary artery, larger diameters of left atrial and LVEDd, and lower LVEF than healthy controls. COL1A1 mutation was correlated to dilated MPA (β = 1.557, P < 0.01), LAD (β = 3.915, P < 0.001), and LVEDd (β = 2.714, P < 0.01), and decreased LVEF (β = -3.249, P < 0.01).ConclusionsCardiovascular alterations were identified in OI children, including increased dimensions of the main pulmonary artery and left chamber, and low LVEF. The cardiovascular abnormalities seemed to be correlated to COL1A1 mutation and defects of type I collagen, which expanded our understandings of the cardiac phenotypes of OI children.

BackgroundAs direct-to-consumer genetic testing services have grown in popularity, the public has increasingly relied upon online forums to discuss and share their test results. Initially, users did so anonymously, but more recently, they have included face images when discussing their results. Various studies have shown that sharing images on social media tends to elicit more replies. However, users who do this forgo their privacy. When these images truthfully represent a user, they have the potential to disclose that user’s identity. ObjectiveThis study investigates the face image sharing behavior of direct-to-consumer genetic testing users in an online environment to determine if there exists an association between face image sharing and the attention received from other users. MethodsThis study focused on r/23andme, a subreddit dedicated to discussing direct-to-consumer genetic testing results and their implications. We applied natural language processing to infer the themes associated with posts that included a face image. We applied a regression analysis to characterize the association between the attention that a post received, in terms of the number of comments, the karma score (defined as the number of upvotes minus the number of downvotes), and whether the post contained a face image. ResultsWe collected over 15,000 posts from the r/23andme subreddit, published between 2012 and 2020. Face image posting began in late 2019 and grew rapidly, with over 800 individuals revealing their faces by early 2020. The topics in posts including a face were primarily about sharing, discussing ancestry composition, or sharing family reunion photos with relatives discovered via direct-to-consumer genetic testing. On average, posts including a face image received 60% (5/8) more comments and had karma scores 2.4 times higher than other posts. ConclusionsDirect-to-consumer genetic testing consumers in the r/23andme subreddit are increasingly posting face images and testing reports on social platforms. The association between face image posting and a greater level of attention suggests that people are forgoing their privacy in exchange for attention from others. To mitigate this risk, platform organizers and moderators could inform users about the risk of posting face images in a direct, explicit manner to make it clear that their privacy may be compromised if personal images are shared.

ObjectivesStudies concerning myocardial involvement (MI) in patients with anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis/clinically amyopathic dermatomyositis (anti-MDA5 Ab+ DM/CADM) are scarce. We aimed to characterize MI in our anti-MDA5 Ab+ DM/CADM cohort and to investigate its association with prognosis.MethodsIn this single-center retrospective study, anti-MDA5 Ab+ hospitalized DM/CADM patients who underwent transthoracic echocardiography (TTE) were enrolled. Myocardial involvement was diagnosed according to abnormal cardiac structure and function detected by TEE. Clinical features and cardiac examination findings of patients with MI were analyzed. Clinical features, laboratory findings, complications, and treatments were compared between MI and non-MI, deceased, and survival patients. Logistic regression analysis was used to explore the independent risk factors for the occurrence of MI and prognostic factors for these patients.ResultsSeventy-six hospitalized patients with anti-MDA5 Ab+ DM/CADM were enrolled. Twelve (15.8%) patients were diagnosed with MI. Of the 12 patients, three underwent cardiac magnetic resonance imaging (CMR) and late gadolinium enhancement (LGE) were noted for them. TEE revealed that eight (66.7%) patients had left atrial and/or ventricular enlargement, three (25.0%) had cardiac hypertrophy, six (50.0%) had diffuse ventricular wall dyskinesia, and seven (58.3%) had diastolic dysfunction. Six (50.0%) patients with MI developed heart failure (HF) during treatment. Of the 12 patients, one patient died of HF caused by myocarditis, three died of infection, and four died of exacerbation of rapidly progressive interstitial lung disease (RP-ILD). Logistic regression analysis revealed that dysphagia (OR 3.923, 95% CI 1.085, 14.181), NT-proBNP >600 pg/ml (OR 18.333, 95% CI 1.508, 222.875), and increased peripheral white blood cells (OR 1.201, 95% CI 1.003, 1.438) were risk factors for the occurrence of MI, but plasma albumin (OR 0.892, 95% CI 0.796, 0.999) was a protective factor. Both MI (OR 5.984, 95% CI 1.174, 30.496) and RP-ILD (OR 11.875, 95% CI 2.796, 50.411) were independent risk factors for the mortality of these anti-MDA5 Ab+ DM/CADM patients.ConclusionMyocardial involvement is not rare and is an independent poor prognostic factor of anti-MDA5 Ab+ DM/CADM patients. Cardiac abnormality screening is necessary for them.

Syncope may have many different causes, requiring careful identification. Recurrent syncope is uncommon as an initial symptom of neck lymphoma. Head and neck tumors involving the carotid artery cause syncope associate with carotid sinus syndrome. We report the case of a 72-year-old man who suffered from recurrent syncope due to compression of the right carotid sinus by diffuse large B-cell lymphoma and was successfully treated with immunochemotherapy. Syncope may be an early or sole sign of a neck or head tumor. We should be aware of the possibility of an underlying malignancy in patients with unexplained syncope after initial evaluation.

Objective: This study evaluated the prognostic value of the multivariable risk assessment for systemic lupus erythematosus (SLE)-associated pulmonary arterial hypertension (PAH). Methods: A multicenter prospective cohort of SLE-associated PAH (CSTAR-PAH cohort) diagnosed based on right heart catheterization (RHC) was established. Baseline and follow-up records were collected. Three methods of risk assessment, including (1) the number of low-risk criteria, based on World Health Organization functional class (WHO FC), 6-min walking distance (6MWD), right atrial pressure (RAP), and cardiac index (CI); (2) the three-strata stratification based on the average risk score of four variables (WHO FC, 6MWD, RAP, and CI); and (3) the four-strata stratification based on COMPARE 2.0 model were applied. A risk-assessment method using three noninvasive low-risk criteria was applied at the first follow-up visit. Survival curves between patients with different risk groups were compared by Kaplan–Meier’s estimation and log-rank test. Results: Three-hundred and ten patients were enrolled from 14 PAH centers. All methods of stratification at baseline and first follow-up significantly discriminated long-term survival. Survival rates were also significantly different based on the noninvasive risk assessment in first follow-up visit. Survival deteriorated with the escalation of risk from baseline to first follow-up. Patients with baseline serositis had a higher rate of risk improvement in their follow-up. Conclusion: The risk assessment has a significant prognostic value at both the baseline and first follow-up assessment of SLE-associated PAH. A noninvasive risk assessment can also be useful when RHC is not available during follow-up. Baseline serositis may be a predictor of good treatment response in patients with SLE-associated PAH.

BackgroundPulmonary arterial hypertension (PAH) is a serious complication of systemic sclerosis (SSc). PAH has high mortality, and risk assessment is critical for proper management. Whether the right ventricle to pulmonary artery (RV-PA) coupling accurately assesses risk status and predicts prognosis in patients with SSc-associated PAH has not been investigated.MethodsBetween March 2010 and July 2018, 60 consecutive patients with SSc-associated PAH diagnosed by right heart catheterization were enrolled prospectively, and the mean follow-up period was 52.9 ± 27.0 months. The RV-PA coupling was assessed by the ratio of tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP) which was obtained by transthoracic echocardiography. The simplified risk stratification strategy was applied to assess the risk level of participants, and the endpoint was a composite of all-cause death and clinical worsening.ResultsThe receiver operating characteristic (ROC) curve of the ability to determine high-risk patients identified the optimal cut-off value of the TAPSE/PASP ratio as 0.194 mm/mmHg, and the ratio appeared to be a reliable indicator in the stratification of patients with high risk (area under the curve = 0.878, ROC P-value = 0.003), which showed the highest positive likelihood ratio (LR) (5.4) and the lowest negative LR (0) among a series of echocardiographic parameters. The TAPSE/PASP ratio was an independent predictive factor (HR = 0.01, 95% CI: 0.00–0.77, P = 0.037) for the composite endpoint, and patients with a TAPSE/PASP ratio >0.194 had a better overall survival for both the composite endpoint (log-rank χ2 = 5.961, P = 0.015) and all-cause mortality (log-rank χ2 = 8.004, P = 0.005) compared to the patients with a TAPSE/PASP ≤ 0.194.ConclusionRV-PA coupling assessed by the TAPSE/PASP ratio provides added value as a straightforward and non-invasive approach for predicting risk stratification of patients with SSc-associated PAH. Meanwhile, a lower TAPSE/PASP ratio identified a subgroup with worse prognosis.

BackgroundIn November 2018, a Chinese researcher reported that his team had applied clustered regularly interspaced palindromic repeats or associated protein 9 to delete the gene C-C chemokine receptor type 5 from embryos and claimed that the 2 newborns would have lifetime immunity from HIV infection, an event referred to as #GeneEditedBabies on social media platforms. Although this event stirred a worldwide debate on ethical and legal issues regarding clinical trials with embryonic gene sequences, the focus has mainly been on academics and professionals. However, how the public, especially stratified by geographic region and culture, reacted to these issues is not yet well-understood. ObjectiveThe aim of this study is to examine web-based posts about the #GeneEditedBabies event and characterize and compare the public’s stance across social media platforms with different user bases. MethodsWe used a set of relevant keywords to search for web-based posts in 4 worldwide or regional mainstream social media platforms: Sina Weibo (China), Twitter, Reddit, and YouTube. We applied structural topic modeling to analyze the main discussed topics and their temporal trends. On the basis of the topics we found, we designed an annotation codebook to label 2000 randomly sampled posts from each platform on whether a supporting, opposing, or neutral stance toward this event was expressed and what the major considerations of those posts were if a stance was described. The annotated data were used to compare stances and the language used across the 4 web-based platforms. ResultsWe collected >220,000 posts published by approximately 130,000 users regarding the #GeneEditedBabies event. Our results indicated that users discussed a wide range of topics, some of which had clear temporal trends. Our results further showed that although almost all experts opposed this event, many web-based posts supported this event. In particular, Twitter exhibited the largest number of posts in opposition (701/816, 85.9%), followed by Sina Weibo (968/1140, 84.91%), Reddit (550/898, 61.2%), and YouTube (567/1078, 52.6%). The primary opposing reason was rooted in ethical concerns, whereas the primary supporting reason was based on the expectation that such technology could prevent the occurrence of diseases in the future. Posts from these 4 platforms had different language uses and patterns when they expressed stances on the #GeneEditedBabies event. ConclusionsThis research provides evidence that posts on web-based platforms can offer insights into the public’s stance on gene editing techniques. However, these stances vary across web-based platforms and often differ from those raised by academics and policy makers.

The Pulmonary Arterial Hypertension Symptoms and Impact Questionnaire (PAH-SYMPACT) is a PAH-specific patient-reported outcome scale assessing patients’ quality of life from four aspects: cardiopulmonary symptoms, cardiovascular symptoms, physical impacts and cognitive/emotional impacts. This study aimed to validate the Chinese version of PAH-SYMPACT and explore its relationship with risk stratification in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH). In addition, 75 patients with CTD-PAH confirmed by right heart catheterization were invited to complete questionnaires including PAH-SYMPACT, the 36-item Medical Outcomes Study Short Form Survey (SF-36) and EuroQol five dimensions questionnaire (EQ-5D). The demographic, clinical, laboratory and treatment data were collected. The endpoint was treatment goal achievement status in 6–12 months after completing the questionnaires, defined as an integrated outcome. Participants’ mean age was 36.4 ± 11.9 years and the mean pulmonary arterial pressure was 38.9 ± 13.67 mmHg. The reliability of the PAH-SYMPACT domains ranged from 0.83 to 0.88. Results of factor analysis basically conformed the original PAH-SYMPACT. The treatment goal achievement (TGA) status in 6–12 months was significantly associated with physical impacts scores (odds ratio: 0.180, 95% confidence interval: 0.036–0.908, P=0.038). The Chinese version of PAH-SYMPACT is a reliable measurement to evaluate quality of life in CTD-PAH patients and is also a potential predictor of patient’s condition change in routine clinical practice.

Abstract Background Metformin is the most widely prescribed drug to lower glucose and has a definitive effect on the cardiovascular system. The goal of this systematic review and meta-analysis is to assess the effects of metformin on mortality and cardiac function among patients with coronary artery disease (CAD). Methods Relevant studies reported before October 2018 was retrieved from databases including PubMed, EMBASE, Cochrane Library and Web of Science. Hazard ratio (HR) was calculated to evaluate the all-cause mortality, cardiovascular mortality and incidence of cardiovascular events (CV events), to figure out the level of left ventricular ejection fraction (LVEF), creatine kinase MB (CK-MB), type B natriuretic peptide (BNP) and to compare the average level of low density lipoprotein (LDL). Results In this meta-analysis were included 40 studies comprising 1,066,408 patients. The cardiovascular mortality, all-cause mortality and incidence of CV events were lowered to adjusted HR (aHR) = 0.81, aHR = 0.67 and aHR = 0. 83 respectively after the patients with CAD were given metformin. Subgroup analysis showed that metformin reduced all-cause mortality in myocardial infarction (MI) (aHR = 0.79) and heart failure (HF) patients (aHR = 0.84), the incidence of CV events in HF (aHR = 0.83) and type II diabetes mellitus (T2DM) patients (aHR = 0.83), but had no significant effect on MI (aHR = 0.87) and non-T2DM patients (aHR = 0.92). Metformin is superior to sulphonylurea (aHR = 0.81) in effects on lowering the incidence of CV events and in effects on patients who don’t use medication. The CK-MB level in the metformin group was lower than that in the control group standard mean difference (SMD) = − 0.11). There was no significant evidence that metformin altered LVEF (MD = 2.91), BNP (MD = − 0.02) and LDL (MD = − 0.08). Conclusion Metformin reduces cardiovascular mortality, all-cause mortality and CV events in CAD patients. For MI patients and CAD patients without T2DM, metformin has no significant effect of reducing the incidence of CV events. Metformin has a better effect of reducing the incidence of CV events than sulfonylureas.

No previous studies have investigated the predictive performance of the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL) prognostic equation and simplified risk score calculator in patients with systemic lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH). We aimed to validate these prediction tools in an external cohort of patients with SLE-PAH. In this study, the validation cohort consisted of patients with SLE-PAH registered in a prospective, multicenter, nationwide database between November 2006 and May2016. The follow-up of patients was censored at 1 year. Discrimination, calibration, model fit, and risk stratification of the REVEAL prognostic equation and simplified risk score calculator were validated. As a result, a total of 306 patients with SLE-PAH were included. The 1-year overall survival rate was 91.5%. The C-index of the prognostic equation was 0.736, demonstrating reasonably good discrimination, and it was greater than that for the simplified risk score calculator (0.710). The overall calibration slope was 0.83, and the Brier score was 0.079. The risk of renal insufficiency and World Health Organization Functional Class III (WHO FC III) were underestimated, and the risk assigned to a heart rate >92 bpm in the REVEAL prognostic models was not observed in our validation cohort. Both model discrimination and calibration were poor in the very high-risk group. In conclusion, the REVEAL models exhibit good discriminatory ability when predicting 1-year overall survival in patients with SLE-PAH. Findings from both models should be interpreted with caution in cases of renal insufficiency, WHO FC III, and heart rate >92 bpm.

Aims: Systemic light-chain (AL) amyloidosis is a multisystemic disorder leading to multiple organ dysfunction and mortality that is often caused by cardiac involvement. Soluble suppression of tumorigenicity 2 (sST2) is a novel biomarker identified for risk stratification of heart disease. The aim of this study was to investigate the value of circulating sST2 levels in prognosis and mortality risk assessments for the AL amyloidosis population.Methods and Results: A total of 56 patients diagnosed with AL amyloidosis were enrolled in Peking Union Medical College Hospital (PUMCH) from January 2015 to May 2018. The relationships between the clinical parameters and overall survival (OS) and risk factors for disease progression were assessed. Additionally, receiver operating characteristic (ROC) curves, Kaplan–Meier analysis, and Cox hazard models were performed to explore the predictive value of sST2 in mortality rates. We found that the median OS of all patients was 7.3 [interquartile range (IQR) 4.4, 15.9] months. The median baseline sST2 level was 12.2 (IQR 5.1, 31.1) ng/ml, and the sST2 high group had more severe patients with a higher Mayo stage. In the ROC analysis, the area under the curve (AUC) was 0.728 [95% confidence interval (CI) 0.603–0.853] for sST2 to predict the outcomes of AL amyloidosis patients, and the optimal cutoff value was 12.34 ng/ml (sensitivity 80.2%, specificity 61.1%). Moreover, in multivariate Cox proportional hazards regression analysis, sST2 acted as an independent predictor of poor functional outcome in patients with AL amyloidosis.Conclusion: In AL amyloidosis patients, sST2 was a strong and independent prognostic biomarker for all-cause mortality, providing complementary prognostic information of a novel scoring system for risk stratification.

Background: Cardiac manifestations are common and life-threatening in eosinophilic granulomatosis with polyangiitis (EGPA), which remains poorly studied in China. We aim to investigate its clinical features, associated factors, treatment, and outcomes. Methods: We reviewed the clinical records of 110 EGPA patients and examined the independent factors associated with cardiac manifestations using multivariate logistic regression. Receiver operating characteristic curves determined the cut-off values, and survival was calculated via Kaplan–Meier curves. Results: Cardiac involvement was present in 36.4% (40/110) of EGPA patients, which mainly manifested as pericardial effusion (16.4%, 18/110), myocardial involvement (13.6%, 15/110), and heart failure (8.2%, 9/110). The mean age was 42.1 ± 14.23 years with no female/male predominance. Compared with the cardiac-unaffected group, the cardiac-affected group showed a lower rate of biopsy-proved vasculitis (0% versus 20%, p = 0.002). The eosinophil count [odds ratio (OR) = 1.142, 95% confidence interval (CI) 1.029–1.267] was independently associated with cardiac manifestations in EGPA, with a cut-off value of 3.66 × 10 9 /L [area under the curve (AUC) = 0.692, p = 0.001]. Regarding treatment, the cardiac-affected group displayed a higher ratio of glucocorticoid pulse combined with intravenous cyclophosphamide (CYC-IV) (40% versus 21.4%, p = 0.037), and intravenous immunoglobulin combined with glucocorticoid plus CYC-IV (17.5% versus 4.3%, p = 0.035) than the control group. Outcomes ( p = 0.131) and survival ( p = 0.1972) were not significantly different between the groups. Conclusion: In this single-center Chinese EGPA cohort, cardiac manifestations are observed in 36.4% of patients, which primarily presents as myocardial involvement, pericardial effusion, and heart failure, independently associated with eosinophil count. Glucocorticoid combined with cyclophosphamide is the treatment cornerstone for EGPA patients with cardiac manifestations.

Abstract Background Cardiomyopathies are the most common clinical and genetic heterogeneity cardiac diseases, and genetic contribution in particular plays a major role in patients with primary cardiomyopathies. The aim of this study is to investigate cases of inherited cardiomyopathy (IC) for potential disease-causing mutations in 64 genes reported to be associated with IC. Methods A total of 110 independent cases or families diagnosed with various primary cardiomyopathies, including hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, left ventricular non-compaction, and undefined cardiomyopathy, were collected after informed consent. A custom designed panel, including 64 genes, was screened using next generation sequencing on the Ion Torrent PGM platform. The best candidate disease-causing variants were verified by Sanger sequencing. Results A total of 78 variants in 73 patients were identified. After excluding the variants predicted to be benign and VUS, 26 pathogenic or likely pathogenic variants were verified in 26 probands (23.6%), including a homozygous variant in the SLC25A4 gene. Of these variants, 15 have been reported in the Human Gene Mutation Database or ClinVar database, while 11 are novel. The majority of variants were observed in the MYH7 (8/26) and MYBPC3 (6/26) gene. Titin (TTN) truncating mutations account for 13% in our dilated cardiomyopathy cases (3/23). Conclusions This study provides an overview of the genetic aberrations in this cohort of Chinese IC patients and demonstrates the power of next generation sequencing in IC. Genetic results can provide precise clinical diagnosis and guidance regarding medical care for some individuals.