Gene and stem cell therapy for inherited cardiac arrhythmias.

Inherited cardiac arrhythmias are a group of genetic diseases predisposing to sudden cardiac arrest, mainly resulting from variants in genes encoding cardiac ion channels or proteins involved in their regulation. Currently available therapeutic options (pharmacotherapy, ablative therapy and device-based therapy) can not preclude the occurrence of arrhythmia events and/or provide complete protection. With growing understanding of the genetic background and molecular mechanisms of inherited cardiac arrhythmias, advancing insight of stem cell technology, and development of vectors and delivery strategies, gene therapy and stem cell therapy may be promising approaches for treatment of inherited cardiac arrhythmias. Recent years have witnessed impressive progress in the basic science aspects and there is a clear and urgent need to be translated into the clinical management of arrhythmic events. In this review, we present a succinct overview of gene and cell therapy strategies, and summarize the current status of gene and cell therapy. Finally, we discuss future directions for implementation of gene and cell therapy in the therapy of inherited cardiac arrhythmias.

Clinical characteristics and mortality predictors among very old patients with pulmonary thromboembolism: a multicenter study report.

BACKGROUND: Clinical characteristics of patients with pulmonary thromboembolism have been described in previous studies. Although very old patients with pulmonary thromboembolism are a special group based on comorbidities and age, they do not receive special attention. OBJECTIVE: This study aims to explore the clinical characteristics and mortality predictors among very old patients with pulmonary thromboembolism in a relatively large population. DESIGN AND PARTICIPANTS: The study included a total of 7438 patients from a national, multicenter, registry study, the China pUlmonary thromboembolism REgistry Study (CURES). Consecutive patients with acute pulmonary thromboembolism were enrolled and were divided into three groups. Comparisons were performed between these three groups in terms of clinical characteristics, comorbidities and in-hospital prognosis. Mortality predictors were analyzed in very old patients with pulmonary embolism. KEY RESULTS: In 7,438 patients with acute pulmonary thromboembolism, 609 patients aged equal to or greater than 80 years (male 354 (58.1%)). There were 2743 patients aged between 65 and 79 years (male 1313 (48%)) and 4095 patients aged younger than 65 years (male 2272 (55.5%)). Patients with advanced age had significantly more comorbidities and worse condition, however, some predisposing factors were more obvious in younger patients with pulmonary thromboembolism. PaO2 < 60 mmHg, eGFR < 60 mL/min/1.73m2, malignancy, anticoagulation as first therapy were mortality predictors for all-cause death in very old patients with pulmonary thromboembolism. The analysis found that younger patients were more likely to have chest pain, hemoptysis (the difference was statistically significant) and dyspnea triad. CONCLUSION: In very old population diagnosed with pulmonary thromboembolism, worse laboratory results, atypical symptoms and physical signs were common. Mortality was very high and comorbid conditions were their features compared to younger patients. PaO2 < 60 mmHg, eGFR < 60 mL/min/1.73m2 and malignancy were positive mortality predictors for all-cause death in very old patients with pulmonary thromboembolism while anticoagulation as first therapy was negative mortality predictors.

Flexible Symmetric-Defection Antenna with Bending and Thermal Insensitivity for Miniaturized UAV.

Flexible conformal-enabled antennas have great potential for various developable surface-built unmanned aerial vehicles (UAVs) due to their superior mechanical compliance as well as maintaining excellent electromagnetic features. However, it remains a challenge that the antenna holds bending and thermal insensitivity to negligibly shift resonant frequency during conformal attachment and aerial flight, respectively. Here, we report a flexible symmetric-defection antenna (FSDA) with bending and thermal insensitivity. By engraving a symmetric defection on the reflective ground, the radiated unit attached to the soft polydimethylsiloxane (PDMS) makes the antenna resonate at the ISM microwave band (resonant frequency = 2.44 GHz) and conformal with a miniaturized UAV. The antenna is also insensitive to both the bending-conformal attachment (20 mm < r < 70 mm) and thermal radiation (20~100 °C) due to the symmetric peripheral-current field along the defection and the low-change thermal effect of the PDMS, respectively. Therefore, the antenna in a non-bending state almost keeps the same impedance matching and radiation when it is attached to a cylinder-back of a UAV. The flexible antenna with bending and thermal insensitivity will pave the way for more conformal or wrapping applications.

Blapstin, a Diapause-Specific Peptide-Like Peptide from the Chinese Medicinal Beetle Blaps rhynchopetera, Has Antifungal Function.

Drug resistance against bacteria and fungi has become common in recent years, and it is urgent to discover novel antimicrobial peptides to manage this problem. Many antimicrobial peptides from insects have been reported to have antifungal activity and are candidate molecules in the treatment of human diseases. In the present study, we characterized an antifungal peptide named blapstin that was isolated from the Chinese medicinal beetle Blaps rhynchopetera used in folk medicine. The complete coding sequence was cloned from the cDNA library prepared from the midgut of B. rhynchopetera. It is a 41-amino-acid diapause-specific peptide (DSP)-like peptide stabilized by three disulfide bridges and shows antifungal activity against Candida albicans and Trichophyton rubrum with MICs of 7 µM and 5.3 µM, respectively. The C. albicans and T. rubrum treated with blapstin showed irregular and shrunken cell membranes. In addition, blapstin inhibited the activity of C. albicans biofilm and showed little hemolytic or toxic activity on human cells and it is highly expressed in the fat body, followed by the hemolymph, midgut, muscle, and defensive glands. These results indicate that blapstin may help insects fight against fungi and showed a potential application in the development of antifungal reagents. IMPORTANCE Candida albicans is one of the conditional pathogenic fungi causing severe nosocomial infections. Trichophyton rubrum and other skin fungi are the main pathogens of superficial cutaneous fungal diseases, especially in children and the elderly. At present, antibiotics such as amphotericin B, ketoconazole, and fluconazole are the main drugs for the clinical treatment of C. albicans and T. rubrum infections. However, these drugs have certain acute toxicity. Long-term use can increase kidney damage and other side effects. Therefore, obtaining broad-spectrum antifungal drugs with high efficiency and low toxicity for the treatment of C. albicans and T. rubrum infections is a top priority. Blapstin is an antifungal peptide which shows activity against C. albicans and T. rubrum. The discovery of blapstin provides a novel clue for our understanding of the innate immunity of Blaps rhynchopetera and provides a template for designing antifungal drugs.

Advances in basic and translational research in atrial fibrillation.

Atrial fibrillation (AF) is a very common cardiac arrhythmia with an estimated prevalence of 33.5 million patients globally. It is associated with an increased risk of death, stroke and peripheral embolism. Although genetic studies have identified a growing number of genes associated with AF, the definitive impact of these genetic findings is yet to be established. Several mechanisms, including electrical, structural and neural remodelling of atrial tissue, have been proposed to contribute to the development of AF. Despite over a century of exploration, the molecular and cellular mechanisms underlying AF have not been fully established. Current antiarrhythmic drugs are associated with a significant rate of adverse events and management of AF using ablation is not optimal, especially in cases of persistent AF. This review discusses recent advances in our understanding and management of AF, including new concepts of epidemiology, genetics and pathophysiological mechanisms. We review the current status of antiarrhythmic drug therapy for AF, new potential agents, as well as mechanism-based AF ablation. This article is part of the theme issue 'The heartbeat: its molecular basis and physiological mechanisms'.

Corrigendum: Artemisinin relieves myocardial ischemia-reperfusion injury via modulating miR-29b-3p and hemicentin 1.

[This corrects the article DOI: 10.3389/fphar.2022.918966.].

Clinical characteristics and electrophysiologic properties of SCN5A variants in fever-induced Brugada syndrome.

BACKGROUND: Brugada syndrome (BrS) is a severe inherited arrhythmia syndrome that can be unmasked by fever. METHODS: A multicentre clinical analysis was performed in 261 patients diagnosed with fever-induced BrS, including 198 (75.9%) and 27 (10.3%) patients who received next-generation genetic sequencing and epicardial arrhythmogenic substrate (AS) mapping, respectively. FINDINGS: In fever-induced BrS patients, pathogenic or likely pathogenic (P/LP) SCN5A variant carriers developed fever-induced BrS at a younger age, and more often in females and those of Caucasian descent. They exhibited significant electrophysical abnormalities, including a larger epicardial AS area, and more prolonged abnormal epicardial electrograms. During a median follow-up of 50.5 months (quartiles 32.5-81.5 months) after the diagnosis, major cardiac events (MCE) occurred in 27 (14.4%) patients. Patients with P/LP SCN5A variants had a higher ratio of MCE compared with the rest. Additionally, history of syncope, QRS duration, and Tpe interval could also predict an increased risk for future MCE according to univariate analysis. Multivariate analysis indicated that only P/LP SCN5A variants were independent significant predictors of MCE. Computational structural modelling showed that most variants are destabilizing, suggesting that Nav1.5 structure destabilization caused by SCN5A missense variants may contribute to fever-induced BrS. INTERPRETATION: In our cohort, P/LP SCN5A variant carriers with fever-induced BrS are more prevalent among patients of Caucasian descent, females, and younger patients. These patients exhibit aggressive electrophysiological abnormalities and worse outcome, which warrants closer monitoring and more urgent management of fever. FUNDING: The current work was supported by the National Natural Science Foundation Project of China (Nos. 82270332 & 81670304), The Fundamental Research Funds for the Central Universities of China - Independent Research Project of Wuhan University (No. 2042022kf1217) from China; the National Institutes of Health of USA [NIH R56 (HL47678), NIH R01 (HL138103), and NIH R01 (HL152201)], the W. W. Smith Charitable Trust and the Wistar and Martha Morris Fund, Sharpe-Strumia Research Foundation, the American Heart Association Postdoctoral Fellowship (20POST35220002) from United States; the Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation, Dutch Federation of University Medical Centers, the Netherlands Organization for Health Research and Development, and the Royal Netherlands Academy of Sciences (PREDICT2) from the Netherlands.

Artemisinin relieves myocardial ischemia-reperfusion injury via modulating miR-29b-3p and hemicentin 1.

Objective: To explore the impact of artemisinin (ARS) on myocardial ischemia-reperfusion (I/R) injury and the underlying mechanism. Methods: Myocardial I/R rat model and cell model were used in this study. The cell viability, morphological changes, apoptosis, and oxidative stress were evaluated in cardiomyocytes H9c2 cells in vitro by using cell counting kit-8, microscope, flow cytometry, and commercial kits. High throughput sequencing is used to identify molecular targets of ARS on myocardial I/R injury, and then the gene-gene interaction network was constructed. MiR-29b-3p, hemicentin 1 (HMCN1), and apoptosis-related genes were tested by qRT-PCR and Western blotting. In the myocardial I/R rat model, echocardiography, (Triphenyl tetrazolium chloride) TTC staining, Hematoxylin-eosin (H&E) staining, Masson Trichrome staining, and TUNEL staining are applied to evaluate the protective effect of ARS on the myocardial injury. Results: In vitro, we demonstrated that ARS alleviated H2O2-induced myocardial I/R injury, manifested by increased H9c2 viability, decreased pathological changes, apoptosis, and oxidative stress biomarker ROS, LDH, and CK-MB. Then, sequencing analysis revealed that miR-29b-3p/HMCN1 was the target of ARS for myocardial I/R injury. Notably, rescue experiments indicated that ARS inhibited myocardial I/R injury through targeted regulation miR-29b-3p/HMCN1. In vivo, we confirmed that ARS reduced myocardial injury, fibrosis, and apoptosis via modulation of miR-29b-3p/HMCN1. Conclusion: This study demonstrated the functional role of the ARS/miR-29b-3p/HMCN1 axis in alleviating myocardial I/R injury, which provided a new direction for myocardial I/R injury therapy.

LMWHs dosage and outcomes in acute pulmonary embolism with renal insufficiency, an analysis from a large real-world study.

BACKGROUND: Renal function is associated with prognoses for acute pulmonary embolism (PE). OBJECTIVE: To investigate the application of anticoagulants and dosage of LMWH among patients with renal insufficiency (RI), and the association between LWMH dosage and the patients' in-hospital outcomes. METHODS: Adult patients diagnosed with non-high risk acute PE from 2009 to 2015, with available data of creatinine clearance (CCr) were enrolled from a multicenter registry in China. Renal insufficiency (RI) was defined as CCr < 60 ml/min. LMWH dosage was converted into IU/kg daily dose and presented as adjusted dose (≤ 100 IU/kg/day) and conventional dose (> 100 IU/kg/day). All-cause death, PE-related death and bleeding events during hospitalization were analyzed as endpoints. RESULTS: Among the enrolled 5870 patients, RI occurred in 1311 (22.3%). 30 ≤ CCr < 60 ml/min was associated with higher rate of bleeding events and CCr < 30 ml/min was associated with all-cause death, PE-related death and major bleeding. Adjusted-dose LMWH was applied in 26.1% of patients with 30 ≤ CCr < 60 ml/min and in 26.2% of CCr < 30 ml/min patients. Among patients with RI, in-hospital bleeding occurred more frequently in those who were administered conventional dose of LMWH, compared with adjusted dose (9.2% vs 5.0%, p = 0.047). Adjusted dose of LMWH presented as protective factor for in-hospital bleeding (OR 0.62, 95%CI 0.27-1.00, p = 0.0496) and the risk of bleeding increased as length of hospital stay prolonged (OR 1.03, 95%CI 1.01-1.06, p = 0.0014). CONCLUSIONS: The proportion of adjusted usage of LMWH was low. The application of adjusted-dose LMWH was associated with lower risk of in-hospital bleeding for RI patients, in real-world setting of PE treatment. Anticoagulation strategy for RI patients should be paid more attention and requires evidence of high quality. TRIAL REGISTRATION: The CURES was registered in ClinicalTrias.gov, identifier number: NCT02943343 .

Clinical Phenotypes With Prognostic Implications in Pulmonary Embolism Patients With Syncope.

OBJECTIVES: There are conflicting data concerning the prognostic significance of syncope in acute pulmonary embolism (PE). This study aimed to investigate the impact of syncope on clinical outcomes of acute PE, and determine the clinical phenotypes of PE patients with syncope and their correlation with prognosis. METHODS: In the ongoing, national, multicenter, registry study, the China pUlmonary thromboembolism REgistry Study (CURES) enrolling consecutive patients with acute PE, patients with and without syncope were investigated. Principal component analysis (PCA) was performed using nine variables relevant to syncope and PE, including age, sex, body mass index, history of cardiovascular disease, recent surgery or trauma, malignancy, pulse, systolic blood pressure, and respiratory rate. Patient classification was performed using cluster analysis based on the PCA-transformed data. The clinical presentation, disease severity and outcomes were compared among the phenotypes. RESULTS: In 7,438 patients with acute PE, 777 (10.4%) had syncope, with younger age, more females and higher body mass index. Patients with syncope had higher frequency of precordial pain, palpitation, and elevated cardiac biomarkers, as well as higher D-Dimer level. In the syncope group, more patients had right ventricular/left ventricular ratio > 0.9 in ultrasonic cardiogram and these patients had higher estimated pulmonary arterial systolic pressure compared with patients without syncope. As the initial antithrombotic treatment, more patients with syncope received systemic thrombolysis. Despite a higher prevalence of hemodynamic instability (OR 7.626, 95% CI 2.960-19.644, P < 0.001), syncope did not increase in-hospital death. Principal component analysis revealed that four independent components accounted for 60.3% of variance. PE patients with syncope were classified into four phenotypes, in which patients with high pulse and respiratory rate had markedly higher all-cause mortality during admission. CONCLUSION: Syncope was associated with hemodynamic instability and more application of thrombolysis, without increasing in-hospital deaths. Different clinical phenotypes existed in PE patients with syncope, which might be caused by various mechanisms and thus correlated with clinical outcomes.

Morphological development of the human fetal striatum during the second trimester.

The morphological development of the fetal striatum during the second trimester has remained poorly described. We manually segmented the striatum using 7.0-T MR images of the fetal specimens ranging from 14 to 22 gestational weeks. The global development of the striatum was evaluated by volume measurement. The absolute volume (Vabs) of the caudate nucleus (CN) increased linearly with gestational age, while the relative volume (Vrel) showed a quadratic growth. Both Vabs and Vrel of putamen increased linearly. Through shape analysis, the changes of local structure in developing striatum were specifically demonstrated. Except for the CN tail, the lateral and medial parts of the CN grew faster than the middle regions, with a clear rostral-caudal growth gradient as well as a distinct "outside-in" growth gradient. For putamen, the dorsal and ventral regions grew obviously faster than the other regions, with a dorsal-ventral bidirectional developmental pattern. The right CN was larger than the left, whereas there was no significant hemispheric asymmetry in the putamen. By establishing the developmental trajectories, spatial heterochrony, and hemispheric dimorphism of human fetal striatum, these data bring new insight into the fetal striatum development and provide detailed anatomical references for future striatal studies.

Distinct Features of Probands With Early Repolarization and Brugada Syndromes Carrying SCN5A Pathogenic Variants.

BACKGROUND: Two major forms of inherited J-wave syndrome (JWS) are recognized: early repolarization syndrome (ERS) and Brugada syndrome (BrS). OBJECTIVES: This study sought to assess the distinct features between patients with ERS and BrS carrying pathogenic variants in SCN5A. METHODS: Clinical evaluation and next-generation sequencing were performed in 262 probands with BrS and 104 with ERS. Nav1.5 and Kv4.3 channels were studied with the use of patch-clamp techniques. A computational model was used to investigate the protein structure. RESULTS: The SCN5A+ yield in ERS was significantly lower than in BrS (9.62% vs 22.90%; P = 0.004). Patients diagnosed with ERS displayed shorter QRS and QTc than patients with BrS. More than 2 pathogenic SCN5A variants were found in 5 probands. These patients displayed longer PR intervals and QRS duration and experienced more major arrhythmia events (MAE) compared with those carrying only a single pathogenic variant. SCN5A-L1412F, detected in a fever-induced ERS patient, led to total loss of function, destabilized the Nav1.5 structure, and showed a dominant-negative effect, which was accentuated during a febrile state. ERS-related SCN5A-G452C did not alter the inward sodium current (INa) when SCN5A was expressed alone, but when coexpressed with KCND3 it reduced peak INa by 44.52% and increased the transient outward potassium current (Ito) by 106.81%. CONCLUSIONS: These findings point to SCN5A as a major susceptibility gene in ERS as much as it is in BrS, whereas the lower SCN5A+ ratio in ERS indicates the difference in underlying electrophysiology. These findings also identify the first case of fever-induced ERS and demonstrate a critical role of Ito in JWS and a higher risk for MAE in JWS probands carrying multiple pathogenic variants in SCN5A.

Clinical and Functional Genetic Characterization of the Role of Cardiac Calcium Channel Variants in the Early Repolarization Syndrome.

Background: Early repolarization syndrome (ERS) is an inherited sudden cardiac death (SCD) syndrome. The present study investigates the role of genetic variants in cardiac calcium-channel genes in the pathogenesis of ERS and probes the underlying mechanisms. Methods: Polymerase chain reaction-based next-generation sequencing was carried out using a targeted gene approach. Unrelated ERS probands carrying calcium-channel variants were evaluated clinically and compared with matched healthy controls. Wild-type (WT) and mutant CACNA1C genes were coexpressed with CACNB2b and CACNA2D1 in HEK293 cells and studied using whole-cell patch-clamp techniques and confocal fluorescence microscope. Results: Among 104 ERS probands, 16 carried pathogenic variants in calcium-channel genes (32.2 ± 14.6 years old, 87.5% male). The symptoms at diagnosis included syncope (56.3%), ventricular tachycardia/fibrillation (62.5%), and SCD (56.3%). Three cases (18.8%) had a family history of SCD or syncope. Eight patients (50.0%) had a single calcium gene rare variant. The other half carried rare variants in other ERS-susceptible genes. Compared with controls, the heart rate was slower (72.7 ± 8.9 vs. 65.6 ± 16.1 beats/min, * p < 0.05), QTc interval was shorter (408.2 ± 21.4 vs. 386.8 ± 16.9 ms, ** p < 0.01), and Tp-e/QT was longer (0.22 ± 0.05 vs. 0.28 ± 0.04, *** p < 0.001) in single calcium mutation carriers. Electrophysiological analysis of one mutation, CACNA1C-P817S (c.2449C>T), revealed that the density of whole-cell calcium current (I Ca) was reduced by ~84.61% compared to WT (-3.17 ± 2.53 vs. -20.59 ± 3.60 pA/pF, n = 11 and 15, respectively, ** p < 0.01). Heterozygous expression of mutant channels was associated with a 51.35% reduction of I Ca. Steady-state inactivation was shifted to more negative potentials and significantly accelerated as well. Confocal microscopy revealed trafficking impairment of CACNA1C-P817S (peripheral/central intensity: 0.94 ± 0.10 in WT vs. 0.33 ± 0.12 in P817S, n = 10 and 9, respectively, ** p < 0.01). Conclusions: ERS associated with loss-of-function (LOF) genetic defects in genes encoding the cardiac calcium channel represents a unique clinical entity characterized by decreased heart rate and QTc, as well as increased transmural dispersion of repolarization. In the case of CACNA1C-P817S, impaired trafficking of the channel to the membrane contributes to the LOF.

Clinical characteristics, risk factors, and cardiac manifestations of cancer patients with COVID-19.

Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been associated with cardiovascular features, which may be deteriorated in patients with cancer. However, cardiac outcomes of cancer patients with COVID-19 have not been closely examined. We retrospectively assessed 1,244 patients with COVID-19 from February 1 to August 31, 2020 (140 cancer and 1,104 noncancer patients). Demographic and clinical data were obtained and compared between cancer and noncancer groups. Including the cardiac biomarkers, we also analyzed laboratory findings between these two groups. Risk factors for in-hospital mortality were identified by multivariable Cox regression models. For cancer group, 56% were in severe and critical status with more diabetes and immune deficiency, whereas the proportion was 10% for noncancer group. Patients with cancer had increased levels of leukocyte, neutrophil count, and blood urea nitrogen (BUN) (all P < 0.01), whereas lymphocyte count was significantly lower (P < 0.001). The most common solid tumor types were gastrointestinal cancer (26%), lung cancer (21%), and breast and reproductive cancer (both 19%). There is a rising for cardiac biomarkers, including pro-B-type natriuretic peptide (Pro-BNP), sensitive troponin I (cTnI), myoglobin (MYO), creatine kinase-MB (CK-MB), as well as D-Dimer in COVID-19 cancer population, especially in deceased subjects with cancer. The 30-day in-hospital mortality in cancer group was dramatically raised than that in noncancer group (12.9% vs. 4.0%, P < 0.01). In multivariable Cox regression models, fever, disease severity status, and underlying diseases were risk factors for mortality. COVID-19 patients with cancer relate to deteriorating conditions and poor cardiac outcomes accompanied by a high in-hospital mortality, which warrants more aggressive treatment.NEW & NOTEWORTHY Our study indicates that the 30-day mortality is higher in COVID-19 patients with cancer; more COVID-19 patients with cancer are in severe and critical status; age, respiratory rate, neutrophil count, AST, BUN, MYO, Pro-BNP, disease severity status, underlying diseases, and fever are risk factors for in-hospital mortality among COVID-19 cancer cases; COVID-19 patients with cancer display severely impaired myocardium, damaged heart function, and imbalanced homeostasis of coagulation; what is more, those with both cancer and CVD have more significantly increased Pro-BNP and D-Dimer level.

Atypical Pathogen Distribution in Chinese Hospitalized AECOPD Patients: A Multicenter Cross-Sectional Study.

Purpose: The proportion of atypical pathogens in patient with AECOPD within mainland China is unknown. The objectives of this study were to determine the distribution of atypical pathogens among Chinese patients with AECOPD, to evaluate the clinical characteristics of different atypical pathogen infections, and to compare different detection methods for atypical pathogens. Patients and Methods: Specimens were collected from patients with AECOPD from March 2016 to November 2018 at eleven medical institutions in eight cities in China. Double serum, sputum, and urine samples were obtained from 145 patients. Serological and nucleic acid tests were used to assess for Mycoplasma pneumonia and Chlamydia pneumoniae; serological, urinary antigen, and nucleic acid tests were applied to detect Legionella pneumophila. The clinical characteristics of atypical pathogen-positive and -negative groups were also compared. Results: The overall positivity rate for Mycoplasma pneumoniae was 20.69% (30/145), with the highest rate being 20.00% (29/145) when determined by passive agglutination.The overall positive rates for Chlamydia pneumoniae and Legionella pneumophila were 29.66% (43/145) and 10.34% (15/145), respectively. The most common serotype of Legionella pneumophila was type 6. The maximum hospitalized body temperature, ratio of eosinophils, C-reactive protein (CRP) level, and procalcitonin (PCT) level of the Mycoplasma pneumoniae-positive group were significantly higher than those of the Mycoplasma pneumoniae-negative group. Patients in the Chlamydia pneumoniae-positive group smoked more, had higher proportions of comorbidities and frequent aggravations in the previous two years than those in the Chlamydia pneumoniae-negative group. Furthermore, the forced expiratory volume in one second to forced vital capacity (FEV1/FVC) ratio assessment of lung function was higher, and the concentration of arterial blood bicarbonate (HCO3-) was lower in the Legionella pneumophila-positive group than in the Legionella pneumophila-negative group. Conclusion: Overall, atypical pathogens play an important role in AECOPD. Regarding the testing method, serological testing is a superior method to nucleic acid testing.

Trends in risk stratification, in-hospital management and mortality of patients with acute pulmonary embolism: an analysis from the China pUlmonary thromboembolism REgistry Study (CURES).

Similar trends of management and in-hospital mortality of acute pulmonary embolism (PE) have been reported in European and American populations. However, these tendencies are not clear in Asian countries. We retrospectively analysed the trends of risk stratification, management and in-hospital mortality for patients with acute PE through a multicentre registry in China (CURES).Adult patients with acute symptomatic PE were included between 2009 and 2015. Trends in disease diagnosis, treatment and death in hospital were fully analysed. Risk stratification was retrospectively classified by haemodynamic status and the simplified Pulmonary Embolism Severity Index (sPESI) score according to the 2014 European Society of Cardiology/European Respiratory Society guidelines.Among 7438 patients, the proportions with high (haemodynamic instability), intermediate (sPESI≥1) and low (sPESI=0) risk were 4.2%, 67.1% and 28.7%, respectively. Computed tomographic pulmonary angiography was the most widely used diagnostic approach (87.6%) and anticoagulation was the most frequently adopted initial therapy (83.7%). Between 2009 and 2015, a significant decline was observed for all-cause mortality (from 3.1% to 1.3%, adjusted pfor trend=0.0003), with a concomitant reduction in the use of initial systemic thrombolysis (from 14.8% to 5.0%, pfor trend<0.0001). The common predictors for all-cause mortality shared by haemodynamically stable and unstable patients were co-existing cancer, older age and impaired renal function.The considerable reduction of mortality over the years was accompanied by changes in initial treatment. These findings highlight the importance of risk stratification-guided management throughout the nation.

Morphological Development Trajectory and Structural Covariance Network of the Human Fetal Cortical Plate during the Early Second Trimester.

During the early second trimester, the cortical plate, or "the developing cortex", undergoes immensely complex and rapid development to complete its major complement of neurons. However, morphological development of the cortical plate and the precise patterning of brain structural covariance networks during this period remain unexplored. In this study, we used 7.0 T high-resolution magnetic resonance images of brain specimens ranging from 14 to 22 gestational weeks to manually segment the cortical plate. Thickness, area expansion, and curvature (i.e., folding) across the cortical plate regions were computed, and correlations of thickness values among different cortical plate regions were measured to analyze fetal cortico-cortical structural covariance throughout development of the early second trimester. The cortical plate displayed significant increases in thickness and expansions in area throughout all regions but changes of curvature in only certain major sulci. The topological architecture and network properties of fetal brain covariance presented immature and inefficient organizations with low degree of integration and high degree of segregation. Altogether, our results provide novel insight on the developmental patterning of cortical plate thickness and the developmental origin of brain network architecture throughout the early second trimester.

Morphological changes in the central sulcus of children with isolated growth hormone deficiency versus idiopathic short stature.

In this study, the morphological changes in the central sulcus between children with isolated growth hormone deficiency (IGHD) and those with idiopathic short stature (ISS) were analyzed. Thirty children with IGHD (peak growth hormone < 5 µg/L) and 30 children with ISS (peak growth hormone > 10.0 µg/L) were included. Morphological measurements of the central sulcus were obtained from T1-weighted MRIs using BrainVISA, including the average sulcal width, maximum depth, average depth, top length, bottom length, and depth position-based profiles (DPPs). The bilateral average width of the central sulci was significantly wider, while the left maximum depth and right average depth of the central sulcus were significantly smaller, in children with IGHD than in children with ISS. There were no significant differences in the right maximum depth, left average depth, or bilateral top length and bottom length of the central sulcus between groups. The DPPs of the middle part of both central sulci (corresponding to the hand motor activation area) and the inferior part of the right central sulcus (corresponding to the oral movement area) near the Sylvian fissure were significantly smaller in children with IGHD than in controls before false discovery rate (FDR) correction. However, all the above significant DPP sites disappeared after FDR correction. There were significant morphological changes in the three-dimensional structure of the central sulcus in children with IGHD, which were the outcome of other more essential cortical or subcortical changes, resulting in their relatively slower development in motor, cognitive, and linguistic functional performance.

[Diagnosis and treatment of community-acquired pneumonia in elderly patients combined with coronavirus disease 2019: analysis of 1 case].

OBJECTIVE: To explore the pathological characteristics and outcomes of elderly patients with community acquired pneumonia (CAP) accompanied by coronavirus disease 2019 (COVID-19). METHODS: The diagnosis and treatment process of one elderly patient with CAP accompanied by COVID-19 who was admitted to COVID-19 Treatment Center of Liaoning Province on February 7, 2020 were reviewed. The experience of treatment by analyzing the characteristics of such type of patients during diagnosis and treatment were summarized. RESULTS: A female patient, aged 79 years ald, was admitted to the Center with following features: fever, dry cough, fatigue with dyspnea, scattered moist rales in both lungs, oxygenation index (PaCO2/FiO2) of 95 mmHg (1 mmHg = 0.133 kPa), and diffuse interstitial pneumonia in both lungs indicated by chest CT, of which the majority were ground glass-like and fibrous lesions. It was confirmed to be consistent with the feature of severe COVID-19 cases. The patient was successfully cured one month later following anti-inflammatory, anti-viral and high-flow oxygen therapies, homeostasis maintenance of the body, psychological counseling, etc. Accordingly, the treatment experience in CAP combined with COVID-19 in the elderly patients was summarized as follows. In respiratory system, the timing of high-flow oxygen therapy and mechanical ventilation should be seized. As for anti-inflammatory and antiviral therapy, attention should be paid to the treatment of CAP as well as antiviral therapy and symptomatic and supportive therapy. With the progression of the disease, the production of drug-resistant bacteria and the possibility of fungal infection should be paid attention to. For the circulatory system, we should pay attention to the stability of fluid volume and internal environment, and strengthen hemodynamic monitoring and bedside ultrasound to evaluate the cardiovascular capacity-load. In the aspect of the immune system, the selection of the application time of immune-enhancers and glucocorticoids should be paid attention to. In terms of enteral nutrition, early low-fat and high-protein diet is conducive to the recovery of intestinal function and the prevention of bacterial translocation. In addition to the protection of the function of important organs, therapies such as reasonable sedation and psychological intervention should also be used. CONCLUSIONS: Elderly patients with CAP accompanied by COVID-19 have complicated conditions and high degree of difficulty in treatment. Comprehensive evaluation of the disease as well as synthetic and effective intervention are the key factors of successful treatment of such patients.