Mitochondrial Protease Oct1p Regulates Mitochondrial Homeostasis and Influences Pathogenicity through Affecting Hyphal Growth and Biofilm Formation Activities in Candida albicans.

Mitochondria, as the core metabolic organelles, play a crucial role in aerobic respiration/biosynthesis in fungi. Numerous studies have demonstrated a close relationship between mitochondria and Candida albicans virulence and drug resistance. Here, we report an octapeptide-aminopeptidase located in the mitochondrial matrix named Oct1p. Its homolog in the model fungus Saccharomyces cerevisiae is one of the key proteins in maintaining mitochondrial respiration and protein stability. In this study, we utilized evolutionary tree analysis, gene knockout experiments, mitochondrial function detection, and other methods to demonstrate the impact of Oct1p on the mitochondrial function of C. albicans. Furthermore, through transcriptome analysis, real-time quantitative PCR, and morphological observation, we discovered that the absence of Oct1p results in functional abnormalities in C. albicans, affecting hyphal growth, cell adhesion, and biofilm formation. Finally, the in vivo results of the infection of Galleria mellonella larvae and vulvovaginal candidiasis in mice indicate that the loss of Oct1p led to the decreased virulence of C. albicans. In conclusion, this study provides a solid theoretical foundation for treating Candida diseases, developing new targeted drugs, and serves as a valuable reference for investigating the connection between mitochondria and virulence in other pathogenic fungi.

Exercise-mediated macrophage polarization modulates the targeted therapeutic effect of NAFLD: a review.

PURPOSE: This review aims to explore the exercise-mediated hepatic macrophage polarization mechanism and its effect on improving and regulating non-alcoholic fatty liver disease (NAFLD) by analyzing the pathogenesis of NAFLD and the cause of the influence of hepatic macrophage polarization. In addition to exploring the varied effects of different exercise types on macrophage polarization regulation in NAFLD, to provide a direction and basis for the treatment of NAFLD. METHODS: The research methodology involved a comprehensive search of the PubMed database using specific keywords such as "NAFLD", "macrophage polarization", and "exercise", to retrieve relevant literature published. RESULTS: (1) The main factors inducing NAFLD were high-fat diet, obesity, insulin resistance (IR), changes in gut microbiota, and genetic variation in susceptibility. (2) Drug treatment, nutrient induction, microfactor induction, physiological environment induction, and other factors can induce the polarization of hepatic macrophages and affect NAFLD. (3) Different intensities, types, and frequencies of exercise have different effects on polarization macrophages, and may also differently effects improving liver inflammation, fibrosis, and NAFLD. Curently, regular moderate-intensity aerobic exercise is the most effective therapy for treating NAFLD. CONCLUSION: Approaches to ameliorate NAFLD with exercise involve strategies to alter macrophage polarization by inhibiting M1 or driving M2 activation. However, research on the different types of exercise-mediated macrophage polarization mechanisms and differences in therapeutic effects is not yet sufficient. Future research is necessary to explore the exact mechanisms and differences in the effects of different exercises on the treatment of NAFLD.

Imaging Characteristics of Primary Cardiac Angiosarcoma / 罕见病研究

Primary cardiac angiosarcoma is a type of soft tissue sarcoma originating in vascular endothelial cells, without obvious gender differences in the incidence rate and specific early clinical manifestations, whilstpericardial effusion often found at the first presentation of most patients. Tumors are mostly located in the right atrium and pericardium. Echocardiography is the preferred examination method for diagnosing cardiac angiosarcoma and multimodal imaging is important in the diagnosis and differential diagnosis of benign and malignant cardiac mass. This article retrospectively analyzes the 25 cases of clinical manifestations and imaging features of primary cardiac angiosarcoma.

The Interpretation and Update of the Diagnosis Pathway of Chinese Expert Consensus on the Diagnosis and Treatment of Transthyretin Cardiac Amyoidosis / 罕见病研究

Transthyretin cardiac amyloidosis (ATTR-CA) is caused by the deposition of transthyretin(TTR) in the myocardial interstitium. Its clinical manifestations are mainly heart failure and arrhythmia, leading to poor life quality and low survival rate. Diagnosis is often delayed or missed due to the lack of disease awareness, the non-specific clinical symptom presentation of the disease, and inadequacy of non-invasive diagnostic methods and medications in the past. The recent availability of effective treatments makes the early recognition and diagnosis especially critical, because treatment is likely more effective earlier in the disease course. Therefore, it is crucial to establish a diagnosis and treatment strategy to facilitate the rapid and accurate identification of the disease. Based on the advances in research and experiences gained ATTR-CA, our team has developed a consensus on diagnosis and treatment for the disease. In this article, we interpret the key points and present the update of diagnostic process, providing clinicians with an overview of key aspects of ATTR-CA in China.

A Case Report of Homozygous Familial Hypercholesterolemia Liver Transplantation / 罕见病研究

Homozygous familial hypercholesterolemia (HoFH) is a rare and serious autosomal genetic metabolic disease. Patients without intervention often die younger than 30 years old from early atherosclerotic cardiovascular disease (ASCVD)incurred by extremely high levels of low-density lipoprotein cholesterol (LDL-C). We present a case of HoFH, a child with compound heterozygous mutation in this study. The effect of conventional lipid-lowering therapy through diet control and lipid-lowering drugs was unsatisfactory. The blood-lipid purification proves effective but has poor compliance and difficult to maintain for a longer time. The patient received orthotopic liver transplantation and had been followed for 2 years, with the patient shows normal LDL-C, well growth and development. We hope the case will provide the clinician with better understanding of the diagnosis and treatment of the rare disease of HoFH.

Preliminary Study on Quantitative Evaluation of Myocardial Fibrosis by CardiacMagnetic Resonance in Patients with Light Chain Cardiac Amyloidosis / 罕见病研究

  Objective  Myocardial fibrosis is a potential mechanism of light-chain myocardial amyloidosis(AL-CA). This research aimed at exploring the correlation between multiparameter cardiac magnetic resonance (CMR) and myocardial fibrosis by relating the CMR myocardial tissue characteristics, the morphological and the functional parameters with gallium-68-labeledfibroblast activation protein inhibitor 04 positron emission tomography (68Ga-FAPI PET).  Methods  We gave the patients diagnosed with AL-CA in Peking Union Medical College Hospital from August to December 2021 the examinations of CMR and 68Ga-FAPI PET/CT. We recorded and analyzed the information on clinical manifestations and examinations of the patients.  Results  A total of 23 patients with AL-CA were included, 15 (65.2%)of which were male and the mean age was 58.3±6.5 years. Patients with high 68Ga-FAPI-04 uptake had shown growth in myocardial extracellular volume (ECV), significantly higher than those in the negative group (P=0.047). In addition, patients' myocardial ECV was positively correlated with myocardial FAPI uptake (r=0.628, P=0.001;r=0.727, P < 0.001;r=0.661, P=0.001). Patients in the positive group showd reduced left ventricular (LV) ejection fraction (EF)(P < 0.001).LVEF (r=-0.798, P < 0.001;r=-0.794, P < 0.001; r=-0.795, P < 0.001) and right ventricular (RV)EF (r=-0.735, P < 0.001;r=-0.739, P < 0.001;r=- 0.684, P < 0.001) showd negatively correlated with myocardial FAPI uptake, LV circumferential strain (r=0.668, P < 0.001;r=0.708, P < 0.001;r=0.705, P < 0.001), LV longitudinal strain (r=0.629, P=0.001;r=0.635, P=0.001; r=0.597, P=0.003), and RV longitudinal strain (r=0.575, P=0.004; r=0.792, P < 0.001;r=0.673, P < 0.001) were negatively correlated with myocardial FAPI uptake.  Conclusions  FAPI-related fibroblast activation is concurrent with CMR-related abnormal myocardial interstitial characteristics that leads to the decreased function of the myocardial movement. Patients with increased FAPI uptake present with increased ECV, decreased EF, and decreased strain with morphological abnormalities.

Progress in New Therapies Targeting the Pathogenesis of Cardiomyopathywith Hypertrophic Phenotype / 罕见病研究

Hypertrophic cardiomyopathy (HCM) is cardiomyopathy with a clinical phenotype of cardiac hypertrophy. The etiology includes genetically defective encoding sarcomeres, congenital metabolic diseases such as lysosomal storage diseases, systemic amyloidosis such as transthyretin amyloidosis(ATTR), and Fabry disease. Previous therapies did not target the etiology and pathogenesis and therefore were less effective. In recent years, treatments targeting different mechanisms of myocardial hypertrophy have achieved good results. Mavacamten can reduce myocardial contractility by inhibiting ATP activity, thereby significantly improving left ventricular outflow tract(LVOT) obstruction, cardiac contractility, ventricular tension, and limitting myocardial damage. By inhibiting the dissociation of transthyretin(TTR) and subsequent formation and deposition of the amyloid fibril, tafamidis can reduce the mortality and morbidity of patients with transthyretin cardiac amyloidosis(ATTR-CA). Gene silencing and gene editing technology can reduce abnormal TTR levels. Synthesis of α-galactosidase A by gene recombination technology in vitro can effectively reduce left ventricular mass index(LVMi), improve cardiac function, reduce angina attacks and decrease mortality of Fabry disease.

Advances in the Diagnosis and Treatment of Rare Cardiovascular Diseases / 罕见病研究

The onset of rare cardiovascular diseases is early and the mortality is high. The patients of the disease face a long time of hardship in diagnosis and a low treatment rate. As a result, it is urgent to improve the diagnosis and treatment level of rare diseases and to accelerate the selection and R&D of drugs of rare cardiovascular diseases. In recent years, with the rapid development of new technology and basic research, the diagnosis and treatment of rare cardiovascular diseases have made breakthroughs. The article summarizes the research progress in diagnosis and treatment of rare cardiovascular diseases and looks into the future of the research.

Impact of orthotopic liver transplantation on serum lipid level and growing development in patients with homozygous or compound heterozygous familial hypercholesterolemia / 中华心血管病杂志

Objective: To investigate the impact of orthotopic liver transplantation on serum lipid and growing development in patients with homozygous (HoFH) or compound heterozygotes (cHeFH) familial hypercholesterolemia. Methods: Patients who were treated in Peking Union Medical College Hospital from August 2019 to August 2021, entered the rare disease database and underwent liver transplantation, were included in this single center retrospective cohort study. The height for age Z score (HAZ) and length for age Z score (WAZ) at birth, at the time of transplantation and one year after transplantation were calculated respectively by collecting demographic characteristics, clinical manifestations, echocardiography, lipid-lowering treatment, blood lipid level data and donor characteristics data of liver transplantation. The serum cholesterol level and growing development changes before and after liver transplantation were evaluated. Results: A total of five patients with HoFH or cHeFH, including two females, were included in this study. The median age was 10 years (6-22 years). The median follow up duration was 28 months (24-33 months). All HoFH or cHeFH patients in this study received the maximum daily dosage of the lipid-lowering drug combined with low salt and low-fat diet control treatment for at least 3 months before orthotopic liver transplantation. The average level of total cholesterol (TC) decreased by 27% compared with that before treatment, the level of low-density lipoprotein cholesterol (LDL-C) decreased by 21% after 3 months treatment. There was no intervention of lipid-lowering therapy after operation. One month after liver transplantation, the average levels of TC and LDL-C further decreased rapidly by 68% and 76% respectively. One year after liver transplantation, the level of LDL-C decreased from (17.1±1.6)mmol/L without any intervention before transplantation to (3.0±0.7)mmol/L, and remained stable thereafter. In addition, compared with no intervention before liver transplantation, the serum triglyceride (TG) level decreased after the maximum daily dosage of the lipid-lowering drug and low salt and low-fat diet control for 3 months ((1.88±0.27) mmol/L vs. (1.12±0.55)mmol/L, P=0.031), and the HDL-C level also decreased significantly ((1.95±0.49)mmol/L vs. (0.95±0.30)mmol/L, P=0.006) at the same time period. TG and HDL-C remained stable after liver transplantation during the 24-month follow-up period (P>0.05). One and two years after liver transplantation, there was no significant difference in height and weight, malnutrition and growth retardation between the patients in this cohort and Chinese children of the same age. Conclusion: Early liver transplantation is a feasible and effective treatment option for HoFH or cHeFH patients with extremely high serum low-density lipoprotein cholesterol levels.

Protective mechanism of tetramethylpyrazine on cardiovascular system / 中国中药杂志

Tetramethylpyrazine is the main component of Ligusticum chuanxiong. Studies have found that tetramethylpyrazine has a good protective effect against cardiovascular diseases. In the heart, tetramethylpyrazine can reduce myocardial ischemia/reperfusion injury by inhibiting oxidative stress, regulating autophagy, and inhibiting cardiomyocyte apoptosis. Tetramethylpyrazine can also reduce the damage of cardiomyocytes caused by inflammation, relieve the fibrosis and hypertrophy of cardiomyocytes in infarcted myocardium, and inhibit the expansion of the cardiac cavity after myocardial infarction. In addition, tetramethylpyrazine also has a protective effect on the improvement of familial dilated cardiomyopathy. Besides, the mechanisms of tetramethylpyrazine on blood vessels are more abundant. It can inhibit endothelial cell apoptosis by reducing oxidative stress, maintain vascular endothelial function and homeostasis by inhibiting inflammation and glycocalyx degradation, and protect vascular endothelial cells by reducing iron overload. Tetramethylpyrazine also has a certain inhibitory effect on thrombosis. It can play an anti-thrombotic effect by reducing inflammatory factors and adhesion molecules, inhibiting platelet aggregation, and suppressing the expression of fibrinogen and von Willebrand factor. In addition, tetramethylpyrazine can also reduce the level of blood lipid in apolipoprotein E-deficient mice, inhibit the subcutaneous deposition of lipids, inhibit the transformation of macrophages into foam cells, and inhibit the proliferation and migration of vascular smooth muscle cells, thereby reducing the formation of atherosclerotic plaque. In combination with network pharmacology, the protective mechanism of tetramethylpyrazine on the cardiovascular system may be mainly achieved through the regulation of phosphatidylinositol 3 kinase/protein kinase B(PI3K/Akt), hypoxia-inducible factor 1(HIF-1), and mitogen-activated protein kinase(MAPK) pathways. Tetramethylpyrazine hydrochloride and sodium chloride injection has been approved for clinical application, but some adverse reactions have been found in clinical application, which need to be paid attention to.

Protective mechanism of salvianolic acid B on blood vessels / 中国中药杂志

Salvianolic acid B(Sal B) is the main water-soluble component of Salvia miltiorrhiza Bunge. Studies have found that Sal B has a good protective effect on blood vessels. Sal B can protect endothelial cells by anti-oxidative stress, inducing autophagy, inhibiting endoplasmic reticulum stress(ERS), inhibiting endothelial inflammation and adhesion molecule expression, inhibiting endothelial cell permeability, anti-thrombosis, and other ways. In addition, Sal B can alleviate endothelial cell damage caused by high glucose(HG). For vascular smooth muscle cell(VSMC), Sal B can reduce the synthesis and secretion of inflammatory factors by inhibiting cyclooxygenase. It can also play a vasodilatory role by inhibiting Ca~(2+) influx. In addition, Sal B can inhibit VSMC proliferation and migration, thereby alleviating vascular stenosis. Sal B also inhibits lipid deposition in the subendothelium, inhibits macrophage conversion to foam cells, and reduces macrophage apoptosis, thereby reducing the volume of subendothelial lipid plaques. For some atherosclerosis(AS) complications, such as peripheral artery disease(PAD), Sal B can promote angiogenesis, thereby improving ischemia. It should be pointed out that the conclusions obtained from different experiments are not completely consistent, which needs further research. In addition, previous pharmacokinetics showed that Sal B was poorly absorbed by oral administration, and it was unstable in the stomach, with a large first-pass effect in the liver. Sal B had fast distribution and metabolism in vivo and short drug action time. These affect the bioavailability and biological effects of Sal B, and the development of clinically valuable Sal B non-injectable delivery systems remains a great challenge.

Sodium houttuyfonate effectively treats acute pulmonary infection of Pseudomonas aeruginosa by affecting immunity and intestinal flora in mice.

Introduction: Pseudomonas aeruginosa is a major nosocomial pathogen that frequently causes ventilator-associated pneumonia in specific populations. Sodium houttuyfonate (SH) has shown mild antibacterial activity against P. aeruginosa in vitro, but the mechanism of potent antimicrobial activity of SH against P. aeruginosa infection in vivo remains unclear. Methods: Here, using the mouse pneumonia model induced by P. aeruginosa nasal drip to explore the therapeutic effects of SH. Results: We found that SH exhibits dose-dependent therapeutic effects of reducing P. aeruginosa burden and systemic inflammation in pneumonia mice. SH ameliorates inflammatory gene expression and production of inflammatory proteins, such as interleukin-6 (IL-6), nuclear factor kappa-B (NF-κB) and toll-like receptor 4 (TLR4), associated with the TLR4/NF-κB pathway in mice with P. aeruginosa pneumonia. Furthermore, we analyzed the intestinal flora of mice and found that compared with the model group, the abundance and diversity of beneficial bacterial flora of SH treatment groups increased significantly, suggesting that SH can improve the intestinal flora disorder caused by inflammation. In addition, SH improves alpha and beta diversity index and reduces species abundance differences of intestinal flora in pneumonia mice. Discussion: Taken together, our presented results indicate that SH may effectively alleviate the acute pulmonary infection induced by P. aeruginosa by reducing the disturbance of regulating immunity and intestinal flora in mice.

3D-printed mesoporous bioactive glass/GelMA biomimetic scaffolds for osteogenic/cementogenic differentiation of periodontal ligament cells.

Integrated regeneration of periodontal tissues remains a challenge in current clinical applications. Due to the tunable physical characteristics and the precise control of the scaffold microarchitecture, three-dimensionally (3D) printed gelatin methacryloyl (GelMA)-based scaffold has emerged as a promising strategy for periodontal tissue regeneration. However, the optimization of the printing biomaterial links the formulation and the relationship between the composition and structures of the printed scaffolds and their comprehensive properties (e.g. mechanical strength, degradation, and biological behaviors) remains unclear. Here, in this work, a novel mesoporous bioactive glass (BG)/GelMA biomimetic scaffold with a large pore size (∼300 µm) was developed by extrusion-based 3D printing. Our results showed that the incorporation of mesoporous bioactive glass nanoparticles (BG NPs) significantly improved shape fidelity, surface roughness, and bioactivity of 3D-printed macroporous GelMA scaffolds, resulting in the enhanced effects on cell attachment and promoting osteogenic/cementogenic differentiation in human periodontal ligament cells. The excellent maintenance of the macropore structure, the visibly improved cells spreading, the release of bioactive ions (Si4+, Ca2+), the upregulation of gene expressions of osteogenesis and cementogensis, and the increase in alkaline phosphatase (ALP) activity and calcium nodules suggested that BG NPs could endow GelMA-based scaffolds with excellent structural stability and the ability to promote osteogenic/cementogenic differentiation. Our findings demonstrated the great potential of the newly formulated biomaterial inks and biomimetic BG/GelMA scaffolds for being used in periodontal tissue regeneration and provide important insights into the understanding of cell-scaffold interaction in promoting the regeneration of functional periodontal tissues.

Gut microbiota contributes to lignocellulose deconstruction and nitrogen fixation of the larva of Apriona swainsoni.

Apriona swainsoni is a vital forest pest prevalent in China. The larvae of A. swainsoni live solely in the branches of trees and rely entirely on the xylem for nutrition. However, there is still a lack of in-depth research on the gut microbiota's use of almost nitrogen-free wood components to provide bio-organic macromolecular components needed for their growth. Thus, in this study, the metagenome, metaproteome, and metabolome of the A. swainsoni larvae in four gut segments (foregut; midgut; anterior hindgut; posterior hindgut) were analyzed by the multi-omics combined technology, to explore the metabolic utilization mechanism of the corresponding gut microbiota of A. swainsoni. Firstly, we found that the metagenome of different gut segments was not significantly different in general, but there were different combinations of dominant bacteria and genes in different gut segments, and the metaproteome and metabolome of four gut segments were significantly different in general. Secondly, the multi-omics results showed that there were significant gradient differences in the contents of cellulose and hemicellulose in different segments of A. swainsoni, and the expression of corresponding metabolic proteins was the highest in the midgut, suggesting the metabolic characteristics of these lignocellulose components in A. swainsoni gut segments. Finally, we found that the C/N ratio of woody food was significantly lower than that of frass, and metagenomic results showed that nitrogen fixation genes mainly existed in the foregut and two hindgut segments. The expression of the key nitrogen fixing gene nifH occurred in two hindgut parts, indicating the feature of nitrogen fixation of A. swainsoni. In conclusion, our results provide direct evidence that the larvae of A. swainsoni can adapt to the relatively harsh niche conditions through the highly organized gut microbiome in four gut segments, and may play a major role in their growth.

Consensus to 99mTechnetium-Pyrophosphate Scintigraphy in the Diagnosis of Transthyretin-related Cardiac Amyloidosis / 罕见病研究

Transthyretin-related amyloid cardiomyopathy (ATTR-CM) is a disease caused by the depo-sition of insoluble amyloid fibers formed by the misfolding of transthyretin precursor protein in the intercellular space of cardiomyocytes. This lesion may lead to myocardial dysfunction, cogestive heart failure, and death.When diagnosed earlier, the patient can be treated with drugs as soon as possible to intervene in the progress of the disease, so as to effectively improve the patient's prognosis.99mtechnetium-pyrophosphate (99Tcm-PYP)single-photon emission computed tomography (SPECT) has been widely used in the imaging examination of cardiac amyloidosis (CA) in recent years. While achieving early non-invasive diagnosis, accurate pathological classification can be obtained through Perugini visual score analysis, semi-quantitative analysis of heart to contralateral lung (H/CL) ratio, and SPECT image analysis. This article presents the application, methods, and the precautions of 99Tcm-PYPSPECT in the diagnosis of ATTR-CM, aiming to provide clinical reference for the application of this technology.

Application value of delay-phase 99Tc m-PYP scintigraphy and SPECT imaging for diagnosis of transthyretin-related cardiac amyloidosis / 中华核医学与分子影像杂志

Objective:To investigate the application of different imaging methods of 99Tc m-pyrophosphate (PYP) in the diagnosis and pathological classification of cardiac amyloidosis (CA). Methods:A total of 31 patients (22 males, 9 females, age 21-81(57.2±13.4) years) with suspected CA who underwent 99Tc m-PYP dual-phase scintigraphy (early-phase: 1 h, delay-phase: 2-3 h) and SPECT/CT (1 h) between December 2018 and December 2019 in Peking Union Medical College Hospital were retrospectively included. Taking clinical diagnosis as the standard, the results of visual score (≥2, positive) and semi-quantitative values (heart to contralateral lung (H/CL)≥1.5, positive) of 99Tc m-PYP uptake in dual-phase scintigraphy and SPECT/CT imaging were analyzed. One-way analysis of variance and Bonferroni test were used to analyze the data. Results:Among 31 patients with suspected CA, 15 were clinically diagnosed as CA (5 patients with transthyretin-related CA (ATTR-CA) and 10 patients with light chain CA (AL-CA)) and 16 were diagnosed as non-CA. All 5 patients with ATTR-CA had positive dual-phase scintigraphy and SPECT/CT imaging results. Three out of 10 patients with AL-CA had positive early-phase scintigraphy whereas negative delay-phase scintigraphy and SPECT/CT imaging results. Sixteen patients who were clinically diagnosed as non-CA had negative dual-phase scintigraphy and SPECT/CT imaging results. The sensitivity (5/5), specificity (10/10), positive predictive value (5/5), negative predictive value (10/10) and accuracy (15/15) of delay-phase scintigraphy and SPECT/CT imaging were the same. Among 31 patients, 16 patients carried transthyretin-related (TTR) gene mutation, and 4 of them who clinically diagnosed as variant ATTR (ATTRv) had positive image findings while 12 of them who not clinically diagnosed as CA had negative image findings. There were significant differences in H/CL between ATTR-CA group and AL-CA group in early-phase (2.11±0.24 vs 1.31±0.07) and delay-phase (2.02±0.19 vs 1.30±0.05; F values: 75.41 and 87.15, Bonferroni test, both P<0.01). Conclusions:99Tc m-PYP delay-phase scintigraphy and SPECT/CT have high diagnostic efficiencies in ATTR-CA, helping to determine the pathological classification of CA; while early-phase scintigraphy has false positive results. Moreover, 99Tc m-PYP imaging is helpful to detect CA in patients with TTR gene mutation.

3D bioprinting of a biomimetic meniscal scaffold for application in tissue engineering.

Appropriate biomimetic scaffolds created via 3D bioprinting are promising methods for treating damaged menisci. However, given the unique anatomical structure and complex stress environment of the meniscus, many studies have adopted various techniques to take full advantage of different materials, such as the printing combined with infusion, or electrospining, to chase the biomimetic meniscus, which makes the process complicated to some extent. Some researchers have tried to tackle the challenges only by 3D biopringting, while its alternative materials and models have been constrained. In this study, based on a multilayer biomimetic strategy, we optimized the preparation of meniscus-derived bioink, gelatin methacrylate (GelMA)/meniscal extracellular matrix (MECM), to take printability and cytocompatibility into account together. Subsequently, a customized 3D bioprinting system featuring a dual nozzle + multitemperature printing was used to integrate the advantages of polycaprolactone (PCL) and meniscal fibrocartilage chondrocytes (MFCs)-laden GelMA/MECM bioink to complete the biomimetic meniscal scaffold, which had the best biomimetic features in terms of morphology and components. Furthermore, cell viability, mechanics, biodegradation and tissue formation in vivo were performed to ensure that the scaffold had sufficient feasibility and functionality, thereby providing a reliable basis for its application in tissue engineering.

Clinical and imaging characteristics of patients with primary cardiac angiosarcoma / 中华心血管病杂志

Objective: To investigate the clinical, cardiac imaging characteristics and prognosis of patients with primary cardiac angiosarcoma. Methods: The clinical data of 14 patients hospitalized with primary cardiac angiosarcoma from January 2001 to December 2017 in Peking Union Medical College Hospital were collected and analyzed. Metastatic cardiac angiosarcoma was not included in this study. Patients were followed up post discharge per telephone call or clinical visit. Results: Of the 14 patients, 8 were males and 6 were females, average age was 48 years. The main clinical symptoms were shortness of breath (8/14), hemoptysis (6/14), fever (5/14), chest pain (4/14) and cough (3/14). Imaging examinations showed that the tumors of 8 patients were located in the right heart and 6 in the pericardial cavity. Tumors in the right heart often infiltrate the atrial wall and cause pericardial effusion (7/8). Tumors in the pericardium were characterized by recurrent bloody pericardial effusion (6/6), prone to progressive constrictive pericarditis (3/6), pericardial fluid cytology was often negative (6/6). MRI showed heterogeneous high signal intensity (cauliflower aspect) on T2-weighted image and heterogeneous enhancement with a"sunray" aspect at the perfusion study. At the time of diagnosis, 8 patients developed lung or adrenal metastasis (8/14). The median survival was only 305 days. Conclusions: Primary cardiac angiosarcoma is a rare disease with non-specific clinical manifestation and poor prognosis. Imaging examinations may help diagnosis. The high invasiveness and the easy-to-metastasis feature of the tumor contribute to the poor prognosis of cardiac angiosarcoma.

Structure Basis for Inhibition of SARS-CoV-2 by the Feline Drug GC376

The pandemic of SARS-CoV-2 coronavirus disease-2019 (COVID-19) caused by SARS-COV-2 continues to ravage many countries in the world. Mpro is an indispensable protein for viral translation in SARS-CoV-2 and a potential target in high-specificity anti-SARS-CoV-2 drug screening. In this study, to explore potential drugs for treating COVID-19, we elucidated the structure of SARS-CoV-2 Mpro and explored the interaction between Mpro and GC376, an antiviral drug used to treat a range of coronaviruses in Feline via inhibiting Mpro. The availability and safety of GC376 were proved by biochemical and cell experiments in vitro. We determined the structure of an important protein, Mpro, in SARS-CoV-2, and revealed the interaction of GC376 with the viral substrate and inhibition of the catalytic site of SARS-CoV-2 Mpro.

Application of 99Tc m-pyrophosphate in transthyretin cardiac amyloidosis / 中华核医学与分子影像杂志

Objective:To evaluate the diagnostic value of 99Tc m-pyrophosphate (PYP) in transthyretin cardiac amyloidosis. Methods:From December 2018 to July 2019, 17 patients (9 males, 8 females, age: (53.4±13.0) years) with suspected cardiac amyloidosis underwent 99Tc m-PYP imaging in Peking Union Medical College Hospital were prospectively included. Visual score and semi-quantitative values (heart to contralateral ratio, H/CL) of 99Tc m-PYP uptake were used to diagnose transthyretin amyloidosis (ATTR). Biopsies and genetic measurements were also developed to evaluate the diagnostic value of the imaging. Results:Five of the 17 patients were diagnosed as ATTR with a visual score of 2-3, H/CL≥1.5, and confirmed with the biopsy or gene test. Four patients were diagnosed as ATTR with positive genetic results but no cardiac symptoms, and their visual scores were between 0 and 1 with H/CL<1.5. Considering the young age of the patients, amyloid deposition might have not yet caused visceral damage. Visual score of other 8 patients with negative 99Tc m-PYP imaging were also between 0 and 1 with H/CL<1.5, 2 of 8 were confirmed with light chain amyloidosis (AL) by biopsy, 3 were clinically diagnosed as AL and 3 were ATTR excluded. The accuracy of 99Tc m-PYP imaging for diagnosing ATTR was 11/11. Conclusion:99Tc m-PYP imaging is helpful for non-invasive diagnosis of transthyretin cardiac amyloidosis.