Dysregulation in nucleic acid-sensing pathway genes is associated with cancer patients' prognosis.

The innate immune system, the first line of defense against pathogens, is activated by nucleic acids from microbial invaders that are recognized by nucleic acid-sensing receptors. Recent evidence affirms the ability of these receptors to respond to nucleic acids released by damaged cancer cells. The innate immune system is also involved in cancer immunosurveillance, and could be modulated for devising effective antitumor therapies by targeting nucleic acid-sensing pathways. A systematic, comprehensive analysis of dysregulation in nucleic acid-sensing pathways in cancer is required to fully understand its role. Based on multidimensional data of The Cancer Genome Atlas pan-cancer cohort, we revealed that upregulation of cytosolic DNA-sensing genes like AIM2 and CGAS was common in tumor tissues. We used 15 genes in the nucleic acid-sensing pathway to cluster all tumor patients into 2 subgroups and found that the subgroup with higher expression of nucleic acid-sensing pathway genes was associated with poorer prognosis across cancer types. However, in homologous recombination deficient patients, the nucleic acid recognition activated subgroup was associated with better prognosis, which confirms the therapeutic effect of nucleic acid recognition. This study contributes to a better understanding of the functions and mechanisms of nucleic acid recognition in cancer, lays the foundation for new therapeutic strategies, and enlarges the scope of development of new drugs.

Synthesis and bioactivities evaluation of l-pyroglutamic acid analogues from natural product lead.

A series of l-pyroglutamic acid analogues from natural product lead were designed and synthesized, as well as their antifungal activities against Phytophthora infestans, neuritogenic activities, antibacterial activities and anti-inflammatory activities are described. The bioassays and SAR study showed that the majority of l-pyroglutamic acid esters have a significant antifungal activity against P. infestans, especially 2d and 2j demonstrated the best activities with EC50 values of 1.44 and 1.21 µg mL-1, which were about seven times that of commercial azoxystrobin (7.85 µg mL-1). Moreover, compounds 2e, 2g and 4d displayed anti-inflammatory activity against LPS-induced NO production in BV-2 microglial cells; neuritogenic activity in NGF-induced PC-12 cells is the same activity. This study demonstrates that compounds 2d and 2j are potential drugs to control P. infestans.

Effect of Zhuang medicine medicated thread moxibustion on protomics in serum of postherpetic neuralgia patient with Herpes zoster.

The aim of this study was to observe the effect of Zhuang medicine medicated thread moxibustion on protomics in serum of postherpetic neuralgia patient with herpes zoster and discuss the action mechanism of Zhuang medicine medicated thread moxibustion in treating postherpetic neuralgia (PHN). Patients were divided into three groups in clinic, namely the pre-treatment group (n=20), post-treatment group (n=20) and healthy group (n=20), patients meeting corresponding conditions were recruited in the voluntary principle to accept PHN pain evaluation and protomics tests respectively. Compared with the pre-treatment group, visual analogue scale (VAS) in post-treatment group obviously reduced, protomics indexes like MFG-ES, Lymphotoxin beta/TNFSF3, IL-19, Neuritin, NCAM-1/CD56 and PECAM-1/CD31 obviously changed. The Zhuang medicine medicated thread moxibustion can treat the postherpetic neuralgia patient with herpes zoster, its internal mechanism is to possibly change the protomics indexes like MFG-ES, Lymphotoxin beta/TNFSF3, IL-19, Neuritin, NCAM-1/CD56 and PECAM-1/CD31.

Simultaneous detection of 5-methylcytosine and 5-hydroxymethylcytosine at specific genomic loci by engineered deaminase-assisted sequencing.

Cytosine modifications, particularly 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), play crucial roles in numerous biological processes. Current analytical methods are often constrained to the separate detection of either 5mC or 5hmC, or the combination of both modifications. The ability to simultaneously detect C, 5mC, and 5hmC at the same genomic locations with precise stoichiometry is highly desirable. Herein, we introduce a method termed engineered deaminase-assisted sequencing (EDA-seq) for the simultaneous quantification of C, 5mC, and 5hmC at the same genomic sites. EDA-seq utilizes a specially engineered protein, derived from human APOBEC3A (A3A), known as eA3A-M5. eA3A-M5 exhibits distinct deamination capabilities for C, 5mC, and 5hmC. In EDA-seq, C undergoes complete deamination and is sequenced as T. 5mC is partially deaminated resulting in a mixed readout of T and C, and 5hmC remains undeaminated and is read as C. Consequently, the proportion of T readouts (P T) reflects the collective occurrences of C and 5mC, regulated by the deamination rate of 5mC (R 5mC). By determining R 5mC and P T values, we can deduce the precise levels of C, 5mC, and 5hmC at particular genomic locations. We successfully used EDA-seq to simultaneously measure C, 5mC, and 5hmC at specific loci within human lung cancer tissue and their normal counterpart. The results from EDA-seq demonstrated a strong concordance with those obtained from the combined application of BS-seq and ACE-seq methods. EDA-seq eliminates the need for bisulfite treatment, DNA oxidation or glycosylation and uniquely enables simultaneous quantification of C, 5mC and 5hmC at the same genomic locations.

Whole-Genome Sequencing of 5-Hydroxymethylcytosine at Base Resolution by Bisulfite-Free Single-Step Deamination with Engineered Cytosine Deaminase.

The epigenetic modification 5-hydroxymethylcytosine (5hmC) plays a crucial role in the regulation of gene expression. Although some methods have been developed to detect 5hmC, direct genome-wide mapping of 5hmC at base resolution is still highly desirable. Herein, we proposed a single-step deamination sequencing (SSD-seq) method, designed to precisely map 5hmC across the genome at single-base resolution. SSD-seq takes advantage of a screened engineered human apolipoprotein B mRNA-editing catalytic polypeptide-like 3A (A3A) protein, known as eA3A-v10, to selectively deaminate cytosine (C) and 5-methylcytosine (5mC) but not 5hmC. During sequencing, the deaminated C and 5mC are converted to uracil (U) and thymine (T), read as T in the sequencing data. However, 5hmC remains unaffected by eA3A-v10 and is read as C during sequencing. Consequently, the presence of C in the sequence reads indicates the original 5hmC. We applied SSD-seq to generate a base-resolution map of 5hmC in human lung tissue. Our findings revealed that 5hmC was predominantly localized to CpG dinucleotides. Furthermore, the base-resolution map of 5hmC generated by SSD-seq demonstrated a strong correlation with prior ACE-seq results. The advantages of SSD-seq are its single-step process, absence of bisulfite treatment or DNA glycosylation, cost effectiveness, and ability to detect and quantify 5hmC directly at single-base resolution.

The Antitriple Negative Breast cancer Efficacy of Spatholobus suberectus Dunn on ROS-Induced Noncanonical Inflammasome Pyroptotic Pathway.

Breast cancer (BCa) is the leading cause of women's death worldwide; among them, triple-negative breast cancer (TNBC) is one of the most troublesome subtypes with easy recurrence and great aggressive properties. Spatholobus suberectus Dunn has been used in the clinic of Chinese society for hundreds of years. Shreds of evidence showed that Spatholobus suberectus Dunn has a favorable outcome in the management of cancer. However, the anti-TNBC efficacy of Spatholobus suberectus Dunn percolation extract (SSP) and its underlying mechanisms have not been fully elucidated. Hence, the present study is aimed at evaluating the anti-TNBC potential of SSP both in vitro and in vivo, through the cell viability, morphological analysis of MDA-MB-231, LDH release assay, ROS assay, and the tests of GSH aborted pyroptotic noninflammasome signaling pathway. Survival analysis using the KM Plotter and TNM plot database exhibited the inhibition of transcription levels of caspase-4 and 9 related to low relapse-free survival in patients with BCa. Based on the findings, SSP possesses anti-TNBC efficacy that relies on ROS-induced noncanonical inflammasome pyroptosis in cancer cells. In this study, our preclinical evidence is complementary to the preceding clinic of Chinese society; studies on the active principles of SPP remain underway in our laboratory.

Antifungal, anti-inflamatory and neuritogenic activity of newly-isolated compounds from Disporopsis aspersa.

A new ester (1) and a terpenoid (2) were isolated from the dried whole plant of Disporopsis aspersa (HUA) ENGL. ex DIELS for the first time and their structures were elucidated, as well as their biological activities are described. The two compounds all showed good antifungal activities, especially furanone (2) exhibited better antifungal activity against Pseudoperonospora cubensis and Phytophthora infestans with EC50 value of 22.82, 18.90 µg/mL, respectively. Compound 1 exhibited a significant promotion on the neurite outgrowth in NGF-induced PC-12 cells, and moderate inhibition on the NO production induced by lipopolysaccharide (LPS) in BV-2 microglial cells.

Clinical characteristics of Danon disease / 中华心血管病杂志

Objective: To review the clinical data of 7 patients with Danon disease and analyze their clinical characteristics. Methods: The medical records of 7 patients with Danon disease, who were hospitalized in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences from April 2008 to July 2021, were reviewed and summarized, of which 6 cases were diagnosed as Danon disease by lysosomal-associated membrane protein-2 (LAMP-2) gene mutation detection and 1 case was diagnosed by clinicopathological features. Clinical manifestations, biochemical indexes, electrocardiogram, echocardiography, skeletal muscle and myocardial biopsy and gene detection results were analyzed, and patients received clinical follow-up after discharge. Results: Six patients were male and average age was (15.4±3.5) years and the average follow-up time was (27.7±17.0) months. The main clinical manifestations were myocardial hypertrophy (6/7), decreased myodynamia (2/7) and poor academic performance (3/7). Electrocardiogram features included pre-excitation syndrome (6/7) and left ventricular hypertrophy (7/7). Echocardiography examination evidenced myocardial hypertrophy (6/7), and left ventricular dilatation and systolic dysfunction during the disease course (1/7). The results of skeletal muscle biopsy in 6 patients were consistent with autophagy vacuolar myopathy. Subendocardial myocardial biopsy was performed in 3 patients, and a large amount of glycogen deposition with autophagosome formation was found in cardiomyocytes. LAMP-2 gene was detected in 6 patients, and missense mutations were found in all these patients. During the follow-up period, implantable cardioverter defibrillator implantation was performed in 1 patient because of high atrioventricular block 4 years after diagnosis, and there was no death or hospitalization for cardiovascular events in the other patients. Conclusion: The main clinical manifestations of Danon disease are cardiomyopathy, myopathy and mental retardation. Pre-excitation syndrome is a common electrocardiographic manifestation. Autophagy vacuoles can be seen in skeletal muscle and myocardial pathological biopsies. LAMP-2 gene mutation analysis is helpful in the diagnose of this disease.

Anti-glioma mechanism of pterostilbene by regulating apoptosis and GSDME-mediated pyroptosis pathways: a study based on network pharmacology and experimental research / 中国中药杂志

This study aimed to explore the anti-glioma effect of natural compound pterostilbene(PTE) through regulating pyroptosis and apoptosis pathways, and to analyze the possible anti-glioma pathways and targets of PTE by network pharmacology and molecular docking. In this study, the action targets of PTE and the glioma targets were obtained by network pharmacology to construct a target network and a protein-protein interaction(PPI) network to predict the possible action targets of PTE against glioma. Molecular docking was performed on the core targets by AutoDock and the action pathways of PTE against glioma were predicted by enrichment analysis. In addition, the effect of PTE on the viability of U87MG and GL261 glioma cells was detected by CCK-8 assay. Clone formation assay and cell scratching assay were used to explore the effect of different concentrations of PTE on the proliferation and migration, respectively of glioma cells. Hoechst staining was used to observe PTE-induced apoptosis in glioma cells. The changes in mitochondrial membrane potential were detected by JC-1 staining. The pyroptosis-inducing effect of PTE on glioma cells was observed by inverted microscopy and lactate dehydrogenase(LDH) assay. Hoechst 33342/PI dual staining assay was performed to detect the integrity of glioma cell membranes. The expressions of pyroptosis and apoptosis-related proteins in glioma cells after PTE induction were determined by Western blot. In this study, 37 anti-glioma targets of PTE were obtained, and enrichment analysis suggested that PTE exerted anti-glioma effects through various signaling pathways including cancer pathway, proteoglycan in cancer, PI3K/AKT pathway, and apoptosis regulatory pathway. Molecular docking revealed that PTE had good binding activity with the main targets. Compared with the control group, PTE significantly reduced the viability as well as the proliferation, migration and adhesion abilities of U87MG and GL261 cells; it induced the apoptosis of the two glioma cells and the decrease of mitochondrial membrane potential in U87MG cells, and the effects increased with the increase of drug concentration. Compared with the conditions in the control group, glioma cells in the PTE group had increased pyroptosis-specific appearance and gradually increased LDH release; the number of PI positive cells was significantly elevated with the increase of PTE concentration as revealed by Hoechst 33342/PI staining; the expression levels of apoptosis-related factors cleaved PARP1 and B-cell lymphoma-2(Bcl-2) associated X(BAX) in the PTE group were markedly up-regulated, while the expression level of Bcl-2 was markedly down-regulated; the activation levels of pyroptosis-related proteins cleaved caspase-3 and gasdermin E-N(GSDME-N) had a remarkable rise in the PTE group, while no significant changes were found in the activation levels of gasdermin D-N(GSDMD-N) and cleaved caspase-1. In summary, PTE plays an anti-glioma role by inhibiting cell viability, proliferation, and migration and activating the caspase-3/GSDME-mediated pyroptosis pathway and mitochondrial apoptosis pathway.

Application and value of intravascular ultrasound for excimer laser ablation combined with drug-coated balloon in the treatment of lower limb arteriosclerotic obliterans / 中华外科杂志

Objective: To examine the value of intravascular ultrasound (IVUS) for excimer laser ablation (ELA) combined with drug-coated balloon (DCB) in treating lower limb arteriosclerotic obliterans (ASO). Methods: As a prospective case series study, patients who underwent ELA combined with DCB for lower limb ASO with the guidance of IVUS from September 2021 to March 2022 at Department of Vascular Surgery, Zhongshan Hospital, Fudan University were enrolled prospectively. Lesion characteristics, procedure-related outcomes and complications were collected. The therapy outcomes were compared with baseline data by paired t test. Results: There were 8 males and 2 females, aged (72.0±5.9) years (range: 61 to 81 years). Of all the 11 lesions, there were 8 lesions in superficial femoral artery and 3 in popliteal artery. The lesion length was (7.0±2.4) cm (range: 3.2 to 9.8 cm). There were 4 chronic totally occlusion and 7 severe stenosis. All patients underwent the operation successfully. The technical success rate was 10/11. Bailout stenting was performed in one lesion because of flow-limiting dissection. Four lesions were grade 3 to 4 in peripheral artery calcium score system, and 9 lesions with calcification arc≥180°. Larger diameter drug-coated balloons were selected in 5 lesions after measurement of intravascular ultrasound. The follow-up time was (6.0±1.9) months (range: 3 to 9 months). The ankle-brachial index of the patient was significantly improved immediately after surgery (0.97±0.13 vs. 0.48±0.18, t=-7.60, P<0.01) and at 3 months after surgery (0.95±0.12 vs. 0.48±0.18, t=-7.17, P<0.01). The 3-month primary patency rate was 11/11, the target lesion reintervention was 0 and ulcer healing rate was 3/4. Conclusion: IVUS assisted ELA in the treatment of lower limb artery lesions is safe and effective in early stage.

Outcomes of excimer laser ablation combined with drug-coated balloon for atherosclerotic lesions in below-the-knee arteries / 中华普通外科杂志

Objective:To investigate the safety and efficacy of excimer laser ablation (ELA) combined with drug-coated balloon (DCB) for the below-the-knee (BTK) artery lesions.Methods:From Jun 2019 to Nov 2022, 22 patients receiving ELA combined with DCB in atherosclerotic lesions of BTK artery at these two centers were retrospectively analyzed.Results:In these 22 patients there were 3 (13.6%) suffering from stenosis and 19 (86.4%) from chronic total occlusion (CTO) lesions. The mean length of lesion was (25.6±5.7) cm. The technical success rate was 95.5%. Flow-limiting dissection was found in 1 (4.5%) patient and a bailout stent was deployed. The mean ankle-brachial index (ABI) significantly improved during the follow-up period compared with that before the treatment. The median follow-up time was 21.5 months. The 1-year primary patency rate was 80.3%Conclusion:ELA combined with DCB was safe and effective in the treatment of atherosclerotic lesions of BTK artery, improving the primary patency.

Traditional Chinese Medicine in Prevention and Treatment of Rheumatoid Arthritis Based on Pyroptosis Theory： A Review / 中国实验方剂学杂志

Pyroptosis is a newly discovered programmed cell death. It is an important natural immune response and has obvious anti-infection function. Studies have shown that pyroptosis plays an important role in the occurrence and development of rheumatoid arthritis. Traditional Chinese medicine（TCM） has unique advantages in the prevention and treatment of rheumatoid arthritis. How to guide TCM to effectively prevent and treat rheumatoid arthritis using pyroptosis theory is a new research hotspot in this field. This paper discussed the overview of pyroptosis theory，its mechanism， signal pathway，and application in the treatment of rheumatoid arthritis as well as the research on the activity of TCM based on pyroptosis theory. It was found that the occurrence of pyroptosis was related to Caspase-1-dependent classical inflammatory body pathway and Caspase-1-independent non classical inflammatory body pathway， and pyroptosis produced distinct regulatory effect on the occurrence，development and treatment of rheumatoid arthritis，which would provide a new strategy for the treatment of rheumatoid arthritis. Additionally，TCM recipes such as Miao ethnomedicine prescription Sidaxue and Duhuo Jishengtang， and a variety of effective components such as punicalagin and paeoniflorin monomer derivatives exerted anti-rheumatic and other biological activities by regulating pyroptosis. This provided a theoretical basis and research ideas for the in-depth study of pyroptosis theory and guiding the prevention and treatment of rheumatoid arthritis with TCM.

Traditional Chinese Medicine in Prevention and Treatment of Rheumatoid Arthritis Based on Pyroptosis Theory： A Review / 中国实验方剂学杂志

Pyroptosis is a newly discovered programmed cell death. It is an important natural immune response and has obvious anti-infection function. Studies have shown that pyroptosis plays an important role in the occurrence and development of rheumatoid arthritis. Traditional Chinese medicine（TCM） has unique advantages in the prevention and treatment of rheumatoid arthritis. How to guide TCM to effectively prevent and treat rheumatoid arthritis using pyroptosis theory is a new research hotspot in this field. This paper discussed the overview of pyroptosis theory，its mechanism， signal pathway，and application in the treatment of rheumatoid arthritis as well as the research on the activity of TCM based on pyroptosis theory. It was found that the occurrence of pyroptosis was related to Caspase-1-dependent classical inflammatory body pathway and Caspase-1-independent non classical inflammatory body pathway， and pyroptosis produced distinct regulatory effect on the occurrence，development and treatment of rheumatoid arthritis，which would provide a new strategy for the treatment of rheumatoid arthritis. Additionally，TCM recipes such as Miao ethnomedicine prescription Sidaxue and Duhuo Jishengtang， and a variety of effective components such as punicalagin and paeoniflorin monomer derivatives exerted anti-rheumatic and other biological activities by regulating pyroptosis. This provided a theoretical basis and research ideas for the in-depth study of pyroptosis theory and guiding the prevention and treatment of rheumatoid arthritis with TCM.

Treatment of Psoriasis Vulgaris with Medicated Thread Moxibustion of Zhuang Medicine: A Multicenter Randomized, Parallel Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To explore the efficacy and safety of Zhuang medicine medicated thread moxibustion (ZMTM) on psoriasis vulgaris.@*METHODS@#A multicenter, randomized, parallel controlled clinical trial was designed. A total of 241 outpatients with psoriasis vulgaris were randomly divided into a control group (120 cases) and a treatment group (121 cases) using a central block randomization from June 2015 to May 2018. The control group was treated with Western medicines alone including pidotimod dispersible tablets, vitamin B compound tablets, and compound cod liver oil-zinc oxide ointment. The treatment group was treated with ZMTM every 2 days combined with Western medicines. The two groups received continuous intervention for 30 days. The primary outcome was Psoriasis Area and Severity Index (PASI), and the secondary outcomes included Itch Rating Scale, Dermatology Quality of Life Index (DLQI), Hamilton Anxiety Rating Scale (HAMA), as well as PASI response rate. Meanwhile, adverse events were evaluated during the whole clinical trial. Follow-up was carried out 30 days after treatment.@*RESULTS@#There were 5 cases of shedding in this trial. In intention-to-treat analysis, 236 cases were included and each group contained 118 cases. On the 30th and 60th days, PASI scores of patients in each group were significantly lower than that at baseline (P<0.01) and the PASI score reduction of the treatment group was greater than that of the control group (P<0.01). Itch Rating Scale, DLQI, and HAMA scale were decreased in both groups after treatment, and the treatment group showed a better therapeutic effect (P<0.01). The response rates of PASI 50 and 75 were significantly higher than those in the control group [81.4% (96/118), 43.2% (51/118) vs. 41.5% (49/118), 11.0% (13/118), respectively, P<0.05]. During follow-up, the improvements in scores of PASI, Itch Rating Scale, DLQI, and HAMA of the treatment group were significantly greater than those of the control group (P<0.01). The response rates of PASI 50 and 75 in the treatment group were significantly higher than those in the control group, respectively (both P<0.05). No obvious adverse reaction was found in either group.@*CONCLUSION@#ZMTM combined with Western medicines showed a better therapeutic effect in the treatment of psoriasis vulgaris without obvious adverse reaction. (Trial Registration No. ChiCTR-IOR-16008159).

Regulatory Mechanism of Zedoary Turmeric Oil on VEGFA， STAT3 and mTOR in Ovarian Cancer / 中国实验方剂学杂志

Objective:To explore the effects and mechanism of zedoary turmeric oil and its active components on the vascular endothelial growth factor A （VEGFA）， signal transducer and activator of transcription 3 （STAT3）， and mechanistic target of rapamycin （mTOR） in the ovarian cancer （OC）. Method:Network pharmacology technology was employed to analyze the mechanism of Curcumae Rhizoma on OC. Bioinformatics was used to analyze the expression of VEGFA， STAT3， and mTOR in OC and the effect on the prognosis of OC to explore the feasibility of zedoary turmeric oil in regulating VEGFA， STAT3， and mTOR in OC.The xenograft tumor model of nude mice was established， and the effects of zedoary turmeric oil and its active components on VEGFA， STAT3， and mTOR in OC were observed by hematoxylin-eosin （HE） staining， real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR）， Western blot， and immunohistochemistry （IHC）. Result:Bioinformatics analysis and literature research showed that VEGFA， STAT3， and mTOR played a special regulatory role in the occurrence and development of OC， and were potential key targets for the proliferation of OC. Network pharmacology analysis revealed that Curcumae Rhizoma could regulate multiple disease targets of OC， and mediate VEGFA， STAT3， and mTOR in OC through these multiple targets. As demonstrated by HE staining， the tumor cells in the model group were densely arranged， with no erosion on the edge and no vesicles inside. Compared with the model group， the cell density in other treatment groups was reduced， and strip-shaped erosion on the edge and small empty vesicles were observed in the tumor tissue， especially in the zedoary turmeric oil group. According to the results of Real-time PCR and IHC， zedoary turmeric oil and its active components could inhibit the mRNA and protein expression of VEGFA， STAT3， and mTOR in the OC tissue （<italic>P</italic><0.05）. Conclusion:Zedoary turmeric oil and its active components could reduce the expression of VEGFA， STAT3， and mTOR in tumor tissue of nude mice， and inhibited the proliferation of OC through VEGFA， STAT3， and mTOR.

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.

Study on the Medical Insurance Budget Impact Analysis Guideline in Some European Countries and Its Enligh- tenment to China / 中国药房

OBJECTIVE：To study the m edical insurance budget impact analysis （BIA）guidelines or nomative documents of some European countries ，and to provide the suggestions for the formulation and implementation of medical insurance BIA guidelines in China. METHODS ：Medical insurance BIA guidelines or related documents in European countries such as Ireland ， France，Poland，Belgium and UK were retrieved to summarize and comparatively analyze the general analysis framework and special specification. The formulation of medical insurance BIA guideline in China and the suggestions were put forward. RESULTS & CONCLUSIONS ：The above-mentioned medical insurance BIA guidelines or documents of the five European countries generally study the impact of the cost of health technology on resources within 3-5 years from the perspective of budget holders. The analysis framework of the guidelines or documents is basically the same ，but the guidelines or documents are adjusted according to the characteristics of national health system in terms of the positioning of medical insurance BIA ，the scope of cost data inclusion ， model design ，population subgroup analysis and so on. For example ，Ireland had special requirements on cost data inclusion ， sensitivity analysis and data source ，while France had detailed regulations on medical insurance BIA model ，sensitivity analysis and presentation of medical insurance BIA results. Our country should pay attention to the role of medical insurance BIA in medical and health decision-making ，formulate China ’s medical insurance BIA guidelines to standardize empirical research ，and combine the characteristics of China ’s health system when formulate the guideline. It is suggested that China ’s medical insurance BIA guidelines should at least include research perspective ，research time limit and discount ，reference situation ，target population ， cost，market share ，data source ，uncertainty analysis and other overall framework or basic elements to ensure the smooth operation of medical and health funds.

MicroRNAs of bone marrow mesenchymal stem cell-derived exosomes regulate acute myeloid leukemia cell proliferation and apoptosis / 中华医学杂志(英文版)

BACKGROUND@#Acute myeloid leukemia (AML) is a malignant hematological disease, originating from hematopoiesis stem cell differentiation obstruction and clonal proliferation. New reagents or biologicals for the treatment of AML are urgently needed, and exosomes have been identified as candidate biomarkers for disease diagnosis and prognosis. This study aimed to investigate the effects of exosomes from bone marrow mesenchymal stem cells (BMSCs) on AML cells as well as the underlying microRNA (miRNA)-mediated mechanisms.@*METHODS@#Exosomes were isolated using a precipitation method, followed by validation using marker protein expression and nanoparticle tracking analysis. Differentially expressed miRNAs were identified by deep RNA sequencing and confirmed by quantitative real-time polymerase chain reaction (qPCR). Cell proliferation was assessed by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt method, and cell cycle progression and apoptosis were detected by flow cytometry. Functional gene expression was analyzed by qPCR and Western blotting (WB). Significant differences were determined using Student's t test or analysis of variance.@*RESULTS@#BMSCs-derived exosomes effectively suppressed cell proliferation (both P < 0.0001 at 10 and 20 μg/mL) and cell cycle progression (P < 0.01 at G0-G1 stage), and also significantly enhanced cell apoptosis (P < 0.001) in KG-1a cells. There were 1167 differentially expressed miRNAs obtained from BMSCs-derived exosomes compared with KG-1a cell-derived exosomes (P < 0.05). Knockdown of hsa-miR-124-5p in BMSCs abrogated the effects of BMSCs-derived exosomes in regulating KG-1a such as the change in cell proliferation (both P < 0.0001 vs. normal KG-1a cell [NC] at 48 and 72 h). KG-1a cells treated with BMSCs-derived exosomes suppressed expression of structural maintenance of chromosomes 4 (P < 0.001 vs. NC by qPCR and P < 0.0001 vs. NC by WB), which is associated with the progression of various cancers. This BMSCs-derived exosomes effect was significantly reversed with knockdown of hsa-miR-124-5p (P < 0.0001 vs. NC by WB).@*CONCLUSIONS@#BMSCs-derived exosomes suppress cell proliferation and cycle progression and promote cell apoptosis in KG-1a cells, likely acting through hsa-miR-124-5p. Our study establishes a basis for a BMSCs-derived exosomes-based AML treatment.

Treatment for arteriosclerosis obliterans complicated with acute thrombosis of lower extremity / 中华普通外科杂志

Objective:To discuss the clinical treatment for arteriosclerosis obliterans combined with acute thrombosis (ASOCAT) of lower extremities.Methods:The treatment methods and results of 30 patients with ASOCAT admitted to our center from Jan 2009 to May 2019 were retrospectively analyzed.Results:The course of acute thrombosis in 30 patients was (9.5±5.2) days, and the average course of ASO was (2.1±1.4) years. Among 30 patients, 13 patients had aortoiliac occlusion (type Ⅰ), and 17 patients had femoropopliteal lesion (type Ⅱ). Twenty-eight patients underwent endovascular treatment, 1 had hybrid operation, and 1 was given aorto-bilateral femoral bypass. One patient died perioperatively. 24 patients were followed up for (16.3±16.1) months. One died during follow-up.Two patients underwent above-knee amputation within 6 months. Two patients had distal superficial femoral artery reocclusion within 12 months. The restenosis/reocclusion rates within 12 months of type Ⅰ and Ⅱ patients were 12.5% and 21.4%, respectively. The 6/12-month amputation-free survival rates for type Ⅰ and type Ⅱ were 87.5%/87.5% and 92.8%/85.7%, respectively.Conclusion:Reasonable and active use of open surgery, endovascular treatment or hybrid operation could achieve acceptable outcomes in patients with ASOCAT.

Rivaroxaban and low molecular heparin in prevention of deep venous thrombosis and blood loss after total hip arthroplasty in elderly patients / 中国组织工程研究

BACKGROUND: Deep venous thrombosis and blood loss are common complications after total hip arthroplasty in elderly patients. Thus, it needs to pick valid treatments to reduce the harm in the clinical treatment. OBJECTIVE: To compare and observe the effects of rivaroxaban and low molecular heparin on preventing deep venous thrombosis and blood loss after total hip arthroplasty in elderly patients. METHODS: 196 cases in Department of Orthopedics, General Hospital of Shuicheng Mining Group of Guizhou Province treated by unilateral total hip arthroplasty were enrolled between January 2015 and January 2017. They were randomly divided into observation group (98 cases) and control group (98 cases). The observation group was treated with oral rivaroxaban 6 hours after surgery for 2 consecutive weeks. The control group was subcutaneously injected with low molecular heparin injection 6 hours after surgery for 5 consecutive weeks. The coagulation index was measured by automatic coagulation analyzer at preoperative, 1 day, 1 and 2 weeks after surgery. Deep venous thrombosis was evaluated in the two groups. The caliber sizes of superficial femoral vein and popliteal vein were measured by color Doppler ultrasound before surgery, 1, 2, 3 and 4 weeks after surgery. Blood loss was recorded in the two groups. RESULTS AND CONCLUSION: (1) The difference in serum D-dimer levels was statistically significant 1 and 2 weeks after surgery in both groups (P < 0.05). Serum D-dimer levels were lower in the observation group than in the control group. (2) The incidence of deep venous thrombosis was lower in the observation group than in the control group (P < 0.05). (3) The caliber size of superficial femoral vein and popliteal vein was significantly different 1, 2, 3 and 4 weeks after surgery in both groups (P < 0.05). The caliber size of superficial femoral vein and popliteal vein was larger in the observation group than in the control group. (4) Hidden blood loss and total blood loss were significantly different between the two groups (P < 0.05). The hidden blood loss and total blood loss were higher in the observation group than in the control group. (5) Results suggest that rivaroxaban has a positive meaning for prevention of deep venous thrombosis after total hip arthroplasty in elderly patients. However, hidden blood loss is worthy of attention.