Obesity is closely associated with arterial stiffening and pathological vascular remodeling, yet its key molecular mechanisms remain incompletely understood. The endocrine function of adipocytes reveals the significance in regulating vascular diseases. This study investigated the adipocyte-derived serine protease inhibitor A3c (Serpina3c) in regulating vascular extracellular matrix (ECM) homeostasis and vascular smooth muscle cell (VSMC) phenotypic switching during obesity-related vascular injury. Serpina3c expression was significantly reduced in perivascular and epididymal adipose tissue in high-fat diet (HFD)-fed mice. Serpina3c deficiency exacerbated arterial stiffening and impaired vascular reactivity in HFD-fed mice, accompanied by ECM disorganization and VSMC switching toward a synthetic phenotype. Conversely, adipocyte-specific restoration of Serpina3c in perivascular/epididymal fat effectively reversed these abnormalities. Mechanistically, adipocyte-derived Serpina3c bound to the ADAMTS4 proteinase domain and inhibited its enzymatic activity, leading to decreased fibronectin cleavage. The reduction in fibronectin fragments suppressed integrin-mediated activation of the AKT1/NF-κB signaling pathway, ultimately maintaining ECM homeostasis and preventing the transition of VSMCs to a synthetic phenotype. Accordingly, the impaired vascular reactivity in HFD-fed Serpina3c knockout mice was rescued by an ADAMTS4 antagonist. Clinically, aneurysmal tissues from patients with a high body mass index showed decreased co‑localization of Kallistatin (the human homolog of Serpina3c) with ADAMTS4, alongside more severe aneurysmal progression and arterial structural damage. In summary, this study identifies the adipokine Serpina3c as a novel endogenous inhibitor of ADAMTS4 that limits ECM proteolysis and VSMC synthetic switching by attenuating fragmented fibronectin-mediated AKT1/NF-κB signaling. Targeting Serpina3c provides a new therapeutic approach for obesity-related arterial remodeling.

Myocardial ischemia-reperfusion (I/R) injury is a significant complication post-revascularization in acute myocardial infarction, with limited effective clinical interventions. Corilagin, a natural polyphenolic compound, exhibits antioxidant and anti-inflammatory properties in various disease models. However, its effects and mechanisms in myocardial I/R injury remain unclear. This study aims to elucidate the specific mechanism by which Corilagin regulates ferroptosis through the PI3K/AKT signaling pathway, thereby laying a theoretical groundwork for the development of innovative cardioprotective agents. A myocardial I/R model was established in mice through left anterior descending (LAD) artery ligation, and Corilagin's effectiveness was assessed using echocardiography, biochemical assays, and histopathological analysis. Additionally, an in vitro H/R model with neonatal rat cardiomyocytes was employed to examine ferroptosis-related markers, oxidative stress, and mitochondrial function. Utilizing network pharmacology and molecular docking analysis, potential targets were identified and subsequently validated through pharmacological inhibition of the PI3K pathway with LY294002. The findings demonstrate that Corilagin exhibited significant cardioprotective effects against I/R injury, as evidenced by reduced myocardial injury markers, decreased infarct size, and improved cardiac function. In vitro studies revealed that Corilagin treatment enhanced cell viability, reduced ROS levels and iron content, and restored mitochondrial membrane potential. Network pharmacology and molecular docking identified PI3K as a crucial target, with subsequent activation of the PI3K/AKT pathway. Notably, PI3K inhibition abolished Corilagin's suppression of ferroptosis, underscoring its pathway-dependent action. Corilagin alleviates myocardial I/R injury by activating the PI3K/AKT pathway to suppress ferroptosis, highlighting its potential as a therapeutic candidate for clinical translation.

Adipose tissue dysfunction leads to abnormal lipid metabolism and high inflammation levels. This research aims to explore the role of Serpina3c, which is highly expressed in adipocytes, in obesity-related hypertriglyceridemia and metaflammation. Serpina3c global knockout (KO) mice, adipocyte-specific Serpina3c overexpressing mice, Serpina3c knockdown (KD) mice, and hypoxia-inducible factor 1 alpha (Hif1α) KD mice were fed a high-fat diet (HFD) for 16 weeks to generate obesity-related hypertriglyceridemia mice models. In the present study, Serpina3c KO mice and adipocyte-specific Serpina3c KD mice exhibited more severe obesity-related hypertriglyceridemia and metaflammation under HFD conditions. Serpina3c KO epididymal white adipose tissue (eWAT) primary stromal vascular fraction (SVF)-derived adipocytes exhibited higher lipid (triglyceride and non-esterified fatty acid) levels and higher fatty acid synthase expression after palmitic acid (PA) stimulation. Adipocyte-specific Serpina3c overexpression in KO mice prevented the KO group phenotype. The RNA-seq and in vitro validation revealed that Hif1α and the glycolysis pathways were up-regulated in Serpina3c KD adipocytes, which were all validated by in vitro and in vivo reverse experiments. Co-immunoprecipitation (co-IP) provided evidence that Serpina3c bound nuclear factor erythroid 2-related factor 2 (Nrf2) regulates Hif1α. Nrf2 KD reduced Hif1α and Fasn expression, decreased lipid content, and reduced the extracellular acidification rate in Serpina3c KO adipocytes. Metabolomics revealed that lactic acid (LD) levels in eWAT were responsible for adipose-associated macrophage inflammation. In summary, Serpina3c inhibits the Hif1α-glycolysis pathway and reduces de novo lipogenesis (DNL) and LD secretion in adipocytes by binding to Nrf2, thereby improving HFD-induced lipid metabolism disorders and alleviating adipose tissue macrophage inflammation.

IntroductionSepsis-induced cardiomyopathy (SICM) is a life-threatening complication characterized by acute cardiac dysfunction during sepsis., and macrophages play a crucial role in SICM pathogenesis. ADAM8 has been implicated in inflammation-driven diseases, yet its role in SICM remains uncharted.MethodsMouse models of SICM were established using lipopolysaccharide (LPS) injection and cecal ligation and puncture (CLP). Macrophage-specific ADAM8 knockout (CKO) mice were generated. RNA transcriptome sequencing was conducted on left ventricular tissues sourced from ADAM8 CKO mice, as well as on RAW264.7 cell lines that were treated with both ADAM8 knockdown (KD) lentivirus and LPS.ResultsHere, we demonstrate that ADAM8 expression is significantly upregulated in cardiac macrophages of SICM mice using single-cell transcriptomics and immunofluorescence. Macrophage-specific ADAM8 CKO mice exhibited preserved cardiac function, reduced myocardial injury markers, attenuated apoptosis (decreased Bax/Bcl2 ratio), and enhanced survival in both LPS-induced and CLP sepsis models. Transcriptomic analysis revealed downregulation of cytokine-cytokine receptor pathways in CKO hearts, suggesting diminished inflammatory responses. Mechanistically, ADAM8 deficiency promoted macrophage efferocytosis by increasing phagocytic receptors (MerTK) while reducing soluble Mer (sMer) generation. Conversely, sMer administration abolished the cardioprotective effects in CKO mice, exacerbating cardiac dysfunction and mortality.ConclusionsOur findings identify ADAM8 as a critical regulator of macrophage-mediated inflammation and impaired macrophage efferocytosis in SICM. Targeting ADAM8 or its downstream effectors may represent a novel therapeutic strategy for sepsis-induced cardiac complications.

The protective mechanism of tetramethylpyrazine (TMP), an alkaloid derived from the Chinese herbal remedy Ligusticum chuanxiong, in relation to myocardial ischemia/reperfusion injury (MIRI) is not yet fully understood. To investigate the therapeutic effects of TMP, we established an in vivo rat model of MIRI and an in vitro hypoxia and reoxygenation (H/R) model using H9c2 cells. First, TMP significantly reduced the infiltration of inflammatory cells in the myocardium, decreased serum levels of myocardial injury markers (CK-MB, cTnT and LDH), and alleviated myocardial infarct size in I/R rats. Additionally, TMP attenuated cell apoptosis and enhanced cell viability in H9c2 cells subjected to H/R. Furthermore, we employed NOD-like receptor protein 3 (NLRP3)-specific inhibitors (MCC950) and agonists (nigericin) to explore the role of the NLRP3 inflammasome in TMP's protective effects against MIRI. TMP was found to inhibit NLRP3 inflammasome activation and reduce caspase-1-dependent pyroptosis. We investigated the potential mechanism underlying the protective effect of TMP on MIRI using drug affinity responsive target stability (DARTS) and liquid chromatography tandem mass spectrometry (LC-MS/MS) techniques. It was found that myosin light chain-2 (Myl2) was the molecule directly responsible for TMP's protective effect on MIRI. Following TMP treatment, the protein levels of Myl2 increased in the heart tissues of the I/R rats and in H9c2 cells subjected to H/R in a dose-dependent manner. Finally, the cardioprotective effects of TMP, including the inhibition of the NLRP3 inflammasome, were partially negated by the genetic silencing of Myl2 using siRNA. This study indicated that TMP mitigated MIRI by regulating the inhibition of the Myl2-mediated NLRP3 signaling pathway.

Introduction A disintegrin and metalloproteinase 8 (ADAM8), a crucial regulator in macrophages, is closely associated with cardiovascular disease progression. Objectives This study aimed to explore how ADAM8 regulates macrophage function to inhibit cardiac repair after myocardial infarction (MI). Methods Macrophage-specific ADAM8 knockout mice (ADAM8flox/flox, Lyz2-Cre, KO) and corresponding control mice (ADAM8flox/flox, Flox) were established using the CRISPR/Cas9 system. Bone marrow transplantation was performed, and macrophage-specific ADAM8-overexpressing adeno-associated virus (AAV6-CD68-Adam8) was produced. Finally, proteomics, RNA sequencing, and co-immunoprecipitation/mass spectrometry (COIP/MS) were used to explore the underlying mechanisms involved. Results ADAM8 was highly expressed in the plasma of patients with acute myocardial infarction (AMI) and in cardiac macrophages derived from AMI mice. ADAM8 KO mice exhibited enhanced angiogenesis, suppressed inflammation, reduced cardiac fibrosis, and improved cardiac function during AMI, which were reversed by overexpressing macrophage-specific ADAM8 and intervention with the clinical anti-angiogenic biologic bevacizumab. Bone marrow transplantation experiments produced ADAM8 KO phenotypes. RNA sequencing showed that autophagy was activated in bone marrow-derived macrophages (BMDMs) with ADAM8 KO, which was confirmed via p-mTOR Ser2448/mTOR, p62, and LC3II/I detection. Autophagy inactivation suppressed angiogenic factor release and promoted inflammation in BMDMs with ADAM8 KO. Mechanistically, ADAM8 could bind to ANXA2 and promote phosphorylation of the ANXA2 Ser26 site. ADAM8 KO impeded ANXA2 phosphorylation, inhibited mTOR Ser2448 site phosphorylation, and activated autophagy, which were demonstrated using the activation or inactivation of ANXA2 phosphorylation. Conclusions ADAM8 was increased in cardiac macrophages after AMI. The ADAM8-ANXA2-mTOR-autophagy axis in macrophages is responsible for regulating angiogenesis and inflammation following MI. Thus, ADAM8 may be a new target in MI treatment.

Background Cuproptosis is known to regulate diverse physiological functions in many diseases, but its role in regulating Myocardial Ischemia-Reperfusion Injury (MI/RI) remains unclear. Methods For this purpose, the MI/RI microarray datasets GSE61592 were downloaded from the Gene Expression Omnibus (GEO) database, and the Differently Expressed Genes (DEGs) in MI/RI were identified using R software. Moreover, the MI/RI mice model was established to confirm further the diagnostic value of Pyruvate Dehydrogenase B (Pdhb), Dihydrolipoamide S-acetyltransferase (Dlat), and Pyruvate dehydrogenase E1 subunit alpha 1 (Pdhα1). Results The analysis of microarray datasets GSE61592 revealed that 798 genes were upregulated and 768 were downregulated in the myocardial tissue of the ischemia-reperfusion injury mice. Furthermore, Dlat, Pdhb, Pdhα1, and cuproptosis-related genes belonged to the downregulated genes. The receiver operating characteristics curve analysis results indicated that the Dlat, Pdhb, and Pdhα1 levels were downregulated in MI/RI and were found to be potential biomarkers for MI/RI diagnosis and prognosis. Similarly, analysis of Dlat, Pdhb, and Pdhα1 levels in the MI/RI mice revealed Pdhb being the key diagnostic marker. Conclusions This study demonstrated the prognostic value of cuproptosis-related genes (Dlat, Pdhb, and Pdhα1), especially Pdhb, MI/RI, providing new insight into the MI/RI treatment.

Doxorubicin is one of the most common antitumor drugs. However, cardiotoxicity's side effect limits its clinical applicability. In the present study, Gene Expression Omnibus (GEO) datasets were applied to reanalyze differentially expressed genes (DEGs) and construct weighted correlation network analysis (WGCNA) modules of doxorubicin-induced cardiotoxicity in wild-type mice. Several other bioinformatics analyses were performed to pick out the hub gene, and then the correlation between the hub gene and immune infiltration was evaluated. In total, 120 DEGs were discovered in a mouse model of doxorubicin-induced cardiotoxicity, and PF-04217903, propranolol, azithromycin, etc. were found to be potential drugs against this pathological condition. Among all the DEGs, 14 were further screened out by WGCNA modules, of which Limd1 was upregulated and finally regarded as the hub gene after being validated in other GEO datasets. Limd1 was upregulated in the peripheral blood mononuclear cell (PBMC) of the rat model, and the area under curve (AUC) of the receiver operating characteristic curve (ROC) in diagnosing cardiotoxicity was 0.847. The GSEA and PPI networks revealed a potential immunocyte regulatory role of Limd1 in cardiotoxicity. The proportion of "dendritic cells activated" in the heart was significantly elevated, while "macrophage M1" and "monocytes" declined after in vivo doxorubicin application. Finally, Limd1 expression was significantly positively correlated with "dendritic cells activation' and negatively correlated with "monocytes" and "macrophages M1'. In summary, our results suggested that limd1 is a valuable biomarker and a potential inflammation regulator in doxorubicin-induced cardiotoxicity.

目的 探讨腔内射频消融术(RFA)联合超声引导下泡沫硬化剂注射(UGFS)治疗非血栓性下肢静脉性溃疡的疗效.方法 回顾性分析135例(患肢152条)经RFA联合UGFS或RFA联合点式剥脱治疗的非血栓性下肢静脉性溃疡患者的临床资料,其中RFA联合UGFS组的患者61例(68条患肢),RFA联合点式剥脱组的患者74例(84条患肢).比较2组患者手术时间、住院时间、手术前后溃疡愈合情况、静脉临床严重程度评分(VCSS)、视觉模拟量表(VAS)评分及术后并发症等指标.结果 2组患者手术时间、住院时间比较差异有统计学意义(P<0.05).2组患者术后1个月、3个月溃疡愈合情况比较,差异无统计学意义(P>0.05);2组患者术前和术后1个月、3个月VCSS评分比较,差异均无统计学意义(P>0.05);2组患者术后1个月、3个月VAS评分比较差异均有统计学意义(P<0.05).2组患者并发症发生率比较差异有统计学意义(P<0.05).结论 两种方式对溃疡愈合的疗效相当,但RFA联合UGFS具有手术创伤更小、住院时间短、恢复快、并发症少等优点.

Objective:To compare the clinical efficacy of endovascular aortic aneurysm repair (EVAR) and open surgery repair (OSR) in the treatment of complex abdominal aortic aneurysm (cAAA).Methods:The clinical data of 144 patients with cAAA were retrospectively analyzed. All patients were diagnosed and treated in Beijing Anzhen Hospital Affiliated to the Capital Medical University, The First Medical Center of Chinese PLA General Hospital, Beijing Hospital, and Xuanwu Hospital of Capital Medical University from June 2016 to December 2021. They were divided into EVAR group ( n=114) and OSR group ( n=30) according to different treatments. The preoperative clinical characteristics, operation, and follow-up results of the two groups were compared. Subgroup analysis was performed in the EVAR group according to different treatments. Two independent samples t-test was used for inter-group comparison of measurement data follow the normal distribution, rank-sum test was used for non-normal data, and Chi-square test or Fisher's exact probability test was used for count data. Results:In EVAR group, the diameter of proximal aneurysm neck was wider than in OSR group, and the proportion of trapezoidal neck was higher than in OSR group, and the differences were statistically significant [(22.03±3.59) mm vs (19.40±4.28) mm, P=0.002; 36.0% vs 16.7%, P=0.044). The operation time, intraoperative bleeding volume, and perioperative blood transfusion volume in EVAR group were lower than those in OSR group. There were statistically significant differences [(158.56±93.06) min vs (368.53±95.96) min, t=-10.915, P<0.001;(92.84±168.83)ml vs (1 370.00±1 019.52) ml, t=-12.579, P<0.001; (14.91±133.85) ml vs (1 375.00±1 300.18)ml, t=-11.055, P<0.001). 144 patients were followed up for (25.6± 10.4) months. The total complication rate and perioperative complication rate in EVAR group were lower than in OSR group. The differences had statistical significance(16.7% vs 40.0%, χ2=7.654, P=0.006; 9.6% vs 40.0%, χ2=16.301, P<0.001).There was no statistically significant difference in the quality of life scores between the two groups at 1-year follow-up. Subgroup analysis showed that the endoleak rate in the conventional EVAR group was significantly higher than that in the unconventional EVAR group (11.9% vs 0%, χ2=6.035, P=0.014). When cervical angle ≥52°, the complication rate of conventional EVAR was significantly higher than that of patients with narrower angle (29.6% vs 0%, χ2=6.486, P=0.011). In the treatment of patients with trapezoidal neck, conventional EVAR group had a higher endoleak rate than unconventional EVAR group (19.0% vs 0%, χ2=6.632, P=0.010). The incidence of complications in OSR group was correlated with concomitant diseases, and the proportion of patients with complications complicated with coronary heart disease and cerebrovascular disease was significantly higher than that of patients without complications (75% vs. 27.8%, χ2=6.451, P=0.011; 25% vs. 0%, χ2=5.000, P=0.025). Conclusion:In the treatment of patients with cAAA, the total complication rate of EVAR, especially the perioperative complication rate, is lower than that of OSR. Choosing appropriate patients and correct treatment may reduce the risk of postoperative complications and endoleak of EVAR.

急性系膜缺血是一严重的疾患，尽管在近20年中，对其认知以及治疗有了长足的进步，但仍是死亡率较高的疾患。对于本病的充分认识，尤其是CTA的实施，能够早期诊断该病，并能制订相应的治疗策略，从而整体提高疾病的治疗转归。

Abstract Objective: The effect of Zinc Finger Protein-Activating Transcription Factor ( ZFP-ATF) stimulating the angiogenesis and maturity of neovascularization with the overexpression of the vascular endothelial growth factor(VEGF )were investigated in a mouse ischemia hindlimb model and rat mesenteric assay；Methods: After the synthesis of ZFP-ATP, the ischemic hindlimb mice were successfully constructed. ZFP-ATF, VEGF165 and saline control were injected into the ischemic muscles, respectively. After 14 days, the number of mice with different ischemic degree was counted, moreover,the ischemic gastrocnemius and soleus muscle were harvested for the immunohistochemical staining and VEGF protein analysis.Besides, in the rat mesenteric assay, ZFP-ATF, VEGF165 and saline control were injected into mesenteric adipose tissues, respectively. After 14 days, the number of neovessels in different groups was calculated. Meanwhile, mesenteric immunofluorescence staining was performed to evaluate the pericyte coverage.Results: In the mouse with the ischemic hindlimb, the expression of VEGF protein in the ZFP-ATF group was significantly higher,at the same time, the number of neovessels in the ZFP-ATF evaluated by CD31 staining was significantly increased than that in the VEGF165 and blank control group. Besides, in the rat mesenteric assay, the number of neovessels in the ZFP-ATF group was dramatically increased compared with VEGF165 and blank group. In mesenteric immunofluorescence staining, the ZFP-ATF group had a more complete and successive pericytes coverage. Conclusion: ZFP-ATF stimulating the endogenous physiological angiogenesis can promote the more mature neovascularization with the complete pericyte coverage.

目的:探讨超声造影一站式检查在重度动脉粥样硬化性肾动脉狭窄经皮肾动脉支架置入术(PRAS)中的应用价值.方法:回顾性分析2017年7月至2021年10月北京医院收治的行PRAS治疗的89例重度动脉粥样硬化性肾动脉狭窄患者,依据狭窄肾动脉(排除术后支架内再狭窄肾动脉)对应的患肾术后6个月核素肾动态显像检测的肾小球滤过率(GFR)的变化,分为肾功能改善组(患肾术后GFR升高≥20％)与对照组(患肾术后GFR升高<20％或降低),应用超声造影诊断肾动脉狭窄程度并对比两组肾皮质血流灌注参数变化.结果:89例患者,术中对比数字减影血管造影(DSA)证实95支肾动脉重度狭窄,术前超声造影诊断出93支重度狭窄,2支中度狭窄,诊断重度肾动脉狭窄准确率为97.9％(93/95).所有患者手术均成功.术后6个月超声造影诊断支架置入术后再狭窄准确率100％(9/9).与支架置入术前相比,肾功能改善组(n=27)术后皮质血流灌注参数上升时间、达峰时间均明显减少,峰值强度明显增高,AUC明显增大(P均<0.05);对照组(n=59)术后上升时间、达峰时间、AUC、峰值强度差异无统计学意义(P均>0.05).两组术前皮质血流灌注参数相比,仅AUC差异有统计学意义(P<0.05).结论:利用超声造影一站式检查诊断重度动脉粥样硬化性肾动脉狭窄及PRAS术后再狭窄结果可靠,肾皮质血流灌注参数在评估PRAS疗效方面具有一定的临床价值,其中AUC价值更高.

低密度脂蛋白胆固醇（LDL-C）是动脉粥样硬化性心血管病（ASCVD）的重要致病性危险因素。他汀时代不断积累的循证医学证据表明LDL-C低一些好一些，各国血脂管理指南的推荐目标值也随之降低。2019年欧洲心脏病学会（ESC）/欧洲动脉粥样硬化学会（EAS）血脂异常管理指南发表，标志着降脂理念向“更低一些，更好一些”转变。随着新型降脂药物的应用，LDL-C大幅度降低，其低水平状态成为常见现象，本文从循证医学角度总结了自他汀时代以来LDL-C低水平状态的临床获益及潜在的风险，为临床决策提供有益参考。.

Objective: To investigate the effect of remote ischemic preconditioning (RIPC) on contrast-induced acute kidney injury (CI-AKI) in patients with chronic total occlusion (CTO) after percutaneous coronary intervention (PCI). Methods: A total of 282 patients undergoing PCI at Zhongda Hospital Affiliated to Southeast University between June 2017 and January 2019 were prospectively enrolled. The patients were randomly divided into RIPC group (n=142) and control group (n=140). CI-AKI was defined as an increase in level of cystatin C (CysC)≥10% above baseline at 24 h after contrast administration. Baseline characteristics and the incidence of CI-AKI were compared between the two groups. The multivariate logistic regression analysis was further used to analyze the independent risk factors of CI-AKI. Results: There were no significant differences in age, gender, smoking, hypertension, diabetes, stroke and old myocardial infarction, coronary artery bypass graft surgery, previous PCI history and laboratory test indicators, target vessel and pathological characteristics of CTO lesions, contrast agent dosage, J-CTO (Multicenter CTO Registry in Japan) score, SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score, PCI success rate and stent number between the two groups (P>0.05). The incidence of CI-AKI was significantly lower (18.3% vs 29.3%, P=0.036) in RIPC group than that of control group. Multivariate logistic analysis found that creatinine [odds ratio (OR)=1.018,95%CI: 1.006-1.030, P=0.003], CysC (OR=5.200, 95%CI:2.714-9.963, P<0.001),contrast agent dosage (OR=1.013,95%CI: 1.007-1.019, P<0.001) and J-CTO score (OR=1.834, 95%CI: 1.145-2.939, P=0.012) were independent risk factors of CI-AKI. However, RIPC was an independent protective factor of CI-AKI (OR=0.391, 95%CI: 0.199-0.765, P=0.006). Conclusion: RIPC before contrast agent administration prevents CI-AKI in CTO patients undergoing PCI.

随着老龄化社会的到来，下肢动脉硬化闭塞症的患者也在逐年增多。介入治疗虽然能够复通血流，改善症状，但血管再狭窄/闭塞仍不能完全避免，从而导致症状复发甚至加重，出现下肢溃疡及坏疽。本文报道一例支架后再狭窄/闭塞的患者，成功地运用了支架下开通技术，使患者得以避免大截肢，随访6个月新支架血流通畅，足部溃疡愈合良好。

BACKGROUND The recent identification of a novel coronavirus, also known as SARS-CoV-2, has caused a global outbreak of respiratory illnesses The rapidly developing pandemic has posed great challenges to diagnosis of this novel infection However, little is known about the metatranscriptomic characteristics of patients with Coronavirus Disease 2019 (COVID-19) METHODS We analyzed metatranscriptomics in 187 patients (62 cases with COVID-19 and 125 with non-COVID-19 pneumonia) Transcriptional aspects of three core elements – pathogens, the microbiome, and host responses – were interrogated Based on the host transcriptional signature, we built a host gene classifier and examined its potential for diagnosing COVID-19 and indicating disease severity RESULTS The airway microbiome in COVID-19 patients had reduced alpha diversity, with 18 taxa of differential abundance Potentially pathogenic microbes were also detected in 47% of the COVID-19 cases, 58% of which were respiratory viruses Host gene analysis revealed a transcriptional signature of 36 differentially expressed genes significantly associated with immune pathways such as cytokine signaling The host gene classifier built on such a signature exhibited potential for diagnosing COVID-19 (AUC of 0 75-0 89) and indicating disease severity CONCLUSIONS Compared to those with non-COVID-19 pneumonias, COVID-19 patients appeared to have a more disrupted airway microbiome with frequent potential concurrent infections, and a special trigger host immune response in certain pathways such as interferon gamma signaling The immune-associated host transcriptional signatures of COVID-19 hold promise as a tool for improving COVID-19 diagnosis and indicating disease severity

Objective:To observe the effect of the cortical blood perfusion parameter of wash-in area under curve (iAUC) with contrast-enhanced ultrasound(CEUS) on the effect of short-term outcomes of stent implantation in patients with severe renal artery stenosis (RAS).Methods:Retrospective analysis was performed on 82 patients with unilateral severe RAS who received stent implantation in Beijing Hospital from October 2017 to December 2019. According to the baseline iAUC before CEUS, all patients were divided into the poorly-perfused group (iAUC<850.0 dB×s) (37 cases) and the well-perfused group (iAUC≥850.0 dB×s) (45 cases). Baseline and perioperative clinical-imaging data were analyzed between the two groups. Followed up for 10-12 (11.5±1.7) months, Kaplan-Meier survival curves and Log-rank test were used to analyze the rate of adverse cardiac and renal vascular events and hypertension control rates.Results:Compared with the well-perfused group, the poorly-perfused group showed a longer course of hypertension, more diabetic patients, higher systolic blood pressure, diastolic blood pressure, 24 h average systolic blood pressure, and 24 h average diastolic blood pressure, lower glomerular filtration rate, and severe renal artery stenosis. Besides, the iAUC, wash-out AUC and the peak intensity were lower, the average transit time was longer, and the hypoglycemic treatment rate was higher (all P<0.05). Kaplan-Meier survival curve and Log-rank test analysis showed that the occurrence of cardio-renal vascular events ( HR=0.361, 95% CI=0.144-0.907, P=0.012) and renal function deterioration rate ( HR=0.286, 95% CI=0.090-0.914, P=0.035) in the well-perfused group were significantly lower than those in the poorly-perfused group. The blood pressure results demonstrated that the effective rate of hypertension treatment in the well-perfused group was significantly higher than that in the poorly-perfused group (93.3% vs 59.5%, P<0.001), but the improvement rate of hypertension (60.0% vs 43.2%) and cure rate (28.9% vs 16.2%) were not statistically significant between the two groups(all P>0.05). Conclusions:Severe RAS patients with decreased baseline iAUC often have diabetes, longer duration of hypertension, significantly reduced glomerular filtration rate and more severe RAS, short-term outcomes are worse with stent implantation.