Fungal invasion-induced accumulation of salicylic acid promotes anthocyanin biosynthesis through MdNPR1-MdTGA2.2 module in apple fruits.

In the field, necrosis area induced by pathogens is usually surrounded by a red circle in apple fruits. However, the underlying molecular mechanism of this phenomenon remains unclear. In this study, we demonstrated that accumulated salicylic acid (SA) induced by fungal infection promoted anthocyanin biosynthesis through MdNPR1-MdTGA2.2 module in apple (Malus domestica). Inoculating apple fruits with Valsa mali or Botryosphaeria dothidea induced a red circle surrounding the necrosis area, which mimicked the phenotype observed in the field. The red circle accumulated a high level of anthocyanins, which was positively correlated with SA accumulation stimulated by fungal invasion. Further analysis showed that SA promoted anthocyanin biosynthesis in a dose-dependent manner in both apple calli and fruits. We next demonstrated that MdNPR1, a master regulator of SA signaling, positively regulated anthocyanin biosynthesis in both apple and Arabidopsis. Moreover, MdNPR1 functioned as a co-activator to interact with and enhance the transactivation activity of MdTGA2.2, which could directly bind to the promoters of anthocyanin biosynthetic and regulatory genes to promote their transcription. Suppressing expression of either MdNPR1 or MdTGA2.2 inhibited coloration of apple fruits, while overexpressing either of them significantly promoted fruit coloration. Finally, we revealed that silencing either MdNPR1 or MdTGA2.2 in apple fruits repressed SA-induced fruit coloration. Therefore, our data determined that fungal-induced SA promoted anthocyanin biosynthesis through MdNPR1-MdTGA2.2 module, resulting in a red circle surrounding the necrosis area in apple fruits.

The AP2/ERF transcription factor MdDREB2A regulates nitrogen utilisation and sucrose transport under drought stress.

Drought stress is one of the main environmental factors limiting plant growth and development. Plants adapt to changing soil moisture by modifying root architecture, inducing stomatal closure, and inhibiting shoot growth. The AP2/ERF transcription factor DREB2A plays a key role in maintaining plant growth in response to drought stress, but the molecular mechanism underlying this process remains to be elucidated. Here, it was found that overexpression of MdDREB2A positively regulated nitrogen utilisation by interacting with DRE cis-elements of the MdNIR1 promoter. Meanwhile, MdDREB2A could also directly bind to the promoter of MdSWEET12, which may enhance root development and nitrogen assimilation, ultimately promoting plant growth. Overall, this regulatory mechanism provides an idea for plants in coordinating with drought tolerance and nitrogen assimilation to maintain optimal plant growth and development under drought stress.

Identification of Hsp20 gene family in Malus domestica and functional characterization of Hsp20 class I gene MdHsp18.2b.

Heat shock protein 20 (Hsp20) is a small molecule heat shock protein that plays an important role in plant growth, development, and stress resistance. Little is known about the function of Hsp20 family genes in apple (Malus domestica). Here, we performed a genome-wide analysis of the apple Hsp20 gene family, and a total of 49 Hsp20s genes were identified from the apple genome. Phylogenetic analysis revealed that the 49 genes were divided into 11 subfamilies, and MdHsp18.2b, a member located in the CI branch, was selected as a representative member for functional characterization. Treatment with NaCl and Botryosphaeria dothidea (B. dothidea), the causal agent of apple ring rot disease, significantly induced MdHsp18.2b transcription level. Further analysis revealed that overexpressing MdHsp18.2b reduced the resistance to salt stress but enhanced the resistance to B. dothidea infection in apple calli. Moreover, MdHsp18.2b positively regulated anthocyanin accumulation in apple calli. Physiology assays revealed that MdHsp18.2b promoted H2O2 production, even in the absence of stress factors, which might contribute to its functions in response to NaCl and B. dothidea infection. Hsps usually function as homo- or heterooligomers, and we found that MdHsp18.2b could form a heterodimer with MdHsp17.9a and MdHsp17.5, two members from the same branch with MdHsp18.2b in the phylogenetic tree. Therefore, we identified 49 Hsp20s genes from the apple genome and found that MdHsp18.2b was involved in regulating plant resistance to salt stress and B. dothidea infection, as well as in regulating anthocyanin accumulation in apple calli.

Evaluation of the analytical and clinical performance of a new high-sensitivity cardiac troponin I assay: hs-cTnI (CLIA) assay.

OBJECTIVES: Cardiac troponin (cTn) is the key biomarker for diagnosis of acute coronary syndrome (ACS). We performed a complete assessment of the high-sensitivity cardiac troponin I (hs-cTnI) (CLIA) assay on the analytical performance and clinical diagnostic performance, which was compared with Abbott ARCHITECT hs-cTnI assay. METHODS: Sex-specific 99th percentile upper reference limits (URLs) were determined from a healthy population of 424 males and 408 females. High-sensitivity performance was assessed by examining the imprecision at sex-specific URLs and the detectable results above LoD in a cohort of healthy population. The diagnostic performance of the hs-cTnI (CLIA) assay was validated in a population of 934 patients with suspected ACS. RESULTS: The 99th percentile URLs were 15.3 ng/L for female, 31.3 ng/L for male and 24.2 ng/L for overall population. The total imprecision near the sex-specific 99th percentile URLs were <5 %. 76.74 % of females, 97.12 % of males and 86.69 % of overall population had cTnI values exceeding the LoD, which met the criteria of high-sensitivity troponin assay. No cross-reactivity or interference was identified. The diagnostic sensitivity, specificity, PPV, NPV, and AUC of hs-cTnI (CLIA) assay were 97.97 , 90.70, 79.02, 99.21 % and 0.9885, respectively, which were comparable to ARCHITECT hs-cTnI assay. CONCLUSIONS: hs-cTnI (CLIA) assay is a high-sensitivity troponin I method with high precision, sensitivity and specificity. The clinical diagnostic performance of hs-cTnI (CLIA) is comparable to the established ARCHITECT hs-cTnI assay. Mindray's hs-cTnI (CLIA) assay is an attractive alternative for diagnosis of myocardial infarction with a high level of accuracy and safety.

Functions of Phytochrome Interacting Factors (PIFs) in Adapting Plants to Biotic and Abiotic Stresses.

Plants possess the remarkable ability to sense detrimental environmental stimuli and launch sophisticated signal cascades that culminate in tailored responses to facilitate their survival, and transcription factors (TFs) are closely involved in these processes. Phytochrome interacting factors (PIFs) are among these TFs and belong to the basic helix-loop-helix family. PIFs are initially identified and have now been well established as core regulators of phytochrome-associated pathways in response to the light signal in plants. However, a growing body of evidence has unraveled that PIFs also play a crucial role in adapting plants to various biological and environmental pressures. In this review, we summarize and highlight that PIFs function as a signal hub that integrates multiple environmental cues, including abiotic (i.e., drought, temperature, and salinity) and biotic stresses to optimize plant growth and development. PIFs not only function as transcription factors to reprogram the expression of related genes, but also interact with various factors to adapt plants to harsh environments. This review will contribute to understanding the multifaceted functions of PIFs in response to different stress conditions, which will shed light on efforts to further dissect the novel functions of PIFs, especially in adaption to detrimental environments for a better survival of plants.

Diagnostic utility of total NT-proBNP testing by immunoassay based on antibodies targeting glycosylation-free regions of NT-proBNP.

OBJECTIVES: The N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) is a widely used heart failure (HF) biomarker. Commercial NT-proBNP immunoassays detect only a subfraction of endogenous NT-proBNP, as the antibodies target a region of NT-proBNP that could be glycosylated at Ser44. The diagnostic utility of immunoassays measuring total NT-proBNP remains unclear. METHODS: NT-proBNP was measured in 183 HF and 200 non-HF patients diagnosed by two independent cardiologists blinded to NT-proBNP results. Plasma samples either non-treated or treated with a mixture of glycosidases were analyzed by the Elecsys proBNP II assay (Roche Diagnostics, based on antibodies targeting a glycosylated region of NT-proBNP) and the SuperFlex NT-proBNP assay (PerkinElmer, based on antibodies targeting regions of NT-proBNP that are free of O-glycans). The diagnostic accuracy of the two assays was analyzed by comparison of ROC curves. RESULTS: The ROC-AUC for the proBNP II assay was 0.943 (95% CI 0.922-0.964) for NT-proBNP measured in untreated samples and 0.935 (0.913-0.958) for NT-proBNP measured in glycosidase-treated samples. The SuperFlex NT-proBNP assay in untreated samples gave a ROC-AUC of 0.930 (95% CI 0.907-0.954). The median percentage of non-glycosylated NT-proBNP to total NT-proBNP was 1.5-1.6-fold lower in the non-HF group compared to that in the HF group. CONCLUSIONS: The clinical value of total NT-proBNP for HF diagnosis was similar to the subfraction of NT-proBNP that was non-glycosylated at Ser44. The lower percentage of non-glycosylated NT-proBNP to total NT-proBNP in non-HF patients suggests that total NT-proBNP might be more sensitive in individuals without current or prior symptoms of HF.

Inhibitory Effect of Tea Saponin on Major Apple-Disease-Inducing Fungi.

Plant secondary metabolites are well known for their biological functions in defending against pathogenic microorganisms. Tea saponin (TS), one type of secondary metabolite of the tea plant (Camellia sinensis), has been shown to be a valuable botanical pesticide. However, its antifungal activity in controlling the fungi Valsa mali, Botryosphaeria dothidea, and Alternaria alternata, which induce major diseases in apple (Malus domestica), has not been determined. In this study, we first determined that TS has higher inhibitory activity than catechins against the three types of fungi. We further utilized in vitro and in vivo assays to confirm that TS showed high antifungal activity against the three types of fungi, especially for V. mali and B. dothidea. In the in vivo assay, application of a 0.5% TS solution was able to restrain the fungus-induced necrotic area in detached apple leaves efficiently. Moreover, a greenhouse infection assay also confirmed that TS treatment significantly inhibited V. mali infection in leaves of apple seedlings. In addition, TS treatment activated plant immune responses by decreasing accumulation of reactive oxygen species and promoting the activity of pathogenesis-related proteins, including chitinase and ß-1,3-glucanase. This indicated that TS might serve as a plant defense inducer to activate innate immunity to fight against fungal pathogen invasion. Therefore, our data indicated that TS might restrain fungal infection in two ways, by directly inhibiting the growth of fungi and by activating plant innate defense responses as a plant defense inducer.

FERONIA Receptor Kinase Integrates with Hormone Signaling to Regulate Plant Growth, Development, and Responses to Environmental Stimuli.

Plant hormones are critical chemicals that participate in almost all aspects of plant life by triggering cellular response cascades. FERONIA is one of the most well studied members in the subfamily of Catharanthus roseus receptor-like kinase1-like (CrRLK1Ls) hormones. It has been proved to be involved in many different processes with the discovery of its ligands, interacting partners, and downstream signaling components. A growing body of evidence shows that FERONIA serves as a hub to integrate inter- and intracellular signals in response to internal and external cues. Here, we summarize the recent advances of FERONIA in regulating plant growth, development, and immunity through interactions with multiple plant hormone signaling pathways.

Cellulose accumulation in the secondary cell walls is negatively correlated with the tenderness of new shoots in Camellia sinensis.

Tea, which is usually made from the new shoots of tea plants (Camellia sinensis), is one of the most popular and healthy beverages. The tenderness of new shoots plays a critical role in the production of high-quality tea; however, the factors affecting the tenderness of the new shoots of tea have not been extensively studied. Here, we show that cellulose accumulation is negatively correlated with the tenderness of new shoots, including leaves and stems, by characterizing the cellulose content and visualizing cellulose in the new shoots of two cultivars ("Huangjinya" and "Yujinxiang") via toluidine blue staining. We further found that the number of cells with secondary cell walls (SCWs) and the thickness of SCWs increased with the maturity degree of stems in both cultivars. Because cellulose is the most abundant polymer in SCW, we next identified three cellulose synthase CsCesAs, CsCesA4, 7, and 8A, through homologous alignment with Arabidopsis AtCesAs. Protein sequence analysis revealed that these proteins were closely related based on the phylogenetic analysis. We finally showed that the gene expression of the three CsCesAs was positively correlated with the maturity degree and cellulose content of the new shoots. Thus, our data suggest that cellulose accumulation, especially in the SCWs, is negatively correlated with the tenderness of new shoots in tea plants.

The ankyrin repeat-containing protein MdANK2B regulates salt tolerance and ABA sensitivity in Malus domestica.

KEY MESSAGE: The ankyrin repeat-containing protein MdANK2B was identified to contribute to increasing resistance to salt stress and decreasing sensitivity to ABA in Malus domestica. Ankyrin (ANK) repeat-containing proteins occur widely in prokaryotes, eukaryotes, and even in some viruses and play a critical role in plant growth and development, as well as the response to biotic and abiotic stress. However, the function of ANK repeat-containing proteins in apple (Malus domestica) has not yet been investigated. Here, we identified apple MdANK2B based on homology analysis with the Arabidopsis ANK repeat-containing proteins AtAKR2A and AtAKR2B. MdANK2B was found to be localized in the cytoplasm, and its encoding gene was highly expressed in both apple leaves and fruits. In addition, MdANK2B gene expression was highly induced by salt stresses and abscisic acid (ABA). Overexpression of MdANK2B increased resistance to salt stress and decreased sensitivity to ABA in both transgenic apple calli and seedlings. In addition, overexpression of MdANK2B reduced the accumulation of reactive oxygen species (ROS) by enhancing the activity of antioxidant enzymes in response to salt stress. Our data revealed the role of MdANK2B in response to salt stress and ABA treatment in apple, which widens the known functions of ANK repeat-containing proteins in response to abiotic stress.

An engineered mutant of a host phospholipid synthesis gene inhibits viral replication without compromising host fitness.

Viral infections universally rely on numerous hijacked host factors to be successful. It is therefore possible to control viral infections by manipulating host factors that are critical for viral replication. Given that host genes may play essential roles in certain cellular processes, any successful manipulations for virus control should cause no or mild effects on host fitness. We previously showed that a group of positive-strand RNA viruses enrich phosphatidylcholine (PC) at the sites of viral replication. Specifically, brome mosaic virus (BMV) replication protein 1a interacts with and recruits a PC synthesis enzyme, phosphatidylethanolamine methyltransferase, Cho2p, to the viral replication sites that are assembled on the perinuclear endoplasmic reticulum (ER) membrane. Deletion of the CHO2 gene inhibited BMV replication by 5-fold; however, it slowed down host cell growth as well. Here, we show that an engineered Cho2p mutant supports general PC synthesis and normal cell growth but blocks BMV replication. This mutant interacts and colocalizes with BMV 1a but prevents BMV 1a from localizing to the perinuclear ER membrane. The mislocalized BMV 1a fails to induce the formation of viral replication complexes. Our study demonstrates an effective antiviral strategy in which a host lipid synthesis gene is engineered to control viral replication without comprising host growth.

Host Pah1p phosphatidate phosphatase limits viral replication by regulating phospholipid synthesis.

Replication of positive-strand RNA viruses [(+)RNA viruses] takes place in membrane-bound viral replication complexes (VRCs). Formation of VRCs requires virus-mediated manipulation of cellular lipid synthesis. Here, we report significantly enhanced brome mosaic virus (BMV) replication and much improved cell growth in yeast cells lacking PAH1 (pah1Δ), the sole yeast ortholog of human LIPIN genes. PAH1 encodes Pah1p (phosphatidic acid phosphohydrolase), which converts phosphatidate (PA) to diacylglycerol that is subsequently used for the synthesis of the storage lipid triacylglycerol. Inactivation of Pah1p leads to altered lipid composition, including high levels of PA, total phospholipids, ergosterol ester, and free fatty acids, as well as expansion of the nuclear membrane. In pah1Δ cells, BMV replication protein 1a and double-stranded RNA localized to the extended nuclear membrane, there was a significant increase in the number of VRCs formed, and BMV genomic replication increased by 2-fold compared to wild-type cells. In another yeast mutant that lacks both PAH1 and DGK1 (encodes diacylglycerol kinase converting diacylglycerol to PA), which has a normal nuclear membrane but maintains similar lipid compositional changes as in pah1Δ cells, BMV replicated as efficiently as in pah1Δ cells, suggesting that the altered lipid composition was responsible for the enhanced BMV replication. We further showed that increased levels of total phospholipids play an important role because the enhanced BMV replication required active synthesis of phosphatidylcholine, the major membrane phospholipid. Moreover, overexpression of a phosphatidylcholine synthesis gene (CHO2) promoted BMV replication. Conversely, overexpression of PAH1 or plant PAH1 orthologs inhibited BMV replication in yeast or Nicotiana benthamiana plants. Competing with its host for limited resources, BMV inhibited host growth, which was markedly alleviated in pah1Δ cells. Our work suggests that Pah1p promotes storage lipid synthesis and thus represses phospholipid synthesis, which in turn restricts both viral replication and cell growth during viral infection.

Identification of Phytochrome-Interacting Factor Family Members and Functional Analysis of MdPIF4 in Malus domestica.

Phytochrome-interacting factors (PIFs), members of the basic helix-loop-helix transcription factor family that have been extensively investigated in Arabidopsis thaliana, play essential roles in plant growth and development. However, PIF members have not been systematically investigated in apples, a worldwide perennial woody crop of economic importance. Here, seven PIF genes were identified from the Malus × domestica reference genome. Chromosomal locations, gene structures, and phylogenetic relationships of these members were analyzed. Analysis of cis-acting elements in promoter regions of MdPIF genes indicated that various elements were related to light, abiotic stress, and plant hormone responsiveness. Subsequently, subcellular localization and transcriptional activity analysis revealed that MdPIFs were typical nuclear transcription factors with transcriptional activation ability. Expression analysis demonstrated that MdPIF genes had different gene expression patterns for various abiotic factors. Moreover, overexpressed MdPIF4 reduced the sensitivity of apple calluses to abscisic acid (ABA). Our work lays foundations for further investigation of PIF functions in plant growth and development in apples.

Positive-strand RNA viruses stimulate host phosphatidylcholine synthesis at viral replication sites.

All positive-strand RNA viruses reorganize host intracellular membranes to assemble their viral replication complexes (VRCs); however, how these viruses modulate host lipid metabolism to accommodate such membrane proliferation and rearrangements is not well defined. We show that a significantly increased phosphatidylcholine (PC) content is associated with brome mosaic virus (BMV) replication in both natural host barley and alternate host yeast based on a lipidomic analysis. Enhanced PC levels are primarily associated with the perinuclear ER membrane, where BMV replication takes place. More specifically, BMV replication protein 1a interacts with and recruits Cho2p (choline requiring 2), a host enzyme involved in PC synthesis, to the site of viral replication. These results suggest that PC synthesized at the site of VRC assembly, not the transport of existing PC, is responsible for the enhanced accumulation. Blocking PC synthesis by deleting the CHO2 gene resulted in VRCs with wider diameters than those in wild-type cells; however, BMV replication was significantly inhibited, highlighting the critical role of PC in VRC formation and viral replication. We further show that enhanced PC levels also accumulate at the replication sites of hepatitis C virus and poliovirus, revealing a conserved feature among a group of positive-strand RNA viruses. Our work also highlights a potential broad-spectrum antiviral strategy that would disrupt PC synthesis at the sites of viral replication but would not alter cellular processes.

D-Dimer to Predict the Clinical Outcomes in Patients with Mechanical Heart Valve Replacement During Oral Anticoagulation Therapy.

Mechanical heart valve replacement (MHVR) entails lifetime oral anticoagulation to eliminate thrombosis. However, adverse events may still occur despite proper anticoagulation therapy. In this study, we investigated whether D-dimer can predict the clinical events in post-MHVR patients during oral anticoagulation therapy.This was a single-center, prospective study. In all, 772 patients who underwent MHVR in the Wuhan Asia Heart Hospital from January 2013 to May 2014 were screened. Patients were assigned to the abnormal D-dimer group and the normal D-dimer group according to the D-dimer levels measured 3 months after the beginning of the oral anticoagulation therapy regime. All patients were followed up for 24 months or until the observation of the endpoints, which included thrombotic events, bleeding events, and all-cause deaths.A total of 718 patients were included in the analysis: 91 had abnormal D-dimer levels, and 627 had normal D-dimer levels. In all, 53 events were observed during 24 months. Compared with the normal D-dimer group, patients with abnormal D-dimer levels had a higher incidence of thrombotic events (10 versus 14; hazard ratio (HR): 5.36; 95% confidence interval (CI): 2.38-12.1; P < 0.001), all-cause mortality (8 versus 13; HR: 4.65; 95% CI: 1.93-11.2; P < 0.001), and a higher incidence of total events (16 versus 37; HR: 3.26; 95% CI: 1.81-5.86; P < 0.001). No significant difference was observed in bleeding events (2 versus 21; HR: 0.72; 95% CI: 0.17-3.07; P = 0.66).D-dimer may be a useful marker to predict thrombotic events and all-cause deaths in post-MHVR patients during oral anticoagulation therapy (ClinicalTrials.gov; NCT01996657).

Influence of the Ge distribution on the first order magnetic transition of the MnFe(P,Ge) magnetocaloric material.

MnFe(P,Ge) is a promising magnetocaloric material for potential refrigeration applications near room temperature. However, its relatively large hysteresis and large temperature/field range of two-phase [paramagnetic (PM) and ferromagnetic (FM)] coexistence displayed in the cyclic first order magnetic transition (FOMT) cause energy losses and reduce the energy conversion efficiency. In this work, we explore the underlying causes of phase coexistence, hysteresis and structural transformation based on determination of the Ge distribution in MnFeP1-xGex (0.10 < x < 0.50) materials. We find that all the samples crystallize in the Fe2P-type structure [P6[combining macron]2m (No. 189), Z = 3] and Ge displays a strong preference for the 2c site. First principles total energy calculations confirm this site preference of Ge, and Ge entering the 2c site changes the electronic structures and enhances the Fe and Mn 3d exchange splitting across the Fermi level as well as the FM exchange interactions, consequently leading to a linear increase in the transition temperature with increasing Ge content. Scanning electron microscopy and energy-dispersive spectroscopy reveal the inhomogeneous distribution of Ge in grains, which makes the grains with larger Ge content transform from the PM to the FM phase first when cooling and thus causes the phase coexistence. Maximum entropy method electron-densities show that weakening the coplanar Fe-P/Ge(2c) and Mn-P(1b) bonding strengths across the PM to FM phase transition can release some 3d-electrons to enhance the Fe-Mn FM exchange interaction and result in coupling between the magnetic and structural degrees of freedom. This provides first direct evidence for the dominant role of Fe-Mn exchange interaction in the ferromagnetic ordering and may provide a method to observe the exchange interaction. Diminishing the variances in covalent bonding strengths across the FOMT gives rise to an exponential decay in the heat hysteresis when increasing the Ge occupancy at the 2c site. To the best of our knowledge, this is the first time a relationship between the variances in covalent bonding strengths and hysteresis is proposed. This material thus provides an example of a FOMT and hysteresis driven by reversible weakening and strengthening of covalent bonds. Based on these, a strategy of designing better magnetocaloric materials is suggested.

Behçet's syndrome masquerading as infective endocarditis: A diagnostic conundrum and therapeutic challenge.

This case report presents a 20-year-old male patient initially diagnosed with infective endocarditis, later correctly identified as Behçet's syndrome. The patient's complex clinical presentation, including chest pain, aortic dilation, severe aortic regurgitation, and aortic root abscess, posed significant diagnostic and therapeutic challenges. Despite initial misdiagnosis and treatment difficulties, the patient's condition significantly improved with appropriate immunosuppressive therapy, underscoring the potential for successful management of this complex condition. This case serves as a valuable reminder of the diagnostic challenges posed by Behçet's syndrome and the importance of considering this condition in patients presenting with symptoms suggestive of infective endocarditis.

Clinical and pathological spectrum of aortitis in a Chinese cohort.

BACKGROUND: This study aimed to explore the clinical and pathological features of aortitis in China, which is a rare disease that is often overlooked preoperatively. METHODS: We reviewed the records of 2950 patients who underwent aortic surgery at Wuhan Asia General Hospital from 2016 to 2023. Clinical and pathological data were collected and compared across different groups. RESULTS: Out of 2950 patients, 15 had healed aortitis, 2 were healed Takayasu aortitis (TAK), and 13 were not further classified. Forty-two had active aortitis, including clinically isolated aortitis ([CIA], 42.9%), infectious aortitis ([IA], 26.2%), TAK (16.7%), and Behçet's syndrome ([BS], 14.3%), half of these cases were not recognized preoperatively. All patients who developed perivalvular leakage during follow-up had concurrent non-infectious valvulitis with mixed inflammatory pattern at the time of initial surgery. Seventeen out of 18 patients with CIA survived without complications, as did 8 out of 11 patients with IA, 6 out of 7 patients with TAK, and 2 out of 6 patients with BS. CONCLUSIONS: Half of the aortitis cases were initially diagnosed by pathologists. Noninfectious valvulitis with mixed inflammatory pattern is a risk factor for perivalvular leakage. BS is associated with a higher rate of complications. Patients with CIA have a good prognosis in China, which is different from the West.