Advances in the mechanism of inflammasomes activation in herpes virus infection.

Herpesviruses, prevalent DNA viruses with a double-stranded structure, establish enduring infections and play a part in various diseases. Despite their deployment of multiple tactics to evade the immune system, both localized and systemic inflammatory responses are triggered by the innate immune system's recognition of them. Recent progress has offered more profound understandings of the mechanisms behind the activation of the innate immune system by herpesviruses, specifically through inflammatory signaling. This process encompasses the initiation of an intracellular nucleoprotein complex, the inflammasome associated with inflammation.Following activation, proinflammatory cytokines such as IL-1ß and IL-18 are released by the inflammasome, concurrently instigating a programmed pathway for cell death. Despite the structural resemblances between herpesviruses, the distinctive methods of inflammatory activation and the ensuing outcomes in diseases linked to the virus exhibit variations.The objective of this review is to emphasize both the similarities and differences in the mechanisms of inflammatory activation among herpesviruses, elucidating their significance in diseases resulting from these viral infections.Additionally, it identifies areas requiring further research to comprehensively grasp the impact of this crucial innate immune signaling pathway on the pathogenesis of these prevalent viruses.

Isolation and pathogenicity comparison of two novel natural recombinant porcine reproductive and respiratory syndrome viruses with different recombination patterns in Southwest China.

Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses in the swine industry. Frequent mutations and recombinations account for PRRSV immune evasion and the emergence of novel strains. In this study, we isolated and characterized two novel PRRSV-2 strains from Southwest China exhibiting distinct recombination patterns. They were designated SCABTC-202305 and SCABTC-202309. Phylogenetic results indicated that SCABTC-202305 was classified as lineage 8, and SCABTC-202309 was classified as lineage 1.8. Amino acid mutation analysis identified unique amino acid substitutions and deletions in ORF5 and Nsp2 genes. The results of the recombination analysis revealed that SCABTC-202305 is a recombinant with JXA1 as the major parental strain and NADC30 as the minor parental strain. At the same time, SCABTC-202309 is identified as a recombinant with NADC30 as the major parental strain and JXA1 as the minor parental strain. In this study, we infected piglets with SCABTC-202305, SCABTC-202309, or mock inoculum (control) to study the pathogenicity of these isolates. Although both isolated strains were pathogenic, SCABTC-202305-infected piglets exhibited more severe clinical signs and higher mortality, viral load, and antibody response than SCABTC-202309-infected piglets. SCABTC-202305 also caused more extensive lung lesions based on histopathology. Our findings suggest that the divergent pathogenicity observed between the two novel PRRSV isolates may be attributed to variations in the genetic information encoded by specific genomic regions. Elucidating the genetic determinants governing PRRSV virulence and transmissibility will inform efforts to control this devastating swine pathogen.IMPORTANCEPorcine reproductive and respiratory syndrome virus (PRRSV) is one of the most critical pathogens impacting the global swine industry. Frequent mutations and recombinations have made the control of PRRSV increasingly difficult. Following the NADC30-like PRRSV pandemic, recombination events involving PRRSV strains have further increased. We isolated two novel field PRRSV recombinant strains, SCABTC-202305 and SCABTC-202309, exhibiting different recombination patterns and compared their pathogenicity in animal experiments. The isolates caused higher viral loads, persistent fever, marked weight loss, moderate respiratory clinical signs, and severe histopathologic lung lesions in piglets. Elucidating correlations between recombinant regions and pathogenicity in these isolates can inform epidemiologic tracking of emerging strains and investigations into viral adaptive mechanisms underlying PRRSV immunity evasion. Our findings underscore the importance of continued genomic surveillance to curb this economically damaging pathogen.

Transcriptome and metabolome analysis reveals PRV XJ delgE/gI/TK protects intracranially infected mice from death by regulating the inflammation.

Pseudorabies virus can cause inflammation in the central nervous system and neurological symptoms. To further investigate the protective mechanism of PRV XJ delgE/gI/TK in the central nervous system, an intracranial PRV-infection mice model was developed. The results demonstrated that immunization with PRV XJ delgE/gI/TK successfully prevented death caused by PRV-intracranial infection. Subsequently, the brains were collected for transcriptome and metabolome analysis. GO and KEGG enrichment analysis indicated that the differentially expressed genes were primarily enriched in pathways such as TNF, NOD-like receptor, JAK-STAT, MAPK, IL-17 and apoptosis signaling. Metabolomics analysis revealed that the differential metabolites were mainly associated with pathways such as fatty acid degradation, arachidonic acid metabolism, linoleic acid metabolism and unsaturated fatty acid biosynthesis. The combined analysis of metabolites and differentially expressed genes revealed a strong correlation between the differential metabolites and TNF, PI3K, and MAPK signaling pathways. Anti-inflammatory metabolites have been shown to inhibit the inflammatory response and prevent mouse death caused by PRV infection. Notably, when glutathione was injected intracranially and dihydroartemisinin was injected intraperitoneally, complete protection against PRV-induced death in mice was observed. Moreover, PRV activates the PI3K/AKT signaling pathway. In conclusion, our study demonstrates that PRV XJ delgE/gI/TK can protects intracranially infected mice from death by regulating various metabolites with anti-inflammatory functions post-immunization.

Relationship between low relative muscle mass and aortic regional morphological changes in adults underwent contrast CT scans for cancer diagnostics.

OBJECTIVES: Low muscle mass is related to cardiovascular risk factors. This study aimed to investigate whether relative low muscle mass is related to the diameter and tortuosity of the aorta. METHODS: We performed a cross-sectional study of 208 adults without known cardiovascular disease who underwent Computed Tomography (CT) enhanced scan between 2020 and 2021. Skeletal muscle index (SMI) was estimated. The morphology of the aorta was measured by diameter and tortuosity using CT. We assessed the relationship between SMI and diameter and tortuosity of the aorta using Spearman correlation analysis and univariate and multivariate-adjusted regression models. RESULTS: Of all -individuals, 124 (59.6%) were male. The average age was 60.13 ± 16.33 years old. SMI was inversely associated with the diameter and tortuosity of the aorta (p < 0.05). Specifically, in a multivariable-adjusted model adjusting for potential confounders, a one-unit increase in the SMI was associated with a -13.56mm(95% confidence intervals (CI): -18.16 to -8.96, p < 0.001), -7.93 mm (95% CI: -10.85 to -5.02, p < 0.001), -8.01 mm (95% CI: -11.30 to -4.73, p < 0.001), -5.16 mm (95% CI: -7.57 to -2.75, p < 0.001) and -2.73 mm (95% CI: -5.18 to -0.27, p = 0.031) increase in L1-L5 diameter respectively, a -0.89 (95% CI: -1.14 to -0.64, p < 0.001) increase in the aorta tortuosity, a -0.48 (95% CI: -0.59 to -0.36, p < 0.001) increase in the descending thoracic aorta tortuosity, and a -0.44 (95% CI: -0.52 to -0.35, p < 0.001) increase in the abdominal aorta tortuosity. CONCLUSIONS: Relative muscle mass was negatively associated with the diameter and tortuosity of the aorta, suggesting muscle mass maintenance may play a role in preventing aortic morphological changes.

A time-course transcriptome analysis revealing the potential molecular mechanism of early gonadal differentiation in the Chinese giant salamander.

The Chinese giant salamander (CGS) Andrias davidianus is the largest extant amphibian and has recently become an important species for aquaculture with high economic value. Meanwhile, its wild populations and diversity are in urgent need of protection. Exploring the mechanism of its early gonadal differentiation will contribute to the development of CGS aquaculture and the recovery of its wild population. In this study, transcriptomic and phenotypic research was conducted on the critical time points of early gonadal differentiation of CGS. The results indicate that around 210 days post-hatching (dph) is the critical window for female CGS's gonadal differentiation, while 270 dph is that of male CGS. Besides, the TRPM1 gene may be the crucial gene among many candidates determining the sex of CGS. More importantly, in our study, key genes involved in CGS's gonadal differentiation and development are identified and their potential pathways and regulatory models at early stage are outlined. This is an initial exploration of the molecular mechanisms of CGS's early gonadal differentiation at multiple time points, providing essential theoretical foundations for its captive breeding and offering unique insights into the conservation of genetic diversity in wild populations from the perspective of sex development.

First report on identification and genomic analysis of a novel porcine circovirus (porcine circovirus 4) in cats.

Porcine circovirus type 4 (PCV4) is an emerging circovirus, which has been detected in domestic pigs across various provinces in China and Korea. In this study, we aimed to investigate whether cats are susceptible to PCV4. For this purpose, we collected 116 cat samples from animal hospitals in Sichuan Province, China, between 2021 and 2022. Using a SYBR Green-based real-time PCR assay, we detected PCV4 in 5 out of the 116 clinical samples, indicating a positive rate of 4.31% (5/116) and confirming the presence of PCV4 in cats from Sichuan Province, China. Moreover, we successfully sequenced and analyzed the complete genome of one PCV4 strain (SCGA-Cat) along with 60 reference sequences deposited in the GenBank database. SCGA-Cat exhibited high nucleotide homology (98.2-99.0%) with PCV4 strains from other species, including dogs, pigs, dairy cows, and fur animals. Notably, the SCGA-Cat strain from cats clustered closely with a PCV4 strain derived from a pig collected in Fujian Province, China. To the best of our knowledge, this study represents the first report on the molecular detection of PCV4 in cats worldwide, which prompted us to understand the genetic diversity and cross-species transmission of the ongoing PCV4 cases. However, further investigations are needed to explore the association between PCV4 infection and clinical syndromes in cats.

Intranasal administration with recombinant vaccine PRVXJ-delgE/gI/TK-S induces strong intestinal mucosal immune responses against PDCoV.

Porcine deltacoronavirus (PDCoV) is a novel coronavirus that causes enteric diseases in pigs leading to substantial financial losses within the industry. The absence of commercial vaccines and limited research on PDCoV vaccines presents significant challenges. Therefore, we evaluated the safety and immunogenicity of recombinant pseudorabies virus (PRV) rPRVXJ-delgE/gI/TK-S through intranasal mucosal immunization in weaned piglets and SPF mice. Results indicated that rPRVXJ-delgE/gI/TK-S safely induced PDCoV S-specific and PRV gB-specific antibodies in piglets, with levels increasing 7 days after immunization. Virus challenge tests demonstrated that rPRVXJ-delgE/gI/TK-S effectively improved piglet survival rates, reduced virus shedding, and alleviated clinical symptoms and pathological damage. Notably, the recombinant virus reduced anti-inflammatory and pro-inflammatory responses by regulating IFN-γ, TNF-α, and IL-1ß secretion after infection. Additionally, rPRVXJ-delgE/gI/TK-S colonized target intestinal segments infected with PDCoV, stimulated the secretion of cytokines by MLVS in mice, stimulated sIgA secretion in different intestinal segments of mice, and improved mucosal immune function. HE and AB/PAS staining confirmed a more complete intestinal mucosal barrier and a significant increase in goblet cell numbers after immunization. In conclusion, rPRVXJ-delgE/gI/TK-S exhibits good immunogenicity and safety in mice and piglets, making it a promising candidate vaccine for PDCoV.

Conversion of primary liver cancer after targeted therapy for liver cancer combined with AFP-targeted CAR T-cell therapy: a case report.

Primary liver cancer (PLC) that originates in the liver is a malignant tumor with the worst prognosis. Hepatocellular carcinoma (HCC) is the most common type of PLC. Most PLC cases are diagnosed at advanced stages mainly due to their insidious onset and rapid progression. Patients with PLC undergo surgical intervention or localized treatment, but their survival is often affected by its high relapse rate. Medical treatment is the primary option for patients with liver cancer, especially with advanced extrahepatic metastases. Molecular targeted therapy exerts an anti-tumor effect by acting on various signaling pathways involved in molecular pathogenesis; however, high drug resistance and low therapeutic responsiveness of PLC to molecular targets challenge the treatment option. In recent years, after surgical intervention, radiotherapy, chemotherapy, and/or molecular targeted therapy, autologous cell immunotherapy has been adopted for PLC. As a typical autologous cell immunotherapy, CAR T-cell therapy uses genetically modified T cells to express tumor-specific chimeric antigen receptors (CARs). Its targeting ability, persistent nature, and tumor-killing function result in a significant impact on the treatment of hematological tumors. However, no breakthrough has happened in the research specific to the curation of lung cancer, liver cancer, breast cancer, and other common solid tumors. In this context, a combination of molecular targeted therapy and CAR T-cell therapy was used to treat a patient with advanced HCC to achieve a partial remission(PR) and facilitate further liver transplantation.

The impact of baseline calcified plaque volume on coronary rapid plaque progression by serial coronary computed tomography angiography in patients with type 2 diabetes.

OBJECTIVES: Patients with type 2 diabetes mellitus (T2DM) are susceptible to coronary artery disease (CAD), and coronary outcomes in these patients are heterogeneous. However, the impact of coronary plaque compositions on rapid plaque progression (RPP) in patients with T2DM has rarely been reported. This study aimed to investigate the association of coronary plaque compositions with rapid lesion volume progression in patients with T2DM. MATERIALS AND METHODS: A total of 159 subjects (aged 62.51 ± 10.3 years, 68.6% were male) who underwent serial coronary computed tomography angiography (CCTA) with type 2 diabetic status were enrolled. Annual change of plaque volume (PV) (mm3/year) was defined as PV change divided by inter-scan period. RPP was defined as the progression of plaque burden (PV divided by vessel volume multiplied by 100) ≥0.59%/year. Plaque components were compared between RPP and no RPP groups. Then all patients were divided into 3 groups according to the baseline calcified plaque volume tertiles. The outcome was whether RPP occurred. RESULTS: The median inter-scan period was 2.09 (range 1.41-3.33) years. The overall incidence of RPP was 61.0%. The calcified plaque volume decreased significantly in the RPP group as compared to the no RPP group. The risk of RPP (odds ratio [OR] 0.39; 95% confidence interval [CI]: 0.17-0.88; p = 0.024) was reduced in tertiles III as compared to that in tertiles I even after adjustment for baseline variables (OR 0.21; 95% CI: 0.07-0.63; p = 0.005). Moreover, adding the calcified plaque volume significantly raised the predictive value for the RPP (0.370, p = 0.030, and 0.059, p = 0.025, NRI, and IDI respectively) as compared to traditional factors. CONCLUSION: The baseline calcified plaque volume is an independent protective factor for the rapid progression of coronary atherosclerosis in patients with T2DM.

The calcified plaque volume of the coronary was significantly lower in T2DM subjects with RPP than in those without RPP.Higher levels of atherosclerotic calcification may have a protective value on plaque stabilization in patients with T2DM.Calcified plaque volume of the coronary should be considered when proposing risk stratification in T2DM patients.

Macrophage Polarization: An Important Candidate Regulator for Lung Diseases.

Macrophages are crucial components of the immune system and play a critical role in the initial defense against pathogens. They are highly heterogeneous and plastic and can be polarized into classically activated macrophages (M1) or selectively activated macrophages (M2) in response to local microenvironments. Macrophage polarization involves the regulation of multiple signaling pathways and transcription factors. Here, we focused on the origin of macrophages, the phenotype and polarization of macrophages, as well as the signaling pathways associated with macrophage polarization. We also highlighted the role of macrophage polarization in lung diseases. We intend to enhance the understanding of the functions and immunomodulatory features of macrophages. Based on our review, we believe that targeting macrophage phenotypes is a viable and promising strategy for treating lung diseases.

Histopathological Changes and Inflammatory Response in Specific Pathogen-Free (SPF) with Porcine Circovirus Type 3 Infection.

Since the first report of PCV3 virus infection in 2016, it has been linked to multisystemic inflammation, reproductive failure, cardiac pathology, and clinical indications resembling porcine dermatitis and nephropathy syndrome (PDNS). However, the pathogenesis and clinical significance of PCV3 is still unclear. In this study, a PCV3 infection model was created using SPF pigs, and histopathology and fluorescence quantitative PCR were utilized to examine PCV3's pathogenicity. Reductions in body weight gain and fever were observed during this study. However, other clinical signs such as Dermatitis and Nephropathy Syndrome were not observed through the study. Viremia was detected in the PCV3-inoculated group from 17 days post-inoculation (p.i.) until the end of the study. Nasal shedding was detected from 21 to 35 dpi and fecal shedding was detected during 25-33 days and 39 days, respectively. Gross lesions and histological evaluation were detected in various tissues and organs, including the lung, heart, kidney, lymph nodes, spleen, liver, small intestine, and testis. The heart, lung, liver, kidney, lymph nodes, and spleen showed pathological changes. The pathological features include swelling, inflammation, cell degeneration, necrosis, and hemorrhage. The lesions are consistent with multisystemic inflammation. Tissue viral load results showed only heart, lung, liver, kidney, lymph nodes, and spleen was positive by qRT-PCR. Moreover, the pro-inflammation cytokines in serum increased a lot in the PCV3-inoculated group compared to the control group, demonstrating that the induced inflammation response may be the cause of tissue damage in PCV3-infection. This study demonstrated that PCV3 can produce mild pathological damage to multiple organs, especially multisystemic inflammatory cell infiltration and prolonged viremia, viral shedding in nasal secretions. This is the first in vivo characterization of PCV3 infection in the SPF piglets model using isolated PCV3 strain, and this is also the first time to show the gross and pathological lesion with all tissue and organs in the PCV3-inoculated group. Our findings might serve as a starting point for more investigation into PCV3's pathogenic mechanism.

Serum marker and CT characteristics of coronary calcified nodule assessed by intravascular ultrasound.

BACKGROUND: Calcified nodule (CN) is a type of potentially vulnerable plaque. Its formation mechanism remains unknown. This study was to assess serum marker and computed tomography angiography (CTA) characteristics of CN validated by intravascular ultrasound (IVUS). METHODS: Patients who underwent coronary CTA followed by invasive coronary angiography and IVUS were retrospectively analyzed. Serum levels of alkaline phosphatase (ALP), gamma-glutamyltransferase, and calcium were collected. RESULTS: IVUS detected 128 de novo calcified lesions in 79 patients with coronary artery disease (CAD). CNs were identified in 11.4% (9/79) of patients and 9.4% (12/128) of lesions. Compared with patients with non-nodular calcified plaques, CN patients had higher serum level of ALP (82.00 vs 65.00 U/L, P = 0.022) and total plaque volume (673.00 vs 467.50 mm3, P = 0.021). Multivariable analyses revealed that serum ALP level and total plaque volume were independently associated with the prevalence of CN in CAD patients with calcified plaques. At lesion level, the CN group had a higher frequency of moderate to heavy calcification on angiography (75.00% vs 40.52%, P = 0.017). In terms of CTA characteristics, plaques with CN had a more severe diameter stenosis (79.00% vs 63.00%, P = 0.007), higher plaque burden (85.40% vs 77.05%, P = 0.005), total plaque density (398.00 vs 283.50 HU, P = 0.008), but lower lipid percentage (14.65% vs 19.75%, P = 0.010) and fiber percentage (17.90% vs 25.65%, P = 0.011). Mean plaque burden is an independent predictor of the prevalence of CN in calcified plaques (odds ratio = 1.102, 95% confidence interval: 1.025-1.185, P = 0.009). The AUC is 0.753 (95% confidence interval: 0.615-0.890, P = 0.004). When using 84.85% as the best cutoff value, the diagnostic sensitivity and specificity of mean plaque burden for predicting the presence of CN within calcified plaques were 66.7% and 80.2%, respectively. CONCLUSIONS: CN had different CTA imaging features from non-nodular coronary calcification. The presence of a CN was associated with a higher serum ALP level and plaque burden.

Investigation of the anti-pseudorabies virus activity of interferon lambda 3 in cultured porcine kidney epithelial cells.

BACKGROUND: It has been reported Interferon-λ (IFN-λ) has stronger antiviral effect than other interferons. IFN-λ can induce antiviral interferon stimulated genes (ISGs) in epithelia to protect against virus. Pseudorabies virus (PRV) infection in pigs resulting in fatal encephalitis in newborn piglets, respiratory disorders in finishing pigs, reproductive disorders in sows and other symptoms. OBJECTIVES: Since the effect of IFN-λ on inhibiting PRV proliferation is still unknown. Inthis study, we investigate the relative contribution of porcine IFN-λ3 toward controlling the infection of PRV in vitro. Our findings may provide a new insight for the prevention and treatment of PRV. METHODS: Therefore, the antiviral assay, western blot, qRT-PCR and ELISA assay were used to investigating the contribution of IFN-λ against PRV in PK-15 cells. RESULTS: Here, we demonstrate that the replication of PRV in PK-15 cells was inhibited after pre-treatment with IFN-λ3, and such inhibition was dose dependent. Overexpression of IFN-λ3 receptor (IFNLR) also restricted virus titre in PK-15 cells. In addition, IFN-λ3 also increased the mRNA and protein expression of interferon-stimulated genes 15 (ISG15), 2'-5'-oligoadenylate synthase 1 (OAS1), IFN-inducible transmembrane 3 (IFITM3) and myxoma resistance protein 1 (Mx1) in PRV-infected PK-15 cells. Other than modulation ISGs, IFN-λ specifically activated IFN-γ mRNA expression not IFN-α or IFN-ß. CONCLUSIONS: IFN-λ3 had antiviral activity against PRV and the upregulation of ISGs and IFN-γ mRNA expression may be the mechanism of IFN-λ3's antiviral activities. Thus, IFN-λ3 has a decisive function that greatly limits PRV replication in PK-15 cells. Our study explores the antiviral activity of IFN-λ3 on PRV for the first time.

Evasion of interferon-mediated immune response by arteriviruses.

IFN is the most potent antiviral cytokine required for the innate and adaptive immune responses, and its expression can help the host defend against viral infection. Arteriviruses have evolved strategies to antagonize the host cell's innate immune responses, interfering with IFN expression by interfering with RIG, blocking PRR, obstructing IRF-3/7, NF-κB, and degrading STAT1 signaling pathways, thereby assisting viral immune evasion. Arteriviruses infect immune cells and may result in persistence in infected hosts. In this article, we reviewed the strategies used by Arteriviruses to antagonize IFN production and thwart IFN-activated antiviral signaling, mainly including structural and nonstructural proteins of Arteriviruses encoding IFN antagonists directly or indirectly to disrupt innate immunity. This review will certainly provide a better insight into the pathogenesis of the arthritis virus and provide a theoretical basis for developing more efficient vaccines.

Mfn2 is responsible for inhibition of the RIG-I/IRF7 pathway and activation of NLRP3 inflammasome in Seneca Valley virus-infected PK-15 cells to promote viral replication.

Seneca Valley virus (SVV), a non-enveloped positive single-stranded virus can cause vesicular disease in swine. However, the mechanisms by which SVV activates an innate immune response remain unknown. Mitofusin-2 (MFN2), a mitochondria-shaping protein regulating mitochondrial fusion and fission, plays a crucial role in innate immune responses. But, the roles of Mfn2 in SVV infection have not been elucidated. Here, we show that SVV inhibited Mfn2 expression and NLRP3 inflammasome, activating RIG-I/IRF7 signaling pathway to increase IFN-λ3 expression. Overexpression of Mfn2 inhibited RIG-I/IRF7 signaling pathway, thus decreasing IFN-λ3 expression and promoting SVV replication. Interestingly, overexpression of Mfn2 also activated NLRP3 inflammasome but did not inhibit SVV proliferation. That may mean the RIG-I/IRF7 signaling pathway plays a more important role in SVV proliferation in PK-15 cells. This study could provide important insights into the modulation of host metabolism during SVV infection and provide a strong theoretical basis for a better understanding of the pathogenic mechanism and immune activation mechanism of SVV.

Antiviral Activity of Porcine IFN-λ3 and IFN-α against Porcine Rotavirus In Vitro.

Interferons (IFNs) play a major role in the host's antiviral innate immunity. In response to viral infection, IFNs bind their receptors and initiate a signaling cascade, leading to the accurate transcriptional regulation of hundreds of IFN-stimulated genes (ISGs). Porcine rotavirus (PoRV) belongs to genus Rotavirus of the Reoviridae family; the infection is a global epidemic disease and a major threat to the pig industry. In this study, we found that IFN-λ3 inhibited the replication of PoRV in both MA104 cells and IPEC-J2 cells, and this inhibition was dose-dependent. Furthermore, the antiviral activity of IFN-λ3 was more potent in IPEC-J2 cells than in MA104 cells. Further research showed that IFN-λ3 and IFN-α might inhibit PoRV infection by activating ISGs, i.e., MxA, OASL and ISG15, in IPEC-J2 cells. However, the co-treatment of IFN-λ3 and IFN-α did not enhance the antiviral activity. Our data demonstrated that IFN-λ3 had antiviral activity against PoRV and may serve as a useful antiviral candidate against PoRV, as well as other viruses in swine.

The Association between Serum Total Bile Acid Level and Long-Term Prognosis in Patients with Coronary Chronic Total Occlusion Undergoing Percutaneous Coronary Intervention.

Background and Aims: Bile acids, the key products for elimination of cholesterol, play an important role in coronary artery disease (CAD). However, few studies focused on the roles of more accessible serum total bile acids (TBA) in the prediction of adverse cardiovascular events for coronary chronic artery occlusion (CTO). The aim of this study was to explore the potential relationship between serum TBA and long-term prognosis in patients with CTO undergoing percutaneous coronary intervention (PCI). Methods: Baseline TBA was determined in 613 patients with CTO after PCI in the present study. All patients were divided into 3 groups according to the median (3.5 µmol/l) and the normal upper limit of the TBA (10 µmol/l). The primary endpoint was all-cause mortality, and the secondary endpoint was major adverse cardiovascular events (MACE). Results: Average age in this study was 65.44 ± 9.94 years old. The median of TBA was 3.5 (2.1-6.1) µmol/l. Over a median follow-up of 33.5 months, compared to those with below 3.5 µmol/l TBA, 3.5 ~ 10 µmol/l TBA was associated with significantly reduced risk for the MACE (hazard ratio (HR): 0.59, 95% confidence interval (CI): 0.40 to 0.88; p = 0.009) even after adjustment for baseline variables. However, TBA did not predict all-cause mortality and cardiovascular death. Spline analyses showed an L-shaped relationship of the serum TBA with the incidence of MACE. Conclusions: Moderate fasting serum TBA level has a predictive value for MACE even after adjusting for lifestyle and clinical risk factors in CTO patients undergoing PCI.

Insights on the cGAS-STING Signaling Pathway During Herpesvirus Infections.

Herpesviruses belong to large double-stranded DNA viruses. They are under a wide range of hosts and establish lifelong infection, which creates a burden on human health and animal health. Innate immunity is the host's innate defense ability. Activating the innate immune signaling pathway and producing type I interferon is the host's first line of defense against infectious pathogens. Emerging evidence indicates that the cGAS-STING signaling pathway plays an important role in the innate immunity in response to herpesvirus infections. In parallel, because of the constant selective pressure imposed by host immunity, herpesvirus also evolves to target the cGAS-STING signaling pathway to inhibit or escape the innate immune responses. In the current review, we insight on the classical cGAS-STING signaling pathway. We describe the activation of cGAS-STING signaling pathway during herpesvirus infections and strategies of herpesvirus targeting this pathway to evade host antiviral response. Furthermore, we outline the immunotherapy boosting cGAS-STING signaling pathway.

Acute Myocardial Infarction and Concomitant Acute Intracranial Hemorrhage: Clinical Characteristics and Outcomes.

This study aimed to evaluate the demographic and clinical characteristics, treatments and outcomes of concomitant acute myocardial infarction (AMI) and acute intracranial hemorrhage (ICH). All patients diagnosed with concomitant AMI and acute ICH admitted to our institution were included retrospectively. The patient demographics, clinical characteristics, neuroimaging and treatment approaches were analyzed, and the outcomes of interest included disability as defined by the modified Rankin Scale (mRS) score and all-cause mortality within 1 year of follow-up. Of a total of 4972 patients with AMI, 8 patients (0.2%) with concomitant acute ICH were recruited for the study, including ST-segment elevation myocardial infarction (STEMI, 5 cases) and non-STEMI (3 cases). New-onset acute ICH in 4 of the 5 patients (80%) occurred within 24 hours after the AMI event, and all these patients had a sudden decrease in the level of consciousness, with an average decrease of 4.6 on the Glasgow Coma Scale. All 5 out of 8 patients had irregular shapes and uncommon sites of hematoma presentation documented on CT scans. Unfortunately, 2 patients died from a progression of ICH within 1 week, and 2 of the 6 survivors had poor functional outcomes (mRS ≥3) at the 1-year follow-up. Concomitant acute ICH and AMI are rare complications displaying unique iconography. Acute ICH caused serious prejudice in AMI with higher mortality and poor functional outcomes, and cardiac catheterization without the administration of antithrombotic or antiplatelet agents was feasible for patients who had unstable hemodynamics or STEMI.