Aggressive vertebral hemangiomas contain no adipose tissue resulting in thoracic spine kyphosis: A case report.

RATIONALE: Aggressive vertebral hemangiomas (AVHs) destroy continuous vertebral bodies and intervertebral discs and resulting in spinal kyphosis is extremely rare. The very aggressive behavior was attributable to its significant vascular component and contained no adipose tissue. PATIENT CONCERNS: We report a case of thoracic spine kyphosis of AVHs with multiple vertebral bodies and intervertebral disc destruction in a 45-year-old woman. DIAGNOSES: Based on the imaging studies, the patient underwent surgical removal of this lesion and spinal reconstruction. Histopathology consistent with vertebral hemangioma and contained no adipose. INTERVENTIONS: The patient underwent surgical removal of the lesion and spinal reconstruction. After subperiosteal dissection of the paraspinal muscles and exposure of the laminae, the laminae of the T5-7 vertebrae were removed and exposing the lesion. The lesion was soft and showed cystic changes, completely curetted and autogenous bone was implanted. Vertebroplasty was performed through T3-T9 pedicles bilaterally. Pedicle screw fixation was performed for segmental fixation and fusion. OUTCOMES: After 9 days of operation, the incision healed cleanly and free of pain. She was discharged in good general condition. The patient remained asymptomatic after follow-up 6 months of postoperative. LESSONS: AVHs destroy multiple vertebral bodies and intervertebral discs and resulting in spinal kyphosis is extremely rare.

Deep Learning Radiomics Nomogram to Predict Lung Metastasis in Soft-Tissue Sarcoma: A Multi-Center Study.

Objectives: To build and evaluate a deep learning radiomics nomogram (DLRN) for preoperative prediction of lung metastasis (LM) status in patients with soft tissue sarcoma (STS). Methods: In total, 242 patients with STS (training set, n=116; external validation set, n=126) who underwent magnetic resonance imaging were retrospectively enrolled in this study. We identified independent predictors for LM-status and evaluated their performance. The minimum redundancy maximum relevance (mRMR) method and least absolute shrinkage and selection operator (LASSO) algorithm were adopted to screen radiomics features. Logistic regression, decision tree, random forest, support vector machine (SVM), and adaptive boosting classifiers were compared for their ability to predict LM. To overcome the imbalanced distribution of the LM data, we retrained each machine-learning classifier using the synthetic minority over-sampling technique (SMOTE). A DLRN combining the independent clinical predictors with the best performing radiomics prediction signature (mRMR+LASSO+SVM+SMOTE) was established. Area under the receiver operating characteristics curve (AUC), calibration curves, and decision curve analysis (DCA) were used to assess the performance and clinical applicability of the models. Result: Comparisons of the AUC values applied to the external validation set revealed that the DLRN model (AUC=0.833) showed better prediction performance than the clinical model (AUC=0.664) and radiomics model (AUC=0.799). The calibration curves indicated good calibration efficiency and the DCA showed the DLRN model to have greater clinical applicability than the other two models. Conclusion: The DLRN was shown to be an accurate and efficient tool for LM-status prediction in STS.

Herpes simplex virus protein UL56 inhibits cGAS-Mediated DNA sensing to evade antiviral immunity.

After herpes simplex virus type 1 (HSV-1) infection, the cytosolic sensor cyclic GMP-AMP synthase (cGAS) recognizes DNA and catalyzes synthesis of the second messenger 2'3'-cGAMP. cGAMP binds to the ER-localized adaptor protein MITA (also known as STING) to activate downstream antiviral responses. Conversely, HSV-1-encoded proteins evade antiviral immune responses via a wide variety of delicate mechanisms, promoting viral replication and pathogenesis. Here, we identified HSV-1 envelop protein UL56 as a negative regulator of cGAS-mediated innate immune responses. Overexpression of UL56 inhibited double-stranded DNA-triggered antiviral responses, whereas UL56-deficiency increased HSV-1-triggered induction of downstream antiviral genes. UL56-deficiency inhibited HSV-1 replication in wild-type but not MITA-deficient cells. UL56-deficient HSV-1 showed reduced replication in the brain of infected mice and was less lethal to infected mice. Mechanistically, UL56 interacted with cGAS and inhibited its DNA binding and enzymatic activity. Furthermore, we found that UL56 homologous proteins from different herpesviruses had similar roles in antagonizing cGAS-mediated innate immune responses. Our findings suggest that UL56 is a component of HSV-1 evasion of host innate immune responses by antagonizing the DNA sensor cGAS, which contributes to our understanding of the comprehensive mechanisms of immune evasion by herpesviruses.

Skin-whitening mechanism of cumin (Cuminum cyminum L.) extract.

Skin-whitening effect is closely linked with the melanogenesis inhibitory activity and free radical scavenging capacity. The purpose of the present study was to evaluate the skin-whitening effect of cumin (Cuminum cyminum L.) extract. The whitening activity was evaluated by cell-free mushroom tyrosinase assay, free radical scavenging assay, cell viability assay, cellular tyrosinase assay and melanin content assay using B16F10 murine melanoma cells. The results showed that cumin extract exhibited concentration-dependent inhibitory effect on both monophenolase and diphenolase activities of mushroom tyrosinase (IC50 values of 1.027mg/mL and 0.977mg/mL, respectively). Kinetic study on diphenolase showed that the cumin extract was a reversible mixed-type inhibitor, and the inhibition constant (KI) was determined to be 0.62mg/mL. In addition, cumin extract significantly suppressed melanin production and cellular tyrosinase activity of B16F10 melanoma cells in a concentration and time dependent manner without cytotoxicity. Moreover, cumin extract exerted strong scavenging capacity on DPPH, hydroxyl and superoxide anion radicals. Taken together, these results strongly suggest that cumin is a potential skin-whitening agent for the cosmetic industry.

Human Cytomegalovirus Protein UL94 Targets MITA to Evade the Antiviral Immune Response.

Cyclic GMP-AMP synthase (cGAS) senses double-stranded DNA and synthesizes the second messenger cyclic GMP-AMP (cGAMP), which binds to mediator of IRF3 activation (MITA) and initiates MITA-mediated signaling, leading to induction of type I interferons (IFNs) and other antiviral effectors. Human cytomegalovirus (HCMV), a widespread and opportunistic pathogen, antagonizes the host antiviral immune response to establish latent infection. Here, we identified HCMV tegument protein UL94 as an inhibitor of the cGAS-MITA-mediated antiviral response. Ectopic expression of UL94 impaired cytosolic double-stranded DNA (dsDNA)- and DNA virus-triggered induction of type I IFNs and enhanced viral replication. Conversely, UL94 deficiency potentiated HCMV-induced transcription of type I IFNs and downstream antiviral effectors and impaired viral replication. UL94 interacted with MITA, disrupted the dimerization and translocation of MITA, and impaired the recruitment of TBK1 to the MITA signalsome. These results suggest that UL94 plays an important role in the immune evasion of HCMV.IMPORTANCE Human cytomegalovirus (HCMV), a large double-stranded DNA (dsDNA) virus, encodes more than 200 viral proteins. HCMV infection causes irreversible abnormalities of the central nervous system in newborns and severe syndromes in organ transplantation patients or AIDS patients. It has been demonstrated that HCMV has evolved multiple immune evasion strategies to establish latent infection. Previous studies pay more attention to the mechanism by which HCMV evades immune response in the early phase of infection. In this study, we identified UL94 as a negative regulator of the innate immune response, which functions in the late phase of HCMV infection.

Application of Neurally Adjusted Ventilatory Assist in Premature Neonates Less Than 1,500 Grams With Established or Evolving Bronchopulmonary Dysplasia.

Background: Very low birth weight premature (VLBW) infants with bronchopulmonary dysplasia (BPD) often need prolonged respiratory support, which is associated with worse outcomes. The application of neurally adjusted ventilatory assist ventilation (NAVA) in infants with BPD has rarely been reported. This study investigated whether NAVA is safe and can reduce the duration respiratory support in VLBW premature infants with established or evolving BPD. Methods: This retrospective matched-cohort study included patients admitted to our NICU between April 2017 to April 2019 who were born at <32 weeks' gestation with birthweight of <1,500 g. The study groups (NAVA group) were infants who received NAVA ventilation as a sequel mode of ventilation after at least 2 weeks of traditional respiratory support after birth. The control group were preterm infants who required traditional respiratory support beyond first 2 weeks of life and were closely matched to the NAVA patients by gestational age and birthweight. The primary outcome was to compare the total duration of respiratory support between the NAVA group and the control group. The secondary outcomes were comparisons of duration of invasive and non-invasive support, oxygen therapy, length of stay, severity of BPD, weight gain and sedation need between the groups. Results: There were no significant differences between NAVA group and control group in the primary and most of the secondary outcomes (all P > 0.05). However, NAVA was well tolerated and there was a decrease in the need of sedation (p = 0.012) after switching to NAVA. Conclusion: NAVA, when used as a sequel mode of ventilation, in premature neonates <1,500 g with evolving or established BPD showed a similar effect compared to conventional ventilation in respiratory outcomes. NAVA can be safely used in this patient population and potentially can decrease the need of sedation.

Human cytomegalovirus protein UL42 antagonizes cGAS/MITA-mediated innate antiviral response.

Cyclic GMP-AMP synthase (cGAS) senses viral DNA in the cytosol and then catalyzes synthesis of the second messenger cGAMP, which activates the ER-localized adaptor protein Mediator of IRF3 Activator (MITA) to initiate innate antiviral response. Human cytomegalovirus (HCMV) proteins can antagonize host immune responses to promote latent infection. Here, we identified HCMV UL42 as a negative regulator of cGAS/MITA-dependent antiviral response. UL42-deficiency enhances HCMV-induced production of type I interferons (IFNs) and downstream antiviral genes. Consistently, wild-type HCMV replicates more efficiently than UL42-deficient HCMV. UL42 interacts with both cGAS and MITA. UL42 inhibits DNA binding, oligomerization and enzymatic activity of cGAS. UL42 also impairs translocation of MITA from the ER to perinuclear punctate structures, which is required for MITA activation, by facilitating p62/LC3B-mediated degradation of translocon-associated protein ß (TRAPß). These results suggest that UL42 can antagonize innate immune response to HCMV by targeting the core components of viral DNA-triggered signaling pathways.

Human Cytomegalovirus DNA Polymerase Subunit UL44 Antagonizes Antiviral Immune Responses by Suppressing IRF3- and NF-κB-Mediated Transcription.

Innate immunity is the first line of host defense against viral invasion. The induction of type I interferons (IFNs) and inflammatory cytokines is essential to host antiviral immune responses, which are also key targets of viral immune evasion. Human cytomegalovirus (HCMV) can establish long-term latent infections, in which immune evasion is a pivotal step. In this study, we identified HCMV protein UL44, a DNA polymerase processivity factor, as an inhibitor of the interferon regulatory factor 3 (IRF3)- and NF-κB-dependent antiviral response. Ectopic expression of UL44 inhibited HCMV-triggered induction of downstream effector genes and enhanced viral replication. Conversely, knockdown of UL44 potentiated HCMV-triggered induction of downstream antiviral genes. UL44 interacted with IRF3 and p65, and it inhibited the binding of IRF3 and NF-κB to the promoters of their downstream antiviral genes. These findings reveal an important mechanism of immune evasion by HCMV at the transcriptional level.IMPORTANCE Induction of type I IFNs and inflammatory cytokines plays pivotal roles in host antiviral innate immune responses. Viruses have evolved various mechanisms to interfere with these processes. HCMV causes severe ailments in immunodeficient populations and is a major cause of birth defects. It has been shown that HCMV antagonizes host innate immune defenses, which is important for establishing immune evasion and latent infection. In this study, we identified the HCMV DNA polymerase subunit UL44 as a suppressor of antiviral innate immune responses. Overexpression of UL44 impaired HCMV-triggered induction of type I IFNs and other antiviral genes and thus potentiated viral replication, whereas UL44 deficiency showed opposite effects. Mechanistic studies indicated that UL44 acts by inhibiting the binding of IRF3 and NF-κB to the promoters of downstream antiviral genes. These findings defined an important mechanism of HCMV immune evasion at the transcriptional level, which may provide a therapeutic target for the treatment of HCMV infection.

Human Cytomegalovirus Protein UL31 Inhibits DNA Sensing of cGAS to Mediate Immune Evasion.

The cytosolic DNA sensor cGAS recognizes viral DNA and synthesizes the second messenger cGAMP upon viral infection. cGAMP binds to the adaptor protein MITA/STING to activate downstream signaling events, leading to induction of type I interferons (IFNs) and antiviral effector genes. Here we identify the human cytomegalovirus (HCMV) protein UL31 as an inhibitor of cGAS. UL31 interacts directly with cGAS and disassociates DNA from cGAS, thus inhibiting cGAS enzymatic functions and reducing cGAMP production. UL31 overexpression markedly reduces antiviral responses stimulated by cytosolic DNA, while knockdown or knockout of UL31 heightens HCMV-triggered induction of type I IFNs and downstream antiviral genes. Moreover, wild-type HCMV replicates more efficiently than UL31-deficient HCMV, a phenotype that is reversed in cGAS null cells. These results highlight the importance of cGAS in the host response to HCMV as well as an important viral strategy to evade this innate immune sensor.

The RNA-binding protein Mex3B is a coreceptor of Toll-like receptor 3 in innate antiviral response.

Recognition of viral dsRNA by Toll-like receptor 3 (TLR3) leads to induction of interferons (IFNs) and proinflammatory cytokines, and innate antiviral response. Here we identified the RNA-binding protein Mex3B as a positive regulator of TLR3-mediated signaling by expression cloning screens. Cells from Mex3b(-/-) mice exhibited reduced production of IFN-ß in response to the dsRNA analog poly(I:C) but not infection with RNA viruses. Mex3b(-/-) mice injected with poly(I:C) was more resistant to poly(I:C)-induced death. Mex3B was associated with TLR3 in the endosomes. It bound to dsRNA and increased the dsRNA-binding activity of TLR3. Mex3B also promoted the proteolytic processing of TLR3, which is critical for its activation. Mutants of Mex3B lacking its RNA-binding activity inhibited TLR3-mediated IFN-ß induction. These findings suggest that Mex3B acts as a coreceptor of TLR3 in innate antiviral response.

[An experimental study of expression of angiotension converting enzyme 2 in myocardium and effect of telmisartan treatment in pressure-overloaded rats].

OBJECTIVE: To study the effect of hypertension and telmisartan treatment on the protein and gene expression of cardiac angiotensin-converting enzyme 2 (ACE2) in pressure-overloaded rats. METHODS: Coarctation of suprarenal abdominal aorta was reproduced in 8 week-old male Sprague-Dawley (SD) rats and then randomized into 4 groups, including a sham group (n=15), a suprarenal aortic coarctation group (model group, n=12), a suprarenal aortic coarctation with low-dose Telmisartan treatment group (low-dose group, 2 mgxkg(-1)xd(-1), n=11) and a suprarenal aortic coarctation with high-dose Telmisartan treatment group(high-dose group, 10 mgxkg(-1)xd(-1), n=13). Telmisartan or equivalent amount of normal saline was gavaged 24 hours before the operation and once every day afterwards for 3 weeks. At the end of 3 weeks, the concentrations of angiotensin (AngII) in plasma and myocardium were measured by radioimmunoassay. Changes in both protein quantity and gene expressions of both ACE2 and ACE were determined by Western blotting analysis and reverse transcription-polymerase chain reaction (RT-PCR) technique, respectively. RESULTS: Suprarenal abdominal aortic coarctation induced a significant increase in the plasma and myocardium AngII concentration [plasma: (495.1+/-55.6) ng/L vs. (269.2+/-39.5)ng/L, myocardium: (103.6+/-23.7) ng/g vs. (49.5+/-13.5) ng/g, both P<0.01] and expressions of gene and protein of ACE (P<0.01) and ACE2 (P<0.05). Telmisartan further increased the concentration of AngII in plasma and myocardium in a dose-dependent manner [plasma: (702.2+/-40.6) ng/L vs. (612.6+/-35.5) ng/L, myocardium (211.5+/-21.5) ng/g vs. (189.6+/-43.6) ng/g, both P<0.05], and induced a dose-dependent increase in both protein and gene expression of ACE2 (protein 1.16+/-0.06 vs. 0.79+/-0.04, gene 0.54+/-0.08 vs. 0.41+/-0.04, both P<0.05). Expression of ACE2 protein in low-dose and high-dose groups was increased by 1.0 and 1.58 folds respectively, and gene was increased by 1.3 and 1.6 folds (all P<0.05). The expression of ACE protein and gene in model group increased significantly (protein: 2.10+/-1.07 vs. 1.02+/-0.05, gene: 1.93+/-0.09 vs. 0.26+/-0.09, both P<0.01). Telmisartan had no significant effect on ACE gene and protein expressions (both P>0.05). CONCLUSION: Suprarenal abdominal aortic coarctation induced a significant increases of ACE and ACE2 gene and protein expressions. Telmisartan induces a dose-dependent increases of cardiac ACE2 gene and protein expression,which may be the mechanism of its therapeutic effects.