The diagnostic value of [18F]FAPI-42 PET/CT for pulmonary artery masses: comparison with [18F]FDG PET/CT.

OBJECTIVES: To investigate the potential utility of [18F]fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT) for evaluating pulmonary artery (PA) masses, and compare it with [18F]fluorodeoxyglucose (FDG) PET/CT. METHODS: Participants with clinically suspected PA malignancy were prospectively enrolled and underwent dual-tracer PET/CT ([18F]FAPI-42 and [18F]FDG) imaging. Visual analysis and semi-quantitative parameters were compared between the two types of radiotracers. The tissue specimen underwent immunohistochemical staining to verify FAP expression in the tissue. RESULTS: Thirty-three patients (18 males/15 females; mean age 53.1 ± 15.4 years) were enrolled. All 21 patients with malignant PA masses were FDG-positive (100%), whereas 20 out of 21 patients were FAPI-positive (95.2%). All 12 patients with benign PA masses were both negative in FDG and FAPI PET. The mean maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR) of FAPI and FDG in malignant PA masses were significantly higher than those of benign masses. Although there was no significant difference in SUVmax between FDG and FAPI in malignant PA masses (11.36 vs. 9.18, p = 0.175), the TBR (liver) and TBR (left ventricle) were more favorable for FAPI than for FDG (13.04 vs. 5.17, p < 0.001); (median: 7.75 vs. 2.75, p = 0.007). Immunohistochemical analysis (n = 16) validated that the level of FAP expression corresponded strongly to the uptake of FAPI in PET/CT scans (rs = 0.712, p = 0.002). For clinical management, FAPI PET found more metastatic lesions than FDG PET in 4 patients, with 2 patients upgrading and 1 patient changing treatment decisions. CONCLUSIONS: FAPI PET/CT is feasible in the diagnosis of PA masses. Although not superior to FDG PET/CT, FAPI PET/CT showed better target-to-background contrast. CLINICAL RELEVANCE STATEMENT: This study found that FAPI PET/CT is not superior to FDG PET/CT in diagnosing PA masses, but FAPI PET/CT displays better target-to-background contrast and more positive lesions, which may help improve disease management. KEY POINTS: Pulmonary malignancies lack specificity in clinical manifestations, laboratory tests, and routine imaging examinations. FAPI PET/CT is not diagnostically better than FDG PET/CT but displays better target-to-background contrast and more positive lesions. Dual-tracer PET/CT ([18F]FAPI-42 and [18F]FDG) imaging improves clinical management of pulmonary artery masses.

Implication of Cerebral Small-Vessel Disease on Perihematomal Edema Progress in Patients With Hypertensive Intracerebral Hemorrhage.

BACKGROUND: Perihematomal edema (PHE) is an important determinant of outcome in spontaneous intracerebral hemorrhage (ICH) due to cerebral small vessel disease (CSVD). However, it is not known to date whether the severity of CSVD is associated with the extent of PHE progression in the acute phase. PURPOSE: To investigate the association between the magnetic resonance imaging (MRI) marker of severe chronic-ischemia cerebral small vessel changes (sciSVC) and PHE growth or hematoma absorption among ICH patients with hypertension. STUDY TYPE: Retrospective. POPULATION: Three hundred and sixty-eight consecutive hypertensive ICH patients without surgical treatment. FIELD STRENGTH/SEQUENCE: 3 T; spin-echo echo-planar imaging-diffusion-weighted imaging (DWI); T2-weighted, fluid-attenuated inversion recovery (FLAIR), T2*-weighted gradient-recalled echo and T1-weighted. ASSESSMENT: The hematoma and PHE volumes at 24 hours and 5 days after symptom onset were measured in 121 patients with spontaneous ICH who had been administered standard medical treatment. Patients were grouped into two categories: those with sciSVC and those without. The imaging marker of sciSVC was defined as white matter hyperintensities (WMHs) Fazekas 2-3 combined cavitating lacunes. STATISTICAL TESTS: Univariable analyses, χ2 test, Mann-Whitney U test, and multiple linear regression. RESULTS: The presence of sciSVC (multiple lacunes and confluent WMH) had a significant negative influence on PHE progress (Beta = -5.3 mL, 95% CI = -10.3 mL to -0.3 mL), and hematoma absorption (Beta = -3.2 mL, 95% CI = -5.9 mL to -0.4 mL) compared to that observed in the absence of sciSVC, as determined by multivariate linear regression analysis. DATA CONCLUSIONS: The presence of sciSVC (multiple lacunes and confluent WMH) negatively influenced hematoma absorption and PHE progress in ICH patients. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 3.

Bilateral versus unilateral balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension.

BACKGROUND: To evaluate the safety and efficacy of bilateral balloon pulmonary angioplasty (BPA) as compared with unilateral BPA for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). METHOD: We reviewed 210 consecutive BPA sessions for 92 CTEPH patients, including 124 unilateral BPA sessions and 86 bilateral BPA sessions. Radiation exposure, operation details, lesions characteristics and the occurrence of complications were compared between unilateral BPA and bilateral BPA. 131 BPA sessions with a hemodynamics follow-up were included for efficacy analysis, in which hemodynamics changes were compared. Logistic regression analysis was used to identify factors associated with the occurrence of complications. RESULT: Bilateral BPA treated more lobes, arteries and lesions [3 (2, 4) vs. 2 (1, 3) lobes, p < 0.001; 8 (5.5, 10) vs. 6 (4, 8) vessels, p = 0.003; 9 (7, 12) vs. 8 (5, 10) lesions, p = 0.01] in one single session than unilateral BPA in a comparable operation duration and amount of contrast media given. Overall, the occurrence of complications was similar between bilateral BPA and unilateral BPA [9 (10.5%) vs. 12 (9.7%), p = 0.83]. Hemodynamics effects didn't differ significantly between bilateral BPA and unilateral BPA in a single session [mPAP, - 4.5 ± 8.6 vs. - 3.6 ± 7.3 mmHg, p = 0.52; PVR, - 1.1 (- 3.5, 0.8) vs. - 1.8 (- 5.2, 0.3) Wood units, p = 0.21]. For the initial BPA session, bilateral BPA also treated more lobes, arteries and lesions than unilateral BPA [3 (2, 4) vs. 2 (1, 2) lobes, p < 0.001; 8.0 (5.8, 9.3) vs. 6.0 (4.0, 8.0) vessels, p = 0.04; 9 (6, 12) vs. 7 (4, 10) lesions, p = 0.02]. The occurrence of complications was also similar [5 (13.2%) vs. 5 (9.3%), p = 0.80], even in patients with poor baseline hemodynamics. Univariate regression analysis reveals the number of lobes treated/session, but not bilateral BPA, as predictive factors of complications. CONCLUSION: Bilateral BPA may be safely and effectively performed in patients with CTEPH without increasing operation duration and radiation burden, even in patients with unfavorable baseline hemodynamics.

Improving the imaging diagnostic strategy for pulmonary artery masses based on 18F-FDG PET/CT integrated with CTPA.

OBJECTIVE: To evaluate the diagnostic accuracy of computed tomography pulmonary angiography (CTPA) and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for pulmonary artery (PA) masses. METHODS: Of 2889 patients with PA filling defects of PA on CTPA, 79 consecutive patients suspicious for PA malignancy who subsequently underwent 18F-FDG PET/CT were enrolled. All masses were diagnosed on the basis of pathological findings or clinical imaging follow-up. For each mass, morphological CT signs, standardized uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on 18F-FDG PET/CT were used as diagnostic markers. RESULTS: Expansive growth, irregular margin, invasion, CT contrast uptake, and wall eclipse sign were strongly associated with the malignant nature of masses. The coexistence of at least 5 CT signs perfectly identified malignant masses, whereas the detection of no more than 4 CT signs did not accurately discriminate between the natures of masses. Mean SUVmax, SUVmean, MTV, and TLG values were significantly higher in malignant masses compared to those in benign masses. The diagnostic accuracy of 18F-FDG PET/CT parameters (SUV, MTV, and TLG) was excellent in detecting malignant masses. Among patients with 3 or 4 pathological CT signs, SUVmax > 3.4 significantly increased the identification of malignancies. CONCLUSIONS: CTPA is a useful imaging modality for diagnosing PA masses, especially when at least 5 abnormal CT signs are identified. Similarly, 18F-FDG PET/CT accurately identified malignant masses and provided additional valuable information on diagnostic uncertainties after CTPA.

Effect of Throat Washings on Detection of 2019 Novel Coronavirus.

The 2019 novel coronavirus was detected in self-collected throat washings. The positive testing rate of throat washing was much higher than that of nasopharyngeal swabs. Throat washing is a promising candidate for 2019-nCoV screening and monitoring due to its noninvasiveness and reliability.

Efficacy and safety of anti-inflammatory agents for the treatment of major depressive disorder: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: To systematically review the efficacy and safety of anti-inflammatory agents for patients with major depressive disorders. METHODS: We searched the literature to identify potentially relevant randomised controlled trials (RCTs) up to 1 January 2019. The primary outcome was efficacy, measured by mean changes in depression score from baseline to endpoint. Secondary outcomes included response and remission rates and quality of life (QoL). Safety was evaluated by incidence of classified adverse events. Heterogeneity was examined using the I2 and Q statistic. Pooled standard mean differences (SMDs) and risk ratios (RRs) were calculated. Subgroup meta-analyses were conducted based on type of treatment, type of anti-inflammatory agents, sex, sponsor type and quality of studies. RESULTS: Thirty RCTs with 1610 participants were included in the quantitative analysis. The overall analysis pooling from 26 of the RCTs suggested that anti-inflammatory agents reduced depressive symptoms (SMD -0.55, 95% CI -0.75 to -0.35, I2=71%) compared with placebo. Higher response (RR 1.52, 95% CI 1.30 to 1.79, I2=29%) and remission rates (RR 1.79, 95% CI 1.29 to 2.49, I2=41%) were seen in the group receiving anti-inflammatory agents than in those receiving placebo. Subgroup analysis showed a greater reduction in symptom severity in both the monotherapy and adjunctive treatment groups. Subgroup analysis of non-steroidal anti-inflammatory drugs, omega-3 fatty acids, statins and minocyclines, respectively, disclosed significant antidepressant effects for major depressive disorder (MDD). For women-only trials, no difference in changes of depression severity was found between groups. Subanalysis stratified by sponsor type and study quality led to the same outcomes in favour of anti-inflammatory agents in both subgroups. Changes of QoL showed no difference between the groups. Gastrointestinal events were the only significant differences between groups in the treatment periods. CONCLUSIONS: Results of this systematic review suggest that anti-inflammatory agents play an antidepressant role in patients with MDD and are reasonably safe.

Application of DynaCT angiographic reconstruction in balloon pulmonary angioplasty.

OBJECTIVES: To investigate the feasibility and accuracy of balloon pulmonary angioplasty (BPA) using DynaCT angiographic reconstruction guidance. METHODS: Thirty-four BPAs (23 CTEPH patients) targeting 175 pulmonary arteries were included. Eleven BPAs (2D group) were guided by DSA two-dimensional angiography. Another twenty-three BPAs (3D group) were guided using DynaCT angiographic reconstruction. The volume rendering (VR) method was used to obtain a three-dimensional image of the blood vessels. This image was used as a reference to continue BPA treatment under the guidance of vascular three-dimensional reconstruction technology. Procedure durations and radiation exposure data were compared between the two groups using Mann-Whitney U test. RESULTS: Using the DynaCT angiographic reconstruction technique, more target vessels were treated in a single BPA procedure (5.83 ± 2.33 vs 3.73 ± 1.10 vessels per BPA, p = 0.008) in a shorter operation time (3.58 ± 0.61 vs 4.49 ± 0.91 h, p = 0.002). Overall, the dose area product (DAP) was significantly higher for the 2D group than for the 3D group (13,901.82 ± 5549.69 vs 4682.82 ± 1950.64, p < 0.001). The use of the DynaCT angiographic reconstruction technique to guide BPA required a lower dose of contrast agent (225.22 ± 48.70 vs 292.73 ± 76.82 mL, p = 0.013) and less radiation exposure. CONCLUSIONS: The use of DynaCT angiographic reconstruction guidance in patients undergoing BPA is feasible and accurate. Images of DynaCT angiographic reconstruction may be beneficial for optimizing the operative process in BPA with reduced radiation exposure. KEY POINTS: • BPA guidance by DynaCT angiographic reconstruction is feasible and accurate. • DynaCT angiographic reconstruction may be beneficial for optimizing the operative process. • DynaCT angiographic reconstruction can reduce patient radiation dose due to multi-times of BPA sessions.

Efficacy and safety of calcitonin-gene-related peptide binding monoclonal antibodies for the preventive treatment of episodic migraine - an updated systematic review and meta-analysis.

BACKGROUND: Migraine is one of the most common neurological disorders that leads to disabilities. However, the conventional drug therapy for migraine might be unsatisfactory at times. Therefore, this meta-analysis aimed to evaluate the efficacy and safety of calcitonin-gene-related peptide binding monoclonal antibody (CGRP mAb) for the preventive treatment of episodic migraine, and provide high-quality clinical evidence for migraine therapy. METHODS: A systematic electronic database search was conducted to identify the potentially relevant studies. Two independent authors performed data extraction and quality appraisal. Mean difference (MD) and risk ratio (RR) were pooled for continuous and dichotomous data, respectively. The significance levels, weighted effect sizes and homogeneity of variance were calculated. RESULTS: Eleven high-quality randomized control trials that collectively included 4402 patients were included in this meta-analysis. Compared to placebo group, CGRP mAb therapy resulted in a reduction of monthly migraine days [weighted mean difference (WMD) = - 1.44, 95% CI = (- 1.68,- 1.19)] and acute migraine-specific medication days [WMD = - 1.28, 95% CI = (- 1.66,- 0.90)], with an improvement in 50% responder rate [RR = 1.51, 95% CI = (1.37,1.66)]. In addition, the adverse events (AEs) and treatment withdrawal rates due to AEs were not significantly different between CGRP mAb and placebo groups. Similar efficacy and safety results were obtained for erenumab, fremanezumab, and galcanezumab in subgroup analysis. CONCLUSIONS: The current body of evidence reveals that CGRP mAb is an effective and safe preventive treatment for episodic migraine.

Ultra-broadband infrared metasurface absorber: reply.

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Incidence and Predictors of Tracheobronchial Tuberculosis in Pulmonary Tuberculosis: A Multicentre, Large-Scale and Prospective Study in Southern China.

BACKGROUND: Patients with pulmonary tuberculosis (PTB) have a high risk of concomitant tracheobronchial tuberculosis (TBTB), which commonly causes severe complications such as tracheobronchial stenosis. The prevalence and predictors of TBTB in China remain unclear due to the lack of prospective and large-scale studies. OBJECTIVES: To investigate the incidence of TBTB in PTB patients in southern China, and elucidate the predictors of TBTB and related tracheobronchial stenosis. METHODS: We prospectively performed bronchoscopy in PTB patients to diagnose TBTB at four medical centres in southern China from September 2015 to August 2016. Clinical and epidemiological data were recorded and analysed to determine predictors of TBTB and related tracheobronchial stenosis. RESULTS: A total of 345 (23.9%) of the 1,442 PTB patients undergoing bronchoscopy were diagnosed with TBTB. Female sex (OR 2.53), age < 50 years (OR 1.88), living in urban (OR 2.19), diabetes (OR 1.84), coughing (OR 2.61), and symptoms ≥4 weeks (OR 1.66) were predictors of PTB concomitant with TBTB. About 59.7% TBTB patients developed tracheobronchial stenosis, of which 23.3% cases presented severe airway narrowing. Female sex (OR 2.27), age < 50 years (OR 2.11), shortness of breath (OR 1.97), and symptoms ≥4 weeks (OR 1.71) were predictors of TBTB-related tracheobronchial stenosis. CONCLUSIONS: About 23.9% of PTB patients undergoing bronchoscopy present with TBTB in Guangdong province, southern China. Young and middle-aged females with symptoms persisting for ≥4 weeks (the main predictors of TBTB and related tracheobronchial stenosis) should receive bronchoscopy immediately when diagnosed with PTB.

Ultra-broadband infrared metasurface absorber.

By using sub-wavelength resonators, metamaterial absorber shows great potential in many scientific and technical applications due to its perfect absorption characteristics. For most practical applications, the absorption bandwidth is one of the most important performance metrics. In this paper, we demonstrate the design of an ultra-broadband infrared absorber based on metasurface. Compared with the prior work [Opt. Express22(S7), A1713-A1724 (2014)], the proposed absorber shows more than twice the absorption bandwidth. The simulated total absorption exceeds 90% from 7.8 to 12.1 um and the full width at half maximum is 50% (from 7.5 to 12.5 µm), which is achieved by using a single layer of metasurface. Further study demonstrates that the absorption bandwidth can be greatly expanded by using two layers of metasurface, i.e. dual-layered absorber. The total absorption of the dual-layered absorber exceeds 80% from 5.2 to 13.7 um and the full width at half maximum is 95% (from 5.1 to 14.1 µm), much greater than those previously reported for infrared spectrum. The absorption decreases with fluctuations as the incident angle increases but remains quasi-constant up to relatively large angles.

[Refractory pulmonary alveolar proteinosis treated with inhaled granulocyte macrophage colony stimulating factor: a case report and review of the literatures].

OBJECTIVE: To observe the efficacy of granulocyte macrophage colony stimulating factor inhalation therapy for pulmonary alveolar proteinosis (PAP) patients and to improve the understanding of the therapy. METHODS: The clinical data of a patient with autoimmune PAP treated with inhaled granulocyte macrophage colony stimulating factor were described and the literatures were reviewed. RESULTS: This 70-year-old female patient was diagnosed with autoimmune PAP and had been treated with whole lung lavage for 10 times, but only achieved short-term symptomatic relief after each operation. Inhalation of granulocyte macrophage colony stimulating factor was then used after the recurrence of PAP, and a significant improvement in oxygenation and clinical symptoms were abserved. The patient remained stable 4 month after the therapy. CONCLUSION: Treatment with inhalation of granulocyte macrophage colony stimulating factor is safe, effective and economic for patients with PAP, and would be the first choice for the recurrence of autoimmune PAP after whole lung lavage.

Alfalfa supplementation timing changes the rumen archaeal and fungal community composition and colonization in pre-weaning lambs.

The establishment of the rumen microbiota plays an important role in the rumen development. However, little is known about the effects of alfalfa supplementation time on rumen microbiota establishment. Here, a total of 42 Hu lambs, seven-day-old, were chosen for the study. After a week of adjustment, six lambs were sacrificed to establish a baseline. The remaining 36 lambs were randomly split into two groups: one receiving alfalfa hay at 14 days (EAF), the other at 42 days (LAF), both groups received milk replacer and starter pellets. Introducing alfalfa at 14 days of age significantly improved total dry matter intake between 28 and 42 days (p = 0.04) and average daily gain from both 14 to 28 days (p = 0.04) and 28 to 42 days (p < 0.01), but this effect disappears from 56 to 70 days (p > 0.05). At 42 days, the abundances of Naganishia, Ascochyta, and Neosetophoma in the EAF group were significantly higher (p < 0.05) than those in the LAF group (17.8% vs. 3.97, 10.89% vs. 1.77, and 1.27% vs. 0.09%, respectively). At 56 days, the abundances of Ascochyta, Wallemia, and Aspergillus in the EAF group were significantly lower (p < 0.05) than in the LAF group (3.53% vs. 16.40, 8.78% vs. 18.89, and 2.14% vs. 4.69%). At 70 days, Aspergillus abundance in the EAF group was significantly higher (p < 0.05) than in the LAF group (2.69% vs. 0.85%). The LEfSe analysis showed that Methanobrevibacter_smithii was the archaeal biomarker at 14 days in both groups. Methanobrevibacter_sp_AbM4 was enriched at 56 days in the LAF group. Compared to the LAF group, the specific fungal biomarkers in the EAF group included Sporobolomyces and Bullera at 14 days, Naganishia, Didymella, Cleistothelebolus, and Alloleptosphaeria at 42 days, Ascochyta, Neoascochyta, and Alfaria at 70 days. Correlation analysis results showed strong patterns of association both within and between archaea and fungi, which were influenced by alfalfa supplementation time. In summary, alfalfa supplementation at 14 days of age promotes the growth performance of lambs before weaning, and alfalfa supplementation timing significantly affects rumen archaeal and fungal communities and dynamical changes.

Characterizing hedgehog pathway features in senescence associated osteoarthritis through Integrative multi-omics and machine learning analysis.

Purpose: Osteoarthritis (OA) is a disease of senescence and inflammation. Hedgehog's role in OA mechanisms is unclear. This study combines Bulk RNA-seq and scRNA-seq to identify Hedgehog-associated genes in OA, investigating their impact on the pathogenesis of OA. Materials and methods: Download and merge eight bulk-RNA seq datasets from GEO, also obtain a scRNA-seq dataset for validation and analysis. Analyze Hedgehog pathway activity in OA using bulk-RNA seq datasets. Use ten machine learning algorithms to identify important Hedgehog-associated genes, validate predictive models. Perform GSEA to investigate functional implications of identified Hedgehog-associated genes. Assess immune infiltration in OA using Cibersort and MCP-counter algorithms. Utilize ConsensusClusterPlus package to identify Hedgehog-related subgroups. Conduct WGCNA to identify key modules enriched based on Hedgehog-related subgroups. Characterization of genes by methylation and GWAS analysis. Evaluate Hedgehog pathway activity, expression of hub genes, pseudotime, and cell communication, in OA chondrocytes using scRNA-seq dataset. Validate Hedgehog-associated gene expression levels through Real-time PCR analysis. Results: The activity of the Hedgehog pathway is significantly enhanced in OA. Additionally, nine important Hedgehog-associated genes have been identified, and the predictive models built using these genes demonstrate strong predictive capabilities. GSEA analysis indicates a significant positive correlation between all seven important Hedgehog-associated genes and lysosomes. Consensus clustering reveals the presence of two hedgehog-related subgroups. In Cluster 1, Hedgehog pathway activity is significantly upregulated and associated with inflammatory pathways. WGCNA identifies that genes in the blue module are most significantly correlated with Cluster 1 and Cluster 2, as well as being involved in extracellular matrix and collagen-related pathways. Single-cell analysis confirms the significant upregulation of the Hedgehog pathway in OA, along with expression changes observed in 5 genes during putative temporal progression. Cell communication analysis suggests an association between low-scoring chondrocytes and macrophages. Conclusion: The Hedgehog pathway is significantly activated in OA and is associated with the extracellular matrix and collagen proteins. It plays a role in regulating immune cells and immune responses.

The Effects of Housing on Growth, Immune Function and Antioxidant Status of Young Female Lambs in Cold Conditions.

Cold conditions in northern China during winter may reduce sheep growth and affect their health, especially if they are young, unless housing is provided. We allocated 45 two-month-old female lambs to be housed in an enclosed building, a polytunnel, or kept outdoors, for 28 days. The daily weight gain and scalp and ear skin temperature of outdoor lambs were less than those of lambs that were housed in either a house or polytunnel; however, rectal temperature was unaffected by treatment. There was a progressive change in blood composition over time, and by the end of the experiment, outdoor lambs had reduced total antioxidant capacity (T-AOC), catalase (CAT), glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) and increased malondialdehyde compared to those in the house or polytunnel. In relation to immune responses in the lambs' serum, in the polytunnel, immunoglobulin A (IgA), tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4) were higher and immunoglobulin G (IgG) lower compared with the concentrations in lambs that were outdoors. Over the course of the experiment, genes expressing heat shock proteins and antioxidant enzymes increased in lambs in the outdoor treatment, whereas they decreased in lambs in the indoor treatments. It is concluded that although there were no treatment effects on core body temperature, the trends for progressive changes in blood composition and gene expression indicate that the outdoor lambs were not physiologically stable; hence, they should not be kept outdoors in these environmental conditions for long periods.

The comprehensive landscape of prognosis, immunity, and function of the GLI family by pan-cancer and single-cell analysis.

The Hedgehog (Hh) signaling pathway has been implicated in the pathogenesis of various cancers. However, the roles of the downstream GLI family (GLI1, GLI2, and GLI3) in tumorigenesis remain elusive. This study aimed to unravel the genetic alterations of GLI1/2/3 in cancer and their association with the immune microenvironment and related signaling pathways. Firstly, we evaluated the expression profiles of GLI1/2/3 in different cancer types, analyzed their prognostic and predictive values, and assessed their correlation with tumor-infiltrating immune cells. Secondly, we explored the relationships between GLI1/2/3 and genetic mutations, epigenetic modifications, and clinically relevant drugs. Finally, we performed enrichment analysis to decipher the underlying mechanisms of GLI1/2/3 in cancer initiation and progression. Our results revealed that the expression levels of GLI1/2/3 were positively correlated in most cancer tissues, suggesting a cooperative role of these factors in tumorigenesis. We also identified tissue-specific expression patterns of GLI1/2/3, which may reflect the distinct functions of these factors in different cell types. Furthermore, GLI1/2/3 expression displayed significant associations with poor prognosis in several cancers, indicating their potential as prognostic biomarkers and therapeutic targets. Importantly, we found that GLI1/2/3 modulated the immune microenvironment by regulating the recruitment, activation, and polarization of cancer-associated fibroblasts, endothelial cells, and macrophages. Additionally, functional enrichment analyses indicated that GLI1/2/3 are involved in the regulation of epithelial-mesenchymal transition (EMT). Together, our findings shed new light on the roles of GLI1/2/3 in tumorigenesis and provide a potential basis for the development of novel therapeutic strategies targeting GLI-mediated signaling pathways in cancer.

Systematic analysis of the prognostic value and immunological function of LTBR in human cancer.

Lymphotoxin beta receptor (LTBR) is a positive T cell proliferation regulator gene. It is closely associated with the tumor immune microenvironment. However, its role in cancer and immunotherapy is unclear. Firstly, the expression level and prognostic value of LTBR were analyzed. Secondly, the expression of LTBR in clinical stages, immune subtypes, and molecular subtypes was analyzed. The correlation between LTBR and immune regulatory genes, immune checkpoint genes, and RNA modification genes was then analyzed. Correlations between LTBR and immune cells, scores, cancer-related functional status, tumor stemness index, mismatch repair (MMR) genes, and DNA methyltransferase were also analyzed. In addition, we analyzed the role of LTBR in DNA methylation, mutational status, tumor mutation burden (TMB), and microsatellite instability (MSI). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the role of LTBR in pan-cancer. Finally, the drugs associated with LTBR were analyzed. The expression of LTBR was confirmed using quantitative real-time PCR and Western blot. LTBR is significantly overexpressed in most cancers and is associated with low patient survival. In addition, LTBR expression was strongly correlated with immune cells, score, cancer-related functional status, tumor stemness index, MMR genes, DNA methyltransferase, DNA methylation, mutational status, TMB, and MSI. Enrichment analysis revealed that LTBR was associated with apoptosis, necroptosis, and immune-related pathways. Finally, multiple drugs targeting LTBR were identified. LTBR is overexpressed in several tumors and is associated with a poor prognosis. It is related to immune-related genes and immune cell infiltration.

A better method to evaluate the reliability of echocardiography for assessment of pulmonary hypertension: comparison of tricuspid regurgitant spectrum quality grading and tricuspid valve regurgitation degree.

Background: Transthoracic echocardiography (TTE) is recommended as the most important noninvasive screening tool for the diagnosis of pulmonary hypertension (PH), sonographers usually measure the volume of regurgitant flow rather than evaluating the spectral quality, so physicians will determine whether the ultrasound measurements of pulmonary arterial systolic pressure (US-PASP) are reliable based on the volume of tricuspid regurgitation (TR). Therefore, for the first time, we grade the quality of TR spectrum (TRS) based on its integrity and clarity, aiming to assess clinical application value of different tricuspid regurgitant spectrum quality grades (TR-SQG), and investigate whether the accuracy of US-PASP is more trustworthy than TR. Methods: We retrospectively analyzed 108 patients with chronic thromboembolic PH (CTEPH) to compare the correlation and agreement between US-PASP and right heart catheterization measurements of PASP (RHC-PASP). TR area (TRA) and TRS were measured in each patient, and TR-SQG was performed. Results: The correlation coefficients between US-PASP and RHC-PASP were r=0.622 (P<0.001), r=0.754 (P<0.001), r=0.595 (P<0.001) in mild, moderate, severe TR, and r=0.301 (P=0.135), r=0.747 (P<0.001), r=0.739 (P<0.001), r=0.828 (P<0.001) in TR-SQG I-IV, respectively. Bland-Altman analysis revealed the mean biases of 5.05, 3.06, 7.62 mmHg in mild, moderate, severe TR, and -16.47, -8.07, 1.82, 6.09 mmHg in TR-SQG I-IV, respectively. In mild TR with the TR-SQG III and IV, the correlation coefficients between US-PASP and RHC-PASP were r=0.779 (P<0.001), intraclass correlation coefficient (ICC) =0.774, paired t-test P=0.160, respectively; and the consistency was significantly higher than that of mild TR without considering TR-SQG. In moderate TR with the TR-SQG III and IV, the r=0.749, ICC =0.746, paired t-test P=0.298 between US-PASP and RHC-PASP. Conclusions: The US-PASP with TR-SQG III or IV is trustworthy, and its accuracy and consistency are better than those predicted by the traditional severity of TR. The establishment of the ultrasound evaluation system of TR-SQG helps clinicians to judge whether the US-PASP is accurate, credible, and reliable.