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.

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.

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.

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.

Corrigendum: Systematic pan-cancer analysis of the potential tumor diagnosis and prognosis biomarker P4HA3.

[This corrects the article DOI: 10.3389/fgene.2023.1045061.].

Percutaneous endovascular biopsy for the diagnosis of pulmonary artery masses: A preliminary study of single-center.

Percutaneous endovascular biopsy (PEB) including forceps biopsy and catheter aspiration has been used to make a pretreatment diagnosis for pulmonary artery (PA) masses. This retrospective study aims to describe the procedure of PEB and compare the diagnostic yield of forceps biopsy and catheter aspiration for a definite diagnosis in patients with PA masses. All consecutive 22 patients (53 ± 14 years), 11 males and 11 females, who underwent PEB for pathologic confirmation between November 2018 and November 2022 were enrolled. All 22 patients performed computed tomography pulmonary angiography or positron emission tomography-computed tomography to confirm the filling defects suspicious for PA malignancy before intervention. And then, all patients underwent PEB successfully without acute or fatal complications, including both forceps biopsy and catheter aspiration in 15 cases, only forceps biopsy in 5 cases, and only catheter aspiration in 2 cases. Histopathological analysis provided a definite diagnosis in all PEBs with a clinical success of 91.0% (20/22). Among them, in 15 patients who underwent both forceps biopsy and aspiration biopsy, the technical success using forceps biopsy was 93.3% (14/15), and aspiration biopsy was 6.7% (1/15), and there was a significant difference in diagnostic accuracy when comparing two techniques. Twenty-one out of 22 PA masses (95.5%) were malignant, of which, the most frequent malignant lesion observed was PA sarcoma (66.7%, 14/21). Benign lesion included one thrombus (4.5%, 1/22). In conclusion, PEB is an effective and safe diagnostic method for differentiating benign and malignant PA masses and could be peformed when PA masses appeared clinically malignant.

Systematic pan-cancer analysis of the potential tumor diagnosis and prognosis biomarker P4HA3.

Purpose: Prolyl 4-hydroxylase subunit alpha 3 (P4HA3) is implicated in several cancers' development. However, P4HA3 has not been reported in other cancers, and the exact mechanism of action is currently unknown. Materials and methods: First, the expression profile of P4HA3 was analyzed using a combination of the University of California Santa Cruz (UCSC) database, Cancer Cell Line Encyclopedia (CCLE) database, and Genotype-Tissue Expression (GTEx) database. UniCox and Kaplan-Meier were used to analyze the predictive value of P4HA3. The expression of P4HA3 was analyzed in clinical staging, immune subtypes, and Molecular subtypes. Secondly, the correlation of P4HA3 with immunomodulatory genes, immune checkpoint genes, RNA modification genes, immune cell infiltration, cancer-related functional status, tumor stemness index, DNA mismatch repair (MMR) genes and DNA Methyltransferase was examined. The role of P4HA3 in DNA methylation, copy number variation (CNV), mutational status, tumor mutational burden (TMB), and microsatellite instability (MSI) was also analyzed. In addition, gene set enrichment analysis (GSEA) was used to explore the potential functional mechanisms of P4HA3 in pan-cancer. Finally, P4HA3-related drugs were searched in CellMiner, Genomics of Drug Sensitivity in Cancer (GDSC), and Cancer Therapeutics Response Portal (CTRP) databases. Results: P4HA3 is significantly overexpressed in most cancers and is associated with poor prognosis. P4HA3 is strongly associated with clinical cancer stage, immune subtypes, molecular subtypes, immune regulatory genes, immune checkpoint genes, RNA modifier genes, immune cell infiltration, cancer-related functional status, tumor stemness index, MMR Gene, DNA Methyltransferase, DNA methylation, CNV, mutational status, TMB, and MSI are closely related. Available enrichment analysis revealed that P4HA3 is associated with the epithelial-mesenchymal transition and immune-related pathways. There are currently 20 drugs associated with P4HA3. Conclusion: In human pan-cancer, P4HA3 is associated with poor patient prognosis and multiple immune cells and may be a novel immunotherapeutic target. It may act on tumor progression through the epithelial-mesenchymal transition (EMT) pathway.

Successful chemotherapy with continuous immunotherapy for primary pulmonary endovascular epithelioid hemangioendothelioma: A case report.

RATIONALE: Epithelioid hemangioendothelioma (EHE) is a rare, low to moderate-grade malignancy, even less in pulmonary endovascular neoplasm. Patients with pulmonary EHE have no optimal treatment, resulting in poor prognoses. PATIENT CONCERNS: We reported a 42-year-old man with multiple mild metabolic uptakes in pulmonary endovascular filling defect with a maximum standardized uptake value of 4.5 by 18-fluorodeoxyglucose/fibroblast associated protein inhibitor-positron emission tomography/ computed tomography. Anticoagulant treatment was not effective with the diagnosis of acute pulmonary embolism. DIAGNOSES: A primary endovascular EHE pulmonary endovascular epithelioid hemangioendothelioma was diagnosed by endovascular biopsy with positive stains for molecular CD31, CD34 and CAMTA1, and it had low proliferative capacity characterized by Ki-67 of 5%. The mutation gene MSH2 (p.Y656 in exon 12) (mutation abundance of 0.07%) from peripheral blood indicates the potential benefit of an immune checkpoint inhibitor, pembrolizumab. INTERVENTIONS AND OUTCOMES: The patient was treated with tri-weekly paclitaxel (175mg/m2) and carboplatin (AUC 5) chemotherapy regimen. He exerted a remarkable response after 5 cycles (21 days per cycle) and Pembrolizumab (200mg once monthly) as maintenance treatment. LESSONS: This case highlights the diagnostic challenge of differentiating endovascular lesions and optimal therapy for pulmonary EHE. Importantly, it indicated that the mutation gene MSH2 (p.Y656) might influence the pathogenesis of EHE.

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.

Effects of Housing and Management Systems on the Growth, Immunity, Antioxidation, and Related Physiological and Biochemical Indicators of Donkeys in Cold Weather.

The study was designed with a 2 × 2 factorial experiment to evaluate the effects of growth performance, immune function, antioxidant status, blood biochemical indexes, and hormone levels of donkeys in different housing and management systems in cold weather. Twenty-four male donkeys with similar body weight and age were randomly allocated into four treatment groups that were as follows: a cold-water-drinking group without a windproof facility, a lukewarm-water-drinking group without windproof facilities, a cold-water-drinking group with a windproof facility, and a lukewarm-water-drinking group with a windproof facility. The experiment lasted for 42 days. The results showed that windproof facilities increased average daily gain (ADG) and decreased average daily feed intake (ADFI) and feed-to-gain ratio (F:G) at all time periods (p < 0.01) of the experiment. Windproof facilities increased the digestibility of dry matter (DM), crude fat (CF), crude protein (CP), ash, calcium (Ca), and phosphate (P) on day 21 (p < 0.01), and increased the digestibility of DM, CF, ash, and P on day 42 (p < 0.01). The respiration rate and the skin temperature of the abdomen and legs increased (p < 0.05) and rectal temperature tended to increase (p = 0.083) by adopting windproof facilities at 07:00; the windproof facilities tended to increase the skin temperature of the ears and abdomen (p = 0.081, p = 0.091) at 14:00. For the blood parameters, with windproof facilities, the concentrations of total protein (TP), blood urea nitrogen (BUN), triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) increased (p < 0.05) and glucose (GLU) concentration decreased (p < 0.05) at 07:00 on day 21; the concentrations of TG and cholesterol (CHO) increased and the concentrations of TP, BUN, and GLU decreased at 07:00 on day 42 (p < 0.05). The concentrations of adrenocorticotropic hormone (ACTH), cortisol (COR), triiodothyronine (T3), and thyroxine (T4) decreased (p < 0.05) at 07:00 on day 21, and T4 concentration decreased (p < 0.05) at 07:00 on day 42. The concentrations of interleukin-4 (IL-4), immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) increased (p < 0.01) and the concentrations of interleukin-1ß (IL-1ß) and tumor necrosis factor-alpha (TNF-α) decreased (p < 0.01) on days 21 and 42. The activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GPx) increased (p < 0.05), and malondialdehyde (MDA) concentration decreased (p < 0.01) on day 21; the activities of T-SOD and catalase (CAT) increased (p < 0.05), and MDA concentration decreased (p < 0.01) on day 42. However, under the conditions of this experiment, water temperature did not affect the above indexes on days 21 and 42. These results indicated that adopting windproof facilities in a cold climate can mitigate the effects of atrocious weather on the production performance of donkeys.

CXCL10 levels in diagnosis and improved hemodynamics in patients with chronic thromboembolic pulmonary hypertension undergoing balloon pulmonary angioplasty.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive pulmonary vascular disease characterized by pulmonary artery stenosis or obstructions resulting from insufficient thrombus resolution. Chemokine (C-X-C motif) ligand 10 (CXCL10) is a chemokine that contributes to the pathogenesis of many autoimmune diseases and cancers. The present study aims to investigate the levels of CXCL10 in patients with CTEPH throughout balloon pulmonary angioplasty (BPA) and its correlation with the improvement of pulmonary hemodynamics. Plasma CXCL10 levels were measured in 38 CTEPH patients with 100 BPA sessions and in 28 healthy controls. Correlations between CXCL10 and pulmonary hemodynamics were investigated. Receiver operating characteristic (ROC) curves were plotted to display the diagnostic value and the predictive ability for perioperative complications of CXCL10 and CXCL10-related models. Nomograms were plotted to visualize the diagnostic value and the predictive ability for perioperative complications of CXCL10 and CXCL10-related models. CXCL10 levels are higher in CTEPH patients compared with healthy controls (36.5 [95% confidence interval {CI}: 25.0-51.1] vs. 14.8 [95% CI: 11.1-30.9], p < 0.0001) and decreased significantly after BPA treatment (36.5 [95% CI: 25.0-51.1] vs. 24.7 [95% CI: 17.2-36.6], p < 0.0005). Preoperative CXCL10 levels positively correlated with mean right atrial pressure (r = 0.25), systolic pulmonary artery pressure (PAP; r = 0.28), diastolic PAP (r = 0.33), mean PAP (r = 0.36), pulmonary vascular resistance (r = 0.31), and N-terminal pro-B-type natriuretic peptide (NT-proBNP; r = 0.46). Furthermore, plasma CXCL10 levels adjusting for age and sex displayed a sensitivity of 86.0% and a specificity of 67.9% for discriminating CTEPH patients from healthy controls. Preoperative CXCL10 levels, in combination with NT-proBNP, predicted perioperative complications with a sensitivity of 100.0% and a specificity of 46.9% as displayed in ROC analysis. In conclusion, circulating CXCL10 might contribute to the evaluation of disease severity in CTEPH patients and be useful to evaluate the treatment effect of BPA. Future studies are warranted to further study the relationship between pulmonary hemodynamics and circulating CXCL10.

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.

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.

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.

miR-331-3p Inhibits Inflammatory Response after Intracerebral Hemorrhage by Directly Targeting NLRP6.

BACKGROUND: The mechanism of inflammatory reaction after intracerebral hemorrhage remains unclear, which to some extent restrains the therapeutic development of hemorrhagic stroke. The present study attempts to verify whether NLRP6 plays an important role in inflammatory reaction after intracerebral hemorrhage and identify the critical microRNA during the process. METHODS: Suitable simulated cerebral hemorrhage environments were established in vitro and in vivo. BV2 cells were treated with hemin to induce cell damage. Collagenase was used to establish a model of mouse cerebral hemorrhage. The relationship among NLRP6, miR-331-3p, and the corresponding inflammatory expression was closely observed during this process. Techniques, such as western blot, real-time quantitative PCR, immunofluorescence, and immunocytochemistry, were used to detect the expression of relative genes and molecules in the in vitro and in vivo models. RESULTS: Downregulated miR-331-3p increased the expression of NLRP6 and alleviated the expression of TNF-α and IL-6. The neurological function recovery of mice was promoted after intracerebral hemorrhage. CONCLUSION: miR-331-3p regulated the inflammatory response after cerebral hemorrhage by negatively regulating the expression of NLRP6.

Efficacy and safety of four interventions for spontaneous supratentorial intracerebral hemorrhage: a network meta-analysis.

OBJECT: To investigate the efficacy and safety of four interventions of spontaneous intracerebral hemorrhage simultaneously. METHODS: PubMed, EmBase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) investigating endoscopic surgery (ES), minimally invasive puncture surgery (MIPS), conventional craniotomy (CC), and/or conservative medical treatment (CMT). Good functional outcome, death, and hemorrhage recurrence rates were evaluated by a network meta-analysis. RESULTS: 20 RCTs with 3603 patients were included. Compared with CMT, a higher rate of good functional outcome was found after ES (RR=2.21, 95% CI 1.37 to 3.55) and MIPS (RR=1.47, 95% CI 1.24 to 1.73). Both ES (RR=0.62, 95% CI 0.44 to 0.86) and MIPS (RR=0.72, 95% CI 0.58 to 0.90) markedly reduced the rate of death. However, there was no significant difference in efficacy and safety between ES and MIPS. The top ranked P score for the efficacy outcome was for ES (P score=0.9810). ES (P-score=0.0709) ranked lowest for the primary safety outcome. There was a higher risk of hemorrhage recurrence after CC (RR=3.80, 95% CI 1.90 to 7.63) and MIPS (RR=2.86, 95% CI 1.70 to 4.82) compared with CMT whereas no significant difference was found for ES (RR=1.46, 95% CI 0.53 to 4.02). CONCLUSIONS: The results suggest that both ES and MIPS significantly improve neurological function and reduce the risk of death compared with CMT, and there is no significant difference between ES and MIPS. Ranking of P scores revealed that ES may be the most optimal intervention to improve functional outcome and prevent death. This needs to be evaluated further.

Appropriate treatment sessions of flexible bronchoscopic balloon dilation for patients with nonmalignant central airway stenosis.

BACKGROUND: Balloon dilation is a primary treatment for nonmalignant tracheobronchial stenosis, but often requires multiple treatment sessions to maintain therapeutic efficacy. No guideline is available to suggest the appropriate maximum number of treatment sessions. This study aimed to investigate the relationship between the number of balloon dilation sessions and its long-term therapeutic effectiveness in Chinese patients with nonmalignant central airway stenosis. METHODS: A total of 111 patients with nonmalignant central airway stenosis treated with flexible bronchoscopic balloon dilation from January 2005 to September 2012 were included. The cumulative long-term effective rate was compared between any two adjacent sessions of balloon dilation treatment by McNemar's test. Multivariate Cox regression was performed to investigate the independent factors associated with long-term effectiveness. RESULTS: The cumulative long-term effective rate was significantly increased between any two adjacent sessions before the 6th session of treatment (all p < 0.05) but was no longer significantly increased after the 6th session. The stenosis diameter was larger in the patients receiving ⩽6 treatment sessions than those receiving ⩾6 treatment sessions. Multivariate Cox regression showed that the treatment session was an independent factor associated with long-term effectiveness (hazard ratio = 0.65, 95% confidence interval: 0.57-0.76, p < 0.001). CONCLUSION: These results suggest that the maximum number of treatment sessions of balloon dilation may be six, and patients requiring more treatment sessions were more likely to have delayed long-term effectiveness.

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.

Promising significance of the association of miR-204-5p expression with clinicopathological features of hepatocellular carcinoma.

Decreased level of miR-204-5p has been documented in various malignancies. However, the expression and clinical significance of miR-204-5p in hepatocellular carcinoma has not been investigated. The aim of this study is to examine the relationship between miR-204-5p expression and clinicopathological features in hepatocellular carcinoma (HCC) as well as to predict the relevant signaling pathways. The miR-204-5p expression level was detected in HCC and in matched paraneoplastic liver from 95 formalin-fixed paraffin-embedded tissues by the real-time reverse transcription polymerized chain reaction (qRT-PCR). The association of miR-204-5p expression with clinicopathological features as well as the prognosis of HCC was examined. Public data portals including the Gene Expression Omnibus and The Cancer Genome Atlas were used to retrieve the HCC-related data in order to perform a comprehensive meta-analysis. Meanwhile, protein-protein interaction (PPI) and enrichment analyses were performed using predicted target genes. The relative expression of miR-204-5p was remarkably reduced in HCC than that in paraneoplastic hepatic tissues. In HCC, the miR-204-5p expression was downregulated in the metastasis, vasoinvasion, and advanced stage (III and IV) subgroups compared with their counterparts. Furthermore, the meta-analysis based on qRT-PCR data demonstrated that miR-204-5p was markedly downregulated in HCC with a standardized mean difference of -5.19 (P < .001). However, no significant association was observed between miR-204-5p and survival outcomes. The potential target genes of miR-204-5p were significantly enriched in several pathways which might be associated with HCC, such as "cell proliferation" from GO terms and "pathways in cancer" from the KEGG analysis. A PPI network of miR-204-5p potential target genes identified prospective core genes potentially involved in the regulation of HCC oncogenesis and progression. Our findings suggested that miR-204-5p might act as a tumor-suppressive gene in the tumorigenesis and progression of HCC via vital signaling pathways and that miR-204-5p could be regarded as a protective factor in HCC.