Acute Coronary Artery Air Embolism Complicating a CT-guided percutaneous lung biopsy: A case report.

Systemic air embolism is a fatal complication of computed tomography-guided percutaneous lung biopsy. Here, we report a case of acute coronary artery air embolism following computed tomography (CT) guided percutaneous lung biopsy. The patient exhibited cardiac symptoms, and CT showed air density in left ventricle and aorta, indicating air embolism. Trendelenburg positioning and coronary angiography were performed during the treatment, and the patient was discharged without obvious complications.

Nintedanib could potentially lead to improvements in anti-melanoma differentiation-associated 5 dermatomyositis-associated interstitial lung disease.

OBJECTIVES: To determine the efficacy and safety of nintedanib in patients with anti-melanoma differentiation-associated gene 5 antibody positive dermatomyositis-associated interstitial lung disease (anti-MDA5+ DM-ILD). METHODS: The study was a retrospective cohort design that evaluated patients with anti-MDA5+ DM who either received or did not receive nintedanib. Clinical symptoms, laboratory tests, and survival were compared in the two groups using a propensity score-matched analysis. The primary endpoint was mortality, while adverse events were recorded descriptively. RESULTS: After propensity score matching, 14 patients who received nintedanib (nintedanib+ group) and matched 56 patients who did not receive nintedanib (nintedanib- group) were enrolled. Compared with the nintedanib- group, the nintedanib+ group had a lower incidence of heliotrope and arthritis, higher lymphocyte counts, lower serum ferritin levels, and greater 12-month survival (all p<0.005). Although lung function, HRCT score, and lung VAS were not statistically different between the two groups, the longitudinal study showed significant improvement in HRCT scores (p=0.028) and pulmonary VAS (p=0.019) in the nintedanib+ group. Adverse events occurred in 28.6% of patients, with the most common adverse event with nintedanib being diarrhoea. CONCLUSIONS: Nintedanib may be effective for improving clinical symptoms, laboratory parameters, lung lesions, and survival in anti-MDA5+ DM. Diarrhoea was the most common adverse event associated with nintedanib, although the drug was well tolerated by most patients.

Black-box attacks on dynamic graphs via adversarial topology perturbations.

Research and analysis of attacks on dynamic graph is beneficial for information systems to investigate vulnerabilities and strength abilities in resisting malicious attacks. Existing attacks on dynamic graphs mainly focus on rewiring original graph structures, which are often infeasible in real-world scenarios. To address this issue, we adopt a novel strategy by injecting both fake nodes and links to attack dynamic graphs. Based on that, we present the first study on attacking dynamic graphs via adversarial topology perturbations in a restricted black-box setting, in which downstream graph learning tasks are unknown. Specifically, we first divide dynamic graph structure perturbations into three sub-tasks and transform them as a sequential decision making process. Then, we propose a hierarchical reinforcement learning based black-box attack (HRBBA) framework to model three sub-tasks as attack policies. In addition, an imperceptible perturbation constraint to guarantee the concealment of attacks is incorporated into HRBBA. Finally, HRBBA is optimized based on the actor-critic process. Extensive experiments on four real-world dynamic graphs show that the performance of diverse dynamic graph learning methods (victim methods) on tasks like link prediction, node classification and network clustering can be substantially degraded under HRBBA attack.

Diagnostic accuracy of perfusion-weighted phase-resolved functional lung magnetic resonance imaging in patients with chronic pulmonary embolism.

Purpose: This study aimed to evaluate the diagnostic performance of perfusion-weighted phase-resolved functional lung (PW-PREFUL) magnetic resonance imaging (MRI) in patients with chronic pulmonary embolism (CPE). Materials and methods: This study included 86 patients with suspected chronic thromboembolic pulmonary hypertension (CTEPH), who underwent PREFUL MRI and ventilation/perfusion (V/Q) single-photon emission computed tomography/computed tomography (SPECT/CT). PREFUL MRI was performed at 1.5 T using a balanced steady-state free precession sequence during free breathing. Color-coded PW images and quantitative parameters were obtained by postprocessing. Meanwhile, V/Q SPECT/CT imaging was performed as a reference standard. Hypoperfused areas in the lungs were scored for each lobe and segment using V/Q SPECT/CT images and PW-PREFUL MR images, respectively. Normalized perfusion (QN) and perfusion defect percentage (QDP) were calculated for all slices. For intra- and interobserver variability, the MRI images were analyzed 2 months after the first analysis by the same radiologist and another radiologist (11 years of lung MRI experience) blinded to the results of the first reader. Results: Of the 86 enrolled patients, 77 met the inclusion criteria (36 diagnosed with CPE using V/Q SPECT/CT and 41 diagnosed with non-CPE etiology). For the PW-PREFUL MRI, the sensitivity, specificity, accuracy, and positive and negative predictive values for the diagnosis of CPE were 97, 95, 96, 95, and 98% at the patient level; 91, 94, 93, 91, and 94% at the lobe level, and 85, 94, 92, 88, and 94% at the segment level, respectively. The detection of segmental and subsegmental hypoperfusion using PW-PREFUL MRI revealed a moderate agreement with V/Q SPECT/CT (κ = 0.65; 95% confidence interval: 0.61-0.68). The quantitative results indicated that the QN was lower in the CPE group than in the non-CPE group [median score (interquartile range, IQR) 6.3 (2.8-9.2) vs. 13.0 (8.8-16.7), p < 0.001], and the QDP was higher [median score (IQR) 33.8 (15.7-51.7) vs. 2.2 (1.4-2.9), p < 0.001]. Conclusion: PREFUL MRI could be an alternative test to detect CPE without requiring breath-hold, contrast agents, or ionizing radiation.

Air embolism after CT-guided localization of pulmonary ground-glass nodules.

OBJECTIVE: To investigate the incidence of air embolism (AE) related to CT-guided localization of pulmonary ground-glass nodules (GGNs) prior to video-assisted thoracoscopic surgery (VATS). METHODS: The data of all patients who received CT-guided localization of GGNs before VATS from May 2020 to October 2021 were retrospectively analyzed. RESULTS: A total of 1395 consecutive patients with 1553 GGNs were enrolled. AEs occurred in seven patients (0.5%). In four of the seven patients with AE, the embolism was detected before the patients left the CT table and emergency treatments were carried out. Among them, one patient had chest tightness and unilateral limb dyskinesia, one patient had convulsions and transient loss of consciousness, and two patients had no definite clinical symptoms. After a short-term high-flow oxygen inhalation, the clinical symptoms of two patients with symptomatic AE disappeared and two patients with asymptomatic AE did not show any symptoms. In the remaining three patients with AE, the embolism were detected retrospectively when evaluating the images in the PACS for this study. Fortunately, these three patients never developed clinical symptoms related to AE. All seven patients with AE underwent VATS on the day of localization and all GGNs were successfully removed under the guidance of markers. CONCLUSION: The incidence of AE related to CT-guided localization of GGNs was 0.5%, which was significantly higher than expected. Post-localization whole thoracic CT should be performed and observed carefully so as to avoid missed AE and delayed treatment. ADVANCES IN KNOWLEDGE: The incidence of AE related to CT-guided localization of GGNs was 0.5%. In order to timely detect AE, whole thoracic CT scan rather than local CT in the lesion area should be performed after localization. A small amount of AE may be missed if the post- localization CT images are not carefully observed.

CTCs Detection and Whole-exome Sequencing Might Be Used to Differentiate Benign and Malignant Pulmonary Nodules.

BACKGROUND: Low-density computed tomography (LDCT) improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data. Hence, accurate diagnosis of early-stage lung cancer remains challenging. The purpose of the study was to assess the feasibility of using circulating tumour cells (CTCs) to differentiate malignant from benign pulmonary nodules. METHODS: 122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited. Peripheral blood samples were collected before surgery, and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis. Laser capture microdissection, MALBAC amplification, and whole-exome sequencing were performed on 8 samples. The diagnostic efficacy of CTCs counting, and the genomic variation profile of benign and malignant CTCs samples were analysed. RESULTS: Using 2.5 cells/5 mL as the cut-off value, the area under the receiver operating characteristic curve was of 0.651 (95% confidence interval: 0.538-0.764), with a sensitivity and specificity of 0.526 and 0.800, respectively, and positive and negative predictive values of 91.1% and 30.3%, respectively. Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples. TP53 mutations were identified in CTCs of four malignant cases; in particular, g.7578115T>C, g.7578645C>T, and g.7579472G>C were exclusively detected in all four malignant samples. CONCLUSIONS: CTCs play an ancillary role in the diagnosis of pulmonary nodules. TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.

Comparison between percutaneous transthoracic co-axial needle CT-guided biopsy and transbronchial lung biopsy for the diagnosis of persistent pulmonary consolidation.

BACKGROUND: Diagnosing persistent pulmonary consolidation still faces challenges. The purpose of this study is to compare the diagnostic yield and the complication rate between percutaneous transthoracic CT-guided coaxial needle biopsy (PTCNB) and transbronchial lung biopsy (TBLB) of persistent pulmonary consolidation. MATERIALS: From January 1, 2016, to December 31, 2020, we have retrospectively enrolled a total of 155 consecutive patients (95 males, 60 females) with persistent pulmonary consolidation who underwent both TBLB and PTCNB. According to the standard reference, the diagnostic yield, accuracy, sensitivity and specificity of PTCNB and TBLB were assessed and compared. RESULTS: According to the standard reference, the final biopsy diagnoses of 11 cases were confirmed true malignant based on the surgical resections, the remaining were confirmed by clinical and imaging follow-up for at least 12 months. The overall diagnostic accuracy, sensitivity and specificity of PTCNB for malignant diagnosis were 91.61%, 72.34% and 100%, whereas of TBLB were 87.74%, 59.57% and 100%. The diagnostic yield of PTCNB and TBLB were 50.32% and 25.16%, respectively. For the TBLB-based negative cases, PTCNB provided a definite diagnostic yield of 37.93%. There were 45 (29.03%), 22 (14.19%) and 13 (8.39%) patients who experienced pneumothorax, intrapulmonary hemorrhage and hemoptysis, respectively, in PTCNB, while there were only 5 (3.22%) cases of mild intraprocedural bleeding occurring in TBLB. CONCLUSIONS: CT-guided co-axial needle biopsy is an effective and safe modality, associated with higher diagnostic yield and better diagnostic accuracy compared to transbronchial lung biopsy for malignancy presenting as persistent consolidation, especially as the complementary method for TBLB-based negative lung lesions. KEY POINTS: Both PTCNB and TBLB showed high diagnostic accuracy for malignancy. PTCNB had a higher diagnostic yield than TBLB for persistent pulmonary consolidation. PTCNB could provide a complementary diagnosis for TBLB-based negative lung consolidation.

The mitochondria-targeted small molecule SS31 delays progression of behavioral deficits by attenuating ß-amyloid plaque formation and mitochondrial/synaptic deterioration in APP/PS1 mice.

Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by progressive cognitive dysfunction and an impaired ability to carry out daily life functions. Mitochondrial dysfunction and ß-amyloid (Aß) deposition are the most common causes of AD. Antioxidants have been shown to delay brain aging and AD development; however, it remains unknown whether the antioxidant peptide SS31 can protect mitochondrial and synaptic function and delay the progression of behavioral deficits in early-stage AD in vivo. Therefore, in this study we compared mitochondrial and synaptic changes, as well as the protective effects of SS31, in APP/PS1 transgenic mice and C57BL/6J control mice. The APP/PS1 transgenic mice exhibited elevated expression of Aß40/Aß42 and mitochondrial fission protein DLP1 and reduced expression of synaptophysin (SYN) and postsynaptic density protein 95 (PSD95) reductions, as well as increased levels of neuronal apoptosis and ROS in the hippocampus, and long-term treatment with SS31 reversed these effects. Furthermore, the cognitive impairments observed in APP/PS1 transgenic mice were reversed by SS31 treatment. Our findings show that SS31 lowers ROS and Aß levels, protecting mitochondrial homeostasis and synaptic integrity, and ultimately improving behavioral deficits in early-stage AD. This suggests that SS31 is a potential pharmacological agent for treating or slowing the progression of AD.

C-reactive protein to albumin ratio (CAR) in predicting surgical site infection (SSI) following instrumented posterior lumbar interbody fusion (PLIF).

Identification of novel markers would contribute to the individualised risk assessment and development of a risk prediction model. This study aimed to investigate the role of the C-reactive protein to albumin ratio (CAR) in predicting surgical site infection (SSI) following instrumented posterior lumbar interbody fusion (PLIF) of lumbar degenerative diseases. This study enrolled patients who underwent PLIF and instrumentation for treatment of lumbar degenerative diseases between 2015 and 2020. Electronic medical records were inquired for data collection, with follow-up register for identifying SSI cases. The optimal cut-off for CAR was determined by constructing the receiver operator characteristic (ROC) curve. Patients with high- or low-CAR value were compared using the univariate analyses, and the association between CAR and the risk of SSI was investigated using multivariate logistics regression analysis. A total of 905 patients were enrolled, twenty-nine (3.2%) had developed an SSI with 72.4% occurring during index hospitalisation, and 11 (1.2%) had deep and 18 (2.0%) superficial SSIs. An SSI was associated with additional 10.7 days of index total hospital stay (P = .001). The CAR was 0-5.43 (median, 0.05), and the optimal cut-off was 0.09 and area under the curve was 0.720 (P < .001). 336 (37.1%) patients had a CAR ≥0.09 and 22 (6.5%) developed an SSI, with a crude risk of 5.6 relative to those with a low CAR. The multivariate analyses showed CAR ≥0.09 was associated with 8.06-fold increased risk of SSI, together with diabetes (P = .018), while hypertension was identified as a protective factor (OR, 0.34; 95%CI, 0.11-1.00, P = .049). High CAR is found to significantly predict the incident SSI following instrumented PLIF of lumbar degenerative diseases, and can be considered as a useful index in practice only after it is verified by future high-level evidences.

Diallyl Trisulfide Suppresses the Renal Cancer Stem-like Cell Properties via Nanog.

Cancer stem-like cells (CSCs), which play an important role in tumor initiation and progression, have been identified in many cancers. Diallyl trisulfide (DATS) is an organosulfur compound extracted from garlic with anticancer activities. Nanog is a transcription factor responsible for maintaining the stemness of CSCs, but its role in the DATS-induced attenuation of renal CSC properties is unknown. In this study, renal CSCs were enriched from human renal cancer cell lines 786-O and ACHN cultured in a serum-free medium (SFM). The properties of CSCs were analyzed by evaluating the ability of the cells in sphere formation and measuring the expression of stem cell markers. We found that downregulation of Nanog inhibited renal CSC properties. DATS suppressed renal CSC activities by reducing tumorsphere formation, decreasing stem cell markers including Nanog, CD44, ALDH1A1, and Oct4, inhibiting cell proliferation and promoting apoptosis. We further revealed that overexpression of Nanog reversed the suppressive effects of DATS on renal CSCs. Taken together, our results demonstrated that DATS inhibited renal CSCs by suppressing Nanog. These novel findings suggested that, through Nanog targeting, DATS can potentially be used as an anti-tumor agent for renal cancer.

Distinguishing mesorectal tumor deposits from metastatic lymph nodes by using diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging in rectal cancer.

OBJECTIVES: This study aimed to identify whether apparent diffusion coefficient (ADC) values and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters are helpful in distinguishing mesorectal tumor deposits (TD) from metastatic lymph nodes (MLN) in rectal cancer (RC). METHODS: Thirty patients (59 lesions, including 30 TD and 29 MLN) with RC who underwent pretreatment-MRI between February 2016 and August 2018 were enrolled. The morphological features, ADC values, and semi-quantitative parameters of DCE-MRI, including relative enhancement (RE), maximum enhancement (ME), maximum relative enhancement (MRE), time to peak (TTP), wash-in rates (WIR), wash-out rates (WOR), brevity of enhancement (BRE), and area under the curve (AUC) were measured on lesions (TD or MLN) and RC. The parameters were compared between TD and MLN, tumor with and without TD group by using Fisher's exact test, independent-samples t-test, and Mann-Whitney U test. The ratio (lesion-to-tumor) of the parameters was compared between TD and MLN. Receiver operating characteristic curve analysis and binary logistic regression analysis were used to assess the diagnostic ability of single and combined metrics for distinguishing TD from MLN. RESULTS: The morphological features, including size, shape, and border, were significantly different between TD and MLN. TD exhibited significantly lower RE, MRE, RE-ratio, MRE-ratio, ADCmin-ratio, and ADCmean-ratio than MLN. RE-ratio showed the highest AUC (0.749) and accuracy (77.97%) among single parameters. The combination of DCE-MRI and DWI parameters together showed higher diagnostic efficiency (AUC = 0.825). CONCLUSIONS: Morphological features, ADC values, and DCE-MRI parameters can preoperatively help distinguish TD from MLN in RC. KEY POINTS: • DWI and DCE-MRI can facilitate early detection and distinguishing mesorectal TD (tumor deposits) from MLN (metastatic lymph nodes) in rectal cancer preoperatively. • TD has some specific morphological features, including relatively larger size, lower short- to long-axis ratio, irregular shape, and ill-defined border on T2-weighted MR images in rectal cancer. • The combination of ADC values and semi-quantitative parameters of DCE-MRI (RE, MRE) can help to improve the diagnostic efficiency of TD in rectal cancer.

Metatranscriptomics Reveals the RNA Virome of Ixodes Persulcatus in the China-North Korea Border, 2017.

In recent years, numerous viruses have been identified from ticks, and some have been linked to clinical cases of emerging tick-borne diseases. Chinese northeast frontier is tick infested. However, there is a notable lack of systematic monitoring efforts to assess the viral composition in the area, leaving the ecological landscape of viruses carried by ticks not clear enough. Between April and June 2017, 7101 ticks were collected to perform virus surveillance on the China-North Korea border, specifically in Tonghua, Baishan, and Yanbian. A total of 2127 Ixodes persulcatus were identified. Further investigation revealed the diversity of tick-borne viruses by transcriptome sequencing of Ixodes persulcatus. All ticks tested negative for tick-borne encephalitis virus. Transcriptome sequencing expanded 121 genomic sequence data of 12 different virus species from Ixodes persulcatus. Notably, a new segmented flavivirus, named Baishan Forest Tick Virus, were identified, closely related to Alongshan virus and Harz mountain virus. Therefore, this new virus may pose a potential threat to humans. Furthermore, the study revealed the existence of seven emerging tick-borne viruses dating back to 2017. These previously identified viruses included Mudanjiang phlebovirus, Onega tick phlebovirus, Sara tick phlebovirus, Yichun mivirus, and three unnamed viruses (one belonging to the Peribunyaviridae family and the other two belonging to the Phenuiviridae family). The existence of these emerging tick-borne viruses in tick samples collected in 2017 suggests that their history may extend further than previously recognized. This study provides invaluable insights into the virome of Ixodes persulcatus in the China-North Korea border region, enhancing our ongoing efforts to manage the risks associated with tick-borne viruses.

PLPP2: Potential therapeutic target of breast cancer in PLPP family.

PLPPs (Phospholipid phosphatases) are widely expressed in different human tissues, regulate cell signal transduction, and are overexpressed in cancers such as gliomas, pancreatic adenocarcinoma, lung adenocarcinoma, and so on. As a member of the PLPP family, PLPP2 (phospholipid phosphatase 2) plays a vital role in the occurrence and development of breast cancer, but its mechanism is still unclear. Our research found that PLPP2 was overexpressed in breast cancer, and the higher expression level of PLPP2 showed a worse prognosis for breast cancer patients. Further analysis showed that overexpression of PLPP2 affected the expression of CDC34 (cell-division cycle 34), LSM7 (Like-Smith 7), and SGTA (small glutamine-rich tetratricopeptide repeat-containing protein alpha) through EMT (epigenetic-mesenchymal transition) related pathways to promote the occurrence and development of breast cancer. In vitro, silencing PLPP2 significantly reduced the proliferation, invasion, and migration abilities of human breast cancer cells MDA-MB-231. ER+ is a common subtype of breast cancer. Furthermore, we found that the overexpression of PLPP2 was significantly related to the poor prognosis of ER+ breast cancer. These results indicate that PLPP2 has value as a potential therapeutic target for breast cancer, especially for ER+ breast cancer.

ADAMDEC1 accelerates GBM progression via activation of the MMP2-related pathway.

The ADAM (a disintegrin and metalloprotease) gene-related family including ADAM, ADAMTS, and ADAM-like decysin-1 has been reported to play an important role in the pathogenesis of multiple diseases, including cancers (lung cancer, gliomas, colorectal cancer, and gastrointestinal cancer). However, its biological role in gliomas remains largely unknown. Here, we aimed to investigate the biological functions and potential mechanism of ADAMDEC1 in gliomas. The mRNA and protein expression levels of ADAMDEC1 were upregulated in glioma tissues and cell lines. ADAMDEC1 showed a phenomenon of "abundance and disappear" expression in gliomas and normal tissues in that the higher the expression of ADAMDEC1 presented, the higher the malignancy of gliomas and the worse the prognosis. High expression of ADAMDEC1 was associated with immune response. Knockdown of ADAMDEC1 could decrease the proliferation and colony-forming ability of LN229 cells, whereas ADAMDEC1 overexpression has opposite effects in LN229 cells in vitro. Furthermore, we identified that ADAMDEC1 accelerates GBM progression via the activation of the MMP2 pathway. In the present study, we found that the expression levels of ADAMDEC1 were significantly elevated compared with other ADAMs by analyzing the expression levels of ADAM family proteins in gliomas. This suggests that ADAMDEC1 has potential as a glioma clinical marker and immunotherapy target.

Primary neuroendocrine carcinoma of the breast with leptomeninges metastasis: A case report and literature review.

Primary neuroendocrine carcinoma of the breast (NECB) is a rare tumour with an incident rate of 0.3-0.5%. The most common metastatic sites of NECB are liver, bones, lung, pancreas, soft tissues and brain, while leptomeninges metastasis (LM) is reported rarely. This current case report describes a 50-year-old female patient with NECB and LM whose overall survival was 2 months. The report also presents the current literature regarding the knowledge of this unusual tumour and metastatic type. The current patient was diagnosed with NECB with right cerebellar metastasis, followed by LM. She underwent modified radical mastectomy of the left breast, left whole breast radiation therapy and incomplete adjuvant chemotherapy until the metastasis occurred. Whole-brain radiation therapy and a first-line salvage regimen of etoposide and cis-platinum were then undertaken. The patient died 2 months after their LM diagnosis. Primary NECB with LM is sporadic, devoid of effective treatment and associated with a poor prognosis. Consequently, it is vitally important to identify LM in order to achieve longer patient survival.

Improving CT-guided transthoracic biopsy diagnostic yield of lung masses using intraprocedural CT and prior PET/CT fusion imaging.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of intraprocedural CT and prior PET/CT fusion imaging in improving the diagnostic yield of CT-guided transthoracic core-needle biopsy (CNB) in lung masses. METHODS: In total, 145 subjects with lung masses suspicious for malignancy underwent image-guided transthoracic CNB. According to imaging modality the subjects were divided into two groups. PET/CT images obtained no more than 14 days before the biopsy were integrated with intraprocedural CT images. The integrated or fused images were then used to plan the puncture sites. The clinical characteristics, diagnostic yield of CNB, diagnostic accuracy rate, procedure-related complications and procedure duration were recorded and compared between the two groups. Final clinical diagnosis was determined by surgical pathology or at least 6-months follow-up. The diagnostic accuracy of CNB was obtained by comparing with final clinical diagnosis. RESULTS: 145 subjects underwent CNB with adequate samples, including 76 in fusion imaging group and 69 in routine group. The overall diagnostic yield and diagnostic accuracy rate were 80.3% (53/66), 82.9% (63/76) for fusion imaging group, 70.7% (41/58), 75.4% (52/69) for routine group, respectively. In addition, the diagnostic yield for malignancy in fusion imaging group (98.1%, 52/53) was higher than that in routine group (81.3%, 39/48). No serious procedure-related complications occurred in both two groups. CONCLUSION: CNB with prior PET/CT fusion imaging is particularly helpful in improving diagnostic yield and accurate rate of biopsy in lung masses, especially in heterogeneous ones, thus providing greater potential benefit for patients.

Vascular endothelial growth factor-165b protects the blood-retinal barrier from damage after acute high intraocular pressure in rats.

AIM: To elucidate the role of vascular endothelial growth factor-165b (VEGF-165b) in blood-retinal barrier (BRB) injury in the rat acute glaucoma model. METHODS: In this study, the rat acute high intraocular pressure (HIOP) model was established before and after intravitreous injection of anti-VEGF-165b antibody. The expression of VEGF-165b and zonula occludens-1 (ZO-1) in rat retina was detected by double immunofluorescence staining and Western blotting, and the breakdown of BRB was detected by Evans blue (EB) dye. RESULTS: The intact retina of rats expressed VEGF-165b and ZO-1 protein, which were mainly located in the retinal ganglion cell layer and the inner nuclear layer and were both co-expressed with vascular endothelial cell markers CD31. After acute HIOP, the expression of VEGF-165b was up-regulated; the expression of ZO-1 was down-regulated at 12h and then recovered at 3d; EB leakage increased, peaking at 12h. After intravitreous injection of anti-VEGF-165b antibody, the expression of VEGF-165b protein was no significantly changed; and the down-regulation of the expression of ZO-1 was more obvious; EB leakage became more serious, peaking at 3d. EB analysis also showed that EB leakage in the peripheral retina was greater than that in the central retina. CONCLUSION: The endogenous VEGF-165b protein may protect the BRB from acute HIOP by regulating the expression of ZO-1. The differential destruction of BRB after acute HIOP may be related to the selective loss of retinal ganglion cells.

Strain Analysis in Patients at High-Risk for COPD Using Four-Dimensional Dynamic-Ventilation CT.

Purpose: To quantitatively identify abnormal lung motion in chronic obstructive pulmonary disease (COPD) using strain analysis, and further clarify the potential differences of deformation in COPD with different severity of airflow limitation. Materials and Methods: Totally, 53 patients at high-risk for COPD were enrolled in this study. All CT examinations were performed on a 320-row MDCT scanner, and strain measurement based on dynamic-ventilation CT data was performed with a computational fluid dynamics analysis software (Micro Vec V3.6.2). The strain-related parameters derived from the whole expiration phase (PSmax-all, PSmean-all, Speedmax-all ), the first 2s of expiration phase (PSmax2s, PSmean2s, Speedmax2s ) were divided respectively by the changes in lung volume to adjust for the degree of expiration. Spearman rank correlation analysis was used to evaluate associations between the strain-related parameters and various spirometric parameters. Comparisons of the strain-related parameters between COPD and non-COPD patients, between GOLD I (mild airflow restriction) and GOLD II-IV (moderate to severe airflow restriction) were made using the Mann-Whitney U-test. Receiver-operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of the strain-related parameters for COPD. P <0.05 was considered statistically significant. Results: Strain-related parameters demonstrated positive correlations with spirometric parameters (ρ=0.275~0.687, P<0.05), suggesting that heterogeneity in lung motion was related to abnormal spirometric results. Strain-related parameters can quantitatively distinguish COPD from non-COPD patients with moderate diagnostic significance with the AUC values ranged from 0.821 to 0.894. Furthermore, parameters of the whole expiration phase (PSmax-all, Speedmax-all) demonstrated significant differences (P=0.005; P=0.04) between COPD patients with mild and moderate to severe airflow limitation. Conclusion: Strain-related parameters derived from dynamic-ventilation CT data covering the whole lung associated with lung function changes in COPD, reflecting the severity of airflow limitation in some degree, even though its utility in severe COPD patients remains to be investigated.

The Identification and Analysis of MicroRNAs Combined Biomarkers for Hepatocellular Carcinoma Diagnosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor with high morbidity and mortality globally. Compared with traditional diagnostic methods, microRNAs (miRNAs) are novel biomarkers with higher accuracy. OBJECTIVE: We aimed to identify combinatorial biomarkers of miRNAs to construct a classification model for the diagnosis of HCC. METHODS: The mature miRNA expression profile data of six cancers (liver, lung, gastric, breast, prostate, and colon) were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database with accession number GSE36915, GSE29250, GSE99417, GSE41970, GSE64333 and GSE35982. The messenger RNA (mRNA) expression profile data of these six cancers were obtained from TCGA. Three R software packages, student's t-test, and a normalized foldchange method were utilized to identify HCC-specific differentially expressed miRNAs (DEMs). Using all combinations of obtained HCC-specific DEMs as input features, we constructed a classification model by support vector machine searching for the optimal combination. Furthermore, target genes prediction was conducted on the miRWalk 2.0 website to obtain differentially expressed mRNAs (DEmRNAs), and KEGG pathway enrichment was analyzed on the DAVID website. RESULTS: The optimal combination consisted of four miRNAs (hsa-miR-130a-3p, hsa-miR-450b-5p, hsa-miR-136-5p, and hsa-miR-24-1-5p), of which the last one has not been currently reported to be relevant to HCC. The target genes of hsa-miR-24-1-5p (CDC7, ACACA, CTNNA1, and NF2) were involved in the cell cycle, AMPK signaling pathway, Hippo signaling pathway, and insulin signaling pathway, which affect the proliferation, metastasis, and apoptosis of cancer cells. Moreover, the area under the receiver operating characteristic curves of the four miRNAs were all higher than 0.85. CONCLUSION: These results suggest that the miRNAs combined biomarkers were reliable for the diagnosis of HCC. Hsa-miR-24-1-5p was a novel biomarker for HCC diagnosis identified in this study.