Association between hyperuricemia and chronic total coronary occlusion in non-chronic kidney disease populations: a cross-sectional study.

BACKGROUND: Chronic total coronary occlusion (CTO) is an extremely hazardous condition that leads to various clinical phenomena and complications and results in social and economic burdens. Hyperuricemia (HU) is often associated with atherosclerosis. Few studies, however, have investigated the risk of CTO in individuals with HU and the role of traditional cardiovascular risk factors in this setting. METHODS: A cohort of 1245 individuals without chronic kidney disease from southwest China who underwent coronary angiography between February 2018 and June 2021 were enrolled. CTO was defined as a total occlusion of any coronary artery or arteries for more than 3 months. HU was defined as a serum uric acid level of ≥420 µmol/L in men and ≥360 µmol/L in women. Univariate and multivariate logistic regression models and subgroup analyses were applied to assess the relationship between HU and CTO. RESULTS: After adjustment, HU was noted to be associated with a 1.47-fold increase in the risk of CTO [odds ratio (OR), 1.47; 95% confidence interval (CI), 1.06-2.58; P = 0.026]. As a continuous variable, uric acid was an independent predictor of CTO (OR, 1.002; 95% CI, 1.001-1.004; P = 0.047). Subgroup analyses showed that the risk of CTO was higher among individuals under 65 years of age (OR, 2.77; 95% CI, 1.3-5.89), nonobese individuals (OR, 1.9; 95% CI, 1.16-3.1), and those with dyslipidemia (OR, 1.8; 95% CI, 1.04-3.11), while sex, smoking, hypertension, and diabetes did not show similar effects. Interaction analyses revealed no interaction among subgroups. CONCLUSION: Among individuals residing in southwest China, HU was associated with an increased risk of CTO in non-CKD individuals, especially those under 65 years of age and nonobese and dyslipidemic individuals.

Ammonia removal and simultaneous immobilization of manganese and magnesium from electrolytic manganese residue by a low-temperature CaO roasting process.

A large amount of open-dumped electrolytic manganese residue (EMR) has posed a severe threat to the ecosystem and public health due to the leaching of ammonia (NH4+) and manganese (Mn). In this study, CaO addition coupled with low-temperature roasting was applied for the treatment of EMR. The effects of roasting temperature, roasting time, CaO-EMR mass ratio and solid-liquid ratio were investigated. The most cost-effective and practically viable condition was explored through response surface methodology. At a CaO: EMR ratio of 1:16.7, after roasting at 187 °C for 60 min, the leaching concentrations of NH4+ and Mn dropped to 10.18 mg/L and 1.05 mg/L, respectively, below their discharge standards. In addition, the magnesium hazard (MH) of EMR, which was often neglected, was studied. After treatment, the MH of the EMR leachate was reduced from 60 to 37. Mechanism analysis reveals that roasting can promote NH4+ to escape as NH3 and convert dihydrate gypsum to hemihydrate gypsum. Mn2+ and Mg2+ were mainly solidified as MnO2 and Mg(OH)2, respectively. This study proposes an efficient and low-cost approach for the treatment of EMR and provides valuable information for its practical application.

Relationship between homocysteine and chronic total coronary occlusion: a cross-sectional study from southwest China.

BACKGROUND: Chronic total coronary occlusion is among the most complex coronary artery diseases. Elevated homocysteine is a risk factor for coronary artery diseases. However, few studies have assessed the relationship between homocysteine and chronic total coronary occlusion. METHODS: 1295 individuals from Southwest China were enrolled in the study. Chronic total coronary occlusion was defined as complete occlusion of coronary artery for more than three months. Homocysteine was divided into quartiles according to its level. Univariate and multivariate logistic regression models, receiver operating characteristic curves, and subgroup analysis were applied to assess the relationship between homocysteine and chronic total coronary occlusion. RESULTS: Subjects in the higher homocysteine quartile had a higher rate of chronic total coronary occlusion (P < 0.001). After adjustment, the odds ratio for chronic total coronary occlusion in the highest quartile of homocysteine compared with the lowest was 1.918 (95% confidence interval 1.237-2.972). Homocysteine ≥ 15.2 µmol/L was considered an independent indicator of chronic total coronary occlusion (odds ratio 1.53, 95% confidence interval 1.05-2.23; P = 0.0265). The area under the receiver operating characteristic curve was 0.659 (95% confidence interval, 0.618-0.701; P < 0.001). Stronger associations were observed in elderly and in those with hypertension and diabetes. CONCLUSIONS: Elevated homocysteine is significantly associated with chronic total coronary occlusion, particularly in elderly and those with hypertension and diabetes.

Autopsy analysis reveals increased macrophage infiltration and cell apoptosis in COVID-19 patients with severe pulmonary fibrosis.

Clinical data indicates that SARS-CoV-2 infection-induced respiratory failure is a fatal condition for severe COVID-19 patients. However, the pathological alterations of different types of respiratory failure remained unknown for severe COVID-19 patients. This study aims to evaluate whether there are differences in the performance of various types of respiratory failure in severe COVID-19 patients and investigate the pathological basis for these differences. The lung tissue sections of severe COVID-19 patients were assessed for the degree of injury and immune responses. Transcriptome data were used to analyze the molecular basis in severe COVID-19 patients. Severe COVID-19 patients with combined oxygenation and ventilatory failure presented more severe pulmonary fibrosis, airway obstruction, and prolonged disease course. The number of M2 macrophages increased with the degree of fibrosis in patients, suggesting that it may be closely related to the development of pulmonary fibrosis. The co-existence of pro-inflammatory and anti-inflammatory cytokines in the pulmonary environment could also participate in the progression of pulmonary fibrosis. Furthermore, the increased apoptosis in the lungs of COVID-19 patients with severe pulmonary fibrosis may represent a critical factor linking sustained inflammatory responses to fibrosis. Our findings indicate that during the extended phase of COVID-19, antifibrotic and antiapoptotic treatments should be considered in conjunction with the progression of the disease.

Effects of electronic personal health information technology on American women's cancer screening behaviors mediated through cancer worry: Differences and similarities between 2017 and 2020.

Backgrounds: Thanks to their accessibility and low cost, electronic personal health information (ePHI) technologies have been widely used to facilitate patient-physician communication and promote health prevention behaviors (e.g. cancer screening). Despite that empirical evidence has supported the association between ePHI technology use and cancer screening behaviors, the underlying mechanism through which ePHI technology use influences cancer screening behaviors remains a topic of discussion. Objective: This study investigates the relationship between ePHI technology uses and cancer screening behaviors of American women and examines the mediating role of cancer worry. Methods: Data for this study were from the Health Information National Trends Survey (HINTS) collected in 2017 (HINTS 5 Cycle 1) and 2020 (HINTS 5 Cycle 4). The final sample included 1914 female respondents in HINTS 5 Cycle 1 and 2204 in HINTS 5 Cycle 4. Mann-Whitney U test, two-sample t-test, and mediation analysis were performed. We also referred to the regression coefficients generated by min-max normalization as percentage coefficients (bp) for the comparison. Results: This study reports increased usage of ePHI technologies (from 1.41 in 2017 to 2.19 to 2020), increased cancer worry (from 2.60 in 2017 to 2.84 in 2020), and a stable level of cancer screening behaviors (from 1.44 in 2017 to 1.34 in 2020) among American women. Cancer worry was found to mediate the ePHI effect on cancer screening behaviors (bp = 0.005, 95% confidence interval [0.001, 0.010]) in a positive complementary mediation in 2020. Conclusions: The research findings support a positive association between ePHI technology use and cancer screening behaviors, and cancer worry has been identified as a salient mediator. An understanding of the mechanism that prompts US women's cancer screening practices provides practical implications for health campaign practitioners.

Neutralizing IL-8 potentiates immune checkpoint blockade efficacy for glioma.

Malignant gliomas are largely refractory to immune checkpoint blockade (ICB) therapy. To explore the underlying immune regulators, we examine the microenvironment in glioma and find that tumor-infiltrating T cells are mainly confined to the perivascular cuffs and express high levels of CCR5, CXCR3, and programmed cell death protein 1 (PD-1). Combined analysis of T cell clustering with T cell receptor (TCR) clone expansion shows that potential tumor-killing T cells are mainly categorized into pre-exhausted/exhausted and effector CD8+ T subsets, as well as cytotoxic CD4+ T subsets. Notably, a distinct subpopulation of CD4+ T cells exhibits innate-like features with preferential interleukin-8 (IL-8) expression. With IL-8-humanized mouse strain, we demonstrate that IL-8-producing CD4+ T, myeloid, and tumor cells orchestrate myeloid-derived suppressor cell infiltration and angiogenesis, which results in enhanced tumor growth but reduced ICB efficacy. Antibody-mediated IL-8 blockade or the inhibition of its receptor, CXCR1/2, unleashes anti-PD-1-mediated antitumor immunity. Our findings thus highlight IL-8 as a combinational immunotherapy target for glioma.

Jujing Zhuyu decoction inhibits apoptosis in rats with asthenozoospermia by regulating the mitochondrial apoptosis pathway.

Jujing Zhuyu decoction (JZD) is a traditional Chinese medicine that effectively improves sperm motility. However, the molecular mechanism of JZD on asthenozoospermia still remains unknown. In this study, we investigated the effect of JZD on the mitochondrial apoptosis pathway in an asthenozoospermia rat model. Sixty Sprague-Dawley rats were randomly divided into five groups-control, tripterygium glycosides (GTW) model, JZD-low (JZD-L), JZD-medium (JZD-M), and JZD-high (JZD-H) groups (n = 12/group). GTW was used to generate the asthenozoospermia model. The JZD-L, JZD-M, and JZD-H groups were administered 5, 10, or 15 g kg-1  day-1 of JZD granules respectively, for 4 weeks. Testicular tissue morphology was examined using histological staining, while sperm count was determined using manual and computer-aided semen analyses. Apoptosis of spermatogenic cells was detected with the TUNEL assay, and the expression of proteins and genes related to mitochondrial apoptosis was detected using western blotting and quantitative reverse transcription-polymerase chain reaction respectively. Histomorphological evaluation revealed superior seminiferous tubule structure and arrangement as well as improved spermatogenic cell morphology in the JZD-L, JZD-M, and JZD-H groups compared to those in the model group. Moreover, semen quality and the apoptotic index were significantly improved in the JZD-L, JZD-M, and JZD-H groups compared to those in the model group. Additionally, the mRNA expression and protein abundance of Apaf-1, Bax, Cyto-c, and caspase-3 was reduced, while those of Bcl-2 were increased in all JZD groups compared to those in the model group. JZD reduces the apoptosis rate of sperm cells and significantly promotes sperm survival by regulating the mitochondrial apoptosis pathway. This mechanism provides experimental support for the treatment of asthenozoospermia by JZD.

Automatic bifurcation detection utilizing pullback characteristics of bifurcation in intravascular optical coherence tomography.

Bifurcation detection in coronary arteries is significant since it influences the treatment strategy selection and optimization. Bifurcations are also reliable landmarks for image registration. Intravascular optical coherence tomography (IVOCT) is a high-resolution imaging modality that is very useful in percutaneous coronary intervention stenting optimization. We present a bifurcation identification method utilizing pullback characteristics for IVOCT, which can effectively identify the bifurcations with a small size. The longitudinal view of the pullback will appear as an outward discontinuity in the bifurcation area. By detecting this discontinuity, bifurcation can be identified with high accuracy. We also use the normal vectors method to extract the ostium of bifurcation. We compare the proposed method with the widely-used distance transformation method by clinical 5302 IVOCT images from 22 pullbacks. The average metrics of true positive rate (TPR), true negative rate (TNR), positive predictive value (PPV), and negative predictive value (NPV) for the proposed method are 86.97%, 98.50%, 85.56%, and 98.67%, respectively. TPR, PPV, and NPV by the proposed method are improved by 40.24%, 9.31%, 3.90%, and TNR is on par compared with the distance transformation method. Especially in the small bifurcation identification, TPR of the proposed method is 64.71% higher than the distance transformation method with a bifurcation area ratio less than 0.2.

Self-Efficacy, Proxy Efficacy, Media Literacy, and Official Media Use in COVID-19 Pandemic in China: A Moderated Mediation Model.

Purpose: COVID-19 pandemic is a significant threat toward the public health. However, the discussion of the mechanism of media literacy's effect in fighting against pandemic is limited. Thus, this study aims to explore the mechanism with a sociocognitive perspective. Methods: A survey was administrated to 420 college students in China. PROCESS macro of SPSS was applied to analyze the data and test the moderated mediation effect. Results: The moderated mediation model of media literacy, proxy efficacy, self-efficacy, and official media use was tested and supported. Official media use was a negative moderator on the association between media literacy and proxy efficacy. Conclusion: The study explored the media literacy's role as a determinant of proxy efficacy and self-efficacy, which contributed to the sociocognitive theory.

The high efficient Sb(III) removal by cauliflower like amorphous nanoscale zero-valent iron (A-nZVI).

In this study, cauliflower like amorphous nanoscale zero-valent iron (A-nZVI) was prepared and its performance on the removal of Sb(III) was investigated and compared with that of nZVI. The results indicated that the removal of Sb(III) by nZVI and A-nZVI followed the pseudo-second-order kinetic model and Langmuir isotherm model, but the removal of Sb(III) by A-nZVI was more stable and its removal capacity (558.2 mg/g) is much higher than that of nZVI (91.3 mg/g). Moreover, the effects of initial Sb(III) concentration, initial pH and anions such as Cl-, NO3-, SO42-, PO43-, and AsO43- were also investigated. A-nZVI showed extremely high selectivity towards Sb(III) in that 500 mg/L of AsO43- and PO43- shows little impact on its removal, while the removal of Sb(III) by nZVI was almost inhibited under the same condition. The combination of SEM-EDS, XPS, XRD and FTIR revealed the removal of Sb(III) by nZVI and A-nZVI were synergistic effects of oxidation and adsorption, but less Sb(III) (39.5%) was oxidized by A-nZVI. More γ-FeOOH and γ-Fe2O3 were formed at the surface of A-nZVI during the reaction. Both oxides have high affinity toward Sb(III), which might cause the higher removal capacity and selectivity for the removal of Sb(III) by A-nZVI. In conclusion, A-nZVI showed great potential for the remediation of Sb(III) in groundwater.

Analysis and reduction of noise-induced depolarization in catheter based polarization sensitive optical coherence tomography.

In catheter based polarization sensitive optical coherence tomography (PS-OCT), a optical fiber with a rapid rotation in the catheter can cause low signal-to-noise ratio (SNR), polarization state instability, phase change of PS-OCT signals and then heavy noise-induced depolarization, which has a strong impact on the phase retardation measurement of the sample. In this paper, we analyze the noise-induced depolarization and find that the effect of depolarization can be reduced by polar decomposition after incoherent averaging in the Mueller matrix averaging (MMA) method. Namely, MMA can reduce impact of noise on phase retardation mapping. We present a Monte Carlo method based on PS-OCT to numerically describe noise-induced depolarization effect and contrast phase retardation imaging results by MMA and Jones matrix averaging (JMA) methods. The peak signal to noise ratio (PSNR) of simulated images processed by MMA is higher than about 8.9 dB than that processed by JMA. We also implement experiments of multiple biological tissues using the catheter based PS-OCT system. From the simulation and experimental results, we find the polarization contrasts processed by the MMA are better than those by JMA, especially at areas with high depolarization, because the MMA can reduce effect of noise-induced depolarization on the phase retardation measurement.

Autophagy-based unconventional secretion of HMGB1 in glioblastoma promotes chemosensitivity to temozolomide through macrophage M1-like polarization.

BACKGROUND: Glioblastoma (GB) is the most common and highly malignant brain tumor characterized by aggressive growth and resistance to alkylating chemotherapy. Autophagy induction is one of the hallmark effects of anti-GB therapies with temozolomide (TMZ). However, the non-classical form of autophagy, autophagy-based unconventional secretion, also called secretory autophagy and its role in regulating the sensitivity of GB to TMZ remains unclear. There is an urgent need to illuminate the mechanism and to develop novel therapeutic targets for GB. METHODS: Cancer genome databases and paired-GB patient samples with or without TMZ treatment were used to assess the relationship between HMGB1 mRNA levels and overall patient survival. The relationship between HMGB1 protein level and TMZ sensitivity was measured by immunohistochemistry, ELISA, Western blot and qRT-PCR. GB cells were engineered to express a chimeric autophagic flux reporter protein consisting of mCherry, GFP and LC3B. The role of secretory autophagy in tumor microenvironment (TME) was analyzed by intracranial implantation of GL261 cells. Coimmunoprecipitation (Co-IP) and Western blotting were performed to test the RAGE-NFκB-NLRP3 inflammasome pathway. RESULTS: The exocytosis of HMGB1 induced by TMZ in GB is dependent on the secretory autophagy. HMGB1 contributed to M1-like polarization of tumor associated macrophages (TAMs) and enhanced the sensitivity of GB cells to TMZ. Mechanistically, RAGE acted as a receptor for HMGB1 in TAMs and through RAGE-NFκB-NLRP3 inflammasome pathway, HMGB1 enhanced M1-like polarization of TAMs. Clinically, the elevated level of HMGB1 in sera may serve as a beneficial therapeutic-predictor for GB patients under TMZ treatment. CONCLUSIONS: We demonstrated that enhanced secretory autophagy in GB facilitates M1-like polarization of TAMs to enhance TMZ sensitivity of GB cells. HMGB1 acts as a key regulator in the crosstalk between GB cells and tumor-suppressive M1-like TAMs in GB microenvironment and may be considered as an adjuvant for the chemotherapeutic agent TMZ.

Comprehensive omics analyses profile genesets related with tumor heterogeneity of multifocal glioblastomas and reveal LIF/CCL2 as biomarkers for mesenchymal subtype.

Rationale: Around 10%-20% patients with glioblastoma (GBM) are diagnosed with more than one tumor lesions or multifocal GBM (mGBM). However, the understanding on genetic, DNA methylomic, and transcriptomic characteristics of mGBM is still limited. Methods: In this study, we collected nine tumor foci from three mGBM patients followed by whole genome sequencing, whole genome bisulfite sequencing, RNA sequencing, and immunohistochemistry. The data were further examined using public GBM databases and GBM cell line. Results: Analysis on genetic data confirmed common features of GBM, including gain of chr.7 and loss of chr.10, loss of critical tumor suppressors, high frequency of PDGFA and EGFR amplification. Through profiling DNA methylome of individual tumor foci, we found that promoter methylation status of genes involved in detection of chemical stimulus, immune response, and Hippo/YAP1 pathway was significantly changed in mGBM. Although both CNV and promoter methylation alteration were involved in heterogeneity of different tumor foci from same patients, more CNV events than promoter hypomethylation events were shared by different tumor foci, implying CNV were relatively earlier than promoter methylation alteration during evolution of different tumor foci from same mGBM. Moreover, different tumor foci from same mGBM assumed different molecular subtypes and mesenchymal subtype was prevalent in mGBM, which might explain the worse prognosis of mGBM than single GBM. Interestingly, we noticed that LIF and CCL2 was tightly correlated with mesenchymal subtype tumor focus in mGBM and predicted poor survival of GBM patients. Treatment with LIF and CCL2 produced mesenchymal-like transcriptome in GBM cells. Conclusions: Together, our work herein comprehensively profiled multi-omics features of mGBM and emphasized that components of extracellular microenvironment, such as LIF and CCL2, contributed to the evolution and prognosis of tumor foci in mGBM patients.

Network Pharmacology and Molecular Docking Verify the Mechanism of Qinshi Simiao San in Treating Chronic Prostatitis in the Rat Model.

BACKGROUND: Using network pharmacology and molecular docking, this study aimed to explore the active pharmaceutical ingredients (APIs) and molecular mechanism of Qinshi Simiao San (QSSMS) in the treatment of chronic prostatitis (CP) and verify our findings in the rat model. METHODS: The APIs of QSSMS and the common targets of QSSMS and CP were screened from the TCMSP database. The STRING database and Cytoscape software were used to construct the network graph. The enriched GO and KEGG pathways were displayed by David software and R software. Molecular docking was performed to visualize key components and target genes. In addition, the rats model of CP was established to verify the molecular mechanism of QSSMS. RESULTS: Network pharmacology showed that the APIs of QSSMS mainly included quercetin, kaempferol, formononetin, isorhamnetin, and calycosin. QSSMS alleviated CP mainly through the negative regulation of the apoptotic process, oxidation-reduction process, inflammatory response, and immune response. Molecular docking showed that the APIs could bind to the corresponding targets. QSSMS repaired the pathological damage of prostate tissue, upregulated the expression of oxidative stress scavenging enzymes CAT and SOD, and downregulated the peroxidative product MDA, inflammatory factors IL-1ß, IL-6, TNF-α, COX-2, PGE2, and NGF, and immune factors IgG and SIgA. CONCLUSION: The APIs in QSSMS may inhibit inflammation in the rat CP model by regulating immune and oxidative stress.

Effectiveness and safety of acupuncture combined with traditional Chinese medicine in the treatment of chronic prostatitis: A systematic review and meta-analysis.

OBJECTIVE: Chronic prostatitis (CP) is a common disease in the outpatient department of males and urology. Clinical studies have found that acupuncture combined with traditional Chinese medicine (TCM) has achieved good results in treating CP, but its efficacy and safety are not completely clear. This study aimed to investigate the efficacy and safety of acupuncture combined with TCM in the treatment of CP. METHODS: Randomized controlled trials of acupuncture combined with TCM in treating CP were screened by searching PubMed, Embase, Cochrane Library, CNKI, etc. The retrieval time was from the database establishment date to March 31, 2021. The Cochrane Collaborative Risk Bias Assessment tool was used to evaluate literature's methodological quality of the literature. The RevMan5.4 software was used for the meta-analysis of outcome indicators. The TSA v0.9 software was used for sequential trial analysis (TSA) of effectiveness. RESULTS: In this study, 19 related randomized controlled trial studies were included, with a total of 1831 cases. The results of the meta-analysis showed that acupuncture combined with TCM could significantly improve the clinical efficacy of CP (OR = 3.76, 95%CI: 2.82 to 5.02, P < .00001), reduce the total score of The National Institutes of Health chronic prostatitis symptom index (MD = -4.00, 95%CI: -4.67 to 3.33, P < .00001), and improve patients' urination symptoms (MD = -1.10, 95%CI: -1.23 to -0.97, P < .00001), alleviated the pain symptoms of patients (MD = -2.38, 95%CI: -2.41 to -2.35, P < .00001), improved the quality of life of patients (MD = -1.69, 95%CI: -1.97 to -1.41, P < .00001), decreased the scores of TCM symptoms of patients (MD = -2.39, 95%CI: -3.45 to -1.33, P < .00001), and did not increase the adverse reactions of patients (MD = 1.09, 95%CI: 0.57 to 2.06, P = .8). The results of publication bias showed that this study was not affected by publication bias, and the conclusion was reliable. TSA showed that acupuncture combined with TCM was effective in treating CP. CONCLUSION: Acupuncture combined with TCM is safe and effective for alleviating CP. It can be used as an effective treatment for chronic prostatitis in the clinic.Registration number: DOI 10.17605/OSF.IO/Z8FJM.

A single-cell transcriptomic landscape of the lungs of patients with COVID-19.

The lung is the primary organ targeted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), making respiratory failure a leading coronavirus disease 2019 (COVID-19)-related mortality. However, our cellular and molecular understanding of how SARS-CoV-2 infection drives lung pathology is limited. Here we constructed multi-omics and single-nucleus transcriptomic atlases of the lungs of patients with COVID-19, which integrate histological, transcriptomic and proteomic analyses. Our work reveals the molecular basis of pathological hallmarks associated with SARS-CoV-2 infection in different lung and infiltrating immune cell populations. We report molecular fingerprints of hyperinflammation, alveolar epithelial cell exhaustion, vascular changes and fibrosis, and identify parenchymal lung senescence as a molecular state of COVID-19 pathology. Moreover, our data suggest that FOXO3A suppression is a potential mechanism underlying the fibroblast-to-myofibroblast transition associated with COVID-19 pulmonary fibrosis. Our work depicts a comprehensive cellular and molecular atlas of the lungs of patients with COVID-19 and provides insights into SARS-CoV-2-related pulmonary injury, facilitating the identification of biomarkers and development of symptomatic treatments.

Differences in the clinical presentation, management, and in-hospital outcomes of acute aortic dissection in patients with and without end-stage renal disease.

BACKGROUND: Few studies have evaluated the clinical presentation, management, and outcomes of patients with end-stage renal disease (ESRD) presenting with acute aortic dissection (AAD) in real-world clinical practice. Thus, this study investigated the clinical characteristics, management, and outcomes of AAD patients with ESRD. METHODS: A total of 217 patients were included. We evaluated the differences in the clinical features, management, and in-hospital outcomes of patients with and without a history of ESRD presenting with AAD. RESULTS: A history of ESRD was present in 71 of 217 patients. Patients with ESRD had atypical clinical manifestations (p < 0.001) and were more likely to be managed medically compared with patients without ESRD (p = 0.002). Hypertension and type B aortic dissection were significantly more common among patients with ESRD. Moreover, patients with ESRD had lower leucocyte and platelet counts than patients without ESRD in laboratory findings (p < 0.001). However, hospitalization days and in-hospital mortality were similar between the two groups (p > 0.05). Multivariate analysis identified Type A aortic dissection as an independent predictor of in-hospital mortality among patients without ESRD (OR, 13.68; 95% CI, 1.92 to 98.90; P = 0.006). CONCLUSIONS: This study highlights differences in the clinical characteristics, management, and outcomes of AAD patients with ESRD. These patients usually have atypical symptoms and more comorbid conditions and are managed more conservatively. However, these patients have no in-hospital survival disadvantage over those without ESRD. Further studies are needed to better understand and optimize care for patients with ESRD presenting with AAD.

Pericytes augment glioblastoma cell resistance to temozolomide through CCL5-CCR5 paracrine signaling.

Glioblastoma (GBM) is a prevalent and highly lethal form of glioma, with rapid tumor progression and frequent recurrence. Excessive outgrowth of pericytes in GBM governs the ecology of the perivascular niche, but their function in mediating chemoresistance has not been fully explored. Herein, we uncovered that pericytes potentiate DNA damage repair (DDR) in GBM cells residing in the perivascular niche, which induces temozolomide (TMZ) chemoresistance. We found that increased pericyte proportion correlates with accelerated tumor recurrence and worse prognosis. Genetic depletion of pericytes in GBM xenografts enhances TMZ-induced cytotoxicity and prolongs survival of tumor-bearing mice. Mechanistically, C-C motif chemokine ligand 5 (CCL5) secreted by pericytes activates C-C motif chemokine receptor 5 (CCR5) on GBM cells to enable DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-mediated DDR upon TMZ treatment. Disrupting CCL5-CCR5 paracrine signaling through the brain-penetrable CCR5 antagonist maraviroc (MVC) potently inhibits pericyte-promoted DDR and effectively improves the chemotherapeutic efficacy of TMZ. GBM patient-derived xenografts with high CCL5 expression benefit from combined treatment with TMZ and MVC. Our study reveals the role of pericytes as an extrinsic stimulator potentiating DDR signaling in GBM cells and suggests that targeting CCL5-CCR5 signaling could be an effective therapeutic strategy to improve chemotherapeutic efficacy against GBM.

Anti-angiogenesis and anti-metastasis effects of Polyphyllin VII on Hepatocellular carcinoma cells in vitro and in vivo.

BACKGROUND: Polyphyllin VII (PP7), a steroidal saponin from P. polyphylla has been found to exert strong anticancer activity. Little is known about the anti-angiogenesis and anti-metastasis properties of PP7. In this study, the anti-angiogenic and anti-metastatic effects of PP7 on HCC and the molecular mechanisms were evaluated. METHODS: Effect of PP7 on angiogenesis was assessed by tube formation assay and applied a transgenic Tg(fli1:EGFP) zebrafish model. Effects of PP7 on tumor metastasis and invasion were examined in cell migration and invasion assay, zebrafish tumor xenograft models and lung metastasis mouse models. The protein levels were examined by Western blotting. RESULTS: PP7 significantly decreased the tube formation of human umbilical vein endothelial cells, the number and length of ISVs and SIVs of transgenic zebrafish, and the metastasis and invasion of cancer cells in vitro and in vivo. The anti-angiogenic and anti-metastatic effects of PP7 in HepG2 cells were attributable, at least partially, to downregulated NF-κB/MMP-9/VEGF signaling pathway. CONCLUSION: This study demonstrates that PP7 possesses strong anti-angiogenesis and anti-metastasis activities, suggesting that PP7 could be a potential candidate agent for HCC treatment.

Automatic lumen segmentation using uniqueness of vascular connected region for intravascular optical coherence tomography.

We present an automatic lumen segmentation method using uniqueness of connected region for intravascular optical coherence tomography (IVOCT), which can effectively remove the effect on lumen segmentation caused by blood artifacts. Utilizing the uniqueness of vascular wall on A-lines, we detect the A-lines shared by multiple connected regions, identify connected regions generated by blood artifacts using traversal comparison of connected regions' location, shared ratio and area ratio and then remove all artifacts. We compare these three methods by 216 challenging images with severe blood artifacts selected from clinical 1076 IVOCT images. The metrics of the proposed method are evaluated including Dice index, Jaccard index and accuracy of 94.57%, 90.12%, 98.02%. Compared with automatic lumen segmentation based on the previous morphological feature method and widely used dynamic programming method, the metrics of the proposed method are significantly enhanced, especially in challenging images with severe blood artifacts.