Progression of functional and structural glaucomatous damage in relation to diurnal and nocturnal dips in mean arterial pressure

Background: Systemic hypoperfusion plays a pivotal role in the pathogenesis of primary open-angle glaucoma (POAG). Extreme dips in mean arterial pressure (MAP) due to high 24-h variability are associated with POAG, however, whether this is driven by diurnal or nocturnal dips remains undocumented. We aimed this study to investigate the association of POAG damage with variability and dips in the diurnal and nocturnal MAP. Methods: We conducted a retrospective longitudinal study that included 110 POAG patients who underwent 24-h ambulatory blood pressure monitoring. Our outcomes included (i) functional [visual field defects expressed as mean deviation (MD)] and (ii) structural (optic disc cupping obtained from cup-to-disc ratio) glaucoma damage. MAP variability independent of the mean (VIMmap) was computed for diurnal and nocturnal MAP. Dips were the five diurnal and three nocturnal lowest drops in MAP. We also calculated the night-to-day ratio. We applied mixed models to evaluate the progression of visual field defects and optic disc cupping in relation to diurnal and nocturnal MAP measures. Results: The mean age was 64.0 y (53% women). The median follow-up was 9 years. In adjusted mixed models, functional progression of glaucoma damage was associated with VIMmap (−2.57 dB change in MD per every 3 mmHg increase in VIMmap; P \u3c 0.001) and diurnal MAP dips (changes in the MD ranged from −2.56 to −3.19 dB; P \u3c 0.001). Every 5 mmHg decrease in the nocturnal MAP level was associated with −1.14 dB changes in MD [95% confidence interval (CI), −1.90 to −0.40] and 0.01 larger optic disc cupping (95% CI, 0.01–0.02). Lower night-to-day ratio was also related to both outcomes (P ≤ 0.012). Functional glaucoma damage worsened if nocturnal hypotension was combined with high variability or extreme dips in the diurnal MAP (P ≤ 0.022). Conclusion: Progression of glaucoma damage in POAG associates with high variability and extreme dips in the diurnal MAP. Structural glaucoma damage seems more vulnerable to nocturnal hypotension. Ambulatory blood pressure monitoring allows the assessment of sporadic diurnal and persistent nocturnal hypotension episodes. These phenotypes might offer an opportunity to improve the risk-stratification of open-angle glaucoma (OAG)

Synthesis and Characterization of New Liquid Crystalline Thermoplastic Elastomers Containing Mesogen-Jacketed Liquid Crystalline Polymers

In order to improve the high-temperature performance of thermoplastic elastomers (TPEs), we designed and synthesized a new kind of ABA triblock copolymer containing a mesogen-jacketed liquid crystalline polymer (MJLCP), poly­{2,5-bis­[(4-methoxy­phenyl)­oxy­carbonyl]­styrene} (PMPCS), as the hard blocks and polybutadiene (PB) as the soft block. The triblock copolymer, PMPCS-<i>b</i>-PB-<i>b</i>-PMPCS (M-B-M), was synthesized by ring-opening metathesis polymerization in the presence of a chain transfer agent and atom transfer radical polymerization. The glass transition temperature (<i>T</i>_g) of the PMPCS hard block is 110–118 °C in the triblock copolymers. In addition, the liquid crystalline (LC) phase of PMPCS is stable before thermal decomposition. All the triblock copolymers form lamellar microphase-separated structures, as demonstrated by small-angle X-ray scattering and transmission electron microscopy results. The triblock copolymer (M-B-M-55) with a mass fraction of 55% of PMPCS exhibits typical properties of an LC thermoplastic elastomer (LCTPE). The maximum elongation at break and the tensile strength of M-B-M-55 are 736% and 10.6 MPa, respectively, and the stretching strength at 300% is 6.9 MPa. Above the <i>T</i>_g of PMPCS, the LC phase of PMPCS provides new physical cross-linking points in the LCTPEs, and the triblock copolymer M-B-M-55 still shows a relatively high modulus

Hierarchical Structures in a Main-Chain/Side-Chain Combined Liquid Crystalline Polymer with a Polynorbornene Backbone and Multi-Benzene Side-Chain Mesogens

A series of main-chain/side-chain combined liquid crystalline polymers (MCSCLCPs) with a polynorbornene backbone and multi-benzene mesogens in the side chain, PNb<i>n</i>PP (<i>n</i> = 2, 6, 10), were synthesized through a controllable polymerization method: ring-opening metathesis polymerization (ROMP). Differential scanning calorimetry, polarized light microscopy, and one-/two-dimensional wide-angle X-ray diffraction were utilized to investigate the phase behavior of PNb<i>n</i>PP. Experimental results reveal that the two fundamentally different liquid crystalline (LC) building blocksthe mesogen-jacketed LC polymer main chain and the multi-benzene calamitic mesogens in the side chaincompete and promote with each other, leading to a complex phase behavior. Because of the coupling effect between the rigid core and the pendants (multi-benzene mesogens) of PNb2PP with a short spacer, PNb2PP forms a simple smectic phase. On the other hand, owing to the decoupling effect of the long spacers, at low temperatures PNb6PP and PNb10PP form hierarchical structures, including the smectic phase of the polymer as a whole and the ordered packing of the multi-benzene mesogens

Time-Resolved Fluorescence Anisotropy of Surface Plasmon Coupled Emission on Metallic Gratings

The unique characteristics of surface plasmon coupled emission (SPCE) made it useful for potential applications in the fields of plasmonic optics and biological sensing. However, the mechanism of SPCE is still under debate. We studied the time-resolved fluorescence anisotropy of SPCE excluding the interference of absorption-enhancement effect by the time-correlated single-photon counting (TCSPC) setups. The value of anisotropy at SPCE peak kept constant at −0.45 during the whole relaxation process, which is in agreement with the calculated value. Our work presented a further step toward the understanding of SPCE

DataSheet_1_Polo-like kinase 1 is related with malignant characteristics and inhibits macrophages infiltration in glioma.zip

BackgroundTumor immune microenvironment (TIM) plays a critical role in tumorigenesis and progression. Recently, therapies based on modulating TIM have made great breakthroughs in cancer treatment. Polo-like kinase 1 (PLK1) is a crucial regulatory factor of the cell cycle process and its dysregulations often cause various pathological processes including tumorigenesis. However, the detailed mechanisms surrounding the regulation of PLK1 on glioma immune microenvironment remain undefined.MethodsPublic databases and online datasets were used to extract data of PLK1 expression, clinical features, genetic alterations, and biological functions. The EdU, flow cytometry, and macrophage infiltration assays as well as xenograft animal experiments were performed to determine the relationship between PLK1 and glioma immune microenvironment in vivo and in vitro.ResultsPLK1 is always highly expressed in multiple cancers especially in glioma. Univariable and Multivariate proportional hazard Cox analysis showed that PLK1 was a prognostic biomarker for glioma. Simultaneously, highly expressed PLK1 is significantly related to prognosis, histological and genetic features in glioma by analyzing public databases. In addition, the enrichment analysis suggested that PLK1 might related to “immune response”, “cell cycle”, “DNA replication”, and “mismatch repair” in glioma. Immune infiltration analysis demonstrated that highly expressed PLK1 inhibited M1 macrophages infiltration to glioblastoma immune microenvironment by Quantiseq and Xcell databases and negatively related to some chemokines and marker genes of M1 macrophages in glioblastoma. Subsequent experiments confirmed that PLK1 knockdown inhibited the proliferation of glioma cells but increased the M1 macrophages infiltration and polarization. Furthermore, in glioma xenograft mouse models, we showed that inhibiting PLK1 blocked tumor proliferation and increased the M1 macrophages infiltration. Finally, PLK1 methylation analysis and lncRNA-miRNA network revealed the potential mechanism of abnormal PLK1 expression in glioma.ConclusionsPLK1 inhibits M1 macrophages infiltration into glioma immune microenvironment and is a potential biomarker for glioma. </p

Table_3_Polo-like kinase 1 is related with malignant characteristics and inhibits macrophages infiltration in glioma.xlsx

BackgroundTumor immune microenvironment (TIM) plays a critical role in tumorigenesis and progression. Recently, therapies based on modulating TIM have made great breakthroughs in cancer treatment. Polo-like kinase 1 (PLK1) is a crucial regulatory factor of the cell cycle process and its dysregulations often cause various pathological processes including tumorigenesis. However, the detailed mechanisms surrounding the regulation of PLK1 on glioma immune microenvironment remain undefined.MethodsPublic databases and online datasets were used to extract data of PLK1 expression, clinical features, genetic alterations, and biological functions. The EdU, flow cytometry, and macrophage infiltration assays as well as xenograft animal experiments were performed to determine the relationship between PLK1 and glioma immune microenvironment in vivo and in vitro.ResultsPLK1 is always highly expressed in multiple cancers especially in glioma. Univariable and Multivariate proportional hazard Cox analysis showed that PLK1 was a prognostic biomarker for glioma. Simultaneously, highly expressed PLK1 is significantly related to prognosis, histological and genetic features in glioma by analyzing public databases. In addition, the enrichment analysis suggested that PLK1 might related to “immune response”, “cell cycle”, “DNA replication”, and “mismatch repair” in glioma. Immune infiltration analysis demonstrated that highly expressed PLK1 inhibited M1 macrophages infiltration to glioblastoma immune microenvironment by Quantiseq and Xcell databases and negatively related to some chemokines and marker genes of M1 macrophages in glioblastoma. Subsequent experiments confirmed that PLK1 knockdown inhibited the proliferation of glioma cells but increased the M1 macrophages infiltration and polarization. Furthermore, in glioma xenograft mouse models, we showed that inhibiting PLK1 blocked tumor proliferation and increased the M1 macrophages infiltration. Finally, PLK1 methylation analysis and lncRNA-miRNA network revealed the potential mechanism of abnormal PLK1 expression in glioma.ConclusionsPLK1 inhibits M1 macrophages infiltration into glioma immune microenvironment and is a potential biomarker for glioma. </p

Table_6_Polo-like kinase 1 is related with malignant characteristics and inhibits macrophages infiltration in glioma.xlsx

BackgroundTumor immune microenvironment (TIM) plays a critical role in tumorigenesis and progression. Recently, therapies based on modulating TIM have made great breakthroughs in cancer treatment. Polo-like kinase 1 (PLK1) is a crucial regulatory factor of the cell cycle process and its dysregulations often cause various pathological processes including tumorigenesis. However, the detailed mechanisms surrounding the regulation of PLK1 on glioma immune microenvironment remain undefined.MethodsPublic databases and online datasets were used to extract data of PLK1 expression, clinical features, genetic alterations, and biological functions. The EdU, flow cytometry, and macrophage infiltration assays as well as xenograft animal experiments were performed to determine the relationship between PLK1 and glioma immune microenvironment in vivo and in vitro.ResultsPLK1 is always highly expressed in multiple cancers especially in glioma. Univariable and Multivariate proportional hazard Cox analysis showed that PLK1 was a prognostic biomarker for glioma. Simultaneously, highly expressed PLK1 is significantly related to prognosis, histological and genetic features in glioma by analyzing public databases. In addition, the enrichment analysis suggested that PLK1 might related to “immune response”, “cell cycle”, “DNA replication”, and “mismatch repair” in glioma. Immune infiltration analysis demonstrated that highly expressed PLK1 inhibited M1 macrophages infiltration to glioblastoma immune microenvironment by Quantiseq and Xcell databases and negatively related to some chemokines and marker genes of M1 macrophages in glioblastoma. Subsequent experiments confirmed that PLK1 knockdown inhibited the proliferation of glioma cells but increased the M1 macrophages infiltration and polarization. Furthermore, in glioma xenograft mouse models, we showed that inhibiting PLK1 blocked tumor proliferation and increased the M1 macrophages infiltration. Finally, PLK1 methylation analysis and lncRNA-miRNA network revealed the potential mechanism of abnormal PLK1 expression in glioma.ConclusionsPLK1 inhibits M1 macrophages infiltration into glioma immune microenvironment and is a potential biomarker for glioma. </p

Medulloblastoma in China: Clinicopathologic Analyses of SHH, WNT, and Non-SHH/WNT Molecular Subgroups Reveal Different Therapeutic Responses to Adjuvant Chemotherapy

<div><p>Medulloblastoma (MB) is one of the most common primary central nervous system tumors in children. Data is lacking of a large cohort of medulloblastoma patients in China. Also, our knowledge on the sensitivity of different molecular subgroups of MB to adjuvant radiation therapy (RT) or chemotherapy (CHT) is still limited. The authors performed a retrospective study of 173 medulloblastoma patients treated at two institutions from 2002 to 2011. Formalin-fixed paraffin embedded (FFPE) tissues were available in all the cases and sections were stained to classify histological and molecular subgroups. Univariate and multivariate analyses were used to investigate prognostic factors. Of 173 patients, there were 118 children and 55 adults, 112 males and 61 females. Estimated 5-year overall survival (OS) rates for all patients, children and adults were 52%, 48% and 63%, respectively. After multivariate analysis, postoperative primary radiation therapy (RT) and chemotherapy (CHT) were revealed as favorable prognostic factors influencing OS and EFS. Postoperative primary chemotherapy (CHT) was found significantly improving the survival of children (p<0.001) while it was not a significant prognostic factor for adult patients. Moreover, patients in WNT subtype had better OS (p = 0.028) than others (SHH and Non-SHH/WNT subtypes) given postoperative adjuvant therapies. Postoperative primary RT was found to be a strong prognostic factor influencing the survival in all histological and molecular subgroups (p<0.001). Postoperative primary CHT was found significantly to influence the survival of classic medulloblastoma (CMB) (OS p<0.001, EFS p<0.001), SHH subgroup (OS p = 0.020, EFS p = 0.049) and WNT subgroup (OS p = 0.003, EFS p = 0.016) but not in desmoplastic/nodular medulloblastoma (DMB) (OS p = 0.361, EFS p = 0.834) and Non-SHH/WNT subgroup (OS p = 0.127, EFS p = 0.055). Our study showed postoperative primary CHT significantly influence the survival of CMB, SHH subgroup and WNT subgroup but not in DMB and Non-SHH/WNT subgroup of MB.</p></div

Multivariate analysis of prognostic factors for OS and EFS in patients with medulloblastoma (n = 173).

<p>OR: odds ratio, CI: confidence interval.</p>a<p>involving brain stem or IV ventricle floor by the tumor.</p>b<p>indicating postoperative primary radiation therapy.</p>c<p>indicating postoperative primary chemotherapy.</p

Univariate analysis of histological and molecular subgroups for OS and EFS in medulloblastoma patients (n = 173).

<p>CMB = Classic medulloblastoma, DMB = Desmoplastic/nodular medulloblastoma, AMB = Large-cell/anaplastic medulloblastoma, SHH = SHH pathway medulloblastoma, WNT = WNT pathway medulloblastoma, Non-SHH/WNT =  Non-SHH/WNT pathway medulloblastoma.</p>a<p>those patients who did not receive any adjuvant therapies after primary resection were excluded.</p