Potential Underestimation of Left Ventricular Mechanical Dyssynchrony in Dyssynchrony and Outcomes Assessment.

Objective: Left ventricular (LV) mechanical dyssynchrony (LVMD) is fundamental to the progression of heart failure and ventricular remodeling. The status of LVMD in different patterns of bundle branch blocks (BBB) is unclear. In this study, we analyzed the relationship between LVMD and left ventricular systolic dysfunction using real-time three-dimensional echocardiography (RT-3DE). Methods: RT-3DE and conventional two-dimensional echocardiography were performed on 68 patients with left bundle branch block (LBBB group), 106 patients with right bundle branch block (RBBB group), and 103 patients without BBB (Normal group). The RT-3DE data sets provided time-volume analysis for global and segmental LV volumes. The LV systolic dyssynchrony index (LVSDI) was calculated using the standard deviation (SD) and maximal difference (Dif) of time to minimum segmental volume (tmsv) for LV segments adjusted by the R-R interval. LVMD was considered if the LVSDI (Tmsv-16-SD) was greater than or equal to 5%. Results: LVSDI is negatively and significantly correlated with left ventricular ejection fraction (LVEF), but not with BBB or QRS duration. The proportion of LVMD in the LBBB, RBBB, and Normal group was 30.88%, 28.30%, and 25.24%, respectively, and there was no significant difference. Conclusion: In dilated cardiomyopathy, LVMD is more closely related to LVEF reduction than QRS morphology and duration.

Perylene-Mediated Cytoskeletal Dysfunction Remodels Cancer-Associated Fibroblasts to Augment Antitumor Immunotherapy.

Targeted reprogramming of cancer-associated fibroblasts (CAFs) is one of the most essential cancer therapies. However, how to reprogram active CAFs toward deactivated state still remains immense challenge. To tackle this challenge, herein, one perylene N, N'-bis(2-((dimethylammonium)ethylene)-2-(methoxylethyl))-1, 6, 7, 12-tetrachloroperylene-3, 4, 9, 10-tetracarboxylic diimide (PDIC-OC) is prepared, which can trigger endogenous reactive oxygen species (ROS) burst to result in cytoskeletal dysfunction and cell apoptosis so that suppress transforming growth factor ß (TGF-ß) production. As a result, PDIC-OC can reprogram the activated CAFs and relieve immunosuppressive tumor microenvironment by efficient polarization of M2-typed macrophages into M1-typed ones, downregulation of alpha-smooth muscle actin (α-SMA), alleviation of hypoxic state to promote infiltration of cytotoxic T lymphocytes, and ultimately realizes outstanding antitumor performance on B16F10 tumor-xenografted and lung-metastatic mouse model even at low concentration of 1 mg kg-1 body weight. This work thus presents a novel strategy that cytoskeleton dysfunction and cell apoptosis cooperatively suppress the secretion of TGF-ß to reprogram CAFs and meanwhile clarifies intrinsic mechanism for perylene-triggered chemo-immunotherapy against hypoxic tumors.

Validation of reliability, repeatability and consistency of three-dimensional choroidal vascular index.

This study aimed to investigate the reliability, repeatability and consistency of choroidal vascularity index (CVI) measurements provided by an artificial intelligence-based software in swept-source optical coherence tomography (SS-OCT) in normal subject, and to evaluate the influencing factors for 3D-CVI. Repeatability of 3D-CVI by SS-OCT was evaluated based on different scanning modes including Macular Cubes (3 mm × 3 mm, 6 mm × 6 mm, 9 mm × 9 mm) and Optic Nerve Head 6 mm × 6 mm. Intraclass Correlation Coefficient (ICC) was used to estimate the repeatability and reproducibility of five repeated measurement by SS-OCT. Consistency of CVI between SS-OCT and spectral-domain optical coherence tomography (SD-OCT) was measured and compared in a pilot study of ten eyes and agreement between SS-OCT and SD-OCT was evaluated by Bland-Altman analysis and Deming regression. The influencing factors for 3D-CVI including age, gender, axial length and spherical equivalent on CVI was further investigated in a prospective study of 125 eyes of 125 healthy subjects. ICC between different measurements by SS-OCT was 0.934 (95% CI 0.812-0.956) indicating good repeatability. Intraclass correlation coefficient between CVI measure by SS-OCT and SD-OCT was 0.887 (95% CI 0.796-0.938, P value < 0.001). The mean difference between 3D-CVI measured by SS-OCT and SD-OCT 0.133. CVI measured with SS-OCTA showed stronger correlations with axial length and age but not correlated with gender. There is good agreement between CVIs obtained from the built-in software that requires less timing in manual quantification. Studies investigating choroidal vascularity can be standardized by the AI-based CVI analyze software.

Multispectral imaging: Review of current applications.

Multispectral imaging (MSI) is a unique layer-by-layer imaging technique that allows the visualization of a wide array of retinal and choroidal pathologies including retinovascular disorders, retinal pigment epithelial changes, and choroidal lesions. Herein, we summarize the basic imaging principles and current applications of MSI together with recent technology advances in the field. MSI detects reflectance signal from both normal chorioretinal tissue and pathological lesions. Either hyperreflectance or hyporeflectance reveals the absorption activity of pigments such as hemoglobin and melanin and the reflection from interfaces such as the posterior hyaloid. Advances in MSI technique include creation of a retinal and choroidal oxy-deoxy map that could provide a better understanding of blood oxygen saturation within lesions as well as better interpretation of reflectance phenomenon of MSI images such as the different reflectance from the Sattler and Haller layers described in this review.

A Lung Ultrasound-Based Nomogram for the Prediction of Refractory Mycoplasma pneumoniae Pneumonia in Hospitalized Children.

Purpose: Early diagnosis of refractory Mycoplasma pneumoniae pneumonia (RMPP) is challenging because of the lack of practical diagnostic imaging tools. Lung ultrasound (LUS) is an emerging tool for diagnosing childhood pneumonia. Hence, we evaluated the role of a nomogram combining LUS findings, clinical features, and laboratory indices in the early prediction of RMPP in children. Patients and Methods: We retrospectively analyzed 225 children with Mycoplasma pneumoniae pneumonia (MPP) admitted to our hospital between Dec 2018 and Aug 2021. Logistic regression analysis incorporated LUS findings and clinical predictors into the nomogram. Ninety patients hospitalized from Sep 2021 to Dec 2021 were used for external validation of the prediction model. Receiver operating characteristics (ROC) and calibration curves were used to evaluate the performance of the nomogram in the early diagnosis of RMPP. Results: Ultimately, Consolidation size /BSA (odds ratio (OR) 1.015, 95% confidence interval (CI) 1.536-2.446), Pleural Effusion (OR 3.551, 95% CI 1.921-15.600), LDH (OR 1.044, 95% CI 1.006-1. 021) and CRP (OR 3.293, 95% CI 1.019-1.098) were independent risk factors for the development of RMPP. The prediction model was represented visually as a nomogram. The area under the ROC curve for the predictive nomogram was 0.955 (95% CI 0.919-0.978) in the training cohort and 0.916 (95% CI 0.838-0.964) in the validation cohort. The calibration curve is close to the diagonal. Conclusion: This is the first-time lung ultrasound was added to the predicted nomogram, which can more comprehensively assess the condition and more accurately predict the occurrence of RMPP early. Therefore, this nomogram can be widely used in the early diagnosis of RMPP, especially in primary care hospitals.

Multi-spectral imaging in adult-onset foveomacular vitelliform dystrophy: Report of two cases.

Purpose: To describe the characteristic findings of non-invasive multi-spectral imaging (MSI) for adult-onset foveomacular vitelliform dystrophy (AFVD). Observations: On examination of MSI, the characteristic performances of AFVD include the nodule-like high-reflecting lesions, the line-like low-reflecting lesions in the high-reflecting lesion, and the scattered high-reflecting and low-reflecting lesions around the nodule-like lesion. MSI has an advantage over color fundus photography (CFP) and fundus autofluorescence (FAF) in finding tiny lesions, which corresponded to drusenoid structures on optical coherence tomography (OCT). MSI showed different characteristics at different stages of AFVD, which may be instructive to the pathogenesis and progression of AFVD. Conclusions and Importance: MSI is a promising diagnostic and follow-up tool that will provide additional information in fundus imaging for AFVD, and the changes on MSI is partially instructive to the pathogenesis and progression of AFVD.

Value of Preoperative Hematological Parameters in the Prognosis of Gastric Cancer Patients Undergoing a Total Gastrectomy.

OBJECTIVE: This study aimed to evaluate the relationships between the albumin/globulin ratio (AGR), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) and clinicopathological information for gastric cancer patients. In addition, the prognostic values of these hematological parameters for resectable gastric cancer patients undergoing a total gastrectomy were determined. METHODS: A total of 245 patients with gastric cancer who underwent a total gastrectomy at our hospital between January 1, 2005, and December 30, 2015, were enrolled into this study. The preoperative AGR, NLR, and PLR in the serum samples of the patients were measured. The relationships between the hematological parameters and the disease-free survival (DFS) as well as overall survival (OS) were analyzed by statistical analysis. RESULTS: The cutoff values of AGR, NLR, and PLR were 1.57, 3.5, and 193, respectively. Univariate analyses demonstrated that a low AGR, a high NLR, and a high PLR were significant risk factors for a poor prognosis. According to multivariate analysis, a high PLR was found to be independently associated with a poor survival. Additionally, when age was considered as a stratified factor, univariate analyses demonstrated that a low AGR had the tendency to be correlated with a shorter DFS in nonelderly patients (<65 years old). A low AGR was significantly correlated with a shorter DFS and OS in elderly patients (≥65 years old). CONCLUSION: AGR, NLR, and PLR are independent risk factors associated with a poor gastric cancer survival by univariate analysis, and AGR is an independent risk factor for predicting DFS and OS in elderly patients (≥65 years old) with gastric cancer after total gastrectomy.

Novel application of multispectral refraction topography in the observation of myopic control effect by orthokeratology lens in adolescents.

BACKGROUND: Myopia, as one of the common ocular diseases, often occurs in adolescence. In addition to the harm from itself, it may also lead to serious complications. Thus, prevention and control of myopia are attracting more and more attention. Previous research revealed that single-focal glasses and orthokeratology lenses (OK lenses) played an important part in slowing down myopia and preventing high myopia. AIM: To compare the clinical effects of OK lenses and frame glasses against the increase of diopter in adolescent myopia and further explore the mechanism of the OK lens. METHODS: Changes in diopter and axial length were collected among 70 adolescent myopia patients (124 eyes) wearing OK lenses for 1 year (group A) and 59 adolescent myopia patients (113 eyes) wearing frame glasses (group B). Refractive states of their retina were inspected through multispectral refraction topography. The obtained hyperopic defocus was analyzed for the mechanism of OK lenses on slowing down the increase of myopic diopter by delaying the increase of ocular axis length and reducing the near hyperopia defocus. RESULTS: Teenagers in groups A and B were divided into low myopia (0D - -3.00 D) and moderate myopia (-3.25D - -6.00 D), without statistical differences among gender and age. After 1-year treatment, the increase of diopter and axis length and changes of retinal hyperopic defocus amount of group A were significantly less than those of group B. According to the multiple linear analysis, the retinal defocus in the upper, lower, nasal, and temporal directions had almost the same effect on the total defocus. The amount of peripheral retinal defocus (15°-53°) in group A was significantly lower than that in group B. CONCLUSION: Multispectral refraction topography is progressive and instructive in clinical prevention and control of myopia.

Regulating Twisted Skeleton to Construct Organ-Specific Perylene for Intensive Cancer Chemotherapy.

The systemic use of pharmaceutical drugs for cancer patients is a compromise between desirable therapy and side effects because of the intrinsic shortage of organ-specific pharmaceutical drug. Design and construction of pharmaceutical drug to achieve the organ-specific delivery is thus desperately desirable. We herein regulate perylene skeleton to effect organ-specificity and present an example of lung-specific distribution on the basis of bay-twisted PDIC-NC. We further demonstrate that PDIC-NC can target into mitochondria to act as cellular respiration inhibitor, inducing insufficient production of adenosine triphosphate, promoting endogenous H2 O2 and . OH burst, elevating calcium overload, efficiently triggering the synergistic apoptosis, autophagy and endoplasmic reticulum stress of lung cancer cells. The antitumor performance of PDIC-NC is verified on in vivo xenografted, metastasis and orthotopic lung cancer, presenting overwhelming evidences for potentially clinical application. This study contributes a proof-of-concept demonstration of twisted perylene to well attain lung-specific distribution, and meanwhile achieves intensive lung cancer chemotherapy.

Controlling Nutritional Status score predict the individualized survival of patients with gastric cancer.

BACKGROUND AND OBJECTIVES: The present study aimed to determine the correlation between Controlling Nutritional Status (CONUT) score and prognosis in gastric cancer patients undergoing total gastrectomy. METHODS AND STUDY DESIGN: The clinical data of 245 gastric cancer patients who underwent total gastrectomy in Peking University, First Hospital between January1st 2005 and December 30th 2015 were retrospectively collected. According to the CONUT level, they were divided into high CONUT (>3) group and low CONUT (≤3) group. The relationship between CONUT and the disease-free survival (DFS) and overall survival (OS) were analyzed by statistical analysis. RESULTS: The results showed that the optimal cutoff value for CONUT to predict the 5-year survival was 3 and CONUT had a higher area under the ROC curve (AUC) for 5-year disease free survival (DFS) and overall survival (OS) prediction. Additionally, when age was considered as a stratified factor, univariate analyses demonstrated that high CONUT correlated with shorter DFS in non-elderly (<65) patients and shorter DFS and OS in elderly (≥65) patients. CONCLUSIONS: High CONUT was significantly correlated with older age, advanced TNM-stage, higher Ki-67 and pathological subtype. Patients with high pre-operative high CONUT levels should be given more observation and constant follow-up after surgery.

SENSITIVITY AND SPECIFICITY OF MULTISPECTRAL IMAGING FOR POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: To evaluate the sensitivity and specificity of multispectral imaging (MSI), a noninvasive imaging technique composed of a series of monochromatic scanning light, for polypoidal choroidal vasculopathy (PCV). METHODS: This was a prospective observational study. Polypoidal lesions on MSI are defined by oval or lobular hyperreflective oval lesion with dark hyporeflective center. Branching vascular networks on MSI is featured by hyperreflective interlacing signal. Detection sensitivity and specificity of polypoidal lesions was compared with indocyanine green angiography, whereas sensitivity and specificity of branching vascular networks, subretinal fluid, and pigment epithelium detachment were compared with optical coherence tomography. RESULTS: Among 67 eyes, 38 eyes (56.7%) were diagnosed with PCV, 7 eyes (10.4%) with neovascular age-related macular degeneration, 13 eyes (19.4%) with central serous chorioretinopathy, 6 eyes (9.0%) with pathological myopia, and 3 eyes (4.5%) with idiopathic choroidal neovascularization. Compared with indocyanine green angiography, the sensitivity and specificity for diagnosing PCV by MSI alone was 84.21% and 93.10%, respectively, and the positive predictive value and the negative predictive value for PCV by MSI was 94.12% and 81.82%, respectively. The sensitivity and specificity for detecting polypoidal lesions were 84.21% and 93.10% compared with indocyanine green angiography. Compared with optical coherence tomography, the sensitivity and specificity for detecting branching vascular networks were 95.83% and 88.37%, for the subretinal fluid were 76.92% and 86.67%, and for the pigment epithelium detachment were 91.11% and 90.91%, respectively. CONCLUSION: Multispectral imaging allowed noninvasive visualization of polypoidal lesions and branching vascular networks and may serve as a new diagnostic option for PCV.

Synergistic non-bonding interactions based on diketopyrrolo-pyrrole for elevated photoacoustic imaging-guided photothermal therapy.

Conjugated polymers have excellent properties and can be used in photothermal therapy (PTT). Nevertheless, the concept to design and optimize the photothermal performance by cooperative non-bonding interactions is still in its infancy. Herein, a series of diketopyrrolopyrrole (DPP) derivatives containing chalcogen and fluorine atoms were synthesized to reveal how intra- and intermolecular interactions affect the therapeutic performance of cancer in vitro and in vivo. The synergistic π-π and FH interactions facilitate fluorine and selenium-substituted DPP-SeF to elevate their photothermal conversion efficiency up to 62% from 32% without fluorine and selenium-substituted DPP-SS, and the half-maximal inhibitory concentration drops to ∼8.36 µg mL-1 for DPP-SeF from 15.14 µg mL-1 for DPP-SS on A549 cells under 808 nm light irradiation. More interestingly, efficient tumor killing ability and magnificent biocompatibility on an animal model of A549 transplanted tumor reassert that DPP-SeF nanoagents have immense potential as photoacoustic/PTT agents. Thus, this work presents an efficient phototherapeutic agent, and meanwhile demonstrates the facile concept of accessing the synergistic effect of non-bonding interactions to promote antitumor efficiency by ingenious molecular engineering.

Novel observations in choroidal osteoma by multispectral imaging: a pilot case series.

PURPOSE: To identify novel tumor-specific features of ossification by using multispectral imaging (MSI) in patients diagnosed with choroidal osteoma. METHODS: Six eyes of 5 patients previously diagnosed with choroidal osteoma by ocular ultrasonography and orbital computerized tomography were observed with multispectral imaging (MSI). Traditional multimodal imaging, including color fundus photograph (CFP) and enhanced depth-imaging-optical coherence tomography (EDI-OCT), fundus autofluorescence (FAF), indocyanine green angiography/fundus fluorescein angiography (ICGA/FFA), was performed. Osseous features detected by MSI such as calcification and decalcification were characterized and compared with other imaging modalities. RESULTS: In all 3 eyes with calcified choroidal osteoma (100%), MSI featured by the homogeneous reflectance in 550 nm but the beehive appearance in 600-680 nm and homogenous hyper-reflectance in 780-850 nm', indicating the compact bone in the outer layers and bone trabecula in the middle layer (Sandwich sign). The pigmentary change showed high agreement between MSI and FAF. In other 3 eyes with extensive decalcification, MSI was able to differentiate the inactive portion of the osteoma from the decalcified area. The inactive portion was characterized by geographic hyper-reflective islands with higher reflectivity border (floating island sign). Decalcified portion was featured by increased definition and reflectivity from osteoma. Partial decalcification and total decalcification can be differentiated in one decalcifying eye (33.3%). MSI revealed better the presence and border of the osteoma compared with FFA, FAF and MC (100%) in all six eyes in our study. CONCLUSIONS: MSI presented characteristic osseous-related features of choroidal osteoma, providing clear evidence for differentiating osteoblastic and osteoclastic regions and noncalcifying regions. It can contribute to en-face visualization of choroidal osteomas at different stages, providing new insight into the spectrum behavior of CO.

Predictive Value of Lymphocyte-Related Blood Parameters at the Time Point of Lymphocyte Nadir During Radiotherapy in Breast Cancer.

PURPOSE: Various reports found a relationship between lymphocyte-related blood parameters (LRBP), including absolute lymphocyte counts (ALC), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) and prognosis of breast cancer. Most of the studies focused on LRBP pre-treatment. Seldom have studies focused on LRBP during radiotherapy. We intended to perform a retrospective cohort study on the prognostic value of LRBP at the time point of lowest ALC during radiotherapy for breast cancer. PATIENTS AND METHODS: A total of 158 female patients were included in radiotherapy group because of the strict limitation standards of complete routine blood test results at pre-treatment and pre-operation, and at least once a week during radiotherapy. Besides 221 patients, including the 158 patients of radiotherapy group, were adopted in pre-treatment group and pre-operation group. RESULTS: ALC and PLR at the time point of lowest ALC during radiotherapy are prognostic predictors of breast cancer, and lower ALC and higher PLR are independent significant predictors of poor DFS. Besides, lower ALC, higher NLR and higher PLR at both pre-treatment and pre-operation were found to be independent variables for predicting poor DFS. CONCLUSION: LRBP at pre-treatment, pre-operation, and during radiotherapy may serve as predictors of outcomes of breast cancer.

Morphological changes of lignin during separation of wheat straw components by the hydrothermal-ethanol method.

The separation efficiencies of wheat straw components by hydrothermal treatment and ethanol extraction have been compared. The results showed that the lignin removal rate by two-step hydrothermal-ethanol method was significantly lower than that of single-step ethanol extraction. Microscopic and adsorption studies (using SEM/AFM, XPS and pore structure analysis) showed that during the hydrothermal treatment a large lignin fraction migrated from the intercellular layer and cell wall and deposited on the fiber surface. Furthermore, the deposited lignin then spread on the fiber surface to form a lignin coating layer, which prevented its dissolution in ethanol. Without prior heating, i.e., upon a single step ethanol extraction, the massive lignin deposition was avoided, presumably due to its efficient dissolution hindering its tight binding with carbohydrate polymers on the fiber surface. Therefore, the lignin removal efficiency was drastically reduced as a result of hydrothermal treatment compared to ethanol extraction.

Free autologous internal limiting membrane transplantation in the treatment of large macular hole.

We evaluated the clinical efficacy of free internal limiting membrane (ILM) flap transplantation for the treatment of large macular hole over 500 µm in 42 consecutive patients. Quantified evaluation of the post-operative macular anatomy restoration was performed by spectral-domain optical coherence tomography in the 12mo follow-up. The results showed 41 eyes achieved successful closure (97.6%). Postoperative best corrected visual acuity, ellipsoid layer, and external limiting membrane disruption were significantly improved at all follow-up time points. The central foveal thickness was significantly higher at 1mo. We concluded that free ILM flap transplantation proves to be effective to achieve anatomical and functional improvement for the treatment of large macular hole.

Changes in Ocular Hemodynamics after Carotid Artery Angioplasty and Stenting (CAAS) in Patients with Different Severity of Ocular Ischemic Syndrome.

PURPOSE: To evaluate the effects of carotid artery angioplasty and stenting (CAAS) on patients who were diagnosed with ocular ischemic syndrome (OIS). METHODS: Sixty-four eyes of 64 OIS patients with ipsilateral internal carotid artery stenosis ≥70% were included in the study. The study eyes were divided into two groups according to the presence of iris neovascularization: NVI-absent group and NVI-present group, with 32 eyes, respectively. All patients received ocular treatment modality according to the presence of non-perfusion area (pan-retinal photocoagulation) and intraocular pressure (medical treatment included timolol maleate eye drops combined with brinzolamide eye drop; trabeculectomy and cyclophotocoagulation). All patients went through CAAS surgery for treatment of internal carotid artery stenosis. Best-corrected visual acuity (BCVA); intraocular pressure (IOP), slit lamp examination, iris fluorescence angiography, fundus fluorescein angiography and color Doppler ultrasound of the internal carotid artery (ICA), ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary arteries (PCA) were performed pre-operatively and 1 month, 3 months, 6 months, and 12 months post-operatively. RESULTS: There was no significant BCVA change postoperatively in the NVI-absent group, while postoperative BCVA in the INV-present group decreased significantly. There was no significant BCVA difference at pre-operative and 1month post-operative follow-up between the two groups. However, post-operative BCVA of NVI-present group starting from 3-months follow-up was significantly worse than NVI-absent group. Arm-retinal artery circulation time and arteriovenous circulation time decreased significantly in NVI-absent group, while showed no statistical difference in NVI-present group during the 12-months follow-up. Postoperative peak systolic velocity (PSV) of the ophthalmic artery, the central retinal artery, and short posterior ciliary artery showed significant increases at 1 month, 3 months, 6 months and 12 months follow-up in both groups. CONCLUSION: CAAS can greatly improve ocular blood in OIS patients with and without iris neovascularization. However, CAAS improved BCVA only in patients without iris neovascularization.