[Differential Analysis of Macular Structure and Microcirculation in Both Eyes of Patients With Myopic Anisometropia].

Objective To compare the macular structure and microcirculation in both eyes of the patients with myopic anisometropia.Methods Optical coherence tomography angiography(OCTA)was employed to scan the macular areas in both eyes of 44 patients with myopic anisometropia.The patients were assigned into high and low groups based on the refractive diopter,and the parameters such as retinal thickness,choroidal thickness,vascular density,and perfusion density in the macular areas of both eyes were compared between the two groups.Results Other macular areas except the central and external nasal areas and the choroid of the fovea in the high group were thinner than those in the low group(all P<0.05).There was no statistically significant difference in retinal vascular density or perfusion density in different areas between the two groups(all P>0.05).Conclusion In the patients with myopic anisometropia,most areas of the retina in the case of high myopia is thinner than that in the case of low myopia,while there is no difference in retinal vascular density or perfusion density in both eyes.

Dihydroxyphenyl-substituted thiosemicarbazone: A potent scaffold for the development of metallo-ß-lactamases inhibitors and antimicrobial.

The superbug infection mediated by metallo-ß-lactamases (MßLs) has grown into anemergent health threat, and development of MßL inhibitors is an ideal strategy to combat the infection. In this work, twenty-five thiosemicarbazones 1a-e, 2a-e, 3a-e, 4a-d, 5a-d and 6a-b were synthesized and assayed against MßLs ImiS, NDM-1 and L1. The gained molecules specifically inhibited NDM-1 and ImiS, exhibiting an IC50 value in the range of 0.37-21.35 and 0.45-8.76 µM, and 2a was found to be the best inhibitor, with an IC50 of 0.37 and 0.45 µM, respectively, using meropenem (MER) as substrate. Enzyme kinetics and dialysis tests revealed and confirmed by ITC that 2a is a time-and dose-dependent inhibitor of ImiS and NDM-1, it competitively and reversibly inhibited ImiS with a Ki value of 0.29 µM, but irreversibly inhibited NDM-1. Structure-activity relationship disclosed that the substitute dihydroxylbenzene significantly enhanced inhibitory activity of thiosemicarbazones on ImiS and NDM-1. Most importantly, 1a-e, 2a-e and 3a-b alone more strongly sterilized E. coli-ImiS and E. coli-NDM-1 than the MER, displaying a MIC value in the range of 8-128 µg/mL, and 2a was found to be the best reagent with a MIC of 8 and 32 µg/mL. Also, 2a alone strongly sterilized the clinical isolates EC01, EC06-EC08, EC24 and K. pneumonia-KPC-NDM, showing a MIC value in the range of 16-128 µg/mL, and exhibited synergistic inhibition with MER on these bacteria tested, resulting in 8-32-fold reduction in MIC of MER. SEM images shown that the bacteria E. coli-ImiS, E. coli-NDM-1, EC24, K. pneumonia-KPC and K. pneumonia-KPC-NDM treated with 2a (64 µg/mL) suffered from distortion, emerging adhesion between individual cells and crumpled membranes. Mice tests shown that monotherapy of 2a evidently limited growth of EC24 cells, and in combination with MER, it significantly reduced the bacterial load in liver and spleen. Docking studies suggest that the 2,4-dihydroxylbenzene of 2a acts as zinc-binding group with the Zn(II) and the residual amino acids in CphA active center, tightly anchoring the inhibitor at active site. This work offered a promising scaffold for the development of MßLs inhibitors, specifically the antimicrobial for clinically drug-resistant isolates.

[Effects of Intravitreal Injection of Anti-vascular Endothelial Growth Factor Drugs on Ocular Blood Vessels and Blood Flow in Patients with Diabetic Retinopathy].

Diabetic retinopathy(DR)is the major microvascular disease in diabetic patients,and it is also one of the main blinding eye diseases in the current population.The typical pathological change of DR in the eyes is vascular endothelial growth factor(VEGF)-mediated neovascularization induced by retinal ischemic stimulation.Therefore,anti-VEGF drugs have gradually become one of the mainstream methods to treat DR and DR-induced diseases such as diabetic macular edema.Recent studies have proved that anti-VEGF drugs have certain effects on ocular blood vessels and blood flow in patients with DR,while the specific mechanism has not been fully elucidated.This article summarizes the research progress on the effects of intravitreal injection of anti-VEGF drugs on the ocular blood vessels and blood flow in patients with DR.

[Research Advances in Ocular Myasthenia Gravis].

Ocular myasthenia gravis(OMG)is an autoimmune disease caused by neuromuscular junction transmission disorders and manifested mainly as fluctuating blepharoptosis and diplopia,with the extraocular muscles as the main involveed sites.While the pathogenesis of OMG remains unclear,some antibodies,complements,and cytokines may be the contributing factors.The diagnosis and treatment of OMG have been defined in recent years.This article reviews the pathogenesis,diagnosis,and treatment of OMG.

[Mechanism of Th1/Th2 Cytokines in HLA-DQ8 Transgenic Mice Model of Ocular Experimental Autoimmune Myasthenia Gravis].

Objective To analyze the levels of cytokines (IL-2,IFN-γ,IL-6,IL-10) associated with Th1 and Th2 cells in HLA-DQ8 transgenic mice model of ocular experimental autoimmune myasthenia gravis (oEAMG) induced by recombinant H-AChR γ subunit immunization.Methods DQ8 mice were immunized with 20 µg of AChR γ subunit,20 µg of crude E. coli extract (E. coli group),or complete Freund's adjuvant (CFA) only (CFA group). All mice were immunized on days 0,30,and 60. Mice were euthanized 28 days after the third immunization,and draining lymph node cells (LNC) and spleen lymphocytes were cultured in vitro. The supernatant was collected to observe the interleukin(IL)-2,interferon(IFN)-γ,IL-6,IL-10 production by ELISA.Results LNCs and spleen lymphocytes of H-AChR γ subunit-immunized mice exhibited significantly enhanced IFN-γ (F=76.332,P<0.001;F=34.865,P<0.001) and IL-2 (F=42.835,P<0.001;F=38.030,P<0.001),which associated with Th1 cells,as compared to E. coli group and CFA group. There were no significant differences in IL-6 (F=1.325,P=0.284;F=1.935,P=0.166) and IL-10 (F=0.908,P=0.417;F=1.189,P=0.322) levels,which secreted by Th2 cells,among these three groups.Conclusion Th1 cytokines play key roles in the pathogenesis of oEAMG,while the mechanism of Th2 cytokines for oEAMG remains unclear.

[Advances in Retinopathy of Prematurity].

Retinopathy of prematurity(ROP)is a pathological neovascularization with fibrotic changes in the fundus of premature infants.It is a major cause of preventable blindness in children in both developing and developed countries.Treatment of ROP has long been a hot research topic in ophthalmology and pediatrics.With a clearer knowledge of the pathogenesis of ROP,more basic and clinical studies have been carried out.The anti-vascular endothelial growth factor therapy and surgical treatment have become mature strategies,and a variety of therapeutic drugs including insulin-like growth factor-1,transforming growth factor-ß,polyunsaturated fatty acids,and ß-adrenergic receptor blockers have been developed.This article reviews the recent advances in ROP.

Renal AML with inferior vena cava thrombus treated by workbench surgery and autotransplantation.

Renal angiomyolipoma may sometimes require surgical intervention. In this paper, we present a case of renal angiomyolipoma which infiltrated the sinus and extended into the inferior vena cava. He was successfully treated with a combined approach of laparoscopic radical nephrectomy, extracorporeal workbench tumor resection, and autotransplantation. Three months postoperatively, no evidence of tumor recurrence or presence of thrombus in the inferior vena cava was noted. Our experience represents the successful application of a combined nephron-sparing approach in the management of angiomyolipoma with extension into a major blood vessel.

Treatment of renal cell carcinoma with a level III or level IV inferior vena cava thrombus using cardiopulmonary bypass and deep hypothermic circulatory arrest.

BACKGROUND: The aim of this study was to investigate the minimally invasive cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) approach in the management of renal cell carcinoma (RCC) with level III or IV inferior vena cava (IVC) thrombus and evaluate the survival outcomes. METHODS: We performed a retrospective analysis on 32 RCC patients with IVC thrombus that underwent nephrectomy and thrombectomy via the minimally invasive CPB/DHCA approach between January 2007 and December 2013. Perioperative variables (for example, operative time, CPB duration, and circulatory arrest duration), estimated blood loss, hospital stay, perioperative complications, and survival data were recorded and analyzed. RESULTS: Thirty-two patients (median age: 56 years) were treated surgically using the CPB and DHCA approach for RCC with a level III (n=25) or level IV (n=7) tumor thrombus. The median operation time was 360 min (interquartile range (IQR): 300 to 435 min) with median CPB and DHCA durations of 149 min and 23 min, respectively. The median estimated blood loss was 2,500 ml. Four complications were observed but no deaths occurred perioperatively. The median follow-up was 25 months (range: 4 to 64 months). The mean overall survival (OS) was 28.2±4.6 months while the disease-free survival (DFS) was 19.5±11.6 months. In patients with M0 disease, ten patients developed metastases and were treated with sorafenib as an adjuvant therapy. The mean OS and DFS of this subgroup were 25.4±12.8 months and 16.0±14.2 months, respectively. CONCLUSIONS: Radical nephrectomy and thrombectomy using CPB and DHCA to treat RCC is a relatively safe approach associated with low morbidity and mortality. This minimally invasive procedure may help minimize surgical trauma and improve perioperative outcomes.

Innovative design of light collimator based on a freeform microlens array.

In developing a daylighting system, the overall system efficiency is crucial. In the daylighting system, whether the light propagates parallel strongly affects the efficiency. In this paper, we simulate a multicurvature lens to collimate rays propagated from different angles. We describe a method based on a freeform microlens array, which increases transmission efficiency. Results show that with the freeform microlens array collimator, the light propagates provide at least 50.26% parallel and the efficiency increases by 24.76%, enhancing the core values of the daylighting system in building illumination.

[Wavelength selection of the oximetry based on test analysis of variance].

In order to improve the precision and reliability of the spectral measurement of blood oxygen saturation, and enhance the validity of the measurement, the method of test analysis of variance was employed. Preferred wavelength combination was selected by the analysis of the distribution of the coefficient of oximetry at different wavelength combinations and rational use of statistical theory. Calculated by different combinations of wavelengths (660 and 940 nm, 660 and 805 nm and 805 and 940 nm) through the clinical data under different oxygen saturation, the single factor test analysis of variance model of the oxygen saturation coefficient was established, the relative preferabe wavelength combination can be selected by comparative analysis of different combinations of wavelengths from the photoelectric volume pulse to provide a reliable intermediate data for further modeling. The experiment results showed that the wavelength combination of 660 and 805 nm responded more significantly to the changes in blood oxygen saturation and the introduced noise and method error were relatively smaller of this combination than other wavelength combination, which could improve the measurement accuracy of oximetry. The study applied the test variance analysis to the selection of wavelength combination in the blood oxygen result measurement, and the result was significant. The study provided a new idea for the blood oxygen measurements and other related spectroscopy quantitative analysis. The method of test analysis of variance can help extract the valid information which represents the measured values from the spectrum.

Discovery of hydroxamate as a promising scaffold dually inhibiting metallo- and serine-ß-lactamases.

The bacterial infection mediated by ß-lactamases MßLs and SßLs has grown into an emergent health threat, however, development of a molecule that dual inhibits both MßLs and SßLs is challenging. In this work, a series of hydroxamates 1a-g, 2a-e, 3a-c, 4a-c were synthesized, characterized by 1H and 13C NMR and confirmed by HRMS. Biochemical assays revealed that these molecules dually inhibited MßLs (NDM-1, IMP-1) and SßLs (KPC-2, OXA-48), with an IC50 value in the range of 0.64-41.08 and 1.01-41.91 µM (except 1a and 1d on SßLs, IC50 > 50 µM), and 1f was found to be the best inhibitor with an IC50 value in the range of 0.64-1.32 and 0.57-1.01 µM, respectively. Mechanism evaluation indicated that 1f noncompetitively and irreversibly inhibited NDM-1 and KPC-2, with Ki value of 2.5 and 0.55 µM, is a time- and dose-dependent inhibitor of both MßLs and SßLs. MIC tests shown that all hydroxamates increased the antimicrobial effect of MER on E. coli-NDM-1 and E. coli-IMP-1 (expect 1b, 1d, 1g and 2d), resulting in a 2-8-fold reduction in MICs of MER, 1e-g, 2b-d, 3a-c and 4b-c decreased 2-4-fold MICs of MER on E. coli-KPC-2, and 1c, 1f-g, 2a-c, 3b, 4a and 4c decreased 2-16-fold MICs of MER on E. coli-OXA-48. Most importantly, 1f-g, 2b-c, 3b and 4c exhibited the dual synergizing inhibition against both E. coli-MßLs and E. coli-SßLs tested, resulting in a 2-8-fold reduction in MICs of MER, and 1f was found to have the best effect on the drug-resistant bacteria tested. Also, 1f shown synergizing antimicrobial effect on five clinical isolates EC04, EC06, EC08, EC10 and EC24 that produce NDM-1, resulting in a 2-8-fold reduction in MIC of MER, but its effect on E. coli and K. pneumonia-KPC-NDM was not to be observed using the same dose of inhibitor. Mice tests shown that the monotherapy of 1f or 4a in combination with MER significantly reduced the bacterial load of E. coli-NDM-1 and E. coli-OXA-48 cells in liver and spleen, respectively. The discovery in this work offered a promising bifunctional scaffold for creating the specific molecules that dually inhibit MßLs and MßLs, in combating antibiotic-resistant bacteria.

Exploration of Hippocampal Functional Connectivity Alterations in Patients with High Myopia via Seed-Based Functional Connectivity Analysis.

Aim: The objective of this study was to examine changes in functional connectivity (FC) in the hippocampus among patients with high myopia (HM) compared to healthy controls (HCs) through the utilization of seed-based functional connectivity (FC) analysis. Methods: Resting-state functional magnetic resonance imaging (fMRI) was conducted on a sample of 82 patients diagnosed with high myopia (HM) and 59 HCs. The two groups were matched based on age, weight and other relevant variables. Using seed-based FC analysis to detect alterations in hippocampal FC patterns in HM patients and HCs. Furthermore, a correlation analysis was performed to examine the associations between the mean functional connectivity (FC) signals in various brain regions of patients with HM and their corresponding clinical manifestations. Results: The FC values in the left temporal pole-temporal gyrus (L-TPOsup), right hippocampus (R-HIP), left medial temporal gyrus (L-MTG) and left hippocampus in HM patients were significantly lower than those of healthy subjects. In the left temporal pole-superior temporal gyrus (L-TPOsup), right orbital part of middle frontal gyrus (RO-MFG), left fusiform gyrus (L-FG), left cerebellum superior (L-Cbe6), left middle temporal gyrus (L-MTG), right thalamus (R-THA), and right hippocampus, FC values were also significantly lower. Conclusion: Brain dysfunction was observed in various regions of the HM patients, suggesting the existence of neurobiological alterations that could lead to impairments in visual cognition, movement, emotional processing, and visual memory.

Exploration of static functional connectivity and dynamic functional connectivity alterations in the primary visual cortex among patients with high myopia via seed-based functional connectivity analysis.

Aim: This study was conducted to explore differences in static functional connectivity (sFC) and dynamic functional connectivity (dFC) alteration patterns in the primary visual area (V1) among high myopia (HM) patients and healthy controls (HCs) via seed-based functional connectivity (FC) analysis. Methods: Resting-state functional magnetic resonance imaging (fMRI) scans were performed on 82 HM patients and 59 HCs who were closely matched for age, sex, and weight. Seed-based FC analysis was performed to identify alterations in the sFC and dFC patterns of the V1 in HM patients and HCs. Associations between mean sFC and dFC signal values and clinical symptoms in distinct brain areas among HM patients were identified via correlation analysis. Static and dynamic changes in brain activity in HM patients were investigated by assessments of sFC and dFC via calculation of the total time series mean and sliding-window analysis. Results: In the left anterior cingulate gyrus (L-ACG)/left superior parietal gyrus (L-SPG) and left V1, sFC values were significantly greater in HM patients than in HCs. In the L-ACG and right V1, sFC values were also significantly greater in HM patients than in HCs [two-tailed, voxel-level P < 0.01, Gaussian random field (GRF) correction, cluster-level P < 0.05]. In the left calcarine cortex (L-CAL) and left V1, dFC values were significantly lower in HM patients than in HCs. In the right lingual gyrus (R-LING) and right V1, dFC values were also significantly lower in HM patients than in HCs (two-tailed, voxel-level P < 0.01, GRF correction, cluster-level P < 0.05). Conclusion: Patients with HM exhibited significantly disturbed FC between the V1 and various brain regions, including L-ACG, L-SPG, L-CAL, and R-LING. This disturbance suggests that patients with HM could exhibit impaired cognitive and emotional processing functions, top-down control of visual attention, and visual information processing functions. HM patients and HCs could be distinguished from each other with high accuracy using sFC and dFC variabilities. These findings may help to identify the neural mechanism of decreased visual performance in HM patients.

Machine learning analysis reveals aberrant dynamic changes in amplitude of low-frequency fluctuations among patients with retinal detachment.

Background: There is increasing evidence that patients with retinal detachment (RD) have aberrant brain activity. However, neuroimaging investigations remain focused on static changes in brain activity among RD patients. There is limited knowledge regarding the characteristics of dynamic brain activity in RD patients. Aim: This study evaluated changes in dynamic brain activity among RD patients, using a dynamic amplitude of low-frequency fluctuation (dALFF), k-means clustering method and support vector machine (SVM) classification approach. Methods: We investigated inter-group disparities of dALFF indices under three different time window sizes using resting-state functional magnetic resonance imaging (rs-fMRI) data from 23 RD patients and 24 demographically matched healthy controls (HCs). The k-means clustering method was performed to analyze specific dALFF states and related temporal properties. Additionally, we selected altered dALFF values under three distinct conditions as classification features for distinguishing RD patients from HCs using an SVM classifier. Results: RD patients exhibited dynamic changes in local intrinsic indicators of brain activity. Compared with HCs, RD patients displayed increased dALFF in the bilateral middle frontal gyrus, left putamen (Putamen_L), left superior occipital gyrus (Occipital_Sup_L), left middle occipital gyrus (Occipital_Mid_L), right calcarine (Calcarine_R), right middle temporal gyrus (Temporal_Mid_R), and right inferior frontal gyrus (Frontal_Inf_Tri_R). Additionally, RD patients showed significantly decreased dALFF values in the right superior parietal gyrus (Parietal_Sup_R) and right paracentral lobule (Paracentral_Lobule_R) [two-tailed, voxel-level p < 0.05, Gaussian random field (GRF) correction, cluster-level p < 0.05]. For dALFF, we derived 3 or 4 states of ALFF that occurred repeatedly. There were differences in state distribution and state properties between RD and HC groups. The number of transitions between the dALFF states was higher in the RD group than in the HC group. Based on dALFF values in various brain regions, the overall accuracies of SVM classification were 97.87, 100, and 93.62% under three different time windows; area under the curve values were 0.99, 1.00, and 0.95, respectively. No correlation was found between hamilton anxiety (HAMA) scores and regional dALFF. Conclusion: Our findings offer important insights concerning the neuropathology that underlies RD and provide robust evidence that dALFF, a local indicator of brain activity, may be useful for clinical diagnosis.

The role of DNA methylation in catechol-enhanced erythroid differentiation of K562 cells.

Catechol is one of phenolic metabolites of benzene in vivo. Catechol is also widely used in pharmaceutical and chemical industries. In addition, fruits, vegetables and cigarette smoke also contain catechol. Our precious study showed that several benzene metabolites (phenol, hydroquinone, and 1,2,4-benzenetriol) inhibited erythroid differentiation of K562 cells. In present study, the effect of catechol on erythroid differentiation of K562 cells was investigated. Moreover, to address the role of DNA methylation in catechol-induced effect on erythroid differentiation in K562 cells, methylation levels of erythroid-specific genes were analyzed by Quantitative MassARRAY methylation analysis platform. Benzidine staining showed that exposure to catechol enhanced hemin-induced hemoglobin accumulation in K562 cells in concentration- and time-dependent manners. The mRNA expression of erythroid specific genes, including α-globin, ß-globin, γ-globin, erythroid 5-aminolevulinate synthase, erythroid porphobilinogen deaminase, and transcription factor GATA-1 genes, showed a significant concentration-dependent increase in catechol-treated K562 cells. The exposure to catechol caused a decrease in DNA methylation levels at a few CpG sites in some erythroid specific genes including α-globin, ß-globin and erythroid porphobilinogen deaminase genes. These results indicated that catechol improved erythroid differentiation potency of K562 cells at least partly via up-regulating transcription of some erythroid related genes, and suggested that inhibition of DNA methylation might be involved in up-regulated expression of some erythroid related genes.

[Improving the signal to noise ratio of spectroscopy for tongue inspection by optical modulation].

In order to solve the problem that the collected spectrum was influenced seriously by the environment light, optical modulation was used to improve the signal to noise ratio of spectroscopy-tongue inspection for the first time. First, reference light was modulated by reticle in this system; second, the reflect spectrum of the same measured object was collected under the condition that it was influenced by green, purple, red laser and environment light respectively; thirdly, the DFT was used to demodulate the collected spectrum data; the maximum harmonic components were extracted and normalized, then the spectral curve was drawn; by comparison, the spectral curves of the same measured object under different condition were almost the same. The experiment result showed that the optical modulation can remove the influence of the environment light; and this method can provide a new way to improve the signal to noise ratio of spectroscopy for tongue inspection.

[The effects of signal to noise ratio of instrument and number of wavelengths on the accuracy of spectral analysis].

In order to study the influence of the two factors, the signal to noise ratio (SNR) of instrument and number of wavelengths, on the accuracy of quantitative analysis in spectral modeling analysis, the influences of different SNRs, the number of wavelengths participating in partial least square regression, and multi-wavelength modeling in different SNR bands were taken into account. The relationships between these factors and quantitative analysis accuracy were explored by modeling analysis experiments. The results show that the analysis accuracy is directly related to the SNR of instrument. And increasing wavelengths, especial the ones with high SNR, reflects a phenomenon that four times of wavelength number will bring 2 times accuracy increasing, which can compensate for the lack of SNR. The research provides the experimental basis and theoretical guidance to improve the model's quality and reduce the prediction error by the utilization and improvement of the instrument's SNR and the reasonable choice of wavelengths and bands of modeling.

[The analysis for improving the SNR of blood components noninvasive measurement with DS method].

In order to increase the accuracy of blood components measurement and enhance the stability of prediction model, the quantitative signal-noise-ratio (SNR) analysis of measuring instruments based on dynamic spectrum (DS) and preprocessing method was conducted. The SNR of DS is increased after adding boxcar integrator, decreasing wavelength revolution, balancing the DS's SNR and excluding gross errors in preprocessing according to experiment results. Two volunteers were tested continuously for many times using the DS data acquiring system. The correlation coefficients of the each volunteer's DS data was increased from 0.934 and 0.953 to 0.991 and 0.987, respectively. Moreover, the gap between the correlation coefficient of the same volunteer's DS and different volunteers' DS is increased too, which shows that the SNR can be improved by these methods. The quantitative SNR analysis can guide the way of choosing preprocessing method efficiently, which will create the condition for clinical application of the blood components noninvasive measurement.

[Equalization of whole-band signal's SNR in the blood components noninvasive measurement].

To fully extend the category of blood components that can be noninvasively measured by dynamic spectrum (DS) method and to increase its measuring precision, an overall consideration of light source, tissue absorption and sensor's sensitivity was made. Compensating the light source and adding the telecentric lens not only expand the spectral effective detecting range, but also balance the signal-to-noise ratio (SNR) of the photoelectric pulse in the whole band equalization. The integral SNR of DS signal was increased and the measurement bandwidth was expanded. The effectiveness of this method was validated by the quality evaluation criterion of DS data: the effective detecting range of visible DS was widened from 600-1 000 nm to 500-1 135 nm; the effective detecting range of near-infrared DS was widened from 900-1 100 nm to 900-1 700 nm. The results show that the design can create the condition for detection of new blood components noninvasively, and enhance the prediction accuracy of the blood components, for which noninvasive measuring using DS method has been achieved.