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AIM: To analyse macular microvascular alterations in myopic choroidal neovascularization (mCNV) and the efficiency of anti-vascular endothelial growth factor (anti-VEGF) therapy for mCNV by optical coherence tomography angiography (OCTA). METHODS: A total of 123 patients were included in this retrospective study, divided into mCNV group, high myopia (HM) group, and normal group at the Affiliated Eye Hospital of Wenzhou Medical University from January 2017 to January 2019. Superficial vessel density, deep capillary density, foveal avascular zone (FAZ) area, A-circularity index (AI) and vessel density around the 300 μm width of the FAZ region density (FD) and the area of choroidal neovascularization (CNV) lesion (only for mCNV group) were measured on 3×3 mm2 OCTA images. FAZ area was corrected for axial length. Central macular thickness (CMT) was measured on OCT in mCNV group. Compared the parameters on OCTA of 3 groups and pre-anti-VEGF and post-anti-VEGF at 1, 2, 3, and 6mo follow-up in mCNV group. RESULTS: There were significant differences among 3 groups in superficial vessel density, deep capillary density and FD (P

Plumbagin, a natural bicyclic naphthoquinone, has diverse pharmacological properties and biological benefits against a number of disorders, including liver disease. Though plumbagin’s hepatoprotective potential attracts attention, currently no experimental evidence exists on its effectiveness against cholestatic liver injury. The present study investigated its hepatoprotection in the rat model of extrahepatic cholestasis using Bile Duct Ligation (BDL). We found that daily plumbagin supplementation protected the liver from cholestatic damage. Hepatoprotective actions of plumbagin were accompanied by reduction of Transforming Growth Factor β1 (TGF-β1)/Smad, High Mobility Group Box-1 (HMGB1)/Toll-Like Receptor-4 (TLR4), Hypoxia-Inducible Factor-1α (HIF-1α), Aryl Hydrocarbon Receptor (AhR), Heat Shock Protein 90 (HSP90), caveolin-1, NF-κB/AP-1, Dynamin Related Protein-1 (Drp1), malondialdehyde level, Interleukin-1β (IL-1β), p62/SQSTM1, and caspase 3 as well as increase of Farnesoid X Receptor (FXR), bile acid efflux transporters, glutathione, LC3-II, Beclin1, and nuclear NF-E2-Related Factor-2 (Nrf2) and Transcription Factor EB (TFEB). The activation of nuclear Nrf2 caused by plumbagin correlated well with the improvement in bile acid retention, liver histology, serum biochemical, ductular reaction, mitochondrial dysfunction, oxidative stress, inflammation, apoptosis, impaired autophagy, and fibrosis, involving interplay of multiple intracellular signaling pathways. Plumbagin is likely a candidate drug to protect the liver from cholestatic damages. Despite the promising findings from this study, translational implication of plumbagin on cholestatic liver injury warrants further investigation.

AIM: To quantify changes in peripapillary vessel density in patients with type 2 diabetic mellitus(DM)without clinical features of diabetic retinopathy(DR)by OCT angiography(OCTA). METHODS:A retrospective clinical study. From January to December 2019, 38 type 2 DM patients without DR(38 eyes, NDR group)and 30 normal subjects(30 eyes, control group)in Eye Hospital of Wenzhou Medical University at Hangzhou were included in the study. The optic nerve head was scanned by OCTA with HD 4.5mm×4.5mm imaging scanning mode for all subjects.The software automatically divides the peripapillary region into 8 sectors, designated as nasal superior(NS), nasal inferior(NI), inferior nasal(IN), inferior tempo(IT), tempo inferior(TI), tempo superior(TS), superior tempo(ST)and superior nasal(SN). Radial peripapillary capillaries vessel density(ppVD)and peripapillary retinal nerve fiber layer(pRNFL)thickness of entire peripapillary area and each sector were measured. The discrepancy of ppVD and pRNFL thickness between the two groups was also analyzed. Pearson correlation analysis was used to analyze the correlation between ppVD and pRNFL in each quadrant of NDR group. RESULTS:The mean ppVD value and NS,NI,IN,IT,TI,TS,ST and SN sector values were all significantly lower in NDR group compared to normal controls(all P0.05). Pearson correlation analysis showed that the significant positive correlation was found between ppVD and pRNFL thickness in TI, TS, SN, NS and NI sector(r=0.578, 0.427, 0.577, 0.397, 0.317; all P

A two-dimensional plasma–wave interaction model, which is based on the cold collisional plasma dielectric tensor, is applied to investigate the wave propagation and power depositions under different magnetic configurations in helicon plasmas. The varied magnetic configurations are formed by changing the radius of the magnetic coil. When the magnetic coil was positioned closer to the plasma, the magnetic field within the plasma became stronger and more curved. Consequently, the simulation results show that the wave propagation and power deposition in plasmas follow the curved magnetic field lines. In the axial direction, the periodic distribution of wave fields and power deposition are clearly observed and keep consistency in helicon plasmas due to the eigenmodes of helicon waves. Furthermore, a concave dark area where the wave cannot propagate is observed in the closest magnetic coil case and leads to limited power deposition. [ABSTRACT FROM AUTHOR]

AIM: To investigate the effects of intravitreal conbercept combined with peripheral laser photocoagulation for ischemic RVO-ME.METHODS: A retrospective clinical study. Totally 39 patients(39 eyes)were included in this study since 2014-10 to 2018-11, who were diagnosed ischemic RVO-ME in Eye Hospital of Wenzhou Medical University. There were 14 CRVO and 25 BRVO. All patients were given intravitreal conbercept combined with peripheral laser photocoagulation. BCVA, OCT were examined before and after treatment. RESULTS:BCVA of 1, 2, 3, 6mo(0.67±0.49, 0.56±0.41, 0.62±0.52, 0.47±0.40)after treatment was significantly improved compared to base line(0.99±0.57)(PPr=0.78, Pr=0.25, P=0.13).CONCLUSION: Intravitreal conbercept combined with peripheral laser photocoagulation is a effective approach for ischemic RVO-ME, which can significantly improve BCVA and decrease CMT.

Abstract Background Several heart failure (HF) risk models exist, however, most of them perform poorly when applied to real-world situations. This study aimed to develop a convenient and efficient risk model to identify patients with high readmission risk within 90 days of HF. Methods A multivariate logistic regression model was used to predict the risk of 90-day readmission. Data were extracted from electronic medical records from January 1, 2017 to December 31, 2017 and follow-up records of patients with HF within 3 months after discharge. Model performance was evaluated using a receiver operating characteristic curve. All statistical analysis was done using R version 3.5.0. Results A total of 350 patients met the inclusion criterion of being readmitted within in 90 days. All data sets were randomly divided into derivation and validation cohorts at a 7/3 ratio. The baseline data were fairly consistent among the derivation and validation cohorts. The variables most clearly related to readmission were logarithm of serum N-terminal pro b-type natriuretic peptide (NT-proBNP) level, red cell volume distribution width (RDW-CV), and Charlson comorbidity index (CCI). The model had good discriminatory ability (C-statistic = 0.73). Conclusions We developed and validated a multivariate logistic regression model to predict the 90-day readmission risk for Chinese patients with HF. The predictors included in the model are derived from electronic medical record (EMR) admission data, making it easier for physicians and pharmacists to identify high-risk patients and tailor more intensive precautionary strategies.

Metformin may offer benefits to certain cancer populations experiencing metabolic abnormalities. To extend the anticancer studies of metformin, a tumor model was established through the implantation of murine Lewis Lung Carcinoma (LLC) cells to Normal Diet (ND)-fed and High-Fat Diet (HFD)-fed C57BL/6 mice. The HFD-fed mice displayed metabolic and pro-inflammatory alterations together with accompanying aggressive tumor growth. Metformin mitigated tumor growth in HFD-fed mice, paralleled by reductions in circulating glucose, insulin, soluble P-selectin, TGF-β1 and High Mobility Group Box-1 (HMGB1), as well as tumor expression of cell proliferation, aerobic glycolysis, glutaminolysis, platelets and neutrophils molecules. The suppressive effects of metformin on cell proliferation, migration and oncogenic signaling molecules were confirmed in cell study. Moreover, tumor-bearing HFD-fed mice had higher contents of circulating and tumor immunopositivity of Neutrophil Extracellular Traps (NETs)-associated molecules, with a suppressive effect from metformin. Data taken from neutrophil studies confirmed the inhibitory effect that metformin has on NET formation induced by HMGB1. Furthermore, HMGB1 was identified as a promoting molecule to boost the transition process towards NETs. The current study shows that metabolic, pro-inflammatory and NET alterations appear to play roles in the obesity-driven aggressiveness of cancer, while also representing candidate targets for anticancer potential of metformin.

We propose and demonstrate a curvature sensor based on long-period fiber grating (LPFG) with asymmetric index modulation. The LPFG is fabricated in single-mode fiber with femtosecond laser micromachining. The grating structure is not introduced in the central fiber core, but is located off-axis with a distance of a few micrometers. Experimental results indicate that the offset distance has direct influence on the grating spectra. By utilizing such an asymmetric structure, two-dimensional vector curvature sensing can be realized. For an LPFG with an offset distance of 6 μm, the curvature sensitivity is around 29 nm/m−1 in the 0° and 180° direction and about 20 nm/m−1 in the 90° and 270° direction. The difference in curvature sensitivity in different bending directions makes the sensor capable of distinguishing the curvature orientation. The temperature response of the sensor is also experimentally investigated, and results indicate that the sensor has a very low temperature cross-sensitivity of 0.003 m−1/°C. The characteristics of high curvature sensitivity, two-dimensional bending direction identification, and compact structure make the device an ideal candidate to be applied in the field of power grid health monitoring and intelligent robotics. [ABSTRACT FROM AUTHOR]

Introduction: Conventionally, a combination of four separate drugs (ethambutol, isoniazid, rifampicin, and pyrazinamide [EHRZ]) is the first-line pharmacotherapy for pulmonary tuberculosis (TB). In recent years, fixed-dose combination (FDC) formulation, where a single tablet contains the active ingredients of four aforementioned drugs, is gaining popularity due to its ease of administration. Objective: To compare the real-world effectiveness of EHRZ and FDC treatment groups on a cohort registry by investigating the sputum conversion rate and treatment outcomes of both groups. Methods: A total of 11,489 patients' data were extracted from the Sabah TB registry between January 2012 and June 2016, including EHRZ (n = 4188) and FDC (n = 7301) patients. Then, 1:1 propensity score matching was adopted to reduce the baseline bias. Caliper matching was conducted with maximum tolerance score set at 0.001. Confounders included in the propensity score matching were gender, nationality, diabetes, HIV status, smoking status, and chest X-ray status. Successful matching provided 4188 matched pairs (n = 8376) for final analysis. Results: In this matched cohort of 4188 pairs, the 2-month sputum conversion rate of FDC group was significantly higher than the EHRZ group (96.3% vs. 94.3%; P < 0.001) whereas 6-month sputum conversion of both groups showed no significant difference. Treatment outcomes such as noncompliance rate, failure rate, and success rate have no significant difference (P > 0.05) in both the treatment groups. There was an incidental finding of reduced death rate among FDC group compared to the EHRZ group (0.2% vs. 0.5%; P = 0.034). Conclusion: The FDC formulation has better sputum conversion rate at 2 months compared to conventional EHRZ regime as separate-drug formulation. It was also observed that FDC has a slight protective effect against all-cause death among TB patients. This protective effect of FDC, however, still needs to be proven further.

Spinal microglia are crucial to neuronal hyper-excitability and pain hypersensitivity. The local anesthetic bupivacaine is commonly used for both peripheral and spinal anesthesia. The pain-relief effects resulting from the peripheral and systemic administration of bupivacaine have been previously reported. In this study, the preventive effects of intrathecal bupivacaine administration against neuropathic pain were revealed in a rat model of sciatic nerve chronic constriction injury (CCI). Using a CCI rat model, pain hypersensitivity, characterized by mechanical allodynia and thermal hyperalgesia, correlated well with microglia M1 polarization, activation and pro-inflammatory cytokine expression in both spinal cord dorsal horns and sciatic nerves. Bupivacaine attenuated pain behaviors and inflammatory alternations. We further identified that the Interferon Regulatory Factor 5 (IRF5)/P2X Purinoceptor 4 (P2X4R) and High Mobility Group Box 1 (HMGB1)/Toll-Like Receptor 4 (TLR4)/NF-κB inflammatory axes may each play pivotal roles in the acquisition of microglia M1 polarization and pro-inflammatory cytokine expression under CCI insult. The relief of pain paralleled with the suppression of microglia M1 polarization, elevation of microglia M2 polarization, and inhibition of IRF5/P2X4R and HMGB1/TLR4/NF-κB in both the spinal cord dorsal horns and sciatic nerve. Our findings provide molecular and biochemical evidence for the anti-neuropathic effect of preventive bupivacaine.

18β-Glycyrrhetinic acid is a nutraceutical agent with promising hepatoprotective effects. Its protective mechanisms against cholestatic liver injury were further investigated in a rodent model of extrahepatic cholestasis caused by Bile Duct Ligation (BDL) in rats. The daily oral administration of 18β-Glycyrrhetinic acid improved liver histology, serum biochemicals, ductular reaction, oxidative stress, inflammation, apoptosis, impaired autophagy, and fibrosis. 18β-Glycyrrhetinic acid alleviated the BDL-induced hepatic and systemic retention of bile acids, matrix-producing cell activation, hepatic collagen deposition, Transforming Growth Factor beta-1/Smad activation, malondialdehyde elevation, glutathione reduction, High Mobility Group Box-1/Toll-Like Receptor-4 activation, NF-κB activation, inflammatory cell infiltration/accumulation, Interleukin-1β expression, Signal Transducer and Activator of Transcription-1 activation, Endoplasmic Reticulum stress, impairment autophagy, and caspase 3 activation. Conversely, the protein expression of Sirt1, Farnesoid X Receptor, nuclear NF-E2-Related Factor-2, Transcription Factor EB, bile acid efflux transporters, and LC3-II, as well as the protein phosphorylation of AMP-Activated Protein Kinase, was promoted in 18β-Glycyrrhetinic acid-treated BDL rats. The hepatoprotective effects of 18β-Glycyrrhetinic acid in the present investigation correlated well with co-activation and possible interactions among Sirt, FXR, and Nrf2. The concurrent or concomitant activation of Sirt1, FXR, and Nrf2 not only restored the homeostatic regulation of bile acid metabolism, but also alleviated oxidative stress, inflammation, apoptosis, impaired autophagy, and fibrosis.

How are limited resources efficiently allocated among different innovation populations? The performances of different innovation populations are quite different with either synergy or competition between them. If the innovation population is kept under an appropriate scale, full use can be made of the allocated resources. The maximization of the development and performance for a certain scale of innovation population is a typical multichoice development problem. Therefore, the scale optimization of the innovation population should be analyzed. According to the population dynamics, a resource constraint model for the growth of innovation population is developed, and the growth of innovation population under resource constraints is in equilibrium accordingly. With the help of a multichoice goal programming model, the scale optimization of innovation population performance can be obtained. The results of the resource constraint model and multichoice goal programming model are used to determine the optimal scale of the innovation population. From the panel data of the innovation population in Jiangsu Province from 2000 to 2017, we have found that R&D investment was the main innovation resource variable and that patent number was the main innovation output variable. Based on these data, the scale optimization of the innovation population under resource constraints can be calculated. The results of the study show that, in the observation period, the enterprise innovation population is often in the appropriate scale state. The scale development of enterprise innovation population is often more suitable for innovation ecosystem than that of scientific research institutions. According to these results, the government can provide appropriate guiding policies and incentives for different innovation populations. The innovative population can adjust its own development strategy and plan in time accordingly.