Dual-responsive nanocarriers for efficient cytosolic protein delivery and CRISPR-Cas9 gene therapy of inflammatory skin disorders.

Developing protein drugs that can target intracellular sites remains a challenge due to their inadequate membrane permeability. Efficient carriers for cytosolic protein delivery are required for protein-based drugs, cancer vaccines, and CRISPR-Cas9 gene therapies. Here, we report a screening process to identify highly efficient materials for cytosolic protein delivery from a library of dual-functionalized polymers bearing both boronate and lipoic acid moieties. Both ligands were found to be crucial for protein binding, endosomal escape, and intracellular protein release. Polymers with higher grafting ratios exhibit remarkable efficacies in cytosolic protein delivery including enzymes, monoclonal antibodies, and Cas9 ribonucleoprotein while preserving their activity. Optimal polymer successfully delivered Cas9 ribonucleoprotein targeting NLRP3 to disrupt NLRP3 inflammasomes in vivo and ameliorate inflammation in a mouse model of psoriasis. Our study presents a promising option for the discovery of highly efficient materials tailored for cytosolic delivery of specific proteins and complexes such as Cas9 ribonucleoprotein.

On-Chip Fabrication-Tolerant Exceptional Points Based on Dual-Scatterer Engineering.

The intriguing and anomalous optical characteristics of exceptional points (EPs) in optical resonators have attracted significant attention. While EP-related phenomena have been observed by perturbing resonators with off-chip components, implementing EPs fully on-chip remains challenging due to their extreme susceptibility to fabrication errors. In this Letter, we propose a succinct and compact approach to reach EP in an on-chip integrated silicon microring resonator by manipulating the evolution of backscatterings with two nanocylinders of disparate diameters. The theoretical analysis unveils that the fabrication constraints could be significantly relieved by increasing the difference in diameters of the nanocylinders. The evolution from non-EP to EP is traced experimentally through the step-by-step tuning of the angular and radial positions of nanocylinders. The proposed method opens a pathway toward the on-chip high-density integration of non-Hermitian devices.

CHOROIDAL AND RETINAL ABNORMALITIES IN CUSHING SYNDROME: Correlation with the Cortisol Level.

PURPOSE: To investigate the structure and blood flow of the retina and choroid in Cushing syndrome and their relationship with cortisol levels. METHODS: A consecutive series of patients with Cushing syndrome with adrenocortical carcinoma were included in this study. Cortisol levels gradually returned to normal after adrenalectomy. Optical coherence tomography and optical coherence tomography angiography were used to assess patients with Cushing syndrome before and after the surgery for retina and choroid. Correlation analysis was performed between cortisol level and fundus changes. RESULTS: Compared with normal cortisol levels, patients with Cushing syndrome had significantly lower central macular thickness with increased cortisol level (220.82 ± 16.59 µ m and 223.68 ± 15.78 µ m, P = 0.019). However, the central choroidal thickness was higher with increased cortisol level (255.18 ± 105.89 µ m and 205.94 ± 87.04 µ m, P < 0.001). The choriocapillaris flow area was higher with increased cortisol level (2.05 ± 0.14 mm 2 and 2.00 ± 0.13 mm 2 , P = 0.02). The change of choriocapillaris flow area was correlated with the score of Huaxi Emotional-distress Index and 24-hour urine-free cortisol (24h-UFC). CONCLUSION: The increased cortisol level was correlated with lesser central macular thickness and thicker central choroidal thickness. The decrease of choriocapillaris flow area was correlated with 24h-UFC, indicating the effect of increased cortisol level on choroidal vessels.

The Association Between Lipid Profile and Subfoveal Choroidal Thickness in Chinese Patients with Proliferative Diabetic Retinopathy Secondary to Type 2 Diabetes.

Introduction: Extensive studies have studied the factors associated with subfoveal choroidal thickness (SFCT). However, studies of the association between lipid profile and SFCT in patients with proliferative diabetic retinopathy (PDR) in type 2 diabetes remain limited. Thus, we aimed to investigate the relationship between lipid profile and SFCT in patients with PDR. Materials and Methods: This was a retrospective cross-sectional study. The included participants were inpatients who underwent vitrectomy for PDR with type 2 diabetes and contralateral eyes of PDR patients meeting the criteria. Multivariate linear regression analysis was used to determine the independent association between lipid profile and SFCT. Results: A total of 131 participants with PDR were enrolled in the final analysis. The average age of the participants was 55.76 ± 9.88 years, and the average SFCT was 276.10 ± 92.92 µm. Multivariate linear regression model results showed that in the fully adjusted model, total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) had a negative association with SFCT (ß = -16.51, 95% CI: -29.57, -3.46; P = 0.0148; ß = -42.65, 95% CI: -82.60, -2.70; P = 0.0390; ß = -17.89, 95% CI: -33.24, -2.54; P = 0.0245, respectively), while triglyceride was not significantly associated with SFCT (ß = 5.23, 95% CI: -18.57, 29.02; P = 0.6678). Furthermore, the results of stratified analysis showed that except for triglyceride, the trends of total cholesterol, HDL-C, LDL-C, and SFCT were consistent among different stratifications in participants. Conclusion: The cholesterol profile had a significant negative association with SFCT in Chinese PDR patients, but triglyceride was not significantly associated with SFCT. This suggests that these systemic imbalances contribute to choroidal changes, and often coexist in diabetic patients.

Optical noise characteristics of injection-locked epitaxial quantum dot lasers on silicon.

This work theoretically investigates the relative intensity noise (RIN) and spectral linewidth characteristics of epitaxial quantum dot (QD) lasers on silicon subject to optical injection. The results show that the RIN of QD lasers can be reduced by optical injection, hence a reduction of 10 dB is achieved which leads to a RIN as low as -167.5 dB/Hz in the stable injection-locked area. Furthermore, the spectral linewidth of the QD laser can be greatly improved through the optical injection locked scheme. It is reduced from 556.5 kHz to 9 kHz with injection ratio of -60 dB and can be further reduced down to 1.5 Hz with injection ratio of 0 dB. This work provides an effective method for designing low intensity noise and ultra-narrow linewidth QD laser sources for photonics integrated circuits on silicon.

Association between the site of clear corneal Phakic intraocular lens implantation incisions and the inflow of ocular surface fluid into the anterior chamber.

Background: Posterior chamber phakic intraocular implantable collamer lens (ICL) implantation is an effective surgical option for the management of myopia. Over the past few years, the number of ICL surgeries has significantly increased. Postoperative inflammation and endophthalmitis are among the most serious complications after successful ICL surgery. Sometimes, when the blepharospasm is removed at the end of surgery, a small amount of the ocular surface fluid will flow into the anterior chamber, which can lead to an increased risk of infection and inflammation. However, little attention has been paid to this phenomenon. Purpose: We conducted a retrospective study to compare the incidence of extraocular fluid inflow into the eye through the clear corneal incision (CCI) at two different positions (superior and temporal sides). Methods: A total of 116 patients with myopia underwent superior CCI ICL implantation (n = 58) or temporal CCI ICL implantation (n = 58) at our hospital from October to December 2021. The incidence of conjunctival sac fluid entering the anterior chamber after eyelid fixative was removed was compared in both groups. Results: Both groups were well matched in all parameters. Ocular surface fluid inflow into the anterior chamber was significantly higher in the superior CCI group (25/58, 47.1%) than in the temporal CCI group (1/58, 1.7%) (p < 0.05). Conclusion: In the patients with ICL implantation, the temporal CCI was better than the superior CCI in avoiding the ocular surface fluid inflow into the anterior chamber, and the potential risk of infection and inflammation was lower.

Efficient intracellular and in vivo delivery of toxin proteins by a ROS-responsive polymer for cancer therapy.

Rational design of efficient cytosolic protein delivery carriers holds enormous promise for biotherapeutics development. Several delivery systems have been developed during the past decades, while tailoring the balance between extracellular protein binding and intracellular cargo release is still challenging. In this study, we synthesized a series of oxygen-sensitive reactive polymers, rich in boron, by radical polymerization and post-modification for cytosolic protein delivery in vitro and in vivo. The introduction of boronate building blocks into the polymer scaffold significantly enhanced its protein binding affinity, and the polymer/protein complexes with high stability were obtained by tailoring the molecular ratios between the boronate ligands and the amine groups. The lead material screened from the polymer library exhibited efficient protein delivery efficacy that can release cargo proteins in cytosol in a reactive oxygen species responsive manner, which enables intracellular delivery of proteins with maintained bioactivity. In addition, the polymer-based nanoformulations efficiently delivered saporin, a toxin protein, into osteosarcoma cells and tumor tissues, and exhibited high therapeutic efficacy in an osteosarcoma mouse model. The synthesized polymer in this study can be developed as a promising nanocarrier for cytosolic delivery of protein therapeutics to treat a variety of diseases.

Retinal pigment epithelium aperture in acute central serous chorioretinopathy: Another novel possible pathological mechanism.

PURPOSE: To present retinal pigment epithelium (RPE) aperture related to an avascular pigment epithelium detachment (PED) secondary to acute central serous chorioretinopathy (CSC). METHODS: Case report. RESULTS: A 47-year-old man diagnosed as acute CSC presented with RPE aperture in the superonasal area of the macula in his left eye during follow-up. At 2-week follow-up, his decimal best-corrected visual acuity (BCVA) was improved from 0.08 to 0.6 and subretinal fluid was partially absorbed. However, the near-infrared reflectance demonstrated a round mild hyperreflective lesion on the superonasal area of the macula. On spectral-domain optical coherence tomography (SD-OCT), RPE band of the round lesion discontinued but RPE fractured edges without shrinkage and curling. Fundus autofluorescence (FAF) showed RPE aperture appeared as round hypoautofluorescence and hyperautofluorescence outlined its borderline. OCT angiography demonstrated that no evidence of neovascularization within the sub-RPE space. En Face OCT confirmed that the RPE aperture developed at the edge of the PED lesion. At 8-month follow-up, his decimal BCVA was improved to 1.0 and SD-OCT demonstrated spontaneous resolution of subretinal fluid and restoration of RPE structure, with complete flattening of PED. However, FAF revealed hypoautofluorescence mingled with slight hyperautofluorescence within the lesion. CONCLUSIONS: To the best of our knowledge, this is the first report of an RPE aperture secondary to acute CSC. Our case indicated another novel possible pathological mechanism that in the relatively healthy RPE, increased hydrostatic pressure simply itself could contribute to RPE aperture.

Fundus changes of Parry-Romberg syndrome: A report of three cases and literature review.

PURPOSE: To report three cases of Parry-Romberg syndrome (PRS) with progressive hemifacial atrophy and similar fundus changes. METHODS: Retrospective case series of three patients who presented to the ophthalmology department with blurred vision in one eye. All of them underwent three-dimensional reconstruction of head computed tomography (CT), related physical examinations, and also monthly ocular examinations of both eyes, including the slit-lamp microscope, fundus autofluorescence, optical coherence tomography (OCT), and fundus fluorescein angiography (FFA). We also reviewed the current literature about the fundus change in PRS from inception to March 2020 via PubMed. RESULTS: Coats-like fundus and exudative retinal detachment were found in all three eyes of three patients during the follow-up. No systematic changes were found except for hemifacial atrophy. The final diagnoses of these three patients were PRS. CONCLUSION: Only a subset of PRS patients have concomitant ocular changes, but it still should be noticed that the diagnosis of PRS should be considered if adults presented with Coats-like retinopathy and hemifacial atrophy.

Comparative Efficacy of Pharmacotherapy for Macular Edema Secondary to Retinal Vein Occlusion: A Network Meta-analysis.

Purpose: This network meta-analysis was conducted to obtain the relative effectiveness of different pharmacotherapy of macular edema secondary to retinal vein occlusion (RVO) by summarizing all available evidences. Methods: PubMed, Embase, and Cochrane Library databases were searched for all relevant randomized controlled trials. The outcomes were estimated through a network meta-analysis, including the mean change in best-corrected visual acuity (BCVA) from baseline, the proportion of patients who gained ≥15 letters in BCVA from baseline, the mean change in central retinal thickness (CRT). Results: We identified 15 randomized controlled trials (RCTs) involving 3,431 patients with RVO in our study. Different therapeutic regimens were compared including three anti-vascular endothelial growth factor (VEGF) agents (ranibizumab, bevacizumab, and aflibercept), ranibizumab with laser, dexamethasone intravitreal implant, and laser. For branch RVO, ranibizumab 0.5 mg monthly [weighted mean difference (WMD) = 11, 95% confidence intervals (CrI) 3.6 to 19], ranibizumab 0.5 mg 3 + pro re nata (WMD = 9.4, 95% CrI 0.43-18) is most effective in terms of changes of BCVA and 15 letters or more of BCVA improvement. For central RVO, three anti-VEGF regimens can improve visual acuity and there is no significant difference of efficacy among ranibizumab, bevacizumab and aflibercept (p > 0.05). Ranibizumab 0.5 mg monthly could achieve additional efficacy in CRT reduction in eyes with branch RVO or central RVO (WMD = -130, 95% CrI -400 to 140 or WMD = -280, 95% CrI -590 to 16)). Dexamethasone intravitreal implant (WMD = 1.7, 95% CrI -4.2 to 7.1 or WMD = 0.38, 95% CrI -9.8 to 8.8)) did not show a significant improvement in visual acuity at the end of 6 months follow-up in eyes with branch RVO or central RVO. Conclusion: In summary, this network meta-analysis demonstrated several anti-VEGF agents had equivalent effects on mean visual acuity changes and anatomical recovery in 6 months in eyes with branch or central RVO. Only one injection of dexamethasone intravitreal implant in 6 months could not maintain the visual benefit. Patients and clinicians could choose pharmacotherapies with further consideration toward personal factors.

Pyroptosis: A New Insight Into Eye Disease Therapy.

Pyroptosis is a lytic form of programmed cell death mediated by gasdermins (GSDMs) with pore-forming activity in response to certain exogenous and endogenous stimuli. The inflammasomes are intracellular multiprotein complexes consisting of pattern recognition receptors, an adaptor protein ASC (apoptosis speck-like protein), and caspase-1 and cause autocatalytic activation of caspase-1, which cleaves gasdermin D (GSDMD), inducing pyroptosis accompanied by cytokine release. In recent years, the pathogenic roles of inflammasomes and pyroptosis in multiple eye diseases, including keratitis, dry eyes, cataracts, glaucoma, uveitis, age-related macular degeneration, and diabetic retinopathy, have been continuously confirmed. Inhibiting inflammasome activation and abnormal pyroptosis in eyes generally attenuates inflammation and benefits prognosis. Therefore, insight into the pathogenesis underlying pyroptosis and inflammasome development in various types of eye diseases may provide new therapeutic strategies for ocular disorders. Inhibitors of pyroptosis, such as NLRP3, caspase-1, and GSDMD inhibitors, have been proven to be effective in many eye diseases. The purpose of this article is to illuminate the mechanism underlying inflammasome activation and pyroptosis and emphasize its crucial role in various ocular disorders. In addition, we review the application of pyroptosis modulators in eye diseases.

Uncovering recent progress in nanostructured light-emitters for information and communication technologies.

Semiconductor nanostructures with low dimensionality like quantum dots and quantum dashes are one of the best attractive and heuristic solutions for achieving high performance photonic devices. When one or more spatial dimensions of the nanocrystal approach the de Broglie wavelength, nanoscale size effects create a spatial quantization of carriers leading to a complete discretization of energy levels along with additional quantum phenomena like entangled-photon generation or squeezed states of light among others. This article reviews our recent findings and prospects on nanostructure based light emitters where active region is made with quantum-dot and quantum-dash nanostructures. Many applications ranging from silicon-based integrated technologies to quantum information systems rely on the utilization of such laser sources. Here, we link the material and fundamental properties with the device physics. For this purpose, spectral linewidth, polarization anisotropy, optical nonlinearities as well as microwave, dynamic and nonlinear properties are closely examined. The paper focuses on photonic devices grown on native substrates (InP and GaAs) as well as those heterogeneously and epitaxially grown on silicon substrate. This research pipelines the most exciting recent innovation developed around light emitters using nanostructures as gain media and highlights the importance of nanotechnologies on industry and society especially for shaping the future information and communication society.

Association between neonatal hyperglycemia and retinopathy of prematurity: a meta-analysis.

Through a meta-analysis, we aimed to investigate whether neonatal hyperglycemia was associated with an increased risk of retinopathy of prematurity (ROP) by summarizing all available observational evidence. We searched online databases for studies published prior to December 2020; 26745 neonates with 3227 cases of ROP in 11 case-control studies and 997 neonates with 496 cases of hyperglycemia in 5 cohort studies were included. The results showed that the association between hyperglycemia and the occurrence of ROP was statistically significant in case-control studies (OR 3.93, 95% CI 2.36-6.53) and cohort studies (OR 1.70, 95% CI 1.11-2.60). Besides, the borderline significant association between the duration of hyperglycemia and ROP was observed in case-control studies (MD = 1.96, 95% CI 0.90-3.03; adjusted OR = 1.08, 95% CI 1.01-1.15). Furthermore, we found that the mean blood glucose level is higher in the ROP group than the non-ROP group in case-control studies (MD = 14.86, 95% CI 5.06-24.66) and the mean blood glucose level is higher in the hyperglycemia group than in the non-hyperglycemia group (MD = 86.54, 95% CI 11.03-162.05). However, after adjusting other confounders, the association between the mean blood glucose level and ROP varied in cohort studies (OR 1.96, 95% CI 1.23-3.13) and case-control studies (OR 1.02, 95% CI 1.00-1.05).Conclusion: This meta-analysis demonstrates that preterm infants with hyperglycemia have a tendency to increase the risk of ROP. Further studies will be required to achieve a firm conclusion for hyperglycemia and ROP and promote a better understanding of the prevention of ROP.Trial registration: CRD42021228733 What is Known: • Hyperglycemia including the duration and daily mean blood glucose concentration has been associated with the risk of developing ROP in some clinical studies. Current evidence cannot reach a consensus on whether neonatal hyperglycemia is a risk factor for ROP. What is New: • This meta-analysis demonstrates that preterm infants with hyperglycemia have a tendency to increase the risk of ROP. • While the association between the mean blood glucose level and ROP remains inconclusive.

Pachychoroid Spectrum Disease: Underlying Pathology, Classification, and Phenotypes.

PURPOSE: Pachychoroid spectrum disease encompasses a set of macular disorders secondary to an abnormally thick choroid. However, the pathological process underlying pachychoroid spectrum disease and its overlap with age-related macular degeneration (AMD) remain unclear. This review aimed to understand the underlying pathology, classification, and phenotypes of pachychoroid spectrum disease. METHODS: This comprehensive literature review was performed based on a search of peer-reviewed published papers relevant to the current knowledge of pachychoroid disease spectrum. RESULTS: Pachychoroid is primarily a bilateral phenomenon; the main pathological lesions include choriocapillaris attenuation and abnormally dilated pachyvessels. Chronic central serous chorioretinopathy (CSC) and pachychoroid neovasculopathy (PNV) show similar morphological changes and angiogenic cytokine levels. The subretinal fluid in PNV may not accurately indicate PNV activity. Besides, types 1 and 2 of choroidal neovascularization (CNV) may be involved in primary pachychoroidal disease. Both choroidal arteriosclerosis and higher hydrostatic pressure contribute to hyalinized choroidal arteries and aneurysmal dilatations, resulting in PNV progression to polypoidal choroidal vasculopathy (PCV). Thus, pachychoroid-related type 2 CNV and chronic CSC could be considered as PNV (IIIc) and as a precursor of PNV (IIIa), respectively. Tangled PCV on optical coherence tomography angiography that fails to develop aneurysms should be classified as a subtype of PNV or a forme fruste of PCV. CONCLUSIONS: Multiple disorders of the pachychoroid spectrum are considered as a continuous disease process, ultimately stimulated by choroidal malfunction. PCV overlaps both AMD and pachychoroid disease, especially for thin-choroid and bilateral types. The terminology and classification of pachychoroid spectrum disease should be used cautiously.

Physical exercise promotes brain remodeling by regulating epigenetics, neuroplasticity and neurotrophins.

Exercise has been shown to have beneficial effects on brain functions in humans and animals. Exercise can improve memory and learning in age-related neurodegenerative diseases. In animal models, physical exercise regulates epigenetics, promotes synaptic plasticity and hippocampal neurogenesis, regulates the expression levels of neurotrophic factors, and improves cognitive function. Therefore, exercise is very important for brain rehabilitation and remodeling. The purpose of this review is to explore the mechanisms by which exercise exerts positive effects on brain function. This knowledge implies that physical exercise can be used as a non-drug therapy for neurological diseases.

Efficacy and safety of the mineralocorticoid receptor antagonist treatment for central serous chorioretinopathy: a systematic review and meta-analysis.

OBJECTIVES: We performed a systematic review and meta-analysis to assess the efficacy and safety of the mineralocorticoid receptor antagonist (MRA) treatment for central serous chorioretinopathy (CSC). METHODS: We searched the PubMed, Embase, and the Cochrane Library to identify relevant clinical studies published prior to March 2020. The primary outcome was change in best-corrected visual acuity (BCVA), and the secondary outcomes included the subretinal fluid (SRF), subfoveal choroidal thickness (SFCT), and central macular thickness (CMT). RESULTS: Five randomized controlled trials (RCT) and four cohort studies met the inclusion criteria with a total of 352 eyes. The MRA treatment was not superior to placebo in BCVA at 1 month (WMD = -0.06, 95% CI -0.15-0.02, P = 0.15, I2 = 86%), 3 months (WMD = -0.04, 95% CI -0.14-0.06, P = 0.44, I2 = 77%) and 6 months (WMD = -0, 95% CI -0.05-0.05, P = 0.92, I2 = 0%). The MRA treatment resulted in significant reduction than the placebo in the SRF (WMD = -60.64, 95% CI -97.91 to -23.37, P = 0.001, I2 = 49%), SFCT (WMD = -39.15, 95% CI -52.58 to -25.72, P < 0.001, I2 = 0%), and CMT (WMD = -60.75, 95% CI -97.85 to -23.65, P = 0.01, I2 = 53%). CONCLUSIONS: Our meta-analysis shows that the MRA treatment can improve anatomical structure in CSC patients, but it is not effective for achieving BCVA gain. The applicant of the MRA is safe and have no severe effect.

Therapeutic Management of Ocular Ischemia in Takayasu's Arteritis: A Case-Based Systematic Review.

Background: Takayasu's arteritis (TA) is a rare, chronic granulomatous large-vessel vasculitis that can lead to ocular ischemia. Ocular outcomes after therapeutic management in TA remain largely unknown. We herein conduct a case-based systematic review to address the current treatment options in this particular cohort. Methods: PubMed, Medline, and EMBASE databases were searched pertaining to ocular outcomes after systemic treatment in TA. Studies reporting ocular examinations before and after treatment in TA patients with ocular ischemia were included. Clinical characteristics, therapies, ocular outcomes, and complications were recorded. Results: A 29-year-old woman with newly diagnosed TA showed dramatic regression of Takayasu's retinopathy (TR) following balloon angioplasty. Optical coherence tomography angiography (OCTA) was used as a novel strategy for subsequent follow-up. A total of 117 eyes of 66 patients with a median age of 27 years were included for systematic review. TR was the most common ocular manifestation. Oral steroids were prescribed in nearly all patients (n = 65), followed by the use of methotrexate and antiplatelet therapy. Of the patients, 65.8% and 34.2% underwent open surgery and endovascular procedure, respectively. The median follow-up period was 12 weeks (interquartile range 8-33.5). Surgical therapy showed better ocular improvement (including visual and imaging responses) in both acute and chronic vision loss, along with fewer complications than medical therapy alone. In the surgical group, the visual prognosis was significantly better in patients with initial visual acuity better than 20/200 (p = 0.03) and those who underwent surgery before stage III TR (p = 0.01). Ocular outcomes were equivalent in the two surgical approaches. Conclusion: Clinicians should be familiar with ophthalmic manifestations of this potentially treatable complication in TA. Compared with medical therapy alone, surgical intervention might be a better choice for both acute and chronic vision loss. Surgery is best recommended before the onset of irreversible ischemia to the globe. A combined regimen (oral steroids, immunosuppressants, and antiplatelet drugs) might be effective for those with surgical contradictions or reluctance to an invasive procedure. Physicians should be aware of the importance of ocular examinations, including OCTA, during the diagnosis and follow-up in TA.

Effect of p-doping on the intensity noise of epitaxial quantum dot lasers on silicon.

This work experimentally investigates the impact of p-doping on the relative intensity noise (RIN) properties and subsequently on the modulation properties of semiconductor quantum dot (QD) lasers epitaxially grown on silicon. Owing to the low threading dislocation density and the p-modulation doped GaAs barrier layer in the active region, the RIN level is found very stable with temperature with a minimum value of -150dB/Hz. The dynamical features extracted from the RIN spectra show that p-doping between zero and 20 holes/dot strongly modifies the modulation properties and gain nonlinearities through increased internal losses in the active region and thereby hinders the maximum achievable bandwidth. Overall, this Letter is important for designing future high-speed and low-noise QD devices integrated in future photonic integrated circuits.

Comparative efficacy of intravitreal pharmacotherapy for macular edema secondary to retinal vein occlusion: A protocol for the systematic review and network meta-analysis.

BACKGROUND: Multiple intravitreal pharmacotherapies including different anti-vascular endothelial growth factors (VEGF), intravitreal steroids, and combined therapy with anti-VEGF and steroids are available for patients with macular edema secondary to retinal vein occlusion (RVO). However, the recommendation of multiple therapies remains unknown. This study aims to evaluate the efficacy and safety of multiple intravitreal pharmacotherapies in patients with macular edema secondary to RVO. METHODS: We will systematically search the PubMed, Embase, and the Cochrane library for eligible studies. Randomized controlled trials (RCTs) with intravitreal pharmacotherapies for patients with macular edema secondary to RVO will be included. The Cochrane Collaboration's tool will be used to assess the risk of bias in the randomized trial. The primary outcome is the mean change in BCVA from baseline. The secondary outcomes are the proportion of patients who gained ≥15 letters in BCVA from baseline, the mean change in central retinal thickness from baseline and the number of serious adverse events. RESULTS: The result will obtain a comprehensive treatment recommendation for macular edema secondary to RVO. CONCLUSION: The results of the network meta-analysis will be submitted in a peer-reviewed journal for publication. ETHICAL STATEMENT: This article does not contain any studies with human or animal subjects performed by any of the authors.

Prognostic value of preoperative weight loss-adjusted body mass index on survival after esophagectomy for esophageal squamous cell carcinoma.

BACKGROUND: The impact of body mass index (BMI) on survival in patients with esophageal squamous cell carcinoma (ESCC) undergoing surgery remains unclear. Therefore, a definition of clinically significant BMI in patients with ESCC is needed. AIM: To explore the impact of preoperative weight loss (PWL)-adjusted BMI on overall survival (OS) in patients undergoing surgery for ESCC. METHODS: This retrospective study consisted of 1545 patients who underwent curative resection for ESCC at West China Hospital of Sichuan University between August 2005 and December 2011. The relationship between PWL-adjusted BMI and OS was examined, and a multivariate analysis was performed and adjusted for age, sex, TNM stage and adjuvant therapy. RESULTS: Trends of poor survival were observed for patients with increasing PWL and decreasing BMI. Patients with BMI ≥ 20.0 kg/m2 and PWL < 8.8% were classified into Group 1 with the longest median OS (45.3 mo). Patients with BMI < 20.0 kg/m2 and PWL < 8.8% were classified into Group 2 with a median OS of 29.5 mo. Patients with BMI ≥ 20.0 kg/m2 and PWL ≥ 8.8% (HR = 1.9, 95%CI: 1.5-2.5), and patients with BMI < 20.0 kg/m2 and PWL ≥ 8.8% (HR = 2.0, 95%CI: 1.6-2.6), were combined into Group 3 with a median OS of 20.1 mo. Patients in the three groups were associated with significantly different OS (P < 0.05). In multivariate analysis, PWL-adjusted BMI, TNM stage and adjuvant therapy were identified as independent prognostic factors. CONCLUSION: PWL-adjusted BMI has an independent prognostic impact on OS in patients with ESCC undergoing surgery. BMI might be an indicator for patients with PWL < 8.8% rather than ≥ 8.8%.