High efficiency and dynamic modulation of nonlinear metasurfaces.

Metasurfaces have facilitated numerous innovative applications in the scope of nonlinear optics. However, dynamically tuning the nonlinear response at the pixel level is very challenging. Recent work proposed a novel method to electrically manipulate the local amplitude and phase of third-harmonics generation (THG) by integrating the giant nonlinear responses resulting from intersubband transitions of multiple quantum wells (MQW) with plasmonic nano-resonator. The demonstrated method may pave the way to realize nonlinear optical elements with versatile functionalities by electrically tuning and promoting the advancements of innovative applications such as lidar, 3D displays, optical encryption, optical computing, and so on.

Fermented soybean meal improved laying performance and egg quality of laying hens by modulating cecal microbiota, nutrient digestibility, intestinal health, antioxidant and immunological functions.

Antinutritional factors in feedstuffs may limit their utilization in livestock production, but fermentation process can be used to improve feed quality; however, studies on fermented soybeans for laying hens remain limited. We investigated the effect of fermented soybean meal (FSBM) at various inclusion levels as a partial replacement for soybean meal (SBM) on egg production, egg quality, amino acid digestibility, gut morphology and microbiota, antioxidant capacity and immune response of young laying hens. A total of 360 Hy-line Brown laying hens aged 18 weeks were selected and divided into 5 groups of 6 replicates each and 12 birds per replicate. The control group received a basal diet while the trial group received the basal diet with FSBM included at 2.5%, 5.0%, 7.5% and 10.0%, respectively, for 12 weeks. Our findings revealed that the nutritional value of FSBM was higher compared to that of SBM in terms of reduced content of trypsin inhibitors and increased contents of crude protein, amino acids and minerals. FSBM enhanced egg production (P < 0.05), feed-to-egg ratio (P < 0.05), and albumen quality (albumen height and Haugh unit) (P < 0.05). Furthermore, FSBM improved apparent fecal amino acid digestibility (P < 0.05), gut morphology (increased villus height, villus width, villus height-to-crypt depth ratio and decreased crypt depth) (P < 0.05), antioxidant capacity (reduced malondialdehyde and increased catalase, total superoxide dismutase, glutathione peroxidase and total antioxidant capacity) (P < 0.05) and immune function (increased concentrations of IgG, IgA, and IgM; increased levels of transforming growth factor beta and Toll-like receptor 2; and reduced levels of interleukin 1ß and tumor necrosis factor alpha) (P < 0.05). Further analysis showed that FSBM altered the composition of the gut microbiota favoring beneficial microbes. These findings suggest that probiotic fermentation improved the nutritional value of SBM. The inclusion of FSBM in the diets of laying hens at 2.5% or 5.0% improved amino acid digestibility, gut health, immune function, egg production and egg quality.

Neutrophil to lymphocyte ratio and five-year mortality in patients with acute ischemic stroke.

Background: Previous studies linked neutrophil to lymphocyte ratio (NLR) with short-term mortality after acute ischemic stroke (AIS), but its relationship with long-term mortality remains unclear. This study investigates the association between NLR and five-year mortality in AIS patients. Method: We analyzed 416 AIS patients from April 2012 to January 2016 at Zhangjiagang TCM Hospital. Admission NLR was divided into quartiles: Q1 (<2.00), Q2 (2.00-3.05), Q3 (3.06-5.46), and Q4 (≥5.46). We assessed 5-year all-cause and vascular mortality using Kaplan-Meier, Cox regression, and receiver operating characteristic (ROC) curve analyses. Results: Over five years, 134 (32.2 %) all-cause deaths and 114 (27.4 %) vascular deaths occurred. Elevated NLR was significantly associated with increased risks of all-cause and vascular mortality. Multivariate Cox analysis identified stroke history (HR: 1.57, 95 % CI 1.08-2.30), baseline National Institutes of Health Stroke Scale (NIHSS) score (HR: 1.09, 95 % CI 1.05-1.12), and NLR (HR: 1.09, 95 % CI 1.05-1.12) as independent risk factors for all-cause mortality. These factors also predicted 5-year vascular mortality: stroke history (HR: 1.65, 95 % CI 1.10-2.49), NIHSS score (HR: 1.10, 95 % CI 1.06-1.13), and NLR (HR: 1.08, 95 % CI 1.05-1.10). NLR quartiles were significantly linked to both outcomes: all-cause mortality HRs were Q2 (1.87, 95 % CI 1.00-3.51), Q3 (2.40, 95 % CI 1.31-4.39), Q4 (2.77, 95 % CI 1.47-5.24), P for trend = 0.001; vascular mortality HRs were Q2 (1.76, 95 % CI 0.88-3.55), Q3 (2.34, 95 % CI 1.14-4.40), Q4 (2.57, 95 % CI 1.28-5.16), P for trend = 0.002. Kaplan-Meier survival analysis revealed significantly higher mortality rates in higher NLR quartiles (log-rank p < 0.001). ROC analysis identified optimal NLR cutoff values of 3.42 for predicting 5-year all-cause mortality (AUC 0.689) and 3.51 for vascular-cause mortality (AUC 0.700), with moderate sensitivity and specificity. Conclusions: Higher NLR at admission was linked with five-year all-cause mortality and mortality attributed explicitly to vascular causes in AIS patients.

Trajectories of body mass index and incident kidney stone disease: a prospective cohort study in Chinese young adults.

The present study aims to explore the potential changing trajectory patterns of body mass index (BMI) for Chinese young adults and identify the relationship of BMI trajectory patterns with kidney stone disease (KSD) incidence. Latent class growth analysis was used to identify distinct trajectories of BMI during young adulthood. Cox proportion hazard models were conducted to explore the association between the BMI trajectory group memberships and incident KSD. Subgroup and sensitivity analyses were undertaken to test the robustness of the findings. In total, 2,966 young adults who attended at least three annual check-ups from 2014 to 2021 without KSD at baseline were enrolled in the cohort analysis. Three district BMI trajectories were identified for young adults, labeled as low-stable in normal BMI (28.5%), medium-rising to high BMI (67.4%), and rapid-rising to high BMI (4.1%). Compared with the low-stable in normal BMI group, Hazard ratios (HRs) of the rapid-rising and medium-rising to high BMI groups were 3.19 (95% CI: 1.54-6.63) and 1.78 (95% CI: 1.08-2.92) after adjusting the covariates. The cumulative incidence curves likewise illustrated that young adults in the rapid-rising to high BMI group had the highest risk of developing KSD compared to the other two groups. The rapid BMI growth trajectories during young adulthood were identified to be independently associated with a higher risk of KSD. The findings supplied novel insights that monitoring the BMI changing pattern may be favorable to early intervention of KSD during young adulthood.

Proteomic landscape profiling of primary prostate cancer reveals a 16-protein panel for prognosis prediction.

Prostate cancer (PCa) is the most common malignant tumor in men. Currently, there are few prognosis indicators for predicting PCa outcomes and guiding treatments. Here, we perform comprehensive proteomic profiling of 918 tissue specimens from 306 Chinese patients with PCa using data-independent acquisition mass spectrometry (DIA-MS). We identify over 10,000 proteins and define three molecular subtypes of PCa with significant clinical and proteomic differences. We develop a 16-protein panel that effectively predicts biochemical recurrence (BCR) for patients with PCa, which is validated in six published datasets and one additional 99-biopsy-sample cohort by targeted proteomics. Interestingly, this 16-protein panel effectively predicts BCR across different International Society of Urological Pathology (ISUP) grades and pathological stages and outperforms the D'Amico risk classification system in BCR prediction. Furthermore, double knockout of NUDT5 and SEPTIN8, two components from the 16-protein panel, significantly suppresses the PCa cells to proliferate, invade, and migrate, suggesting the combination of NUDT5 and SEPTIN8 may provide new approaches for PCa treatment.

Radiationless optical modes in metasurfaces: recent progress and applications.

Non-radiative optical modes attracted enormous attention in optics due to strong light confinement and giant Q-factor at its spectral position. The destructive interference of multipoles leads to zero net-radiation and strong field trapping. Such radiationless states disappear in the far-field, localize enhanced near-field and can be excited in nano-structures. On the other hand, the optical modes turn out to be completely confined due to no losses at discrete point in the radiation continuum, such states result in infinite Q-factor and lifetime. The radiationless states provide a suitable platform for enhanced light matter interaction, lasing, and boost nonlinear processes at the state regime. These modes are widely investigated in different material configurations for various applications in both linear and nonlinear metasurfaces which are briefly discussed in this review.

The double-edged nature of nicotine: toxicities and therapeutic potentials.

Nicotine is the primary addictive component of cigarette smoke and is associated with various smoking-related diseases. However, recent research has revealed its broader cognitive-enhancing and anti-inflammatory properties, suggesting its potential therapeutic applications in several conditions. This review aims to examine the double-edged nature of nicotine, encompassing its positive and negative effects. We provide a concise overview of the physiochemical properties and pharmacology of nicotine, including insights into nicotine receptors. Therefore, the article is divided into two main sections: toxicity and therapeutic potential. We comprehensively explored nicotine-related diseases, focusing on specific signaling pathways and the underlying mechanisms that contribute to its effects. Furthermore, we addressed the current research challenges and future development perspectives. This review aims to inspire future researchers to explore the full medical potential of nicotine, which holds significant promise for the clinical management of specific diseases.

Plasma Proteomics Analysis of Early Biomarkers for Predicting Female Fecundability: A Nested Case-Control Study.

The present study aimed to identify and verify new plasma protein markers to predict the female fecundability level. A nested case-control study was conducted involving couples who participated in the Chinese National Free Preconception Check-up Project. Women who successfully conceive within one year were defined as the high fecundability group, and those unable to conceive were defined as the low fecundability group. In the training cohort, potential protein biomarkers were identified using proteomics technology and were further tested in a validation cohort by the Western blotting assay, enzyme-linked immunosorbent assay, and biochemical tests. Meanwhile, receiver operating characteristic curve analysis were used to evaluate the predictive value. Cox proportional hazard regression analyses were conducted to calculate hazard ratios; restricted cubic spline analysis was used to assess the linear relationship between the the protein level and hazard ratios for fecundability. Pyruvate, a key product of glycolysis, was significantly increased in the high fecundability group (P < 0.01) compared to the low fecundability group, and its area under the curve value was 0.68 (P < 0.05). There was a linear positive dose-response association between the pyruvate level and fecundability possibility (hazard ratios = 1.66, 95% CI: 1.07-2.59, p for trend = 0.025, nonlinearity, p-value = 0.2927).

Perinatal factors and early neonatal outcomes of abnormal birthweight infants in Hangzhou, China, 2015-2021: a retrospective cohort study.

BACKGROUND: This study aimed to investigate the perinatal factors and early neonatal outcomes of abnormal birth weight (ABW) in Hangzhou, China from 2015 to 2021. METHODS: A retrospective cohort study was designed to analyse the data of 76 847 newborns, in which the case groups included 3042 cases of low birth weight (LBW) and 2941 cases of fetal macrosomia (MAC), and 70 864 cases of normal weight were as the reference group. RESULTS: The incidence of LBW and MAC was 3.96% and 3.83% in Hangzhou, China from 2015 to 2021. Prematurity (<37 weeks), multiple births, hospitalisation >7 days, fetal anomalies, caesarean section, pregnancy complications, maternal coinfection with pathogens and summer births would be correlated with the incidence of LBW (ORs=43.50, 7.60, 2.09, 1.89, 1.57, 1.28, 1.19 and 1.18, all p<0.05). Factors such as post-term pregnancy (>41 weeks), scarred uterus, anterior vaginal incision and gravidity ≥2 were correlated with decreased incidence of LBW, with ORs of 0.05, 0.54, 0.65 and 0.80. Moreover, caesarean delivery, post-term pregnancy (> 41 weeks), parity ≥1, lateral vaginal incision, gravidity ≥2, hospitalisation >7 days, winter births and pregnancy complications also have association with the incidence of MAC (ORs=3.92, 2.73, 2.19, 1.87, 1.22, 1.20, 1.17 and 1.13, all p<0.05) while prematurity (<37 weeks), scarred uterus and anterior vaginal incision have close association with decreased incidence of MAC, with ORs of 0.07, 0.21 and 0.74 (all p<0.05). CONCLUSION: There was a trend of yearly increase in ABW in Hangzhou, China from 2015 to 2021. Several neonatal and maternal-related variables such as caesarean section, pregnancy complications and hospitalisation >7 days are associated with the odds of LBW and MAC, however, factors such as pregnancy with scarred uterus relate to the decrease of ABW. Close monitoring and intervention during pregnancy are essential to reduce the occurrence of ABW.

A Case Report of Pregnancy Complicated with Primary Hemophagocytic Lymphohistiocytosis.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome characterized by excessive activation of NK cells and cytotoxic T lymphocytes, subsequently leading to macrophage activation and increased cytokine production. Misdiagnosis due to nonspecific clinical presentations and inadequate understanding of the disease can significantly jeopardize the safety of both the mother and the infant. We report a case of pregnancy combined with HLH and conduct a literature review to provide insights into the diagnosis and treatment of pregnancy-related HLH. Case Presentation: We discussed a case of a pregnant woman with persistent postpartum fever, serum ferritin, and elevated liver function, who failed to respond to repeated anti-infective therapy and was diagnosed with HLH after multidisciplinary diagnostic treatment. We gave dexamethasone treatment, and the patient's temperature and blood cells quickly returned to normal. Finally, exome sequencing revealed heterozygous variation in UNC13D gene, so we considered this case as pregnancy combined with primary HLH (pHLH). Conclusion: We report the case of HLH diagnosed during pregnancy and show that early diagnosis and timely intervention can prevent rapid disease progression, reduce maternal mortality rates, and improve survival rates. Additionally, molecular genetic testing can confirm pathogenic gene mutations, providing essential genetic counseling for patients with pHLH who plan to conceive a healthy child.

FYB1-targeted modulation of CAPG promotes AML progression.

Acute myeloid leukemia (AML) is a rare and heterogeneous disease. Over the past few decades, patient prognosis has improved with continuous improvements in treatment, but outcomes for some patients with primary drug resistance or relapse after treatment remain poor. Additional therapies to improve outcomes for these patients are urgently needed. FYB1 expression differs substantially between AML tissues and normal tissues. High FYB1 expression is correlated with poorer overall survival (OS), indicating that FYB1 may regulate AML progression. Therefore, understanding the effect of FYB1 on AML could improve the success rate of therapeutic approaches and prognosis for patients with AML. In this study, through analysis of large databases and both in vivo and in vitro experiments, we assessed the expression and role of FYB1 in AML and the relationship of FYB with patient prognosis. Downstream targets of the FYB1 gene were analyzed by RNA-seq. Database mining and in vitro experiments were used to further clarify the effect of the downstream target gelsolin-like actin-capping protein (CAPG) on AML cells and its relationship with patient prognosis. FYB1 expression was significantly higher in AML tissue and corresponded with a poor prognosis. FYB1 knockdown inhibited AML cell proliferation, promoted cell apoptosis, reduced cell adhesion capability and significantly reduced the tumor formation rate in mice. In addition, FYB1 knockdown induced a notable decrease in CAPG expression. The suppression of CAPG significantly inhibited cell proliferation and increased cell apoptosis. The conclusions of this study underscore the pivotal role of the FYB1/CAPG axis in promoting AML. We propose that the FYB1/CAPG axis could serve as a new thread in the development of therapeutic strategies for AML.

Retrospective Investigation and Research on Fall Events Among Hospitalized Patients in the Rehabilitation Department.

Objective: We investigated the clinical characteristics, fall outcomes, and related factors of falls in patients who were hospitalized in the rehabilitation department, and explored strategies to reduce the incidence of falls and prevent falls in patients. Methods: Data from 60 patients who fell in the rehabilitation department between 2016 and 2021 were analyzed for clinical characteristics, associated factors, incidence of falls, injuries, and patient demographics. Under the random stratified sampling method, 60 patients who did not fall during the same period were selected as the control group, and relevant data was collected. Measurement data were compared using an independent sample t-test. Enumeration data were compared using chi-squared (χ2) test was employed to compare these data between the two groups. Non-parametric data were analyzed using the Mann-Whitney U-test. Factors potentially influencing falls were scrutinized through both univariate and binary logistic regression analyses. Results: The median annual incidence of falls among patients who were hospitalized in the rehabilitation department was 0.04%, while the overall fall injury rate was 60%. Falls were most prevalent within 30 days of hospitalization (71.67%). The most common fall-related condition was craniocerebral disease (83.33%). The incidents of falls location of fall were mainly reported in nearby areas of rehabilitation ward (70%). Most accidents occurred between 7:00 a.m.-12:00 p.m. and 3:01 p.m.-6:00 p.m. (63.33%), and dyskinesia was the most common cause of falls (71.67%). There were 39 patients (65.00%) with Barthel Index (BI) scores ranging between 40-60. Conclusion: Patients in the rehabilitation department had a greater incidence of falls and fall injuries. Within 30 days of admission, patients with moderately dependent craniocerebral disorders and dyskinesia frequently experienced falls during typical daytime shifts in areas characterized by endemic conditions.

Meta-Attention Network Based Spectral Reconstruction with Snapshot Near-Infrared Metasurface.

Near-infrared (NIR) spectral information is important for detecting and analyzing material compositions. However, snapshot NIR spectral imaging systems still pose significant challenges owing to the lack of high-performance NIR filters and bulky setups, preventing effective encoding and integration with mobile devices. This study introduces a snapshot spectral imaging system that employs a compact NIR metasurface featuring 25 distinct C4 symmetry structures. Benefitting from the sufficient spectral variety and low correlation coefficient among these structures, center-wavelength accuracy of 0.05 nm and full width at half maximum accuracy of 0.13 nm are realized. The system maintains good performance within an incident angle of 1°. A novel meta-attention network prior iterative denoising reconstruction (MAN-IDR) algorithm is developed to achieve high-quality NIR spectral imaging. By leveraging the designed metasurface and MAN-IDR, the NIR spectral images, exhibiting precise textures, minimal artifacts in the spatial dimension, and little crosstalk between spectral channels, are reconstructed from a single grayscale recording image. The proposed NIR metasurface and MAN-IDR hold great promise for further integration with smartphones and drones, guaranteeing the adoption of NIR spectral imaging in real-world scenarios such as aerospace, health diagnostics, and machine vision.

Function of mast cell and bile-cholangiocarcinoma interplay in cholangiocarcinoma microenvironment.

OBJECTIVE: The correlation between cholangiocarcinoma (CCA) progression and bile is rarely studied. Here, we aimed to identify differential metabolites in benign and malignant bile ducts and elucidate the generation, function and degradation of bile metabolites. DESIGN: Differential metabolites in the bile from CCA and benign biliary stenosis were identified by metabonomics. Biliary molecules able to induce mast cell (MC) degranulation were revealed by in vitro and in vivo experiments, including liquid chromatography-mass spectrometry (MS)/MS and bioluminescence resonance energy transfer assays. Histamine (HA) receptor expression in CCA was mapped using a single-cell mRNA sequence. HA receptor functions were elucidated by patient-derived xenografts (PDX) in humanised mice and orthotopic models in MC-deficient mice. Genes involved in HA-induced proliferation were screened by CRISPR/Cas9. RESULTS: Bile HA was elevated in CCA and indicated poorer prognoses. Cancer-associated fibroblasts (CAFs)-derived stem cell factor (SCF) recruited MCs, and bile N,N-dimethyl-1,4-phenylenediamine (DMPD) stimulated MCs to release HA through G protein-coupled receptor subtype 2 (MRGPRX2)-Gαq signalling. Bile-induced MCs released platelet-derived growth factor subunit B (PDGF-B) and angiopoietin 1/2 (ANGPT1/2), which enhanced CCA angiogenesis and lymphangiogenesis. Histamine receptor H1 (HRH1) and HRH2 were predominantly expressed in CCA cells and CAFs, respectively. HA promoted CCA cell proliferation by activating HRH1-Gαq signalling and hastened CAFs to secrete hepatocyte growth factor by stimulating HRH2-Gαs signalling. Solute carrier family 22 member 3 (SLC22A3) inhibited HA-induced CCA proliferation by importing bile HA into cells for degradation, and SLC22A3 deletion resulted in HA accumulation. CONCLUSION: Bile HA is released from MCs through DMPD stimulation and degraded via SLC22A3 import. Different HA receptors exhibit a distinct expression profile in CCA and produce different oncogenic effects. MCs promote CCA progression in a CCA-bile interplay pattern.

Impacts of Unethical Behavior on Self-Esteem: A Contingent Dual-Process Model.

Previous studies have reported mixed findings on how and why unethical behavior affects self-esteem. To address this issue, a contingent dual-process model is proposed and tested. The model postulates a negative impact of unethical behavior on self-esteem through decreased morality, a positive effect through increased competence, and the relative strength of these two paths depending on system-justifying motives. Studies using unethical behavior for self-interest (Studies 1 and 2), involving ingroup interest (Study 3), and measuring (Studies 1 and 3) and manipulating general system justification (Study 2) provide support for the model. By identifying the effects of system-justifying motives and linking the two competing paths, the model reconciles inconsistencies in previous research regarding how self-esteem is influenced by unethical behavior and reveals the underlying mechanism of this association. Accordingly, the current research constructs a motivational and superordinate framework to clarify the dynamic consequences of unethical behavior.

Ultracompact polarization multiplexing meta-combiner for augmented reality display.

Augmented reality (AR) display, as a next-generation innovative technology, is revolutionizing the ways of perceiving and communicating by overlaying virtual images onto real-world scenes. However, the current AR devices are often bulky and cumbersome, posing challenges for long-term wearability. Metasurfaces have flexible capabilities of manipulating light waves at subwavelength scales, making them as ideal candidates for replacing traditional optical elements in AR display devices. In this work, we propose and fabricate what we believe is a novel reflective polarization multiplexing gradient metasurface based on propagation phase principle to replace the optical combiner element in traditional AR display devices. Our designed metasurface exhibits different polarization modulations for reflected and transmitted light, enabling efficient deflection of reflected light while minimizing the impact on transmitted light. This work reveals the significant potential of metasurfaces in next-generation optical display systems and provides a reliable theoretical foundation for future integrated waveguide schemes, driving the development of next-generation optical display products towards lightweight and comfortable.

[Analysis and clinical application of preimplantation genetic testing for monogenic disorders in a case with Spinal muscular atrophy "2+0" genotype].

OBJECTIVE: To explore the clinical application of preimplantation genetic testing for monogenic disorders (PGT-M) in an unique case with Spinal muscular atrophy (SMA) type 2+0. METHODS: A special SMA family presented at the Third Affiliated Hospital of Guangzhou Medical University on October 19, 2020 was selected as the study subject. Multiple ligation-dependent probe amplification (MLPA) and molecular tagging linkage analysis were carried out to identify the SMN1 genotype of the couple and their fetus. Subsequently, next-generation sequencing (NGS), molecular tagging linkage analysis, and chromosomal microarray analysis were employed to determine the haplotypes and validate the result of PGT-M on the 11 embryos derived for the couple. RESULTS: The female partner was identified as a carrier of the rare SMN1[2+0] variant, and prenatal diagnosis confirmed the fetus to be affected by SMA. Ultimately, PGT-M has successfully selected four embryos free from the pathogenic SMN1 variants and X chromosome deletion. CONCLUSION: PGT-M can effectively prevent the transmission of rare genetic variants such as the SMA 2+0 subtype in the families. Above finding has provided guidance for genetic counseling and family planning for the couple.

Multi-Dimensional Multiplexed Metasurface Holography by Inverse Design.

Multi-dimensional multiplexed metasurface holography extends holographic information capacity and promises revolutionary advancements for vivid imaging, information storage, and encryption. However, achieving multifunctional metasurface holography by forward design method is still difficult because it relies heavily on Jones matrix engineering, which places high demands on physical knowledge and processing technology. To break these limitations and simplify the design process, here, an end-to-end inverse design framework is proposed. By directly linking the metasurface to the reconstructed images and employing a loss function to guide the update of metasurface, the calculation of hologram can be omitted; thus, greatly simplifying the design process. In addition, the requirements on the completeness of meta-library can also be significantly reduced, allowing multi-channel hologram to be achieved using meta-atoms with only two degrees of freedom, which is very friendly to processing. By exploiting the proposed method, metasurface hologram containing up to 12 channels of multi-wavelength, multi-plane, and multi-polarization is designed and experimentally demonstrated, which exhibits the state-of-the-art information multiplexing capacity of the metasurface composed of simple meta-atoms. This method is conducive to promoting the intelligent design of multifunctional meta-devices, and it is expected to eventually accelerate the application of meta-devices in colorful display, imaging, storage and other fields.

Successful Treatment of Clinically Diagnosed Cancer-Associated Retinopathy with Intravitreal Dexamethasone Implant Followed by 0.18 mg Fluocinolone Implant without Systemic Immunosuppression.

PURPOSE: To report a case of clinically diagnosed cancer-associated retinopathy (CAR) successfully treated with intravitreal corticosteroid implants without systemic immunosuppression. METHODS: Case report with multimodal imaging. RESULTS: An 80-year-old man without known systemic malignancy presented with debilitating shimmering, hemeralopia and rapidly progressive bilateral vision loss following uncomplicated cataract surgery. Mild vitritis, extensive photoreceptor loss, mottling of retinal pigmentary epithelium (RPE), and mild vascular attenuation were found in both eyes. Full field electroretinogram (ffERG) showed severe bilateral rod-cone dysfunction. Infectious etiologies and vitreoretinal lymphoma were ruled out. During cancer workup, intravitreal corticosteroid treatment was offered. Significant anatomical improvement with reconstitution of ellipsoid zone, improved RPE irregularities and functional improvement, were observed 3 weeks after bilateral intravitreal dexamethasone implants (Ozurdex). 2 months later, patient received bilateral intravitreal 0.18mg fluocinolone acetonide implants (YUTIQ). Later, a colonic adenocarcinoma was found (pathologic stage pT3 pN0). Patient recovered well from surgery and no chemotherapy was needed. 9 months since bilateral intravitreal fluocinolone acetonide implants (11 months since bilateral intravitreal dexamethasone implants), best corrected vision maintained at 20/25-2 OD, 20/20 OS without ongoing treatments. Bilateral reconstitution of ellipsoid zones and nearly resolution of RPE irregularities remained stable. Repeat ffERG demonstrated improved cone response OS and stable diminished rod response OU. Patient reports resolution of ocular symptoms. CONCLUSION: The sustained improvements with intravitreal corticosteroid monotherapy suggest potential advantages using local therapy over systemic treatment. Long term follow-up is warranted. Further research is needed to evaluate the efficacy of using 0.18mg fluocinolone implant (YUTIQ) to treat CAR.

Associations between multiple metal exposure and fertility in women: A nested case-control study.

Metal pollution can cause a decline in female fertility, however, previous studies have focused more on the effect of a single metal on fertility. In this study, we evaluated the effect of metal mixtures on female fertility based on nested case-control samples. The plasma levels of 22 metal elements from 180 women were determined by an inductively coupled plasma mass spectrometer (ICP-MS). Minimum absolute contraction and selection operator (LASSO) penalty regression selected metals with the greatest influence on clinical outcome. Logistic regression was used to analyze the correlation between single metals and fertility while a Bayesian kernel function regression (BKMR) model was used to analyze the effect of mixed metals. Eight metals (Calcium (Ca), Chromium (Cr), Cobalt (Co), Copper (Cu), Zinc (Zn), Rubidium (Rb), Strontium (Sr) and Zirconium (Zr)) were selected by LASSO regression for subsequent analysis. After adjusting for covariates, the logistic model showed that Cu (Odds Ratio(OR):0.33, 95% CI: 0.13 - 0.84) and Co (OR:0.38, 95% CI: 0.15 -0.94) caused a significant reduction in fertility, and identified the protective effect of Zn (OR: 2.96, 95% CI:1.21 -7.50) on fertility. Trend tests showed that increased Cr, Cu, and Rb levels were associated with reduced fertility. The BKMR model showed that Cr, Co, Cu, and Rb had a nonlinear relationship with fertility decline when controlling for the concentrations of other metals and suggested that Cu and Cr might exert an influence on fertility. Analysis showed a negative correlation between Cu, Cr, Co, Rb, and fertility, and a positive correlation between Zn and fertility. Furthermore, we found evidence for the interaction between Cu and Cr. Our findings require further validation and may identify new mechanisms in the future.