The central retinal thickness and its related genotype in ABCA4-related retinopathy.

PURPOSE: To further explore the influence of genotype, including mutation type and structural domain, on the severity of macular atrophy, we measured the central retinal thickness (CRT) in patients with ABCA4-related retinopathy. METHODS: A total of 66 patients were included in the cohort. This was a retrospective investigation. The patients were tested using whole exon sequencing and ophthalmic exams, including slip lamp exams, best-corrected visual acuity, optical coherence tomography, fundus photo, and fundus autofluorescence. RESULTS: In this study, we discovered that mutations on nucleotide binding domains (NBD) lead to less CRT (45.00 ± 25.25µm, 95% CI: 31.54-58.46) had significantly less CRT than the others (89.75 ± 71.17µm, 95% CI: 30.25-149.25, p = 0.032), and could accelerate the rate of CRT decrease. CONCLUSIONS: Our study provides new perspectives in the understanding of ABCA4-related retinopathy.

Generation of an induced pluripotent stem cell line (SJTUGHi003-A) from a patient with Sorsby fundus dystrophy carrying c.484G>A mutation in TIMP3 gene.

Sorsby fundus dystrophy (SFD) is a rare autosomal dominant disorder with macular dystrophy and severe visual loss. Mutations in TIMP3 gene has been related to SFD with mechanisms unclear. We have successfully reprogrammed the peripheral blood mononuclear cells (PBMCs) from an SFD patient carrying c.484G>A mutation in TIMP3 gene to induced pluripotent stem cells (iPSCs) and characterized their pluripotency and genetic stability. This line may serve as a useful tool to explore the role of TIMP3 in SFD pathogenesis.

The prognostic value of absolute lymphocyte count and neutrophil-to-lymphocyte ratio for patients with metastatic breast cancer: a systematic review and meta-analysis.

Background: Neutrophil-to-lymphocyte ratio (NLR) is considered a potential prognostic marker in early breast cancer. However, the prognosis of absolute lymphocyte count (ALC) and NLR in metastatic breast cancer (MBC) has been reported in a few studies, and conclusions are still conflicting. This present manuscript aims to provide further solid evidence regarding the prognostic values of ALC and NLR in MBC patients. Method: Eligible studies that reported the associations between ALC or NLR and MBC were included by searching relative electronic databases. Overall survival (OS) and progression-free survival (PFS) were used as outcome measures. The hazard ratio (HR) values and 95% confidence interval (CI) of the outcome measures were collected as effect sizes, and further analysis and discussion were conducted according to the pooled HR, subgroup analysis, publication bias, and interstudy heterogeneity. Results: Twenty-nine studies comprising 3,973 patients with MBC were included. According to our findings, lower ALC was significantly associated with poorer prognosis of OS (HR = 0.57, 95% CI 0.48 to 0.68) and PFS (HR = 0.68, 95% CI 0.58 to 0.79), and greater NLR was associated with poorer OS (HR = 1.50, 95% CI 1.35 to 1.67) and PFS (HR = 1.82, 95% CI 1.42 to 2.35). Furthermore, the prognostic values of ALC and NLR in MBC were also observed in the subgroup analyses regarding cutoff values and ethnicities. Conclusion: Low ALC and elevated NLR were observed to be significantly associated with adverse OS and PFS in MBC, indicating that ALC and NLR may act as potential prognostic biomarkers of MBC patients. Meanwhile, our results will also provide some novel evidence and research clues for the selection and development of clinical treatment strategies for MBC patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021224114.

Understanding the effect of foreign atoms occupation on the metamagnetic behaviors in MnCoSi-based alloys: taking Pt-doping as an example.

Present research on TiNiSi-type MnCoSi-based alloys focuses on finding a suitable doping element to effectively reduce the critical magnetic field (µ0Hcri) required to induce a metamagnetic transition. This paper provides a guide to achieve this goal through an experimental investigation of Mn1-xPtxCoSi and MnCo1-xPtxSi alloys. In Mn1-xPtxCoSi, asxincreases,µ0Hcriat room temperature decreases, while in MnCo1-xPtxSi, it increases. This phenomenon can be attributed to the fact that larger Pt atoms prefer Co sites over Mn sites, as predicted by our density-functional theory. Consequently, in Mn1-xPtxCoSi, larger Co atoms are extruded into the Mn atoms chain, increasing the nearest Mn-Mn distance and resulting in a reducedµ0Hcri. This finding suggests that transition-metal atoms with more valence electrons preferably occupy the Co site, while those with fewer valence electrons preferably occupy the Mn site. Adhering to this rule, one can easily obtain a lowµ0Hcriand large magnetostrain under a low magnetic field by selecting a suitable foreign element and chemical formula, as demonstrated by the Mn1-xPtxCoSi alloy.

GFRAL Is Widely Distributed in the Brain and Peripheral Tissues of Mice.

In 2017, four independent publications described the glial cell-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) as receptor for the growth differentiation factor 15 (GDF15, also MIC-1, NAG-1) with an expression exclusively in the mice brainstem area postrema (AP) and nucleus tractus solitarii (NTS) where it mediates effects of GDF15 on reduction of food intake and body weight. GDF15 is a cell stress cytokine with a widespread expression and pleiotropic effects, which both seem to be in contrast to the reported highly specialized localization of its receptor. This discrepancy prompts us to re-evaluate the expression pattern of GFRAL in the brain and peripheral tissues of mice. In this detailed immunohistochemical study, we provide evidence for a more widespread distribution of this receptor. Apart from the AP/NTS region, GFRAL-immunoreactivity was found in the prefrontal cortex, hippocampus, nucleus arcuatus and peripheral tissues including liver, small intestine, fat, kidney and muscle tissues. This widespread receptor expression, not taken into consideration so far, may explain the multiple effects of GDF-15 that are not yet assigned to GFRAL. Furthermore, our results could be relevant for the development of novel pharmacological therapies for physical and mental disorders related to body image and food intake, such as eating disorders, cachexia and obesity.

GENETIC FACTORS AND CHARACTERISTICS ON SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY ARE ASSOCIATED WITH CHOROIDAL THICKNESS IN ABCA4 -RELATED RETINOPATHY.

PURPOSE: To investigate the possible correlation factors of choroidal thickness in ABCA4 -related retinopathy. METHODS: A total of 66 patients were included in the cohort. It is a retrospective, cross-sectional laboratory investigation. The patients were tested using whole-exon sequencing and ophthalmic examinations, including slit-lamp examinations, best-corrected visual acuity, spectral-domain optical coherence tomography, fundus photograph, and fundus autofluorescence. RESULTS: Besides demographic characteristics (age, onset age, duration), we selected genetic factors and ocular characteristics on spectral-domain optical coherence tomography as the candidates related to choroidal thickness. Mutation type (inframe mutation or premature termination codon), epiretinal membrane, retinal pigment epithelium- Bruch membrane integrity, and macular curvature changes were identified as related factors to choroidal thickness in ABCA4 -related retinopathy after the adjustment of Logistic LASSO regression. CONCLUSION: Mutation type, epiretinal membrane, retinal pigment epithelium-Bruch membrane integrity, and macular curvature changes are related factors to choroidal thinning. These findings could provide us a further understanding for the pathological process and clinical features of ABCA4 mutation.

Prevalence and optical coherence tomography analyses of outer retinal tubulations in Chinese population with inherited retinal diseases.

BACKGROUND: To investigate the prevalence of outer retinal tubulation (ORT) and its correlations with optical coherence tomography (OCT) parameters in Chinese population with inherited retinal diseases (IRDs). METHODS: This retrospective study enrolled consecutive patients identified with IRDs and referred for genetic testing between February 2016 and April 2021. Clinical characteristics from medical records and features of cross-sectional B-scans were reviewed and analysed. The associations of patient-specific and ocular features with the presence of ORT were evaluated using univariate and multivariate analyses. RESULTS: Two hundred and three patients (401 eyes) with a mean age of 49.7 ± 16.7 years were enrolled. ORT was observed in 41 eyes (10.2%), including 26 of 28 eyes (92.9%) with Bietti crystalline corneoretinal dystrophy (BCD), 14 of 338 eyes (4.1%) with retinitis pigmentosa (RP), and 1 of 26 eyes (3.8%) in eyes with cone-rod dystrophy. Eyes with ORT showed significantly worse visual acuity than those without ORT (P = 0.002). Multivariate analysis indicated that the presence of ORT was positively correlated with choroidal atrophy and inner nuclear layer (INL) cysts (P < 0.01). ORTs were detected more frequently in eyes with BCD than RP (P = 0.024), most of which located exclusively within the extrafoveal area. Large choroidal vessels were detected underneath the corresponding ORTs in both patients with BCD and RP. CONCLUSIONS: The prevalence of ORT varies among different IRDs phenotypes, with the highest prevalence in BCD. The presence of choroidal atrophy and INL cysts may be associated with an increased risk of ORT formation in patients with IRD.

Liuwei Dihuang pills attenuate ovariectomy-induced bone loss by alleviating bone marrow mesenchymal stem cell (BMSC) senescence via the Yes-associated protein (YAP)-autophagy axis.

CONTEXT: Liuwei Dihuang pill (LWDH) has been used to treat postmenopausal osteoporosis (PMOP). OBJECTIVE: To explore the effects and mechanisms of action of LWDH in PMOP. MATERIALS AND METHODS: Forty-eight female Sprague-Dawley rats were divided into four groups: sham-operated (SHAM), ovariectomized (OVX), LWDH high dose (LWDH-H, 1.6 g/kg/d) and LWDH low dose (LWDH-L, 0.8 g/kg/d); the doses were administered after ovariectomy via gavage for eight weeks. After eight weeks, the bone microarchitecture was evaluated. The effect of LWDH on the differentiation of bone marrow mesenchymal stem cells (BMSCs) was assessed via osteogenesis- and lipogenesis-induced BMSC differentiation. The senescence-related biological indices were also detected using senescence staining, cell cycle analysis, quantitative real-time polymerase chain reaction and western blotting. Finally, the expression levels of autophagy-related proteins and Yes-associated protein (YAP) were evaluated. RESULTS: LWDH-L and LWDH-H significantly modified OVX-induced bone loss. LWDH promoted osteogenesis and inhibited adipogenesis in OVX-BMSCs. Additionally, LWDH decreased the positive ratio of senescence OVX-BMSCs and improved cell viability, cell cycle, and the mRNA and protein levels of p53 and p21. LWDH upregulated the expression of autophagy-related proteins, LC3, Beclin1 and YAP, in OVX-BMSCs and downregulated the expression of p62. DISCUSSION AND CONCLUSIONS: LWDH improves osteoporosis by delaying the BMSC senescence through the YAP-autophagy axis.

Microfluidic Wearable Devices for Sports Applications.

This study aimed to systematically review the application and research progress of flexible microfluidic wearable devices in the field of sports. The research team thoroughly investigated the use of life signal-monitoring technology for flexible wearable devices in the domain of sports. In addition, the classification of applications, the current status, and the developmental trends of similar products and equipment were evaluated. Scholars expect the provision of valuable references and guidance for related research and the development of the sports industry. The use of microfluidic detection for collecting biomarkers can mitigate the impact of sweat on movements that are common in sports and can also address the issue of discomfort after prolonged use. Flexible wearable gadgets are normally utilized to monitor athletic performance, rehabilitation, and training. Nevertheless, the research and development of such devices is limited, mostly catering to professional athletes. Devices for those who are inexperienced in sports and disabled populations are lacking. Conclusions: Upgrading microfluidic chip technology can lead to accurate and safe sports monitoring. Moreover, the development of multi-functional and multi-site devices can provide technical support to athletes during their training and competitions while also fostering technological innovation in the field of sports science.

Diagnostic Challenges in PD-1 Inhibitor Induced Panuveitis in a Teenage Girl with Chest Soft Tissue Sarcoma - A Case Report.

PURPOSE: To report a case of programmed cell death receptor-1 (PD-1) inhibitor induced panuveitis. METHOD: Observational case report of a 13-year-old Chinese girl presented as panuveitis. The clinical course, imaging performance, laboratory examination, differential diagnosis, treatment and prognosis were described. RESULT: Patient presented with bilateral anterior granulomatous uveitis, vitritis, papillitis, and various creamy yellow nodular lesions in the mid-peripheral fundus. She had a history of biopsy proven alveolar soft tissue sarcoma on the chest wall and pulmonary metastasis, and a PD-1 inhibitor (sintilimab) was intravenously administered. Blood tests, magnetic resonance imaging of the cranium and the orbit, aqueous humor assay of inflammatory cytokines and microbial DNA were performed to distinguish infectious and non-infectious uveitis, choroidal metastases, and intravenous injection-related endophthalmitis. The oncologist evaluated that the sarcoma was stable and terminated sintilimab dosage. After sintilimab withdrawal, the blurred vision improved. Then, the patient received oral corticosteroids, resulted in resolution of the panuveitis. A diagnosis of PD-1 inhibitor induced panuveitis was made. CONCLUSION: For patients taking PD-1 inhibitors, the major diagnostic challenge is to identify whether the cause of the uveitis is due to the antitumor treatment or not. It is suggested to be screened by eye care specialist and timely referral to uveitis specialist with any suspicion of intraocular inflammation for these patients.

Appearance of retinal arterial macroaneurysms in patients using swept-source optical coherence tomographic angiography.

BACKGROUND: Retinal arterial macroaneurysm (RAM) is a common clinical disease leading to vision loss in elderly individuals. The appropriate interpretation of swept-source optical coherence tomographic angiography (SS-OCTA), a noninvasive examination, is easy and convenient for detecting the status of RAMs and guiding treatment. METHODS: The objectives of this study were to describe the morphologic characteristics of RAMs using SS-OCTA and to observe whether there are differences in the morphologies of RAMs between SS-OCTA and fundus fluorescein angiography (FFA), before and after treatment. We retrospectively evaluated twenty-two eyes of 22 patients who were diagnosed with RAMs. All patients underwent a complete ophthalmologic examination, including a review of medical records, best-corrected visual acuity (BCVA), fundus photography, FFA and SS-OCTA. RAMs were recorded by SS-OCTA before any treatment or observation decisions were made. The morphologic findings of the RAMs on SS-OCTA were investigated. RESULTS: On SS-OCTA, RAMs can show local dilatation or an irregular linear blood flow signal, and the dilated cystic lumen may show thrombosis with a low reflection signal. After treatment, the shape of the RAMs will show reactive changes. The findings on SS-OCTA are not very consistent with those on FFA. CONCLUSIONS: The same RAM may have different manifestations on OCTA and FFA, and OCTA can more conveniently reflect the changes in blood flow signals and treatment response of RAMs.

Exploring the mechanism of JiGuCao capsule formula on treating hepatitis B virus infection via network pharmacology analysis and in vivo/vitro experiment verification.

The JiGuCao capsule formula (JCF) has demonstrated promising curative effects in treating chronic hepatitis B (CHB) in clinical trials. Here, we aimed to investigate JCF's function and mechanism in diseases related to the hepatitis B virus (HBV). We used mass spectrometry (MS) to identify the active metabolites of JCF and established the HBV replication mouse model by hydrodynamically injecting HBV replication plasmids into the mice's tail vein. Liposomes were used to transfect the plasmids into the cells. The CCK-8 kit identified cell viability. We detected the levels of HBV s antigen (HBsAg) and HBV e antigen (HBeAg) by the quantitative determination kits. qRT-PCR and Western blot were used to detect the genes' expression. The key pathways and key genes related to JCF on CHB treatment were obtained by network pharmacological analysis. Our results showed that JCF accelerated the elimination of HBsAg in mice. JCF and its medicated serum inhibited HBV replication and proliferation of HBV-replicating hepatoma cells in vitro. And the key targets of JCF in treating CHB were CASP3, CXCL8, EGFR, HSPA8, IL6, MDM2, MMP9, NR3C1, PTGS2, and VEGFA. Furthermore, these key targets were related to pathways in cancer, hepatitis B, microRNAs in cancer, PI3K-Akt signaling, and proteoglycans in cancer pathways. Finally, Cholic Acid, Deoxycholic Acid, and 3', 4', 7-Trihydroxyflavone were the main active metabolites of JCF that we obtained. JCF employed its active metabolites to perform an anti-HBV effect and prevent the development of HBV-related diseases.

A Protocol for a Single-Centered, Pragmatic, Randomized, Controlled, Parallel Trial Comparing Comprehensive Nonsurgical Therapy Options for Individuals with Lumbar Spinal Stenosis.

Aim: Lumbar spinal stenosis (LSS) is a long-term degenerative disease. Considering the risks and advantages of the patient's age range and the characteristics of the condition, non-surgical treatment is recommended. To determine the best first-line non-surgical therapy for LSS, few studies have examined different non-surgical therapies. Therefore, the main objective of this study is to determine whether the selection of comprehensive Chinese medicine (CM) treatment for LSS is more successful than non-surgical conservative treatment. Patients and Methods: In this two-armed, parallel, single-centered, pragmatic randomized controlled study, 94 LSS participants will be randomized to receive 24 sessions of comprehensive CM therapy or conservative treatment for 3 months, with follow-up assessments at 6, 9, 12, and 15 months. The primary outcome will be based on the success rate of the Zurich Claudication Questionnaire (ZCQ) for the most clinical important difference (MCID) at 3 and 15 months. Secondary outcomes include Numerical Rating Scale (NRS) scores for back and leg pain, ZCQ scores, Oswestry Disability Index scores for lumbar dysfunction, and Short-Form 12 scores for health-related quality of life at 3, 6, 9, 12, and 15 months. Adverse events and incidences of surgery will be reported anytime during the trial and follow-up. Conclusion: This protocol examines the comparative efficacy of comprehensive CM therapy compared with conventional care through a pragmatic randomized controlled trial to present data to facilitate clinical or policy decision-making. The outcomes will make it easier to decide which patient-centered treatments to prioritize for LSS.

A Zn(II)-Metal-Organic Framework Based on 4-(4-Carboxy phenoxy) Phthalate Acid as Luminescent Sensor for Detection of Acetone and Tetracycline.

As hazardous environmental pollutants, residual tetracycline (TC) and acetone are harmful to the ecosystem. Therefore, it is necessary to detect the presence of these pollutants in the environment. In this work, using Zn (II) salt, 4-(4-carboxy phenoxy) phthalic acid (H3L), and 3,5-bis(1-imidazolyl) pyridine (BMP), a new metal-organic framework (Zn-MOF) known as [Zn3(BMP)2L2(H2O)4]·2H2O was synthesized using a one-pot hydrothermal method. The Zn-MOF has a three-dimensional framework based on the [Zn1N2O2] and [Zn2N2O4] nodes linked by a tridentate bridge BMP ligand and an L ligand with the µ1:η1η0/µ1:η1η0/µ0:η0η0 coordination mode. There were two kinds of left- and right-handed helix chains, Zn1-BMP and Zn1-BMP-Zn1-L. The complex was stable in aqueous solutions with pH values of 4-10. The Zn-MOF exhibited a strong emission band centered at 385 nm owing to the π*→π electron transition of the ligand. It showed high luminescence in some common organic solvents as well as in the aqueous solutions of pH 4-10. Interestingly, TC and acetone effectively quenched the luminescence of the Zn-MOF in aqueous solution and enabled the Zn-MOF to be used as a sensor to detect TC and acetone. The detection limits of TC and acetone were observed to be 3.34 µM and 0.1597%, respectively. Even in acidic (pH = 4) and alkaline (pH = 10) conditions, the Zn-MOF showed a stable luminescence sensing capability to detect TC. Luminescence sensing of the Zn-MOF for TC in urine and aquaculture wastewater systems was not affected by the interfering agent. Furthermore, the mechanism of sensing TC was investigated in this study. Fluorescence resonance energy transfer and photoinduced electron transfer were found to be the possible quenching mechanisms via UV-Vis absorption spectra/the excitation spectra measurements and DFT calculations.

OUTER RETINAL TUBULATION IN BIETTI CRYSTALLINE DYSTROPHY ASSOCIATED WITH THE RETINAL PIGMENT EPITHELIUM ATROPHY.

PURPOSE: To determine the prognostic value of outer retinal tubulation (ORT) in the eyes of a Chinese cohort with Bietti crystalline dystrophy (BCD). METHODS: This retrospective, multicenter cohort study enrolled 42 patients with clinically and genetically diagnosed BCD. Eighty eyes with good-quality images of spectral domain optical coherence tomography were included. Demographic details and clinical data were collected. The characteristics of ORT, including prevalence, location, and morphologic characteristics were analyzed. RESULTS: Forty-two patients with BCD harbored potentially CYP4V2 disease-causing mutations. The mutation spectrum comprised 17 unique variants, 9 of which were novel. Fifty-two of these 80 eyes demonstrated evidence of ORT. The incidence of ORT is significantly higher in Stage 2 than other stages ( P < 0.001). ORT was mainly bilateral and located at the margin of the atrophic area of retinal pigment epithelium (RPE), and dynamically changed with the progressive RPE atrophy. The process of RPE atrophy was slower in eyes with ORT ( P = 0.017), with significantly longer intact RPE width in Stage 3 ( P = 0.024). Eyes with ORT had slower vision loss than eyes without ORT ( P = 0.044). CONCLUSION: ORT may be a sign of the onset of RPE atrophy in early-stage BCD and may suggest less risk of rapid progression in late-stage BCD.

A Novel Bispecific Fusion Protein Targeting C3b/C4b and VEGF in Patients With nAMD: A Randomized, Open-Label, Phase 1b Study.

PURPOSE: To evaluate the safety, tolerability, and efficacy of efdamrofusp alfa in patients with neovascular age-related macular degeneration (nAMD). DESIGN: Prospective randomized, open-label, multiple ascending-dose, phase 1b study. METHODS: Patients aged 50 years or older with active choroid neovascularization (CNV) secondary to nAMD were screened from 2 hospitals in 2 provinces in China. The first 9 patients were randomized 2:1 to intravitreally receive efdamrofusp alfa 2 mg at weeks 0, 4, and 8 or aflibercept 2 mg at weeks 0, 4, 8, and 16. After the dose-limiting toxicity assessment, 9 additional patients were randomized 2:1 to intravitreally receive efdamrofusp alfa 4 mg at weeks 0, 4, and 8 or aflibercept 2 mg at weeks 0, 4, 8, and 16. All patients were followed until week 20. Primary outcomes were safety and tolerability of efdamrofusp alfa. Secondary outcomes included changes from baseline in best-corrected visual acuity (BCVA), central subfield thickness (CST) as measured by spectral domain optical coherence tomography (SD-OCT), and CNV area as measured by fluorescein angiography (FA). RESULTS: A total of 18 patients were enrolled. Six each of them received efdamrofusp alfa 2 mg, efdamrofusp alfa 4 mg, or aflibercept 2 mg, respectively. No dose-limiting toxicity was reported, and all patients completed the study. No ocular serious adverse events were reported. All ocular treatment-emergent adverse events were intravitreal injection related and were mild or moderate in severity. At week 20, mean changes from baseline in BCVA were 5.64 ± 3.56, 8.93 ± 3.59, and 7.92 ± 3.55 letters for patients receiving efdamrofusp alfa 2 mg, efdamrofusp alfa 4 mg and aflibercept 2 mg, respectively. Meanwhile, CST and CNV area reductions indicative of anatomic improvement were observed in the majority of the patients receiving both doses of efdamrofusp alfa and aflibercept. CONCLUSIONS: Intravitreal efdamrofusp alfa dosed up to 4 mg every 4 weeks was well tolerated in nAMD patients with similar vision acuity and anatomic improvements.