In chronic spontaneous urticaria, increased Galectin-9 expression on basophils and eosinophils is linked to high disease activity, endotype-specific markers, and response to omalizumab treatment.

BACKGROUND: Galectin-9 (Gal-9) has been implicated in allergic and autoimmune diseases, but its role and relevance in chronic spontaneous urticaria (CSU) are unclear. OBJECTIVES: To characterize the role and relevance of Gal-9 in the pathogenesis of CSU. METHODS: We assessed 60 CSU patients for their expression of Gal-9 on circulating eosinophils and basophils as well as T cell expression of the Gal-9 receptor TIM-3, compared them with 26 healthy controls (HCs), and explored possible links with disease features including disease activity (urticaria activity score, UAS), total IgE, basophil activation test (BAT), and response to omalizumab treatment. We also investigated potential drivers of Gal-9 expression by eosinophils and basophils. RESULTS: Our CSU patients had markedly increased rates of circulating Gal-9+ eosinophils and basophils and high numbers of lesional Gal-9+ cells. High rates of blood Gal-9+ eosinophils/basophils were linked to high disease activity, IgE levels, and BAT negativity. Serum levels of TNF-α were positively correlated with circulating Gal-9+ eosinophils/basophils, and TNF-α markedly upregulated Gal-9 on eosinophils. CSU patients who responded to omalizumab treatment had more Gal-9+ eosinophils/basophils than non-responders, and omalizumab reduced blood levels of Gal-9+ eosinophils/basophils in responders. Gal-9+ eosinophils/basophils were negatively correlated with TIM-3+TH17 cells. CONCLUSION: Our findings demonstrate a previously unrecognized involvement of the Gal-9/TIM-3 pathway in the pathogenesis CSU and call for studies that explore its relevance.

Hg2+ removal characteristics of a strain of mercury-tolerant bacteria screened from heavy metal-contaminated soil in a molybdenum-lead mining area.

In this study, the mercury-tolerant strain LTC105 was isolated from a contaminated soil sample collected from a molybdenum-lead mine in Luanchuan County, Henan Province, China. The strain was shown to be highly resistant to mercury, with a minimum inhibitory concentration (MIC) of 32 mg·L-1. After a 24-h incubation in LB medium with 10 mg·L-1 Hg2+, the removal, adsorption, and volatilization rates of Hg2+ were 97.37%, 7.3%, and 90.07%, respectively, indicating that the strain had significant influence on mercury removal. Based on the results of Fourier infrared spectroscopy (FTIR) and scanning electron microscopy (SEM), the investigation revealed that the primary function of LTC105 was to encourage the volatilization of mercury. The LTC105 strain also showed strong tolerance to heavy metals such as Mn2+, Zn2+, and Pb2+. According to the results of the soil incubation test, the total mercury removal rate of the LTC105 inoculation increased by 16.34% when the initial mercury concentration of the soil was 100 mg·L-1 and by 62.28% when the initial mercury concentration of the soil was 50 mg·kg-1. These findings indicate that LTC105 has certain bioremediation ability for Hg-contaminated soil and is a suitable candidate strain for microbial remediation of heavy metal-contaminated soil in mining areas.

Synthesis of highly sensitive and multi-response Eu-MOF, fluorescence sensing properties and anti-counterfeiting applications.

A new Europium metal-organic framework (Eu-MOF), namely [Eu(dpa) (H2O)]·0.5(bpy)·4H2O}n (H4dpa = 5-(3,4-dicarboxyphenoxy) isophenic acid, bpy = protonated 4,4'-bipyridine) was synthesized and structurally characterized by elemental analyses, infrared spectroscopy, and X-ray single-crystal diffraction analyses. Eu-MOF shows a three-dimensional network structure based on EuIII ions and (dpa)4- ligands via µ4: η1, η2, η2, η2 coordination mode. Fluorescence analysis shows that Eu-MOF has excellent fluorescence sensing characteristics, which can efficiently and sensitively detect various pollutants in water: the limit of detection (LOD) of ratiometric fluorescence detection of ANI in water was 42.9 nM, which was better than the single-peak detection limit. In addition, the peak detection limits of Eu-MOF for Flu, ORN and NB were 120 nM, 27 nM and 94 nM, respectively. In addition, XPS, LUMO orbital energy level, fluorescence lifetime, ultraviolet absorption and other principles are used to explore the mechanism of fluorescence quenching. Surprisingly, Eu-MOF not only has excellent anti- counterfeiting ability and stability, can be used as anti-counterfeiting material in life, but also has good selectivity to Flu. Eu-MOF has obvious fluorescence quenching effect on Flu on paper under ultraviolet light, which can be used for rapid in situ imaging test paper of pesticide residues.

A multifunctional sensor for detecting tetracycline, 4-nitrophenol, and pesticides.

In recent years, due to the abuse of antibiotics, nitro explosives and pesticides, which have caused great harm to the environment and human health, social concerns have prompted researchers to develop more sensitive detection platforms for these pollutants. In this paper, a novel two-dimensional Zn (II) coordination polymer, [Zn(L)0.5(1,2-bimb)]·DMF (1), [H4L=[1,1':4',1''-terphenyl]-2, 2'',4, 4'' -tetracarboxylic acid, 1,2-bimb = 1,2-bis(imidazol-1-ylmethyl)benzene] was synthesized using a hydro-solvothermal method. Among commonly used organic solvents, 1 exhibits significant stability. Fast and efficient fluorescence response can be achieved for tetracycline (TET), 4-nitrophenol (4-NP), fluazinam (FLU), and abamectin benzoate (AMB) with low detection limits. A binary intelligent logic gate device with FLU and AMB as chemical input signals is successfully constructed, which provides a new idea for biochemical detection. In addition, a portable visual test paper has been prepared, which has high sensitivity, good selectivity, and simple operation. It can be used for rapid detection of pollutants in daily life and has broad application prospects. Finally, a detailed discussion was conducted on the fluorescence sensing mechanism of 1 for detecting TET, 4-NP, AMB and FLU.

Efficacy of type A botulinum toxin treatment for androgenetic alopecia using ultrasound combined with trichoscopy.

OBJECTIVE: This study aimed to assess the efficacy of type A botulinum toxin treatment for androgenetic alopecia (AGA) using a combination of ultrasound and trichoscopy. METHODS: Ninety patients with AGA who visited the Department of Dermatology at the Second Affiliated Hospital of Soochow University from September 2021 to December 2022 were prospectively selected. These patients met the diagnostic criteria outlined in the Chinese Guidelines for the Diagnosis and Treatment of Androgenetic Alopecia. The alopecia severity in the male patients ranged between grades 2 and 4 on the Norwood-Hamilton Scale. The patients were randomly assigned to receive injections of the same type of biological agent in a double-blind manner, with injection sites being the vertex or bilateral temporal-frontal hairline. In this study, the botulinum toxin group comprised 72 patients who received a biological agent with 100 units of type A botulinum toxin. The control group included 18 patients, and the biological agent administered to them contained 0 units of type A botulinum toxin. The patients were observed using 22-MHz ultrasound and trichoscopy before treatment, and 1 month and 3 months after treatment to compare the differences in various parameters at the injection sites. The ultrasound parameters included average follicle width, length, and count. The trichoscopy parameters were the number of hairs within a 1-cm2 area on the counting scale. No artificial interventions were performed at the injection sites, and all examination conditions were consistent. RESULTS: The patients in the botulinum toxin group had wider and longer average follicle width and length at the vertex 1 month and 3 months after treatment (p < 0.05), and wider and longer average follicle width and length in the left frontal area 3 months after treatment (p < 0.05) compared with those in the control group. The average follicle width and length gradually increased after treatment in the botulinum toxin group (p < 0.05), but no statistically significant differences were found in the control group (p > 0.05). The patients in the botulinum toxin group exhibited greater average follicle lengths after treatment at the vertex compared with the left frontal area (p < 0.05). No statistically significant differences were found in follicle count (p > 0.05) or hair count (p > 0.05) between the botulinum toxin and control groups after injection treatment. CONCLUSIONS: The follicle width and length are effective parameters for evaluating the efficacy of type A botulinum toxin treatment for AGA. Ultrasound revealed that the changes in follicles at the vertex occurred earlier than those in the left frontal area following treatment. Additionally, the changes in follicles were detected earlier than the changes in hair count using ultrasound. Ultrasound combined with trichoscopy provided more parameters for evaluating the efficacy of type A botulinum toxin treatment for AGA, resulting in a more comprehensive evaluation.

OMGMed: Advanced System for Ocular Myasthenia Gravis Diagnosis via Eye Image Segmentation.

This paper presents an eye image segmentation-based computer-aided system for automatic diagnosis of ocular myasthenia gravis (OMG), called OMGMed. It provides great potential to effectively liberate the diagnostic efficiency of expert doctors (the scarce resources) and reduces the cost of healthcare treatment for diagnosed patients, making it possible to disseminate high-quality myasthenia gravis healthcare to under-developed areas. The system is composed of data pre-processing, indicator calculation, and automatic OMG scoring. Building upon this framework, an empirical study on the eye segmentation algorithm is conducted. It further optimizes the algorithm from the perspectives of "network structure" and "loss function", and experimentally verifies the effectiveness of the hybrid loss function. The results show that the combination of "nnUNet" network structure and "Cross-Entropy + Iou + Boundary" hybrid loss function can achieve the best segmentation performance, and its MIOU on the public and private myasthenia gravis datasets reaches 82.1% and 83.7%, respectively. The research has been used in expert centers. The pilot study demonstrates that our research on eye image segmentation for OMG diagnosis is very helpful in improving the healthcare quality of expert doctors. We believe that this work can serve as an important reference for the development of a similar auxiliary diagnosis system and contribute to the healthy development of proactive healthcare services.

Aberrant expression of B7-H4 and B7-H5 contributes to the development of cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (CSCC) is the second most common malignant tumor of the skin. B7 homolog 4 (B7-H4) and B7-H5 (B7 homolog 5) are associated with a variety of tumors. Investigate the potential role of B7-H4 and B7-H5 in regulating the tumorigenesis and progression of CSCC. B7-H4 and B7-H5 transcriptome data were collected from GEO and TCGA databases and subjected to bioinformatical analysis by protein-protein interaction (PPI) network, functional enrichment analysis, immune analysis, and drug-gene interaction prediction analysis. We characterized the expression of B7-H4 and B7-H5 in carcinoma tissues of CSCC patients by immunohistochemistry. Meanwhile, the clinical correlation of B7-H4 and B7-H5 in CSCC was explored by statistical analysis. B7-H4 and B7-H5 genes were under-expressed in CSCC and correlated with tumor staging. According to GO and KEGG Pathway enrichment analysis, B7-H4, and B7-H5 can regulate the proliferation and activation of T cells, lymphocytes, and monocytes, and the expression of cytokines, such as IL-6 and IL-10, in CSCC. B7-H4 and B7-H5 are also jointly involved in the occurrence and development of CSCC via the JAK-STAT and Notch signaling pathways. We found that B7-H4 and B7-H5 proteins were abnormally highly expressed in CSCC tissue and correlated with tumor size and stage. Our findings offer new insights into the pathogenesis of CSCC and suggest that B7-H4 and B7-H5 are novel tissue biomarkers and promising therapeutic targets for CSCC.

The potential value of ultrasound in predicting local refractory/relapse events in primary thyroid lymphoma patients.

BACKGROUND: Primary thyroid lymphoma (PTL) is a rare malignant disorder, and ultrasound plays an important role in PTL diagnosis and follow-up surveillance. Prediction of refractory/relapse events in PTL patients is an essential issue, yet no ultrasonic PTL features have been discovered to be related to refractory/local relapse events. METHODS: From January 2008 to September 2022, newly diagnosed PTL patients in our center who underwent standard first-line treatment and received an ultrasound examination before treatment were enrolled. Data regarding patients' clinical and sonographic features, as well as their therapeutic responses were collected. Subjects with an ideal prognosis were compared to those with refractory/relapse events. RESULTS: In total, 37 PTL patients were analyzed, including 26 with diffuse large B-cell lymphoma, 2 with follicular lymphoma and 9 with mucosa-associated lymphoid tissue lymphoma. During the median follow-up of 25 months, 30 patients obtained a complete response, 4 were refractory patients, and 3 experienced local relapse. No significant difference was detected in the baseline clinical characteristics between patients with an ideal prognosis and those with refractory/local relapse events. In terms of sonographic features, however, an event-free survival (EFS) curve comparison revealed that patients with bilobar enlargement (defined as an anterior-posterior diameter > 2.5 cm on both sides of thyroid lobes) had a poorer EFS than those without (P < 0.0001), and patients with diffuse type had a poorer EFS than those with mixed/nodular types (P = 0.043). No significant difference was observed in EFS between patients with or without signs of suspicious cervical lymph node metastasis, rich blood signal distribution or symptoms of trachea compression. CONCLUSIONS: PTL patients with an anterior-posterior diameter > 2.5 cm for both thyroid lobes or PTL patients of the diffuse ultrasound type could be prone to refractory/local relapse events.

Prognostic Significance of KIF-12 Functioning as a Tumour Suppressor in Papillary Thyroid Carcinoma.

Objective: To explore the potential value of a novel marker, KIF-12, in the progression and prognosis of papillary thyroid carcinoma (PTC) through integrative bioinformatics analysis, and clinical sample validation of the prognostic value of KIF-12. Materials and Methods: We extracted the clinicopathological data of 502 PTC patients from The Cancer Genome Atlas-Thyroid Cancer (TCGA-THCA) dataset to identify reliable differentially expressed genes (DEGs) between high and low KIF12 expression groups. Functional enrichment analysis was performed on upregulated DEGs. Gene set enrichment analysis (GESA) was performed to identify the biological pathways. We further applied Cox analysis to determine independent risk factors associated with the PTC progression-free interval (PFI), and a nomogram was established to predict disease outcome. Finally, the prognostic value of KIF12 was validated by means of clinical samples from PTC patients with and without lateral lymph node metastasis. Results: On the basis of the TCGA-THCA database, we found that low KIF-12 expression was significantly related to a higher TNM stage (p<0.05), BRAF mutation status (p = 0.019), and extrathyroidal extension (p<0.001). KIF-12 was an independent prognostic factor of PTC (OR=0.319, 95% CI=0.130-0.784, P=0.013). The prognostic value of KIF12 was also successfully validated in clinical samples from twenty-nine PTC patients with lateral lymph node metastasis by comparison with twenty-two PTC patients without lymph node metastasis (P = 0.004). Conclusions: We report that KIF-12 has a tumor suppressive function in PTC and may be a useful prognostic tool to predict patient outcomes.

The impact of preoperative biliary drainage on postoperative healthcare-associated infections and clinical outcomes following pancreaticoduodenectomy: a ten-year retrospective analysis.

BACKGROUND: Pancreaticoduodenectomy (PD) is a complex procedure and easily accompanied by healthcare-associated infections (HAIs). This study aimed to assess the impact of PBD on postoperative infections and clinical outcomes in PD patients. METHODS: The retrospective cohort study were conducted in a tertiary hospital from January 2013 to December 2022. Clinical and epidemiological data were collected from HAIs surveillance system and analyzed. RESULTS: Among 2842 patients who underwent PD, 247 (8.7%) were diagnosed with HAIs, with surgical site infection being the most frequent type (n = 177, 71.7%). A total of 369 pathogenic strains were detected, with Klebsiella pneumoniae having the highest proportion, followed by Enterococcu and Escherichia coli. Although no significant association were observed generally between PBD and postoperative HAIs, subgroup analysis revealed that PBD was associated with postoperative HAIs in patients undergoing robotic PD (aRR = 2.174; 95% CI:1.011-4.674; P = 0.047). Prolonging the interval between PBD and PD could reduce postoperative HAIs in patients with cholangiocarcinoma (≥4 week: aRR = 0.292, 95% CI 0.100-0.853; P = 0.024) and robotic PD (≤2 week: aRR = 3.058, 95% CI 1.178-7.940; P = 0.022). PBD was also found to increase transfer of patients to ICU (aRR = 1.351; 95% CI 1.119-1.632; P = 0.002), extended length of stay (P < 0.001) and postoperative length of stay (P = 0.004). CONCLUSION: PBD does not exhibit a significant association with postoperative HAIs or other outcomes. However, the implementation of robotic PD, along with a suitable extension of the interval between PBD and PD, appear to confer advantages concerning patients' physiological recuperation. These observations suggest potential strategies that may contribute to enhanced patient outcomes.

m6A-Mediated Upregulation of Imprinted in Prader-Willi Syndrome Induces Aberrant Apical-Basal Polarization and Oxidative Damage in RPE Cells.

Purpose: To reveal the clinical significance, pathological involvement and molecular mechanism of imprinted in Prader-Willi syndrome (IPW) in RPE anomalies that contribute to AMD. Methods: IPW expression under pathological conditions were detected by microarrays and qPCR assays. In vitro cultured fetal RPE cells were used to study the pathogenicity induced by IPW overexpression and to analyze its upstream and downstream regulatory networks. Results: We showed that IPW is upregulated in the macular RPE-choroid tissue of dry AMD patients and in fetal RPE cells under oxidative stress, inflammation and dedifferentiation. IPW overexpression in fetal RPE cells induced aberrant apical-basal polarization as shown by dysregulated polarized markers, disrupted tight and adherens junctions, and inhibited phagocytosis. IPW upregulation was also associated with RPE oxidative damages, as demonstrated by intracellular accumulation of reactive oxygen species, reduced cell proliferation, and accelerated cell apoptosis. Mechanically, N6-methyladenosine level of the IPW transcript regulated its stability with YTHDC1 as the reader. IPW mediated RPE features by suppressing MEG3 expression to sequester its inhibition on the AKT serine-threonine kinase (AKT)/mammalian target of rapamycin (mTOR) pathway. We also noticed that the mTOR inhibitor rapamycin suppresses the AKT/mTOR pathway to alleviate the IPW-induced RPE anomalies. Conclusions: We revealed that IPW overexpression in RPE induces aberrant apical-basal polarization and oxidative damages, thus contributing to AMD progression. We also annotated the upstream and downstream regulatory networks of IPW in RPE. Our findings shed new light on the molecular mechanisms of RPE dysfunctions, and indicate that IPW blockers may be a promising option to treat RPE abnormalities in AMD.

Mapping the intellectual structure of the research of omalizumab in chronic spontaneous urticaria: A bibliometric analysis.

Background: The guidelines for treating chronic spontaneous urticaria (CSU) recommend using the IgE-targeted biologic omalizumab in patients with antihistamine-refractory disease. Objective: Our aim was to present a bibliometric review of publications related to omalizumab and CSU over the past 2 decades. Methods: Relevant publications from 2003 to 2022 were extracted from the Science Citation Index-Expanded (SCI-EXPANDED) database in the Web of Science Core Collection database as of January 8, 2023. We utilized CiteSpace (version 6.1.R3), VOSviewer (version 1.6.18), and the R package (version 4.2.1) to analyze and visualize the data. The R package bibliometrix (version 4.2.1) was also used. Results: Between 2003 and 2022, a total of 566 articles on omalizumab and CSU were published. Since 2014, there has been a rapid increase in publication output. According to the collaboration network, the most influential country, institute, and scholar were the United States, Charité Universitätsmedizin Berlin, and Marcus Maurer, respectively. The study identified the Journal of Allergy and Clinical Immunology: In Practice as the most productive journal and the Journal of Allergy and Clinical Immunology as the most cocited journal. The analysis of key words revealed the presence of high-frequency terms such as angioedema, IgE, treatment, anti-IgE, asthma, and atopic dermatitis. Moreover, recent studies in this area have concentrated mainly on biomarkers, dupilumab, and coronavirus 2019 (COVID-19). Conclusion: There has been a growing interest in the use of omalizumab in CSU in recent years. The current trending topics in this research are the identification of biomarkers and the development of new mAbs for the treatment of CSU.

Feasibility of whole-exome sequencing in fine-needle aspiration specimens of papillary thyroid microcarcinoma for the identification of novel gene mutations.

Genetic profiling is important for assisting the management of papillary thyroid microcarcinoma (PTMC). Although whole-exome sequencing (WES) of surgically resected PTMC tissue has been performed and revealed potential prognostic biomarkers, its application in PTMC fine-needle aspiration (FNA) specimens has not been explored. This study aimed to evaluate the feasibility of WES using FNA specimens of PTMC. Five PTMC patients were enrolled with clinical characteristics gathered. Fine aspiration cytology needle (23 gauges) was used to collect FNA biopsy with ultrasound guidance. WES analysis of FNA specimens from five PTMC patients and matched blood samples was performed. The WES of FNA samples yielded an average sequencing depth of 281× and average coverage of 99.5%. We identified 534 somatic single-nucleotide variants and 13 indels in total, and per sample, we found a mean of 24 exonic mutations, which affected a total of 120 genes. In the PTMC FNA samples, the most frequently mutated genes were BRAF and ANKRD18B, and the four driver genes were BRAF, AFF3, SRCAP, and EGFR. We also identified several germline cancer predisposing gene mutations. The results suggest that WES of FNA specimens is feasible for PTMC and can identify novel genetic mutations.

Lactylation-driven FTO targets CDK2 to aggravate microvascular anomalies in diabetic retinopathy.

Diabetic retinopathy (DR) is a leading cause of irreversible vision loss in working-age populations. Fat mass and obesity-associated protein (FTO) is an N6-methyladenosine (m6A) demethylase that demethylates RNAs involved in energy homeostasis, though its influence on DR is not well studied. Herein, we detected elevated FTO expression in vitreous fibrovascular membranes of patients with proliferative DR. FTO promoted cell cycle progression and tip cell formation of endothelial cells (ECs) to facilitate angiogenesis in vitro, in mice, and in zebrafish. FTO also regulated EC-pericyte crosstalk to trigger diabetic microvascular leakage, and mediated EC-microglia interactions to induce retinal inflammation and neurodegeneration in vivo and in vitro. Mechanistically, FTO affected EC features via modulating CDK2 mRNA stability in an m6A-YTHDF2-dependent manner. FTO up-regulation under diabetic conditions was driven by lactate-mediated histone lactylation. FB23-2, an inhibitor to FTO's m6A demethylase activity, suppressed angiogenic phenotypes in vitro. To allow for systemic administration, we developed a nanoplatform encapsulating FB23-2 and confirmed its targeting and therapeutic efficiency in mice. Collectively, our study demonstrates that FTO is important for EC function and retinal homeostasis in DR, and warrants further investigation as a therapeutic target for DR patients.

Key genes and immune infiltration in chronic spontaneous urticaria: a study of bioinformatics and systems biology.

Background: Chronic spontaneous urticaria (CSU) is defined by the spontaneous occurrence of wheals and/or angioedema for >6 weeks. The pathogenesis involves skin mast cells, but the complex causes of their activation remain to be characterized in detail. Objectives: To explore disease-driving genes and biological pathways in CSU. Methods: Two microarray data sets, e.g., GSE57178 and GSE72540, with mRNA information of skin from CSU patients, were downloaded from the Gene Expression Omnibus (GEO) database. An integrated bioinformatics pipeline including identification of differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction (PPI) network analysis, co-expression and drug prediction analysis, and immune and stromal cells deconvolution analyses were applied to identify hub genes and key drivers of CSU pathogenesis. Results: In total, we identified 92 up-regulated and 7 down-regulated genes in CSU lesions. These were significantly enriched in CSU-related pathways such as TNF, NF-κB, and JAK-STAT signaling. Based on PPI network modeling, four genes, i.e., IL-6, TLR-4, ICAM-1, and PTGS-2, were computationally identified as key pathogenic players in CSU. Immune infiltration analyses indicated that dendritic cells, Th2 cells, mast cells, megakaryocyte-erythroid progenitor, preadipocytes, and M1 macrophages were increased in lesional CSU skin. Conclusion: Our results offer new insights on the pathogenesis of CSU and suggest that TNF, NF-κB, JAK-STAT, IL-6, TLR-4, ICAM-1, and PTGS-2 may be candidate targets for novel CSU treatments.

Eltrombopag with or without Tacrolimus for relapsed/refractory acquired aplastic anaemia: a prospective randomized trial.

This trial compared eltrombopag (EPAG)+tacrolimus and EPAG monotherapy in patients with refractory/relapsed acquired aplastic anaemia (AA). Patients with refractory/relapsed AA were randomly assigned to receive either EPAG+tacrolimus or EPAG monotherapy at a ratio of 2:1. Patient response, safety, clonal evolution and survival were compared. In total, 114 patients were included in the analysis, with 76 patients receiving EPAG+tacrolimus and 38 receiving EPAG only. With a median follow-up of 18 (6-24) months, the overall response rate (ORR) for patients treated with EPAG+tacrolimus and EPAG alone was 38.2% vs. 31.6% (P = 0.490) at the 3rd month, 61.8% vs. 39.5% (P = 0.024) at the 6th month, 64.5% vs. 47.1% (P = 0.097) at the 12th month, and 60.5% vs. 34.2% (P = 0.008) at the last follow-up. The rate of each adverse event, overall survival curves (P = 0.635) and clonal evolution rate (P = 1.000) were comparable between the groups. A post hoc subgroup analysis showed that EPAG+tacrolimus could have advantage over EPAG monotherapy in terms of the ORR at the 6th month (P = 0.030)/last follow-up (P = 0.013) and the cumulative relapse-free survival (RFS) curves (P = 0.048) in patients <60 years old.

Corrigendum: Transarterial chemoembolization combined with lenvatinib versus transarterial chemoembolization combined with sorafenib for unresectable hepatocellular carcinoma: a systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fonc.2023.1074793.].

ALKBH5 causes retinal pigment epithelium anomalies and choroidal neovascularization in age-related macular degeneration via the AKT/mTOR pathway.

Retinal pigment epithelium (RPE) dysfunction and choroidal neovascularization (CNV) are predominant features of age-related macular degeneration (AMD), with an unclear mechanism. Herein, we show that RNA demethylase α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5) is up-regulated in AMD. In RPE cells, ALKBH5 overexpression associates with depolarization, oxidative stress, disturbed autophagy, irregular lipid homeostasis, and elevated VEGF-A secretion, which subsequently promotes proliferation, migration, and tube formation of vascular endothelial cells. Consistently, ALKBH5 overexpression in mice RPE correlates with various pathological phenotypes, including visual impairments, RPE anomalies, choroidal neovascularization (CNV), and interrupted retinal homeostasis. Mechanistically, ALKBH5 regulates retinal features through its demethylation activity. It targets PIK3C2B and regulates the AKT/mTOR signaling pathway with YTHDF2 as the N6-methyladenosine reader. IOX1, an ALKBH5 inhibitor, suppresses hypoxia-induced RPE dysfunction and CNV progression. Collectively, we demonstrate that ALKBH5 induces RPE dysfunction and CNV progression in AMD via PIK3C2B-mediated activation of the AKT/mTOR pathway. Pharmacological inhibitors of ALKBH5, like IOX1, are promising therapeutic options for AMD.

Using preoperative ultrasound vascularity characteristics to estimate medullary thyroid cancer.

BACKGROUND: The early diagnosis of medullary thyroid carcinoma (MTC) is still a challenge in clinical practice. Based on ultrasound features, many MTC cases without suspicious characteristics are not categorized as high risk for malignancy. This study was designed to comprehensively investigate the ultrasonic features of MTC on ultrasound and help identify thyroid nodules with a high risk of MTC. METHODS: Between 2017 and 2023, we retrospectively reviewed 116 consecutive thyroid nodules with a histologic diagnosis of MTC who had undergone preoperative ultrasound examination. According to the ultrasonic criteria for risk classification, nodules were classified as "ultrasound-high suspicious" (h-MTC) and "ultrasound-low suspicious" (l-MTC). Using the same database, a tumour size- and risk evaluation-matched control group comprising 62 lesions was randomly selected to compare the vascularity features of l-MTC disease. RESULTS: We identified 85 h-MTC nodules (73.3%) and 31 l-MTC nodules (26.7%). For patients with l-MTC disease, 22/31 (71.0%) of the lesions were followed up for a period before fine needle aspiration (FNA) or surgery. We observed more penetrating branching vascularity in the l-MTC group than in the benign nodule group (23/31, 74.2% vs. 5/59, 4.8%, P < 0.001). We also showed that more CHAMMAS IV patterns (central blood flow greater than perinodular flow) (87.1% vs. 32.3%, P < 0.001)) and CHEN IV patterns (penetrating vascularity) (100% vs. 25.8%, P < 0.001) were found in l-MTC than benign nodules. CONCLUSIONS: Vascularity features can help differentiate l-MTC from benign nodules; moreover, we report a novel sonographic vascularity pattern of l-MTC disease, penetrating branching vascularity. The utilization of vascularity features will help to identify MTC among nodules with low-intermediate suspicion by ultrasound risk classification to ensure appropriate clinical management.

Responsive photonic hydrogel for colorimetric detection of formaldehyde.

Formaldehyde (FA) can damage DNA, cause liver and kidney dysfunction, and ultimately lead to malignant tumors. Therefore, it is essential to develop a method that can conveniently detect FA with high detection sensitivity. Here, a responsive photonic hydrogel was prepared by embedding three-dimensional photonic crystal (PC) into amino-functionalized hydrogel to construct a colorimetric sensing film for FA. The amino groups on the polymer chains of the photonic hydrogel reacts with FA to increase the crosslinking density of the hydrogel, resulting in its volume shrinkage and a decrease in microsphere spacing of the PC. That causes the reflectance spectra blue-shift of more than 160 nm and color change from red to cyan for the optimized photonic hydrogel, achieving the sensitive, selective and colorimetric detection of FA. The constructed photonic hydrogel shows good accuracy and reliability for practical determination of FA in air and aquatic products, providing a new strategy for designing other target analytes responsive photonic hydrogels.