Image-based remote evaluation of PASI scores with psoriasis by the YOLO-v4 algorithm.

As a chronic relapsing disease, psoriasis is characterized by widespread skin lesions. The Psoriasis Area and Severity Index (PASI) is the most frequently utilized tool for evaluating the severity of psoriasis in clinical practice. Nevertheless, long-term monitoring and precise evaluation pose difficulties for dermatologists and patients, which is time-consuming, subjective and prone to evaluation bias. To develop a deep learning system with high accuracy and speed to assist PASI evaluation, we collected 2657 high-quality images from 1486 psoriasis patients, and images were segmented and annotated. Then, we utilized the YOLO-v4 algorithm to establish the model via four modules, we also conducted a human-computer comparison through quadratic weighted Kappa (QWK) coefficients and intra-class correlation coefficients (ICC). The YOLO-v4 algorithm was selected for model training and optimization compared with the YOLOv3, RetinaNet, EfficientDet and Faster_rcnn. The model evaluation results of mean average precision (mAP) for various lesion features were as follows: erythema, mAP = 0.903; scale, mAP = 0.908; and induration, mAP = 0.882. In addition, the results of human-computer comparison also showed a median consistency for the skin lesion severity and an excellent consistency for the area and PASI score. Finally, an intelligent PASI app was established for remote disease assessment and course management, with a pleasurable agreement with dermatologists. Taken together, we proposed an intelligent PASI app based on the image YOLO-v4 algorithm that can assist dermatologists in long-term and objective PASI scoring, shedding light on similar clinical assessments that can be assisted by computers in a time-saving and objective manner.

Preparation of Cobalt-Nitrogen Co-Doped Carbon Nanotubes for Activated Peroxymonosulfate Degradation of Carbamazepine.

Cobalt-nitrogen co-doped carbon nanotubes (Co3@NCNT-800) were synthesized via a facile and economical approach to investigate the efficient degradation of organic pollutants in aqueous environments. This material demonstrated high catalytic efficiency in the degradation of carbamazepine (CBZ) in the presence of peroxymonosulfate (PMS). The experimental data revealed that at a neutral pH of 7 and an initial CBZ concentration of 20 mg/L, the application of Co3@NCNT-800 at 0.2 g/L facilitated a degradation rate of 64.7% within 60 min. Mechanistic investigations indicated that the presence of pyridinic nitrogen and cobalt species enhanced the generation of reactive oxygen species. Radical scavenging assays and electron spin resonance spectroscopy confirmed that radical and nonradical pathways contributed to CBZ degradation, with the nonradical mechanism being predominant. This research presents the development of a novel PMS catalyst, synthesized through an efficient and stable method, which provides a cost-effective solution for the remediation of organic contaminants in water.

MicroRNA-98-5p Inhibits IFI44L-Mediated Differentiation of Dendritic Cells and Activation of Interferon Pathway in Systemic Lupus Erythematosus.

MicroRNA-98-5p (miR-98-5p) plays a protective role in the pathogenesis of autoimmune diseases through anti-inflammatory effects, but little is known about its role in Systemic lupus erythematosus (SLE). Our previous study suggested Interferon-inducible 44 like (IFI44L) overexpressed in monocytes which contributes to the pathogenesis of SLE by enhancing the maturation and functions of monocyte-derived dendritic cells (Mo-DCs), and miR-98-5p can regulate the expression of IFI44L. In this study, we identified miR-98-5p lowly expressed in both peripheral blood mononuclear cells (PBMCs) and monocytes of SLE patients along with high expression of IFI44L. IFI44L serves as target gene of miR-98-5p which inhibits differentiation of Mo-DCs and IFI44L-mediated activation of interferon pathway. We further showed that miR-98-5p promotes methylation of the IFI44L promoter to down-regulate its expression in SLE. Our results reveal an important role for miR-98-5p in the IFI44L-mediated immune imbalance of SLE and suggest a potential therapeutic target for SLE in the future.

Evaluation of Dry Eye Severity and Ocular Surface Inflammation in Patients with Pemphigus and Pemphigoid.

PURPOSE: To evaluate ocular surface involvement, tear cytokine levels, and histopathological changes in pemphigus and pemphigoid patients. METHODS: A total of 22 patients (15 pemphigus and 7 pemphigoids) and 21 non-diseased controls were enrolled in our study. All participants underwent ocular surface evaluation, which included ocular surface disease index test, slit lamp observation, dry eye-related examination, tear multicytokine analysis, and conjunctival impression cytology. RESULTS: Pemphigus and pemphigoid patients presented much more severe conjunctivochalasis, corneal epithelial defects, corneal opacity, symblepharon   and dry eye. Severe ocular surface squamous metaplasia and a significant increase of tear macrophage inflammatory protein-1beta, tumor necrosis factor-alpha, interleukin (IL)-1ß, IL -6, and IL-8 occurred in pemphigus and pemphigoid patients. CONCLUSIONS: Our results revealed that ocular surface inflammation and dry eye persist in most pemphigus and pemphigoid patients, and do not occur in parallel with the systemic course. Regular ophthalmological examinations and local anti-inflammatory should be provided for pemphigus and pemphigoid patients.

Facile Synthesis of Basic Copper Carbonate Nanosheets for Photoacoustic Imaging-Guided Tumor Apoptosis and Ferroptosis and the Extension Exploration of the Synthesis Method.

Elimination of tumor cells using carbonate nanomaterials with tumor microenvironment-responsive capacity has been explored as an effective strategy. However, their therapeutic outcomes are always compromised by the relatively low intratumoral accumulation and limited synthesis method. Herein, a novel kind of basic copper carbonate nanosheets was designed and prepared using a green synthesis method for photoacoustic imaging-guided tumor apoptosis and ferroptosis therapy. These nanosheets were synthesized with the assistance of dopamine and ammonium bicarbonate (NH4HCO3) and the loading of glucose oxidase (GOx). NH4HCO3 could not only provide an alkaline environment for the polymerization of dopamine but also supply carbonates for the growth of nanosheets. The formed nanosheets displayed good acid and near-infrared light responsiveness. After intercellular uptake, they could be degraded to release Cu2+ and GOx, generating hydroxyl radicals through a Cu+-mediated Fenton-like reaction, consuming glucose, up-regulating H2O2 levels, and down-regulating GSH levels. Tumor elimination could be achieved by hydroxyl radical-induced apoptosis and ferroptosis. More amusingly, this synthesis method can be extended to several kinds of mono-element and multi-element carbonate nanomaterials (e.g., Fe, Mn, and Co), showing great potential for further tumor theranostics.

Ocular surface involvement and histopathologic changes in the acute stage of Stevens-Johnson syndrome and toxic epidermal necrolysis: a cross-sectional study.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and extremely serious drug-induced dermatological disorders. The ocular surface condition at the early stage has been little studied and should contribute to novel perspectives in early and effective topical therapy of these diseases. The objectives of the study were to evaluate the acute phase of ocular surface involvement and histopathologic changes in patients with acute SJS/TEN. METHODS: Ten patients with acute phase of SJS/TEN onset and eleven age- and sex-matched healthy volunteers were recruited. Ocular surface symptoms and signs, conjunctival impression cytology, and tear multi-cytokine were assessed. RESULTS: Ocular surface objective signs were normal at the acute stage of SJS/TEN, while most patients have abnormal ocular surface subjective symptoms and meibomian gland secretion. Conjunctival impression cytology showed a significant decrease in goblet cell density and severe ocular surface squamous metaplasia in acute SJS/TEN patients. Tear multi-cytokine analysis showed all 21 pro- and anti-inflammatory cytokines all sharply elevated. Goblet cell density was significantly negatively correlated with tear C-X3-C motif chemokine ligand 1 (CX3CL1) and interleukin 13. CONCLUSIONS: Severe pathologic squamous metaplasia and inflammation onset in the ocular surface at the acute stage of the SJS/TEN, even if the ocular surface condition seemed basically normal with adequate systemic immunosuppressant and general supportive treatment. Early topical anti-inflammatory therapy should be carried out actively.

The differential panorama of clinical features of lupus erythematosus patients with different onset ages: a cross-sectional multicenter study from China.

OBJECTIVES: This study aims to compare the differences among patients of different onset ages in various subtypes of lupus erythematosus (LE) and to draw a panorama of the clinical characteristics of patients with different onset ages. METHOD: Subjects were recruited from the Lupus Erythematosus Multicenter Case-control Study in Chinese populations (LEMCSC), grouped by the age of onset (childhood-onset: onset < 18 years, adult-onset: onset 18-50 years, late-onset: onset > 50 years). The data collected included demographic characteristics, LE-related systemic involvement, LE-related mucocutaneous manifestations, and laboratory results. All included patients were assigned into three groups: systemic LE (SLE) group (with systemic involvement, with or without mucocutaneous lesions), cutaneous LE (CLE) group (patients who were accompanied by any type of LE-specific cutaneous manifestations), and isolated cutaneous LE (iCLE) group (patients who were in CLE group without systemic involvements). Data were analyzed using R version 4.0.3. RESULTS: A total of 2097 patients were involved, including 1865 with SLE and 232 with iCLE. We also identified 1648 patients with CLE among them, as there was some overlap between the SLE population and CLE population (patients with SLE and LE-specific cutaneous manifestations). Later-onset lupus patients seemed to be less female predominance (p < 0.001) and have less systemic involvement (except arthritis), lower positive rates of autoimmune antibodies, less ACLE, and more DLE. Moreover, childhood-onset SLE patients presented a higher risk of LE family history (p = 0.002, vs adult-onset SLE). In contrast to other LE-nonspecific manifestations, the self-reported photosensitivity history decreased with the age of onset in SLE patients (51.8%, 43.4%, and 39.1%, respectively) but increased in iCLE patients (42.4%, 64.9%, and 89.2%, respectively). There was also a gradual increase in self-reported photosensitivity from SLE, CLE, to iCLE in both adult-onset and late-onset lupus patients. CONCLUSIONS: A negative correlation was suggested between the age of onset and the likelihood of systemic involvement, except for arthritis. As the age of onset increases, patients have a greater propensity to exhibit DLE compared to ACLE. Moreover, the presence of rapid response photodermatitis (i.e., self-reported photosensitivity) was associated with a lower rate of systemic involvement. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2100048939) on July 19, 2021, retrospectively registered. Key Points • We confirmed some phenomena that have been found in patients with SLE, such as the highest proportion of females of reproductive age, the higher risk of LE family history in childhood-onset SLE patients, and the less self-reported photosensitivity in the late-onset SLE group. We also compared the similarities and differences of these phenomena in patients with CLE or iCLE for the first time. • In patients with SLE, the proportion of females peaked in adult-onset patients, but this phenomenon disappeared in iCLE patients: the female-male ratio tends to decrease from childhood-onset iCLE, adult-onset iCLE, to late-onset iCLE. • Patients with early-onset lupus are more likely to have acute cutaneous lupus erythematosus (ACLE), and patients with late-onset lupus are more likely to have discoid lupus erythematosus (DLE). • In contrast to other LE-nonspecific manifestations, the incidence of rapid response photodermatitis (i.e., self-reported photosensitivity) decreased with the age of onset in SLE patients but increased with the age of onset in iCLE patients.

Panoramic view of clinical features of lupus erythematosus: a cross-sectional multicentre study from China.

OBJECTIVE: Lupus erythematosus (LE) is a complicated disease with highly heterogeneous clinical manifestations. Previous studies have rarely included all subgroups of patients with lupus and have overlooked the importance of the cutaneous manifestations thereof. We aimed to compare the demographic and clinical differences among patients with different subtypes of lupus. METHODS: This is the first real-world study with a relatively large sample size that simultaneously includes patients with isolated cutaneous lupus erythematosus (iCLE) and SLE. All samples were obtained from the Lupus Erythematosus Multicenter Case-control Study in Chinese populations (LEMCSC) (registration number: ChiCTR2100048939). Comparative analyses between different LE subgroups were performed. RESULTS: A total of 2097 patients with lupus were included, with 1865 patients with SLE, 1648 with cutaneous lupus erythematosus (CLE), and 232 with iCLE. Among the patients with CLE, 1330 had acute cutaneous lupus erythematosus (ACLE); 160 had subacute cutaneous lupus erythematosus (SCLE); and 546 had chronic cutaneous lupus erythematosus (CCLE). The study included a relatively large number of patients with CCLE subtypes, including 311 with discoid lupus erythematosus (DLE), 262 with chilblain lupus erythematosus (CHLE) and 45 with lupus erythematosus profundus (LEP). Demographic characteristics, systemic involvement, mucocutaneous manifestations and autoantibodies were significantly different among the groups. CONCLUSIONS: CLE and iCLE are two distinct disease states, and the selection of broad or narrow CLE definitions should be emphasised in scientific reports. LE-non-specific cutaneous lesions imply more severity, while self-reported photosensitivity and LE-specific cutaneous manifestations imply milder severity. Generalised ACLE appears to be a more severe state than localised ACLE, and CHLE appears to be more severe than DLE. Anti-Sjögren's syndrome-related antigen B (SSB) antibodies have higher specific directivity than anti-Sjögren's syndrome-related antigen A (SSA) antibodies for SCLE lesions. Anti-double-stranded DNA antibodies have a higher co-occurrence with ACLE and a lower co-occurrence with SCLE and CCLE. Compared with DLE, CHLE has significantly higher positive rates of anti-SSA/Ro60 (71%) and anti-SSA/Ro52 (42.4%) antibodies, whereas LEP is associated with a higher positive rate of antinucleosome antibodies (31.1%).

Novel polymorphism of IFI44L associated with the susceptibility and clinical characteristics of systemic lupus erythematosus in a Chinese population.

BACKGROUND: Interferon-inducible 44 like (IFI44L) is a newly discovered gene which has been reported to associate with the susceptibility of some infectious diseases, but there is no data on IFI44L SNP polymorphism associated with Systemic lupus erythematosus (SLE). In this study, we aimed to evaluate the association of IFI44L rs273259 polymorphism with the susceptibility and clinical characteristics of SLE in a Chinese population. METHODS: 576 SLE patients and 600 controls were recruited in this case-control study. Blood DNA was extracted and IFI44L rs273259 polymorphism was detected by TaqMan SNP Genotyping Assay Kit. The expression levels of IFI44L in Peripheral blood mononuclear cells were detected by RT-qPCR. The DNA methylation levels of IFI44L promoter were detected by bisulfite pyrosequencing. RESULTS: The genotype and allele frequencies of IFI44L rs273259 in SLE patients have a significantly difference compared to healthy controls (P < 0.001). The genotype AG (vs. AA: OR = 2.849; P < 0.001) and the allele G (vs. A: OR = 1.454; P < 0.001) were associated with increased susceptibility of SLE. IFI44L rs273259 polymorphism was associated with clinical characteristics of SLE including malar rash (P < 0.001), discoid rash (P < 0.001), lupus nephritis (P < 0.001) and anti-Smith antibodies (P < 0.001). The expression levels of IFI44L were most significantly increased in genotype AG than genotype AA and GG (P < 0.01). The DNA methylation levels of IFI44L promoter were most significantly decreased in genotype AG than genotype AA and GG (P < 0.01). CONCLUSIONS: Our results indicate novel polymorphism of IFI44L rs273259 was associated with the susceptibility and clinical characteristics of SLE in the Chinese population.

Consecutive injections of low-dose interleukin-2 improve symptoms and disease control in patients with chronic spontaneous urticaria.

PURPOSE: To describe the effectiveness and tolerability of low-dose interleukin (IL)-2 in treating patients with chronic spontaneous urticaria (CSU) refractory to H1-antihistamines. METHODS: This retrospective study included CSU patients who received treatment with at least one cycle of IL-2, injected intramuscularly at a dose of 1.0 million international units daily for 7 consecutive days, after failing treatment with H1-antihistamines. Patients were followed up for ≥12 weeks. RESULTS: Of the 15 patients, 7 (46.7%) and 11 (73.3%) achieved complete response at Week 2 and Week 12, respectively. The mean change of urticaria control test (UCT) and weekly urticaria activity score (UAS7) from baseline was 6.6 (95% CI, 4.2 to 8.9) and - 16.9 (95% CI, -24.0 to -9.8), respectively, at Week 12. Local injection-site reactions were the most common adverse events. No serious adverse events were reported. CONCLUSION: Low-dose IL-2 treatment improves symptoms and disease control for CSU patients refractory to H1-antihistamines.

Bach2 in CD4+ T cells from SLE patients modulates B-cell differentiation and IgG production.

T and B cells participate in the development of systemic lupus erythematosus (SLE). BTB and CNC homology 2 (Bach2) is an irreplaceable regulator in the T and B lineages that helps to maintain immune homeostasis. However, the function of Bach2 in the pathogenesis of SLE has not been studied in depth. Flow cytometry and qRT-PCR were used to assess Bach2 levels, bisulfite sequencing PCR was used to measure the methylation level, and silencing by electroporation and stimulation with a cytokine concentration gradient were used to investigate the effect of Bach2 on T cells. Bach2 expression was elevated in the helper T-cell subsets (T follicular helper, Th1, Th2, Th17, and Treg cells) of SLE patients and negatively correlated with disease severity and autoantibody levels. CD4+ T cells from SLE patients had decreased methylation levels in the Bach2 promoter region. Silencing Bach2 in CD4+ T cells induced increases in the CD19+ B-cell count, plasmablasts, and secretion of IgG by prompting the secretion of cytokines. The activation signals CD3/CD28, IL-6, and IL-21 upregulated Bach2 expression in CD4+ T cells. The regulation of Bach2 by cytokines and T-cell activation signals in CD4+ T cells was shown to act on B cells and play a protective role against SLE.

Repolarizing tumor-associated macrophages by layered double hydroxide-based deacidification agent for tumor chemodynamic therapy and immunotherapy.

Tumor-associated macrophages (TAMs)-mediated immunotherapy has attracted extensive attention in tumor elimination. However, the acidic tumor microenvironment (TME) severely limits the phenotype of TAMs to pro-tumoral M2 state, suppressing immune response efficacy against tumors. Herein, novel poly(acrylic acid) (PAA)-coated, doxorubicin (DOX)-loaded layered double hydroxide (LDH) nanosheets (NSs) were developed as deacidification agent to repolarize TAMs from pro-tumoral M2 to anti-tumoral M1 phenotype for tumor elimination through combined chemodynamic therapy and immunotherapy. When located in tumor regions, LDH-PAA@DOX NSs display good deacidification capacity to neutralize acidic TME, achieving the repolarization of TAMs to M1 phenotype and further activating CD8+ T cells. During the deacidification process, these NSs are acid-responsive and degrade to release Fe3+ and DOX. The former can be reduced to Fe2+ by intracellular glutathione, meanwhile disrupting the antioxidant defense system of tumor cells. The latter can damage tumor cells directly and further stimulate the production of hydrogen peroxide, providing abundant substrate for the Fenton reaction. Toxic hydroxyl radical is excessively produced through Fe2+-mediated Fenton reaction to cause intratumoral oxidative stress. In vivo data revealed that significant tumor elimination can be achieved under LDH-PAA@DOX treatment. This work not only provides a promising paradigm for neutralizing acidic TME using deacidification agent but also highlights the effectiveness of combined chemodynamic therapy and immunotherapy in tumor treatment.

Ocular surface disorders affect quality of life in patients with autoimmune blistering skin diseases: a cross-sectional study.

BACKGROUND: Autoimmune blistering skin diseases (AIBD) are a group of rare chronic autoimmune diseases which are associated with ocular surface diseases especially dry eye disease. This study is designed to investigate the relationship between ocular surface disorders and quality of life among patients with autoimmune blistering skin diseases. METHODS: Twenty-four AIBD patients (18 pemphigus and 7 pemphigoid) and twenty-five non-AIBD controls were included. Ocular surface disease index (OSDI), ocular surface evaluation, including slit-lamp examination, Schirmer I test, tear break-up time, corneal fluorescein staining, lid-parallel conjunctival folds, meibomian gland evaluation, presence of symblepharon and corneal opacity were assessed. Life quality was evaluated by multiple questionnaires, including Medical Outcomes Study 36-Item Short Form Questionnaire (SF-36), Hospital Anxiety and Depression Scale (HADS), Pittsburgh Sleep Quality Index (PSQI) and Health Assessment Questionnaire-Disability Index (HAQ-DI). Ocular surface tests and quality of life were compared between AIBD patients and non-AIBD controls. In the AIBD patients, the associations between ocular surface parameters and quality of life were also evaluated. RESULTS: 92% of AIBD patients and 87.5% of age- and sex-matched non-AIBD controls were diagnosed with dry eye in this study. Compared with non-AIBD controls, AIBD patients reported lower SF-36 scores (P < 0.05) and severer OSDI, Schirmer I test, tear break-up time, corneal fluorescein staining, presence of symblepharon and corneal opacity measures (P < 0.05). OSDI, Schirmer I test were correlated with SF-36 composite scores or scores on the SF-36 subscales. CONCLUSIONS: AIBD patients experience reduced quality of life and more severe ocular surface disorders including dry eye, symblepharon and corneal opacity. Early treatments of dry eye and collaborations among multidisciplinary physicians are necessary in patients with AIBD.

Sorafenib-Loaded Copper Peroxide Nanoparticles with Redox Balance Disrupting Capacity for Enhanced Chemodynamic Therapy against Tumor Cells.

Chemodynamic therapy (CDT) is a promising hydroxyl radical (•OH)-mediated tumor therapeutic method with desirable tumor specificity and minimal side effects. However, the efficiency of CDT is restricted by the pH condition, insufficient H2O2 level, and overexpressed reductive glutathione (GSH), making it challenging to solve these problems simultaneously to improve the efficacy of CDT. Herein, a kind of polyvinylpyrrolidone-stabilized, sorafenib-loaded copper peroxide (CuO2-PVP-SRF) nanoparticle (NPs) was designed and developed for enhanced CDT against tumor cells through the synergetic pH-independent Fenton-like, H2O2 self-supplying, and GSH depletion strategy. The prepared CuO2-PVP-SRF NPs can be uptaken by 4T1 cells to specifically release Cu2+, H2O2, and SRF under acidic conditions. The intracellular GSH can be depleted by SRF-induced system xc- dysfunction and Cu2+-participated redox reaction, causing the inactivation of GPX4 and generating Cu+. A great amount of •OH was produced in this reducing capacity-disrupted condition by the Cu+-mediated Fenton-like reaction, causing cell apoptosis and lipid hydroperoxide accumulation-induced ferroptosis. They display an excellent 4T1 cell killing outcome through the improved •OH production capacity. The CuO2-PVP-SRF NPs display elevated therapeutic efficiency of CDT and show good promise in further tumor treatment applications.

A Rare Case of Pediatric Xanthoma Disseminatum With Diabetes Insipidus and BRAF p.V600E Mutation.

ABSTRACT: Xanthoma disseminatum (XD) is a rare non-Langerhans cell histiocytosis characterized by xanthomatous lesions in the absence of hyperlipidemia. XD usually develops in young adults, and there are rare cases among children. BRAF mutations are frequent in Langerhans cell histiocytosis and Erdheim-Chester disease but absent or only rarely detected in other histiocytosis. Herein, we described a 6-year-old Chinese girl presented with generalized skin lesions and diabetes insipidus for 5 months. There were multiple periorbital xanthelasma with histopathological features of foamy histiocytes infiltration with Touton cells. Pituitary magnetic resonance imaging showed pituitary enlargement and pituitary stalk thickening. The presence of BRAF p.V600E mutation makes this case distinctive and also offers a potential therapeutic target. According to our review of the literature, this is the first pediatric XD with diabetes insipidus and BRAF mutation.