Novel glucomannan-like polysaccharide from Lycium barbarum L. ameliorates renal fibrosis via blocking macrophage-to-myofibroblasts transition.

The macrophage to myofibroblasts transition (MMT) has been reported as a newly key target in renal fibrosis. Lycium barbarum L. is a traditional Chinese medicine for improving renal function, in which its polysaccharides (LBPs) are the mainly active components. However, whether the role of LBPs in treating renal fibrosis is related to MMT process remain unclear. The purpose of this study was to explore the relationship between the regulating effect on MMT process and the anti-fibrotic effect of LBPs. Initially, small molecular weight LBPs fractions (LBP-S) were firstly isolated via Sephadex G-100 column. Then, the potent inhibitory effect of LBP-S on MMT process was revealed on bone marrow-derived macrophages (BMDM) model induced by TGF-ß. Subsequently, the chemical structure of LBP-S was elucidated through monosaccharide, methylation and NMR spectrum analysis. In vivo biodistribution characteristics studies demonstrated that LBP-S exhibited effectively accumulation in kidney via intraperitoneal administration. Finally, LBP-S showed a satisfactory anti-renal fibrotic effect on unilateral ureteral obstruction operation (UUO) mice, which was significantly reduced following macrophage depletion. Overall, our findings indicated that LPB-S could alleviate renal fibrosis through regulating MMT process and providing new candidate agents for chronic kidney disease (CKD) related fibrosis treatment.

A sensitive fluorescence assay of serum dipeptidyl peptidase IV activity to predict the suitability of its inhibitors in patients with type 2 diabetes mellitus.

DPP-IV inhibitors, which are close to the natural hypoglycemic pathway of human physiology and have few side effects, have been extensively employed in the management of type 2 diabetes mellitus (T2DM). However, there are currently no specific blood indicators that can indicate or predict a patient's suitability for DPP-IV inhibitors. In this study, based on the self-developed high-specificity fluorescent substrate glycyl-prolyl-N-butyl-4-amino-1, 8-naphthimide (GP-BAN), a detection method of human serum DPP-IV activity was established and optimized. The method demonstrates a favorable lower limit of detection (LOD) at 0.32 ng/mL and a satisfactory lower limit of quantification (LOQ) of 1.12 ng/mL, and can be used for the detection of DPP-IV activity in trace serum (2 µL). In addition, Vitalliptin and Sitagliptin showed similar IC50 values when human recombinant DPP-IV and human serum were used as enzyme sources, and the intra-day and inter-day precision obtained by the microplate analyzer were less than 15 %. These results indicate that the microplate reader based detection technique has good accuracy, repeatability and reproducibility. A total of 700 volunteers were recruited, and 646 serum samples were tested for DPP-IV activity. The results showed that serum DPP-IV activity was higher in patients with T2DM than in controls (P < 0.01). However, the statistical data of family history of diabetes, gender and age of diabetic patients showed no statistical significance, and there was no contrast difference. The DPP-IV activity of serum in T2DM patients ranged from 2.4 µmol/min/L to 78.6 µmol/min/L, with a huge difference of up to 32-fold. These results suggest that it is necessary to test DPP-IV activity in patients with T2DM when taking DPP-IV inhibitors to determine the applicability of DPP-IV inhibitors in T2DM patients. These results suggest that it is necessary to detect the activity of DPP-IV in blood before taking DPP-IV inhibitors in patients with T2DM to judge the applicability of DPP-IV inhibitors in patients with T2DM.

Resolving the Stellar-Collapse and Hierarchical-Merger Origins of the Coalescing Black Holes.

Spin and mass properties provide essential clues in distinguishing the origins of coalescing black holes (BHs). With a dedicated semiparametric population model for the coalescing binary black holes (BBHs), we identify two distinct categories of BHs among the GWTC-3 events, which is favored over the one population scenario by a logarithmic Bayes factor (lnB) of 7.5. One category, with a mass ranging from ∼25M_{⊙} to ∼80M_{⊙}, is distinguished by the high spin magnitudes (∼0.75) and consistent with the hierarchical merger origin. The other category, characterized by low spins, has a sharp mass cutoff at ∼40M_{⊙}, which is natural for the stellar-collapse origin and in particular the pair-instability explosion of massive stars. We infer the local hierarchical merger rate density as 0.46_{-0.24}^{+0.61} Gpc^{-3} yr^{-1}. Additionally, we find that a fraction of the BBHs has a cosine-spin-tilt-angle distribution concentrated preferentially around 1, and the fully isotropic distribution for spin orientation is disfavored by a lnB of -6.3, suggesting that the isolated field evolution channels are contributing to the total population.

PruΔcdpk2 Protects Pigs against Acute Toxoplasmosis Depending on T-Lymphocyte Subsets and Natural Killer Cell Responses.

Toxoplasma gondii is a widespread protozoan parasite approximately infecting one-third of the world population and can cause serious public health problems. In this study, we investigated the protective effect of the attenuated vaccine Pru:Δcdpk2 against acute toxoplasmosis and explored the underlying immune mechanisms of the protection in pigs. The systemic T-cell and natural killer (NK) cell responses were analyzed, including kinetics, phenotype, and multifunctionality (interferon [IFN]-γ, tumor necrosis factor [TNF]-α), and the IFN-γ levels were analyzed in PBMCs. Our results showed that T. gondii-specific antibodies were induced by Pru:Δcdpk2. After challenging with RH, the antibodies were able to respond quickly in the immunized group, and the expression level was significantly higher than that in the unimmunized group. The expression level of IFN-γ significantly increased after vaccination, and the CD3+ γδ-, NK, and CD3+ γδ+ cell subsets also significantly increased. At the same time, functional analysis indicated that these cells were polarized toward a Th1 phenotype, showing the ability to secrete IFN-γ and TNF-α. The CD4+CD8α-T cell population exhibited a higher frequency of IFN-γ+ producing cells compared with the CD4-CD8α+ and CD4+CD8α+ cell populations during the early days of vaccination. Our results indicated that the attenuated vaccine could induce the expression of NK, γδ, and CD3αß cells in pigs, and IFN-γ and TNF-α secreted by these cells are important for resistance to T. gondii infection.

Effects of tranexamic acid preconditioning on the incidence of postpartum haemorrhage in vaginal deliveries with identified risk factors in China: a prospective, randomized, open-label, blinded endpoint trial.

OBJECTIVE: This study aimed to evaluate the effects of tranexamic acid (TXA) in preventing postpartum haemorrhage (PPH) among women with identified risk factors for PPH undergoing vaginal delivery in China. METHODS: This prospective, randomized, open-label, blinded endpoint (PROBE) trial enrolled 2258 women with one or more risk factors for PPH who underwent vaginal delivery. Participants were randomly assigned in a 1:1 ratio to receive an intravascular infusion of 1 g TXA or a placebo immediately after the delivery of the infant. The primary outcome assessed was the incidence of PPH, defined as blood loss ≥500 mL within 24 h after delivery, while severe PPH was considered as a secondary outcome and defined by total blood loss ≥1000 mL within 24 h. RESULTS: 2245 individuals (99.4%) could be followed up to their primary outcome. PPH occurred in 186 of 1128 women in the TXA group and in 215 of 1117 women in the placebo group (16.5% vs. 19.2%; RR, 0.86; 95% CI, 0.72 to 1.02; p = 0.088). Regarding secondary outcomes related to efficacy, women in the TXA group had a significant lower rate of severe PPH than those in the placebo group (2.7% vs. 5.6%; RR, 0.49; 95% CI, 0.32 to 0.74; p = 0.001; adjusted p = 0.002). Similarly, there was a significant reduction in the use of additional uterotonic agents (7.8% vs. 15.6%; RR, 0.50; 95% CI, 0.39 to 0.63; p < 0.001; adjusted p = 0.001). No occurrence of thromboembolic events and maternal deaths were reported in both groups within 30 days after delivery. CONCLUSIONS: In total population with risk factors for PPH, the administration of TXA following vaginal delivery did not result in a statistically significant reduction in the incidence of PPH compared to placebo; however, it was associated with a significantly lower incidence of severe PPH.

Prophylactic administration of TXA did not yield a statistically significant reduction in the incidence of PPH among women with risk factors in vaginal deliveries.Prophylactic use of TXA may help to reduce the incidence of severe PPH.

A comparison of wild boar and domestic pig microbiota does not reveal a loss of microbial species but an increase in alpha diversity and opportunistic genera in domestic pigs.

The microbiome of wild animals is believed to be co-evolved with host species, which may play an important role in host physiology. It has been hypothesized that the rigorous hygienic practices in combination with antibiotics and diets with simplified formulas used in the modern swine industry may negatively affect the establishment and development of the gut microbiome. In this study, we evaluated the fecal microbiome of 90 domestic pigs sampled from nine farms in Canada and 39 wild pigs sampled from three different locations on two continents (North America and Europe) using 16S rRNA gene amplicon sequencing. Surprisingly, the gut microbiome in domestic pigs exhibited higher alpha-diversity indices than wild pigs (P < 0.0001). The wild pig microbiome showed a lower Firmicutes-to-Bacteroidetes ratio and a higher presence of bacterial phyla Elusimicrobiota, Verrucomicrobiota, Cyanobacteria, and Fibrobacterota when compared to their domestic counterparts. At the genus level, the wild pig microbiome had enriched genera that were known for fiber degradation and short-chain fatty acid production. Interestingly, the phylum Fusobacteriota was only observed in domestic pigs. We identified 31 ASVs that were commonly found in the pig gut microbiome, regardless of host sources, which could be recognized as members of the core gut microbiome. Interestingly, we found five ASVs missing in domestic pigs that were prevalent in wild ones, whereas domestic pigs harbored 59 ASVs that were completely absent in wild pigs. The present study sheds light on the impact of domestication on the pig gut microbiome, including the gain of new genera, which might provide the basis to identify novel targets to manipulate the pig gut microbiome for improved health. IMPORTANCE: The microbiome of pigs plays a crucial role in shaping host physiology and health. This study sought to identify if domestication and current rearing practices have resulted in a loss of co-evolved bacterial species by comparing the microbiome of wild boar and conventionally raised pigs. It provides a comparison of domestic and wild pigs with the largest sample sizes and is the first to examine wild boars from multiple sites and continents. We were able to identify core microbiome members that were shared between wild and domestic populations, and on the contrary to expectation, few microbes were identified to be lost from wild boar. Nevertheless, the microbiome of wild boars had a lower abundance of important pathogenic genera and was distinct from domestic pigs. The differences in the microbial composition may identify an opportunity to shift the microbial community of domestic pigs towards that of wild boar with the intent to reduce pathogen load.

Enhancement of Corrosion and Wear Resistance of Ni-P Coatings Stems from the Synergistic Effects of Cr3C2 and Heat Treatment.

This study describes the preparation of Ni-P-Cr3C2 composite coatings using pulsed electrodeposition, with varying Cr3C2 concentrations (0, 1, 2, 3, 4, and 5 g/L). Subsequently, the Ni-P-Cr3C2 composite coatings are heat-treated at different temperatures (200, 400, and 600 °C) using the characteristic of Cr3C2 oxidizing to Cr2O3 at high temperatures. The Ni-P coatings, Ni-P-Cr3C2 composite coatings, and heat-treated-state Ni-P-Cr3C2 composite coatings are compared and discussed. The results show that the hardness, wear resistance, and corrosion resistance of the composite coatings are optimized when the Cr3C2 content is 3 g/L and the heat-treatment temperature is 400 °C. This is due to the presence of oxides such as Cr2O3 on the surface of the composite coatings after heat treatment at 400 °C. By efficiently enhancing the coating's densification to the substrate, these oxides raise the composite coating's resistance to corrosion and wear. The Ni-P-Cr3C2 composite coating in its heat-treated makeup at 400 °C is found to have long-term corrosion resistance in the 3.5 wt % NaCl solution immersion test. This study provides a new idea in the field of corrosion.

PARP11 inhibition inactivates tumor-infiltrating regulatory T cells and improves the efficacy of immunotherapies.

Tumor-infiltrating regulatory T cells (TI-Tregs) elicit immunosuppressive effects in the tumor microenvironment (TME) leading to accelerated tumor growth and resistance to immunotherapies against solid tumors. Here, we demonstrate that poly-(ADP-ribose)-polymerase-11 (PARP11) is an essential regulator of immunosuppressive activities of TI-Tregs. Expression of PARP11 correlates with TI-Treg cell numbers and poor responses to immune checkpoint blockade (ICB) in human patients with cancer. Tumor-derived factors including adenosine and prostaglandin E2 induce PARP11 in TI-Tregs. Knockout of PARP11 in the cells of the TME or treatment of tumor-bearing mice with selective PARP11 inhibitor ITK7 inactivates TI-Tregs and reinvigorates anti-tumor immune responses. Accordingly, ITK7 decelerates tumor growth and significantly increases the efficacy of anti-tumor immunotherapies including ICB and adoptive transfer of chimeric antigen receptor (CAR) T cells. These results characterize PARP11 as a key driver of TI-Treg activities and a major regulator of immunosuppressive TME and argue for targeting PARP11 to augment anti-cancer immunotherapies.

FGF21-dependent alleviation of cholestasis-induced liver fibrosis by sodium butyrate.

Background: The beneficial effects of fibroblast growth factor 21 (FGF21) and sodium butyrate (NaB) on protection against cholestasis-induced liver fibrosis are not well known. This study aimed to explore the effects of FGF21 and NaB on bile duct ligation (BDL)-induced liver fibrosis. Methods: Wild-type (WT) and FGF21 knockout (KO) mice received BDL surgery for 14 days. Liver fibrosis was assessed by Masson's staining for fibrosis marker expressions at the mRNA or protein levels. Adenovirus-mediated FGF21 overexpression in the WT mice was assessed against BDL damage. BDL surgeries were performed in WT and FGF21 KO mice that were administered either phosphate-buffered saline or NaB. The effects of NaB on the energy metabolism and gut microbiota were assessed using stable metabolism detection and 16S rRNA gene sequencing. Results: BDL-induced liver fibrosis in the WT mice was accompanied by high induction of FGF21. Compared to the WT mice, the FGF21 KO mice showed more severe liver fibrosis induced by BDL. FGF21 overexpression protected against BDL-induced liver fibrosis, as proved by the decreasing α-SMA at both the mRNA and protein levels. NaB administration enhanced the glucose and energy metabolisms as well as remodeled the gut microbiota. NaB alleviated BDL-induced liver fibrosis in the WT mice but aggravated the same in FGF21 KO mice. Conclusion: FGF21 plays a key role in alleviating cholestasis-induced liver damage and fibrosis. NaB has beneficial effects on cholestasis in an FGF21-dependent manner. NaB administration can thus be a novel nutritional therapy for treating cholestasis via boosting FGF21 signaling and regulating the gut microbiota.

Effects of diets on risks of cancer and the mediating role of metabolites.

Research on the association between dietary adherence and cancer risk is limited, particularly concerning overall cancer risk and its underlying mechanisms. Using the UK Biobank data, we prospectively investigate the associations between adherence to a Mediterranean diet (MedDiet) or a Mediterranean-Dietary Approaches to Stop Hypertension Diet Intervention for Neurodegenerative Delay diet (MINDDiet) and the risk of overall and 22 specific cancers, as well as the mediating effects of metabolites. Here we show significant negative associations of MedDiet and MINDDiet adherence with overall cancer risk. These associations remain robust across 14 and 13 specific cancers, respectively. Then, a sequential analysis, incorporating Cox regression, elastic net and gradient boost models, identify 10 metabolites associated with overall cancer risk. Mediation results indicate that these metabolites play a crucial role in the association between adherence to a MedDiet or a MINDDiet and cancer risk, independently and cumulatively. These findings deepen our understanding of the intricate connections between diet, metabolites, and cancer development.

Congenital Cutaneous Sinus at the Sternoclavicular Joint.

A 32-year-old female patient presented with chronic discharging sinus with recurrent infection at the left sternoclavicular joint. What is your diagnosis?

Artemisia argyi polyphenols Attenuates DSS-induced colitis in mice by regulating the structural composition of gut microbiota.

BACKGROUND: Intestinal health is affected by heredity, lifestyle, and structure of gut microbiota. The imbalance of symbiotic and harmful bacteria in gut microbiota may increase the occurrence of colonic inflammation. Supplementary A. muciniphila can improve the survival rate of colitis mice, reduce colon tissue injury, and the expression of anti-inflammatory factors was upregulated. Artemisia argyi has been reported to have anti-inflammatory, antioxidant, bactericidal, and immunomodulatory effects. However, its anti-inflammatory effect and mechanism, and its influence on gut microbiota and metabolites are still unclear yet. PURPOSE: To explore whether Artemisia argyi Polyphenols(AAPs) can alleviate ulcerative colitis (UC) by changing gut microbiota. METHODS: The therapeutic effect of AAPs on colitis was investigated by inducing ulcerative colitis in mice using dextran sodium sulfate (DSS) and administering different doses of AAPs orally to mice. Exploring the levels of inflammatory proteins, oxidative stress proteins, and barrier proteins using western blotting and immunofluorescence, and explored the structural changes of gut microbiota and its metabolites. Meanwhile, in order to explore whether the role of AAPs in alleviating colitis is based on the regulation of gut microbiota structure, we conducted fecal microbiota transplantation (FMT). RESULTS: It showed that AAPs and FMT trial alleviated DSS-induced colonic injury, including clinical parameters and pathological injury of colon tissue, reduction in the expression of inflammatory proteins: IL-6, TNF-α, p-p65, p-IκBα, and increase in the expression of antioxidant proteins: Nrf2, NQO-1 and HO-1 and barrier proteins: Claudin-1, Occludin, ZO-1 and MUC2. AAPs and FMT promoted the content of beneficial bacteria, such as Butyricimonas and Lactobacillus, and the content of beneficial metabolites for instance acetic acid, butyric acid, and valeric acid has also increased. CONCLUSION: These results suggested that AAPs might improve DSS-induced colonic injury by changing the structural of gut microbiota while promoting the synthesis of fatty acids in the intestine, thereby providing a theoretical basis for using AAPs to treat ulcerative colitis.

Effects of artificial light with different spectral compositions on refractive development and matrix metalloproteinase 2 and tissue inhibitor of metalloproteinases 2 expression in the sclerae of juvenile guinea pigs.

Artificial light can affect eyeball development and increase myopia rate. Matrix metalloproteinase 2 (MMP-2) degrades the extracellular matrix, and induces its remodeling, while tissue inhibitor of matrix MMP-2 (TIMP-2) inhibits active MMP-2. The present study aimed to look into how refractive development and the expression of MMP-2 and TIMP-2 in the guinea pigs' remodeled sclerae are affected by artificial light with varying spectral compositions. Three weeks old guinea pigs were randomly assigned to groups exposed to five different types of light: natural light, LED light with a low color temperature, three full spectrum artificial lights, i.e. E light (continuous spectrum in the range of ~390-780 nm), G light (a blue peak at 450 nm and a small valley 480 nm) and F light (continuous spectrum and wavelength of 400 nm below filtered). A-scan ultrasonography was used to measure the axial lengths of their eyes, every two weeks throughout the experiment. Following twelve weeks of exposure to light, the sclerae were observed by optical and transmission electron microscopy. Immunohistochemistry, Western blot and RT-qPCR were used to detect the MMP-2 and TIMP-2 protein and mRNA expression levels in the sclerae. After four, six, eight, ten, and twelve weeks of illumination, the guinea pigs in the LED and G light groups had axial lengths that were considerably longer than the animals in the natural light group while the guinea pigs in the E and F light groups had considerably shorter axial lengths than those in the LED group. Following twelve weeks of exposure to light, the expression of the scleral MMP-2 protein and mRNA were, from low to high, N group, E group, F group, G group, LED group; however, the expression of the scleral TIMP-2 protein and mRNA were, from high to low, N group, E group, F group, G group, LED group. The comparison between groups was statistically significant (p<0.01). Continuous, peaks-free or valleys-free artificial light with full-spectrum preserves remodeling of scleral extracellular matrix in guinea pigs by downregulating MMP-2 and upregulating TIMP-2, controlling eye axis elongation, and inhibiting the onset and progression of myopia.

PredGCN: a Pruning-enabled Gene-Cell Net for automatic cell annotation of single cell transcriptome data.

MOTIVATION: The annotation of cell types from single-cell transcriptomics is essential for understanding the biological identity and functionality of cellular populations. Although manual annotation remains the gold standard, the advent of automatic pipelines has become crucial for scalable, unbiased, and cost-effective annotations. Nonetheless, the effectiveness of these automatic methods, particularly those employing deep learning, significantly depends on the architecture of the classifier and the quality and diversity of the training datasets. RESULTS: To address these limitations, we present a Pruning-enabled Gene-Cell Net (PredGCN) incorporating a Coupled Gene-Cell Net (CGCN) to enable representation learning and information storage. PredGCN integrates a Gene Splicing Net (GSN) and a Cell Stratification Net (CSN), employing a pruning operation (PrO) to dynamically tackle the complexity of heterogeneous cell identification. Among them, GSN leverages multiple statistical and hypothesis-driven feature extraction methods to selectively assemble genes with specificity for scRNA-seq data while CSN unifies elements based on diverse region demarcation principles, exploiting the representations from GSN and precise identification from different regional homogeneity perspectives. Furthermore, we develop a multi-objective Pareto pruning operation (Pareto PrO) to expand the dynamic capabilities of CGCN, optimizing the sub-network structure for accurate cell type annotation. Multiple comparison experiments on real scRNA-seq datasets from various species have demonstrated that PredGCN surpasses existing state-of-the-art methods, including its scalability to cross-species datasets. Moreover, PredGCN can uncover unknown cell types and provide functional genomic analysis by quantifying the influence of genes on cell clusters, bringing new insights into cell type identification and characterizing scRNA-seq data from different perspectives. AVAILABILITY AND IMPLEMENTATION: The source code is available at https://github.com/IrisQi7/PredGCN and test data is available at https://figshare.com/articles/dataset/PredGCN/25251163.

Effect of acupuncture on tic disorder: a randomized controlled clinical trial based on energy metabolomics and infrared thermography.

BACKGROUND: Acupuncture is a method for treating tic disorder. However, there is a lack of sufficient clinical objective basis in regards of its treatment efficacy. Indeed, there are structural abnormalities present in energy metabolism and infrared thermography in children with tic disorder. Therefore, this study proposes a clinical trial scheme to explore the possible mechanism of acupuncture in treating tic disorder. METHODS: This randomized controlled trial will recruit a total of 90 children, in which they will be divided into non-intervention group and intervention group. The non-intervention group consists of 30 healthy children while the intervention group consists of 60 children with tic disorder. The intervention group will be randomly allocated into either the treatment group or the control group, with 30 children randomly assigned in each group. Children either received acupuncture treatment and behavioral therapy (treatment group) or sham acupuncture treatment and behavioral therapy (control group), 3 treatment sessions per week for a period of 12 weeks, with a total of 36 treatment sessions. Outcome measures include YGTSS, urinary and fecal metabolomics, infrared thermography of body surface including governor vessel. For the intervention group, these outcome measures will be collected at the baseline and 90th day prior to intervention. Whereas for the non-intervention group, outcome measures (excluding YGTSS) will be collected at the baseline. DISCUSSION: The main outcome will be to observe the changes of the severity of tic condition, the secondary outcome will be to observe the changes of structural characteristic of infrared thermography of body surface/acupoints along the governor vessel and to evaluate the changes of urinary and fecal metabolomics at the end of the treatment, so as to analyze the relationship between them and to provide further knowledge in understanding the possible mechanism of acupuncture in improving the clinical symptoms via regulating and restoring the body metabolomics network, which in future it can develop as a set of clinical guideline (diagnosis, treatment, assessment, prognosis) in treating tic disorder. ChiCTR2300075188(Chinese Clinical Trial Registry, http://www.chictr.org.cn , registered on 29 August 2023).

Investigation of the differential susceptibility of extraocular muscles in patients diagnosed with ocular myasthenia gravis based on the computerized diplopia test and the Ocular Motor Nerve Palsy Scale.

Introduction: The pattern of extraocular muscle involvement in ocular myasthenia gravis varies across different reports, diverging from our own observations. Thus, we employed two novel tools to discern this pattern. Methods: A retrospective analysis was conducted to collect and organize clinical data from 43 patients diagnosed with ocular myasthenia gravis. Each patient underwent both the computerized diplopia test and the Ocular Motor Nerve Palsy Scale assessment to evaluate the involvement of extraocular muscles. Results: Among the patients, there were 30 male and 13 female individuals, with a total of 113 affected extraocular muscles identified. Among all the affected extraocular muscles, the involvement of the levator palpebrae superioris muscle accounted for 35.40%, medial rectus muscle 7.7%, lateral rectus muscle 16.81%, superior rectus muscle 13.27%, inferior rectus muscle 12.39%, superior oblique muscle 1.77%, and inferior oblique muscle 2.65% of the total affected extraocular muscles. The positivity rates of the Neostigmine test were 89.19%, AChR antibody detection was 59.38%, and repetitive nerve stimulation was 34.38%. The AChR antibody positive rate among patients with only diplopia was 100%; among those with only ptosis, it was 80%; and among those with both diplopia and ptosis, it was 86.67%. Conclusion: The involvement of the extraocular muscles is not uniform. The levator palpebrae superioris exhibits the highest incidence rate, followed by the four rectus muscles and two oblique muscles. The inferior oblique involvement typically occurs when four or more EOMs are affected. Moreover, the levator palpebrae superioris and medial rectus show a higher tendency for bilateral involvement compared with other extraocular muscles.

Reduced atopic march risk in pediatric atopic dermatitis patients prescribed dupilumab versus conventional immunomodulatory therapy: A population-based cohort study.

BACKGROUND: Dupilumab effectively treats atopic dermatitis (AD); however, its role in halting the atopic march remains uncertain. OBJECTIVE: To investigate dupilumab's effect on atopic march in pediatric AD patients versus conventional immunomodulators. METHODS: This retrospective cohort study utilized data from the TriNetX US Collaborative Network (2011-2024). Pediatric AD patients (≤18 years) were categorized into DUPI-cohort (newly prescribed dupilumab) or CONV-cohort (prescribed conventional immunomodulators without dupilumab). After 1:1 propensity-score matching, we analyzed atopic march progression, defined by the incident asthma or allergic rhinitis (AR). Cumulative incidence was plotted using Kaplan-Meier, with risk assessment via Cox regression. RESULTS: The study included 2192 patients in each cohort. The 3-year cumulative incidence of atopic march progression was lower in the DUPI-cohort than the CONV-cohort (20.09% vs 27.22%; P < .001). The DUPI-cohort demonstrated significant risk reduction in atopic march progression (hazard ratio [HR] 0.68, 95% CI 0.55-0.83), individual asthma (HR 0.60, 0.45-0.81), and individual AR (HR 0.69, 0.54-0.88). Younger patients on dupilumab exhibited a greater risk reduction for atopic march progression and individual asthma, contrasting with the opposite age-related pattern for individual AR. LIMITATIONS: Observational study. CONCLUSION: Among pediatric AD patients, dupilumab was associated with reduced risk of atopic march progression compared with conventional therapies.