NAMPT enhances LOX expression and promotes metastasis in human chondrosarcoma cells by inhibiting miR-26b-5p synthesis.

Chondrosarcoma is a malignant bone tumor that emerges from abnormalities in cartilaginous tissue and is related with lung metastases. Nicotinamide phosphoribosyltransferase (NAMPT) is an adipocytokine reported to enhance tumor metastasis. Our results from clinical samples and the Gene Expression Omnibus data set reveal that NAMPT levels are markedly higher in chondrosarcoma patients than in normal individuals. NAMPT stimulation significantly increased lysyl oxidase (LOX) production in chondrosarcoma cells. Additionally, NAMPT increased LOX-dependent cell migration and invasion in chondrosarcoma by suppressing miR-26b-5p generation through the c-Src and Akt signaling pathways. Overexpression of NAMPT promoted chondrosarcoma metastasis to the lung in vivo. Furthermore, knockdown of LOX counteracted NAMPT-facilitated metastasis. Thus, the NAMPT/LOX axis presents a novel target for treating the metastasis of chondrosarcoma.

Community-based Intervention for Obstructive Sleep Apnea in the General Population: A Randomized Controlled Trial.

STUDY OBJECTIVES: To investigate the engagement and health outcomes of community-based intervention for obstructive sleep apnea (OSA) in the general population. METHODS: We conducted a 3-month randomized controlled trial in two communities in southern China. We initially screened the general population for high-risk OSA and further diagnosis using home sleep testing. Eligible participants were randomly (1:1) assigned to either a control or continuous positive airway pressure-based integrated intervention group. The primary outcomes were multimodal indicators reflecting health outcomes, including health-related quality of life (Short Form-36 [SF-36]), sleep-related symptoms, and cardiometabolic risk. RESULTS: Of the 2,484 participants screened, 1,423 identified as having high-risk OSA were considered for telephone invitations to participate in the trial. Of these, 401 participants responded positively (28.2%), 279 were diagnosed with OSA, and 212 were randomized. The intervention significantly improved several domains of SF-36, including physical functioning (intergroup difference, 2.8; P=0.003), vitality (2.3; P=0.031), and reported health transition (6.8; P=0.005). Sleep-related symptoms, including Epworth Sleepiness Scale (-0.7; P=0.017), Fatigue Severity Scale (-3.0; P=0.022), Insomnia Severity Index (-1.8; P<0.001), and Pittsburgh Sleep Quality Index (-0.7; P=0.032), also showed significant improvements. Although the intervention did not significantly alter glycolipid metabolism, ventricular function, or cardiac structural remodeling, it achieved a significant reduction in systolic (-4.5 mmHg; P=0.004) and diastolic blood pressure (-3.7 mmHg; P<0.001). CONCLUSIONS: Community-based intervention for previously undiagnosed OSA in the general population yielded improvements in health-related quality of life, sleep-related symptoms, and blood pressure. However, engagement in the intervention program was low.

Safety assessment of enzymatically converted chicken bile as a novel food material: Genotoxicity, teratogenicity, and acute and subchronic toxicity studies.

Enzymatically converted chicken bile (CB), prepared by converting taurine deoxycholic acid (TCDCA) to taurine ursodeoxycholic acid (TUDCA) in CB, possesses various functional activities. But their nutrient composition and safety assessment have not been fully investigated yet. CB was mainly composed of proteins and steroids. CB did not show genotoxic effects based on Ames test, mammalian erythrocyte micronucleus test, and in vitro mammalian chromosomal aberration test. There were no growth abnormalities or deaths in the acute toxicity test for mice, indicating that CB is nontoxic with an LD50 > 10 g/kg·body weight (BW). Subchronic toxicity test and genotoxicity test were performed based on intake of 0.5 g CB per person daily at expanded doses of 33.3, 100, and 300 times (278, 833, and 2500 mg/kg·BW). The result indicated that CB at 833 mg/kg·BW showed no toxicity on BW, body weight gain, food intake, hematological, serum biochemistry, absolute/relative organ weights, urinalysis, and pathological features of rats in the subchronic toxicity test, while CB at 833 mg/kg·BW induced maternal toxicity with no fetus teratogenicity or embryotoxicity in the teratogenicity test. In conclusion, CB did not show toxic effects and a long-term daily intake of CB at 0.5 g per person is considered safe, but pregnant women should avoid it. These findings could provide a reference for the safe use of CB in functional food.

Fluorescence-based reagent and spectrum-based optical reader for lactoferrin detection in tears: differentiating Sjögren's syndrome from non-Sjögren's dry eye syndrome.

Identification of an early biomarker and effective testing device to differentiate dry eye disease secondary to autoimmune disease (Sjögren's syndrome dry eye disease) from non-Sjögren's dry eye disease are prerequisites for appropriate treatment. We aimed to demonstrate the capacity of a new photo-detection device to evaluate tear lactoferrin levels as a tool for differentiating systemic conditions associated with dry eye disease. Patients with non-Sjögren's and Sjögren's syndrome dry eye disease (n = 54 and n = 52, respectively) and controls (n = 11) were enrolled. All participants completed the Ocular Surface Disease Index questionnaire. Tear collection was performed with Schirmer test, and tear break-up time was examined using a slit lamp. Tear lactoferrin was evaluated using our newly developed photo-detection device. The average lactoferrin concentration was significantly lower in samples from patients with non-Sjögren's dry eye disease (0.337 ± 0.227 mg/mL, n = 54) and Sjögren's syndrome dry eye disease (0.087 ± 0.010 mg/mL, n = 52) than in control samples (1.272 ± 0.54 mg/mL, n = 11) (p < 0.0001). Further, lactoferrin levels were lower in patients with Sjögren's syndrome dry eye disease than in those with non-Sjögren's dry eye disease (p < 0.001). Our cost-effective, antibody-free, highly sensitive photo-detection device for evaluating tear lactoferrin levels can assist ophthalmologists in differentiating different types of dry eye diseases.

Twin prime editing mediated exon skipping/reinsertion for restored collagen VII expression in recessive dystrophic epidermolysis bullosa.

Gene editing nucleases, base editors, and prime editors are potential locus specific genetic treatment strategies for recessive dystrophic epidermolysis bullosa (RDEB); however, many RDEB COL7A1 mutations are unique, making the development of personalized editing reagents challenging. 270 of the ∼320 COL7A1 EB mutations reside in exons that can be skipped, and antisense oligonucleotides (ASO) and gene editing nucleases have been used to create in-frame deletions. ASOs are transient and nucleases generate deleterious double stranded DNA breaks (DSB) and uncontrolled mixtures of allele products. We developed a twin prime editing (twinPE) strategy using the PEmax and recently evolved PE6 prime editors and dual prime editing guide RNAs flanking COL7A1 exon five. Prime editing-mediated deletion of exon 5 with a homozygous premature stop codon was achieved in RDEB fibroblasts, keratinocytes, and iPSC with minimal DSBs, and collagen type VII (C7) protein was restored. TwinPE can replace the target exon with recombinase attachment sequences, and we exploited this to re-insert a normal copy of exon 5 using the Bxb1 recombinase. These findings demonstrate that twinPE can facilitate locus-specific, predictable, in-frame deletions and sequence replacement with few DSBs as a strategy that may enable a single therapeutic agent to treat multiple RDEB patient cohorts.

Convolutional Neural Network-Based Prediction of Axial Length Using Color Fundus Photography.

Purpose: To develop convolutional neural network (CNN)-based models for predicting the axial length (AL) using color fundus photography (CFP) and explore associated clinical and structural characteristics. Methods: This study enrolled 1105 fundus images from 467 participants with ALs ranging from 19.91 to 32.59 mm, obtained at National Taiwan University Hospital between 2020 and 2021. The AL measurements obtained from a scanning laser interferometer served as the gold standard. The accuracy of prediction was compared among CNN-based models with different inputs, including CFP, age, and/or sex. Heatmaps were interpreted by integrated gradients. Results: Using age, sex, and CFP as input, the mean ± standard deviation absolute error (MAE) for AL prediction by the model was 0.771 ± 0.128 mm, outperforming models that used age and sex alone (1.263 ± 0.115 mm; P < 0.001) and CFP alone (0.831 ± 0.216 mm; P = 0.016) by 39.0% and 7.31%, respectively. The removal of relatively poor-quality CFPs resulted in a slight MAE reduction to 0.759 ± 0.120 mm without statistical significance (P = 0.24). The inclusion of age and CFP improved prediction accuracy by 5.59% (P = 0.043), while adding sex had no significant improvement (P = 0.41). The optic disc and temporal peripapillary area were highlighted as the focused areas on the heatmaps. Conclusions: Deep learning-based prediction of AL using CFP was fairly accurate and enhanced by age inclusion. The optic disc and temporal peripapillary area may contain crucial structural information for AL prediction in CFP. Translational Relevance: This study might aid AL assessments and the understanding of the morphologic characteristics of the fundus related to AL.

Targeting nerve growth factor-mediated osteosarcoma metastasis: mechanistic insights and therapeutic opportunities using larotrectinib.

Osteosarcoma (OS) therapy presents numerous challenges, due largely to a low survival rate following metastasis onset. Nerve growth factor (NGF) has been implicated in the metastasis and progression of various cancers; however, the mechanism by which NGF promotes metastasis in osteosarcoma has yet to be elucidated. This study investigated the influence of NGF on the migration and metastasis of osteosarcoma patients (88 cases) as well as the underlying molecular mechanisms, based on RNA-sequencing and gene expression data from a public database (TARGET-OS). In osteosarcoma patients, the expression of NGF was significantly higher than that of other growth factors. This observation was confirmed in bone tissue arrays from 91 osteosarcoma patients, in which the expression levels of NGF and matrix metallopeptidase-2 (MMP-2) protein were significantly higher than in normal bone, and strongly correlated with tumor stage. In summary, NGF is positively correlated with MMP-2 in human osteosarcoma tissue and NGF promotes osteosarcoma cell metastasis by upregulating MMP-2 expression. In cellular experiments using human osteosarcoma cells (143B and MG63), NGF upregulated MMP-2 expression and promoted wound healing, cell migration, and cell invasion. Pre-treatment with MEK and ERK inhibitors or siRNA attenuated the effects of NGF on cell migration and invasion. Stimulation with NGF was shown to promote phosphorylation along the MEK/ERK signaling pathway and decrease the expression of microRNA-92a-1-5p (miR-92a-1-5p). In in vivo experiments involving an orthotopic mouse model, the overexpression of NGF enhanced the effects of NGF on lung metastasis. Note that larotrectinib (a tropomyosin kinase receptor) strongly inhibited the effect of NGF on lung metastasis. In conclusion, it appears that NGF promotes MMP-2-dependent cell migration by inhibiting the effects of miR-92a-1-5p via the MEK/ERK signaling cascade. Larotrectinib emerged as a potential drug for the treatment of NGF-mediated metastasis in osteosarcoma.

Consistent survival in consecutive cases of life-supporting porcine kidney xenotransplantation using 10GE source pigs.

Xenotransplantation represents a possible solution to the organ shortage crisis and is an imminent clinical reality with long-term xenograft survival in pig-to-nonhuman primate (NHP) heart and kidney large animal models, and short-term success in recent human decedent and clinical studies. However, concerns remain about safe clinical translation of these results, given the inconsistency in published survival as well as key differences between preclinical procurement and immunosuppression and clinical standards-of-care. Notably, no studies of solid organ pig-to-NHP transplantation have achieved xenograft survival longer than one month without CD40/CD154 costimulatory blockade, which is not currently an FDA-approved immunosuppression strategy. We now present consistent survival in consecutive cases of pig-to-NHP kidney xenotransplantation, including long-term survival after >3 hours of xenograft cold preservation time as well as long-term survival using FDA-approved immunosuppression. These data provide critical supporting evidence for the safety and feasibility of clinical kidney xenotransplantation. Moreover, long-term survival without CD40/CD154 costimulatory blockade may provide important insights for immunosuppression regimens to be considered for first-in-human clinical trials.

Disulfiram treatment suppresses antibody-producing reactions by inhibiting macrophage activation and B cell pyrimidine metabolism.

Antibody responses, involving B cells, CD4 + T cells, and macrophages, are implicated in autoimmune diseases and organ transplant rejection. We have previously shown that inhibiting FROUNT with disulfiram (DSF) suppresses macrophage activation and migration, effectively treating inflammatory diseases. In this study, we investigated the effectiveness of DSF in antibody-producing reactions. Using a heart transplantation mouse model with antibody-mediated rejection, we administered anti-CD8 antibody to exclude cellular rejection. DSF directly inhibited B cell responses in vitro and significantly reduced plasma donor-specific antibodies and graft antibody deposition in vivo, resulting in prolonged survival of the heart graft. DSF also mediated various effects, including decreased macrophage infiltration and increased Foxp3+ regulatory T-cells in the grafts. Additionally, DSF inhibited pyrimidine metabolism-related gene expression induced by B-cell stimulation. These findings demonstrate that DSF modulates antibody production in the immune response complexity by regulating B-cell and macrophage responses.

Acetaminophen overdose-induced acute liver injury can be alleviated by static magnetic field.

Acetaminophen (APAP), the most frequently used mild analgesic and antipyretic drug worldwide, is implicated in causing 46% of all acute liver failures in the USA and between 40% and 70% in Europe. The predominant pharmacological intervention approved for mitigating such overdose is the antioxidant N-acetylcysteine (NAC); however, its efficacy is limited in cases of advanced liver injury or when administered at a late stage. In the current study, we discovered that treatment with a moderate intensity static magnetic field (SMF) notably reduced the mortality rate in mice subjected to high-dose APAP from 40% to 0%, proving effective at both the initial liver injury stage and the subsequent recovery stage. During the early phase of liver injury, SMF markedly reduced APAP-induced oxidative stress, free radicals, and liver damage, resulting in a reduction in multiple oxidative stress markers and an increase in the antioxidant glutathione (GSH). During the later stage of liver recovery, application of vertically downward SMF increased DNA synthesis and hepatocyte proliferation. Moreover, the combination of NAC and SMF significantly mitigated liver damage induced by high-dose APAP and increased liver recovery, even 24 h post overdose, when the effectiveness of NAC alone substantially declines. Overall, this study provides a non-invasive non-pharmaceutical tool that offers dual benefits in the injury and repair stages following APAP overdose. Of note, this tool can work as an alternative to or in combination with NAC to prevent or minimize liver damage induced by APAP, and potentially other toxic overdoses.

Combined islet and kidney xenotransplantation for diabetic nephropathy: an update in ongoing research for a clinically relevant application of porcine islet transplantation.

Combined islet and kidney xenotransplantation for the treatment of diabetic nephropathy represents a compelling and increasingly relevant therapeutic possibility for an ever-growing number of patients who would benefit from both durable renal replacement and cure of the underlying cause of their renal insufficiency: diabetes. Here we briefly review immune barriers to islet transplantation, highlight preclinical progress in the field, and summarize our experience with combined islet and kidney xenotransplantation, including both challenges with islet-kidney composite grafts as well as our recent success with sequential kidney followed by islet xenotransplantation in a pig-to-baboon model.

NGF facilitates ICAM-1-dependent monocyte adhesion and M1 macrophage polarization in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder in which monocytes adhering to synovial tissue differentiate into the pro-inflammatory M1 macrophage phenotype. Nerve growth factors (NGF) referred to as neurotrophins have been associated with inflammatory events; however, researchers have yet to elucidate the role of NGF in RA. Our examination of clinical tissue samples and analysis of data sourced from the Gene Expression Omnibus dataset unveiled elevated expression levels of M1 macrophage markers in human RA synovial tissue samples compared to normal tissue, with no such distinction observed for M2 markers. Furthermore, immunofluorescence data depicted increased expression levels of NGF and M1 macrophages in RA mice in contrast to normal mice. It appears that NGF stimulation facilitates macrophage polarization from the M0 to the M1 phenotype. It also appears that NGF promotes ICAM-1 production in human RA synovial fibroblasts, which enhances monocyte adhesion through the TrkA, MEK/ERK, and AP-1 signaling cascades. Our findings indicate NGF/TrkA axis as a novel target for the treatment of RA.

Tenon excision with fibrin glue-assisted reattachment of conjunctiva flap (T.E.F.A.R.C) for the treatment of conjunctivochalasis.

To observe the surgical outcome of "Tenon Excision with Fibrin Glue-Assisted Reattachment of Conjunctiva Flap" (T.E.F.A.R.C.) for the treatment of symptomatic conjunctivochalasis (CCH). This is a retrospective case series of CCH patients undergoing T.E.F.A.R.C. from January 2017 to December 2020 were reviewed. Seven patients (14 eyes) with symptomatic CCH received T.E.F.A.R.C. in both eyes. The symptoms before and after the procedures were compared and surgical complication was evaluated. The mean follow-up time was 13.7 ± 2.14 months. After the operation, resolution of the symptoms was reported in 12 eyes (86%). The grade of CCH decreased from 3 to 0 in all 14 eyes, and the restoration of inferior conjunctival surface and fornix within 1 day was also observed in all eyes. Most patients had localized injection and mild chemosis after the operation, which mostly recovered within 3 weeks. No complication or recurrence of CCH was reported after 1 year of follow-up. In conclusion, T.E.F.A.R.C. is a simple and effective treatment option for CCH with less surgical complication. Future larger studies are needed to confirm its clinical applicability.

Corneal structural alterations in autism spectrum disorder: An in vivo confocal microscopy study.

Individuals with autism spectrum disorder (ASD) often exhibit joint hypermobility and connective tissue disorders. However, it remains unclear if ASD individuals also have structural alterations in the connective tissue of the cornea. This study aims to determine whether the Kobayashi structure (K-structure) characteristics differ between adults with ASD and typically developing controls (TDC) and explore the clinical correlates of the K-structure abnormality. We recruited 30 ASD adults and 35 TDC. Corneal structures, particularly the K-structure in the Bowman's layer, of the participants were examined using in vivo confocal microscopy (IVCM), and a K-grading ranging from 1 to 4 was given to each eye based on the level of morphological mosaicism. The ASD participants' eyes received a significantly higher single-eye K-grading than that of the TDC eyes (p < 0.001), and the medians [25th, 75th percentile] of bilateral-eye summed K-grading were 8 [7, 8] and 5 [4, 6] in ASD and TDC, respectively (p < 0.001). A significantly higher K-grading in the ASD participants' eyes was still observed after adjusting for the within-subject inter-eye correlation (p < 0.001). Youden Index showed the optimal cutoffs to differentiate ASD from TDC by bilateral-eye summed K-grading and single-eye K-grading was >6 and >3, respectively. Additionally, a higher K-grading was associated with fewer visual sensation seeking in ASD (Spearman's correlation coefficient ρ = -0.518, p = 0.008) and low visual registration (i.e., higher sensory threshold) in TDC (ρ = 0.446, p = 0.023). This study provided novel evidence of corneal structural alterations in ASD by IVCM. Our findings may not only support the prior hypothesis of the association between ASD and connective tissue abnormalities but also shed light on the relationship between connective tissue disorder and neurodevelopmental disorders.

Follistatin (FST) is expressed in buffalo (Bubalus bubalis) ovarian follicles and promotes oocyte maturation and early embryonic development.

Follistatin (FST), a member of the transforming growth factor-ß (TGF-ß) superfamily, has been identified as an inhibitor of follicle-stimulating hormone. Previous studies showed that it plays an important role in animal reproduction. Therefore, this study aims to investigate its effect on the maturation of buffalo oocytes in vitro, and the underlying mechanism of FST affecting oocyte maturation was also explored in buffalo cumulus cells. Results showed that FST was enriched in the ovary and expressed at different stages of buffalo ovarian follicles as well as during oocyte maturation and early embryo development. The FST expression level was up-regulated in MII buffalo oocytes compared with the GV stage (p < .05). To study the effects of FST on buffalo oocytes' maturation and early embryonic development, we added the pcD3.1 skeleton vector and PCD3.1-EGFP-FST vector into the maturation fluid of buffalo oocytes, respectively. It was demonstrated that FST promoted the in vitro maturation rate of buffalo oocytes and the blastocyst rate of embryos cultured in vitro (p < .05). By interfering with FST expression, we discovered that FST in cumulus cells plays a crucial role in oocyte maturation. Interference with the FST expression during the buffalo oocyte maturation did not affect the first polar body rate of buffalo oocyte (p > .05). In contrast, the location of mitochondria in oocytes was abnormal, and the cumulus expansion area was reduced (p < .05). After parthenogenetic activation, the cleavage and blastocyst rates of the FST-interfered group were reduced (p < .05). Furthermore, RT-qPCR was performed to investigate further the underlying mechanism by which FST enhances oocyte maturation. We found that overexpression of FST could up-regulate the expression level of apoptosis suppressor gene Bcl-2 and TGF-ß/SMAD pathway-related genes TGF-ß, SMAD2, and SMAD3 (p < .05). In contrast, the expression levels of SMAD4 and pro-apoptotic gene BAX were significantly decreased (p < .05). The FST gene could affect buffalo oocyte maturation by regulating the oocyte mitochondria integrity, the cumulus expansion, cumulus cell apoptosis, and the expression levels of TGF-ß/SMAD pathway-related genes.

Insight into regulation of adventitious root formation by arbuscular mycorrhizal fungus and exogenous auxin in tea plant (Camellia sinensis L.) cuttings.

Introduction: Adventitious root (AR) development, affected by various biotic and abiotic factors, is the most important procedure in tea plant (Camellia sinensis L.) cutting propagation. Establishing symbiotic relationships with most terrestrial plants, AMF (Arbuscular mycorrhizal fungus) can mediate the AR formation of several herbaceous and woody plants in previous studies. Methods: In this paper, effects of combined application of AMF and exogenous auxin on AR formation of cuttings from different tea plant varieties ('Pingyangtezao', 'Longjing 43' and 'Longjingchangye') were studied. Then we also performed RNA-Seq analysis with 'Pingyangtezao' cuttings aiming to find the possible auxin-related pathway of AM fungal regulation on AR formation. To accurately uncover the regulatory mechanism of AMF on AR formation of tea cuttings, rooting process were separated into four stages (S0, non-rooting; S1, AR protrusion; S2, AR formation and S3, AR elongation) at the same sampling time. Results and Discussion: Results showed that IBA treatment increased the mycorrhizal colonization rate, especially in 'Pingyangtezao' variety (from 37.58% to 46.29%). Both inoculating AMF and addition of IBA promoted the AR formation, and rooting of different tea plant varieties showed different dependence on auxin. AMF could alleviate the effect of auxin-related inhibitors (2,3,5-triiodobenzoic acid, L-α-(Aminooxy)-ß-phenylpropionic acid and α-(phenylethyl-2-oxo)-IAA) on rooting of tea cuttings, even though the colonization of AMF was hindered at various degrees. Transcriptomic analysis showed that different numbers of differentially expressed genes (DEGs) at various rooting stages of tea cuttings with the most at S2 stage (1360 DEGs), indicating the increasing regulation by AMF with the development of AR. Similar trend was found in auxin-related DEGs, and family genes of YUC, GH, PIN, LAX, SAUR, AUX, and ABP involved in the AM fungal regulation on AR formation of tea cuttings. Additionally, AMF strongly mediated auxin transport and signal transduction pathways in tea cuttings as showed by the results of correlation analysis. Overall, interaction of AMF and exogenous auxin in promoting rooting and the preliminary mechanism of AMF regulating AR formation of tea cuttings was deciphered in this paper, which may provide a basis for further deep mechanistic research and cutting propagation of tea production.

The diagnostic value of interleukin-36 cytokines in pleural effusions of varying etiologies.

BACKGROUND: The clinical management of pleural effusion (PE) poses challenges due to its diverse etiologies. The objective of this research was to investigate the concentrations of interleukin-36 (IL-36) cytokines in pleural fluid (PF) from different etiologies and assess their diagnostic efficacy in distinguishing the causes of PE. METHODS: This study enrolled 89 patients with confirmed PE, comprising 11 cases classified as transudate, 24 cases as malignant pleural effusion (MPE), 24 cases as tuberculous pleural effusion (TPE), and 30 cases as parapneumonic pleural effusion (PPE). The PPE group was further subdivided into 20 cases of uncomplicated parapneumonic effusion (UPPE) and 10 cases of complicated parapneumonic effusion (CPPE)/empyema. The concentrations of IL-36 cytokines in the PF of all 89 patients were quantified by the enzyme-linked immunosorbent assay (ELISA). RESULTS: IL-36α exhibited excellent diagnostic accuracy in TPE, achieving a sensitivity of 91.7 % and specificity of 83.1 %, along with a cut-off value of 435.3 pg/ml. IL-36Ra also demonstrated relatively favorable diagnostic performance in PPE, with a sensitivity of 80.0 % and specificity of 76.3 %, along with a cut-off value of 390.8 pg/ml. Multivariable logistic regression models were successfully developed for both TPE and PPE, confirming their diagnostic utility. Furthermore, the levels of IL-36Ra were notably elevated in CPPE/empyema in comparison to UPPE. Moreover, in PF, IL-36γ exhibited positive associations with both IL-36α and IL-36Ra. CONCLUSION: IL-36α and IL-36Ra may serve as novel biomarkers for diagnosing TPE and PPE, respectively. The multivariate models established significantly enhance the diagnostic efficacy of both TPE and PPE. Furthermore, IL-36Ra can function as an indicator for assessing the extent of pleural inflammation. Additionally, the interaction among IL-36 cytokines in PF may contribute to their expression modulation.

Deficits in neuromuscular control of increasing force in patients with chronic lateral epicondylitis.

Objective: This study investigated the neuromuscular control of increasing and releasing force in patients with chronic lateral epicondylitis (CLE). Methods: Fifteen patients with CLE (10 males, 5 females, 46.5 ± 6.3 years) and fifteen healthy participants (9 males, 6 females, 45.3 ± 2.5 years) participated in this study. In addition to power grip and maximal voluntary contraction (MVC) of wrist extension, force fluctuation dynamics and characteristics of inter-spike intervals (ISI) of motor units (MUs) with various recruitment thresholds in the extensor carpi radialis brevis (ECRB) and extensor carpi radialis longus (ECRL) during a designated force-tracking task with a trapezoidal target (0%-75%-0% MVC) were assessed. Results: Besides a smaller MVC of wrist extension, the patients exhibited significantly greater task errors (p = 0.007) and force fluctuations (p = 0.001) during force increment than the healthy counterparts. Nevertheless, no force variables significantly differed between groups during force release (p > 0.05). During force increment, the amplitudes of the motor unit action potential of the ECRB and ECRL muscles of the patients were smaller than those of the heathy counterparts (p < 0.001). The patient group also exhibited a higher percentage of motor units (MU) with lower recruitment threshold (<5% MVC) in the ECRL/ECRB muscles and a lower percentage of MU with higher recruitment threshold (>40% MVC) in the ECRB muscle, compared to the healthy group. During force increment, the patient group exhibited a higher rate of decrease in inter-spike intervals (ISIs) of motor units with lower recruitment thresholds (<10% MVC) in the ECRB and ECRL muscles, compared to the control group (p < 0.005). Conclusion: The patients with CLE exhibited more pronounced impairment in increasing force than in releasing force. This impairment in increasing force is attributed to deficits in tendon structure and degenerative changes in the larger motor units of the wrist extensors. To compensate for the neuromuscular deficits, the rate of progressive increase in discharge rate of the remaining smaller motor units (MUs) is enhanced to generate force. Significance: The deficits in neuromuscular control observed in CLE with degenerative changes cannot be fully explained by the experimental pain model, which predicts pain-related inhibition on low-threshold motor units.

Ophthalmologic diagnoses in youths with autism spectrum disorder: Prevalence and clinical correlates.

Autism spectrum disorder (ASD) is associated with a high prevalence of visual dysfunction. This study aimed to investigate the rates of amblyopia, refractive errors, and strabismus, as well as their clinical correlates in ASD. This population-based matched-cohort study used data from the Taiwan National Health Insurance Research Database. A total of 3,551 youths with ASD and 35,510 non-autistic control participants matched by age and sex were included. All the participants were followed-up until they were 18 years old. The prevalence of amblyopia, refractive errors, and strabismus was compared between the ASD and control groups. Effect modifiers, including sex, ASD subgroup, and co-diagnosis of intelligence disability, were examined. Compared to the control group, youths with ASD had a significantly increased risk of amblyopia (adjusted odds ratio [aOR] = 1.75), anisometropia (aOR = 1.66), astigmatism (aOR = 1.51), hypermetropia (aOR = 2.08), exotropia (aOR = 2.86), and esotropia (aOR = 2.63), but a comparable likelihood of myopia according to age. Males with ASD had a significantly lower likelihood of exotropia, but a higher likelihood of myopia than females with ASD. The autism subgroup had a higher OR for hypermetropia, but a lower OR for myopia than the other ASD subgroups. ASD youths with intelligence disabilities demonstrated significantly higher ORs for amblyopia, hypermetropia, and all types of strabismus and lower OR for myopia than those without intelligence disabilities. In conclusion, the rates of amblyopia, refractive errors, and strabismus were higher in youths with ASD. Ocular abnormalities in youths with ASD require a comprehensive assessment and management.

Acupoint Thread Embedding Combined With Wenshen Bugu Decoction for the Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptom Among Postmenopausal Breast Cancer Patients: Study Protocol of a Randomized Controlled Trial.

BACKGROUND: Aromatase inhibitors (AIs) are recommended as the preferred therapy for postmenopausal women with hormone receptor-positive (HR+) breast cancer. As a result, aromatase inhibitor-associated musculoskeletal symptom (AIMSS) have become a major problem leading to therapy discontinuation and decreased quality of life in patients receiving adjuvant AIs treatment. Multiple therapies have been attempted, but have yielded limited clinical results. This study will be performed to determine whether acupoint thread embedding (ATE) combined with Wenshen Bugu Decoction can effectively treat AIMSS, so as to improve the AIs medication compliance of postmenopausal breast cancer patients. METHODS: This study will utilize a randomized, 2 parallel groups controlled trial design. A total of 128 eligible postmenopausal breast cancer women with AIMSS will be randomized to receive a 12-week treatment with Wenshen Bugu Decoction alone (control group) or in combination with ATE (treatment group) in a 1:1 ratio. The primary outcome will be the 12 week Brief Pain Inventory Worst Pain (BPI-WP) score. The secondary outcome measures will include response rate, Brief Pain Inventory-Short Form (BFI-SF), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Functional Assessment of Cancer Therapy-Endocrine Symptom (FACT-ES), Functional Assessment of Cancer Therapy-Breast (FACT-B), bone marrow density (BMD), blood markers of bone metabolite, Morisky medication adherence scale-8 (MMAS-8), credibility and expectancy, and survival outcomes. DISCUSSION: This trial may provide clinical evidence that ATE combined with Wenshen Bugu Decoction can be beneficial for treating AIMSS among postmenopausal breast cancer survivors. Our findings will be helpful to enhance the quality of life and reduce the occurrence of AIs withdrawal.