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Evaluations of treatment efficacy in Duchenne muscular dystrophy (DMD), a rare genetic disease that results in progressive muscle wasting, require an understanding of the meaningfulness of changes in functional measures. We estimated the minimal detectable change (MDC) for selected motor function measures in ambulatory DMD, i.e., the minimal degree of measured change needed to be confident that true underlying change has occurred rather than transient variation or measurement error. MDC estimates were compared across multiple data sources, representing >1000 DMD patients in clinical trials and real-world clinical practice settings. Included patients were ambulatory, aged ≥4 to 80% confidence in true change were 2.8 units for the North Star Ambulatory Assessment (NSAA) total score, 1.3 seconds for the 4-stair climb (4SC) completion time, 0.36 stairs/second for 4SC velocity and 36.3 meters for the 6-minute walk distance (6MWD). MDC estimates were similar across clinical trial and real-world data sources, and tended to be slightly larger than MCIDs for these measures. The identified thresholds can be used to inform endpoint definitions, or as benchmarks for monitoring individual changes in motor function in ambulatory DMD.

Long-term exposure to ultraviolet (UV) radiation induces skin photoaging, which manifests as oxidative stress, inflammation, and collagen degradation. Multiple approaches (topical or systemic retinoids, antioxidants, alpha-hydroxy acids, laser, surgery) are used in the treatment of photoaged skin, and the use of topical retinoids is currently a primary clinical treatment. Previous studies revealed that retinoic acid promotes keratinocyte proliferation and reduces melanin deposition and matrix metalloproteinase (MMP) secretion; it also causes potential allergic and inflammatory damage to the skin. This study aimed to investigate the therapeutic effects and mechanisms of trifarotene, a functional retinoic acid analog, on UV-irradiated photoaging ICR and BALB/c nude mice and UVB photodamaged human epidermal keratinocyte (HaCaT) cells by examining indicators such as collagen, oxidoreductase, and inflammatory factor presence through histochemical staining, Western blot, and ELISA. Results suggested that trifarotene significantly reduced UV-induced photoaging in mouse skin tissue, potentially by reducing oxidative stress damage and inflammatory factor release, and inhibiting melanin deposition and collagen degradation by downregulating MMP expression. Concentrations of malondialdehyde, tyrosinase, interleukin-6, interleukin- 12, and tumor necrosis factor-alpha in photoaged skin decreased, while SOD content in photodamaged HaCaT cells significantly increased. Trifarotene (3.3 μmol L–1) inhibited phosphorylated JNK and c-Jun expression both independently and collaboratively with the JNK activator anisomycin, demonstrating that trifarotene mitigates UV-induced collagen degradation and apoptosis through inhibition of the JNK/c-Jun/MMPs signaling pathway.

Abstract Background Posterior fossa malformation (PFM) is a relatively uncommon prenatal brain malformation. Genetic diagnostic approaches, including chromosome karyotyping, copy number variant (CNV) testing, and whole-exome sequencing (WES), have been applied in several cases of fetal structural malformations. However, the clinical value of appropriate genetic diagnostic approaches for different types of PFMs has not been confirmed. Therefore, in this study, we aimed to analyze the value of different combined genetic diagnostic approaches for various types of fetal PFMs. Methods This retrospective study was conducted at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital. Fifty-one pregnant women diagnosed with fetal PFMs who underwent genetic testing in our hospital from January 1, 2017 to December 31, 2022 were enrolled; women with an isolated enlarged cisterna magna were excluded. All participants were categorized into two groups according to the presence of other abnormalities: isolated and non-isolated PFMs groups. Different combined approaches, including karyotype analysis, CNV testing, and trio-based WES, were used for genetic analysis. The detection rates of karyotype analysis, CNV testing, and WES were measured in the isolated and non-isolated groups. Results In isolated PFMs, pathogenic/likely pathogenic (P/LP) CNVs were detected in four cases (36.36%, 4/11), whereas G-banding karyotyping and WES showed negative results. In non-isolated PFMs, a sequential genetic approach showed a detection rate of 47.5% (19/40); karyotyping revealed aneuploidies in five cases (16.67%, 5/30), CNV testing showed P/LP CNVs in five cases (16.13%, 5/31), and WES identified P/LP variants (in genes CEP20, TMEM67, OFD1, PTPN11, ARID1A, and SMARCA4) in nine cases (40.91%, 9/22). WES showed a detection rate of 83.33% (5/6) in fetuses with Joubert syndrome. Only six patients (five with Blake’s pouch cyst and one with unilateral cerebellar hemisphere dysplasia) survived. Conclusions We recommend CNV testing for fetuses with isolated PFMs. A sequential genetic approach (karyotyping, CNV testing, and WES) may be beneficial in fetuses with non-isolated PFMs. Particularly, we recommend WES as the first-line genetic diagnostic tool for Joubert syndrome.

Abstract Treating Multiple sclerosis (MS), a well-known immune-mediated disease characterized by axonal demyelination, is challenging due to its complex causes. Naphthalenedione, present in numerous plants, is being explored as a potential medicine for MS due to its immunomodulatory properties. However, its effects on lymphocytes can vary depending on factors such as the specific compound, concentration, and experimental conditions. In this study, we aim to explore the therapeutic potential of 2-bromo-1,4-naphthalenedione (BrQ), a derivative of naphthalenedione, in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and to elucidate its underlying mechanisms. We observed that mice treated with BrQ exhibited reduced severity of EAE symptoms, including lower clinical scores, decreased leukocyte infiltration, and less extensive demyelination in central nervous system. Furthermore, it was noted that BrQ does not directly affect the remyelination process. Through cell-chat analysis based on bulk RNA-seq data, coupled with validation of flow analysis, we discovered that BrQ significantly promotes the expansion of CD8+ T cells and their interactions with other immune cells in peripheral immune system in EAE mice. Subsequent CD8+ T cell depletion experiments confirmed that BrQ alleviates EAE in a CD8+ T cell-dependent manner. Mechanistically, expanded CD8+ cells were found to selectively reduce antigen-specific CD4+ cells and subsequently inhibit Th1 and Th17 cell development in vivo, ultimately leading to relief from EAE. In summary, our findings highlight the crucial role of BrQ in modulating the pathogenesis of MS, suggesting its potential as a novel drug candidate for treating MS and other autoimmune diseases.

Abstract Chemotherapy is currently one of the most effective methods in clinical cancer treatment. However, chemotherapy resistance is an important reason for poor chemotherapy efficacy and prognosis, which has become an urgent problem to be solved in the field of cancer chemotherapy. Therefore, it is very important to deeply study and analyze the mechanism of cancer chemotherapy resistance and its regulatory factors. Long non-coding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1) has been shown to be closely associated with chemotherapy resistance in cancer. NEAT1 induces cancer cell resistance to chemotherapeutic drugs by regulating cell apoptosis, cell cycle, drug transport and metabolism, DNA damage repair, EMT, autophagy, cancer stem cell characteristics, and metabolic reprogramming. This indicates that NEAT1 may be an important target to overcome chemotherapy resistance and is expected to be a potential biomarker to predict the effect of chemotherapy. This article summarizes the expression characteristics and clinical characteristics of NEAT1 in different cancers, and deeply discusses the regulatory role of NEAT1 in cancer chemotherapy resistance and related molecular mechanisms, aiming to clarify NEAT1 as a new target to overcome cancer chemotherapy resistance and the feasibility of chemotherapy sensitizers, with a view to providing a potential therapeutic direction for overcoming the dilemma of cancer resistance in the future.

In this paper, we design a multimodal visible/near-infrared photoacoustic microscopy and optical coherence tomography (VIS/NIR-PAM-OCT) system for imaging both retina and retinal pigment epithelium (RPE)/choroid complex layer. F127 and DSPE-PEG-cRGD encapsulated IR-1048 nanoparticles (FINPs) exhibiting absorption peak up to 1,064 nm were utilized as contrast agents to enhance NIR-PAM for in vivo imaging of fundus tissues. The fundus structure and vessels are clearly visualized by the multimodal imaging, and their parameters were quantitatively analyzed. NIR-PAM and OCT imaging of fundus were time-serially monitored over 60 min following the intravenous injection of FINPs into rats. The results indicated a 134 % increase in image signals in PAM at 1 min, along with an 8.23 % intensity enhancement in OCT. Moreover, laser-induced choroidal neovascularization (CNV) was specifically detected and accurately quantified using VIS/NIR-PAM-OCT. Lastly, FINPs demonstrated excellent biocompatibility in hematology analysis and pathology testing.

Abstract Background Frontonasal dysplasia (FND) is a rare congenital anomaly resulting from the underdevelopment of the frontonasal process, and it can be syndromic or nonsyndromic. The typical features of FND include a deformed nose and ocular hypertelorism, which are sometimes associated with cleft lip and/or palate. Only approximately 10 cases of prenatally diagnosed nonsyndromic FND have been reported in the past 30 years. Case presentation A 33-year-old woman (G2P1) was referred to our center at 20 gestational weeks for bilateral hydrocephaly. We detected typical features of FND, including severe hypertelorism, median nasal bifidity, a minor cleft lip, and multiple limb anomalies using three-dimensional (3D) ultrasound. A hypoplastic corpus callosum, unilateral microtia, and a ventricular septal defect were also detected. Genetic testing, including karyotype analysis, copy number variation (CNV) analysis, trio-whole exome sequencing (trio-WES), and trio-whole-gene sequencing (trio-WGS), was performed; however, we did not find any de novo gene variants in the fetus as compared to the parents. Postmortem examination confirmed the prenatal diagnosis of FND. Conclusion The present case expands the wide phenotypic spectrum of prenatal FND patients. 3D ultrasound is a useful tool for detecting facial and limb deformities.

Pathological myopia (PM) is a severe ocular disease leading to blindness. As a traditional noninvasive diagnostic method, fundus color photography (FCP) is widely used in detecting PM due to its high fidelity and precision. However, manual examination of fundus photographs for PM is time-consuming and prone to high error rates. Existing automated detection technologies have yet to study the detailed classification in diagnosing different stages of PM lesions. In this paper, we proposed an intelligent system which utilized Resnet101 technology to multi-categorically diagnose PM by classifying FCPs with different stages of lesions. The system subdivided different stages of PM into eight subcategories, aiming to enhance the precision and efficiency of the diagnostic process. It achieved an average accuracy rate of 98.86% in detection of PM, with an area under the curve (AUC) of 98.96%. For the eight subcategories of PM, the detection accuracy reached 99.63%, with an AUC of 99.98%. Compared with other widely used multi-class models such as VGG16, Vision Transformer (VIT), EfficientNet, this system demonstrates higher accuracy and AUC. This artificial intelligence system is designed to be easily integrated into existing clinical diagnostic tools, providing an efficient solution for large-scale PM screening.

BackgroundBy the end of 2021, the new wave of COVID-19 sparked by the Omicron variant spread rapidly due to its highly contagious nature, affecting more than 170 countries worldwide. Nucleic acid testing became the gold standard for diagnosing novel coronavirus infections. As of July 2022, numerous cities and regions in China have implemented regular nucleic acid testing policies, which have had a significant impact on socioeconomics and people’s lives. This policy has garnered widespread attention on social media platforms. ObjectiveThis study took the newly issued regular nucleic acid testing policy during the COVID-19 pandemic as an example to explore the sentiment responses and fluctuations of netizens toward new policies during public health emergencies. It aimed to propose strategies for managing public opinion on the internet and provide recommendations for policy making and public opinion control. MethodsWe collected blog posts related to nucleic acid testing on Weibo from April 1, 2022, to July 31, 2022. We used the topic modeling technique latent Dirichlet allocation (LDA) to identify the most common topics posted by users. We used Bidirectional Encoder Representations from Transformers (BERT) to calculate the sentiment score of each post. We used an autoregressive integrated moving average (ARIMA) model to examine the relationship between sentiment scores and changes over time. We compared the differences in sentiment scores across various topics, as well as the changes in sentiment before and after the announcement of the nucleic acid price reduction policy (May 22) and the lifting of the lockdown policy in Shanghai (June 1). ResultsWe collected a total of 463,566 Weibo posts, with an average of 3799.72 (SD 1296.06) posts published daily. The LDA topic extraction identified 8 topics, with the most numerous being the Shanghai outbreak, nucleic acid testing price, and transportation. The average sentiment score of the posts was 0.64 (SD 0.31), indicating a predominance of positive sentiment. For all topics, posts with positive sentiment consistently outnumbered those with negative sentiment (χ27=24,844.4, P

Introduction Physical inactivity is prevalent and associated with adverse outcomes among patients with chronic kidney disease (CKD). Most previous studies have relied on subjective questionnaires to assess levels of physical activity (PA) and mainly focused on patients undergoing dialysis. Therefore, the Physical Activity Elements and Adverse Outcomes in Patients with Chronic Kidney Disease in Guangdong study aims to investigate the levels and types of PA elements and their association with adverse outcomes in Chinese non-dialysis CKD (ND-CKD) patients.Methods and analysis In this prospective cohort study, 374 patients with ND-CKD will be recruited from Guangdong province, South of China. The primary exposure will be levels of PA assessed by ActiGraph GT3X+ accelerometer including the intensity, duration, frequency and type of PA. The traditional Chinese exercises such as tai chi and Baduanjin will also be assessed. The primary outcomes will be all-cause mortality. Other variables including demographics, comorbidities, medication and laboratory markers will be registered. All data will be updated annually for at least 5 years, or until the occurrence of death or initiation of renal replacement therapy. The Spearman correlation coefficient will be used to investigate the correlation between questionnaire-derived and accelerometry-derived PA. The Cox proportional hazards model will be used to investigate the association between level of PA and adverse outcomes. Non-linear associations between PA levels and outcomes, as well as the minimum desirable PA level, will be evaluated using restricted cubic splines.Ethics and dissemination The ethical permission for this study was obtained from the ethics committee of Guangdong Provincial Hospital of Chinese Medicine in Guangzhou, China (B2015-152-02). Written informed consent is obtained from all participants. The results will be disseminated by publication in a peer-reviewed journal and presented at relevant conferences.

BackgroundFew studies have compared the influencing factors of postpartum depression between primiparous and multiparous women. Therefore, this study is aimed to investigate the prevalence and influencing factors of postpartum depression in primiparous and multiparous women, and provide reference suggestions for clinical nursing.MethodsA total of 429 postpartum women who gave birth at a Maternal and Child Health Hospital in Shandong Province, China, from April to June 2024, were recruited by convenience sampling. A Sociodemographic Questionnaire, Edinburgh Postpartum Depression Scale, Pittsburgh Sleep Quality Index, and Perceived Social Support Scale were used for investigation. SPSS 26.0 was used to analyze the data, and multivariate regression was employed to analyze the influencing factors of postpartum depression between primiparous and multiparous women.ResultsThe total prevalence of postpartum depression among 429 postpartum women (191 primiparas and 238 multiparas) was 22.14%. The prevalence of postpartum depression among primiparous and multiparous women were 21.99% and 22.27%, respectively, with no statistically significant difference [OR=1.016, 95% CI (0.642, 1.608)]. Sleep quality is a common protective factor for postpartum depression in both primiparous and multiparous women, while perceived social support is another protective factor for multiparous women. The risk factors are different in both two group, there is no risk factor found in primiparous women, the newborns health and women’s expectation on newborns gender are risk factors for postpartum depression in multiparous women.ConclusionsBoth primiparous and multiparous women have a high risk of postpartum depression. In order to promote the mental health of postpartum women, precise nursing measures should be adopted for different parity of postpartum women in clinical practice.

BackgroundSchizophrenia, a severe mental disorder, is often complicated by Type 2 Diabetes Mellitus (T2DM), which can further impact patients’ psychological health. This study investigated the differences in eating attitudes, depression, and insight between schizophrenic patients with and without comorbid T2DM and explored the correlations among these factors to provide empirical support for clinical interventions.MethodsThis case-control study was conducted in Guangdong Province, China. From December 2022 to May 2023, a total of 300 hospitalized patients with schizophrenia (92 with comorbid T2DM and 208 without T2DM) were recruited. Data were collected using the Personal Information Form, Eating Attitudes Test (EAT-26), Hamilton Depression Scale (HAMD), and Insight and Treatment Attitudes Questionnaire (ITAQ). Statistical analyses, including t-tests, ANOVA, and multiple linear regression, were performed to examine differences and predictive factors of eating attitudes among patients. This study was approved by the Ethics Committee of the Affiliated Brain Hospital of Guangzhou Medical University (approval number: 2020028), and written informed consent was obtained from all participants.ResultsPatients with schizophrenia and comorbid T2DM exhibited significantly higher risks of eating disorders (EAT-26: 12.54 ± 9.77 vs. 9.07 ± 7.90, P=0.003), more severe depression (HAMD: 14.71 ± 7.36 vs. 11.80 ± 6.04, P=0.001), and poorer insight (ITAQ: 10.46 ± 6.01 vs. 12.16 ± 6.09, P=0.025) compared to those without T2DM. Regression analysis revealed that gender, weekly exercise frequency, depression, and insight were significant predictors of eating attitudes among patients with T2DM. For patients without T2DM, weekly exercise frequency, smoking status, and insight were significant predictors.ConclusionSchizophrenic patients with comorbid T2DM are facing increasing risks related to eating attitudes, depression, and insight which highlight the need for targeted interventions. Regular psychological assessment and tailored support strategies might improve their mental health and quality of life. Future research should focus on longitudinal studies to clarify causal relationships and develop more effective interventions.

In environments with high humidity or water exposure, the performance of polyurethane materials could be adversely affected by water and its penetration, which could compromise their long-term utility. The influence of water on polyurethane materials is affected by water transport and various factors. This article summarizes the factors affecting the water absorption of polyurethane, introduces research methods for water transport in polyurethane, analyzes the pathways of water transport, and reviews the influence of water on the mechanical properties of polyurethane and its composite materials. The ultimate goal of this paper is to furnish a comprehensive theoretical foundation and a valuable reference for the research and practical application of polyurethane materials in water environments.