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BACKGROUND: There is limited knowledge about the effect of leisure activities on cognitive decline related to different multimorbidity patterns. The study aimed to examine the role of leisure activities in the association between multimorbidity patterns and cognitive function. METHODS: We conducted a community-based cohort study based on the 2002-2018 Chinese Longitudinal Health Longevity Survey (CLHLS). Multimorbidity patterns were examined by exploratory factor analysis. Multivariable linear and logistic regression models were used to assess the associations between multimorbidity, leisure activities and cognitive function. RESULTS: The study included 14,093 older adults. Those with specific multimorbidity patterns had lower MMSE scores. Compared to individuals with cardio-metabolic and sensory patterns who frequently engaged in activities such as housework, garden work, and watching TV/listening to the radio, those who participated in these activities less regularly had lower MMSE scores. Furthermore, a higher frequency change of participation and a greater variety of leisure activities were associated with better cognitive function. CONCLUSIONS: The older individuals with multimorbidity are associated with lower MMSE scores, while those who participated in more leisure activities had higher cognitive function. Diverse, and frequent leisure activities may help delay cognitive decline in Chinese older adults with different multimorbidities.

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BACKGROUND: Localized scleroderma (LoS) is an autoimmune disease characterized by fibrosis of the skin and atrophy of the subcutaneous fat tissue. Adipose-derived mesenchymal stem cells (ASCs) is a promising treatment approach for LoS. However, ASCs from scleroderma patients (LoS-ASCs) have been shown to exhibit altered characteristics compared to ASCs from healthy donors (healthy-ASCs). This study aimed to compare the abilities of LoS-ASCs and healthy-ASCs in treating skin fibrosis. METHODS: The paracrine ability of ASCs was tested with cytokine array. Bleomycin-challenged mice models received subcutaneous injection of LoS-ASCs and healthy-ASCs. Pathological staining and western blotting of COL1, α-SMA was performed. Fibroblasts derived from LoS lesions (LoS-FB) was co-cultured with ASCs, and subjected to RNA sequencing to further explore the similarities and differences in the treatment mechanism. RESULTS: In vivo comparison revealed that healthy ASCs had a stronger proliferation ability and secreted higher levels of growth factors and cytokines, including VEGFA, PDGFB, and IL-10. Pathological staining of the skin in mice models treated with ASCs demonstrated that healthy ASCs were more effective in reducing dermal thickness and collagen deposition, while increasing microvessel density and the proportion of M2 macrophages. Co-culture with both healthy-ASCs and LoS-ASCs reduced the proliferation and migration abilities of LoS-FB, as well as the protein expression of α-SMA and COL1. RNA sequencing and validation revealed potential difference in the canonical Wnt pathway. CONCLUSIONS: Healthy-ASCs exhibited stronger proliferation, paracrine, anti-fibrosis, pro-angiogenesis, and immunomodulation abilities in treating skin fibrosis in scleroderma mouse models. CLINICAL RELEVANCE STATEMENT: Allogenic ASCs obtained from healthy donors are more efficient in treating skin fibrosis, and could serve as a potential alternative for patients who are not suitable candidates for liposuction surgery in the future.

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Epsilon toxin (ETX), a potential agent of biological and toxic warfare, causes the death of many ruminants and threatens human health. It is crucial to understand the toxic mechanism of such a highly lethal and rapid course toxin. In this study, we detected the effects of ETX on the proteome and phosphoproteome of MDCK cells after 10 min and 30 min. A total of 44 differentially expressed proteins (DEPs) and 588 differentially phosphorylated proteins (DPPs) were screened in the 10 min group, while 73 DEPs and 489 DPPs were screened in the 30 min group. ETX-induced proteins and phosphorylated proteins were mainly located in the nucleus, cytoplasm, and mitochondria, and their enrichment pathways were related to transcription and translation, virus infection, and intercellular junction. Meanwhile, the protein-protein interaction network screened out several hub proteins, including SRSF1/2/6/7/11, SF3B1/2, NOP14/56, ANLN, GTPBP4, THOC2, and RRP1B. Almost all of these proteins were present in the spliceosome pathway, indicating that the spliceosome pathway is involved in ETX-induced cell death. Next, we used RNAi lentiviruses and inhibitors of several key proteins to verify whether these proteins play a critical role. The results confirmed that SRSF1, SF3B2, and THOC2 were the key proteins involved in the cytotoxic effect of ETX. In addition, we found that the common upstream kinase of these key proteins was SRPK1, and a reduction in the level of SRPK1 could also reduce ETX-induced cell death. This result was consistent with the phosphorylated proteomics analysis. In summary, our study demonstrated that ETX induces phosphorylation of SRSF1, SF3B2, THOC2, and SRPK1 proteins on the spliceosome pathway, which inhibits normal splicing of mRNA and leads to cell death.

Assuntos

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Oxidative phosphorylation (OXPHOS) in the mitochondrial inner membrane is a therapeutic target in many diseases. Neural stem cells (NSCs) show progress in improving mitochondrial dysfunction in the central nervous system (CNS). However, translating neural stem cell-based therapies to the clinic is challenged by uncontrollable biological variability or heterogeneity, hindering uniform clinical safety and efficacy evaluations. We propose a systematic top-down design based on membrane self-assembly to develop neural stem cell-derived oxidative phosphorylating artificial organelles (SAOs) for targeting the central nervous system as an alternative to NSCs. We construct human conditionally immortal clone neural stem cells (iNSCs) as parent cells and use a streamlined closed operation system to prepare neural stem cell-derived highly homogenous oxidative phosphorylating artificial organelles. These artificial organelles act as biomimetic organelles to mimic respiration chain function and perform oxidative phosphorylation, thus improving ATP synthesis deficiency and rectifying excessive mitochondrial reactive oxygen species production. Conclusively, we provide a framework for a generalizable manufacturing procedure that opens promising prospects for disease treatment.

Assuntos

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This article presents a brief overview of the researches on ICOPE in China, the barriers influencing the implementation of ICOPE are identified, and the recommendations are proposed to advance the ICOPE practice in China.

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Background: Patients with unprotected left main (UPLM) disease who underwent percutaneous coronary intervention (PCI) were found to have inconsistent results compared to those treated with coronary artery bypass grafting (CABG). Methods: We identified and enrolled randomized controlled trials (RCTs) and observational studies (OSs) comparing PCI versus CABG for UPLM disease. A meta-analysis was performed using Stata 17.0. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCEs). Additionally, all-cause death, cardiac death, myocardial infarction (MI), stroke, target vessel revascularization (TVR), and stent thrombosis (ST) were included as secondary endpoints. The odds ratios and 95% confidence intervals (CIs) were calculated. Sensitivity analyses were implemented if I 2 > 50% or p < 0.01. Publication bias analysis was conducted if more than 10 studies were included. Results: A total of 5 RCTs and 18 OSs involving 35,409 patients were included. The CABG strategy had a significantly lower incidence of MACCEs, primarily due to TVR. A significantly lower stroke rate was observed with the PCI strategy, as well as a significantly lower all-cause death, cardiac death, MI, and ST rate compared with the CABG strategy. Conclusions: MACCE rates were significantly lower in patients who underwent CABG, primarily due to TVR, but stroke rates were higher. RCTs with different study types need further investigation to confirm the most effective strategy.

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Motivation is a key factor for child development, but very few studies have examined child and family predictors of both child task and perceived motivation. Thus, the three aims of this 6-month longitudinal study in preschoolers with global developmental delays (GDD) were to explore: 1) differences between task and perceived motivation in cognitive domain; 2) differences among three domains of perceived motivation: cognitive, gross motor, and social; and 3) early child and family predictors of cognitive task motivation and the three domains of perceived motivation 6 months later. Results indicated that preschoolers with GDD showed higher cognitive task motivation than cognitive perceived motivation, and lower perceived cognitive motivation than the other two perceived motivation domains. Different child and family factors predicted cognitive task motivation and the three domains of perceived motivation. Practitioners should educate caregivers on how to observe children's motivation to enhance children's active participation.

Assuntos

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Glioblastoma (GBM) is a malignant Grade VI cancer type with a median survival duration of only 8-16 months. Earlier detection of GBM could enable more effective treatment. Hyperpolarized magnetic resonance spectroscopy (HPMRS) could detect GBM earlier than conventional anatomical MRI in glioblastoma murine models. We further investigated whether artificial intelligence (A.I.) could detect GBM earlier than HPMRS. We developed a deep learning model that combines multiple modalities of cancer data to predict tumor progression, assess treatment effects, and to reconstruct in vivo metabolomic information from ex vivo data. Our model can detect GBM progression two weeks earlier than conventional MRIs and a week earlier than HPMRS alone. Our model accurately predicted in vivo biomarkers from HPMRS, and the results inferred biological relevance. Additionally, the model showed potential for examining treatment effects. Our model successfully detected tumor progression two weeks earlier than conventional MRIs and accurately predicted in vivo biomarkers using ex vivo information such as conventional MRIs, HPMRS, and tumor size data. The accuracy of these predictions is consistent with biological relevance.

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Clinical diagnostics is a fundamental course required for clinical medical students and serves as a prerequisite for several advanced clinical subjects. However, recent observations indicate a decline in interest among eight-year clinical medicine students at Peking Union Medical College regarding clinical diagnostics courses. Instead, these students seem to prioritize the publication of high-impact articles and involvement in scientific research over their medical coursework, leading to a lack of sufficient attention to clinical diagnostics. In the clinical diagnostics course conducted in the first half of 2024, our objective was to engage medical students by presenting the subject matter in an interesting and relevant manner. We curated textual information regarding the health condition of Lin Daiyu, the protagonist from the Chinese literary classic "The Dream of the Red Chamber," and encouraged students to deduce potential diseases she may have experienced based on the original text. Additionally, we sourced historical photographs of Empress Dowager Cixi from the Qing Dynasty, which facilitated the hypothesis that she likely suffered from goiter. These images were employed as a practical examination question during the mid-semester assessment to evaluate the students' proficiency in conducting neck physical examinations. Furthermore, we shared an inspiring anecdote about healthcare professionals who repurposed potato chip packaging into stethoscopes during the COVID-19 pandemic, underscoring the critical role of physical diagnosis and examination in urgent situations. Following the mid-term exam in clinical diagnosis, a questionnaire survey was administered to the medical students who participated in the examination. The results indicated that 93% of the students found the question regarding Lin Daiyu to be highly engaging, while 89% found the question about Empress Dowager Cixi equally captivating. These innovative teaching strategies significantly enhanced the medical students' enthusiasm for learning clinical diagnostics.

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Mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade malignant lymphoproliferative disease, representing a low percentage of newly diagnosed lymphoma cases. Although its exact cause is still unclear, it is commonly associated with infections or autoimmune diseases. The stomach is the most frequent site for MALT lymphoma, with primary hepatic MALT lymphoma being exceptionally rare. Cases of primary hepatic MALT lymphoma often coincide with viral hepatitis. In this report, we present a case of primary hepatic MALT lymphoma in a patient with no history of hepatitis but complicated by primary biliary cholangitis (PBC) and Hashimoto's thyroiditis.

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Intestinal obstruction, a rare manifestation of immunotherapy-related gastrointestinal adverse events, can be severe and even life-threatening with intestinal perforation. We present a 64-year-old man with HCC and currently under the therapy with Pembrolizumab, who was admitted in our hospital with abdominal distension. Radiologic findings were consistent with small bowel ileus. After conservative treatment, the patient underwent colonoscopy where no cause of ileus was discovered. The patient received high-dose prednisone due to the side effects of immune checkpoint inhibitor therapy. This resulted in a gradual improvement of symptoms.

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[This corrects the article DOI: 10.7759/cureus.62300.].

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This article presents a case study of diffuse large B-cell lymphoma in an elderly patient whose initial clinical manifestation was rapidly developing abdominal distension. The article delves into the patient's diagnostic and treatment journey, highlights treatment insights, and reviews relevant literature. The aim is to enhance the clinical diagnosis accuracy for elderly lymphoma patients presenting with a singular atypical symptom, ultimately optimizing treatment plans and enriching clinicians' knowledge of the disease.

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Diabetic foot ulcers (DFUs) pose a critical medical challenge, significantly im-pairing the quality of life of patients. Adipose-derived stem cells (ADSCs) have been identified as a promising therapeutic approach for improving wound healing in DFUs. Despite extensive exploration of the mechanical aspects of ADSC therapy against DFU, its clinical applications remain elusive. In this review, we aimed to bridge this gap by evaluating the use and advancements of ADSCs in the clinical management of DFUs. The review begins with a discussion of the classification and clinical management of diabetic foot conditions. It then discusses the current landscape of clinical trials, focusing on their geographic distribution, reported efficacy, safety profiles, treatment timing, administration techniques, and dosing considerations. Finally, the review discusses the preclinical strategies to enhance ADSC efficacy. This review shows that many trials exhibit biases in study design, unclear inclusion criteria, and intervention protocols. In conclusion, this review underscores the potential of ADSCs in DFU treatment and emphasizes the critical need for further research and refinement of therapeutic approaches, with a focus on improving the quality of future clinical trials to enhance treatment outcomes and advance the field of diabetic wound care.

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Sarcopenic obesity, characterized by both obesity and sarcopenia, significantly impacts health and independence of affected individuals. There is an urgent need to explore effective strategies for addressing or preventing sarcopenic obesity. An initial critical step is to promptly assess the impact of academic research in this field, considering factors such as geographical regions, authors, journals, and institutions. It is also essential to analyze current trends and identify potential areas that may inspire future researchers to conduct further studies, ultimately improving public health outcomes for individuals with sarcopenic obesity. To achieve this, bibliometric research was conducted using the Web of Science Core Collection database to identify English language articles and reviews focusing on sarcopenic obesity interventions published between January 1, 2004, and June 15, 2024, followed by a literature review. A total of 929 English-language articles were collected, consisting of 645 research articles and 284 reviews. Research output in the field has shown significant growth since 2017, reaching a peak of 139 papers in 2022. The United States leads in publication output with 234 papers and a total of 13,971 citations, highlighting substantial international collaboration. Both the United States and Europe are recognized as key academic hubs for sarcopenic obesity intervention research, characterized by robust academic interactions. Moreover, there has been a notable increase in publication volume from China, South Korea, and Japan. Noteworthy authors in this field include Boirie Y from Université Clermont Auvergne in France, Prado CM from the University of Alberta in Canada, Cruz-Jentoft AJ from Hospital Universitario Ramon y Cajal in Spain, and Prado CM from the University of Alberta, known for their high citation count. The University of Alberta leads in the number of publications, while the University of Verona in Italy leads in citation frequency. Journals with higher publication volumes in sarcopenic obesity intervention include Nutrients, Clinical Nutrition, and Journal of Cachexia Sarcopenia and Muscle. Among the top 20 keywords, the most relevant interventions for sarcopenic obesity are exercise, nutrition, resistance training, physical activity, and muscle strength. The primary evidence currently available suggests that resistance training is the most effective method for enhancing muscle strength in sarcopenic obesity patients. Additionally, combining protein supplementation with resistance exercise has shown encouraging results in reducing fat mass in these individuals. To progress in this field, it is crucial to foster collaboration among countries, regions, and academic institutions, promoting multidisciplinary partnerships.

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This case study highlights a 79-year-old man with chronic low back pain attributed to severe lumbar scoliosis. Physical examination revealed the unilateral absence of pectoral muscles and ipsilateral hand anomalies, indicative of Poland syndrome (PS). The patient also experienced depression due to chronic pain and PS-related anomalies. A multi-disciplinary approach proved effective in alleviating both pain and depression.

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Cushing's disease (CD) is a rare and serious condition characterized by a persistent increase in cortisol levels, resulting in various complications across multiple bodily systems. Elderly individuals often face a multitude of chronic illnesses and geriatric syndromes, which can complicate the diagnosis and treatment of CD in this demographic. This case study details the presentation of an elderly patient with adrenocorticotropic hormone (ACTH)-dependent CD, who initially presented with an acute exacerbation of chronic obstructive pulmonary disease. The article delves into the unique onset characteristics and treatment strategies for CD in the elderly, providing valuable insights for the comprehensive management of similar clinical cases.

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Efficiently fabricating a cavity that can achieve strong interactions between terahertz waves and matter would allow researchers to exploit the intrinsic properties due to the long wavelength in the terahertz waveband. Here we show a terahertz detector embedded in a Tamm cavity with a record Q value of 1017 and a bandwidth of only 469 MHz for direct detection. The Tamm-cavity detector is formed by embedding a substrate with an Nb5N6 microbolometer detector between an Si/air distributed Bragg reflector (DBR) and a metal reflector. The resonant frequency can be controlled by adjusting the thickness of the substrate layer. The detector and DBR are fabricated separately, and a large pixel-array detector can be realized by a very simple assembly process. This versatile cavity structure can be used as a platform for preparing high-performance terahertz devices and opening up the study of the strong interactions between terahertz waves and matter.

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INTRODUCTION: Older adults with multimorbidity are at high risk of cognitive impairment development. There is a lack of research on the associations between different multimorbidity measures and cognitive function among older Chinese adults living in the community. METHODS: We used the Chinese Longitudinal Healthy Longevity Survey from 2002 to 2018 and included data on dementia-free participants aged ≥65 years. Multimorbidity measures included condition counts, multimorbidity patterns, and trajectories. The association of multimorbidity measures with cognitive function was examined by generalized estimating equation and linear and logistic regression models. RESULTS: Among 14,093 participants at baseline, 43.2% had multimorbidity. Multimorbidity patterns were grouped into cancer-inflammatory, cardiometabolic, and sensory patterns. Multimorbidity trajectories were classified as "onset-condition," "newly developing," and "severe condition." The Mini-Mental State Examination scores were significantly lower for participants with more chronic conditions, with cancer-inflammatory/cardiometabolic/sensory patterns, and with developing multimorbidity trajectories. DISCUSSION: Condition counts, sensory pattern, cardiometabolic pattern, cancer-inflammatory pattern, and multimorbidity developmental trajectories were prospectively associated with cognitive function. HIGHLIGHTS: Elderly individuals with a higher number of chronic conditions were associated with lower MMSE scores in the Chinese Longitudinal Healthy Longevity Survey data. MMSE scores were significantly lower for participants with specific multimorbidity patterns. Individuals with developing trajectories of multimorbidity were associated with lower MMSE scores and a higher risk of mild cognitive impairment.