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Background: The efficacy of acupoint application in the treatment of ulcerative colitis (UC) is still controversial. The purpose of this study is to systematically evaluate the clinical efficacy and safety of acupoint application in the treatment of ulcerative colitis., Methods: The databases of China National Knowledge Infrastructure (CNKI), Chinese Biology Medicine (CBM), VIP, Wanfang, Embase, PubMed, the Cochrane Library and Web of Science were searched. The time limit was from the establishment of the database to July 2022. The published randomized controlled trials of acupoint application in the treatment of UC were analyzed by meta-analysis and trial sequential analysis., Results: A total of 13 studies were included, with a total sample size of 878 cases. Compared with conventional western medicine, acupoint application can effectively improve the effective rates of clinical comprehensive (risk ratio [RR] 1.13, 95% confidence interval [CI] 1.06-1.20, P = .0003), syndrome (RR 1.13, 95% CI 1.03-1.24, P = .009), and interleukin-4 (IL-4) (mean differences 2.62, 95% CI 1.96-3.28, P < .00001) in the treatment of UC, and reduce interferon-γ (mean differences -5.38, 95% CI -6.81 to -3.94, P < .00001). The effective rates of colonoscopy (RR 0.94, 95% CI 0.84-1.05, P = .25), pathological examination (RR 1.04, 95% CI 0.90-1.20, P = .60) and rate of adverse reaction (RR 0.55, 95% CI 0.25-1.21, P = .14) were the same. Trial sequential analysis indicated that the benefits of effective rates of clinical comprehensive and syndrome, IL-4, and interferon-γ were conclusive. Harbord regression showed no publication bias (P = .98). The evaluation of evidence quality suggested that the evidence quality of effective rates of clinical comprehensive and syndrome was moderate and the evidence quality of other indicators was low or very low., Conclusion: Acupoint application is a safe and effective method for the treatment of UC, and has the prospect of clinical application., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Artificial intelligence (AI) in health care is the future that is already here. Despite its potential as a transformational force for primary care, most primary care providers (PCPs) do not know what it is, how it will impact them and their patients, and what its key limitations and ethical pitfalls are. This article is a beginner's guide to health care AI, written for the frontline PCP. Primary care-as the dominant force at the base of the health care pyramid, with its unrivaled interconnectedness to every part of the health system and its deep relationship with patients and communities-is the most uniquely suited specialty to lead the health care AI revolution. PCPs can advance health care AI by partnering with technologists to ensure that AI use cases are relevant and human-centered, applying quality improvement methods to health care AI implementations, and advocating for inclusive and ethical AI that combats, rather than worsens, health inequities., Competing Interests: Conflict of interest: The author is a principal investigator working with companies and nonprofit organizations through grants and sponsored research agreements administered by Stanford University. Current and previous collaborators include Amazon, American Academy of Family Physicians, American Board of Artificial Intelligence in Medicine, American Board of Family Physicians, Center for Professionalism and Value in Health Care, Codex Health, DeepScribe, Eko Health, Google Health, Quadrant Technologies, Soap Health, Society of Teachers of Family Medicine, University of California, San Francisco, and Verily. Neither the author, nor members of his immediate family, has any financial interest in these organizations., (© Copyright 2022 by the American Board of Family Medicine.)

Knowledge of the survival and stability of a pathogen is important for understanding its risk, reducing its transmission, and establishing control measures. Lassa virus is endemic in West Africa, causes severe disease, and is an emerging pathogen of concern. Our study examined the survival of Lassa virus in blood and tissue culture media at two different temperatures. The stability of Lassa virus held within a small particle aerosol was also measured. In liquids, Lassa virus was found to decay more quickly at 30 °C compared to room temperature. Sealed samples protected from environmental desiccation were more stable than samples open to the environment. In a small particle aerosol, the decay rate of Lassa virus was determined at 2.69% per minute. This information can contribute to risk assessments and inform mitigation strategies in the event of an outbreak of Lassa virus.

Modelo do estudo: Estudo experimental. Introdução: A Doença Renal Crônica (DRC) refere-se a um diagnóstico sindrômico de perda progressiva e irreversível da função renal. O paciente submetido à hemodiálise pode apresentar limitações na capacidade funcional, função pulmonar e força muscular respiratória, com consequentes prejuízos na qualidade de vida. Objetivo: Avaliar os efeitos de um programa de exercício físico sobre a função pulmonar, capacidade funcional, qualidade de vida e dor, em pacientes que realizam hemodiálise. Metodologia: Participaram do estudo 28 pacientes de ambos os sexos, com idade entre 40 e 60 anos, em programa de hemodiálise no Instituto do Rim da Santa Casa de Misericórdia de Presidente Prudente-SP. A força muscular respiratória foi avaliada pela manovacuometria, a capacidade funcional, pelo TC6', a qualidade de vida, pelo questionário KDQOLSF, a função pulmonar, pela espirometria e a dor, pela EVA. Após as avaliações, os pacientes iniciaram o programa de exercícios, que foi desenvolvido três vezes por semana, durante 40 minutos em hemodiálise, por oito semanas. Ao final do programa, os pacientes foram reavaliados. Resultados: Não houve diferença significativa dos valores da CVF e VEF1 pré e pós-programa de exercícios, assim como do Índice de Tiffenau. O valor da PImax pós-programa foi significativamente maior que o obtido na avaliação pré-programa. Para a variável PEmax, não foi encontrada diferença significativa. As avaliações da capacidade funcional inicial e final não apresentaram diferenças significativas (p>0,05). A avaliação da qualidade de vida, quanto aos domínios das áreas específicas da DRC, mostrou que houve significância estatística, ao comparar a lista de sintomas e problemas com a sobrecarga da DRC e papel profissional. Os indicadores relativos à dor foram reduzidos, após o programa (p

Abstract Highly accurate nighttime cloud detection in satellite imagery is challenging due to the absence of visible to near-infrared (0.38–3 μm, VNI) data, which is critical for distinguishing clouds from other ground features. Fortunately, Machine learning (ML) techniques can more effectively leverage the limited wavelength information and show high-accuracy cloud detection based on vast sample volume. However, accurately distinguishing cloud pixels solely through thermal infrared bands (8–14 μm, TIR) is challenging, and acquiring numerous, high-quality and representative samples of nighttime images for ML proves to be unattainable in practice. Given the thermal infrared radiation transmission process and the fact that daytime and nighttime have the same source of radiance in TIR, we propose a sample generation idea that uses daytime images to provide samples of nighttime cloud detection, which is different from the traditional sample construction methods (e.g., manually label, simulation and transfer learning method), and can obtain samples effectively. Based on this idea, nighttime cloud detection experiments were carried out for MODIS, GF-5 (02) and Himawari-8 satellites, respectively. The results were validated by the Lidar cloud product and manual labels and show that our nighttime cloud detection result has higher accuracy than MYD35 (78.17%) and the ML model trained by nighttime manual labels (75.86%). The accuracy of the three sensors is 82.19%, 88.71%, and 79.34%, respectively. Moreover, we validated and discussed the performance of our algorithm on various surface types (vegetation, urban, barren and water). The results revealed that the accuracy of the three sensors over barren was found to be poor and varied with surface types but overall high. Our study can provide a novel perspective on nighttime cloud detection of muti-spectral satellite imagery.

Abstract Low temperatures are a key factor affecting the growth, development, and geographical distribution of prickly ash. This study investigated the impact of ecological and geographical factors on the freezing tolerance of prickly ash germplasm. Thirty-seven germplasm samples from 18 different origins were collected, and their freezing tolerance was comprehensively evaluated. The correlation between freezing tolerance and the ecological and geographical factors of their origins was also analyzed. Significant differences in freezing tolerance were observed among germplasm from different origins. The semi-lethal temperature of the germplasm ranged from − 12.37 to 1.08 °C. As temperatures decreased, the relative conductivity (REC) and catalase (CAT) activity of the germplasm gradually increased, while soluble sugar (SS), soluble protein (SP), free proline (Pro), and Peroxidase (POD) activities decreased and then increased. Superoxide dismutase (SOD) activity initially increased and then decreased. A comprehensive evaluation of freezing tolerance was conducted using a logistic equation, membership function, and cluster analysis. Germplasm from Tongchuan and Hancheng (Shaanxi Province, China), Asakura (Japan), and Yuncheng (Shanxi Province, China) exhibited the highest freezing tolerance, whereas those from Rongchang (Chongqing Municipality, China), Qujing (Yunnan Province, China), and Honghe (Yunnan Province, China) had the lowest. The correlation analysis revealed a significant positive correlation between freezing tolerance and latitude, and a significant negative correlation with the temperature of origin. Germplasm from higher latitudes showed higher SS content, SOD and CAT activities, stronger antioxidant enzyme activity, and better freezing tolerance compared to those from lower latitudes. REC was lower in germplasm originating from low-temperature areas than in those from high-temperature areas. Additionally, SP, Pro content, SOD, and POD activities were higher, indicating effective scavenging of active oxygen free radicals. No significant correlation was found between altitude and longitude of origin and freezing tolerance. However, at similar latitudes, prickly ash from higher altitudes displayed higher antioxidant enzyme activity and stronger freezing tolerance compared to those from lower altitudes. These findings provide a scientific basis for breeding prickly ash cultivars suited to different ecological regions.

Objective To investigate short-term clinical efficacy of autologous leukocyte-poor platelet-rich plasma(LP-PRP) treatment of knee osteoarthritis(KOA). Methods 85 cases of patients with Keligren Lawrence grade Ⅰ-Ⅲ knee osteoarthritis in Peking University First Hospital Taiyuan Hospital (Taiyuan Central Hospital) from 2022 to 2023 were collected for autologous LP-PRP collection and quality assessment using a blood component separator, and all patients were treated with autologous LP-PRP. The degree and function of knee pain were assessed by visual analog scale(VAS) and knee arthritis index scale(WOMAC) at 1, 3 and 6 months after injection. Knee MRI was performed after 6 months of treatment, and the MRI imaging changes before and after treatment were compared. Different influencing factors in the treatment results were grouped and analyzed, mainly including platelet concentration in LP-PRP and K-L grading of knee joint. According to the platelet concentration in LP-PRP, it was divided into three grades, which are low concentration[(1 000)×109/L]; According to the K-L grade of the knee joint, the severity of knee osteoarthritis was divided into three grades: Ⅰ、Ⅱ、Ⅲ. Results The VAS and WOMAC scores at 1, 3 and 6 months after LP-PRP treatment were significantly lower than those before treatment, and the difference was statistically significant (P

Abstract The ecological compensation mechanism is a tool for managing regional development and promoting the green economy. This paper proposes a revised model for carbon emissions and absorption based on IPCC, then analyses the spatial and temporal variations of carbon emissions, absorption, and deficit in 31 provinces of China from 2001 to 2019. A model was developed to redistribute carbon deficits and compensate for ecological imbalances, with the aim of eliminating background differences between regions. The concept of ecological compensation sensitivity was proposed, and a redundancy analysis (RDA) was conducted to detect possible influencing factors. Results indicate that: (1) The carbon deficits were relatively substantial in the centre and developed coastal regions, which were the subject regions of China’s ecological compensation. Meanwhile, the northwest and southwest regions were the object regions of ecological compensation, and the compensated object regions tended to extend towards the southeast. The majority of compensated subject areas are generally less sensitive than compensated object regions. (2) The graph of carbon deficit volume over time shows that China’s two carbon targets are closely aligned. The distribution of China’s ecological compensation amounts follows the pattern of provincial economic development levels, with higher compensation amounts concentrated in the central and coastal regions. There is a positive correlation between GDP, year, and population size with carbon emission and carbon deficit. Additionally, there is a positive correlation between year, region, and carbon absorption. (3) This compensation model can strongly incentivise the compensation subject area to proactively adjust its economic development model to cope with the significant compensation pressure. Additionally, it can fully encourage the compensation recipient area to continue adhering to the green economic development model. The conclusions of the study hold significant reference value for promoting the development of a green, low-carbon economy.

Abstract Myocardial ischemia-reperfusion injury (MIRI) is a significant complication following reperfusion therapy after myocardial infarction. Mitochondrial oxidative stress is a critical factor in MIRI, and Sirtuin 3 (SIRT3), as a major mitochondrial deacetylase, plays a key protective role, with its activity potentially regulated by O-GlcNAcylation. This study used the H9C2 cell line to establish a simulated ischemia/reperfusion (SI/R) model, we utilized co-immunoprecipitated to validate the relationship between O-GlcNAc transferase (OGT) and SIRT3, demonstrated SIRT3 O-GlcNAcylation sites through LC–MS/MS, and performed site mutations using CRISPR/Cas9 technology. The results were validated using immunoblotting. SIRT3 and superoxide dismutase 2 (SOD2) activities were detected using a fluorometric assay, while mitochondrial reactive oxygen species (MROS) levels and cellular apoptosis were assessed using immunofluorescence. We have identified an interaction between SIRT3 and OGT, where SIRT3 undergoes dynamic O-GlcNAcylation at the S190 site, facilitating SIRT3 deacetylase activity. During SI/R, elevated levels of O-GlcNAcylation activate SOD2 by promoting SIRT3 enzyme activity, thereby inhibiting excessive MROS production. This significantly mitigates the occurrence of malignant autophagy in myocardial cells during reperfusion, promoting their survival. Conversely, blocking SIRT3 O-GlcNAcylation at the S190 site exacerbates SI/R injury. We demonstrate that O-GlcNAcylation is a crucial post-translational modification (PTM) of SIRT3 during SI/R, shedding light on a promising mechanism for future therapeutic approaches.

Abstract This study aimed to reveal the diversity and variation in panicle traits of the Chinese prickly ash and clarify their influence on the its systematic classification to provide a theoretical basis and technical support for the efficient utilization of Chinese prickly ash germplasm resources and breeding. Sixteen panicle traits were identified from 35 Chinese prickly ash germplasm resources from 2021 to 2022. The diversity of these panicle traits and their role in the plant’s systematic classification were studied using variance, correlation, cluster, and principal component analyses. Cluster analysis showed that the 35 Chinese prickly ash germplasm resources could be divided into two groups with Euclidean distances of 25. Further analysis showed that yield traits such as panicle length, panicle width, primary branching, grain number per panicle, and grain weight per panicle were significantly positively correlated with grain chlorophyll content, while grain anthocyanin content was negatively correlated with both panicle (panicle length, panicle width, panicle length to width ratio, primary branching, grain number per panicle, and grain weight per panicle) and grain characteristics (single grain weight, thousand-grain weight, grain length, grain width and fruit shape index). In conclusion, Chinese prickly ash germplasms have diverse panicle traits. Z. armatum has dark green grains, long and wide panicles, a long conical shape, many primary branches, high grain weight, and high grain number per panicle. In contrast, Z. bungeanum has bright red seeds, a panicle width larger than its length, short and conical panicles, a small number of primary branches, and low grain weight per panicle and number of grains per panicle. Overall, Z. armatum had a significant yield advantage over Z. bungeanum.

Abstract The sole use of single modality data often fails to capture the complex heterogeneity among patients, including the variability in resistance to anti-HER2 therapy and outcomes of combined treatment regimens, for the treatment of HER2-positive gastric cancer (GC). This modality deficit has not been fully considered in many studies. Furthermore, the application of artificial intelligence in predicting the treatment response, particularly in complex diseases such as GC, is still in its infancy. Therefore, this study aimed to use a comprehensive analytic approach to accurately predict treatment responses to anti-HER2 therapy or anti-HER2 combined immunotherapy in patients with HER2-positive GC. We collected multi-modal data, comprising radiology, pathology, and clinical information from a cohort of 429 patients: 310 treated with anti-HER2 therapy and 119 treated with a combination of anti-HER2 and anti-PD-1/PD-L1 inhibitors immunotherapy. We introduced a deep learning model, called the Multi-Modal model (MuMo), that integrates these data to make precise treatment response predictions. MuMo achieved an area under the curve score of 0.821 for anti-HER2 therapy and 0.914 for combined immunotherapy. Moreover, patients classified as low-risk by MuMo exhibited significantly prolonged progression-free survival and overall survival (log-rank test, P

Abstract The ceiling structure in a long-narrow space has a significant impact on the thickness of the fire smoke layer. This paper mainly studies the influence of the height of the ceiling structure on the thickness of the smoke layer before the ceiling structure. Firstly, a theoretical analysis is conducted on the relationship between the critical thickness that affects the smoke flow state and the smoke layer thickness directly below the ceiling structure, and a formula for calculating the smoke layer thickness under gradient flow conditions is derived. Then a small-scale experimental platform was built to study the deviation of actual fire smoke relative to theoretical calculations. Experimental results show that due to the smoke cannot maintain gradient flow when crossing the ceiling structure, there is difference with theoretical calculations in the smoke layer thickness directly below the ceiling structure and some distance before the ceiling structure (which may be of greater concern for personnel evacuation). The gradient flow coefficient and thickness coefficient are defined to represent the above differences. After analysis, it was found that the gradient flow coefficient and thickness coefficient showed different linear variation patterns when the height of the ceiling structure was longer than 35 cm or shorter than 30 cm. Through numerical analysis, this study suggests that the main reason for the change in this linear pattern is whether the potential energy conversed from kinetic energy of the thin layer close to the ceiling structure can directly make the smoke to cross the ceiling structure. The research conclusions of this paper can assist in the engineering design of building smoke control and personnel evacuation.

Abstract Convenient and effective biomarkers are essential for the early diagnosis and treatment of Alzheimer’s disease (AD). In the cross-sectional study, 103 patients with AD, 82 patients with aMCI and 508 normal controls (NC) were enrolled. The single‐molecule array (Simoa) technique was used to assess the levels of plasma proteins, including NfL, T-tau, P-tau-181, Aβ40, Aβ42. Montreal Cognitive Assessment (MoCA) was used to assess the overall cognitive function of all subjects. Moreover, Amyloid PET and structural head MRI were also performed in a subset of the population. In the follow-up, the previous 508 normal older adults were followed up for two years, then COX regression analysis was used to investigate the association between baseline plasma proteins and future cognitive outcomes. NfL, T-tau, P-tau-181, Aβ40, Aβ42 and Aβ42/40 were altered in AD dementia, and NfL, Aβ42 and Aβ42/40 significantly outperformed all plasma proteins in differentiating AD dementia from NC, while NfL and Aβ42/40 could effectively distinguish between aMCI and NC. However, only plasma NfL was associated with future cognitive decline, and it was negatively correlated with MoCA (r = − 0.298, p

Abstract Objectives This study aimed to investigate the associations between changes in blood pressure (BP) and cerebral small vessel disease (CSVD). Methods This study included 401 participants in the magnetic resonance imaging (MRI) sub-study conducted between 2018 and 2020 as a part of the Multidomain Interventions to Delay Dementia and Disability in Rural China project. MRI markers of CSVD were assessed based on international criteria. Individualized linear regression models evaluated changes in BP by estimating the trend of blood pressure changes over time and fitting a straight line from 2014 to 2018. The data were analyzed using logistic and general linear regression models. Result The mean age of the participants was 64.48 ± 2.69 years, with 237 (59.1%) being females. Increases in systolic BP in later life were significantly associated with larger volumes of periventricular white matter hyperintensity (WMH), greater perivascular spaces in the basal ganglia (BG-PVS) burden, and the presence of deep lacunes and cerebral microbleeds. Additionally, increases in diastolic BP in later life were significantly associated with the presence of infratentorial and deep lacunes. Conclusions CSVDs are associated with increased exposure to elevated BP later in life.

Abstract Immunoinflammation is associated with the development of post-stroke cognitive impairment (PSCI), however, peripheral immunity has not been fully explored. We aimed to investigate the association between PSCI and peripheral immune indicators, including neutrophil, lymphocyte, and mononuclear percentages and counts; the systemic immune inflammation index; platelet-to-lymphocyte ratio; neutrophil-to-lymphocyte ratio (NLR); and lymphocyte-to-monocyte ratio. A total of 224 patients with acute minor ischemic stroke or transient ischemic attack with 6–12 months of follow-up were included. PSCI was defined as a Montreal Cognitive Assessment score

Abstract Background This study is to propose a clinically applicable 2-echelon (2e) diagnostic criteria for the analysis of thyroid nodules such that low-risk nodules are screened off while only suspicious or indeterminate ones are further examined by histopathology, and to explore whether artificial intelligence (AI) can provide precise assistance for clinical decision-making in the real-world prospective scenario. Methods In this prospective study, we enrolled 1036 patients with a total of 2296 thyroid nodules from three medical centers. The diagnostic performance of the AI system, radiologists with different levels of experience, and AI-assisted radiologists with different levels of experience in diagnosing thyroid nodules were evaluated against our proposed 2e diagnostic criteria, with the first being an arbitration committee consisting of 3 senior specialists and the second being cyto- or histopathology. Results According to the 2e diagnostic criteria, 1543 nodules were classified by the arbitration committee, and the benign and malignant nature of 753 nodules was determined by pathological examinations. Taking pathological results as the evaluation standard, the sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) of the AI systems were 0.826, 0.815, 0.821, and 0.821. For those cases where diagnosis by the Arbitration Committee were taken as the evaluation standard, the sensitivity, specificity, accuracy, and AUC of the AI system were 0.946, 0.966, 0.964, and 0.956. Taking the global 2e diagnostic criteria as the gold standard, the sensitivity, specificity, accuracy, and AUC of the AI system were 0.868, 0.934, 0.917, and 0.901, respectively. Under different criteria, AI was comparable to the diagnostic performance of senior radiologists and outperformed junior radiologists (all P 0.05). Conclusions The proposed 2e diagnostic criteria are consistent with real-world clinical evaluations and affirm the applicability of the AI system. Under the 2e criteria, the diagnostic performance of the AI system is comparable to that of senior radiologists and significantly improves the diagnostic capabilities of junior radiologists. This has the potential to reduce unnecessary invasive diagnostic procedures in real-world clinical practice.

Abstract Prolonged ventricular repolarization has been associated with cardiovascular disease. We sought to investigate the association of prolonged ventricular repolarization with mild cognitive impairment (MCI) and the potential underlying neuropathological mechanisms in older adults. This cross-sectional study included 4328 dementia-free participants (age ≥ 65 years; 56.8% female) in the baseline examination of the Multidomain INterventions to delay dementia and Disability in rural China; of these, 989 undertook structural brain magnetic resonance imaging (MRI) scans. QT, QTc, JT, JTc, and QRS intervals were derived from 12-lead electrocardiograph. MCI, amnestic MCI (aMCI), and non-amnestic MCI (naMCI) were defined following the Petersen’s criteria. Volumes of gray matter (GM), white matter, cerebrospinal fluid, total white matter hyperintensities (WMH), periventricular WMH (PWMH), and deep WMH (DWMH) were automatically estimated. Data were analyzed using logistic and general linear regression models. Prolonged QT, QTc, JT, and JTc intervals were significantly associated with an increased likelihood of MCI and aMCI, but not naMCI (p

Objectives Detection and diagnosis of Chlamydia psittaci (C. psittaci) pneumonia is often overlooked due to conventional methods limitations and similarity to other atypical community acquired pneumonia (CAP). Using mNGS, we aimed to distinguish psittacosis from legionellosis for early C. psittaci pneumonia diagnosis and better prognosis.Methods Thirty-seven patients diagnosed with atypical CAP were enrolled in this retrospective study, including 14 C. psittaci pneumonia and 23 Legionella pneumophila (L. pneumophila) pneumonia. We collected and compared baseline, lab results, radiology imaging, conventional microbiological methods and more importantly, mNGS results of clinical samples, as well as the treatments and prognosis between psittacosis and legionellosis.Results Patients with C. psittaci and L. pneumophila had similar symptoms and were presented with high levels of inflammatory markers. However, patients with C. psittaci pneumonia were more likely to have exposure to birds or parrots [11 (78.6%) vs. 2 (8.7%), p

Summary: This study explored the feasibility of adjuvant immunotherapy after NICT and surgery. A retrospective study was conducted on NSCLC patients who underwent NICT and surgery. Two patient groups were defined based on their adjuvant therapy after NICT and surgery: the Chemo group (chemotherapy alone) and the Immuno+Chemo group (chemotherapy combined with immunotherapy). Disease-free survival (DFS) and overall survival (OS) were also analyzed. In total, 209 patients were enrolled. The median DFS for the Immuno+Chemo group and the Chemo group was not reached vs. 26 months (hazard ratio [HR]: 0.498, 95% confidence interval [CI]: 0.315–0.787, p = 0.002). A significant difference in OS was also observed; however, the median OS was not reached in either group (HR: 0.526, 95% CI: 0.287–0.965, p = 0.034). Postoperative adjuvant chemotherapy combined with immunotherapy was significantly more effective than adjuvant chemotherapy alone in patients with NSCLC treated with NICT and surgery.

AbstractIn recent years, the incidence and mortality rates of lymphoma have gradually increased worldwide. Tumorigenesis and drug resistance are closely related to intracellular inflammatory pathways in lymphoma. Therefore, understanding the biological role of inflammatory pathways and their abnormal activation in relation to the development of lymphoma and their selective modulation may open new avenues for targeted therapy of lymphoma. The biological functions of inflammatory pathways are extensive, and they are central hubs for regulating inflammatory responses, immune responses, and the tumour immune microenvironment. However, limited studies have investigated the role of inflammatory pathways in lymphoma development. This review summarizes the relationship between abnormal activation of common inflammatory pathways and lymphoma development to identify precise and efficient targeted therapeutic options for patients with advanced, drug-resistant lymphoma.

Background The rapid pace of knowledge production has introduced a phenomenon termed “knowledge anxiety”, a psychological state where researchers feel inadequate in keeping up with emerging information. This state can negatively affect productivity and mental well-being, yet there is no comprehensive tool to measure knowledge anxiety across different research domains. Methods We employed a mixed-methods approach to develop a multidimensional scale for assessing knowledge anxiety. Initial items were generated through a literature review and qualitative interviews with 313 researchers. After pilot testing, the main study involved 26 participants. The scale was refined through exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to ensure its structural validity and reliability. Results EFA resulted in a 16-item scale with four distinct factors: cognitive, emotional, behavioral, and capability-related anxieties. CFA confirmed a strong model fit, with standardized factor loadings between 0.549 and 0.887. The scale demonstrated high reliability, with a composite Cronbach’s alpha of 0.883. Conclusions This newly developed scale offers a reliable and valid measure of knowledge anxiety, providing researchers with a valuable tool to assess the psychological impacts of knowledge overload.

Increasing researches reveal gut microbiota was associated with the development of tuberculosis (TB). How to prevent or reduce Mycobacterium tuberculosis colonization in the lungs is a key measure to prevent TB. However, the data on gut microbiota preventing Mycobacterium colonization in the lungs were scarce. Here, we established the clindamycin-inducing intestinal microbiome dysbiosis and fecal microbial transplantation models in mice to identify gut microbiota’s effect on Mycobacterium’s colonization in the mouse lungs and explore its potential mechanisms. The results showed that clindamycin treatment altered the diversity and composition of the intestinal bacterial and fungal microbiome, weakened the trans-kingdom network interactions between bacteria and fungi, and induced gut microbiome dysbiosis in the mice. Gut microbiota dysbiosis increases intestinal permeability and enhances the susceptibility of Mycobacterium colonization in the lungs of mice. The potential mechanisms were gut microbiota dysbiosis altered the lung transcriptome and increased Nos2 expression through the ‘gut–lung axis’. Nos2 high expression disrupts the intracellular antimicrobial and anti-inflammatory environment by increasing the concentration of nitric oxide, decreasing the levels of reactive oxygen species and Defb1 in the cells, and promoting Mycobacteria colonization in the lungs of mice. The present study raises a potential strategy for reducing the risks of Mycobacteria infections and transmission by regulating the gut microbiome balance.

Small cell lung cancer (SCLC) is the most common neuroendocrine tumor in the lungs. SCLC is characterized by high malignancy and high recurrence and metastasis rates. The improvement of the prognosis of patients with SCLC relies on early diagnosis, correct staging, and accurate assessment of efficacy and prognosis. In this paper, we comprehensively analyze the application progress of 18F-fluorodeoxyglucose (FDG) PET/CT as well as the tumor markers neuron-specific enolase (NSE) and gastrin-releasing peptide precursor (ProGRP) in the diagnosis and treatment of SCLC. Our results can be useful for the diagnosis and treatment of SCLC patients in clinical practice.

Abstract Epidermal growth factor receptor (EGFR) is reportedly overexpressed in most esophageal squamous cell carcinoma (ESCC) patients, but anti-EGFR treatments offer limited survival benefits. Our preclinical data showed the promising antitumor activity of afatinib in EGFR-overexpressing ESCC. This proof-of-concept, phase II trial assessed the efficacy and safety of afatinib in pretreated metastatic ESCC patients (n = 41) with EGFR overexpression (NCT03940976). The study met its primary endpoint, with a confirmed objective response rate (ORR) of 39% in 38 efficacy-evaluable patients and a median overall survival of 7.8 months, with a manageable toxicity profile. Transcriptome analysis of pretreatment tumors revealed that neurotrophic receptor tyrosine kinase 2 (NTRK2) was negatively associated with afatinib sensitivity and might serve as a predictive biomarker, irrespective of EGFR expression. Notably, knocking down or inhibiting NTRK2 sensitized ESCC cells to afatinib treatment. Our study provides novel findings on the molecular factors underlying afatinib resistance and indicates that afatinib has the potential to become an important treatment for metastatic ESCC patients.

Abstract CD8+ T cell immune responses are regulated by multi-layer networks, while the post-translational regulation remains largely unknown. Transmembrane ectodomain shedding is an important post-translational process orchestrating receptor expression and signal transduction through proteolytic cleavage of membrane proteins. Here, by targeting the sheddase A Disintegrin and Metalloprotease (ADAM)17, we defined a post-translational regulatory mechanism mediated by the ectodomain shedding in CD8+ T cells. Transcriptomic and proteomic analysis revealed the involvement of post-translational regulation in CD8+ T cells. T cell-specific deletion of ADAM17 led to a dramatic increase in effector CD8+ T cell differentiation and enhanced cytolytic effects to eliminate pathogens and tumors. Mechanistically, ADAM17 regulated CD8+ T cells through cleavage of membrane CD122. ADAM17 inhibition led to elevated CD122 expression and enhanced response to IL-2 and IL-15 stimulation in both mouse and human CD8+ T cells. Intriguingly, inhibition of ADAM17 in CD8+ T cells improved the efficacy of chimeric antigen receptor (CAR) T cells in solid tumors. Our findings reveal a critical post-translational regulation in CD8+ T cells, providing a potential therapeutic strategy of targeting ADAM17 for effective anti-tumor immunity.

Abstract A method has been developed to increase computational efficiency in Monte Carlo simulations of electron transport and interactions in matter. The method serves as the computational engine for the open-source code AMCSET (Aggie Monte Carlo Simulations of Electron and Ion Transport). The key is to combine n consecutive neighboring free flying distances into groups. Within each group, both flying distance and Mott scattering angles are obtained using Monte Carlo sampling under an equal energy approximation. This reduces the number of integrations of the tabulated differential Mott scattering cross-section in scattering angle selection, i.e., from 1000 to 1 if n = 1000. The method increases efficiency by more than 100 times. At the same time, the calculation still guarantees accuracy in calculating electron trajectory, excitation/ionization energy deposition, elastic scattering energy deposition, and displacement creation. For demonstration, 10 MeV electron bombardments of pure Fe with n up to 1000 are used as examples. The method, due to the availability of tabulated scattering cross-sections, is applicable for targets of the entire elemental table up to Z = 118, and for electron energies up to 900 MeV.

Abstract Background Deep brain stimulation (DBS) is a promising therapy for refractory Gilles de la Tourette syndrome (GTS). However, its long-term efficacy, safety, and recommended surgical age remain controversial, requiring evidence to compare different age categories. Methods This retrospective cohort study recruited 102 GTS patients who underwent DBS between October 2006 and April 2022 at two national centers. Patients were divided into two age categories: children (aged 0.05), and the children group received significantly higher improvement in GTS-QOL scores than adults (55.9% vs. 47.9%, p = 0.049). Conclusions DBS showed acceptable long-term efficacy and safety for both children and adults with GTS. Surgeries performed for patients younger than 18 years seemed to show acceptable long-term efficacy and safety and were not associated with increased risks of loss of benefit compared to patients older than 18 at the time of surgery. However, surgeries for children should also be performed cautiously to ensure their refractoriness and safety.

Abstract For the first time, a control strategy based on Fuzzy Sliding Mode Control is implemented in the control of a large amplitude limit cycle of a composite cantilever beam in a multi-dimensional nonlinear form. In the dynamic model establishment of the investigated structure, the higher-order shearing effect is applied, as well as the second-order discretization. Numerical simulation demonstrates that a multi-dimensional nonlinear dynamic system of the investigated structure is demanded for accurate estimation of large amplitude limit cycle responses. Therefore, a control strategy is employed to effectively suppress such responses of the beam in multi-dimensional nonlinear form.

Objective To discuss the possible etiology, pathogenesis, clinical features, diagnosis and treatment of epidermoid cysts of the jaw and to provide a reference for clinical diagnosis and treatment. Methods A case of an epidermoid cyst in the right mandible with retained deciduous teeth and succedaneous impacted teeth was reviewed and analyzed in combination with the relevant literature. Results A patient presented with a mass in the right mandible that had persisted for 1 month after being found at imaging examination. Tooth 83 was retained, and tooth 43 was unerupted. Swelling was characterized by no obvious tenderness, fluctuation, or table tennis sensation and was observed in the lingual alveoli of teeth 83, 44, and 45. Imaging revealed a low-density shadow in the apex of teeth 83, 44, 45, and 46, approximately 1.9 cm × 2.6 cm × 1.6 cm in size, which wrapped around the dental crown of tooth 43. Preliminary diagnoses were as follows: right mandibular mass thought to be a dentigerous cyst; impacted tooth 43; and retained primary tooth 83. The mass in the right mandible was removed, and teeth 43 and 83 were extracted under intravenous and inhalation anesthesia. During the operation, the mass was observed to have a thin cyst wall and contained bean-like residue. Histopathological examination indicated an epidermoid cyst in the right mandible. At the 1-week follow-up examination, the patient reported no discomfort, and the surgical area showed good recovery. According to the literature, epidermoid cysts are benign cysts originating from ectopic ectodermal tissue that can occur throughout the body but rarely in the oral cavity and are even extremely rarer in the jaw. Epidermoid cysts of the jaw, which have no specific clinical manifestations, can be confused with odontogenic cysts such as dentigerous cysts and odontogenic tumors. Dental pulp tests and other techniques can serve as a reference for clinicians. The diagnosis is confirmed via histopathology. Surgical removal is a common treatment, with a good prognosis and a low recurrence rate. Conclusion The principle of treatment for an epidermoid cyst of the jaw is similar to that for a jaw cyst. The prognosis is good when the cyst is removed completely.

Objective To investigate the risk factors of acute kidney injury （AKI） in patients with severe acute pancreatitis （SAP）. Methods Clinical data of 66 patients with SAP were collected in this retrospective study. All patients were divided into the AKI and non-AKI groups according to whether they were complicated with AKI. The risk factors of AKI in patients with SAP were identified by using Logistic regression analysis and receiver operating characteristic （ROC） curve. Results The overall age and Acute Physiology and Chronic Health Evaluation （APACHE） Ⅱscore of SAP patients complicated with AKI were higher than those without AKI， but diabetes mellitus was more common in non-AKI patients （all P < 0.05）. Patients in the AKI group had higher levels of hypersensitive C-reactive protein （CRP）， systemic inflammatory response index （SIRI）， creatinine （Scr）， CRP/Albumin （Alb） index and D-dimer （DDI） upon admission， whereas had lower fasting triglyceride and glucose simple index （TyG）， Alb， total cholesterol， high density lipoprotein cholesterol （HDL-C） and blood calcium levels compared with their counterparts without AKI， and the differences were statistically significant （all P < 0.05）. Stepwise regression analysis showed that increased APACHEⅡ score， increased SIRI index， increased PLR index， decreased SII index and decreased blood calcium were the independent risk factors for SAP patients complicated with AKI （all P < 0.05）. ROC curve results showed that in addition to Scr， APACHEⅡ score， SIRI index and blood calcium had certain diagnostic value in SAP patients complicated with AKI， among which the area under the ROC curve （AUC） of APACHEⅡ score was 0.880 （95% CI 0.787-0.974， optimal cutoff value 11.50）， 0.662 （95% CI 0.521-0.804， optimal cutoff value 10.89） for SIRI index， and 0.754 （95% CI 0.627-0.881， optimal cutoff value 2.07 mmol/L） for blood calcium level （all P < 0.05）. The combination of the above three indexes with Scr could further improve the diagnostic value for AKI in SAP patients， among which the AUC of Scr + blood calcium was the largest， reaching 0.969 （95% CI 0.929-1.000， P < 0.05）. Conclusions APACHEⅡ score， SIRI index， PLR index， SII index and blood calcium level are the independent risk factors of AKI in SAP patients. APACHEⅡ score， SIRI index and blood calcium have diagnostic value in SAP patients complicated with AKI. The combination of these three indexes with Scr can significantly improve the diagnostic efficiency for AKI， providing a novel diagnostic approach for AKI in SAP patients.

Abstract Macrophage responses to activation are fluid and dynamic in their ability to respond appropriately to challenges, a role integral to host defence. While bacteria can influence macrophage differentiation and polarization into pro-inflammatory and alternatively activated phenotypes through direct interactions, many questions surround indirect communication mechanisms mediated through secretomes derived from gut bacteria, such as lactobacilli. We examined effects of secretome-mediated conditioning on THP-1 human monocytes, focusing on the ability of the Lacticaseibacillus rhamnosus R0011 secretome (LrS) to drive macrophage differentiation and polarization and prime immune responses to subsequent challenge with lipopolysaccharide (LPS). Genome-wide transcriptional profiling revealed increased M2-associated gene transcription in response to LrS conditioning in THP-1 cells. Cytokine and chemokine profiling confirmed these results, indicating increased M2-associated chemokine and cytokine production (IL-1Ra, IL-10). These cells had increased cell-surface marker expression of CD11b, CD86, and CX3CR1, coupled with reduced expression of the M1 macrophage-associated marker CD64. Mitochondrial substrate utilization assays indicated diminished reliance on glycolytic substrates, coupled with increased utilization of citric acid cycle intermediates, characteristics of functional M2 activity. LPS challenge of LrS-conditioned THP-1s revealed heightened responsiveness, indicative of innate immune priming. Resting stage THP-1 macrophages co-conditioned with LrS and retinoic acid also displayed an immunoregulatory phenotype with expression of CD83, CD11c and CD103 and production of regulatory cytokines. Secretome-mediated conditioning of macrophages into an immunoregulatory phenotype is an uncharacterized and potentially important route through which lactic acid bacteria and the gut microbiota may train and shape innate immunity at the gut-mucosal interface.

Abstract This study aimed to investigate structural synaptic plasticity in the medial prefrontal cortex of rats under treadmill exercise pretreatment or naive conditions in a vascular dementia model, followed by recognition memory performance in a novel object recognition task. In this study, 24 Sprague–Dawley rats were obtained and randomly assigned into 4 groups as follows: control group (Con group, n = 6), vascular dementia (VD group, n = 6), exercise and vascular dementia group (Exe + VD group, n = 6), and exercise group (Exe group, n = 6). Initially, 4 weeks of treadmill exercise intervention was administered to the rats in the Exe + VD and Exe groups. Then, to establish the vascular dementia model, the rats both in the VD and Exe + VD groups were subjected to bilateral common carotids arteries surgery. One week later, open-field task and novel recognition memory task were adopted to evaluate anxiety-like behavior and recognition memory in each group. Then, immunofluorescence and Golgi staining were used to evaluate neuronal number and spine density in the rat medial prefrontal cortex. Transmission electron microscopy was used to observe the synaptic ultrastructure. Finally, microdialysis coupled with high-performance liquid chromatography was used to assess the levels of 5-HT and dopamine in the medial prefrontal cortex. The behavior results showed that 4 weeks of treadmill exercise pretreatment significantly alleviated recognition memory impairment and anxiety-like behavior in VD rats (P

Abstract The morphological, physiological, and biochemical characteristics of leaves result from the long-term adaptation of plants to their environment and are closely related to plant growth and development. In this study, 37 prickly ash germplasm resources from 18 production areas were utilized as the subjects of research. Logistic equations, principal component analysis, and cluster analysis were employed to comprehensively evaluate the leaf traits of prickly ash germplasm resources, with an analysis of their correlation with ecological and geographical factors in the production areas. The results showed that the leaf traits of prickly ash germplasms of different origins are substantially different and diverse. The coefficient of variation for the 14 leaf traits was greater than 10%. The coefficient of variation of the compound leaflet number was the highest among all the considered leaf traits, and the coefficient of variation of leaf thickness was the lowest, at 49.86% and 11.37%, respectively. The leaf traits of the prickly ash germplasm originating from Chongqing in Yongchuan, Chongqing in Rongchang, and Yunnan in Honghe ranked highest, whereas the leaf traits of the prickly ash germplasm from Henan in Jiaozuo, Gansu in Tianshui, and Shanxi in Yuncheng ranked lowest. The results of the correlation analysis showed that among the ecological and geographical factors of the origins, latitude had the strongest correlation with the leaf traits of the prickly ash germplasm. As latitude increased, the leaves of prickly ash gradually decreased in size, weight, and leaf shape index. The factor with the second strongest correlation was temperature. The leaves of the prickly ash germplasm originating from warmer climate areas were larger and heavier than those from areas with colder climates. Altitude and longitude did not significantly affect the leaf traits of the prickly ash germplasm, but at similar latitudes, the leaves of the prickly ash germplasm in high-altitude areas were smaller, and the leaves of the prickly ash germplasm in low-altitude areas were larger. These findings can provide valuable references for breeding and the sustainable utilization of new varieties of prickly ash resources.

ObjectiveTo present the exploration and application of a prospective follow-up research method for acute infectious disease surveillance based on natural community populations， using COVID-19 infection as an example， and to provide a reference for improving the infectious disease surveillance and early warning system.MethodsA multi-stage probability proportional sampling method was employed to sample residents from all communities of 16 administrative districts in Shanghai， with households as the units. A cohort for acute infectious diseases based on natural community populations was established. The baseline survey was conducted for all cohort subjects， and COVID-19 antigen test kits were distributed. From December 21， 2022 to September 30， 2023， prospective follow-up monitoring of COVID-19 antigen and nucleic acid was carried out on the study subjects on a weekly basis. The baseline characteristics and follow-up information of the cohort subjects were described.ResultsThe cohort for acute infectious diseases included a total of 12 881 subjects， comprising 6 098 males （47.3%） and 6 783 females （52.7%）. The baseline survey revealed that 35.2% （4 540/12 881） of the subjects had a history of COVID-19 infection. During the follow-up period from December 21， 2022 to September 30， 2023， the average incidence density in the cohort was 0.61/person-year， with a higher incidence density in females （0.63/person-year） compared to males （0.59/person-year）. Individuals aged 60 and above （0.64/person-year） and those with underlying health conditions （0.67/person-year） had a higher incidence density. Healthcare workers showed a notably higher incidence density （0.84/person-year） than that in other occupational groups. As of September 30， 2023， a total of 340 subjects in the cohort experienced secondary infections， with a median interval of 170 days between the first and second infections.ConclusionThis study applies cohort study method to acute infectious disease surveillance， providing crucial data support for estimating infection rates and forecasting alerts for acute infectious diseases in the community. This method can be promoted and applied as a new approach for acute infectious disease surveillance.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a hereditary heart disease characterized by bidirectional or polymorphic ventricular tachycardia and an increased risk of sudden cardiac death. Although trans-2,3-enoyl-CoA reductase like (TECRL) is a newly reported pathogenic gene leading to CPVT that can influence intracellular calcium regulation, the unidentified mechanism underlying the pathogenesis of TECRL deficiency-mediated CPVT remains mainly elusive. In the present study, Tecrl knockout (KO) mice were established and the differentially expressed genes (DEGs) were investigated by RNA-sequencing from the heart tissues. In addition, 857 DEGs were identified in Tecrl KO mice. Subsequently, a weighted gene co-expression network analysis was conducted to discern the pivotal pathways implicated in the Tecrl-mediated regulatory network. Moreover, pathway mapping analyses demonstrated that essential metabolism-related pathways were significantly enriched, notably the fatty acid metabolic process and calcium regulation. Collectively, the data suggested a synergistic relationship between Tecrl deficiency and cardiometabolic and calcium regulation during the development of CPVT. Therefore, further studies on the potential function of TECRL in cardiac tissues would be beneficial to elucidate the pathogenesis of CPVT.

Abstract Purposes The influence of gender on the epidemiology of and outcome from SA-AKI in ICU has not been fully clarified. Our aim is to elucidate these differences. Methods This study included adult patients with sepsis in MIMIC IV (V 2.2), and propensity matching analysis, cox regression and logistic regression were used to analyze gender differences in incidence, mortality and organ support rate. Results Of the 24,467 patients included in the cohort, 18,128 were retained after propensity score matching. In the matched cohort, the incidence of SA-AKI in males is higher than that in females (58.6% vs. 56.2%; P = 0.001).males were associated with a higher risk of SA-AKI (OR:1.07(1.01–1.14), P = 0.026;adjusted OR:1.07(1.01–1.14), P

Abstract Background Claudin-18.2 (CLDN18.2) has emerged as an alluring therapeutic target against gastrointestinal tumors in recent years. However, a thorough understanding of its regulatory mechanism in gastric cancer remains elusive. Methods We presented a comprehensive study comprising 185 gastric cancer patients, which included 112 cases with high CLDN18.2 expression and 73 cases with low CLDN18.2 expression as determined by immunohistochemistry. After overdressed CLDN18.2 in AGS and NUGC4 cell lines, we elucidated the functions of CLDN18.2 in connecting gastric cancer cells and cancer-associated fibroblasts (CAFs) through an in vitro adhesion models and in vivo lung colonization models. The molecular mechanism underlying CLDN18.2-mediated interaction between gastric cancer cells and CAFs was identified through RNA sequencing and protein-proximity labeling techniques in vivo. Results In our own cohort, a correlation was observed between high levels of CLDN18.2 expression and advanced cancer stage, poor prognosis, and heightened infiltration of CAFs. We elucidated a pivotal role of CLDN18.2 in mediating adhesion between gastric cancer cells and CAFs, which leads to the adhesion of cancer cells to stroma tissue and facilitates the clustering of cancer cells and CAFs into embolus, enhancing gastric cancer’s metastatic progression and the risk of embolic death. Mechanistically, it was discovered that CAFs can activate adhesion and metastasis-related signaling pathways in CLDN18.2-positive gastric cancer cells. Furthermore, using an in vivo protein-proximity labeling approach, we identified S100 calcium binding protein A4 (S100A4) as a distinctive marker of CAFs that interacts with CLDN18.2 to enhance gastric cancer progression. Conclusions Our findings illuminated the role of the CLDN18.2-mediated interaction between cancer cells and CAFs in promoting gastric cancer progression and embolism, thereby providing insight into potential therapeutic avenues for CLDN18.2 positive cancers. Video Abstract