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Abstract To evaluate the distribution of metastases after radiotherapy using 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT). 67 patients with 501 new metastases revealed by 18F-FDG PET/CT after radiotherapy were included in this retrospective study. The metastases were divided into radiation area (RA) and non-radiation area (NRA), based on their locations inside or outside the radiation exposure field. Patients were divided into two groups based on the comparison of lesions number between RA and NRA: group A (NRA ≤ RA) and group B(NRA > RA). The distribution characteristics of metastases and their relationship with clinical data were analyzed. 67 patients were included in the study. A total of 501 lesions were detected: 122 in RA and 379 in NRA. 28 patients resulted in group A and 39 in group B. Patients with lesion number (LN) ≤ 5 were primarily assigned to Group A (56.1%, 23/41), whereas those with LN > 5 were primarily assigned to Group B (80.8%, 21/26). A statistically significant difference in lesion count was observed between the two groups (χ2 = 8.809, P = 0.003).Among 19 patients with RA = 0, 17 had LN ≤ 5 and 2 had LN > 5. In contrast, among 25 patients with NRA = 0, 10 had LN ≤ 5 and 15 had LN > 5. A significant difference was noted between patients with RA = 0 and those with NRA = 0 (χ2 = 4.728, P = 0.030). An notable characteristic in the distribution of metastases following radiotherapy is their tendency to occur outside the irradiation area. This indicated that the radiotherapy exposure area acquires a certain tumor growth inhibitory effect, potentially lasting over time. Based on these observations, there may be potential for developing novel preventive irradiation techniques.

Abstract Big Data Analysis from the worldwide field shows that lost circulation is a common phenomenon in drilling and the success ratio of remedial treatment for lost circulation is low. It is not only because of these complexities of the formation, but also because of the poor performances of the lost-circulation materials (LCM) and technologies. This paper proposes a new method in plugging, which is based on a particular physical method for lost circulation controlling and plugging while drilling. This method is different from these traditional treatments, which only use chemical methods. When pore-permeable and fractured leakage formations are encountered while drilling, We can use this new hydraulic tool, the drilling fluid will have a diffluence at a constant rate from the jet of the hydraulic tool which is installed on the drilling pipe and the fluid laden with particles can be injected into the natural or induced fractures of the borehole wall which may lead to lost circulation. Combined with the corresponding drilling fluids which have been tested in the laboratory, the additives such as ground marble, ground nutshells, and graphite in the drilling fluid are quickly pushed into the fractures because of the differential pressure provide by the hydraulic tool, then form a firm seal at the mouth of the fractures which could isolate fluid pressure in the wellbore and prevent effective pressure communication to interfere the extension of the fracture. What’s more, according to the stress cage theory, when these sealing particles which prop the fracture open, act as wedges to compress the rock around the wellbore, the hoop stress could be increased, so that the wellbore pressure containment (WPC) could be improved. Since the annular flow may have some interference with the side nozzle jet, this paper also numerically simulates the flow field of the annular air section through the fluid simulation software Fluent, and the simulation results show that the interference of the annular flow on the jet is very weak and basically has no effect. In addition, through the oilfield field test, it is known that this new physical plugging method has good plugging effect, and it can obviously improve the pressure-bearing capacity of the formation, which has great popularization value.

Abstract We aimed to differentiate and evaluate the clinical imaging features of pulmonary cryptococcosis with different therapeutic responses. The clinical imaging data of 70 patients with PC (complete response PC 37 cases and incomplete response PC 33 cases) were collected and compared to determine the independent risk factors for different therapeutic responses, and their diagnostic performances were verified by receiver operating characteristic curve analysis. Compared with complete response PC, incomplete response PC was more common with immunosuppression (10.8% vs. 45.5%, P = 0.001), intermediate progress (8.1% vs. 39.4%, P = 0.002), bilateral distribution (21.6% vs. 78.8%, P

Abstract Yeo’s index, the product of the mitral leaflet separation index and dimensionless index of mitral valve (MV), was recently described to accurately identify severe rheumatic mitral stenosis (MS). We assess the association between Yeo’s index and clinical outcomes in patients with rheumatic MS. We studied 297 patients with rheumatic MS. Clinical and echocardiographic data were obtained from the electronic medical record and Yeo’s index was measured in all cases. The outcome studied was a composite of all cause death, heart failure (HF) hospitalisation, MV intervention and stroke or transient ischaemic attack. We also performed subgroup analysis of patients without pre-existing atrial fibrillation (AF) to assess for association with new onset AF. The median follow up was 6.3 years; 145 patients (48.8%) developed the composite outcome. Yeo’s index (p

Abstract Bloodstream infections are globally occurring life-threatening diseases that impose significant societal and economic burdens. This study explored the red cell distribution width (RDW) to albumin ratio (RAR), a novel index derived from RDW, to investigate its relationship with prognosis of bacteremia using propensity score matching (PSM). This retrospective observational cohort study included patients with bacteremia admitted to Yantai Yuhuangding Hospital’s intensive care units from June 2019 to December 2022. PSM was performed to adjust for confounding factors. The relationship between RAR and mortality was assessed using receiver operating characteristic curves, multivariate, and Kaplan–Meier analyses. A total of 411 patients were included. The RAR threshold of 5.824% /g/dL was determined by maximizing the Youden index; the study population was divided into two groups based on this cutoff value. After PSM, 125 pairs of score-matched patients were generated. Using logistic regression analysis, patients with RAR ≥ 5.824% /g/dL exhibited significantly higher mortality than did those with RAR ＜ 5.824% /g/dL in the entire cohort (OR = 3.926, 95% confidence interval (CI): 2.408–6.400, p

Abstract Roof breaking is the root cause of rock burst and mine earthquake. However, the classical “thin plate theory” and “thick plate theory” cannot fully reveal the mechanical mechanism of the influence of roof thickness-span ratio on the fracture mode. In this paper, based on the cohesive element technology, the mechanical behavior of cohesive element failure was studied according to the maximum nominal stress criterion and BK fracture criterion, and the fracture mechanical behavior of roofs with different thicknesses fixed on four sides under uniform load was numerically simulated. The fracture pattern and the maximum principal stress evolution laws of roofs with different thicknesses were obtained. The results show that there are three fracture modes of the plates with different thickness: pure tensile fracture mode at the bottom surface, mixed fracture mode around the “X” shape crack, and pure shear fracture mode along the long edge boundary. The crack morphology of thin plate is the transverse “O−X” type, and the crack morphology of thick plate is the “O−❋” type. With the increase of thickness, the tensile-shear mixed failure mode gradually changes from the tensile dominant to the shear dominant.

Abstract To assess the accuracy of a nomogram for predicting the risk of lower-extremity amputation (LEA) in individuals with diabetic foot ulcers (DFUs). We retrospectively analyzed data from 144 patients with DFUs at the Department of Orthopedics of the First Affiliated Hospital of Nanchang University, collected between January 2020 and December 2023. Univariate analysis determined primary predictive factors for amputation, followed by single and multifactor logistic regression analyses to indentify independent factors. These were utilized to develop a prediction model using R4.3.3, and a nomogram was created. Its performance was verified using receiver operating characteristic (ROC), corrected calibration, and clinical decision curves. Twelve primary predictive factors were identified from 20 variables, including age, Wagner grades, peripheral angiopathy of diabetes (PAD), chronic kidney disease(CKD), C-reactive protein(CRP) and the number of blood sugar abnormalities(BSA) etc. Multivariate logical regression analysis illustrated that Wagner grades, PAD, CRP, CKD, and the number of BSA were independent risk factors. The area under the curve (AUC) of the ROC curve was 0.967, and the revised calibration curve of the nomogram demonstrated strong fitting ability. This prediction model is a valuable tool for screening LEA risk and preventing DFU from progressing into amputation.

Abstract Given the limited head-to-head comparison of cardiovascular and renal outcomes between liraglutide and dulaglutide, our study aimed to investigate the clinical outcomes between dulaglutide and liraglutide in a real-world setting. In this new-user design, comparative and retrospective cohort study, patients with type 2 diabetes mellitus with prescription for GLP-1RAs from January 1, 2016 to December 31, 2022 (n = 8,278) were included. Primary outcome was composite cardiovascular outcomes which was composed of cardiovascular death, non-fatal myocardial infarction, and non-fatal ischemic stroke. The composite renal outcome was also interested, including new macroalbuminuria, doubling of serum creatinine, worsening of estimated glomerular filtration rate (eGFR), and progression to dialysis. A total of 3,210 subjects receiving liraglutide and 5,068 subjects receiving dulaglutide were identified. In the adjusted cohort by applying inverse probability of treatment weighting, the incidence of composite cardiovascular outcomes was 18.4 and 18.7 events per 1000 person-years in the liraglutide and dulaglutide groups, respectively. The risk of cardiovascular outcomes did not significantly differ between groups (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.85–1.15). Moreover, the risk of composite renal outcomes was also comparable between groups (subdistribution HR 1.07, 95% CI 0.995–1.16). Liraglutide and dulaglutide demonstrated comparable cardiovascular and renal outcomes in a real-world setting.

Abstract Subarachnoid hemorrhage (SAH), a stroke subtype associated with high mortality, is closely linked to neuroinflammation. Phloretin, a naturally occurring flavonoid abundant in fruits, possesses anti-inflammatory properties. However, its specific role in SAH remains unclear. Therefore, we aimed to investigate the potential role of phloretin in SAH. We established in vitro and in vivo SAH models to assess the effects of phloretin. Subsequently, utilizing SAH-related public datasets from the GEO database, we identified key genes associated with SAH and investigated the potential mechanism of action of phloretin. Our findings reveal that phloretin significantly improves prognostic outcomes and mitigates inflammation in SAH mice. Moreover, our results suggest that phloretin mitigates neuroinflammation by inhibiting the TLR2/MYD88/NF-κB pathway.

Abstract Oncogenic RET alteration is an important, tissue-agnostic therapeutic target across diverse cancers. We conducted a first-in-human phase 1 study on SY-5007, a potent and selective RET inhibitor, in patients with RET-altered solid tumors. Primary endpoints were safety, maximum tolerated dose (MTD), and recommended phase 2 dose (RP2D). Secondary endpoints included pharmacokinetics and preliminary anti-tumor activity. A total of 122 patients were enrolled (17 in dose-escalation phase and 105 in dose-expansion phase), including 91 with non-small cell lung cancer, 23 with medullary thyroid cancer, 7 with papillary thyroid cancer and 1 with gastric cancer. Treatment-related adverse events (TRAEs) were reported in 96.7% of patients, with the most common grade ≥ 3 TRAEs being hypertension (22.1%), diarrhea (16.4%), hypertriglyceridemia (6.6%), and neutropenia (6.6%). The exposure to SY-5007 was dose proportional. Among the 116 efficacy-evaluable patients, the overall objective response rate (ORR) was 57.8%, with 70.0% in treatment-naïve patients and 51.3% in previously treated patients. The median progression-free survival (PFS) was 21.1 months. Efficacy was observed regardless of tumor types and previous therapies. Biomarker analysis of 61 patients with circulating tumor DNA (ctDNA)-detectable RET alterations showed an ORR of 57.4% and median PFS of 13.8 months. Rapid ctDNA clearance of RET alteration correlated with faster responses and improved outcomes. In relapsed patients, off-target induced resistance was observed in 57.1% (12/21), with no on-target RET alterations identified. In conclusion, SY-5007 was well-tolerated and showed promising efficacy in patients with RET-altered solid tumors. Serial ctDNA monitoring may unveil treatment response and potential resistance mechanisms (NCT05278364).

Abstract Background Sepsis-induced myocardial injury (SIMI) is a severe complication of sepsis, contributing significantly to mortality. Mitochondrial dysfunction and dysregulated autophagy are implicated in SIMI pathogenesis. Long non-coding RNA MALAT1 has been associated with various diseases, including sepsis, but its role in SIMI remains unclear. Objective This study aimed to investigate the role of lncRNA MALAT1 in SIMI, specifically in the regulation of mitochondrial autophagy. Methods A sepsis-induced cardiomyopathy model was established in mice, and the cardiac tissues were analyzed. The expression of lncRNA MALAT1 was modulated and its effects on mitochondrial autophagy, myocardial injury, inflammation, and apoptosis were assessed. Furthermore, the interaction between MALAT1 and miR-146a was explored, as well as the involvement of the TLR4/NF-kB/MAPK signaling pathway. Results Activation of mitochondrial autophagy by urolithin A (UA) alleviated SIMI, inflammation, and cardiac dysfunction. Downregulation of MALAT1 enhanced mitochondrial autophagy, stabilized the mitochondrial membrane potential, and inhibited mitochondrial reactive oxygen species (ROS) production, leading to improved cell viability and reduced myocardial injury. Furthermore, MALAT1 interacted with miR-146a, and their modulation influenced mitochondrial autophagy, myocardial injury, and inflammation. The TLR4/NF-kB/MAPK signaling pathway was implicated in these processes. Conclusion Our findings suggest that lncRNA MALAT1 plays a crucial role in SIMI by modulating miR-146a-mediated mitochondrial autophagy and the TLR4/NF-kB/MAPK signaling pathway. These results provide new insights into the pathogenesis of SIMI and potential therapeutic targets.

Growth arrest and DNA damage-inducible 45b (GADD45b) was initially discovered to be involved in processes such as cell cycle arrest, differentiation and apoptosis. It is an important signal regulatory molecule in cells, responsible for signal transduction under various physiological or environmental stimuli. The GADD45b gene belongs to the GADD45 gene family. This gene is commonly expressed in human and fetal tissues, but the expression is tissue-specific, with high expression in the liver and bone marrow. The GADD45b protein is a small, evolutionarily conserved acidic protein distributed in both the cytoplasm and nucleus. Research has shown that GADD45b is closely associated with signaling pathways such as p38/MAPK and TGFβ/Smad3, and it has functions including improving tissue fibrosis and inflammation progression, inhibiting cell autophagy, and enhancing neural function recovery. GADD45b plays a significant role in tumors, innate immunity, neurological diseases, and disorders of hepatic glucose and lipid metabolism. The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing year by year in China and has become a serious public health issue in the country. Disorders in hepatic glucose and lipid metabolism are major causes of NAFLD. Multiple studies have shown that GADD45b gene and protein exhibit abnormal expression in liver diseases with hepatic glucose and lipid metabolism disorders. Previous research has found that GADD45b can increase the stability of the FoxO1 protein in hepatocytes, and enhance the expression of PGC1a, thereby promoting hepatic gluconeogenesis. Additionally, GADD45b can inhibit fatty acid transport in hepatocytes by binding to FABP1 and reduce hepatic steatosis by interacting with HSP72 protein. Therefore, the roles of GADD45b in promoting hepatic gluconeogenesis, inhibiting fatty acid transport, and reducing steatosis may form the basis for research into treatments for hepatic glucose and lipid metabolism disorders and liver diseases. This paper reviews the characteristics and functions of the GADD45b protein, as well as recent advances in the study of hepatic glucose and lipid metabolism and liver diseases, aiming to provide reference for further GADD45b research.

Abstract Severe psoriasis has a long course and poor outcome, and it has long been a problem for patients. Understanding the independent risk factors that contribute to patients with severe psoriasis is critical for the development of effective treatment strategies. This large, multicenter study recruited 2,109 plaque psoriasis patients from 12 hospitals across China (October 31, 2019 – May 31, 2022). The logistic regression model underwent internal validation and external validation using two independent cohorts over future time periods (June 1, 2022 – January 31, 2023). The discriminative power of our model was substantiated by a C-index of 0.863 (95% CI: 0.848–0.879) in internal validation, further affirmed through 1,000 bootstrap validation (C-index: 0.860, 95% CI: 0.836–0.885) and external validation cohorts, where the C-index reached up to 0.910 (95% CI: 0.868–0.953) and 0.951 (95% CI: 0.924–0.977) in 2 external validation cohorts. To enhance accessibility for clinicians, the model has been made available as a dynamic nomogram and QR code. Our study identified 10 risk factors (the “DELPHI” consensus dichotomy, the DLQI index, the extent of skin involvement as measured by body surface area, the age of the patient at the time of clinical visit, sex, body weight in kilograms, career, the presence of scalp involvement, facial involvement, and arthropathy) for the overall severity of psoriasis (PASI ≥ 10). “Nomogram-10” provides clinicians with a practical tool to develop personalized intervention strategies based on an individual’s risk profile. Trial registration: Chinese Clinical Trial Registry: ChiCTR1900024852.

Abstract Background Accurate differentiation between malignant and benign pulmonary nodules, especially those measuring 5–10 mm in diameter, continues to pose a significant diagnostic challenge. This study introduces a novel, precise approach by integrating circulating cell-free DNA (cfDNA) methylation patterns, protein profiling, and computed tomography (CT) imaging features to enhance the classification of pulmonary nodules. Methods Blood samples were collected from 419 participants diagnosed with pulmonary nodules ranging from 5 to 30 mm in size, before any disease-altering procedures such as treatment or surgical intervention. High-throughput bisulfite sequencing was used to conduct DNA methylation profiling, while protein profiling was performed utilizing the Olink proximity extension assay. The dataset was divided into a training set and an independent test set. The training set included 162 matched cases of benign and malignant nodules, balanced for sex and age. In contrast, the test set consisted of 46 benign and 49 malignant nodules. By effectively integrating both molecular (DNA methylation and protein profiling) and CT imaging parameters, a sophisticated deep learning-based classifier was developed to accurately distinguish between benign and malignant pulmonary nodules. Results Our results demonstrate that the integrated model is both accurate and robust in distinguishing between benign and malignant pulmonary nodules. It achieved an AUC score 0.925 (sensitivity = 83.7%, specificity = 82.6%) in classifying test set. The performance of the integrated model was significantly higher than that of individual methylation (AUC = 0.799, P = 0.004), protein (AUC = 0.846, P = 0.009), and imaging models (AUC = 0.866, P = 0.01). Importantly, the integrated model achieved a higher AUC of 0.951 (sensitivity = 83.9%, specificity = 89.7%) in 5–10 mm small nodules. These results collectively confirm the accuracy and robustness of our model in detecting malignant nodules from benign ones. Conclusions Our study presents a promising noninvasive approach to distinguish the malignancy of pulmonary nodules using multiple molecular and imaging features, which has the potential to assist in clinical decision-making. Trial registration: This study was registered on ClinicalTrials.gov on 01/01/2020 (NCT05432128). https://classic.clinicaltrials.gov/ct2/show/NCT05432128 .

Abstract The impact force of debris flow is not only an important indicator of the risk assessment of debris flow and the strength impact resistance of buildings against debris flow, but also an important parameter in the design of various debris flow prevention projects (such as the check dam and the drainage channel, etc.). The pressure sensors are arranged at different positions (monitoring points) on the upstream face of the check dam. By changing the slope of the drainage channel, the bulk density of debris flow and the slope gradient of the upstream face of the check dam, the time history curves of the impact force at the monitoring points under different experiment conditions are obtained. The characteristic value of the impact force of debris flow acting on the surface of the sand retaining dam is analyzed, and the evolution law of mean value and maximum value of impact force of debris flow at the same detection location with the above conditions is obtained. The mean value and maximum value of debris flow impact force at different detection locations under the same working condition are analyzed to obtain the evolution law of debris flow impact force at different locations, and then the distribution trend of debris flow impact force on the upstream face of the check dam is obtained. The research results provide scientific and reasonable theoretical basis and technical support for the stability analysis of the check dam, so as to better serve the disaster prevention and reduction of debris flow, which will improve the technical level of the debris flow prevention project to a certain extent.

Abstract Research exploring the link between immune cell profiles and the development of endometritis remains scant. This gap necessitates further study to decode the complex interrelations influencing this condition. In this analysis, we leveraged two-sample Mendelian randomization to examine the causal ties between the phenotypes of immune cells and the incidence of endometritis. Our evaluation hinged on data from 3757 participants hailing from Sardinia, focusing on a diverse array of 731 immune phenotypes, and cross-referenced with endometritis data sourced from the UK Biobank. To ensure rigor, we performed sensitivity analyses, utilized MR-Egger and MR-Presso to check for pleiotropy, and applied Cochran’s Q test for assessing the heterogeneity of our findings. Our investigation identified numerous immune characteristics associated with endometritis. For certain immune traits, a lower risk of endometritis was observed, including: Absolute Counts of CD39 + CD4 + T cells, CD25 + CD39 + CD4 regulatory T cells, and CD25 + + CD8 + T cells; Absolute Counts of Switched Memory B cells; CD19 expression on IgD + CD38dim and Switched Memory B cells; CD20 expression on IgD + CD38− Unswitched Memory B cells; percentage of Switched Memory B cells among lymphocytes; CD16-CD56 expression on HLA DR + Natural Killer cells; percentage of CD11c + CD62L− monocytes; CD86 expression on monocytes; CCR2 expression on CD14 + CD16 + monocytes; and CD14 expression on Monocytic Myeloid-Derived Suppressor Cells, with Odds Ratios (ORs) between 0.413 and 0.703. On the contrary, increased risks of endometritis were linked with: the percentage of Effector Memory CD4 + T cells within the CD4 + T cell population; percentages of HLA DR + T cells and HLA DR + CD8 + T cells among T cells; CD4 expression on CD28 + CD4 + T cells; CD20 expression on CD20- CD38- B cells; percentage of IgD + CD24 + B cells within the B cell population; CD62L expression on CD62L + myeloid Dendritic Cells; and Absolute Counts of Plasmacytoid Dendritic Cells, with ORs from 1.473 to 2.677, indicating these traits potentially elevate the risk of developing endometritis. Our research delineates distinct causal links between specific immune cell phenotypes and endometritis, offering new perspectives that could contribute to the pinpointing of new therapeutic avenues for this condition.

Abstract Currently, despite the vast amounts of time and money invested in cancer treatment, cancer remains one of the primary threats to human life. The primary factor contributing to the low treatment efficacy is cancer heterogeneity. The unclear molecular mechanisms underlying tumorigenesis, coupled with the complexity of human physiology, and the inability of animal models to accurately replicate the human tumor microenvironment, pose significant hurdles in the development of novel cancer therapies. Tumor-microenvironment-on-chip (TMOC) represents a research platform that integrates three-dimensional cell culture with microfluidic systems, simulating the essential components and physiological traits of the in vivo tumor microenvironment. It offers a dynamic setting within the chip system to study tumor progression, potentially heralding a breakthrough in cancer research. In this review, we will summarize the current advancements in this platform, encompassing various types of TMOCs and their applications in different types of cancer. From our perspective, the TMOC platform necessitates enhanced integration with tissue engineering techniques and microphysiological environments before it can evolve into a more refined preclinical model for cancer research.

Abstract Accumulating evidence supports that glucocorticoid treatment for viral pneumonia (VPA) can shorten the disease course and improve survival. However, currently, the use of glucocorticoids in treating VPA remains controversial. Moreover, a unified standard for the dosage and duration of glucocorticoid therapy has not been presented in published articles. A retrospective analysis was conducted in patients who were hospitalized for severe influenza virus-associated pneumonia, and they received sequential treatment with high-dose glucocorticoids and short-course oral glucocorticoids. Patients were followed up for 3 months. A total of 11 patients were included in the study (average age 56 years). There was no gender difference, but age and underlying diseases could be risk factors for severe influenza virus-associated pneumonia. The types of viruses causing pneumonia included influenza A/B. The main clinical symptoms of patients were fever, cough, sputum production, and dyspnea. Chest computed tomography showed multiple ground-glass shadows in the lobes, and the presence of bacterial and fungal infections was accompanied by consolidation shadows. After glucocorticoid therapy, the symptoms improved. None of the patients underwent tracheal intubation, and all survived. After a 3-month follow-up, lung CT absorption in all patients had reached more than 80%, and lung imaging absorption in 20% patients was complete. No serious complications occurred in any of the patients. Sequential treatment with high-dose steroids and short-course oral glucocorticoids may be helpful for reducing the tracheal intubation rate and mortality rate in patients with severe influenza virus-associated pneumonia. Additionally, short-course oral glucocorticoids may reduce pulmonary fibrosis in patients with severe influenza virus-associated pneumonia without any serious complications.

Abstract Background Posterior reversible encephalopathy syndrome is a rare neurological syndrome that refers to reversible subcortical vasogenic brain edema disorder in patients with acute neurological symptoms. Case presentation Whether there is a direct causal relationship between pancreatitis and posterior reversible encephalopathy syndrome needs further study. We here report a 39-year-old Chinese woman who was diagnosed with pancreatitis followed by vision disturbance. The patient was finally diagnosed with posterior reversible encephalopathy syndrome. On the basis of this rare case, we analyzed the causes of visual disturbance and proposed diagnostic ideas. Conclusions For posterior reversible encephalopathy syndrome, early identification and treatment of the primary disease are particularly important. Imaging and clinical characteristics in posterior reversible encephalopathy syndrome are usually reversible.

Abstract Community detection is a critical component of network analysis and a hot topic in social computing. Detecting community structure in dynamic networks has important theoretical and practical implications for understanding the intrinsic function of networks and predicting network behavior. However, the majority of existing dynamic community detection methods adopt shallow models, which have limited ability to excavate complex non-linear structures and tend to generate undesirable community structures. In order to obtain an accurate and robust community structure in dynamic networks, we are inspired by network representation learning and utilize the deep learning to detect evolving communities in dynamic networks. In this paper, we propose a novel dynamic community detection method by fusing Deep Learning and Evolutionary Clustering (DLEC). This work attempts to combine deep learning and evolutionary clustering into a unified framework. First, we propose a matrix construction strategy to fully reveal the inherent community structures via the underlying community memberships. Then, we develop a novel multi-layer deep autoencoder framework that consists of multiple non-linear functions to extract the latent deep representation of the dynamic network. Based on the evolutionary clustering framework, a graph regularization term is introduced to ensure the smoothness of the community evolution. Finally, we employ the K-means clustering algorithm on the low-dimensional network space to obtain the community structure. Extensive experimental results on synthetic and real-world networks show that the proposed DLEC algorithm can effectively detect high-quality communities in dynamic networks.

Abstract Aryl hydrocarbon receptor (AhR) plays an important role in inflammation and immunity as a new therapeutic target for infectious disease and sepsis. Punicalagin (PUN) is a Chinese herbal monomer extract of pomegranate peel that has beneficial anti-inflammatory, antioxidant and anti-infective effects. However, whether PUN is a ligand of AhR, its effect on AhR expression, and its signaling pathway remain poorly understood. In this study, we found that PUN was a unique polyphenolic compound that upregulated AhR expression at the transcriptional level, and regulated the AhR nongenomic pathway. AhR expression in lipopolysaccharide-induced macrophages was upregulated by PUN in vitro and in vivo in a time- and dose-dependent manner. Using specific inhibitors and siRNA, induction of AhR by PUN depended on sequential phosphorylation of 90-kDa ribosomal S6 kinase (p90RSK), which was activated by the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) and phosphoinositide-dependent protein kinase (PDK)1 pathways. PUN promoted p90RSK-mediated activator protein-1 (AP-1) activation. AhR knockout or inhibitors reversed suppression of interleukin (IL)-6 and IL-1β expression by PUN. PUN decreased Listeria load and increased macrophage survival via AhR upregulation. In conclusion, we identified PUN as a novel selective AhR modulator involved in AhR expression via the MEK/ERK and PDK1 pathways targeting p90RSK/AP-1 in inflammatory macrophages, which inhibited macrophage inflammation and promoted bactericidal activity.

Objective(s): Hepatic ischemia-reperfusion (HIR) is a severe process in pathophysiology that occurs clinically in hepatectomy, and hepatic transplantations. The present study aimed to investigate the effect of PKC θ deletion against HIR injury and elucidate its mechanism in pathophysiology.Materials and Methods: HIR injury was induced in wild-type and PKC θ deletion mice treated with or without heme. The ALT and AST levels were determined to evaluate liver function. HIR injury was observed via histological examination. Oxidative stress and inflammatory response markers, and their signaling pathways were detected.Results: The study found that PKC θ knockout decreased serum AST and ALT levels when compared to the WT mice. Furthermore, heme treatment significantly reduced the ALT and AST levels of the PKC θ deletion mice compared with the untreated PKC θ deletion mice. PKC θ deletion markedly elevated superoxide dismutase activity in the liver tissue, reduced malondialdehyde content in the tissue, and the serum TNF-α and IL-6 levels compared with the WT mice. Heme treatment was observed to elevate the activity of SOD and reduced MDA content and serum of TNF-α and IL 6 in the PKC θ deletion animals. Meanwhile, heme treatment increased HO-1 and Nrf 2 protein expression, and reduced the levels of TLR4, phosphorylated NF-κB, and IKB-α.Conclusion: These findings suggested that PKC θ deletion ameliorates HIR, and heme treatment further improves HIR, which is related to regulation of PKC θ deletion on Nrf 2/HO-1 and TLR4/NF-κB/IKB α pathway.

Background Thyroid hormones are very important for normal growth and development of fetus. Hypothyroidism during pregnancy and Graves' hyperthyroidism in pregnancy are well-known risk factors for small for gestational age (SGA). However, the influence of isolated maternal hypothyroxinemia (IMH) in the first trimester during pregnancy on birthweight is less analyzed and controversial. Objective To examine the correlation of IMH in the first trimester during pregnancy with birthweight. Methods This was a retrospective cohort study involving singleton pregnant women with medical files and receiving prenatal examination, delivery or termination of pregnancy in the Beijing Obstetrics and Gynecology Hospital, Capital Medical University from January 2016 to October 2020. According to the 2.5th and 97.5th percentiles of free thyroxine (FT4) and thyroid stimulating hormone (TSH), participants were assigned into IMH group (n=344) and control group (n=19 426). Binary Logistic regression was used to analyze the correlation of IMH in the first trimester during pregnancy with birthweight. Then according to the pre-pregnancy body mass index (PPBMI), participants were assigned into the overweight/obesity group (PPBMI≥24.0 kg/m2, 69 cases in IMH group and 3 376 cases in control group) and non-overweight/obesity group (PPBMI0.05). Among participants with PPBMI0.05) . Conclusion IMH in the first trimester increases the risks of macrosomia and LGA during pregnancy, especially in pre-pregnancy non-overweight/obese women. Among pre-pregnancy overweight /obese women, IMH in the first trimester does not increase the risks of macrosomia and LGA. However, the incidences of LBW and SGA are comparable in the total cohort, women with pre-pregnancy overweight/obese or those without pre-pregnancy overweight/obese.

Background Given the increased risk of adverse pregnancy outcomes in pregnant women with type 2 diabetes, in addition to glycemic control, it is crucial to understand the relationship between gestational weight gain and adverse pregnancy outcomes. Objective To investigate the gestational weight gain in pregnant women with type 2 diabetes and its relationship with pregnancy outcomes. Methods A retrospective analysis was conducted on 691 cases of pregnant women with type 2 diabetes who underwent prenatal care and delivery at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, from 2012 to 2020. According to the Chinese "Standard of Recommendation for Weight Gain during Pregnancy Period", the participants were categorized into the inadequate weight gain group (n=143), appropriate weight gain group (n=289), and excessive weight gain group (n=259). The gestational weight gain characteristics, maternal outcomes, and neonatal outcomes were compared among the three groups. Multivariate Logistic regression analysis was employed to explore the impact of gestational weight gain on pregnancy outcomes. Results The results of multivariate Logistic regression analysis showed that compared to the appropriate weight gain group, the excessive weight gain group had increased risks of cesarean section (aOR=1.626, 95%CI=1.110-2.382), preeclampsia (aOR=1.997, 95%CI=1.071-3.677), macrosomia (aOR=1.948, 95%CI=1.175-3.230), and large for gestational age (LGA) (aOR=2.090, 95%CI=1.321-3.306), while reducing the rate of vaginal delivery (aOR=0.617, 95%CI=0.415-0.918). The inadequate weight gain group was associated with a reduced risk of delivering LGA (aOR=0.497, 95%CI=0.255-0.970), with no impact on small for gestational age (SGA) (P>0.05). Further stratified analysis revealed that excessive weight gain group with pre-pregnancy BMI≥24.0 kg/m2 increased the risks of cesarean section, preeclampsia, LGA [aOR and 95%CI were 1.673 (1.082-2.587), 1.961 (1.022-3.761), 2.031 (1.221-3.379), respectively], while reducing the rate of vaginal delivery (aOR=0.589, 95%CI=0.372-0.933). The inadequate weight gain group with pre-pregnancy BMI≥24.0 kg/m2 showed a decreased risk of delivering LGA (aOR=0.487, 95%CI=0.237-0.999). Excessive weight gain during early, middle, and late pregnancy was identified as a risk factor for macrosomia [aOR and 95%CI were 1.07 (1.00-1.15), 1.16 (1.03-1.31), and 1.16 (1.06-1.27), respectively] and LGA [aOR and 95%CI were 1.08 (1.01-1.16), 1.13 (1.02-1.26), and 1.16 (1.07-1.26), respectively]. Excessive weight gain during late pregnancy was associated with gestational hypertension and preeclampsia (aOR=1.13, 95%CI=1.02-1.24; aOR=1.14, 95%CI=1.03-1.26), while excessive weight gain during middle and late pregnancy was a risk factor for cesarean section (aOR=1.11, 95%CI=1.02-1.21; aOR=1.09, 95%CI=1.02-1.17) . Conclusion Excessive gestational weight gain increases the risk of adverse pregnancy outcomes such as LGA, macrosomia, preeclampsia, and cesarean section in women with type 2 diabetes during pregnancy. Inadequate gestational weight gain reduces the risk of LGA, but does not increase the risk of SGA. There is a clear correlation between gestational weight gain during different stages of pregnancy and adverse pregnancy outcomes. Therefore, optimizing blood glucose levels during pregnancy in patients with type 2 diabetes should be accompanied by enhanced education and interventions on weight gain management from preconception and early pregnancy stages.

Background The phenomenon of coronary slow flow (CSF) is characterized by recurrent angina pectoris, which may lead to acute myocardial infarction, fatal arrhythmia and sudden cardiac death, and reduce the quality of life of patients. With the improvement of the safety, feasibility and reliability of coronary angiography (CAG), the detection rate of CSF increased gradually. However, there are few studies on the mechanism of early-onset CSF and clinical characteristics of young patients with CSF. Objective To explore the clinical characteristics in young patients with CSF and compare them with the elderly patients in order to provide its pathogenesis. Methods Continuity analysis from January 2017 to January 2019, 86 young patients (18 years ≤ age

Abstract Leaf senescence represents the final stage of leaf development, involving transcription factors (TFs)-mediated genetic reprogramming events. The timing of crop leaf senescence has a major influence on the yield and quality of crop in agricultural production. As important regulator of plant growth, the significance of TFs in the regulation of leaf senescence have been highlighted in various plant species by recent advances in genetics. However, studies on underlying molecular mechanisms are still not adequately explained. In this study, for analyzing the regulation of TFs on senescence of tobacco leaves, we combined gene differential expression analysis with weighted gene co-expression network analysis (WGCNA) to analyze the time-series gene expression profiles in senescing tobacco leaf. Among 3517 TF genes expressed in tobacco leaves, we identified 21, 35, and 183 TFs that were associated with early, middle, and late stages of tobacco leaf senescence, respectively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation results reveal that these senescence response TFs are correlated with several biological pathways such as plant hormone signal transduction, ubiquitin mediated proteolysis and MAPK signaling pathway, indicating the roles of TFs in regulating leaf senescence. Our results provide implications for future studies of the potential regulatory mechanisms of TFs involved in senescence of tobacco leaves.

Abstract Recognition of the translocation of NLRP3 to various organelles has provided new insights for understanding how the NLRP3 inflammasome is activated by different stimuli. Mitochondria have already been demonstrated to be the site of NLRP3 inflammasome activation, and the latest research suggests that NLRP3 is first recruited to mitochondria, then disassociated, and subsequently recruited to the Golgi network. Although some mitochondrial factors have been found to contribute to the recruitment of NLRP3 to mitochondria, the detailed process of NLRP3 mitochondrial translocation remains unclear. Here, we identify a previously unknown role for Signal transducer and activator of transcription-3 (STAT3) in facilitating the translocation of NLRP3 to mitochondria. STAT3 interacts with NLRP3 and undergoes phosphorylation at Ser727 in response to several NLRP3 agonists, enabling the translocation of STAT3 and thus the bound NLRP3 to mitochondria. Disruption of the interaction between STAT3 and NLRP3 impairs the mitochondrial localization of NLRP3, specifically suppressing NLRP3 inflammasome activation both in vitro and in vivo. In summary, we demonstrate that STAT3 acts as a transporter for mitochondrial translocation of NLRP3 and provide new insight into the spatial regulation of NLRP3.

Abstract Exposure to mercury has been associated with adverse effects on pregnancy outcomes. However, there is limited literature on mercury exposure and pregnancy outcomes in Chinese pregnant women. Our study was to investigate the possible association between maternal mercury exposure and spontaneous preterm birth and birth weight. This study was a nested case-control study. The association between blood mercury concentration and both spontaneous preterm birth and birth weight was analyzed using conditional logistic regression and linear regression adjusted for the potential confounding factors, respectively. The dose-response relationship between mercury concentration and birth outcomes was estimated using restricted cubic spline regression. The mean concentration of mercury was 2.8 ± 2.2 µg/L. A positive relationship was observed between maternal blood mercury concentration and SPB when analyzed as a continuous variable. However, it was not found to be statistically significant (adjusted OR = 1.10, 95% CI = 0.95–1.26, P = 0.202). Moderate mercury exposure was associated with a higher risk of SPB (Q3 vs. Q1: crude OR = 2.50, 95% CI = 1.16–5.41, P = 0.02; adjusted OR = 3.49, 95% CI = 1.33–9.11, P = 0.011). After considering the combined effects of chemicals other than mercury exposure (including lead, selenium, and cadmium), the results remained consistent. There was no statistically significant association between blood mercury levels and birth weight (adjusted coefficient = 18.64, P-value = 0.075). There were no statistically significant dose-response associations between mercury concentration and birth outcomes (SPB: P = 0.076; birth weight: P = 0.885). Public health policies should focus on reducing environmental releases of mercury, improving food safety standards, and providing education to pregnant women about the risks of mercury exposure and preventive measures.

Abstract Vitamin C (VC), due to its chemical properties, can provide more oxygen-containing functional groups such as hydroxyl groups for biochar (BC), which promotes the adsorption of tetracycline on biochar. Therefore, in this study, cow dung biochar (CDBC) was modified with VC and VC-modified CDBC (CDBC-VC) was synthesized. The modified biochar was characterized and related factors, adsorption kinetics, isotherms and adsorption mechanisms were investigated. Adsorption kinetics indicate a fast rate of adsorption. The adsorption isotherms showed that the maximum adsorption capacity was 31.72 mg/g (CDBC) and 50.90 mg/g (CDBC-VC), respectively, and the adsorption process was inhomogeneous with multiple molecular layers and the adsorbent has a higher affinity. Mechanistic studies showed that hydrogen bonding interactions, π-π electron donor-acceptor interactions, hydrophobic interactions, and electrostatic interactions were the key to the adsorption process. The analysis of adsorbent regeneration showed that CDBC-VC had good adsorption performance. CDBC and CDBC-VC showed the best performance in simulated industrial wastewater with removal rates of 78.81% and 93.69%. The adsorption mechanism was comprehensively analyzed using six machine learning models. The extreme gradient boosting model gave the best fit. Analysis of the weights of the input variables for predicting adsorption efficiency showed that the ratio of initial TC concentration to BC dosage (29.8%), specific surface area (23%), isoelectric point (8.8%), and ash content (7.7%) had a significant effect on the predicted results.

Abstract The peripheral nervous system consists of ganglia, nerve trunks, plexuses, and nerve endings, that transmit afferent and efferent information. Regeneration after a peripheral nerve damage is sluggish and imperfect. Peripheral nerve injury frequently causes partial or complete loss of motor and sensory function, physical impairment, and neuropathic pain, all of which have a negative impact on patients’ quality of life. Because the mechanism of peripheral nerve injury and healing is still unclear, the therapeutic efficacy is limited. As peripheral nerve injury research has processed, an increasing number of studies have revealed that biological scaffolds work in tandem with progenitor cells to repair peripheral nerve injury. Here, we fabricated collagen chitosan nerve conduit bioscaffolds together with collagen and then filled neuroepithelial stem cells (NESCs). Scanning electron microscopy showed that the NESCs grew well on the scaffold surface. Compared to the control group, the NESCs group contained more cells with bigger diameters and myelinated structures around the axons. Our findings indicated that a combination of chitosan-collagen bioscaffold and neural stem cell transplantation can facilitate the functional restoration of peripheral nerve tissue, with promising future applications and research implications.

Background: Tongue inspection, an essential diagnostic method in Traditional Chinese Medicine (TCM), has the potential for early-stage disease screening. This study aimed to evaluate the effectiveness of deep learning-based analysis of tongue images for hepatic fibrosis screening. Methods: A total of 1083 tongue images were collected from 741 patients and divided into training, validation, and test sets. DenseNet-201, a convolutional neural network, was employed to train the AI model using these tongue images. The predictive performance of AI was assessed and compared with that of FIB-4, using real-time two-dimensional shear wave elastography as the reference standard. Results: The proposed AI model achieved an accuracy of 0.845 (95% CI: 0.79–0.90) and 0.814 (95% CI: 0.76–0.87) in the validation and test sets, respectively, with negative predictive values (NPVs) exceeding 90% in both sets. The AI model outperformed FIB-4 in all aspects, and when combined with FIB-4, the NPV reached 94.4%. Conclusion: Tongue inspection, with the assistance of AI, could serve as a first-line screening method for hepatic fibrosis.

Background Long COVID is a common problem in the recovery period of coronavirus disease (COVID-19). The prevention and treatment of long COVID has become the focus of the medical fields of COVID-19. It is important to clarify the situation of long COVID in China and find out the follow-up research route, thus providing evidence-based evidence for clinical practice. Objective To explore the characteristics of long COVID in China, aiming to provide references for the follow-up research. Methods From January 2023 to August 2023, a self-made survey questionnaire was used to investigate the current situation of long COVID in China. The questionnaire included general information, such as gender and age, treatment expectations, symptoms and signs in acute and recovery period, etc. Results A total of 1 001 questionnaires were collected, including 901 people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and 585 (64.9%) people with long COVID. Binary Logistic regression analysis showed that female (OR=2.000, 95%CI=1.477-2.705, P

Abstract The optimal discrete element model and bonding parameters that match the structural features of cornstalks during harvest were obtained. Based on the differences in mechanical properties of the stem bark and stem pith in the inter-nodal cornstalk, the biomechanical-specific parameters were measured using the compression, shear, and bending tests. The bonded particle models of stem bark and stem pith were constructed using fraction particles with radii of 1 mm and 1.47 mm, which were further bound to form a bilayer-bonded particle model of the cornstalk. The Plackett–Burman, steepest ascent, and response surface tests were conducted to identify the factors and their optimal values that significantly impacted the stem bark-stem bark, stem pith-stem pith, and stem bark-stem pith bonding parameters. The cornstalk’s shear and bending mechanical properties were assessed to verify the overall characteristic parameters. The findings revealed that the cornstalk model created, and the calibrated bonding parameters, were highly accurate and capable of simulating the shearing and bending behaviors of the real cornstalk. The inter-nodal cornstalk’s bonded particle model created and the identified bonding parameters for the cornstalk could contribute to a theoretical and research basis for the next stage in cornstalk modeling with nodes and other applications.

Introduction: Subthalamic nucleus deep brain stimulation (STN-DBS) is a proven treatment modality for Parkinson’s disease (PD), reducing dyskinesia and time spent in the “OFF” state. This study evaluates the long-term outcomes of STN-DBS in PD patients up to 10 years post-surgery in Singapore. Method: We conducted a retrospective review of Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) scores, activities of daily living (ADLs), disease milestones, dopaminergic drug prescriptions, and adverse events in patients before and after STN-DBS surgery. Results: A total of 94 PD patients who underwent bilateral STN-DBS were included. STN-DBS reduced time in the “OFF” state by 36.9% at 1 year (P=0.034) and 40.9% at 5 years (P=0.006). Time with dyskinesia did not significantly change. Levodopa equivalent daily dose was reduced by 35.1% by 5 years (P less than 0.001). MDS-UPDRS-II and III scores increased from 5 years post-DBS by 40.5% and 35.4%, respectively. Independence in ADLs decreased, though not significantly. The prevalence of frequent falls increased at 5 years. Surgery- and device-related adverse events were uncommon and generally mild. Conclusion: STN-DBS provides sustained relief from motor complications and reduced medication requirements in PD patients in Singapore. This study highlights STN-DBS as an effective treatment option, significantly enhancing the quality of life for those with PD.

Abstract Background It is well-established that thrombus aspiration during primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) indicates a higher thrombus burden and necessitates more intensive antithrombotic therapy. The bidirectional association between adverse events in AMI patients and platelet reactivity is typically observed during dual antiplatelet therapy (DAPT). Objective To investigate platelet reactivity after DAPT in AMI patients with thrombus aspiration performed during PCI. Methods In this retrospective study, we examined 269 consecutive AMI patients who underwent PCI and recorded their demographic, clinical and laboratory data. The platelet reactivity was measured with thromboelastogram (TEM). Results Ultimately, 208 patients were included in this study and divided into a Thrombus Aspiration group (N = 97) and a PCI Alone group (N = 111) based on whether thrombus aspiration was performed or not. The adenosine diphosphate (ADP)-induced platelet inhibition rate in the Thrombus Aspiration group was higher than that in the PCI Alone group (P

Abstract Purpose This current study attempted to investigate whether one-stitch method (OM) of temporary ileostomy influenced the stoma-related complications after laparoscopic low anterior resection (LLAR). Methods We searched for eligible studies in four databases including PubMed, Embase, Cochrane Library, and CNKI from inception to July 20, 2023. Both surgical outcomes and stoma-related complications were compared between the OM group and the traditional method (TM) group. The Newcastle–Ottawa Scale (NOS) was adopted for quality assessment. RevMan 5.4 was conducted for data analyzing. Results Totally 590 patients from six studies were enrolled in this study (272 patients in the OM group and 318 patients in the TM group). No significant difference was found in baseline information (P > 0.05). Patients in the OM group had shorter operative time in both the primary LLAR surgery (MD = − 17.73, 95%CI = − 25.65 to − 9.80, P

Objective To study the changes in erythrocyte osmotic fragility(EOF) in patients with hypercythemia, polycythemia and anemia under a high altitude environment. Methods A total of 174 outpatients, inpatients and people undergoing physical examination in Tibet Autonomous Region People′s Hospital in October 2020 were enrolled and divided into four groups according to hemoglobin levels: the polycythemia group(n=42), the physiologic increase group(n=48), the anemia group(n=29) and the healthy control group(n=55). They were compared with 67 anemia patients and 67 healthy people in the laboratory of Peking Union Medical College Hospital in the same period as the plain control group. The classic EOF test method was used to compare the results of each group′s EOF. The concentrations of NaCl solution for starting hemolysis (STH) and NaCl solution for complete hemolysis (CTH) were included, and the data were statistically analyzed by SPSS software. Results There was a significant difference in CTH between Zang and Han healthy people (P

Abstract The current study aimed to evaluate the effect of lymph node ratio (LNR) on the short-term and long-term outcomes of colorectal cancer (CRC) patients who underwent radical CRC surgery. We retrospectively collected CRC patients who underwent radical surgery from Jan 2011 to Jan 2020 in a single-center hospital. The patients were divided into the high LNR group and the low group according to the median. The baseline information and the short-term outcomes were compared between the high group and the low group. Univariate and multivariate logistic regression was performed to analyze the independent predictors for overall survival (OS) and disease-free survival (DFS). A 1:1 proportional propensity score matching (PSM) was used to reduce the selection bias between the two groups. Kaplan–Meier method was used to estimate the OS and DFS between the two groups in different T stages. A total of 1434 CRC patients undergoing radical surgery were enrolled in this study, and there were 730 (50.9%) patients in the low LNR group and 704 (49.1%) patients in the high LNR group. After the PSM, there were 618 patients in both groups, the baseline characteristics between the two groups had no significant difference (p > 0.05). After comparing the Surgery-related information and The Short-term outcomes, the high LNR group had a longer hospital stay (after PSM, p

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. Background:. Understanding willingness to undergo pulmonary function tests (PFTs) and the factors associated with poor uptake of PFTs is crucial for improving early detection and treatment of chronic obstructive pulmonary disease (COPD). This study aimed to understand willingness to undergo PFTs among high-risk populations and identify any barriers that may contribute to low uptake of PFTs. Methods:. We collected data from participants in the “Happy Breathing Program” in China. Participants who did not follow physicians’ recommendations to undergo PFTs were invited to complete a survey regarding their willingness to undergo PFTs and their reasons for not undergoing PFTs. We estimated the proportion of participants who were willing to undergo PFTs and examined the various reasons for participants to not undergo PFTs. We conducted univariable and multivariable logistic regressions to analyze the impact of individual-level factors on willingness to undergo PFTs. Results:. A total of 8475 participants who had completed the survey on willingness to undergo PFTs were included in this study. Out of these participants, 7660 (90.4%) were willing to undergo PFTs. Among those who were willing to undergo PFTs but actually did not, the main reasons for not doing so were geographical inaccessibility (n = 3304, 43.1%) and a lack of trust in primary healthcare institutions (n = 2809, 36.7%). Among the 815 participants who were unwilling to undergo PFTs, over half (n = 447, 54.8%) believed that they did not have health problems and would only consider PFTs when they felt unwell. In the multivariable regression, individuals who were ≤54 years old, residing in rural townships, with a secondary educational level, with medical reimbursement, still working, with occupational exposure to dust, and aware of the abbreviation “COPD” were more willing to undergo PFTs. Conclusions:. Willingness to undergo PFTs was high among high-risk populations. Policymakers may consider implementing strategies such as providing financial incentives, promoting education, and establishing community-based programs to enhance the utilization of PFTs.

Abstract Purpose Our study aimed to develop and validate a homologous recombination deficiency (HRD) scoring algorithm in the Chinese breast cancer population. Methods and materials Ninety-six in-house breast cancer (BC) samples and 6 HRD-positive standard cells were analyzed by whole-genome sequencing (WGS). Besides, 122 BCs from the TCGA database were down-sampled to ~ 1X WGS. We constructed an algorithm named AcornHRD for HRD score calculated based on WGS at low coverage as input data to estimate large-scale copy number alteration (LCNA) events on the genome. A clinical cohort of 50 BCs (15 cases carrying BRCA mutation) was used to assess the association between HRD status and anthracyclines-based neoadjuvant treatment outcomes. Results A 100-kb window was defined as the optimal size using 41 in-house cases and the TCGA dataset. HRD score high threshold was determined as HRD score ≥ 10 using 55 in-house BCs with BRCA mutation to achieve a 95% BRCA-positive agreement rate. Furthermore, the HRD status agreement rate of AcornHRD is 100%, while the ShallowHRD is 60% in standard cells. BRCA mutation was significantly associated with a high HRD score evaluated by AcornHRD and ShallowHRD (p = 0.008 and p = 0.003, respectively) in the TCGA dataset. However, AcornHRD showed a higher positive agreement rate than did the ShallowHRD algorithm (70% vs 60%). In addition, the BRCA-positive agreement rate of AcornHRD was superior to that of ShallowHRD (87% vs 13%) in the clinical cohort. Importantly, the high HRD score assessed by AcornHRD was significantly correlated with a residual cancer burden score of 0 or 1 (RCB0/1). Besides, the HRD-positive group was more likely to respond to anthracycline-based chemotherapy than the HRD-negative group (pCR [OR = 9.5, 95% CI 1.11–81.5, p = 0.040] and RCB0/1 [OR = 10.29, 95% CI 2.02–52.36, p = 0.005]). Conclusion Using the AcornHRD algorithm evaluation, our analysis demonstrated the high performance of the LCNA genomic signature for HRD detection in breast cancers.

Abstract Background To systematically analyze differences in atherosclerotic cardiovascular disease (ASCVD) burden between young and older adults. Methods We estimated the prevalence, mortality, and disability-adjusted life years (DALYs) of ASCVD, including ischemic heart disease (IHD), ischemic stroke (IS), and peripheral artery disease (PAD), in individuals aged 20–54 and > 55 years from 1990–2019, utilizing data from the 2019 Global Burden of Disease Study. The annual percentage changes (EAPCs) for age-specific prevalence, mortality, or DALY rates were calculated to quantify the temporal trends of ASCVD burden. We also analyzed population attribution fractions (PAF) of premature ASCVD mortality and DALYs for different risk factors and compared the burden of extremely premature, premature, and non-premature ASCVD cases based on clinical classifications. Results From 1990–2019, the global prevalence rates of IHD, IS, and PAD in the 20–54 years age group increased by 20.55% (from 694.74 to 837.49 per 100,000 population), 11.50% (from 439.48 to 490.03 per 100,000 population), and 7.38% (from 384.24 to 412.59 per 100,000 population), respectively. Conversely, the ASCVD prevalence in > 55years age group decreased. Adverse outcome burdens, including mortality and DALYs, varied among ASCVD subtypes. The decrease in the mortality/DALY burden of IHD and IS was lower in the 20–54 years group than in the > 55 years group. For PAD, DALYs among those aged 20–54 increased but decreased among those aged > 55 years. When grouped according to socio-demographic index (SDI) values, lower SDI regions exhibited a higher proportion of young ASCVD burden. The prevalence of young IHD, IS, and PAD in low SDI regions reached 20.70%, 40.05%, and 19.31% in 2019, respectively, compared with 12.14%, 16.32%, and 9.54%, respectively, in high SDI regions. Metabolic risks were the primary contributors to the ASCVD burden in both age groups. Increased susceptibility to ambient particulate matter pollution and inadequate control of high body-mass index and high fasting plasma glucose in young individuals may partially explain the differing temporal trends between young and older individuals. Conclusions The ASCVD burden in young individuals may become a growing global health concern, especially in areas with lower socioeconomic development levels that require more effective primary prevention strategies.

Abstract Background The heightened risk of cardiovascular and cerebrovascular events is associated with the increased instability of atherosclerotic plaques. However, the lack of effective diagnostic biomarkers has impeded the assessment of plaque instability currently. This study was aimed to investigate and identify hub genes associated with unstable plaques through the integration of various bioinformatics tools, providing novel insights into the detection and treatment of this condition. Methods Weighted Gene Co-expression Network Analysis (WGCNA) combined with two machine learning methods were used to identify hub genes strongly associated with plaque instability. The cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) method was utilized to assess immune cell infiltration patterns in atherosclerosis patients. Additionally, Gene Set Variation Analysis (GSVA) was conducted to investigate the potential biological functions, pathways, and mechanisms of hub genes associated with unstable plaques. To further validate the diagnostic efficiency and expression of the hub genes, immunohistochemistry (IHC), quantitative real-time polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA) were performed on collected human carotid plaque and blood samples. Immunofluorescence co-staining was also utilized to confirm the association between hub genes and immune cells, as well as their colocalization with mitochondria. Results The CIBERSORT analysis demonstrated a significant decrease in the infiltration of CD8 T cells and an obvious increase in the infiltration of M0 macrophages in patients with atherosclerosis. Subsequently, two highly relevant modules (blue and green) strongly associated with atherosclerotic plaque instability were identified. Through intersection with mitochondria-related genes, 50 crucial genes were identified. Further analysis employing least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) algorithms revealed six hub genes significantly associated with plaque instability. Among them, NT5DC3, ACADL, SLC25A4, ALDH1B1, and MAOB exhibited positive correlations with CD8 T cells and negative correlations with M0 macrophages, while kynurenine 3-monooxygenas (KMO) demonstrated a positive correlation with M0 macrophages and a negative correlation with CD8 T cells. IHC and RT-qPCR analyses of human carotid plaque samples, as well as ELISA analyses of blood samples, revealed significant upregulation of KMO and MAOB expression, along with decreased ALDH1B1 expression, in both stable and unstable samples compared to the control samples. However, among the three key genes mentioned above, only KMO showed a significant increase in expression in unstable plaque samples compared to stable plaque samples. Furthermore, the expression patterns of KMO in human carotid unstable plaque tissues and cultured mouse macrophage cell lines were assessed using immunofluorescence co-staining techniques. Finally, lentivirus-mediated KMO silencing was successfully transduced into the aortas of high-fat-fed ApoE-/- mice, with results indicating that KMO silencing attenuated plaque formation and promoted plaque stability in ApoE-/- mice. Conclusions The results suggest that KMO, a mitochondria-targeted gene associated with macrophage cells, holds promise as a valuable diagnostic biomarker for assessing the instability of atherosclerotic plaques.

Abstract Volatile organic compounds (VOCs) represent a significant component of air pollution. However, studies evaluating the impact of VOC exposure on chronic obstructive pulmonary disease (COPD) have predominantly focused on single pollutant models. This study aims to comprehensively assess the relationship between multiple VOC exposures and COPD. A large cross-sectional study was conducted on 4983 participants from the National Health and Nutrition Examination Survey. Four models, including weighted logistic regression, restricted cubic splines (RCS), weighted quantile sum regression (WQS), and the dual-pollution model, were used to explore the association between blood VOC levels and the prevalence of COPD in the U.S. general population. Additionally, six machine learning algorithms were employed to develop a predictive model for COPD risk, with the model’s predictive capacity assessed using the area under the curve (AUC) indices. Elevated blood concentrations of benzene, toluene, ortho-xylene, and para-xylene were significantly associated with the incidence of COPD. RCS analysis further revealed a non-linear and non-monotonic relationship between blood levels of toluene and m-p-xylene with COPD prevalence. WQS regression indicated that different VOCs had varying effects on COPD, with benzene and ortho-xylene having the greatest weights. Among the six models, the Extreme Gradient Boosting (XGBoost) model demonstrated the strongest predictive power, with an AUC value of 0.781. Increased blood concentrations of benzene and toluene are significantly correlated with a higher prevalence of COPD in the U.S. population, demonstrating a non-linear relationship. Exposure to environmental VOCs may represent a new risk factor in the etiology of COPD.

Abstract. Background:. Although significant advances have been made in the treatment of multiple myeloma (MM), leading to unprecedented response and survival rates among patients, the majority eventually relapse, and a cure remains elusive. This situation is closely related to an incomplete understanding of the immune microenvironment, especially monocytes/macrophages in patients with treatment-naïve MM. The aim of this study was to provide insight into the immune microenvironment, especially monocytes/macrophages, in patients with treatment-naïve MM. Methods:. This study used the single-cell RNA sequencing (scRNA-seq) data of both patients with MM and heathy donors to identify immune cells, including natural killer (NK) cells, T cells, dendritic cells (DCs), and monocytes/macrophages. Transcriptomic data and flow cytometry analysis of monocytes/macrophages were used to further examine the effect of monocytes/macrophages in treatment-naïve MM patients. Results:. A significant difference was observed between the bone marrow (BM) immune cells of the healthy controls and treatment-naïve MM patients through scRNA-seq. It is noteworthy that, through an scRNA-seq data analysis, this study found that interferon (IFN)-induced NK/T cells, terminally differentiated effector memory (TEMRA) cells, T-helper cells characterized by expression of IFN-stimulated genes (ISG+Th cells), IFN-responding exhausted T cells, mannose receptor C-type 1 (MRC1)+ DCs, IFN-responding DCs, MHCII+ DCs, and immunosuppressive monocytes/macrophages were enriched in patients with treatment-naïve MM. Significantly, transcriptomic data of monocytes/macrophages demonstrated that “don’t eat me”-related genes and IFN-induced genes increase in treatment-naïve MM patients. Furthermore, scRNA-seq, transcriptomic data, and flow cytometry also showed an increased proportion of CD16+ monocytes/macrophages and expression level of CD16. Cell–cell communication analysis indicated that monocytes/macrophages, whose related important signaling pathways include migration inhibitory factor (MIF) and interleukin 16 (IL-16) signaling pathway, are key players in treatment-naïve MM patients. Conclusions:. Our findings provide a comprehensive and in-depth molecular characterization of BM immune cell census in MM patients, especially for monocytes/macrophages. Targeting macrophages may be a novel treatment strategy for patients with MM.

Abstract Background Preserved ratio impaired spirometry (PRISm) is a type of abnormal lung function. PRISm and mortality have been explored in several studies, but a comprehensive evaluation of the associations is limited. The current study aims to conduct a systematic review and meta-analysis in order to investigate the mortality and cardiovascular diseases in patients with PRISm. Methods PubMed, Embase, and Web of Science databases, as well as gray literature sources, were searched for relevant studies published up to 7 September 2023 without language restrictions. This review included all published observational cohort studies that investigated the association of PRISm with mortality in the general population, as well as subgroup analyses in smokers and pre-bronchodilation spirometry studies. The outcomes of interest were all-cause mortality, cardiovascular mortality, and respiratory-related mortality. The Newcastle–Ottawa scale assessed study quality. Sensitivity and subgroup analyses explored heterogeneity and robustness. Publication bias was assessed with Egger’s and Begg’s tests. Results Overall, eight studies were included in this meta-analysis. The pooled HR was 1.60 (95% CI, 1.48–1.74) for all-cause mortality, 1.68 (95% CI, 1.46–1.94) for CVD mortality, and 3.09 (95% CI, 1.42–6.71) for respiratory-related mortality in PRISm group compared to normal group. In the subgroup analysis, participants with PRISm had a higher effect (HR, 2.11; 95% CI, 1.74–2.54) on all-cause mortality among smokers relative to participants with normal spirometry. Furthermore, the association between PRISm and mortality risk was consistent across several sensitivity analyses. Conclusions People with PRISm were associated with an increased risk of all-cause mortality, CVD mortality, and respiratory-related mortality as compared to those with normal lung function in the general population. Systematic review registration PROSPERO CRD42023426872.

Abstract Background To date, multiple cases of adverse reactions to COVID-19 vaccines have been reported worldwide. Alopecia areata (AA) is an uncommon type of adverse reaction reported in some articles and has a significant social and psychological impact on patients. Our study aimed to review the AA and COVID-19 vaccine literature. Methods This systematic review was conducted by searching for articles on AA following COVID-19 vaccines in international databases such as Embase, MEDLINE, PubMed, Web of Knowledge, and Ovid from December 2019 to December 30, 2023. We included studies that provided data for AA patients following COVID-19 vaccination with at least one dose. Data on sex, age, country/region of origin, vaccine type, days between vaccination and symptom presentation, manifestations of AA, trichoscopy and histopathological findings, treatment, and outcomes were included. Results In total, 579 explored studies were identified and assessed, and 25 articles with a total of 51 patients were included in the review. Twenty-seven (52.9%) patients developed new-onset AA following receiving the COVID-19 vaccine, and AA recurrence or exacerbation occurred after receiving the COVID-19 vaccine in 24 (47.1%) patients with preexisting disease. Five vaccines were reported to cause AA in all cases. The Pfizer vaccine (45.1%) was the most frequently reported, followed by the ChAdOx1 nCoV-19 vaccine (27.5%), Moderna mRNA-1273 (19.6%), Sinopharm (3.9%) and SinoVac (3.9%). AA occurred most frequently within one month after the 1st dose, and then, the incidence decreased gradually with time. Topical or systemic corticosteroids were used in 38 patients. Eleven patients were treated with a Janus Kinase inhibitor (jakinib) inhibitor, eight with tofacitinib, and three with an unspecified jakinib. However, 3 of the 11 patients experienced exacerbations after treatment. Conclusion AA after COVID-19 vaccination is rare, and physicians should be aware of this phenomenon to improve early diagnosis and appropriate treatment.

Abstract Maritime objects frequently exhibit low-quality and insufficient feature information, particularly in complex maritime environments characterized by challenges such as small objects, waves, and reflections. This situation poses significant challenges to the development of reliable object detection including the strategies of loss function and the feature understanding capabilities in common YOLOv8 (You Only Look Once) detectors. Furthermore, the widespread adoption and unmanned operation of intelligent ships have generated increasing demands on the computational efficiency and cost of object detection hardware, necessitating the development of more lightweight network architectures. This study proposes the EL-YOLO (Efficient Lightweight You Only Look Once) algorithm based on YOLOv8, designed specifically for intelligent ship object detection. EL-YOLO incorporates novel features, including adequate wise IoU (AWIoU) for improved bounding box regression, shortcut multi-fuse neck (SMFN) for a comprehensive analysis of features, and greedy-driven filter pruning (GDFP) to achieve a streamlined and lightweight network design. The findings of this study demonstrate notable advancements in both detection accuracy and lightweight characteristics across diverse maritime scenarios. EL-YOLO exhibits superior performance in intelligent ship object detection using RGB cameras, showcasing a significant improvement compared to standard YOLOv8 models.

Background The diagnosis and treatment of general practice often involve multi-system and multi-organ diseases, resulting in a large number of consultations. However, there is limited research on the current state of general practice consultation. Objective This study aims to collect relevant data on general practice consultation at Fuxing Hospital Affiliated with Capital Medical University, a tertiary general hospital and analyze the current situation of general practice consultation to improve the quality of general practice consultation at Fuxing Hospital and provide insights for hierarchical diagnosis and treatment. Methods The data of general practice consultation in Fuxing Hospital Affiliated to Capital Medical University from 2021 to 2022 were obtained through the hospital information system, and the basic information, consultation departments, consultation reasons, consultation diagnosis, and consultation opinions were classified and summarized. Results From 2021 to 2022, a total of 1 441 inpatients were admitted to the general practice department at Fuxing Hospital. Among them, 908 inpatients had consultation records. A total of 2 269 in-hospital consultations were issued, 966 consultations were executed while 303 were cancelled. Among the executed consultations, there were 987 males and 979 females. The age ranged from 17 to 101 years old, with an average age of (77.4±13.9) years old. A total of 31 clinical departments were involved, among which the top 6 departments with the most consultations were rehabilitation department, otolaryngology, ophthalmology, dermatology, infectious disease department and psychiatry. The most common diagnoses among these departments included dysfunction, sensorineural deafness, cataract , dermatitis, pulmonary infection and anxiety. The reasons for consultation included formulating initial treatment plans, adjusting current treatment plans, improving specialist examinations, assisting with specialized treatment and conducting specialist evaluations. The consultation treatment opinions can be roughly divided into professional evaluation, improving examinations, clarifying diagnosis, drug therapy, clinical operations, surgical treatment, nutritional therapy and rehabilitation acupuncture. Conclusion The diagnosis and treatment scope of general medicine includes common diseases and frequently occurring diseases in various systems, with a large demand for consultation. The spectrum of consultation diseases reflects the clinical needs and characteristics of the general medicine department of Fuxing Hospital Affiliated to Capital Medical University. Analyzing the current situation of consultation is conducive to making up for the shortcomings of general medicine, improving the quality of general consultation, and taking the first step towards referral between general medicine and specialists.