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Background: Long non-coding RNA (lncRNA)-NONMMUT020270.2 is downregulated and co-expressed with inositol 1,4,5-trisphosphate receptor type 2 (ITPR2) in the hippocampus of Alzheimer's disease (AD) mice. However, whether the expression of ITPR2 was regulated by lncRNA-NONMMUT020270.2 remains unclear. we aimed to investigate regulating relationship of lncRNA-NONMMUT020270.2 and ITPR2. Methods: HT22 cells were firstly transfected with the pcDNA3.1-lncRNA-NONMMUT020270.2 overexpression plasmid or with the lncRNA-NONMMUT020270.2 smart silencer, and then were stimulated with lipopolysaccharide (LPS) for 24h. The mRNA expression levels of lncRNA-NONMMUT020270.2 and ITPR2 were measured by reverse transcription-quantitative PCR. Cell viability was assessed using a Cell Counting Kit 8 assay. The expression of Aβ1-42 was detected by ELISA. The expression levels of p-tau, caspase-1, and inositol trisphosphate receptor (IP3R) proteins were detected by western-blotting. Nuclear morphological changes were detected by Hoechst staining. Flow cytometry and Fluo-3/AM were carried out to determine cell apoptosis and the intracellular Ca2+. Results: LPS significantly decreased cell viability, and ITPR2 mRNA and IP3R protein expression levels. While it markedly enhanced the expression levels of p-tau and Aβ1-42, cell apoptosis rate, as well as intracellular Ca2+ concentration (P

Background and purposeAt 12 months in the phase 2 TOPAZ study, treatment with apitegromab was associated with both an improved motor function in patients with Type 2 or 3 spinal muscular atrophy (SMA) and with a favorable safety profile. This manuscript reports the extended efficacy and safety in the nonambulatory group of the TOPAZ study at 36 months.MethodsPatients who completed the primary study (NCT03921528) could enroll in an open-label extension, during which patients received apitegromab 20 mg/kg by intravenous infusion every 4 weeks. Patients were assessed periodically via the Hammersmith Functional Motor Scale–Expanded (HFMSE), Revised Upper Limb Module (RULM), World Health Organization (WHO) motor development milestones, Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) Daily Activities and Mobility domains, and Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue questionnaire.ResultsOf the 58 patients enrolled in TOPAZ, 35 were nonambulatory (mean age 7.3 years). The mean change at 36 months in HFMSE score from baseline was +4.0 (standard deviation [SD]: 7.54), and + 2.4 (3.24) for RULM score (excluding n = 7 after scoliosis surgery). Caregiver-reported outcomes (PEDI-CAT and PROMIS Fatigue) showed improvements from baseline over 36 months. In addition, most patients (28/32) improved or maintained WHO motor milestones achieved at baseline. The most frequently reported treatment-emergent adverse events were pyrexia (48.6%), nasopharyngitis (45.7%), COVID-19 infection (40.0%), vomiting (40.0%), and upper respiratory tract infection (31.4%).ConclusionThe benefit of apitegromab treatment observed at 12 months was sustained at 36 months with no new safety findings.

Abstract Background Preoperative prediction of International Federation of Gynecology and Obstetrics (FIGO) stage in patients with epithelial ovarian cancer (EOC) is crucial for determining appropriate treatment strategy. This study aimed to explore the value of contrast-enhanced CT (CECT) radiomics in predicting preoperative FIGO staging of EOC, and to validate the stability of the model through an independent external dataset. Methods A total of 201 EOC patients from three centers, divided into a training cohort (n = 106), internal (n = 46) and external (n = 49) validation cohorts. The least absolute shrinkage and selection operator (LASSO) regression algorithm was used for screening radiomics features. Five machine learning algorithms, namely logistic regression, support vector machine, random forest, light gradient boosting machine (LightGBM), and decision tree, were utilized in developing the radiomics model. The optimal performing algorithm was selected to establish the radiomics model, clinical model, and the combined model. The diagnostic performances of the models were evaluated through receiver operating characteristic analysis, and the comparison of the area under curves (AUCs) were conducted using the Delong test or F-test. Results Seven optimal radiomics features were retained by the LASSO algorithm. The five radiomics models demonstrate that the LightGBM model exhibits notable prediction efficiency and robustness, as evidenced by AUCs of 0.83 in the training cohort, 0.80 in the internal validation cohort, and 0.68 in the external validation cohort. The multivariate logistic regression analysis indicated that carcinoma antigen 125 and tumor location were identified as independent predictors for the FIGO staging of EOC. The combined model exhibited best diagnostic efficiency, with AUCs of 0.95 in the training cohort, 0.83 in the internal validation cohort, and 0.79 in the external validation cohort. The F-test indicated that the combined model exhibited a significantly superior AUC value compared to the radiomics model in the training cohort (P

Abstract Background The effectiveness of flipped classroom (FC) on puncture skills in medical education is still uncertain. This study aimed to assess the role of the FC model in puncture skills and investigate the acceptance and approval of FC among medical students and instructors. Methods A mixed research approach of quasi-experimental research design and descriptive qualitative research was conducted in September 2022 for one month, using an FC teaching method that combined instructional videos and group learning. The study participants were 71 fifth-year medical students from two classes at a Chinese medical school and four instructors. The medical students were randomly divided into two groups: the traditional classroom (TC) group (Group A) and the FC group (Group B). For teaching, Group B used FC, and Group A used PowerPoint-based TC. The effectiveness of the two teaching models was assessed with Objective Structured Clinical Examination (OSCE), and questionnaires were distributed to the medical students and instructors after the assessment. Two independent sample t-tests were used to analyse the differences in demographic data and the OSCE scores of the two groups of medical students. Results Group B scored higher in puncture skills than Group A, especially regarding abdominal puncture (p = 0.03), thoracentesis (p 0.409). The medical students thought that the FC improved their self-learning ability and helped them acquire knowledge. Regarding the OSCE of their skills, most medical students thought that it was more innovative and objective than traditional examinations and that it was better for assessing their overall abilities. Both the FC and OSCE were supported by the medical students. The instructors were also satisfied with the students’ performance in the FC and supported the teaching model, agreeing to continue using it. Conclusions This study shows that FC teaching that combines instructional videos and group learning is a reliable and well-received teaching method for puncture skills, which supplements and expands existing teaching methods in the medical field.

Abstract Background Diabetic nephropathy (DN) and atherosclerosis (AS) are prevalent and severe complications associated with diabetes, exhibiting lesions in the basement membrane, an essential component found within the glomerulus, tubules, and arteries. These lesions contribute significantly to the progression of both diseases, however, the precise underlying mechanisms, as well as any potential shared pathogenic processes between them, remain elusive. Methods Our study analyzed transcriptomic profiles from DN and AS patients, sourced from the Gene Expression Omnibus database. A combination of integrated bioinformatics approaches and machine learning models were deployed to identify crucial genes connected to basement membrane lesions in both conditions. The role of integrin subunit alpha M (ITGAM) was further explored using immune infiltration analysis and genetic correlation studies. Single-cell sequencing analysis was employed to delineate the expression of ITGAM across different cell types within DN and AS tissues. Results Our analyses identified ITGAM as a key gene involved in basement membrane alterations and revealed its primary expression within macrophages in both DN and AS. ITGAM was significantly correlated with tissue immune infiltration within these diseases. Furthermore, the expression of genes encoding core components of the basement membrane was influenced by the expression level of ITGAM. Conclusion Our findings suggest that macrophages may contribute to basement membrane lesions in DN and AS through the action of ITGAM. Moreover, therapeutic strategies that target ITGAM may offer potential avenues to mitigate basement membrane lesions in these two diabetes-related complications.

Introduction Invasive micropapillary carcinoma (IMPC) treatment only relies on the standard treatment of nonspecific invasive breast cancer (NSIBC), and it remains controversial whether the survival of patients improves. Therefore, this study aimed to analyze the clinicopathological features of IMPC and to investigate the factors affecting its prognosis. Material and methods This retrospective cohort study included 104 IMPC patients who met the study’s inclusion criteria out of a total of 4,532 patients with invasive breast cancer between January 2015 and December 2019. A contemporaneous cohort of 230 patients with non-specific invasive breast cancer (NSIBC) who underwent surgery was identified and matched using propensity scores. Results The survival rate for patients with IMPC ranged from 1.12% to 7.03%. Statistically significant differences were observed in the proportion of endocrine treatment, lymphatic invasion, estrogen receptor (ER)-positive rate, molecular subtypes, molecular typing, and 5-year loco-regional recurrence-free survival (LRRFS) between the two cohorts (p < 0.05). The univariate analysis showed that T stage, N stage, lymphatic invasion, vascular invasion, ER-positive rate, and progesterone receptor (PR)-negative rate were all prognosis risk factors (p < 0.05) for IMPC. Furthermore, the multivariate analysis indicated that lymphatic invasion and N stage were independent prognostic factors (p < 0.05). Conclusions The incidence of micropapillary IMPC, among other pathological subtypes, is steadily increasing. ER-positive and PR-positive rates, as well as luminal subtypes, are frequent, with a concurrent increase in the 5-year locoregional recurrence rate. It would be interesting to compare the effect following these therapeutic modifications in larger cohorts in future studies.

Abstract Background Inflammatory response has been recognized as a pivotal pathophysiological process during cerebral ischemia. ChemR23 signaling is involved in the pathophysiology of various inflammatory diseases. Nevertheless, the role of ChemR23 signaling in ischemic stroke remains largely unknown. Methods Permanent ischemic stroke mouse model was accomplished by middle cerebral artery occlusion (MCAO). Resolvin E1 (RvE1) or chemerin-9 (C-9), the agonists of ChemR23, were administered by intracerebroventricular (i.c.v) injection before MCAO induction. Then, analysis of neurobehavioral deficits and brain sampling were done at Day 1 after MCAO. The brain samples were further analyzed by histological staining, immunofluorescence, RNA sequencing, ELISA, transmission electron microscope, and western blots. Furthermore, oxygen–glucose deprivation (OGD) was employed in SH-SY5Y to mimic MCAO in vitro, and ChemR23 signaling pathway was further studied by overexpression of ChemR23 or administration of related agonists or antagonists. Analysis of cell death and related pathway markers were performed. Results ChemR23 expression was upregulated following MCAO. Under in vitro and in vivo ischemic conditions, ChemR23 deficiency or inhibition contributed to excessive NLRP3-mediated maturation and release of IL-1β and IL-18, as well as enhanced cleavage of GSDMD-N and neuronal pyroptosis. These influences ultimately aggravated brain injury and neuronal damage. On the other hand, ChemR23 activation by RvE1 or C-9 mitigated the above pathophysiological abnormalities in vivo and in vitro, and overexpression of ChemR23 in SH-SY5Y cells also rescued OGD-induced neuronal pyroptosis. Blockade of NLRP3 mimics the protective effects of ChemR23 activation in vitro. Conclusion Our data indicated that ChemR23 modulates NLRP3 inflammasome-mediated neuronal pyroptosis in ischemic stroke. Activation of ChemR23 may serve as a promising potential target for neuroprotection in cerebral ischemia.

Abstract Background This study aimed to uncover the changing prevalence of obesity and its association with hypertension across socioeconomic gradients in rural southwest China. Methods Data were collected from two cross-sectional health interviews and surveys from 2011 to 2021 among individuals aged ≥ 35 years in rural China. Each participant’s height, weight, waist circumference, and blood pressure were measured. The overall prevalence of obesity, central obesity, and hypertension was directly standardized by age based on the total population of the two surveys. Multivariate logistic regression was used to analyze the association between obesity and prevalence of hypertension and an individual socioeconomic position (SEP) index was constructed using principal component analysis. Results From 2011 to 2021, the prevalence of obesity, central obesity, and hypertension increased substantially, from 5.9%, 50.2%, and 26.1–12.1%, 58.0%, and 40.4% (P

Abstract In the context of the proliferated evolution of network service types and the expeditious augmentation of network resource deployment, the requisition for copious labeled datasets to facilitate superior performance in traffic classification methods, particularly those hinging on deep learning, is imperative. Nonetheless, the procurement and annotation of such extensive datasets necessitate considerable temporal and human resource investments. In response to this predicament, this work introduces a methodology, termed MTEFU, leveraging a deep learning model-based multi-task learning algorithm, strategically designed to mitigate the reliance on substantial labeled training samples. Multiple classification tasks, encompassing duration, bandwidth size, and business traffic category, are incorporated, with a shared parameter strategy implemented amongst tasks to assure the transference of information across disparate tasks. Employing CNN, SAE, GRU, and LSTM as multi-task learning classification models, training validation and experimental testing were conducted on the QUIC dataset. A comparative analysis with single-task and ensemble learning methods reveals that, in the context of predicting network traffic types, the accuracy derived from the multi-task learning strategy, even with a mere 150 labeled samples, can emulate the 94.67% accuracy achieved through single-task learning with a fully labeled dataset of 6139 samples.

Curing modulation is one of the important processes in tobacco production, so it is crucial to recognize tobacco flue-curing states effectively and accurately. This study created a dataset of the complete tobacco flue-curing process in a bulk curing barn environment and proposed a lightweight recognition model based on a feature skip connections module. Firstly, the image data was enhanced using a color correction matrix, which was used to recover the true color of the tobacco leaf in order to reduce the misidentification of adjacent states. Secondly, the convolutional neural network model proposed in this paper introduced Spatially Separable convolution to enhance the extraction of tobacco leaf texture features. Then, the standard convolution in Short-Term Dense Concatenate (STDC) was replaced with Depthwise Separable Convolutional blocks with different expansion rates to reduce the number of model parameters and FLOPs (Floating Point Operations Per Second). Finally, the Tobacco Flue-Curing State Recognition Network (TFSNet) was constructed by combining the SimAm attention mechanism. The experimental results showed that the model accuracy was improved by 1.63 percentage points after the color correction process. The recognition accuracy of TFSNet for the seven states of tobacco flue-curing was as high as 98.71%. The number of params and the FLOPs of the TFSNet model were 203,058 and 172.39 M, which were 98.18% and 90.55% lower than that of the ResNet18 model, respectively. The size of the model was 0.78 mb, and the time consumed per frame was only 21 ms. Compared with the mainstream model, TFSNet significantly improved the detection speed while maintaining high accuracy, and it provided effective technical support for the intelligentization of the tobacco flue-curing process.

Abstract Background Mutations in TP53 gene is considered a main driver of hepatocellular carcinoma (HCC). While TP53 mutations are the leading cause of p53 dysfunction, their occurrence rates may drop to approximately 10% in cohorts without hepatitis B virus and aflatoxin exposure. This observation suggests that the deactivation of wild-type p53 (p53wt) may be a critical factor in the majority of HCC cases. However, the mechanism undermining p53wt activity in the liver remains unclear. Methods Microarray analysis and luciferase assay were utilized to confirm target associations. Gain- and/or loss-of-function methods were employed to assess alterations in signaling pathways. Protein interactions were analyzed by molecular immunological methods and further visualized by confocal microscopy. Bioinformatic analysis was performed to analyze clinical significance. Tumor xenograft nude mice were used to validate the findings in vivo. Results Our study highlights the oncogenic role of Rictor, a key component of the mammalian target of rapamycin complex 2 (mTORC2), in hepatocytes. Rictor exerts its oncogenic function by binding to p53wt and subsequently blocking p53wt activity based on p53 status, requiring the involvement of mTOR. Moreover, we observed a dynamic nucleocytoplasmic distribution pattern of Rictor, characterized by its translocation from the nucleus (in precancerous lesions) to the cytoplasm (in HCCs) during malignant transformation. Notably, Rictor is directly targeted by the liver-enriched microRNA miR-192, and the disruption of the miR-192-Rictor-p53-miR-192 signaling axis was consistently observed in both human and rat HCC models. Clinical analysis associated lower miR-192/higher Rictor with shorter overall survival and more advanced clinical stages (P

Abstract Background Skeletal muscle mass and quality assessed by computed tomography (CT) images of the third lumbar vertebra (L3) level have been established as risk factors for poor clinical outcomes in several illnesses, but the relevance for dialysis patients is unclear. A few studies have suggested a correlation between CT‐determined skeletal muscle mass and quality at the first lumbar vertebra (L1) level and adverse outcomes. Generally, chest CT does not reach beyond L1. We aimed to determine whether opportunistic CT scan (chest CT)‐determined skeletal muscle mass and quality at L1 are associated with mortality in initial‐dialysis patients. Methods This 3‐year multicentric retrospective study included initial‐dialysis patients from four centres between 2014 and 2017 in China. Unenhanced CT images of the L1 and L3 levels were obtained to assess skeletal muscle mass [by skeletal muscle index, (SMI), cm2/m2] and quality [by skeletal muscle density (SMD), HU]. Skeletal muscle measures at L1 were compared with those at L3. The sex‐specific optimal cutoff values of L1 SMI and L1 SMD were determined in relation to all‐cause mortality. The outcomes were all‐cause death and cardiac death. Cox regression models were applied to investigate the risk factors for death. Results A total of 485 patients were enrolled, of whom 257 had both L1 and L3 images. Pearson's correlation coefficient between L1 and L3 SMI was 0.84 (P 0.05). Low L1 SMD (n = 280, 57.73%) was diagnosed based on the optimal cutoff value (

Abstract Background Clinically, a large part of inflammatory bowel disease (IBD) patients is complicated by oral lesions. Although previous studies proved oral microbial dysbiosis in IBD patients, the bacterial community in the gastrointestinal (GI) tract of those IBD patients combined with oral ulcers has not been profiled yet. Methods In this study, we enrolled four groups of subjects, including healthy controls (CON), oral ulcer patients (OU), and ulcerative colitis patients with (UC_OU) and without (UC) oral ulcers. Bio-samples from three GI niches containing salivary, buccal, and fecal samples, were collected for 16S rRNA V3-V4 region sequencing. Bacterial abundance and related bio-functions were compared, and data showed that the fecal microbiota was more potent than salivary and buccal microbes in shaping the host immune system. ~ 22 UC and 10 UC_OU 5-aminosalicylate (5-ASA) routine treated patients were followed-up for six months; according to their treatment response (a decrease in the endoscopic Mayo score), they were further sub-grouped as responding and non-responding patients. Results We found those UC patients complicated with oral ulcers presented weaker treatment response, and three oral bacterial genera, i.e., Fusobacterium, Oribacterium, and Campylobacter, might be connected with treatment responding. Additionally, the salivary microbiome could be an indicator of treatment responding in 5-ASA routine treatment rather than buccal or fecal ones. Conclusions The fecal microbiota had a strong effect on the host’s immune indices, while the oral bacterial microbiota could help stratification for ulcerative colitis patients with oral ulcers. Additionally, the oral microbiota had the potential role in reflecting the treatment response of UC patients. Three oral bacteria genera (Fusobacterium, Oribacterium, and Campylobacter) might be involved in UC patients with oral ulcers lacking treatment responses, and monitoring oral microbiota may be meaningful in assessing the therapeutic response in UC patients.

Abstract Neuroinflammation plays critical roles in vascular dementia (VaD), the second leading cause of dementia, which can be induced by chronic cerebral hypoperfusion (CCH). NLRP3 inflammasome-induced pyroptosis, the inflammatory programmed cell death, has been reported to contribute to the development of VaD. ChemR23 is a G protein-coupled receptor that has emerging roles in regulating inflammation. However, the role of ChemR23 signalling in NLRP3 inflammasome-induced pyroptosis in CCH remains elusive. In this study, a CCH rat model was established by permanent bilateral common carotid artery occlusion (BCCAO) surgery. Eight weeks after the surgery, the rats were intraperitoneally injected with the ChemR23 agonist Resolvin E1 (RvE1) or chemerin-9 (C-9). Additionally, primary rat hippocampal neurons and SH-SY5Y cells were adopted to mimic CCH injury in vitro. Our results showed that the levels of ChemR23 expression were decreased from the 8th week after BCCAO, accompanied by significant cognitive impairment. Further analysis revealed that CCH induced neuronal damage, synaptic injury and NLRP3-related pyroptosis activation in hippocampal neurons. However, pharmacologic activation of ChemR23 with RvE1 or C-9 counteracted these changes. In vitro experiments also showed that ChemR23 activation prevented primary neuron pyroptosis induced by chronic hypoxia. In addition, manipulating ChemR23 expression markedly regulated NLRP3 inflammasome-induced neuronal pyroptosis through PI3K/AKT/Nrf2 signalling in SH-SY5Y cells under hypoglycaemic and hypoxic conditions. Collectively, our data demonstrated that ChemR23 activation inhibits NLRP3 inflammasome-induced neuronal pyroptosis and improves cognitive function via the PI3K/AKT/Nrf2 signalling pathway in CCH models. ChemR23 may serve as a potential novel therapeutic target to treat CCH-induced cognitive impairment.

Abstract Background Hyperglycemic crises are associated with high morbidity and mortality. Previous studies have proposed methods to predict adverse outcomes of patients in hyperglycemic crises; however, artificial intelligence (AI) has never been used to predict adverse outcomes. We implemented an AI model integrated with the hospital information system (HIS) to clarify whether AI could predict adverse outcomes. Methods We included 2,666 patients with hyperglycemic crises from emergency departments (ED) between 2009 and 2018. The patients were randomized into a 70%/30% split for AI model training and testing. Twenty-two feature variables from the electronic medical records were collected. The performance of the multilayer perceptron (MLP), logistic regression, random forest, Light Gradient Boosting Machine (LightGBM), support vector machine (SVM), and K-nearest neighbor (KNN) algorithms was compared. We selected the best algorithm to construct an AI model to predict sepsis or septic shock, intensive care unit (ICU) admission, and all-cause mortality within 1 month. The outcomes between the non-AI and AI groups were compared after implementing the HIS and predicting the hyperglycemic crisis death (PHD) score. Results The MLP had the best performance in predicting the three adverse outcomes, compared with the random forest, logistic regression, SVM, KNN, and LightGBM models. The areas under the curves (AUCs) using the MLP model were 0.852 for sepsis or septic shock, 0.743 for ICU admission, and 0.796 for all-cause mortality. Furthermore, we integrated the AI predictive model with the HIS to assist decision making in real time. No significant differences in ICU admission or all-cause mortality were detected between the non-AI and AI groups. The AI model performed better than the PHD score for predicting all-cause mortality (AUC 0.796 vs. 0.693). Conclusions A real-time AI predictive model is a promising method for predicting adverse outcomes in ED patients with hyperglycemic crises. Further studies recruiting more patients are warranted.

This study examined the impact of brief mindfulness meditation (BMM) training on attention function and dispositional mindfulness in young males. 126 male participants aged 18–26 from the security industry were recruited, with 66 participants (M = 22.84, SD = 2.41) undergoing 4-week mindfulness meditation training and 60 participants (M = 23.07, SD = 2.29) in the active control group. The intervention was integrated into the participants' schedules. Measures included Five Facets Mindfulness Questionnaires (FFMQ), concentration and assignment attention tasks, Attention Network Test (ANT), and saliva cortisol concentration. Findings indicate that brief mindfulness meditation training led to significant improvements in participants' FFMQ scores), with marginally significant enhancements in the executive control network. However, it had no discernible effect on alertness and orientation networks. Additionally, brief mindfulness meditation training enhanced attention allocation to light stimulation and prolonged individual attention. Surprisingly, there was no observed decrease in saliva cortisol concentration among meditation training participants. However, this study did not find a decrease in saliva cortisol concentration in the brief mindfulness meditation group. In conclusion, this study highlights the potential of a 4-week brief mindfulness meditation training program to enhance dispositional mindfulness and specific aspects of attention function in young men, offering practical insights into the benefits of mindfulness meditation practices for this demographic.

BackgroundPrevious studies have revealed the sex-specific features of pituitary–thyroid hormone (TH) actions and the prevalence of thyroid nodules (TNs) in children and adolescents. However, it was unclear in adults. We aimed to investigate the features of pituitary–TH actions in women and men at different ages, and the associations of thyrotropin (TSH), THs, and central sensitivity to THs indices including the thyroid feedback quantile-based index by FT4 (TFQIFT4) and the thyroid feedback quantile-based index by FT3(TFQIFT3) with of TNs in Chinese euthyroid adults.Methods8771 euthyroid adults from the communities in China were involved. Demographic, behavioral, and anthropometric data were gathered through the questionnaires. Ultrasound was performed to evaluate the TNs. TSH and THs levels were measured. The multivariable logistic regression and multivariable ordinal logistic regression were conducted.ResultsTFQIFT3 among both genders, except women aged 43 to 59 years, where it increased slightly. Additionally, there was an age-related decline in TFQIFT4 levels in both women and men at ages < 50 and < 53, respectively, but a marked increase after that. Lower TSH levels were significantly associated with a higher prevalence and lower odds of having fewer TNs using multiple nodules as the base category in both men and women (both P for trend < 0.05). Additionally, lower TFQIFT3 and TFQIFT4 levels were significantly associated with a higher prevalence of TNs in women (both P for trend < 0.05), and lower TFQIFT3 levels were significantly associated with a higher prevalence of TNs in men. Both higher TFQIFT3 and TFQIFT4 levels were significantly associated with higher odds of having fewer TNs using multiple nodules as the base category in women. However, the relationships between TFQIFT4 and the prevalence or number of TNs in men were not found.ConclusionsThe trends of THs, TSH, TFQIFT4, and TFQIFT3 at different ages were sex-dependent. Both TFQIFT4 and TFQIFT3 levels were negatively associated with the prevalence and number of TNs in women. The present results may lead to a better understanding of the sex-specific relationships between the development of the pituitary-TH axis and the formation of TNs.

Salidroside (SAL), a phenylpropanoid bioactive compound, has various pharmacological properties, including antioxidant, anti-inflammatory, and hepatoprotective effects. However, the pharmacological effects and mechanisms of action of SAL on cholestatic liver injury are unclear. This study investigated the mechanism and effects of salidroside (SAL) on intestinal flora distribution and hepatic stellate cell (HSC) activation in cholestatic hepatic fibrosis. Bile duct ligation was used to cause cholestasis BALB/c mice. The therapeutic efficacy of SAL in liver fibrosis was assessed via serum/tissue biochemical analyses and liver tissue hematoxylin and eosin and Masson staining. Inflammation and oxidative stress were analyzed using enzyme-linked immunosorbent assay and western blotting. HSC were activated in vitro using lipopolysaccharide, and the effects of SAL on HSC migration and inflammatory factor expression were detected via scratch, transwell, and western blotting assays. The effects of SAL on the PI3K/AKT/GSK-3β pathway in vivo and in vitro were detected using western blotting. 16sRNA sequencing was used to detect the effect of SAL on the diversity of the intestinal flora. Ileal histopathology and western blotting were used to detect the protective effect of SAL on the intestinal mucosal barrier. SAL reduces liver inflammation and oxidative stress and protects against liver fibrosis with cholestasis. It inhibits HSC activation and activates the PI3K/AKT/GSK-3β pathway in vitro and in vivo. Additionally, SAL restores the abundance of intestinal flora, which contributes to the repair of the intestinal mucosal barrier, inhibits endotoxin translocation, and indirectly inhibits HSC activation, reversing the course of cholestatic liver fibrosis. SAL inhibits HSC activation through the PI3K/AKT/GSK-3β pathway and improves intestinal flora distribution, thereby protecting and reversing the progression of hepatic fibrosis.

IntroductionAllergic rhinitis (AR) is a respiratory immune system disorder characterized by dysregulation of immune responses. Within the context of AR, gut microbiota and its metabolites have been identified as contributors to immune modulation. These microorganisms intricately connect the respiratory and gut immune systems, forming what is commonly referred to as the gut-lung axis. Xiaoqinglong Decoction (XQLD), a traditional Chinese herbal remedy, is widely utilized in traditional Chinese medicine for the clinical treatment of AR. In this study, it is hypothesized that the restoration of symbiotic microbiota balance within the gut-lung axis plays a pivotal role in supporting the superior long-term efficacy of XQLD in AR therapy. Therefore, the primary objective of this research is to investigate the impact of XQLD on the composition and functionality of the gut microbiota in a murine model of AR.MethodsAn ovalbumin-sensitized mouse model to simulate AR was utilized, the improvement of AR symptoms after medication was investigated, and high-throughput sequencing was employed to analyze the gut microbiota composition.ResultsXQLD exhibited substantial therapeutic effects in AR mice, notably characterized by a significant reduction in allergic inflammatory responses, considerable alleviation of nasal symptoms, and the restoration of normal nasal function. Additionally, following XQLD treatment, the disrupted gut microbiota in AR mice displayed a tendency toward restoration, showing significant differences compared to the Western medicine (loratadine) group.DiscussionThis results revealed that XQLD may enhance AR allergic inflammatory responses through the regulation of intestinal microbiota dysbiosis in mice, thus influencing the dynamics of the gut-lung axis. The proposal of this mechanism provides a foundation for future research in this area.

Breast cancer is the most common malignant tumor in women, posing a serious threat to women’s health. HER2 has been identified as a key oncogene and prognostic factor in breast cancer. Recent studies have reported inconsistencies in ER, PR, and/or HER2 expression between primary breast tumors and metastatic lesions. Rarely is it reported that all three biomarkers experience conversion. In this report, we present the case of a female patient with relapsed and metastatic breast cancer, whose histology transformed from initially triple-negative to Luminal-B type (HER2 positive) (i.e., ER, PR, and HER2 positive). She underwent systematic chemotherapy, targeted therapy, and cranial radiotherapy, which was followed by maintenance treatment with targeted and endocrine therapy. Currently, she has been in nearly complete remission (nCR) for more than 12 months. For recurrent and metastatic breast cancer, it is necessary to perform the second biopsy for metastases, which would contribute to precision treatment and prognosis improvement.

ObjectiveThe purpose of this study is to develop and evaluate a nomogram that is capable of predicting poor operative visibility during functional endoscopic sinus surgery.MethodTo identify potential risk factors, patients with chronic rhinosinusitis who underwent functional endoscopic sinus surgery (FESS) between January 2019 and December 2022 were selected from our hospital’s electronic medical record system. Data on general patient information, clinical manifestations, clotting-related test indices, Lund-Machay score of sinuses CT scanning, Lund-kennedy score of nasal endoscopies, anesthesia methods, intraoperative blood pressure and heart rate, and Boezaart bleeding score were collected. Minimum absolute convergence and selection operator (LASSO) regression, as well as multivariate logistic regression, were used to determine the risk factors. A nomogram was developed in order to predict poor operating visibility during FESS, and its performance was evaluated utilizing both the training and verification datasets via various measures including receiver operating characteristic (ROC) curve analysis, area under the curve (AUC), Hosmer-Lemeshow goodness-of-fit test, calibration curve, and decision curve analysis.ResultsOf the 369 patients who met the inclusion criteria, 88 of them exhibited POV during FESS. By deploying LASSO and multivariate logistic regression analyses, six risk factors were identified and used to construct a nomogram for predicting POV during FESS. These factors include prothrombin time (PT), prothrombin activity (PTA), Lund-Mackay score (LMS), Lund-Kennedy score (LKS), anesthetic method, and intraoperative hypertension. The AUC of the training set was found to be 0.820 while that of the verification set was 0.852. The Hosmer-Lemeshow goodness-of-fit test and calibration curve analysis revealed good consistency between predicted and actual probabilities. Also, the decision curve demonstrated that the nomogram had a high degree of clinical usefulness and net benefit.ConclusionThe constructed nomogram has a strong ability to predict the poor intraoperative field in patients with chronic rhinosinusitis, which can help preoperative judgment of high-risk patients and provide evidence for perioperative management and preoperative plan formulation.

Abstract Background and rationale Cerebral venous thrombosis (CVT) is a rare cerebrovascular disorder that mainly affects young and middle‐aged adults. Epidemiological data on the incidence, risk factors, diagnosis, treatment, and prognosis of CVT are lacking in China. In addition, there is a lack of evidence from large, multicenter, real‐world studies on the efficacy and safety of endovascular. Aim To understand the incidence, diagnosis and treatment status of CVT in China and to estimate the effectiveness and safety of endovascular treatment in the real‐world. Methods A multicenter, retrospective observational cohort study will be conducted on CVT patient records from 104 hospitals, between January 1, 2018 and June 30, 2022, identified using a 2‐stage cluster sampling design based on per capita gross domestic product. Each enrolled participant is required to complete a further follow‐up, which includes the current situation and the assessment at 3 and 12 months after discharge. Study outcomes The outcomes of this study will include the current status of the incidence, pathogenesis, etiology, clinical symptoms, diagnosis, and treatment of CVT in China, as well as the effectiveness and safety of endovascular treatment in the real‐world. Discussion Results from this study will provide evidence on the incidence, specific risk factors, symptomatic and imaging features, and clinical outcomes of CVT in China as well as indicate whether endovascular treatment is superior to medical management alone for patients with acute CVT in the real‐world. Trial registration http://www.clinicaltrials.gov. Identifier NCT05448248

Abstract Background Since the connection between muscle atrophy and vitamin D and estradiol status ambiguous, this study was thus conducted to determine whether low skeletal muscle mass (SMM) in middle-aged and elderly women was affected by estradiol and vitamin D levels together. Methods Baseline data from a sub-cohort of the China Northwest Natural Population Cohort: Ningxia Project (CNC-NX) were analyzed. Serum 25-hydroxyvitamin D (25(OH) D) and estradiol were measured by chemiluminescence immunoassay analyzer. Bivariate logistic regression and multiplicative interaction analyses were used to assess the impact of estradiol level and vitamin D status on low SMM, as well as the combined impact of estradiol and low vitamin D status on low SMM. Results A total of 287 (9.49%) participants had low SMM, which had lower levels of estradiol and vitamin D concentration than normal SMM group. While, after adjusting the confounding variables, these correlations were maintained in estradiol Q1, Q2, Q3 and vitamin D Q1. Furthermore, the significant combined effect of the highest quartile of estradiol concentrations and non-vitamin D deficiency, and interactions between vitamin D Q1 and estradiol Q2, vitamin D Q1 and estradiol Q3, vitamin D Q2 and estradiol Q1, vitamin D Q3 and estradiol Q3 on low SMM were stably reflected (P for interaction

ObjectiveTo compare the prevalence of asthma and the impact of socioeconomic position (SEP) on economic burden of asthma among rural residents in Yunnan province in 2011 and 2021, and to provide evidence for the prevention and treatment of asthma in the population. MethodsUsing stratified multistage random sampling, we conducted face-to-face surveys during 2011 and 2021 among 8 187 and 7 572 rural residents aged ≥ 35 years in Yunnan province. A self-designed questionnaire was used to collect information on demographics, SEP, asthma clinically diagnosed at township and upper level hospitals, and asthma-related economic burden for analyses on asthma prevalence and the influence of SEP on asthma-induced economic burden among the participants. ResultsAmong the rural adults surveyed in 2011 and 2021, totally 111 and 122 asthma cases were identified, with the asthma prevalence rate of 1.36% and 1.61% and without significant difference between the two prevalence rates. Compared to those reported by the adults with asthma incidence in 2011, significantly higher per capita asthma-related direct cost (4 230.11 vs. 2 776.85 Chinese Yuan), indirect cost (69.57 vs. 49.86), and total cost (4 299.68 vs. 2826.71) were reported by the adults with asthma incidence in 2021 (all P < 0.05). Contrasting to that in 2011, the per capita asthma-related total cost increased significantly in 2021 for the asthma sufferers of various SEP groups (P < 0.05 for all) and the total cost increment varied in a descending order for the asthma sufferers with high, low, lower-middle, and upper-middle SEP. Conclusion Among the rural adult residents in Yunnan province, the prevalence of asthma was not significantly different but the economic burden of asthma sufferers increased substantially between 2011 and 2022 and the sufferers' economic burden varied with their socioeconomic position.

Acute myeloid leukemia (AML) is a large class of heterogeneous hematological malignancies with the highest incidence rate in acute leukemia. Its pathogenesis is still unclear, which may be related to genetics. According to the latest AML NCCN guidelines, genes involved in AML family genetic changes include RUNX1, ANKRD26, CEBPA. Finding new genes related to AML genetics is of great significance for predicting the prognosis of patients, developing targeted drugs, and selecting transplant donors. Here, we report a case of adult female AML patient whose three relatives suffered from hematological malignancies, including Waldenstrom macroglobulinemia, NK/T-cell lymphoma, and angioimmunoblastic T-cell lymphoma. The screen for genetic susceptibility genes related to blood and immune system diseases was carried out, and the result showed that the patient herself, her son, her daughter, and her two cousins all had STK11 p.F354L and/or THBD p.D486Y mutations. At present, there is no research or case report on the relationship between STK11/THBD and family aggregation of hematological malignancies. We report for the first time that an AML patient with STK11 and THBD mutations has a family aggregation of hematological malignancies, and consider that STK11 and THBD may be related to family genetic changes which ultimately cause the family aggregation of hematological malignancies.

Abstract Immunotherapy combined with antiangiogenic targeted therapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for refractory recurrent/metastatic nasopharyngeal carcinoma (RM-NPC). We conducted a phase 2 trial to evaluate the safety and activity of camrelizumab plus apatinib in platinum-resistant (cohort 1, NCT04547088) and PD-1 inhibitor resistant NPC (cohort 2, NCT04548271). Here we report on the primary outcome of objective response rate (ORR) and secondary endpoints of safety, duration of response, disease control rate, progression-free survival, and overall survival. The primary endpoint of ORR was met for cohort 1 (65%, 95% CI, 49.6–80.4, n = 40) and cohort 2 (34.3%; 95% CI, 17.0–51.8, n = 32). Grade ≥ 3 treatment-related adverse events (TRAE) were reported in 47 (65.3%) of 72 patients. Results of our predefined exploratory investigation of predictive biomarkers show: B cell markers are the most differentially expressed genes in the tumors of responders versus non-responders in cohort 1 and that tertiary lymphoid structure is associated with higher ORR; Angiogenesis gene expression signatures are strongly associated with ORR in cohort 2. Camrelizumab plus apatinib combination effectiveness is associated with high expression of PD-L1, VEGF Receptor 2 and B-cell-related genes signatures. Camrelizumab plus apatinib shows promising efficacy with a measurable safety profile in RM-NPC patients.

Abstract In this paper, using the notion of w-distance in metric spaces, we introduce two types of nonlinear contractions, ( ι , ψ , φ , ϕ , p ) $(\iota ,\psi ,\varphi ,\phi ,p)$ and rational- ( ι , ψ , φ , ϕ , p ) $(\iota ,\psi , \varphi ,\phi ,p)$ contractions. Based on these contractions, we prove the existence and uniqueness of a φ-fixed point for the corresponding contraction. We also provide some examples to demonstrate the correctness and practicability of our results, along with a numerical experiment. Finally, we apply the obtained results to linear matrix equations and nonlinear Fredholm integral equations.

This study explores the reasons behind the variations in the enantioselectivity of the sulfoxidation of methyl phenyl sulfide by marine-derived vanadium-dependent haloperoxidases (VHPOs). Twelve new VHPOs of marine organisms were overexpressed, purified, and tested for their ability to oxidize sulfide. Most of these marine enzymes exhibited nonenantioselective behavior, underscoring the uniqueness of AnVBPO from the brown seaweed Ascophyllum nodosum and CpVBPO from the red seaweed Corallina pilulifera, which produce (R)- and (S)-sulfoxides, respectively. The enantioselective sulfoxidation pathway is likely due to direct oxygen transfer within the VHPO active site. This was demonstrated through molecular docking and molecular dynamics simulations, which revealed differences in the positioning of sulfide within AnVBPO and CpVBPO, thus explaining their distinct enantioselectivities. Nonenantioselective VHPOs probably follow a different oxidation pathway, initiating with sulfide oxidation to form a positively charged radical. Further insights were gained from studying the catalytic effect of VO43− on H2O2-driven sulfoxidation. This research improves the understanding of VHPO-mediated sulfoxidation and aids in developing biocatalysts for sulfoxide synthesis.

Background: Intravenous thrombolysis is one of the most effective therapies for the treatment of acute ischemic stroke (AIS), with urokinase offering a cost-effective alternative to newer agents like alteplase and tenecteplase, especially in resource-limited settings. Methods: This review provides a comprehensive overview of the application of intravenous thrombolysis with urokinase for AIS in the clinical practice of stroke management, including the efficacy, safety, and cost-effectiveness of urokinase compared to other thrombolytic agents. Results: Urokinase, a first-generation thrombolytic drug, is a non-specific plasminogen activator that offers a cost-effective alternative. It has been used in clinical practice for over two decades to improve neurological outcomes in patients with AIS if administered within 6 h of ictus. Numerous studies have indicated that urokinase remains a viable option for patients who cannot access alteplase or tenecteplase because of economic constraints, time window limitations, availability, or other reasons. Conclusions: In low- and middle-income countries, urokinase is a cost-effective alternative thrombolytic drug. High-level evidence-based medical research is therefore urgently needed to confirm that urokinase is not inferior to new-generation thrombolytic drugs, and to assess whether it may even be superior in some patient populations.

BackgroundMetabolic syndrome (MetS) and sarcopenia (SP) have emerged as significant public health concerns in contemporary societies, characterized by shared pathophysiological mechanisms and interrelatedness, leading to profound health implications. In this prospective cohort study conducted within a US population, we aimed to examine the influence of MetS and SP on all-cause and cardiovascular mortality.MethodsThis study analyzed data from the National Health and Nutrition Examination Survey (NHANES) III for the years 1999-2006 and 2011-2018, and death outcomes were ascertained by linkage to National Death Index (NDI) records through December 31, 2019. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause and cardiovascular mortality. In addition, subgroup and sensitivity analyses were conducted to test the robustness of the results.ResultsOver a median follow-up period of 13.3 years (95% CI: 12.8-13.8), 1714 deaths were observed. The groups characterized by MetS−/SP+, MetS+/SP−, and MetS+/SP+ exhibited higher all-cause mortality rates in comparison to the MetS-/SP- group, with the MetS+/SP+ group (HR 1.76, 95% CI: 1.37-2.25) displaying the highest all-cause mortality. Increased cardiovascular mortality was observed in the MetS+/SP− (HR 1.84, 95% CI: 1.24-2.72), and MetS+/SP+ groups (HR 2.39, 95% CI: 1.32-4.35) compared to the MetS−/SP− group, whereas it was not statistically significant in the MetS-/SP+ group. However, among males and individuals aged < 60, the presence of both MetS and SP (MetS+/SP+ group) was found to be significantly associated with a higher risk of all-cause and cardiovascular mortality.ConclusionThe coexistence of MetS and SP increased the risk of all-cause and cardiovascular mortality, particularly in males and in nonelderly populations. Individuals with either MetS or SP may require more careful management to prevent the development of other diseases and thereby reduce mortality.

The micro-actuator is a key element of the MEMS-based initiator. In order to ensure safety and achieve the function of detonation energy isolation and transmission of the micro-pyrotechnic sequence, it is necessary to set up a safety and arming device between the micro-heater and energetic materials on the next level in the initiator. In this paper, the MEMS safety and arming device was simulated and analyzed, and the actuator chip was made based on MEMS technology and then tested. The results showed that the maximum temperature and displacement generated by the silicon-based micro-actuator increased with increasing actuation voltage. When the actuation voltage was larger than 16 V, the device could not work normally because the maximum temperature of the device was higher than the melting point of silicon. Furthermore, the influence factors on the state-recoverable property of the device were studied by changing the actuation voltage, length, width, and thickness of the V-shaped beam in a single way. The results showed that when the actuation voltage remained unchanged and the other factors were changed in a single way, the smaller structural parameters resulted in the shorter response time and recovery time, while the displacement generated was smaller. Meanwhile, the larger structural parameters resulted in larger displacements, while the response time and recovery time were larger. In addition, the state-recoverable characteristics of the device were affected by the working environmental temperature. It is of great significance to the design of the MEMS-based initiator.

Rural landscapes have significant ecological, historical, and cultural value including numerous green spaces and forest spaces that should be protected and utilized. With the growing demand for green tourism in rural areas in recent years, rural greenways have become increasingly crucial for promoting urban–rural development by connecting linear spatial corridors such as landscape patches, scenic pathways, and strip woodlands. The accuracy and universality of landscape visual quality assessment affect the construction and enhancement of linear landscapes. The previous studies predominantly focused on individual perceptions of greenway landscapes, neglecting the comprehensive visual characteristics of both internal composition and visible surroundings.The evaluation model usually are purely subjective and overall evaluations, lacking the exploration of prediction mechanisms and specific analyses of constituent elements. This study correlates the percentage of elements obtained from image segmentation with subjective evaluation, aims to derive the influence ranking of constituent elements and the visual quality prediction model of visual space, and compares it with the results of objective experiments to further improve the objectivity of the conclusions. Based on visual quality assessment, this study utilize deep learning, eye movement analysis, and visual elements assessment to obtain objective results for visual quality assessment of rural greenways, analyze their influencing factors. A quantitative evaluation model based on the subjective and objective influence of visual landscape components was constructed by combining deep learning and eye movement information processing with human–machine–environment synchronous quantitative analysis technology. This model reveals then relationship between visual influence elements and the influence strength of rural greenway landscapes. The attractiveness strength of spatial visual elements of rural greenway landscapes is consistent with human aesthetic preferences, visual perception, and physiological responses. This study validated the scientific, appropriate, and precise methodologies of eye movement analysis and physiological analysis for quantitatively evaluating the aesthetic preferences of rural greenway landscapes.

Phthalates (PEs) are widely used plasticizers in polymer products, and humans are increasingly exposed to them. This study was designed to investigate the alleviative effect of phytochemicals quercetin (Que) against male reproductive toxicity caused by the mixture of three commonly used PEs (MPEs), and further to explore the underlying mechanism. Forty-eight male SD rats were randomly and evenly divided into control group, Que group, MPEs group and MPEs+Que group (n = 12); The oral exposure doses of MPEs and Que were 450 mg/kg/d and 50 mg/kg/d, respectively. After 91 days of continuous intervention, compared with control group, the testes weight, epididymis weight, serum sex hormones, and anogenital distance were significantly decreased in MPEs group (P

BackgroundThe results of current studies on metabolic-dysfunction associated steatotic liver disease (MASLD)-related diseases, cognition and dementia are inconsistent. This study aimed to elucidate the effects of MASLD-related diseases on cognition and dementia.MethodsBy using single-nucleotide polymorphisms (SNPs) associated with different traits of NAFLD (chronically elevated serum alanine aminotransferase levels [cALT], imaging-accessed and biopsy-proven NAFLD), metabolic dysfunction-associated steatohepatitis, and liver fibrosis and cirrhosis, we employed three methods of mendelian randomization (MR) analysis (inverse-variance weighted [IVW], weighted median, and MR-Egger) to determine the causal relationships between MASLD-related diseases and cognition and dementia. We used Cochran's Q test to examine the heterogeneity, and MR-PRESSO was used to identify outliers (NbDistribution = 10000). The horizontal pleiotropy was evaluated using the MR-Egger intercept test. A leave-one-out analysis was used to assess the impact of individual SNP on the overall MR results. We also repeated the MR analysis after excluding SNPs associated with confounding factors.ResultsThe results of MR analysis suggested positive causal associations between MASLD confirmed by liver biopsy (p of IVW = 0.020, OR = 1.660, 95%CI = 1.082-2.546) and liver fibrosis and cirrhosis (p of IVW = 0.009, OR = 1.849, 95%CI = 1.169-2.922) with vascular dementia (VD). However, there was no evidence of a causal link between MASLD-related diseases and cognitive performance and other types of dementia (any dementia, Alzheimer's disease, dementia with lewy bodies, and frontotemporal dementia). Sensitivity tests supported the robustness of the results.ConclusionsThis two-sample MR analysis suggests that genetically predicted MASLD and liver fibrosis and cirrhosis may increase the VD risk. Nonetheless, the causal effects of NAFLD-related diseases on VD need more in-depth research.

BackgroundChatGPT is a large language model designed to generate responses based on a contextual understanding of user queries and requests. This study utilised the entrance examination for the Master of Clinical Medicine in Traditional Chinese Medicine to assesses the reliability and practicality of ChatGPT within the domain of medical education.MethodsWe selected 330 single and multiple-choice questions from the 2021 and 2022 Chinese Master of Clinical Medicine comprehensive examinations, which did not include any images or tables. To ensure the test's accuracy and authenticity, we preserved the original format of the query and alternative test texts, without any modifications or explanations.ResultsBoth ChatGPT3.5 and GPT-4 attained average scores surpassing the admission threshold. Noteworthy is that ChatGPT achieved the highest score in the Medical Humanities section, boasting a correct rate of 93.75%. However, it is worth noting that ChatGPT3.5 exhibited the lowest accuracy percentage of 37.5% in the Pathology division, while GPT-4 also displayed a relatively lower correctness percentage of 60.23% in the Biochemistry section. An analysis of sub-questions revealed that ChatGPT demonstrates superior performance in handling single-choice questions but performs poorly in multiple-choice questions.ConclusionChatGPT exhibits a degree of medical knowledge and the capacity to aid in diagnosing and treating diseases. Nevertheless, enhancements are warranted to address its accuracy and reliability limitations. Imperatively, rigorous evaluation and oversight must accompany its utilization, accompanied by proactive measures to surmount prevailing constraints.

Objective The aim of this study was to investigate risk factors for cognitive impairment (CI) and explore the relationship between obesity and cognition in hospitalised middle-aged patients with type 2 diabetes (T2DM).Methods Subjects were divided into normal cognitive function (NCF) (n=320) and CI (n=204) groups based on the results of the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). The risk factors for CI were determined by logistic regression analysis and generalised linear modelling. The associations between obesity parameters (body mass index (BMI) and waist circumference (WC)) and cognitive ability were studied with the use of linear regression analysis, piecewise regression modelling and interaction analysis. The receiver operating characteristic curve analysis was used to examine the diagnostic value of influencing factors for ccResults The prevalence of CI was 38.9% in hospitalised middle-aged T2DM patients (median age, 58 years). Age, WC, hypoglycaemic episode within past 3 months and cerebrovascular disease (CVD) were identified as independent risk factors for CI, while the independent protective factors were education, diabetic dietary pattern, overweight and obesity. BMI was a protective factor for the MoCA score within a certain range, whereas WC was a risk factor for the MMSE and MoCA scores. The area under the curve for the combination of BMI and WC was 0.754 (p

Objective. This study aims to develop and evaluate a nomogram for predicting the risk of chronic fatigue syndrome (CFS)-like symptoms in university students diagnosed with infectious mononucleosis (IM), using clinical characteristics and laboratory findings as predictive variables. The nomogram will be designed to assist healthcare providers in assessing the likelihood of CFS-like symptoms developing post-IM, rather than providing a definitive diagnosis of CFS. Methods. Clinical data and laboratory findings were collected from university students with IM. The variables included age, gender, smoking and drinking habits, relationship status, university grade, residence registration, number of symptoms and signs (NSS), body mass index (BMI), C-reactive protein (CRP) level, neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), monocyte–lymphocyte ratio (MLR), aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT, DeRitis), basophil percentage (Baso%), eosinophil percentage (Eos%), and albumin-to-globulin ratio (ALB/GLO). LASSO regression analysis was employed to identify significant predictors of CFS-like symptoms. A nomogram model was constructed based on these predictors and evaluated using performance metrics such as the concordance index (C-index), area under the curve (AUC), calibration curves, and decision curve analysis. Results. The LASSO regression analysis identified the NSS, CRP, NLR, and MLR as significant predictors of CFS-like symptoms in university students with IM. The nomogram demonstrated robust predictive performance, with a C-index of 0.846 (95% CI: 0.790–0.902) in the training set and 0.867 (95% CI: 0.8–0.954) in the validation set. High AUC values indicated excellent overall predictive accuracy. Calibration curves revealed a close match between predicted and observed probabilities. Additionally, decision curve analysis showed positive net benefits across a broad spectrum of threshold probabilities, underscoring the nomogram’s clinical applicability. Conclusion. The nomogram developed in this study serves as a valuable predictive tool for assessing the risk of CFS-like symptoms in university students with IM. The identified predictors, including NLR, the NSS, CRP, and MLR, can assist clinicians in evaluating individual risk profiles and inform decision-making processes. This nomogram model advances personalized risk assessment for the development of CFS-like symptoms in IM-affected university students.

The macroscopic fundamental diagram (MFD) is a nonuniversal changing process over network traffic status which indicates different shapes in different networks. Hysteresis is observed in the MFD of some urban networks. It is a unique phenomenon when the network remains at low stability level and usually appears around the congestion period. This paper analyzed network peak stability through focusing on hysteresis. The formation mechanism of hysteresis is deduced from the mathematical method based on previous research studies. The precondition of hysteresis and the changing process of network state can be figured by mathematical deduction. It indicates that hysteresis only occurs conditionally in the period of macroscopic congestion and is not a universal phenomenon. Heterogeneity is an important factor leading to network instability. The hysteresis patterns of different peaks in MFD are different due to the variation of network flow. Real data are collected from Atlanta’s urban network to verify the analysis of hysteresis. To discuss the changing process of hysteresis in different peaks, a three-stage division is proposed and time series is presented as a third dimension in MFD. It is worth noticing that the existence and form of hysteresis in morning and evening peaks are different. Although there is a higher peak flow in the morning peak, the stability of the evening peak performs better when hysteresis occurs in the network. The different fluctuations in the morning and evening peaks are exhibited through the 3D version of MFD. The otherness of hysteresis in different peaks is explained through a 3D coordinate system with cross-compared corresponding indexes.

In this paper, we present a new approach to construct fractional 2-point right Radau type integral inequalities using a novel identity, for functions with s-convex first derivatives in the second sense via Riemann–Liouville fractional integral operators. We then demonstrate the accuracy of our results through a 2D example, as well as practical applications of the integral inequalities to quadrature formulas and special means such as arithmetic and p-logarithmic means.