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IntroductionEndotoxemia is a common issue for patients with biliary obstruction. The lung is the most affected organ by endotoxins. Exercise training can alleviate lipopolysaccharide (LPS)-induced lung inflammation and resveratrol has biological effects similar to exercise. In this study, we evaluated the protective effects of exercise preconditioning, resveratrol, and their combination on LPS-induced lung injury and mortality in rats with obstructive jaundice.MethodsEndotoxemia was simulated in rats by common bile duct ligation (CBDL) and intraperitoneal injection of low-dose LPS. The treatment groups were pretreated with exercise and/or resveratrol to assess their effects on lung injury and mortality. Immunohistochemistry, immunofluorescence, and ELISA were subsequently used to evaluate the impact of exercise and/or resveratrol on inflammation in lung tissue and bronchoalveolar lavage fluid.ResultsWe found that even in the early stages, compared to sham-LPS rats, low-dose LPS induced excessive systemic inflammatory responses in CBDL rats, as evidenced by a significant increase in TNF-α and IL-6, severe lung inflammation, lung injury, and higher mortality rates, indicating that cholestasis increased rats’ susceptibility to endotoxins. Exercise training reduced neutrophil infiltration in the lungs of model rats and IL-6 levels in bronchoalveolar lavage fluid. Both exercise training and resveratrol exhibited synergistic effects in reducing macrophage accumulation in lung tissues, lowering TNF-α and IL-6 levels in the lungs, and decreasing TNF-α concentration in bronchoalveolar lavage fluid. Additionally, exercise and combined interventions both significantly increased the expression of IL-10. The interventions induced a marked improvement in lung tissue pathological damage and lung edema in model rats and prolonged the survival time of rats with obstructive jaundice.DiscussionThis study demonstrates that exercise preconditioning and/or resveratrol can significantly reduce rats’ susceptibility to endotoxins after CBDL and alleviate lung injuries through their anti-inflammatory effects, thereby decreasing the mortality risk.

BackgroundImproving system coordination is a pivotal strategy and a critical pathway for social governance. Chinese society is currently facing a significant challenge in aligning the allocation of health resources with economic development. Evaluating the level of coordinated development within the system can provide valuable insights to support the construction of a more coordinated China and foster high-quality development.MethodsBased on a systematically constructed indicator framework, our study selected data from five eastern provinces of China to establish a ten-year panel dataset covering the period from 2011 to 2020. The comprehensive evaluation index and the relative development degree were employed to comprehensively evaluate the development level of the system. The coupling coordination degree model was applied to analyze the coupling coordination relationship and spatiotemporal evolution trend of the two systems. Additionally, the fixed effects model was used to identify the driving factors behind the coordinated development of the two systems.ResultsFrom 2011 to 2020, the comprehensive indices of health resource allocation and economic development in the five eastern provinces of China exhibited a consistent year-on-year increase, and the relative development degree experienced two critical values of 0.8 and 1.2, which changed from the lagging allocation of health resources to the lagging economic development. The system coordination index generally ranged between 0.35 and 0.90, with the coordination phase undergoing a transition from an antagonistic stage to a coordinated stage. The coordination type also gradually shifted from mild imbalance to good coordination. Furthermore, the levels of economic development, economic structure, technological investment, as well as the allocation of health human and material resources, all serve as critical drivers in enhancing the coordinated development of the system.ConclusionThe coordinated development of eastern China’s provinces produces substantial spillover effects, and the realization of a Healthy China initiative must strategically harness their radiative and demonstrative effects. Achieving a superior level of coordination requires urgent efforts to rectify the existing deficiencies in the distribution of grassroots healthcare resources. Furthermore, cultivating innovative drivers of economic growth and enhancing the capacity for economic support are critical to ensuring high-quality and sustainable development.

BackgroundPsoriasis is commonly associated with metabolic dysfunction-associated steatotic liver disease, raising concerns about the hepatic effects of systemic treatments on psoriasis and its comorbid conditions. This study evaluates liver stiffness measurement (LSM) alterations and identifies predictors of abnormal LSM in psoriatic patients following systemic treatments, including biologics and methotrexate.MethodsThis prospective cohort study is based on the PSOWCH database (Psoriasis Cohort of West China Hospital). We initially included psoriatic patients who had undergone sound touch elastography (STE), then recruited patients who had STE before systemic treatment and reassessed them after at least six months. Three treatment subgroups were formed (interleukin inhibitors, tumor necrosis factor inhibitors, and methotrexate), classifying post-treatment STE outcomes using threshold values of 6.5 kPa and 10.3 kPa.ResultsAmong the 52 recruited patients, overall STE values significantly increased during follow-up. Univariate regression analysis showed that age, gender, psoriasis severity, psoriatic arthritis status, and current treatment type were not significantly correlated with abnormal STE outcomes at cutoff values of 6.5 kPa and 10.3 kPa. In the multivariate model, body mass index (BMI) was identified as a risk factor for post-treatment STE ≥ 6.5 kPa (odds ratio [OR], 1.26; 95% CI, 1.04 to 1.60, P=0.031).ConclusionsThis exploratory study reveals that systemic treatment type is not associated with abnormal post-treatment LSM. However, a significant association exists between BMI and abnormal LSM outcomes. These findings highlight the critical importance of BMI management in therapeutic interventions for psoriasis.

BackgroundPrevious studies have shown that surgery under general anesthesia may diminish cognitive function; however, the proposed mechanisms need further elucidation. The purpose of the current study was twofold: (1) to compare overall and domain-specific differences in cognitive function between the surgery under general anesthesia group and the control group, and (2) to investigate the possible mechanisms of surgery under general anesthesia affecting cognitive function, using T1-structural magnetic resonance imaging.MethodsA total of 194 older adults were included in this study. Patients were divided into a surgery under general anesthesia group (n = 92) and a control group (n = 104). The two groups were matched for age, sex, and educational level. All participants underwent clinical evaluation, neuropsychological testing, blood biochemistry analysis, and T1 phase structural magnetic resonance imaging.ResultsWe found that older adults with a history of surgery under general anesthesia had lower Montreal Cognitive Assessment (MoCA) scores and smaller right putamen volumes (p

BackgroundHypoxia in the tumor microenvironment (TME) plays a pivotal role in the progression and prognosis of colorectal cancer (CRC). However, effective methods for assessing TME hypoxia remain lacking. This study aims to develop a novel hypoxia-related prognostic score (HPS) based on hypoxia-associated genes to improve CRC prognostication and inform treatment strategies.MethodsTranscriptomic data from CRC patients were analyzed using Lasso regression to identify hypoxia-associated genes with the strongest prognostic significance. The identified genes were validated in vitro by assessing their expression under normoxic and hypoxic conditions in normal intestinal epithelial cells and CRC tumor cell lines. Functional relevance was explored through differential gene expression analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and protein-protein interaction (PPI) network construction. The association of HPS with extracellular matrix (ECM) composition, immune cell infiltration, and immune suppression was also investigated.ResultsSeven hypoxia-associated signature genes were identified, each demonstrating a strong correlation with CRC prognosis. The hypoxia-related prognostic score (HPS), derived from these genes, was significantly linked to changes in the TME. Specifically, HPS values were associated with alterations in ECM composition and distinct immune cell infiltration patterns. Higher HPS values corresponded to increased infiltration of immune-suppressive cells and reduced presence of anti-tumor immune cells. This imbalance promoted an immune-suppressive TME, facilitating tumor progression and immune evasion.ConclusionsThe hypoxia-related prognostic score (HPS) captures the regulatory influence of TME hypoxia on immune responses, offering valuable insights into its role in tumor progression. HPS holds promise as a prognostic tool and a guide for developing personalized treatment strategies in CRC.

BackgroundClinically ineffective reperfusion (CIR) refers to the discrepancy between successful reperfusion and a favorable functional outcome in patients with large vessel occlusion (LVO) stroke after endovascular treatment (EVT). The Improving Neuroprotective Strategy for Ischemic Stroke with Sufficient Recanalization after Thrombectomy by Intra-arterial Cocktail Therapy (INSIST-CT) trial aimed to explore the safety, feasibility, and efficacy of intra-arterial cocktail therapy using argatroban, dexamethasone, and edaravone in patients who achieved sufficient reperfusion after EVT.MethodsIn this prospective, single-arm, pilot study, eligible patients with anterior circulation LVO who achieved sufficient reperfusion after EVT were enrolled in the INSIST-CT trial. Consecutive patients who met the inclusion/exclusion criteria were included in the control group retrospectively. In the INSIST-CT group, argatroban, dexamethasone, and edaravone were continuously administered for 30 min into the culprit artery after sufficient recanalization. The primary endpoint was the proportion of favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0–2 at 90 days. The primary safety outcome was symptomatic intracranial hemorrhage (sICH). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analyses were performed to account for multiple confounders.ResultsA total of 30 patients were included in the INSIST-CT group, and 261 patients were included in the control group. The proportion of the patients with the primary endpoint was 60% in the INSIST-CT group and 55.9% in the control group (unadjusted odds ratio [OR] 1.18, 95% CI 0.55–2.61, p = 0.67; adjusted OR 1.42, 95% CI 0.62–3.26, p = 0.41). No significant difference in sICH at 48 h after treatment was observed between the two groups (unadjusted OR 0.96, 95% CI 0.15–3.56, p = 0.96; adjusted OR 0.82 95% CI 0.17–3.97, p = 0.809). Similar results were observed after the PSM and IPTW analyses.ConclusionIn anterior circulation, LVO patients who achieved sufficient reperfusion after EVT, bridging intra-arterial cocktail therapy with argatroban, dexamethasone, and edaravone may be safe and feasible. However, it did not improve the 90-day functional outcomes. A numerically higher probability of a favorable outcome in the INSIST-CT group suggests the potential promise of this cocktail therapy in reducing clinically ineffective reperfusion.Clinical trial registrationClinicalTrials.gov, NCT04202549.

BackgroundDistant metastasis of gastric cancer can seriously affect the treatment strategy of gastric cancer patients, so it is essential to identify patients at high risk of distant metastasis of gastric cancer earlier.MethodIn this study, we retrospectively collected research data from 18,472 gastric cancer patients from the SEER database. We applied six machine learning algorithms to construct a model that can predict distant metastasis of gastric cancer. We constructed the machine learning model using 10-fold cross-validation. We evaluated the model using the area under the receiver operating characteristic curves (AUC), the area under the precision-recall curve (AUPRC), decision curve analysis, and calibration curves. In addition, we used Shapley’s addition interpretation (SHAP) to interpret the machine learning model. We used data from 1595 gastric cancer patients in the First Hospital of Jilin University for external validation. We plotted the correlation heat maps of the predictor variables. We selected an optimal model and constructed a web-based online calculator for predicting the risk of distant metastasis of gastric cancer.ResultThe study included 18,472 patients with gastric cancer from the SEER database, including 4,202 (22.75%) patients with distant metastases. The results of multivariate logistic regression analysis showed that age, race, grade of differentiation, tumor size, T stage, radiotherapy, and chemotherapy were independent risk factors for distant metastasis of gastric cancer. In the ten-fold cross-validation of the training set, the average AUC value of the random forest (RF) model was 0.80. The RF model performed best in the internal test set and external validation set. The RF model had an AUC of 0.80, an AUPRC of 0.555, an accuracy of 0.81, and a precision of 0.78 in the internal test set. The RF model had a metric AUC of 0.76 in the external validation set, an AUPRC of 0.496, an accuracy of 0.82, and a precision of 0.81. Finally, we constructed a network calculator for distant metastasis of gastric cancer using the RF model.ConclusionWith the help of pathological and clinical indicators, we constructed a well-performing RF model for predicting the risk of distant metastasis in gastric cancer patients to help clinicians make clinical decisions.

IntroductionHydrocephalus is a form of communication hydrocephalus syndrome characterized by ventricular enlargement and normal intraventricular pressure. The primary clinical manifestations include gait disturbances, cognitive dysfunction, urinary incontinence, and either elevated or normal intracranial pressure. This paper presents a case of a mental disorder resulting from inadequate drainage following a ventriculoperitoneal shunt procedure for hydrocephalus. The case report aims to enhance clinicians’ understanding of such organic brain lesions, which are prone to misdiagnosis and inappropriate treatment, thereby improving differential diagnostic skills.Case presentationThis case report describes a 34-year-old male with a 16-year history of depressive disorder, previously managed with 150 mg of venlafaxine daily, 7.5 mg of zopiclone every night, and 2.4 g of piracetam every day. The patient underwent a ventriculoperitoneal shunt procedure for hydrocephalus, leading to the development of a mental disorder attributable to poor drainage from the shunt tube. Initial symptoms consisted of low mood, decreased interest, and cognitive impairment. Despite psychiatric consultation and antidepressant treatment, there was no improvement in his condition. The final diagnosis was an organic mental disorder. Following an increase in shunt drainage and the administration of a low dose of olanzapine, the patient’s psychiatric symptoms showed significant improvement.ConclusionReporting this case seeks to enhance clinicians’ awareness of the psychiatric manifestations of organic brain lesions, expand the differential diagnostic approach for psychiatrists, and improve diagnostic accuracy. Additionally, it emphasizes the need for cautious use of psychiatric medications, appropriate symptomatic management, and timely referral when necessary.

BackgroundThe calcium-sensitive receptor (CaSR) has been identified as a key factor in the formation of kidney stones. A substantial body of research has illuminated the function of CaSR in stone formation with respect to oxidative stress, epithelial injury, crystal adhesion, and stone-associated proteins. Nevertheless, as a pivotal molecule in renal calcium excretion, its pathway that contributes to stone formation by regulating calcium supersaturation remains underexplored.MethodsAn in vitro rat calcium oxalate kidney stone model was established through the co-cultivation of calcium oxalate monohydrate (COM) with NRK-52E cells, while an in vivo model was constructed using the ethylene glycol method. Subsequently, the level of the CaSR-claudin-14 pathway was determined. To further elucidate the molecular pathway of CaSR-mediated regulation of claudin-14, drugs were selectively added to the in vitro and ex vivo kidney stone models, and the expression of claudin-14 and the levels of stone formation were detected. Moreover, the direct regulation of claudin-14 by CaSR with STAT3 serving as a transcription factor was examined via the dual luciferase assay. Eventually, a Cldn-14 knockout rat model and a model of kidney stone induction by ethylene glycol were generated using CRISPR-Cas9 technology to further clarify the role of claudin-14 in the CaSR-regulated formation of kidney stones.ResultsIn vitro and in vivo observations revealed that calcium oxalate induces high expression of CaSR-claudin-14. Specifically, CaSR regulates claudin-14 expression through phosphorylation modification of STAT3 via protein kinase A (PKA). In vitro, the intervention of PKA and STAT3 reversed the elevated claudin-14 levels and stone formation induced by CaSR. Finally, we generated cldn-14 knockout rats using CRISPR-Cas9 technology and observed that ethylene glycol still induced stone formation in these animals. Nevertheless, the specific activation or inhibition of CaSR demonstrated no notable impact on stone formation.ConclusionThe results of our study indicate that calcium oxalate crystals induce the activation of the pro-stone pathway of CaSR. That is, activated CaSR regulates claudin-14 levels via the PKA-STAT3 pathway, which further promotes calcium salt stone formation. The role of CaSR in the regulation of stone homeostasis is further enriched.

The spatially varying geographic-parameters introduce significant uncertainty into the ocean model. Due to the impracticality of manually tuning spatial varying parameters, data assimilation methods are widely used for geographic-parameter optimization (GPO). Practically, the limited observations do not contain enough information to perform GPO directly on the entire grid. Therefore, techniques are required to reduce the complexity of the parameters. A full-grid GPO scheme based on the ensemble adjustment Kalman filter (EAKF) is developed. Via smoothing the spatial distribution of posterior parameter members, the EAKF-smoothing (EAKF-S) introduces additional spatial correlations among parameters. Meanwhile, the small-scale correlation between the state and the parameters, which exhibit strong pseudo-correlations, is filtered out. A tide model of the Bohai Sea and Yellow Sea, considering 8 principal tidal constituents. is constructed using the Princeton Ocean Model with the generalized coordinate system (POMgcs). The EAKF-S is employed for optimizing the full-grid bathymetry. In twin experiment, based on idealized water level observations, EAKF-S effectively reduced model errors and approximately inverted the “true” bathymetry. After GPO, the lowest mean absolute error of the parameter ensemble is 0.83 m. A series of practical GPO experiments based on synthetic water level observations calculated from NAO.99Jb data are performed. First, the improvement of EAKF-S in accuracy and efficiency over standard EAKF is proven using an M2 tide model. After that, a practical experiment on an 8 constituents tide model is performed. The results show that the forecasting performance of all 8 constituents is improved after GPO, indicating the efficacy of EAKF-S.

BackgroundCollision tumors are defined as two or more distinctly bordered, mutually invasive tumors in the same anatomical region. Characterized by low incidence and lack of specificity, they often pose a significant challenge to disease diagnosis. Among these, collision tumors in the sella region are incredibly rare.Case descriptionOn 13 June 2023, the Department of Neurosurgery at Drum Tower Hospital admitted a patient with a pituitary adenoma in the sella region complicated by spindle cell sarcoma. After reviewing the literature, no related cases were reported. A patient presenting with complex clinical symptoms and preoperative imaging showing occupancy in the sella region is considered to have a recurrence of pituitary adenoma. After thorough preoperative evaluation and discussion, a trans-sphenoidal approach (with the aid of an endoscope) was performed to resect the pituitary lesions. Combined with postoperative pathological tissue and imaging, the patient was diagnosed with a pituitary adenoma (postoperative recurrence) in the sella region complicated by spindle cell sarcoma. The patient made a fair recovery and was discharged on the 8th postoperative day.ConclusionThis case report aims to elucidate and discuss the diagnosis and screening of rare collision tumors in the sella region to reduce the misdiagnosis rate and provide accurate treatment.

BackgroundAlcoholic hepatitis (AH) is characterized by intense systemic and liver inflammation, posing significant risks of health complications and mortality. While inflammation is a crucial defense mechanism against injury and infection, its timely resolution is essential to prevent tissue damage and restore tissue homeostasis. The resolution of inflammation is primarily governed by specialized pro-resolving mediators (SPMs), lipid metabolites derived from w-6 and w-3 poly-unsaturated fatty acids (PUFAs). Currently, the balance between pro-inflammatory lipid mediators (PLMs) and SPMs in the w-6 and w-3 PUFA metabolic pathways and the impact of alcohol abstinence on profiles of PLMs and SPMs in AH patients are not well studied.MethodsIn this study, we used LC-MS/MS and ELISA to quantify levels of lipid mediators (LMs) and their precursors in the plasma samples from 58 AH patients, 29 heavy drinkers without overt liver diseases (HDCs), and 35 healthy controls (HCs). Subsequently, we assessed correlations of altered LMs with clinical parameters and inflammatory mediators. Furthermore, we conducted a longitudinal study to analyze the effects of alcohol abstinence on LMs over 6- and 12-month follow-ups.ResultsAH patients exhibited significantly higher plasma levels of w-6 PLMs (PGD2 and LTB4) and SPM RvE1 compared to HDCs or HCs. Conversely, the SPM LXA4 was significantly downregulated in AH patients. Some of these altered LMs were found to correlate with AH disease severity and various inflammatory cytokines. Particularly, the LTB4/LXA4 ratio was substantially elevated in AH patients relative to HDCs and HCs. This altered ratio displayed a positive correlation with the MELD score. Importantly, the majority of dysregulated LMs, particularly PLMs, were normalized following alcohol abstinence.

IntroductionApolipoprotein E (APOE) epsilon 4 is regarded as the most significant genetic contributor linked to mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Daily life elements might also influence cognitive abilities to some extent. This research aimed to investigate whether carrying APOE ε4 alters the effects of lifestyle on cognitive ability.MethodsThe research included 1871 senior community members with APOE gene data, all participating in clinical, neuropsychological, and daily living factor assessments. Based on their APOE ε4 status, they were categorized into two groups: the APOE ε4 group (n = 362) and the non-APOE ε4 group (n = 1,509). Subsequently, a multivariate logistic regression analysis was employed to investigate the link between cognitive deficits and APOE ε4, along with lifestyle patterns.ResultsOur research revealed a reduced incidence of MCI (OR = 0.745, 95% CI: 0.587–0.945, p = 0.015) and dementia (OR = 0.422, 95% CI: 0.259–0.688, p = 0.001) in the non-APOE ε4 carriers. Furthermore, the general linear regression analysis revealed a notable interplay between APOE ε4 and sleep disturbances, potentially impacting cognitive deterioration together (F = 6.817, p = 0.001).ConclusionsThe research indicates that possessing APOE ε4 alters the impact of everyday life factors on cognitive decline. In addition, there is a significant interaction between APOE ε4 and sleep disorders, which may jointly lead to the appearance of cognitive impairment.

ObjectiveGut health is critical to the health of the host. This study was conducted to investigate the effects of Chitooligosaccharides (COS) on intestinal morphology, intestinal barrier, intestinal immunity and cecum microbiota of blue foxes.MethodsSeventy-two 125-day-old blue foxes were randomly divided into basal diet (BD) group, 200 ppm COS1 (1.5 kDa) group and 200 ppm COS2 (3 kDa) group for 8 weeks.ResultsWe elucidated that dietary COS1 supplementation promoted the development of intestinal villus morphology in blue foxes. Importantly, COS1 increased the number of goblet cells in duodenum, jejunum and ileum by 27.71%, 23.67%, 14.97% and S-IgA secretion in duodenum, jejunum and ileum by 71.59% and 38.56%, and up-regulate the expression of Occludin and ZO-1 by 50.18% and 148.62%, respectively. Moreover, COS1 promoted the pro-inflammatory and anti-inflammatory balance of small intestinal mucosa, and increased the diversity of cecum microbiota of blue foxes, especially Lactobacillus_agilis and Lactobacillus_murinus, and up-regulated the signaling pathways related to polysaccharide decomposition and utilization.ConclusionHere, we present dietary COS1 (1.5 kDa) can promote intestinal villus development, enhance intestinal barrier function, regulate intestinal immune balance and cecum microbiota homeostasis.

Pyroptosis is a form of inflammatory programmed cell death, and is activated by pathogen infections or endogenous danger signals. The canonical pyroptosis process is characterized by the inflammasome (typically NLRP3)-mediated activation of caspase-1, which in turn cleaves and activates IL-1β and IL-18, as well as gasdermin D, which is a pore-forming executor protein, leading to cell membrane rupture, and the release of proinflammatory cytokines and damage-associated molecular pattern molecules. Pyroptosis is considered a part of the innate immune response. A certain level of pyroptosis can help eliminate pathogenic microorganisms, but excessive pyroptosis can lead to persistent inflammatory responses, and cause tissue damage. In recent years, pyroptosis has emerged as a crucial contributor to the development of chronic inflammatory respiratory diseases, such as asthma. The present study reviews the involvement of pyroptosis in the development of asthma, in terms of its role in different inflammatory phenotypes of the disease, and its influence on various immune and non-immune cells in the airway. In addition, the potential therapeutic value of targeting pyroptosis for the treatment of specific phenotypes of asthma is discussed.

ObjectiveRobust evidence has demonstrated that inflammation plays an important role in the occurrence and development of abdominal aortic aneurysms (AAA). The serum uric acid (UA)/high-density lipoprotein cholesterol (HDL-C) ratio (UHR) has recently been recognized as a new biomarker for evaluating inflammatory and anti-inflammatory interactions. However, whether UHR is associated with AAA remains unclear. This study aimed to explore the association between UHR and presence of AAA.MethodsWe prospectively performed a hospital-based and community-based AAA screening program using ultrasonography in 9,064 individuals at Guangdong Provincial People’s Hospital and two communities in China. Logistic regression analysis was used to explore the association between UHR and presence of AAA. In addition, the restricted cubic spline (RCS) regression method was used to visually investigate the dose-response relationship between UHR and the presence of AAA. Propensity score matching (PSM) analysis was conducted to adjust for baseline variations and diminish selection bias, and subgroup analysis was performed to investigate the consistency of the conclusions.ResultsThe prevalence of AAA was 2.45% (222/9,064) in the present study. The optimal cut-off value of UHR was 17.0%, which was selected according to the receiver operator characteristic curve. The prevalence of AAA was 3.96% in the high-UHR group (UHR ≥ 17%) and 1.54% in the low-UHR group (UHR

BackgroundA standard treatment recommendation for third-line and subsequent treatments for advanced HER2-positive breast cancer is still missing, especially for low HER2 expression. Nevertheless, there is evidence that these patients might benefits from antibody-drug conjugates (ADCs) treatment. Therefore, this study aimed to evaluate the clinical efficacy, safety, and factors affecting efficacy of Disitamab Vedotin (RC48) for treating HER2-positive and HER2-low metastatic breast cancer (MBC) in the real-world setting.MethodsA retrospective study at five clinical sites was conducted in China, enrolling MBC patients treated with RC48 from July 01, 2021 and May 31, 2023. Patient demographics, treatment patterns, and adverse events (AEs) were recorded and analyzed.ResultsA total of 154 patients were included: 104 (67.53%) patients with HER2-positive and 50 (32.47%) patients with HER2-low MBC. The median progression-free survival (mPFS) was 5.06 months. The objective response rate (ORR) and disease control rate (DCR) were 36.36% and 68.83%, respectively. HER2-positive patients exhibited a mPFS of 5.93 and an ORR of 41.35%. In contrast, patients with low-HER2 had a mPFS of 4.28 months and an ORR of 26.00%. The most common AEs included neutropenia (54.55%), increased AST (53.25%), leukopenia (51.95%), and fatigue (43.51%), mostly graded mild to moderate (grade 1-2).ConclusionsThis extensive study in China demonstrated that RC48 has excellent therapeutic potential for both HER2-positive and HER2-low MBC with a favorable safety profile. The study also suggests that combination therapy significantly boosts efficacy beyond monotherapy, indicating a promising avenue for future ADC development.

A penetrating brain injury is a rare type of neurosurgical trauma associated with extremely high mortality and disability rates. Penetrating skull base injuries caused by arrows seldom occur because injuries caused by such weapons are more likely to be accidental. However, the number of self-inflicted injuries is increasing, and these injuries have varying patterns and high mortality rates. We report a case of a transoral penetrating craniocerebral injury caused by an arrow in a suicidal patient. Preoperative imaging is crucial for detecting and planning the surgical approach. Surgery is an effective treatment for this type of injury. Additionally, we reviewed previous case reports on this type of injury to provide recommendations for its clinical detection and treatment.

IntroductionAs rural-to-urban migration accelerates, rural areas are experiencing a significant increase in empty-nesters among the older adults. Influenced by traditional concepts of filial piety, older adults in rural areas heavily rely on the family-based old care model, creating a complex interplay between supply and demand for older adults’ care. This study investigates the relationship between intergenerational support and older adults’ care expectations in rural areas. We construct measures of financial and care expectations of older adults’ care to reflect older adults’ intentions and choices.MethodsThis study uses data from the 2018 China Health and Retirement Longitudinal Study and rural case studies to employ a binomial logit regression model, moderation effect analysis, and in-depth interviews.ResultsOur research reveals that the level of financial expectations for older adults’ care is inversely related to the extent of financial support from the parental generation but positively related to the level of financial support from the offspring. However, the older adults’ care expectations do not appear to be influenced by intergenerational support. Furthermore, population characteristics of the parental generation, such as educational attainment, age, and marital status, moderate the relationship between intergenerational support and older adults’ care expectations. Educational attainment negatively moderates the impact of parental financial support on financial expectations, age positively moderates offspring’s financial support on financial expectations. However, age negatively moderates offspring’s financial support on care expectations, while marital status positively moderates offspring’s financial support on care expectations.DiscussionThese findings help to elucidate the older adults’ care expectations of rural residents during the process of urbanization and social transformation, offering family-centered solutions such as ‘promoting cohabitation or proximity of children to their parents, developing diverse older adults’ care models based on different family situations, and ensuring the provision of basic older adults’ care services’ to address the current challenges of rural older adults’ care in China.

BackgroundAlthough the number of studies on treatment-resistant schizophrenia (TRS) has been increasing, the global research hotspots and future research trends have not yet been established.ObjectiveThis study identify the hotspots of TRS research and predict future research trends using a bibliometric analysis.MethodsThe Web of Science Core Collection was searched using the keyword “TRS”, econometric and co-occurrence analyses were conducted using CiteSpace and VOSviewer software, and the results were visualised. PRISMA reporting guidelines were used for this study.ResultsIn total, 912 publications were included in the analysis. The number of publications on TRS has shown an increasing trend over the past 20 years. The United States and University of London were the countries and institutions with the highest total number of publications, respectively. Schizophrenia Research was the journal with the highest number of articles. American Journal of Psychiatry was the most cited journal. Based on the results of this analysis, cognitive impairment, clozapine-resistant schizophrenia, early-onset schizophrenia, and early recognition of TRS will be hotspots for future research in this field.ConclusionThere has been an upward trend in the number of publications on TRS each year. However, issues such as how to use antipsychotics more efficiently to treat TRS and how to predict the emergence of TRS as early as possible are still in urgent need of research and are current challenges for clinicians. The results of this study not only predict and analyse future research hotspots but also help researchers identify appropriate research directions and partners.

IntroductionPanicle number (PN) is one of the three key yield components in rice, maintaining stable tiller and PN is a crucial characteristic of an ideal plant architecture. Understanding the molecular mechanisms underlying PN is essential for breeders aiming to improve rice yield.MethodsTo dissect the genetic architecture of panicle number, a genome-wide association study (GWAS) was conducted in 411 japonica rice varieties. GWAS analysis was carried out with the mixed linear model using 743,678 high-quality SNPs.ResultsOver two experimental years, we detected a total of seven quantitative trait loci (QTLs), located on chromosomes 1, 4, 6, 8, 11, and 12; notably, qPN1.1 and qPN8 were detected consistently in both years. By combining haplotype and expression analyses, OsCKX11 was identified as the candidate gene for qPN8, while LOC_Os01g07870 and LOC_Os01g07950 were identified as candidate genes for qPN1.1. Significant differences were observed among the haplotypes of these candidate genes. Additionally, qRT-PCR results showed that LOC_Os01g07870 expression levels were significantly lower in accessions with high panicle numbers compared to those with low panicle numbers.DiscussionTo understand the natural biological function of these candidate genes, further research involving overexpression or silencing in rice is needed. Despite these challenges, our results will lay the foundation for further study of panicle development and provide valuable genetic resources for developing high-panicle-number rice cultivars using genetic engineering and molecular breeding.

IntroductionThe periacetabular bone defects caused by metastatic disease often necessitate acetabular reconstruction and various techniques have been employed with varying degrees of success. The purpose of this study was to evaluate the efficacy and safety of acetabular reconstruction in conjunction with adjuvant microwave ablation as a surgical intervention for patients with periacetabular metastases.MethodsBetween January 2019 and September 2023, 17 consecutive patients with different tumor subtypes required surgical intervention for periacetabular metastases. The acetabular reconstruction was performed by utilizing an acetabular reconstructive cage and cement total hip arthroplasty with microwave ablation. A retrospective review was performed to assess pain relief, intraoperative details and postoperative complications. Functional status following procedures was determined by the 1993 Musculoskeletal Tumor Society (MSTS) score and the overall survival of patients was estimated by Kaplan-Meier analysisResultsIn total, 8 males and 9 females were included with an average age of 48.6 years (range 34-66). Patients reported a significant improvement in the level of pain and the mean VAS score declined from 7.7 preoperatively to 2.2 postoperatively. Of the 17 patients, 16 could ambulate either independently (6 patients) or using a walking aid (10 patients) with a mean MSTS score of 18.9. The median follow‐up was 9.0 months. Nine patients were alive at the most recent follow-up with overall survival of 40.9% at 12 months and 30.7% at 36 months, respectively.ConclusionIn selected patients with periacetabular metastasis, the utilization of an acetabular cage and cement total hip arthroplasty presents a less invasive reconstruction technique. The incorporation of adjuvant microwave ablation has shown promise in providing long-lasting pain relief, reducing intraoperative bleeding, and improving local tumor control. However, further research and extended follow-up are necessary to establish the effectiveness of this procedure.

Urologic malignancies, characterized by their high aggressiveness and metastatic potential, pose a significant public health challenge globally. Ferroptosis, a novel mode of cell death, typically arises from intracellular iron ion overload and the accumulation of lipid peroxides. This process has been shown to play a crucial regulatory role in various pathological conditions, particularly in cancer, including urologic cancers. However, the comprehensive regulatory mechanisms underlying ferroptosis remain poorly understood, which somewhat limits its broader application in cancer therapy. Non-coding RNAs (ncRNAs), which encompass microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are non-coding transcripts that play pivotal roles in various physiological processes, such as proliferation, differentiation, apoptosis, and cell cycle regulation, by modulating the expression of target genes. The biological functions and potential regulatory mechanisms of ncRNAs in the context of cancer-related ferroptosis have been partially elucidated. Research indicates that ncRNAs can influence the progression of urologic cancers by affecting cell proliferation, migration, and drug resistance through the regulation of ferroptosis. Consequently, this review aims to clarify the functions and mechanisms of the ncRNA-ferroptosis axis in urologic cancers and to evaluate the clinical significance of ferroptosis-related ncRNAs, thereby providing new insights into cancer biology and therapeutic strategies that may ultimately benefit a diverse range of cancer patients.

IntroductionSARS-CoV-2 pandemic has presented a significant threat to global health and the economy, necessitating urgent efforts to develop effective antiviral drugs. The main protease (3CLpro) of SARS-CoV-2 is a critical target for antiviral therapy due to its essential role in viral replication.MethodsIn order to find new structural types of 3CLpro inhibitors to facilitate the solution to the problem of new virus resistance. Six potential pharmacologically bioactive compounds were identified by utilizing structure-based virtual screening and in vitro assays from the Topscience database containing 10 million compounds.Results and DiscussionAmong these, compounds 34 and 36 exhibited potent inhibitory activity with IC50 values of 6.12 ± 0.42 μM and 4.47 ± 0.39 μM, respectively. To elucidate their binding mechanisms with 3CLpro, all-atom molecular dynamics (MD) simulations were conducted. Principal component analysis (PCA), free energy landscapes (FEL) and dynamic cross-correlation maps (DCCM) revealed that the binding of compounds 34 and 36 to 3CLpro significantly enhanced the structural stability of 3CLpro, reducing conformational flexibility and internal motions. The results of protein-ligand interaction showed that compounds 34 and 36 formed strong and stable interactions to key residues at active site of 3CLpro with different binding modes from S-217622. And HOMO-LUMO gap and molecular electrostatic potential distribution revealed the quantum chemical properties of compounds 34 and 36. These findings suggested that compounds 34 and 36 can be as novel SARS-CoV-2 3CLpro inhibitors and promising lead-like drug candidates for developing COVID-19 treatments.

IntroductionMetabolic dysfunction-associated steatotic liver disease (MASLD) is a major public health concern that is exacerbated by the obesity pandemic. Dietary interventions have the potential to alleviate obesity-associated MASLD through variable mechanisms, including optimizing the gut microbiota. Previously, we reported that soy protein concentrate (SPC) with low or high levels of isoflavone (LIF or HIF) protected young obese Zucker rats from developing liver steatosis. The current study was designed to test whether SPC-LIF and SPC-HIF diets would reverse liver steatosis and alter fecal microbial composition in adult obese Zucker rats with existing steatosis.MethodsSix-week-old male obese Zucker rats (n = 26) were fed a casein control diet (CAS) for 8 weeks and 7 rats were randomly selected and sacrificed to confirm liver steatosis. The remaining rats were randomly assigned to receive CAS, SPC-LIF, or SPC-HIF diet (n = 6–7/group) for an additional 10 weeks.ResultsCompared to CAS diet, feeding SPC-LIF and SPC-HIF diets resulted in significantly lower liver weight, liver steatosis score, and liver microvesicular score (p < 0.05), but did not lead to difference in body weight, liver macrovesicular score, serum ALT, or serum AST. Isoflavone levels (e.g., LIF vs. HIF) did not affect any of these measurements except in the SPC-HIF group, which had an additional decrease in liver weight (p < 0.05) compared to the SPC-LIF group. The SPC-HIF group also had significantly higher levels of the aglycone forms of daidzein, genistein, and equol as well as the total levels of daidzein, genistein, and equol compared to SPC-LIF or CAS diet fed rats (p < 0.05). The distribution of microbial communities based on measures of beta diversity of both SPC-LIF and SPC-HIF groups were significantly different to that of the CAS group (p ≤ 0.005). Alpha-diversity did not differ between any of the groups.ConclusionTaken together, dietary soy protein can reverse liver steatosis in adult Zucker rats, and the reversal of steatosis is accompanied by alterations in gut microbial composition.

The volumetric efficiency of the hydrogen circulation pump (HCP) is mainly affected by the amount of leakage in working clearances. Studying the leakage characteristics of working clearances is of great significance for optimizing the performance of the HCP. Therefore, this paper developed a three-blade elliptical conjugate rotor HCP, and compared the results of experiments and simulations for different working conditions. On this basis, the flow rate, pressure, and internal flow field changes of radial clearance models and axial clearance models with four different scales of 0.1mm, 0.14mm, 0.18mm, and 0.22 mm were studied. The results indicate that: under four different pressure ratios and rotational speeds, the simulation results using the overlapping grid method showed a maximum difference of 4.17% compared to the experimental results, verifying the reliability of the simulation calculation method; the average flow rate of the HCP is linearly inversely proportional to both the radial clearance and the axial clearance, with a decrease rate of 11.6 Nm3/h and 5.8 Nm3/h as the clearance size increases by 0.04 mm; the radial clearance leakage of the same size is higher than the axial clearance, the leakage value in the radial clearance between the rotors is higher than that between the rotor and the pump casing, and the internal leakage of axial clearance is not evenly distributed, with higher leakage value in the middle area than that in the left and right areas.

PurposeThe overall survival of patients with pancreatic cancer is extremely low. We aimed to establish machine learning (ML) based model to accurately predict three-year survival and prognosis of pancreatic cancer patients.MethodsWe analyzed pancreatic cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2021. Univariate and multivariate logistic analysis were employed to select variables. Recursive Feature Elimination (RFE) method based on 6 ML algorithms was utilized in feature selection. To construct predictive model, 13 ML algorithms were evaluated by area under the curve (AUC), area under precision-recall curve (PRAUC), accuracy, sensitivity, specificity, precision, cross-entropy, Brier scores and Balanced Accuracy (bacc) and F Beta Score (fbeta). An optimal ML model was constructed to predict three-year survival, and the predictive results were explained by SHapley Additive exPlanations (SHAP) framework. Meanwhile, 101 ML algorithm combinations were developed to select the best model with highest C-index to predict prognosis of pancreatic cancer patients.ResultsA total of 20,064 pancreatic cancer patients from SEER database was consecutively enrolled. We utilized eight clinical variables to establish prediction model for three-year survival. CatBoost model was selected as the best prediction model, and AUC was 0.932 [0.924, 0.939], 0.899 [0.873, 0.934] and 0.826 [0.735, 0.919] in training, internal test and external test sets, with 0.839 [0.831, 0.847] accuracy, 0.872 [0.858, 0.887] sensitivity, 0.803 [0.784, 0.825] specificity and 0.832 [0.821, 0.853] precision. Surgery type had the greatest effects on three-year survival according to SHAP results. For prognosis prediction, “RSF+GBM” algorithm was the best prognostic model with C-index of 0.774, 0.722 and 0.674 in training, internal test and external test sets.ConclusionsOur ML models demonstrate excellent accuracy and reliability, offering more precise personalized prognostic prediction to pancreatic cancer patients.

ObjectivesDespite the evident potential benefits of engaging in physical activity (PA) for older adults with subjective cognitive decline (SCD), their PA levels remains low. Previous research has predominantly focused on PA behaviors in individuals with dementia/mild cognitive impairment, with limited attention given to those with SCD. Therefore, this study aims to identify key factors influencing PA behavior in older adults with SCD based on the Self-Determination Theory (SDT) and the capability-opportunity-motivation (COM-B) model.MethodsThree hundred and three individuals aged 60 and above with SCD participated in this study. A face-to-face structured questionnaire survey was conducted. Data were analyzed using Structural Equation Modeling (SEM) and Fuzzy Set Qualitative Comparative Analysis (fsQCA).ResultsSEM results indicate that PA social support primarily influences PA behavior through three indirect pathways: the separate mediating effect of basic psychological needs, the separate mediating effect of motivation, and the chained mediating effect of both. Physical literacy, on the other hand, influences PA behavior through the separate mediating effect of motivation. Necessary conditions analysis by fsQCA reveals that no single factor is necessary for promoting PA behavior in older adults with SCD, while sufficiency analysis identifies four different combinations of factors leading to PA behavior.ConclusionThe model derived from the framework of SDT and the COM-B model effectively explains and predicts the interrelationships among variables. Physical activity behavior in older individuals with SCD is the result of multifactorial synergies.

IntroductionWith the rapid development of digital agriculture, digitalization has gradually become a key factor affecting the resilience of China’s pig farming industry.MethodsFrom both the test results and the theoretical point of view, the individual fixed-effect model is more suitable for this paper’s study. Therefore, based on the panel data of 31 provinces in China from 2011 to 2022, this study constructs an individual fixed-effect model to examine how digitization affects the resilience of China’s pig farming industry.Results and discussionThe findings indicated that digitization significantly enhanced the resilience of China’s hog breeding industry, especially in potential growth areas. Improving breeding technology and scale is a crucial avenue for digitalization to bolster the industry’s resilience. Digitalization exerts a double threshold effect on the industry’s resilience, with its promotional impact only realized within a specific range. The article proposes policy suggestions, such as strengthening infrastructure construction and giving play to regional advantages.

BackgroundImage-guided surgical navigation systems are widely regarded as the benchmark for computer-assisted surgical robotic platforms, yet a persistent challenge remains in addressing intraoperative image drift and mismatch. It can significantly impact the accuracy and precision of surgical procedures. Therefore, further research and development are necessary to mitigate this issue and enhance the overall performance of these advanced surgical platforms.ObjectiveThe primary objective is to improve the precision of image guided puncture navigation systems by developing a computed tomography (CT) and structured light imaging (SLI) based navigation system. Furthermore, we also aim to quantifying and visualize intraoperative image drift and mismatch in real time and provide feedback to surgeons, ensuring that surgical procedures are executed with accuracy and reliability.MethodsA CT-SLI guided orthopedic navigation puncture system was developed. Polymer bandages are employed to pressurize, plasticize, immobilize and toughen the surface of a specimen for surgical operations. Preoperative CT images of the specimen are acquired, a 3D navigation map is reconstructed and a puncture path planned accordingly. During surgery, an SLI module captures and reconstructs the 3D surfaces of both the specimen and a guiding tube for the puncture needle. The SLI reconstructed 3D surface of the specimen is matched to the CT navigation map via two-step point cloud registrations, while the SLI reconstructed 3D surface of the guiding tube is fitted by a cylindrical model, which is in turn aligned with the planned puncture path. The proposed system has been tested and evaluated using 20 formalin-soaked lower limb cadaver specimens preserved at a local hospital.ResultsThe proposed method achieved image registration RMS errors of 0.576 ± 0.146 mm and 0.407 ± 0.234 mm between preoperative CT and intraoperative SLI surface models and between preoperative and postoperative CT surface models. In addition, preoperative and postoperative specimen surface and skeletal drifts were 0.033 ± 0.272 mm and 0.235 ± 0.197 mm respectively.ConclusionThe results indicate that the proposed method is effective in reducing intraoperative image drift and mismatch. The system also visualizes intraoperative image drift and mismatch, and provides real time visual feedback to surgeons.

IntroductionEpidemiological studies have assessed the correlation between daily dietary branch chain amino acid (BCAA) intakes and the risk of obesity, however, the findings from these studies were inconsistent and investigations among GDM women were few.ObjectiveThe present study was to investigate the associations of daily BCAA intakes with the risks of overweight and abdominal obesity among women with prior gestational diabetes mellitus (GDM) postpartum.MethodWe performed a cross-sectional study of 1,263 women with prior GDM at 1–5 years post-delivery. Logistic regression models were used to estimate the associations of daily dietary intakes of BCAAs with the risks of overweight and abdominal obesity.ResultsThe multivariable-adjusted odds ratios (ORs) across quartiles of daily BCAA intakes postpartum were 1.42 (95% confidence interval [CI] 1.02–1.97), 1.00 (reference), 1.21 (95% CI 0.88–1.68), and 1.31 (95% CI 0.95–1.81) for general overweight, and 1.38 (95% CI 0.99–1.90), 1.00, 1.19 (95% CI 0.86–1.64), and 1.43 (95% CI 1.04–1.98) for abdominal obesity, respectively. Women with the lowest quartile of daily BCAA intakes significantly increased the risks of general overweight (OR 1.49; 95 %CI 1.06–2.09) and abdominal obesity (OR 1.50; 95 %CI 1.08–2.11) compared with women at quartile 2 of daily BCAA intakes after further adjustment of daily energy intake.ConclusionThe present study indicated that daily lower BCAA intakes were associated with increased risks of general overweight and abdominal obesity among women with prior GDM.

BackgroundPatients with unruptured intracranial aneurysms (UIAs) often experience emotional changes and cognitive impairments. However, the specific mechanisms underlying these impairments are still not fully understood.MethodsIn the present study, voxel-based morphometry (VBM) and surface-based morphometry (SBM) were employed to investigate structural alterations in 49 patients diagnosed with UIAs compared with 50 healthy controls. Additionally, this study aimed to analyze the correlations among cortical morphological indices, cerebral blood perfusion values and neuropsychological test results.ResultsCompared with control group, UIA patients exhibited increased gray matter volume in the right anterior orbitofrontal cortex and decreased gray matter volume in the left thalamus pulvinar and hippocampus. Furthermore, the fractal dimension was lower in the right postcentral gyrus and entorhinal cortex. The cerebral perfusion values in the abnormal brain regions demonstrated a downward trend, which was associated with a reduction in gray matter volume in the left thalamus pulvinar and hippocampus, elevated anxiety levels and impaired executive function.ConclusionUIA patients are prone to cognitive impairment and emotional dysregulation, which are accompanied by subtle changes in local gray matter volume and decreases in fractal dimension and cerebral blood flow. These findings provide new insights into the potential mechanisms underlying the cognitive impairment observed in UIA patients.

IntroductionThis study addresses the challenge of active power (AP) balance control in wind-photovoltaic-storage (WPS) power systems, particularly in regions with a high proportion of renewable energy (RE) units. The goal is to effectively manage the AP balance to reduce the output of thermal power generators, thereby improving the overall efficiency and sustainability of WPS systems.MethodsTo achieve this objective, we propose the transfer learning double deep Q-network (TLDDQN) method for controlling the energy storage device within WPS power systems. The TLDDQN method leverages the benefits of transfer learning to quickly adapt to new environments, thereby enhancing the training speed of the double deep Q-network (DDQN) algorithm. Additionally, we introduce an adaptive entropy mechanism integrated with the DDQN algorithm, which is further improved to enhance the training capability of agents.ResultsThe proposed TLDDQN algorithm was applied to a regional WPS power system for experimental simulation of AP balance control. The results indicate that the TLDDQN algorithm trains agents more rapidly compared to the standard DDQN algorithm. Furthermore, the AP balance control method based on TLDDQN can more accurately manage the storage device, thereby reducing the output of thermal power generators more effectively than the particle swarm optimization-based method.DiscussionOverall, the TLDDQN algorithm proposed in this study can provide some insights and theoretical references for research in related fields, especially those requiring decision making.

Timely and accurate monitoring of typical coastal targets using remote sensing technology is crucial for maintaining marine ecological stability. Hyperspectral target detection technology proves to be an effective tool in extracting various typical materials along the coastline. Traditional target detection methods using spectral domain information can effectively retain the intrinsic properties of the material. However, it is difficult to effectively recognize targets in homogeneous regions by using only spectral domain information, which may lead to insufficient utilization of spatial information. In this study, a detector based on signal-to-noise ratio fusion constrained energy minimization with low-rank sparse decomposition (SFLRSD) is proposed. This detector improves the separability of background and target by obtaining spatial domain information from hyperspectral images and fusing spectral domain information. First, total variation regularization and fractional Fourier transform are applied to process spatial and spectral domain information, respectively. The constrained energy minimization (CEM) detector is used to improve the separability between the target and background of the processed data. Then, the background and anomalies are represented as low-rank and sparse components, respectively, using low-rank sparse matrix factorization. This transforms the model solution into a covariance matrix problem, which is then solved using marginal distance difference (MDD) to isolate anomalous parts. Subsequently, the anomaly parts are fused with CEM detector results, weighted by their respective signal-to-noise ratios. This detection model leverages unified hyperspectral image features, enhancing spectral discreteness of anomalous targets and backgrounds. Finally, experiments on custom created hyperspectral dataset show that the proposed method outperforms other baseline methods in terms of visualization and quantitative performance. In this paper, we not only propose a new hyperspectral target detection method, but we also collect three typical marine litter of different materials by means of airborne hyperspectral remote sensing and construct four hyperspectral datasets in a real environment. All the simulation experiments in this paper are conducted in these four datasets.

BackgroundWhile hilar cholangiocarcinoma (HCCA) patients commonly undergo radioactive stent (RS) insertion treatment, the relative benefits of unilateral versus bilateral RS insertion procedures remain to be established. Accordingly, this study was designed to evaluate the relative safety and efficacy of percutaneous bilateral and unilateral RS insertion for patients with HCCA.MethodsIn total, 126 HCCA patients who underwent unilateral (n=64) or bilateral (n=62) RS insertion from January 2017 - December 2021 were included in this analysis. Treatment efficacy and long-term outcomes were compared between groups. The primary endpoint was stent patency, and the secondary endpoints included technical success rate, clinical success rate, local control rate, overall survival (OS), and complications.ResultsThe respective technical success rates in the unilateral and bilateral groups were 90.6% (58/64) and 93.5% (58/62) (P = 0.782). The clinical success rates were 82.8% and 86.2% in unilateral and bilateral groups, respectively (P = 0.608). Both groups exhibited comparable medial post-intervention bilirubin levels (100 vs. 99 μmol/L; P = 0.501), and restenosis occurred in 12 (20.7%) and 15 (25.9%) patients over the follow-up interval (P = 0.510). The stent reintervention rate was significantly higher in the unilateral group than bilateral group (66.7% vs. 0.0%, P < 0.001). The median stent patency in the unilateral and bilateral groups was 189 and 210 days, respectively (P = 0.796), while the median OS interval was 222 and 229 days, respectively (P = 0.969). Comparable cholangitis (17.2% vs. 22.4%, P = 0.485) and cholecystitis (3.4% vs. 3.4%, P = 1.000) rates were also detected in these two groups.ConclusionsIn summary, HCCA patients exhibit comparable efficacy when undergoing unilateral and bilateral radioactive stenting, suggesting that unilateral RS can be routinely performed owing to the simpler nature of this procedure.

BackgroundSystem coordination is an effective way to achieve high-quality development, and the debate on the interaction between health investment and economic development is still ongoing. To strengthen previous research and offer feasible advice and references for relevant stakeholders, we provide empirical evidence for exploring intersystem coordination and enhancement pathways using data from China.MethodsBased on the data published by the National Bureau of Statistics of China, the current status of the interaction and coordination between health investment and economic development in China was measured by calculating the comprehensive evaluation index, relative development degree, and coupling coordination degree. Subsequently, a fuzzy-set qualitative comparative analysis method was introduced to explore pathways for enhancing system interaction and coordination.ResultsThere are obvious inter-provincial and regional differences between health investment and economic development in China. Provinces in the west and north are lagging in economic development, while provinces in the east and south are lagging in health investment. There is a clear synergy between health investment and economic development, and there is still much room for improving the degree of coupling coordination between systems. The five conditional configurations derived from the fuzzy-set qualitative comparative analysis yield three pathways for enhancing system coordination: a health expenditure-driven path, an economic development-driven path, and a balanced health investment and economic development-driven path.ConclusionHealth expenditure is sufficient for high coordination, and the level and equity of investment in health expenditure should be improved. The gross regional product is a necessary and sufficient condition for high coordination, and consideration must be given to strengthening the regional economic support capacity. Health investment and economic development can drive the coordinated development of the system in a balanced way. This enlightens us to give full play to the positive synergy between health investment and economic development based on promoting the benign interaction of subsystems.

ObjectiveTo investigate the dynamic changes of perioperative deep venous thrombosis (DVT) in patients with spinal cord injury complicated with cervical fracture and analyze the risk factors of postoperative DVT exacerbation or new DVT.MethodsFrom January 2018 to December 2023, a total of 232 patients with spinal cord injury complicated with cervical fracture in our hospital were retrospectively analyzed. Ultrasonography of both lower limbs was performed before and after surgery. According to whether there was aggravation of DVT or new thrombosis, the group was divided into DVT exacerbation or new DVT group and non-DVT exacerbation group. Clinical data were used to study the dynamic changes of perioperative DVT. Logistic regression analysis and receiver operating characteristic (ROC) curve were used to explore the risk factors.ResultsThe DVT was found in 47 patients before surgery, including 26 cases of distal thrombus, 14 cases of mixed thrombus and 7 cases of proximal thrombus. Postoperative DVT increased to 81, including 31 distal thrombus, 35 mixed thrombus and 15 proximal thrombus. A total of 53 patients (22.8%, 53/232) experienced postoperative DVT exacerbation or new DVT. Logistic regression analysis revealed that age, American Spinal Injury Association (ASIA) score, time from injury to surgery, surgery time and blood loss were risk factors for postoperative DVT exacerbation.ConclusionsIn patients with spinal cord injury complicated with cervical fracture, the risk of postoperative DVT exacerbation is very high. Age, ASIA score A-B, time from injury to surgery, surgery time and blood loss were risk factors for postoperative DVT exacerbation or new DVT.

The ketogenic diet (KD) is a popular option for managing body weight, though its influence on glucose and lipid metabolism was still inconclusive. Gut microbiota is modulated by dietary pattens and has been associated with the changes of metabolic homeostasis induced by KD. Here, we found that two types of KDs, KD1 (8.8% carbohydrate, 73.4% fat, 17.9% protein, 5.7 kcal/g) and KD2 (0.4% carbohydrate, 93.2% fat, 6.4% protein, 6.7 kcal/g), induced changes of gut microbiota and its metabolites, contributing to glucose intolerance but not lipid accumulation in mice. Following a 2-week intervention with KDs, mice fed on KD1 displayed symptoms related to obesity, whereas KD2-fed mice exhibited a decrease in body weight but had severe hepatic lipid accumulation and abnormal fatty acid metabolism, while both KDs led to significant glucose intolerance. Compared to the mice fed on a standard chow diet, the conventional mice fed on both KD1 and KD2 had significant shifted gut microbiota, lower levels of short chain fatty acids (SCFAs) and composition alteration of cecal bile acids. By using an antibiotic cocktail (ABX) to deplete most of the gut microbiota in mice, we found the disturbances induced by KDs in lipid metabolism were similar in the ABX-treated mice to their conventional companions, but the disturbances in glucose metabolism were absent in the ABX-treated mice. In conclusion, these findings suggest that ketogenic diets disrupted glucose and lipid metabolism, at least in mice, and highlight the gut microbial culprits associated with KD induced glucose intolerance rather than lipid accumulation.

Whole-genome bisulfite sequencing (WGBS) has been extensively utilized for DNA methylation profiling over the past decade. However, it has shown limitations in terms of high costs and inefficiencies. The productivity and accuracy of DNA methylation detection rely critically on the optimization of methodologies and the continuous refinements of related sequencing platforms. Here, we describe a detailed protocol of guide positioning sequencing (GPS), a bisulfite-based, location-specific sequencing technology designed for comprehensive DNA methylation characterization across the genome. The fundamental principle of GPS lies in the substitution of dCTP with 5-methyl-dCTP (5 mC) at the 3′-end of DNA fragments by T4 DNA polymerase, which protects cytosines from bisulfite conversion to preserve the integrity of the base composition. This alteration allows the 3′-end to independently facilitate genetic variation profiling and guides the 5′-end, enriched with methylation information, to align more rapidly to the reference genome. Hence, GPS enables the concurrent detection of both genetic and epigenetic variations. Additionally, we provide an accessible description of the data processing, specifically involving certain software and scripts. Overall, the entire GPS procedure can be completed within a maximum of 15 days, starting with a low initial DNA input of 100–500 ng, followed by 4–5 days for library construction, 8–10 days for high-throughput sequencing (HTS) and data analysis, which can greatly facilitate the promotion and application of DNA methylation detection, especially for the rapid clinical diagnosis of diverse disease pathologies associated with concurrent genetic and epigenetic variations.

ObjectiveThe aim of this study was to develop and validate a machine learning-based model to predict the development of impaired fasting glucose (IFG) in middle-aged and older elderly people over a 5-year period using data from a cohort study.MethodsThis study was a retrospective cohort study. The study population was 1855 participants who underwent consecutive physical examinations at the First Affiliated Hospital of Soochow University between 2018 and 2022.The dataset included medical history, physical examination, and biochemical index test results. The cohort was randomly divided into a training dataset and a validation dataset in a ratio of 8:2. The machine learning algorithms used in this study include Extreme Gradient Boosting (XGBoost), Support Vector Machines (SVM), Naive Bayes, Decision Trees (DT), and traditional Logistic Regression (LR). Feature selection, parameter optimization, and model construction were performed in the training set, while the validation set was used to evaluate the predictive performance of the models. The performance of these models is evaluated by an area under the receiver operating characteristic (ROC) curves (AUC), calibration curves and decision curve analysis (DCA). To interpret the best-performing model, the Shapley Additive exPlanation (SHAP) Plots was used in this study.ResultsThe training/validation dataset consists of 1,855 individuals from the First Affiliated Hospital of Soochow University, yielded significant variables following selection by the Boruta algorithm and logistic multivariate regression analysis. These significant variables included systolic blood pressure (SBP), fatty liver, waist circumference (WC) and serum creatinine (Scr). The XGBoost model outperformed the other models, demonstrating an AUC of 0.7391 in the validation set.ConclusionsThe XGBoost model was composed of SBP, fatty liver, WC and Scr may assist doctors with the early identification of IFG in middle-aged and elderly people.

IntroductionSepsis poses a serious threat to individual life and health. Early and accessible diagnosis and targeted treatment are crucial. This study aims to explore the relationship between microbes, metabolic pathways, and blood test indicators in sepsis patients and develop a machine learning model for clinical diagnosis.MethodsBlood samples from sepsis patients were sequenced. α-diversity and β-diversity analyses were performed to compare the microbial diversity between the sepsis group and the normal group. Correlation analysis was conducted on microbes, metabolic pathways, and blood test indicators. In addition, a model was developed based on medical records and radiomic features using machine learning algorithms.ResultsThe results of α-diversity and β-diversity analyses showed that the microbial diversity of sepsis group was significantly higher than that of normal group (p < 0.05). The top 10 microbial abundances in the sepsis and normal groups were Vitis vinifera, Mycobacterium canettii, Solanum pennellii, Ralstonia insidiosa, Ananas comosus, Moraxella osloensis, Escherichia coli, Staphylococcus hominis, Camelina sativa, and Cutibacterium acnes. The enriched metabolic pathways mainly included Protein families: genetic information processing, Translation, Protein families: signaling and cellular processes, and Unclassified: genetic information processing. The correlation analysis revealed a significant positive correlation (p < 0.05) between IL-6 and Membrane transport. Metabolism of other amino acids showed a significant positive correlation (p < 0.05) with Cutibacterium acnes, Ralstonia insidiosa, Moraxella osloensis, and Staphylococcus hominis. Ananas comosus showed a significant positive correlation (p < 0.05) with Poorly characterized and Unclassified: metabolism. Blood test-related indicators showed a significant negative correlation (p < 0.05) with microorganisms. Logistic regression (LR) was used as the optimal model in six machine learning models based on medical records and radiomic features. The nomogram, calibration curves, and AUC values demonstrated that LR performed best for prediction.DiscussionThis study provides insights into the relationship between microbes, metabolic pathways, and blood test indicators in sepsis. The developed machine learning model shows potential for aiding in clinical diagnosis. However, further research is needed to validate and improve the model.

The autophagy-lysosome pathway plays an essential role in promoting lipid catabolism and preventing hepatic steatosis in non-alcoholic fatty liver disease (NAFLD). Transcription factor EB (TFEB) enhances the autophagy-lysosome pathway by regulating the expression of genes related to autophagy and lysosome biogenesis. Therefore, targeting TFEB provides a novel strategy for the treatment of lipid metabolic diseases. In this study, the antiallergic drug desloratadine was screened and identified as a novel TFEB agonist. Desloratadine effectively induced translocation of TFEB to the nucleus and promoted autophagy and lysosome biogenesis. Desloratadine-induced TFEB activation was dependent on AMPK rather than mTORC1. Moreover, desloratadine treatment enhanced clearance of lipid droplets in cells induced by fatty acids oleate and palmitate. Furthermore, high-fat diet (HFD) induced obesity mouse model experiments indicated treatment with desloratadine markedly reduced the body weight of HFD-fed mice, as well as the levels of hepatic triglycerides and total cholesterol, serum glutamic pyruvic transaminase and glutamic-oxaloacetic transaminase. Oil red O staining showed the liver fat was significantly reduced after desloratadine treatment, and H&E staining analysis demonstrated hepatocellular ballooning was improved. In addition, autophagy and lysosomal biogenesis was stimulated in the liver of desloratadine treated mice. Altogether, these findings demonstrate desloratadine ameliorates hepatic steatosis through activating the TFEB-mediated autophagy-lysosome pathway, thus desloratadine has an exciting potential to be used to treat fatty liver disease.

BackgroundInterleukin-1 receptor-associated kinase 3 (IRAK3) modulates neuroinflammation. This study aimed to determine the prognostic role of serum IRAK3 in acute intracerebral hemorrhage (ICH).MethodsIn this prospective observational cohort study, 152 patients with supratentorial ICH, along with 63 healthy controls, were recruited. Serum IRAK3 levels were measured at the time of enrollment for controls, at admission for all patients, and on poststroke days 1, 3, 5, 7, 10, and 15 in a subset of 63 patients. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) and hematoma volume. Poststroke 6-month modified Rankin Scale (mRS) scores were registered, with scores of 3–6 representing a poor prognosis. Multivariate models were established to investigate severity correlation and prognosis association.ResultsSerum IRAK3 levels were significantly elevated at the admission of patients, peaked at day 1, plateaued at day 3, gradually declined until day 15, and were substantially higher over the first 15 days poststroke than in controls. Admission serum IRAK3 levels were independently associated with NIHSS scores, hematoma volume, and 6-month mRS scores in a multivariate linear regression model. They were linearly correlated with the risk of poor prognosis in a restricted cubic spline analysis and were independently predictive of poor prognosis in a binary logistic regression model. Additionally, they demonstrated strong prognostic ability in the receiver operating characteristic curve analysis. Using subgroup analysis, no interactions were found between admission serum IRAK3 levels and some routine variables, such as age, gender, hypertension, and diabetes mellitus. Moreover, the model combining admission serum IRAK3, NIHSS scores, and hematoma volume demonstrated stability and clinical value in calibration and decision curve analyses.ConclusionA significant increase in serum IRAK3 levels during the early phase after ICH, strongly correlated with disease severity, is independently associated with a poor 6-month prognosis, establishing serum IRAK3 as a valuable prognostic biomarker for ICH.

ObjectivesTo investigate the safety and cost analysis of oral propranolol treatment for high-risk infantile hemangiomas starting from the outpatient setting.MethodsA total of 41 high-risk infantile hemangioma patients from outpatient settings and 43 from inpatient settings were selected for the study. After routine pre-treatment examinations, patients were administered propranolol in a stepwise incremental dosing regimen over three consecutive days in the outpatient clinic. Changes in heart rate, blood pressure and PR interval before and after medication were compared. On the 10th day post-medication, liver and kidney functions, fasting blood glucose, tumor ultrasonography, and electrocardiogram were re-evaluated. The costs of treatment starting from the outpatient clinic (including pre-treatment examinations and the first three days of treatment) were calculated and compared with those of similarly managed inpatient cases.ResultsThe majority of patients exhibited a reduction in heart rate and blood pressure, as well as an extended PR interval after treatment of medication (P < 0.05), which remained within normal limits without clinical symptoms. On the 10th day post-medication, statistical differences in blood biochemistry and electrocardiograms were observed when compared to pre-treatment values (P < 0.05), but all values remained within normal ranges. No severe adverse reactions such as hypoglycemia occurred. Additionally, the cost of treatment from the outpatient clinic was significantly lower than that of inpatient care.ConclusionOral propranolol treatment for high-risk infantile hemangiomas starting from the outpatient setting is associated with few adverse reactions and significantly reduced treatment costs. It is worthy of broader application in hospitals without dermatology wards.

ObjectiveVulvar carcinoma exhibits a robust correlation alongside HPV infection; however, the impact of HPV rank on the prognostic outcomes of radiation therapy within vulvar malignancies stays ambiguous. In the present study, we performed a comprehensive examination as well as meta-analysis to assess the influence of infection with HPV upon the long-term outlook as well as sensitivity of individuals with vulvar cancer undergoing radiation therapy.MethodsA meticulous examination of the existing research was conducted in accordance with the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A thorough search was conducted in the PubMed, Embase, Web of Science, as well as Cochrane Library databases, covering the entire available literature till April 1, 2023. The studies that met the inclusion criteria contained data about HPV infection and oncological outcomes in patients with vulvar cancer who received radiation therapy. This study was registered in PROSPERO (CRD42023417957).ResultsWe identified 12 retrospective studies meeting our inclusion criteria, which included a total of 3967 patients. Patients with HPV-associated vulvar cancer achieved a better overall survival rate after radiotherapy (HR=0.71, 95%CI: 0.54-0.93, P=0.01), and showed a significant improvement in disease-free survival (HR=0.75, 95%CI: 0.58-0.97, P=0.09) and progression-free survival (HR=0.31, 95%CI: 0.22-0.45, P,

Far red photon flux accelerates photosynthetic electron transfer rates through photosynthetic pigments, influencing various biological processes. In this study, we investigated the impact of differing red and far-red light ratios on plant growth using LED lamps with different wavelengths and Ca1.8Mg1.2Al2Ge3O12:0.03Cr3+ phosphor materials. The control group (CK) consisted of a plant growth special lamp with 450 nm blue light + 650 nm red light. Four treatments were established: F1 (650 nm red light), F2 (CK + 730 nm far-red light in a 3:2 ratio), F3 (650 nm red light + 730 nm far-red light in a 3:2 ratio), and F4 (CK + phosphor-converted far-red LED in a 3:2 ratio). The study assessed changes in red and far-red light ratios and their impact on the growth morphology, photosynthetic characteristics, fluorescence characteristics, stomatal status, and nutritional quality of cream lettuce. The results revealed that the F3 light treatment exhibited superior growth characteristics and quality compared to the CK treatment. Notably, leaf area, aboveground fresh weight, vitamin C content, and total soluble sugar significantly increased. Additionally, the addition of far-red light resulted in an increase in stomatal density and size, and the F3 treatments were accompanied by increases in net photosynthetic rate (Pn), transpiration rate (Tr), intercellular CO2 concentration (Ci), and stomatal conductance (Gs). The results demonstrated that the F3 treatment, with its optimal red-to-far-red light ratio, promoted plant growth and photosynthetic characteristics. This indicates its suitability for supplementing artificial light sources in plant factories and greenhouses.

BackgroundEvidence shows that the total flavonoids of Rhizoma Drynariae (TFRD) can improve bone mineral density (BMD). However, there is no evidence to summarize the improvement of biochemical indicators of bone metabolism (BIBM).MethodsThe PubMed, Web of Science, Cochrane Library, Embase, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, Chongqing VIP Information Database (VIP) and SinoMed were searched from inception to 6 May 2024. The final included studies performed meta-analyses using RevMan 5.3.ResultsNine randomized controlled trials (RCTs) were ultimately included. The TFRD group had higher bone gla protein (BGP) and type I procollagen-N-propeptide (PINP) compared to the Other therapies (WMD: 5.11; 95% CI: 3.37, 6.84; p < 0.00001; WMD: 13.89; 95% CI: 11.81, 15.97; p < 0.00001). The tartrate-resistant acid phosphatase (TRACP) decreased significantly (WMD: −1.34; 95% CI: −1.62, −1.06; p < 0.00001). The alkaline phosphatase (ALP) increased significantly (WMD: 7.47; 95% CI: 6.29, 8.66; p < 0.00001). There were no significant differences in serum calcium (SC) or serum phosphorus (SP) levels between the TFRD and control groups (WMD: 0.08; 95% CI: −0.04, 0.20; p = 0.17; WMD: 0.02; 95% CI: −0.02, 0.05; p = 0.36).ConclusionTFRD can stimulate bone formation and prevent bone resorption in osteoporosis (OP) patients, but it has no effect on SC and SP.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/.

Ultrasound is a mechanical wave that can non-invasively penetrate the skull to deep brain regions to activate neurons. Transcranial focused ultrasound neuromodulation is a promising approach, with the advantages of noninvasiveness, high-resolution, and deep penetration, which developed rapidly over the past years. However, conventional transcranial ultrasound’s spatial resolution is low-precision which hinders its use in precision neuromodulation. Here we focus on methods that could increase the spatial resolution, gain modulation efficiency at the focal spot, and potential mechanisms of ultrasound neuromodulation. In this paper, we summarize strategies to enhance the precision of ultrasound stimulation, which could potentially improve the ultrasound neuromodulation technic.

Rapid urbanization induces significant changes in land use, exerting a profound impact on regional habitat quality. Understanding the interconnectedness of urbanization and habitat quality is crucial for safeguarding the regional ecological environment and promoting sustainable urban development. Cities along the Yangtze River, as the core region of the Yangtze River Economic Belt in China, serve as a typical and critically important area to investigate the dynamic response of habitat quality to rapid urbanization. This study employs the InVEST model and entropy method to assess the spatiotemporal dynamics of habitat quality and urbanization in Yangtze River cities. Using the coupling coordination degree model, it analyzes the interplay between urbanization and habitat quality, elucidating dynamic response patterns and emphasizing the need for pertinent policy measures. Our findings reveal that from 1990 to 2019, urbanization levels in the study area surged by over six times, while habitat quality consistently declined, reflecting a 4.5% decrease. Notably, spatial variances were observed along the upstream, midstream, and downstream segments of the river. Although an inverse relationship between urbanization and habitat quality predominates, three cities demonstrated a positive correlation. The study also indicates a stable increase in the coupling coordination degree between urbanization and habitat quality, evolving from a phase of urbanization lag to one of synchronization followed by habitat quality lag. Among the cities, Chongqing emerges as an exemplary model for the coordinated development of urbanization and habitat quality. These insights provide a theoretical foundation and policy guidance for enhancing sustainable urban and ecological strategies in the region.

AimsMesenchymal stem cells (MSCs) are key components in promoting glioblastoma (GBM) progression. This study aimed to explore new therapeutic targets and related pathogenic mechanisms based on different MSCs infiltration levels in GBM patients.MethodsWe estimated the relationship between cell infiltration and prognosis of GBM. Subsequently, key risk genes were identified and prognostic models were constructed by LASSO-Cox analysis. The risk genes were validated by five independent external cohorts, single-cell RNA analysis, and immunohistochemistry of human GBM tissues. TIDE analysis predicted responsiveness to immune checkpoint inhibitors in different risk groups.ResultsThe MSCs infiltration level was negatively associated with survival in GBM patients. LOXL1, LOXL4, and GUCA1A are key risk genes that promote GBM progression and may act through complex intercellular communication.ConclusionThis research has provided a comprehensive study for exploring the MSCs infiltration environment on GBM progression, which could shed light on novel biomarkers and mechanisms involved in GBM progression.