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Background The gradual increase in blood lipid levels is becoming a significant public health concern. The role of diet in the development of dyslipidemia is crucial. Traditional nutritional epidemiology mainly focuses on individual foods or food groups. However, in our daily lives, we do not only consume isolated nutrients or specific foods, which makes it challenging to determine the specific impact of individual dietary components on dyslipidemia. Currently, there is a lack of research both domestically and internationally that investigates the relationship between dietary patterns and dyslipidemia in the population of Southern Jiangxi (Gannan) . Objective To analyze the relationship between dietary patterns and dyslipidemia in Southern Jiangxi, with the aim of contributing to evidence-based nutritional policies. Methods Data from the Gannan chronic disease cohort 2020 survey data. A multi-stage stratified cluster random sampling method was used to select research participants among permanent residents aged 35 and above in Southern Jiangxi from July to August 2020. Demographic data were collected through standardized questionnaires and physical examinations. Fasting blood glucose and lipid levels were measured. Dietary surveys utilized a food frequency questionnaire, and patterns were identified through factor analysis. The patterns were categorized into quartiles (Q1-Q4) based on factor scores. Logistic regression was used to assess the impact of patterns on dyslipidemia. Results The study included 1 508 residents, with a prevalence of dyslipidemia of 36.07% (544/1 508). Residents who consumed adequate amounts of water, did not have a history of hypertension, and had a history of diabetes showed a higher prevalence of dyslipidemia (P

Objective: Cardiac surgeons experience unpredictable overnight operative responsibilities, with variable rest before same-day, first-start scheduled cases. This study evaluated the frequency and associated impact of a surgeon's overnight operative workload on the outcomes of their same-day, first-start operations. Methods: A statewide cardiac surgery quality database was queried for adult cardiac surgical operations between July 1, 2011, and March 1, 2021. Nonemergency, first-start, Society of Thoracic Surgeons predicted risk of mortality operations were stratified by whether or not the surgeon performed an overnight operation that ended after midnight. A generalized mixed effect model was used to evaluate the effect of overnight operations on a Society of Thoracic Surgeons composite outcome (5 major morbidities or operative mortality) of the first-start operation. Results: Of all first-start operations, 0.4% (239/56,272) had a preceding operation ending after midnight. The Society of Thoracic Surgeons predicted risk of morbidity and mortality was similar for first-start operations whether preceded by an overnight operation or not (overnight operation: 11.3%; no overnight operation: 11.7%, P = .42). Unadjusted rates of the primary outcome were not significantly different after an overnight operation (overnight operation: 13.4%; no overnight operation: 12.3%, P = .59). After adjustment, overnight operations did not significantly impact the risk of major morbidity or mortality for first-start operations (adjusted odds ratio, 1.1, P = .70). Conclusions: First-start cardiac operations performed after an overnight operation represent a small subset of all first-start Society of Thoracic Surgeons predicted risk operations. Overnight operations do not significantly influence the risk of major morbidity or mortality of first-start operations, which suggests that surgeons exercise proper judgment in determining appropriate workloads.

Abstract Exosomes play a crucial role in intercellular communication and can be used as biomarkers for diagnostic and therapeutic clinical applications. However, systematic studies in cancer-associated exosomal nucleic acids remain a big challenge. Here, we developed ExMdb, a comprehensive database of exosomal nucleic acid biomarkers and disease-gene associations curated from published literature and high-throughput datasets. We performed a comprehensive curation of exosome properties including 4,586 experimentally supported gene-disease associations, 13,768 diagnostic and therapeutic biomarkers, and 312,049 nucleic acid subcellular locations. To characterize expression variation of exosomal molecules and identify causal factors of complex diseases, we have also collected 164 high-throughput datasets, including bulk and single-cell RNA sequencing (scRNA-seq) data. Based on these datasets, we performed various bioinformatics and statistical analyses to support our conclusions and advance our knowledge of exosome biology. Collectively, our dataset will serve as an essential resource for investigating the regulatory mechanisms of complex diseases and improving the development of diagnostic and therapeutic biomarkers.

Objective: Professional standards recommend stopping cardiotomy suction at the termination of cardiopulmonary bypass before protamine administration based on perceived safety concerns. This study evaluated a multidisciplinary collaborative quality-improvement intervention promoting this agreed-upon cardiotomy suction practice during coronary artery bypass grafting (CABG). Methods: A statewide intervention (eg, unblinded surgeon and perfusionist feedback, evidence-based lectures, evaluating barriers to change) involved 32 centers participating in the PERForm (ie, Perfusion Measures and Outcomes) Registry to standardize cardiotomy suction practices at cardiopulmonary bypass termination during CABG. Four non-Michigan registry participating centers were not exposed to collaborative learning. Cardiotomy suction practice was defined as the absence of or stopping cardiotomy suction before protamine administration. The practice changes attributed to the intervention, including Michigan and non-Michigan comparisons, were evaluated with the change of time effect modeled using splines. Multivariable regression was used to evaluate the intervention's associated impact (eg, mortality, reoperation, transfusion). Results: Among 10,394 patients undergoing CABG at Michigan centers, 80.7% achieved agreed-upon cardiotomy suction practices. The Michigan centers had nonsignificant changes in agreed-upon cardiotomy suction practices during the preintervention period (P = .24), with significant increased monthly change in practice thereafter, absent adjusted morbidity and mortality increases. The Michigan centers achieved a significantly greater adjusted monthly improvement in agreed-upon practices relative to non-Michigan centers within 7 months after the intervention (adjusted odds ratio for change of trends: 2.53, P

Objective: The incidence of Crohn's disease (CD) and rheumatoid arthritis (RA) co-morbidity, as well as the number of individuals affected, is on the rise due to their shared molecular and cellular factors. This study aimed to identify potential therapeutic targets and medicines for comorbid CD and RA. Methods: We integrated single-cell RNA sequencing, Mendelian randomization, and colocalization analysis results from public databases to analyse immune cell subgroups in CD and RA patients and identify candidate therapeutic targets. We further screened potential medicines for the identified candidate targets using the Comparative Toxicogenomics Database (CTD) and molecular docking and molecular dynamics simulations. Results: The proportion of CD8 effector memory T cells (Tem) was consistently elevated in the peripheral blood mononuclear cells (PBMCs) of both CD and RA patients. MYBL1 had a causal effect on the onset of both CD (OR = 1.23; 95 % CI, 1.05–1.45; P = 0.046) and RA (OR = 1.45; 95 % CI, 1.14–1.85; P = 0.04). Four potential therapeutic molecules were retrieved from the CTD database, among which tretinoin (docking score: −6.3 kcal/mol) showed the best potential. Conclusion: Our comprehensive analysis suggests that CD8 Tem cells are a key cell group in comorbid RA and CD and that MYBL1 has a causal effect. Tretinoin was identified as a potential targeted therapeutic drug, which is of great clinical research value.

Abstract Background Numerous studies have demonstrated that brain metastases patients may benefit from intracranial radiotherapy combined with immune checkpoint inhibitors (ICIs). However, it is unclear whether this treatment is effective for patients with small cell lung cancer brain metastases (SCLC‐BMs). Methods We conducted a retrospective study by analyzing medical records of patients with SCLC‐BMs from January 1, 2017 to June 1, 2022. Data related to median overall survival (mOS), median progression‐free survival (mPFS), and intracranial progression‐free survival (iPFS) were analyzed. Results A total of 109 patients were enrolled, of which 60 received WBRT and 49 received WBRT‐ICI. Compared to the WBRT alone cohort, the WBRT‐ICI cohort showed longer mOS (20.4 months vs. 29.3 months, p = 0.021), mPFS (7.9 months vs. 15.1 months, p

Objective: This study evaluated interhospital variability and determinants of failure-to-rescue for patients undergoing surgical aortic valve replacement. Methods: An observational study was conducted among 28,842 patients undergoing aortic valve replacement with or without coronary artery bypass grafting between July 2011 and June 2017 across 90 hospitals participating in the Society of Thoracic Surgeons Adult Cardiac Surgery Database. Postoperative complications were defined as major (stroke, renal failure, reoperation, prolonged ventilation, sternal infection) and overall (major plus 14 other morbidities). Hospital terciles of observed to expected (O/E) mortality were compared on crude rates of major and overall complications, operative mortality, and failure to rescue (among major and overall complications). The correlation between hospital observed and expected failure-to-rescue rates was assessed. Results: Median Society of Thoracic Surgeons Adult Cardiac Surgery Database predicted mortality risk was similar across hospital O:E mortality terciles (P = .10). As expected, mortality rates significantly increased across terciles (low O/E tercile: 1.6%, high O/E tercile: 4.7%; P

Abstract Background Complement component 3a and its receptor (C3a/C3aR) and the nucleotide-binding oligomerization domain-like receptor protein-3 (NLRP3) inflammasome contribute to epithelial-mesenchymal transition (EMT). However, the relationship between C3a/C3aR and the NLRP3 inflammasome in EMT remains unclear. This study aimed to elucidate the roles of C3a/C3aR and the NLRP3 inflammasome involved in TGF-β-induced EMT. Method Mouse renal tubular epithelial cells (TCMK-1) were exposed to C3a and TGF-β for 48 h. C3aR antagonist, MCC950, an inhibitor of the NLRP3 inflammasome and PD98059, an inhibitor of ERK signaling, were respectively applied to pretreat the cells at 30 min before C3a and TGF-β administration.The cells were collected for western blot, immunofluorescence staining and ELISA. Unilateral ureteral obstruction (UUO) models were established using male C57BL/6 wild-type (WT) mice and age-matched C3aR-deficient mice. MCC950 was intraperitoneally injected in UUO mice. Kidney samples were collected for immunohistochemistry staining. Results In vitro, C3a synergized with TGF-β to promote EMT and the activation of the NLRP3 inflammasome. Inhibition of C3aR attenuated EMT and the activation of the NLRP3 inflammasome. Inhibition of the NLRP3 inflammasome alleviated EMT but didn’t affect the expression of C3aR. Inhibition of ERK signaling inhibited the activation of the NLRP3 inflammasome. In vivo, the expression of IL-1β was significantly higher in UUO mice compared to the sham-operated mice. C3aR deficiency and inhibition of the NLRP3 Inflammasome contributed to decreased IL-1β in UUO mice. Conclusion Our data revealed that C3a/C3aR synergies with TGF-β to activate the NLRP3 inflammasome to promote epithelial-mesenchymal transition of renal tubular epithelial cells through ERK signaling, and the way in which C3aR activates the inflammasome is to promote the assembly of the NLRP3 inflammasome.

Abstract Background Patients with epithelial ovarian carcinoma (EOC) are usually diagnosed at an advanced stage with tumour cell invasion. However, identifying the underlying molecular mechanisms and biomarkers of EOC proliferation and invasion remains challenging. Results Herein, we explored the relationship between tumour microenvironment (TME) reprogramming and tissue invasion based on single-cell RNA sequencing (scRNA-seq) datasets. Interestingly, hypoxia, oxidative phosphorylation (OXPHOS) and glycolysis, which have biologically active trajectories during epithelial mesenchymal transition (EMT), were positively correlated. Moreover, energy metabolism and anti-apoptotic activity were found to be critical contributors to intratumor heterogeneity. In addition, HMGA1, EGR1 and RUNX1 were found to be critical drivers of the EMT process in EOC. Experimental validation revealed that suppressing EGR1 expression inhibited tumour cell invasion, significantly upregulated the expression of E-cadherin and decreased the expression of N-cadherin. In cell components analysis, cancer-associated fibroblasts (CAFs) were found to significantly contribute to immune infiltration and tumour invasion, and the accumulation of CAFs was associated with poorer patient survival. Conclusion We revealed the molecular mechanism and biomarkers of tumour invasion and TME reprogramming in EOC, which provides effective targets for the suppression of tumour invasion.

Abstract Nonsteroidal anti-inflammatory drugs compose one of the most widely used classes of medications, but the risks for early development remain controversial, especially in the nervous system. Here, we utilized zebrafish larvae to assess the potentially toxic effects of nonsteroidal anti-inflammatory drugs and found that sulindac can selectively induce apoptosis of GABAergic neurons in the brains of zebrafish larvae brains. Zebrafish larvae exhibit hyperactive behaviour after sulindac exposure. We also found that akt1 is selectively expressed in GABAergic neurons and that SC97 (an Akt1 activator) and exogenous akt1 mRNA can reverse the apoptosis caused by sulindac. Further studies showed that sulindac binds to retinoid X receptor alpha (RXRα) and induces autophagy in GABAergic neurons, leading to activation of the mitochondrial apoptotic pathway. Finally, we verified that sulindac can lead to hyperactivity and selectively induce GABAergic neuron apoptosis in mice. These findings suggest that excessive use of sulindac may lead to early neurodevelopmental toxicity and increase the risk of hyperactivity, which could be associated with damage to GABAergic neurons.

Objective: To explore the protective effect of the freeze-dried fruit powder of Phyllanthus emblica L. (PEFP) against acute and chronic hyperuricemia (HUA) and liver and kidney injuries in mice. Methods: Mouse models of acute and chronic HUA were established by intraperitoneal injection of hypoxanthine and potassium oxazinate, respectively. Meanwhile, PEFP at 75, 150 and 300 mg/kg mb were orally given to the mice in the intervention group for seven days. The levels of uric acid (UA), creatinine (CRE), blood urea nitrogen (BUN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the serum, and the activities of xanthine oxidase (XOD) and adenosine deaminase (ADA) in the serum and liver were detected. Liver and kidney indexes were calculated, and the pathological characteristics of liver and kidney tissues were observed by hematoxylin and eosin (HE) staining. Results: Compared with the model group, PEFP at 150 and 300 mg/kg mb significantly reduced the liver and kidney indexes (P < 0.01) and lowered serum UA, BUN, CRE, and AST levels in mice with acute hyperuricemia (P < 0.05 or P < 0.01). PEFP at 75, 150 and 300 mg/kg mb significantly inhibited serum and liver XOD and ADA activities (P < 0.01), and PEFP at 300 mg/kg mb lowered serum ALT levels in mice with acute hyperuricemia (P < 0.01). Meanwhile, all three doses of PEFP significantly reduced the liver and kidney indexes (P < 0.01), lowered serum UA, BUN and ALT levels (P < 0.01), and inhibited serum and liver XOD activities and serum ADA activity in mice with chronic hyperuricemia (P < 0.01). PEFP at 150 and 300 mg/kg mb lowered serum CRE and AST levels and liver ADA activity (P < 0.01). PEFP ameliorated the pathological changes of the liver and kidney in mice with acute and chronic hyperuricemia. Conclusion: PEPP can effectively decrease serum UA levels in mice with acute and chronic hyperuricemia, which may be related to the inhibition of XOD and ADA activities in the serum and liver, and the promotion of renal uric acid excretion, and can also exert renal and hepatoprotective effects.

Abstract Background In China, adolescents account for about a quarter of those treated for mental disorders each year, and adolescent mental health issues have become a social hotspot. Although several epidemiological surveys of mental disorders have been conducted in China, no study has yet focused on the prevalence of mental disorders among adolescents in a certain region of Zhejiang. Methods In the first stage, 8219 middle school students aged 12–18 years in a city of Zhejiang Province (Shaoxing) were screened with the mental health screening checklist. In the second stage, participants who screened positive were tested with the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Then, the prevalence of mental disorders were calculated. Results The overall prevalence in this population was 12.4%, with prevalence rates exceeding 20% in both the 17- and 18-year-old age groups. The most common mental disorders were obsessive–compulsive disorder (OCD) (9.1%) and major depressive disorder (MDD) (8.9%). Conclusions Mental disorders are common among middle school students, and girls are at higher risk than boys. As the most prevalent mental disorders, OCD and MDD should receive timely attention, especially for upper grade students.

Objective: Transcriptomic characteristics and prognosis of tertiary lymphoid structures (TLS) and infiltrating B cells in nasopharyngeal carcinoma (NPC) remain unclear. Here, NPC transcriptomic data and clinical samples were used to investigate the role of infiltrating B cells and TLS in NPC. Methods: We investigated the gene expression and infiltrating immune cells of NPC patients and further investigated the clinical relevance of B cell and TLS signatures. Transcriptional features of infiltrating B cell subsets were revealed by single-cell RNA sequencing (scRNA-seq) analysis. Immunohistochemical (IHC) and HE staining were performed to validate the clinical relevance of infiltrating B cells and TLS in NPC samples. Results: 27 differentially expressed immune-related genes (IRGs) associated with prognosis were identified, including B cell marker genes CD19 and CD79B. The higher B cells and TLS signature scores were associated with better outcomes and early pathological staging in 88 NPC patients. ScRNA-seq identified five distinct B cell subsets in NPC, including the BC-4 cluster associated with poor outcomes and the BC-0 cluster associated with better outcomes. EBV infection was positively associated with the formation of TLS. Furthermore, experimental results showed that the infiltration of B cells in NPC tissues was higher than that of normal tissues, and the density of TLS in an early stage of NPC was higher than that in advanced-stage TLS. Conclusion: Our findings demonstrate the functional importance of distinct B cell subsets in the prognosis of NPC. Additionally, we confirmed that B cells and TLS may serve as prognostic biomarkers of survival for NPC patients.

ABSTRACT: This experiment aims to evaluate the effect of bile acids (BAs) in alleviating fatty liver disease induced by a high-fat diet (HFD) in broilers, and the modulation of the gut microbiota involved in this process. A total of 192 one-day-old Arbor Acres (AA) commercial male broilers were randomly divided into 4 groups and treated with the following diet: a basal-fat diet (BFD), a basal-fat diet plus bile acids (BFD + BAs), an HFD, and a high-fat diet plus bile acids (HFD + BAs). Bile acids were supplemented at the early growth stage (3–7 d), middle stage (17–21 d), and late stage (31–35 d). Results showed that BAs treatment had a significant effect on body weight on 14 d and 35 d, and increased the breast muscle weight and its index, but decreased the liver weight and abdominal fat weight on 35 d (P < 0.05). The supplementation of BAs significantly improved the serum lipid profile and decreased the level of triglycerides (TG), total cholesterol (TCHO), and nonesterified fatty acids (NEFA) on 35 d (P < 0.05). Dietary BAs supplementation significantly alleviated the hepatic TG deposition induced by HFD (P < 0.05), which was accompanied by upregulation of peroxisome proliferator-activated receptor gamma (PPARγ) and lipoprotein lipase (LPL) gene expression (P < 0.05). Moreover, the expression levels of hepatic gene adipose triglyceride lipase (ATGL), peroxisome proliferator-activated receptor α (PPARα), and apolipoprotein B (APOB) were greatly increased by BAs treatment. The analysis of 16S rRNA sequencing showed that the microbial diversity of the cecal digesta was increased by BAs in broilers with elevated abundances of Firmicutes, Lactobacillus, Anaerostipes, Sellimonas, and CHKCI002 and decreased abundances of Barnesiella and Akkermansia genus (P < 0.05). Hepatic TG content was positively correlated with the abundance of Oscillospiraceae, but it was negatively correlated with the abundance of Lactobacillus in cecal digesta (P < 0.05). These results indicate that dietary BAs can improve growth performance and alleviate fatty liver disease induced by an HFD via modulating gut microbiota in broilers.

Objective: The study objective was to evaluate the progression of dissected distal aorta in patients with acute type A aortic dissection with malperfusion syndrome treated with endovascular fenestration/stenting and delayed open aortic repair. Methods: From 1996 to 2021, 927 patients presented with acute type A aortic dissection. Of these, 534 had DeBakey I dissection with no malperfusion syndrome and underwent emergency open aortic repair (no malperfusion syndrome group), whereas 97 patients with malperfusion syndrome underwent fenestration/stenting and delayed open aortic repair (malperfusion syndrome group). Sixty-three patients with malperfusion syndrome treated with fenestration/stenting were excluded due to no open aortic repair, including death from organ failure (n = 31), death from aortic rupture (n = 16), and discharged alive (n = 16). Results: Compared with the no malperfusion syndrome group, the malperfusion syndrome group had more patients with acute renal failure (60% vs 4.3%, P

Wearing masks is an effective protective measure for residents to prevent respiratory infectious diseases when going out. Due to issues such as a small target size, target occlusion leading to information loss, false positives, and missed detections, the effectiveness of face mask-wearing detection needs improvement. To address these issues, an improved YOLOv7 object detection model is proposed. Firstly, the C2f_SCConv module is introduced in the backbone network to replace some ELAN modules for feature extraction, enhancing the detection performance of small targets. Next, the SPPFCSPCA module is proposed to optimize the spatial pyramid pooling structure, accelerating the model convergence speed and improving detection accuracy. Finally, the HAM_Detect decoupled detection head structure is introduced to mitigate missed and false detections caused by target occlusion, further accelerating model convergence and improving detection performance in complex environments. The experimental results show that improved YOLOv7 achieved an mAP of 90.1% on the test set, a 1.4% improvement over the original YOLOv7 model. The detection accuracy of each category improved, effectively providing technical support for mask-wearing detection in complex environments.

Controllable Text Generation (CTG) aims to modify the output of a Language Model (LM) to meet specific constraints. For example, in a customer service conversation, responses from the agent should ideally be soothing and address the user’s dissatisfaction or complaints. This imposes significant demands on controlling language model output. However, demerits exist among traditional methods. Promoting and fine-tuning language models exhibit the “hallucination” phenomenon and cannot guarantee complete adherence to constraints. Conditional language models (CLM), which map control codes into LM representations or latent space, require training the modified language models from scratch and a high amount of customized dataset is demanded. Decoding-time methods employ Bayesian Rules to modify the output of the LM or model constraints as a combination of energy functions and update the output along the low-energy direction. Both methods are confronted with the efficiency sampling problem. Moreover, there are no methods that consider the relation between constraints weights and the contexts, as is essential in actual applications such as customer service scenarios. To alleviate the problems mentioned above, we propose Controllable Text Generation with Generative Adversarial Networks (CTGGAN), which utilizes a language model with logits bias as the Generator to produce constrained text and employs the Discriminator with learnable constraint weight combinations to score and update the generation. We evaluate the method in the text completion task and Chinese customer service dialogues scenario, and our method shows superior performance in metrics such as PPL and Dist-3. In addition, CTGGAN also exhibits efficient decoding compared to other methods.

Radiation resistance results in the recurrence and metastasis of non-small cell lung cancer (NSCLC) after radiotherapy. A major cause of radiation resistance is subversion of immune surveillance and clearance. Although our previous research has demonstrated that programmed death-ligand 1 (PD-L1) is responsible for radiation resistance in NSCLC, PD-L1 alone was not a reliable predictor of radiotherapy efficacy. For further exploration of the predictors of radiotherapy efficacy, which could add accuracy to the single biomarker – PD-L1, immunoprecipitation followed by mass spectrometry assay was performed to identify proteins that interact with PD-L1, and flotillin-1 (FLOT1) was detected as a candidate. However, the role of FLOT1 in radiation resistance in NSCLC is largely unknown. Here, we defined FLOT1 as a positive regulator of PD-L1 at the cell level, and the expression of PD-L1 was reduced following FLOT1 depletion. Furthermore, we found that the knockdown of FLOT1 impeded radiation-mediated cell migration and epithelial–mesenchymal transition process. Moreover, FLOT1 depletion enhanced radiation-induced DNA damage, thereby increasing the radiation lethality for NSCLC cells and promoting radiation-mediated tumor regression in animal models and patients with NSCLC. Furthermore, FLOT1 depletion-boosted DNA damage activated STING signaling pathway and promoted the production of CCL5 and CXCL10 that can drive CD8+ T lymphocytes chemotaxis, thereby reprogramming tumor immune microenvironment and triggering the antitumor immune response. Indeed, FLOT1 expression correlated with infiltration of immune cells in NSCLC tumor tissue samples. Taken together, our findings reported an unexplored role of FLOT1 in radiotherapy and also provided an evidence base for FLOT1 as a promising biomarker to predict the response to radiotherapy and a potential therapeutic target for enhancing radiotherapy effects.

Objective: To evaluate the effect of autologous blood use on blood product consumption and outcomes after acute type A aortic dissection repair. Methods: From 2010 to October 2020, 497 patients underwent open acute type A aortic dissection repair, including those with autologous blood harvesting before cardiopulmonary bypass and transfusion after cardiopulmonary bypass (autologous blood transfusion [ABT], n = 397) and without autologous blood harvesting and transfusion (No-ABT, n = 100). The median ABT volume was 900 mL. Using propensity score matching, 89 matched pairs were identified based on age, sex, body mass index, preoperative hemoglobin, acute preoperative stroke, previous cardiac surgery, and cardiogenic shock. Results: After propensity score matching, both groups were similar in demographic characteristics and aortic procedures. The ABT group required significantly less intraoperative transfusion of blood products (6 vs 11 units; P

Abstract Bone metastasis (BM) is one of the most common sites of metastasis in prostate adenocarcinoma (PA). PA with BM can significantly diminish patients’ quality of life and result in a poor prognosis. The objective of this study was to establish two web-based nomograms to estimate the risk and prognosis of BM in PA patients. From the Surveillance, Epidemiology, and End Results (SEER) database, data on 308,332 patients diagnosed with PA were retrieved retrospectively. Logistic and Cox regression, respectively, were used to determine independent risk and prognostic factors. Then, We constructed two web-based nomograms and the results were validated by receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA) , and the Kaplan-Meier analyses. The independent risk factors for BM in PA patients included race, PSA, ISUP, T stage, N stage, brain, liver, lung metastasis, surgery, radiation and chemotherapy. The independent prognostic predictors for overall survival (OS) were age, marital status, PSA, ISUP and liver metastasis. Both nomograms could effectively predict risk and prognosis of BM in PA patients according to the results of ROC curves, calibration, and DCA in the training and validation sets. And the Kaplan-Meier analysis illustrated that the prognostic nomogram could significantly distinguish the population with different survival risks. We successfully constructed the two web-based nomograms for predicting the incidence of BM and the prognosis of PA patients with BM, which may assist clinicians in optimizing the establishment of individualized treatment programs and enhancing patients’ prognoses.

Background: Inflammatory bowel disease (IBD) is a complex and multifactorial inflammatory condition, comprising Crohn’s disease (CD) and ulcerative colitis (UC). While numerous studies have explored the immune response in IBD through transcriptional profiling of the enteric mucosa, the subtle distinctions in the pathogenesis of Crohn’s disease and ulcerative colitis remain insufficiently understood.Methods: The intact bowel wall specimens from IBD surgical patients were divided based on their inflammatory status into inflamed Crohn’s disease (iCD), inflamed ulcerative colitis (iUC) and non-inflamed (niBD) groups for RNA sequencing. Differential mRNA GO (Gene Ontology), and KEGG (Kyoto Encyclopedia of Genes and Genomes), and GSEA (Gene Set Enrichment Analysis) bioinformatic analyses were performed with a focus on the enteric autonomic nervous system (ANS) and smooth muscle cell (SMC). The transcriptome results were validated by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC).Results: A total of 2099 differentially expressed genes were identified from the comparison between iCD and iUC. Regulation of SMC apoptosis and proliferation were significantly enriched in iCD, but not in iUC. The involved gene PDE1A in iCD was 4-fold and 1.5-fold upregulated at qPCR and IHC compared to that in iUC. Moreover, only iCD was significantly associated with the gene sets of ANS abnormality. The involved gene SEMA3D in iCD was upregulated 8- and 5-fold at qPCR and IHC levels compared to iUC.Conclusion: These findings suggest that PDE1A and SEMA3D may serve as potential markers implicated in enteric smooth muscle apoptosis, proliferative disorders, and dysautonomia specifically in Crohn’s disease.

A bearing fault is one of the major causes of rotating machinery faults. However, in real industrial scenarios, the harsh and complex environment makes it very difficult to collect sufficient fault data. Due to this limitation, most of the current methods cannot accurately identify the fault type in cases with limited data, so timely maintenance cannot be conducted. In order to solve this problem, a bearing fault diagnosis method based on the fractional order Siamese deep residual shrinkage network (FO-SDRSN) is proposed in this paper. After data collection, all kinds of vibration data are first converted into two-dimensional time series feature maps, and these feature maps are divided into the same or different types of fault sample pairs. Then, a Siamese network based on the deep residual shrinkage network (DRSN) is used to extract the features of the fault sample pairs, and the fault type is determined according to the features. After that, the contrastive loss function and diagnostic loss function of the sample pairs are combined, and the network parameters are continuously optimized using the fractional order momentum gradient descent method to reduce the loss function. This improves the accuracy of fault diagnosis with a small sample training dataset. Finally, four small sample datasets are used to verify the effectiveness of the proposed method. The results show that the FO-SDRSN method is superior to other advanced methods in terms of training accuracy and stability under small sample conditions.

Objectives: The optimal management of active endocarditis in intravenous (IV) drug users is still lacking. Methods: From the years 1997 to 2017, 536 patients with active infectious endocarditis were surgically treated, including 83 (15%) with IV drug use (IVDU) and 453 (85%) without IV drug use (non-IVDU). Initial data were obtained from the Society of Thoracic Surgeons database and supplemented with chart review and national death index data. Results: The IVDU group was significantly younger (43 vs 56 years old) than the non-IVDU group and had greater rates of psychiatric disorders, drug use, and tricuspid valve endocarditis (28% vs 8.6%). Hypertension, dyslipidemia, and diabetes mellitus were significantly more common in the non-IVDU group. Perioperative complications and operative mortality (7.2% vs 7.9%) were similar. IVDU was not a significant risk factor for operative mortality. Kaplan–Meier survival was significantly lower in the IVDU group (5-year survival, 46% vs 67%). Significant risk factors for long-time mortality included IV drug use (hazard ratio [HR], 1.92), age ≥65 years (HR, 1.78), congestive heart failure (HR, 1.87), and enterococcus endocarditis (HR, 1.54). The 5-year rate of reoperation was similar between IVDU and non-IVDU groups (2.4% vs 2.7%). Conclusions: IVDU is a significant risk factor for long-term mortality. A multidisciplinary approach was preferred for IVDU patients to treat both endocarditis and substance use disorder and improve long-term survival.

Abstract Background Langerhans cell histiocytosis (LCH) is a heterogeneous neoplastic disorder that is rarely seen in patients aged 60 years and older. It is reported that elderly patients with LCH have a higher chance of having malignancies. In the oral cavity, patients with LCH can present with mucosal ulcers and extensive osteolysis, making it difficult for clinicians to make a proper diagnosis. Case presentation We reported an 82-year-old Chinese woman with oral symptoms as the first presentation of LCH, and eventually developed acute myeloid leukemia (AML). She suffered diffuse ulcers involving the entire gingival mucosa and the left half hard palate, and had lost several teeth. Genomic DNA sequencing of the cells from LCH revealed multiple mutations in TET2, BRAF, SRSF2, NRAS, MAP2K4 and so on. The patient declined the BRAF V600E inhibitor (Vemurafenib). Although a dramatic improvement of the oral ulcers was achieved after symptomatic treatment, the patient developed acute myeloid leukemia (AML) and died. Conclusions This report presented the diagnostic difficulties of LCH with oral manifestations and highlighted the importance of radiological assessments and laboratory tests. Moreover, many of the mutations detected in our LCH patient are frequently seen in AML, suggesting that AML and LCH cells in this patient share the same origin.

Abstract Introduction The main emphasis of the research about adjuvant imatinib for high‐risk gastrointestinal stromal tumors (GISTs) is prolonging the treatment duration and ignores the heterogeneous that 10‐year recurrence rates ranged from about 20%–100%. Thus, this study evaluated the effect of different durations of adjuvant imatinib on outcomes in high‐risk GISTs to explore the feasibility of individual treatment. Methods We analyzed 855 high‐risk GIST patients from three centers who underwent macroscopically complete resection between December 2007 and September 2020. The patients were divided into training (n =564) and two validation cohorts (n = 238 and53) based on their source. Recurrence‐free survival (RFS) was the primary point. Cox multivariate analysis was used to develop the nomogram. C‐index, time‐dependent area under the curves, and calibration plots were used to assess the performance of the nomogram. Results Univariate analysis showed that longer adjuvant imatinib was significantly associated with better 5‐year RFS (p

BackgroundAntidepressants still have some side effects in treating major depressive disorder (MDD), and acupuncture therapy is a complementary therapy of research interest for MDD. Acupoints are sensitive sites for disease response and stimulation points for acupuncture treatment. Prior studies suggest that the biological specificity of acupoints is altered in physiological and pathological situations. Therefore, we hypothesize that the biological specificity of acupoints is associated with the diagnosis of MDD and that stimulating acupoints with significant biological specificity can achieve a better therapeutic effect than clinical common acupoints. This study aims to investigate the efficacy and safety of intradermal acupuncture (IA) treatment for MDD based on changes in the biological specificity of acupoints.MethodsThe first part of the study will enroll 30 MDD patients and 30 healthy control (HC) participants to assess pain sensitivity and thermal specificity of MDD-related acupoints using a pressure pain threshold gauge (PTG) and infrared thermography (IRT). The potentially superior acupoints for treating MDD will be selected based on the results of PTG and IRT tests and referred to as pressure pain threshold strong response acupoints (PSA) and temperature strong response acupoints (TSA).The second part of the study will enroll 120 eligible MDD patients randomly assigned to waiting list (WL) group, clinical common acupoint (CCA) group, TSA group, and PSA group in a 1:1:1:1 ratio. The change in the Patient Health Questionnaire-9 Items (PHQ-9), the MOS item short-form health survey (SF-36), pressure pain threshold, temperature of acupoints, and adverse effects will be observed. The outcomes of PHQ-9 and SF-36 measures will be assessed before intervention, at 3 and 6 weeks after intervention, and at a 4-week follow-up. The biological specificity of acupoint measures will be assessed before intervention and at 6 weeks after intervention. All adverse effects will be assessed.DiscussionThis study will evaluate the therapeutic effect and safety of IA for MDD based on changes in the biological specificity of acupoints. It will investigate whether there is a correlation between the biological specificity of MDD-related acupoints and the diagnosis of MDD and whether stimulating strong response acupoints is superior to clinical common acupoints in the treatment of MDD. The study’s results may provide insights into the biological mechanisms of acupuncture and its potential as a complementary therapy for MDD.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT05524519.

BackgroundMajor depressive disorder (MDD) has emerged as the fifth leading cause of years lived with disability, with a high prevalent, affecting nearly 4% of the global population. While available evidence suggests that intradermal acupuncture may enhance the effectiveness of antidepressants, whether its efficacy is a specific therapeutic effect or a placebo effect has not been reported. Moreover, the cerebral mechanism of intradermal acupuncture as a superficial acupuncture (usually subcutaneous needling to a depth of 1–2 mm) for MDD remains unclear.MethodsA total of 120 participants with MDD will be enrolled and randomized to the waiting list group, sham intradermal acupuncture group and active intradermal acupuncture group. All 3 groups will receive a 6-week intervention and a 4-week follow-up. The primary outcome will be measured by the Hamilton Depression Rating Scale-17 and the secondary outcome measures will be the Self-Rating depression scale and Pittsburgh sleep quality index. Assessments will be conducted at baseline, 3 weeks, 6 weeks, and during the follow-up period. In addition, 20 eligible participants in each group will be randomly selected to undergo head magnetic resonance imaging before and after the intervention to explore the effects of intradermal acupuncture on brain activity in MDD patients.DiscussionIf the intradermal acupuncture is beneficial, it is promising to be included in the routine treatment of MDD.Clinical Trial RegistrationClinicaltrials.gov, NCT05720637.

Objective: To assess the outcomes of emergency revascularization with endovascular fenestration/stenting followed by delayed open aortic repair in patients with acute type A aortic dissection with lower extremity (LE) malperfusion syndrome (MPS); that is, necrosis and dysfunction of the lower extremity. Methods: From 1996 to 2019, among 760 consecutive acute type A aortic dissection patients 512 patients had no malperfusion syndrome (Non-MPS), whereas 26 patients had LE-MPS with/without renal MPS and underwent endovascular fenestration/stenting, open aortic repair, or both. Patients with coronary, cerebral, mesenteric, and celiac MPS, or managed with thoracic endovascular aortic repair, were excluded (n = 222). All patients with LE-MPS underwent upfront endovascular fenestration/stenting except 1 patient (with signs of rupture) who initially underwent emergency open aortic repair. Results: Among the LE-MPS patients, 17 (65%) had LE pain, 15 (58%) had abnormal motor function with 8 (31%) having paralysis, 10 (38%) had LE pallor, 17 (65%) had LE paresthesia, and 20 (77%) had LE pulselessness. Of the 25 patients undergoing upfront endovascular fenestration/stenting, 16 went on to open aortic repair, 3 survived to discharge without aortic repair, and 6 died before aortic repair (3-aortic rupture and 3-organ failure). In-hospital mortality among all patients was significantly higher in the LE-MPS group (31% vs 6.3%; P = .0003). Among those undergoing open aortic repair, postoperative outcomes were similar between groups, including operative mortality (18% vs 6.5%; P = .10). LE-MPS was a significant risk factor for in-hospital mortality (odds ratio, 6.0 [1.9, 19]; P = .002). Conclusions: In acute type A aortic dissection, LE-MPS was associated with high in-hospital mortality. Emergency revascularization with endovascular fenestration/stenting followed by delayed open aortic repair may be a reasonable approach. : Video Abstract:

Electroencephalogram (EEG) electrodes are critical devices for brain-computer interface and neurofeedback. A pre-gelled (PreG) electrode was developed in this paper for EEG signal acquisition with a short installation time and good comfort. A hydrogel probe was placed in advance on the Ag/AgCl electrode before wearing the EEG headband instead of a time-consuming gel injection after wearing the headband. The impedance characteristics were compared between the PreG electrode and the wet electrode. The PreG electrode and the wet electrode performed the Brain-Computer Interface (BCI) application experiment to evaluate their performance. The average impedance of the PreG electrode can be decreased to 43 $\text{k}\Omega $ or even lower, which is higher than the wet electrode with an impedance of 8 $\text{k}\Omega $ . However, there is no significant difference in classification accuracy and information transmission rate (ITR) between the PreG electrode and the wet electrode in a 40 target BCI system based on Steady State Visually Evoked Potential (SSVEP). This study validated the efficiency of the proposed PreG electrode in the SSVEP-based BCI. The proposed PreG electrode will be an excellent substitute for wet electrodes in an actual application with convenience and good comfort.

Background. Both low skeletal muscle mass and delirium are prevalent in older hospitalized patients, while their associations are unclear. This systematic review and meta-analysis aim to investigate the associations between low skeletal muscle mass and the incidence of delirium in hospitalized patients. Methods. The PubMed, Web of Science, and Embase were searched for relevant studies published before May 2022, and we conducted this systematic review and meta-analysis according to the PRISMA and MOOSE guidelines. The summary odds ratios (OR) and 95% confidence intervals (CI) were estimated, and subgroup analyses were also conducted according to the age and major surgeries. Results. Finally, nine studies with 3 828 patients were included. The pooled result showed no significant association between low skeletal muscle mass and the incidence of delirium (OR 1.69, 95% CI 0.85 to 2.52). However, sensitivity analysis suggested that one study caused a significant alteration of the summary result, and the meta-analysis of the remaining 8 studies showed that low skeletal muscle mass was significantly associated with an 88% increased incidence of delirium (OR 1.88, 95% CI 1.43 to 2.33). Furthermore, subgroup analyses indicated that low skeletal muscle mass was associated with a higher incidence of delirium in patients ≥75 years old or undergoing major surgeries instead of those

Background. There are many variations in valve-sparing aortic root replacement techniques. Our aim is to determine the impact of the graft on mid-term outcomes: Valsalva graft vs. two straight tubular grafts. Methods. From 2004 to 2020, 332 patients underwent valve-sparing aortic root replacement with either a Valsalva graft (Valsalva group: n = 270) or two straight tubular grafts (two-graft group: n = 62). Data were obtained through chart review and the National Death Index. Primary outcomes were mid-term survival and freedom from reoperation. Results. The preoperative characteristics of the groups were similar, but the two-graft group had more type A dissections (32% vs. 19%) and emergent operations (26% vs. 15%) and was younger (45 vs. 50 years). Intraoperatively, the groups were similar, but the two-graft group had longer cross-clamp (245 vs. 215 minutes) and cardiopulmonary bypass times (284 vs. 255 minutes). Postoperative complications including reoperation for bleeding, stroke, pacemaker implantation, and renal failure were slightly more frequent in the Valsalva group, but the differences were not significant. Operative mortality was similar between the Valsalva and two-graft groups (0.7% vs. 0%). Five-year survival in the two-graft group was 100% compared to 96% in the Valsalva group (p=0.56). Five-year freedom from reoperation in the two-graft group was 100% compared to 93% in the Valsalva group (p=0.29). Conclusions. The Valsalva and two-graft techniques both have excellent short- and mid-term outcomes. The two-graft technique might have slightly better survival and freedom from reoperation, but a larger sample size and longer follow-up are needed to determine if these advantages are significant.

Objective: To determine the long-term survival and rate of reoperation after surgical treatment of infective endocarditis (IE) in patients with a bicuspid aortic valve (BAV) and patients with a tricuspid aortic valve (TAV). Methods: Between 1997 and 2017, 210 patients underwent surgical treatment for native aortic valve endocarditis, including 51 patients with BAV (24%) and 159 patients with TAV (76%). Data were obtained from the Society of Thoracic Surgeons data warehouse and hospital medical record review, supplemented with surveys and national death index data for more complete follow-up. Results: Compared with the TAV IE group, the BAV IE group was significantly younger (42 years vs 54 years) and had lower incidence rates of hypertension, coronary artery disease, and congestive heart failure (CHF). There were no significant between-group differences in postoperative stroke, sepsis, pacemaker requirement, or in-hospital mortality (2.0% vs 4.4%). Liver disease was a risk factor for operative mortality (odds ratio [OR], 13; 95% CI, 3.3-30; P = .0002). The 10-year survival rate was 64% for the BAV group versus 46% for the TAV group (P = .0191). Significant risk factors for long-term mortality were intravenous drug use (hazard ratio [HR], 4.5; P

Objective: To determine long-term survival and reoperation rate in patients with a bicuspid aortic valve (BAV) and patients with a tricuspid aortic valve (TAV) after stentless aortic valve replacement (AVR)/aortic root replacement (ARR). Methods: Between 1992 and 2014, 1293 patients underwent first AVR/ARR with a stentless aortic valve using the modified inclusion operating technique, including 741 patients with a TAV and 552 with a BAV. Using propensity scoring with 26 variables, 330 matched pairs were identified with AVR with or without ascending aorta/arch replacement. Data were obtained through chart review, surveys, and the National Death Index. Results: Patient demographics were similar in the propensity score–matched groups. Both groups had similar cardiopulmonary bypass, cross-clamp, and hypothermia circulatory arrest times, cerebral protection strategies, and rate of aortic arch replacement. The median size of implanted valves was similar (BAV: 27 mm [range, 25-29 mm] vs TAV: 27 mm [range, 25-27 mm]). Compared with the TAV group, the BAV group had a shorter hospital stay (6 days vs 7 days; P = .001) but similar 30-day mortality (1.8% vs 1.2%). The BAV group had better long-term (15-year) survival (46% vs 33%; P = .002) but a higher cumulative incidence of reoperation for structural valve deterioration (15-year: 15% vs 11%; P = .048). Cox proportional hazard analysis identified a BAV as a protective factor for long-term mortality (hazard ratio [HR], 0.71; 95% CI, 0.56-0.91; P = .006), but a risk factor for reoperation due to structural valve deterioration (HR, 1.4 [95% CI, 0.8-2.6; P = .27] in the matched cohort and 2.2 [95% CI, 1.3-3.7; P = .004] in the unmatched cohort). Conclusions: The BAV patients had better long-term survival but a higher reoperation rate compared with TAV patients after stentless AVR. Our findings suggest caution in the use of bioprostheses for BAV patients.