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Abstract Background Previous studies have suggested a potential link between the crown-to-root ratio (CRR) and root morphology in patients with mild chronic periodontitis, which may be associated with tooth mobility. However, these findings have not been thoroughly investigated. Our previous study found that 76% of patients with aggressive periodontitis, particularly those with premolar involvement, exhibited abnormal root morphology, severe alveolar bone loss, and increased tooth mobility, leading to poor clinical outcomes. This study aims to investigate the specific correlations among alveolar bone resorption, root morphology, CRR, and periodontal clinical indicators with premolar mobility in stage III/IV grade C periodontitis patients aged ≤ 35 years. Materials and methods A total of 1,064 premolars from 151 stage III/IV grade C periodontitis patients aged ≤ 35 years were included in the study. Clinical periodontal parameters and radiographic measurements were recorded. Logistic regression analysis was used to explore the relationships between these indicators and tooth mobility. Results Significant variations in premolar root lengths were observed, ranging from 6.80 mm to 20.96 mm. Teeth with shorter roots (mean length: 10.22 mm) exhibited grade I mobility with only 28% alveolar bone resorption, whereas those with medium-length (mean length: 12.67 mm) and longer roots (mean length: 14.91 mm) exhibited mobility at 34% and 37% bone resorption, respectively. Regression models incorporating the bone-level CRR, average probing depth, and root length demonstrated strong predictive accuracy for tooth mobility (P

Abstract Background A systematic review of the evidence was conducted to assess the efficacy of low-intensity extracorporeal shock wave therapy (LI-ESWT) for patients with Peyronie`s Disease (PD). Methods A comprehensive search of the Cochrane Registry, PubMed and Embase databases was conducted to identify all controlled trials, including randomised controlled trials (RCTs), cohort studies and case-control studies, focusing on the efficacy of LI-ESWT in treating PD, and published before February 2023. The size of plaques, curvature deviation, visual analog scale [VAS] and International Index of Erectile Function (IIEF) were the most commonly used tool to evaluate the treatment effectiveness of LI-ESWT. Results There were 7 studies including 475 patients from 1999 to 2023. The meta-analysis of the data revealed that LI-ESWT could considerably enhance the proportion of men experiencing a reduction in penile plaques (RD 0.27, 95% CI: 0.04–0.50, P = 0.02), improvement in penile curvature (RD: 0.13; 95% CI, 0–0.26; p = 0.05), alleviation of pain (RD 0.22, 95% CI: 0.01–0.42, P = 0.04), and complete remission (RD 0.38, 95% CI 0.23–0.52, P

Abstract The variability of renewable energy within microgrids (MGs) necessitates the smoothing of power fluctuations through the effective scheduling of internal power equipment. Otherwise, significant power variations on the tie‐line connecting the MG to the main power grid could occur. This study introduces an innovative scheduling strategy that utilizes a data‐driven approach, employing a deep reinforcement learning algorithm to achieve this smoothing effect. The strategy prioritizes the scheduling of MG's internal power devices, taking into account the stochastic charging patterns of electric vehicles. The scheduling optimization model is initially described as a Markov decision process with the goal of minimizing power fluctuations on the interconnection lines and operational costs of the MG. Subsequently, after preprocessing the historical operational data of the MG, an enhanced scheduling strategy is developed through a neural network learning process. Finally, the results from four scheduling scenarios demonstrate the significant impact of the proposed strategy. Comparisons of reward curves before and after data preprocessing underscore its importance. In contrast to optimization results from deep deterministic policy gradient, soft actor‐critic, and particle swarm optimization algorithms, the superiority of the deep deterministic policy gradient algorithm with the addition of a priority experience replay mechanism is highlighted.

Abstract Background End-stage renal disease (ESRD) causes numerous physical and psychological problems in patients, so that they must adhere to their treatment regimen to recover their disease, alleviate these problems, and increase their lifespan. The present study aimed to determine the predictive role of spiritual health, resilience, and mental well-being in treatment adherence among hemodialysis patients. Methods This correlational cross-sectional study investigated some variables related to treatment adherence in 184 patients undergoing hemodialysis referred to two dialysis centers in Kerman, southeastern Iran. A census method was used to select the participants and data were collected using socio-demographic characteristics questionnaire, Adherence to Treatment Questionnaire (ATQ), Conner-Davidson Resilience Scale, Reef Psychological well-being Questionnaire, and Spiritual Well-Being Scale (SWBS). Results The overall treatment adherence score was 155.42 ± 27.98 and we found a positive significant correlation between spiritual health, resilience, psychological well-being, and treatment adherence (p

Abstract Fibroblast growth factor 21 (FGF21) is essential for modulating hepatic homeostasis, but the impact of FGF21 on liver graft injury remains uncertain. Here, we show that high FGF21 levels in liver graft and serum are associated with improved graft function and survival in liver transplantation (LT) recipients. FGF21 deficiency aggravates early graft injury and activates arachidonic acid metabolism and regional inflammation in male mouse models of hepatic ischemia/reperfusion (I/R) injury and orthotopic LT. Mechanistically, FGF21 deficiency results in abnormal activation of the arachidonate 15-lipoxygenase (ALOX15)/15-hydroxy eicosatetraenoic acid (15-HETE) pathway, which triggers a cascade of innate immunity-dominated pro-inflammatory responses in grafts. Notably, the modulating role of FGF21/ALOX15/15-HETE pathway is more significant in steatotic livers. In contrast, pharmacological administration of recombinant FGF21 effectively protects against hepatic I/R injury. Overall, our study reveals the regulatory mechanism of FGF21 and offers insights into its potential clinical application in early liver graft injury after LT.

Abstract Background Sarcopenia is associated with unfavourable long‐term survival in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC). However, the impact of myosteatosis and muscle loss on patient prognosis has not been investigated. Methods Seven hundred fifty‐six HCC patients who received LT at 3 transplant centres were included. Computed tomography (CT) images of recipients were collected to measure skeletal muscle index (SMI) and skeletal muscle radiodensity (SMRA). The impact of myosteatosis on the prognosis of sarcopenic and non‐sarcopenic patients was studied separately. Muscle status was evaluated based on the presence of sarcopenia and myosteatosis. The muscle loss of 342 males was calculated as the relative change of SMI between pre‐ and post‐LT evaluations. Cox regression models were used to identify predictors of overall survival (OS) and recurrence‐free survival (RFS). Results The study comprised 673 males and 83 females. The median follow‐up time was 31 months (interquartile range, 19–43 months). Prior to LT, 267 (39.7%) and 187 (27.8%) males were defined as sarcopenic (low‐SMI) and myosteatotic (low‐SMRA), respectively. For sarcopenic recipients, the presence of myosteatosis was followed by a 23.6% decrease in 5 year OS (P 14.2% was an independent risk factor for poor OS (HR, 2.286; 95% CI, 1.358–3.849; P = 0.002) and RFS (HR, 2.219; 95% CI, 1.418–3.471; P

Abstract Lenvatinib is a targeted drug used for first-line treatment of hepatocellular carcinoma (HCC). A deeper insight into the resistance mechanism of HCC against lenvatinib is urgently needed. In this study, we aimed to dissect the underlying mechanism of lenvatinib resistance (LR) and provide effective treatment strategies. We established an HCC model of acquired LR. Cell counting, migration, self-renewal ability, chemoresistance and expression of stemness genes were used to detect the stemness of HCC cells. Molecular and biochemical strategies such as RNA-sequencing, immunoprecipitation, mass spectrometry and ubiquitination assays were used to explore the underlying mechanisms. Patient-derived HCC models and HCC samples from patients were used to demonstrate clinical significance. We identified that increased cancer stemness driven by the hypoxia-inducible factor-1α (HIF-1α) pathway activation is responsible for acquired LR in HCC. Phosphorylated non-muscle myosin heavy chain 9 (MYH9) at Ser1943, p-MYH9 (Ser1943), could recruit ubiquitin-specific protease 22 (USP22) to deubiquitinate and stabilize HIF-1α in lenvatinib-resistant HCC. Clinically, p-MYH9 (Ser1943) expression was upregulated in HCC samples, which predicted poor prognosis and LR. A casein kinase-2 (CK2) inhibitor and a USP22 inhibitor effectively reversed LR in vivo and in vitro. Therefore, the p-MYH9 (Ser1943)/USP22/HIF-1α axis is critical for LR and cancer stemness. For the diagnosis and treatment of LR in HCC, p-MYH9 (Ser1943), USP22, and HIF-1α might be valuable as novel biomarkers and targets.

Compared with the widely used rodents, pigs are anatomically, physiologically, and genetically more similar to humans, making them high-quality models for the study of liver diseases. Here, we review the latest research progress on pigs as a model of human liver disease, including methods for establishing them and their advantages in studying cystic fibrosis liver disease, acute liver failure, liver regeneration, non-alcoholic fatty liver disease, liver tumors, and xenotransplantation. We also emphasize the importance of genetic engineering techniques, mainly the CRISPR/Cas9 system, which has greatly enhanced the utility of porcine models as a tool for substantially advancing liver disease research. Genetic engineering is expected to propel the pig as one of the irreplaceable animal models for future biomedical research.

Abstract The growing prevalence of mental health issues underscores the need for innovative screening methods. Large-scale, internet-based psychological screening has emerged as a vital tool to accurately determine morbidity rates and facilitate early diagnosis of mental disorders. However, conventional psychological screening methods often struggle with non-genuine responses and lack objective metrics. To bridge this gap, we have compiled a novel dataset derived from an expansive screening initiative at Xinxiang Medical University. The study, conducted from February 27 to March 17, 2021, yielded a dataset comprising responses from 24,292 students to four well-established psychological scales—PHQ-9, GAD-7, ISI, and PSS. A distinctive feature of this dataset is the inclusion of response time data, which captures the temporal dynamics of participants’ interactions with the scales, offering valuable insights into their response behaviour. The release of this dataset offers a substantial opportunity for researchers in the domains of psychology and public health to explore new insights into mental health, scale reliability, and the dynamics of psychological assessment.

Abstract Background Spontaneous Coronary Artery Dissection (SCAD) is an acute coronary event of uncertain origin. SCAD occurs when the coronary artery wall dissects non-traumatically and non-atherosclerotically, leading to the formation of an intramural hematoma or intimal tear, ultimately compressing and restricting the true lumen, or even occluding it. The management of SCAD remains controversial despite modern imaging techniques. In addition to supportive drug therapy, percutaneous coronary intervention (PCI) is another option that can be used as an effective treatment modality. Case presentation We describe A 50-year-old male with SCAD presented to the hospital emergency department complaining of chest pain. Coronary angiography incidentally showed spiral dissection from the proximal to distal right coronary artery (RCA). Three overlapping coroflex stents were deployed from the distal to the proximal RCA. Conclusions To stabilize the coronary artery in Acute Coronary Syndrome (ACS) patients due to SCAD, prompt interventions such as stenting and angioplasty are needed. However, it is necessary to pay attention to the clinical condition of patients and quick diagnosis for the recovery of patients and reduction of complications.

Abstract Purpose This study aimed to preliminarily investigate the association and possible mechanisms between Helicobacter. pylori (H. pylori) infection and type 2 diabetes mellitus (T2DM) through data collection, statistical analysis, and bioinformatics analysis. Methods A retrospective cohort study, including a total of 4406 participants who attended annual health checkups at Xian GEM Flower Changqing Hospital, was conducted to explore the correlation between the incidence of T2DM and H. pylori infection. To uncover the potential mechanisms underlying the interaction between the two diseases, differentially expressed genes (DEGs) common to T2DM and H. pylori infection were identified using the GEO database and Venn diagrams. These DEGs were then analyzed through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) analysis. Results In total, 2053 participants were classified into the H. pylori-positive group and 2353 into the H. pylori-negative group. H. pylori infection was associated with a higher risk of T2DM occurrence (adjusted HR 1.59; 95% CI 1.17–2.15, P = 0.003). The average disease-free survival time was 34.81 months (95% CI 34.60-35.03 months) in the H. pylori positive group and 35.42 months (95% CI 35.28–35.56 months) in the H. pylori negative group. Multivariate analysis and subgroup analyses also showed that H. pylori infection increased the risk of developing T2DM. A total of 21 DEGs between T2DM and H. pylori infection were identified and enriched in 7 signaling pathways, indicating specific protein interactions. Conclusions The prevalence of T2DM was associated with H. pylori infection. T2DM and H. pylori infection may interact with each other through metabolic and immune pathways.

Abstract Background TSPAN7 is an important factor in tumor progression. However, the precise function of TSPAN7 and its role in pan-cancer are not clear. Methods Based on Xinhua cohort incorporating 370 patients with kidney neoplasm, we conducted differential expression analysis by immunohistochemistry between tumor and normal tissues, and explored correlations of TSPAN7 with patients’ survival. Subsequently, we conducted a pan-cancer study, and successively employed differential expression analysis, competing endogenous RNA (ceRNA) analysis, protein-protein interaction (PPI) analysis, correlation analysis of TSPAN7 with clinical characteristics, tumor purity, tumor genomics, tumor immunity, and drug sensitivity. Last but not least, gene set enrichment analysis was applied to identify enriched pathways of TSPAN7. Results In Xinhua cohort, TSPAN7 expression was significantly up-regulated (P-value = 0.0019) in tumor tissues of kidney neoplasm patients. High TSPAN7 expression was associated with decreases in overall survival (OS) (P-value = 0.009) and progression-free survival (P-value = 0.009), and it was further revealed as an independent risk factor for OS (P-value = 0.0326, HR = 5.66, 95%CI = 1.155–27.8). In pan-cancer analysis, TSPAN7 expression was down-regulated in most tumors, and it was associated with patients’ survival, tumor purity, tumor genomics, tumor immunity, and drug sensitivity. The ceRNA network and PPI network of TSPAN7 were also constructed. Last but not least, the top five enriched pathways of TSPAN7 in various tumors were identified. Conclusion TSPAN7 served as a promising biomarker of various tumors, especially kidney neoplasms, and it was closely associated with tumor purity, tumor genomics, tumor immunology, and drug sensitivity in pan-cancer level.

Abstract Background Chitinase-3 like-protein-1 (CHI3L1) is a member of the mammalian chitinase-like proteins and elevated serum CHI3L1 level has been proved to be associated with poor prognosis in hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between serum CHI3L1 levels and body composition parameters in patients with HCC after liver transplantation (LT). Methods This retrospective study enrolled 200 patients after LT for HCC. Blood samples were collected and serum concentrations of CHI3L1 were measured by enzyme-linked immunosorbent assay. Computer tomography (CT) were used to estimate skeletal muscle and adipose tissue mass. Spearman’s rank correlation test was performed to assess associations between serum CHI3L1 levels and these body composition parameters. A Cox proportional-hazards regression model was performed to identify independent prognostic factors. Overall survival (OS) and recurrence-free survival (RFS) curves were constructed using the Kaplan-Meier method and compared by the log-rank test. Results Total 71 patients (35.5%) were diagnosed with myosteatosis according to skeletal muscle radiation attenuation (SMRA). The 5-year OS rates were 66.9% in non-myosteatosis group, significantly higher than 49.5% in myosteatosis group (p = 0.025), while the RFS of myosteatosis group (5-year RFS: 52.6%) or non-myosteatosis group (5-year RFS: 42.0%) shown no significant difference (p = 0.068). The serum CHI3L1 level were significantly negative correlated with SMRA (r = -0.3, p

Abstract Background This study aims to evaluate the association of metabolic syndrome (MetS) with the risk of all-cause mortality in elderly patients with acute respiratory distress syndrome (ARDS). Methods Elderly ARDS patients (≥ 65 years) enrolled from our hospital between January 2018 and July 2023 were divided into the MetS group or the non-MetS group. The outcomes were 28-day and 90-day all-cause mortality rates in the total population and two subgroups stratified by age (65–75 years and ≥ 75 years). Multivariate Cox regression was employed to assess the association of MetS with all-cause mortality, after controlling for potential cofounding factors. Results A total of 946 patients were divided into the MetS group (n = 410) or the non-MetS group (n = 536). The 28-day and 90-day all-cause mortality rates were significantly higher for MetS group compared to non-MetS group in the total population and two subgroups (all P

Abstract Although immune checkpoint inhibitors (anti-PD-1 antibody, anti-PD-L1 antibody, and anti-CTLA-4 antibody) have displayed considerable success in the treatment of malignant tumors, the therapeutic effect is still unsatisfactory for a portion of patients. Therefore, it is imperative to develop strategies to enhance the effect of these ICIs. Increasing evidence strongly suggests that the key to this issue is to transform the tumor immune microenvironment from a state of no or low immune infiltration to a state of high immune infiltration and enhance the tumor cell-killing effect of T cells. Therefore, some combination strategies have been proposed and this review appraise a summary of 39 strategies aiming at enhancing the effectiveness of ICIs, which comprise combining 10 clinical approaches and 29 foundational research strategies. Moreover, this review improves the comprehensive understanding of combination therapy with ICIs and inspires novel ideas for tumor immunotherapy.

Abstract Background Eosinophilic esophagitis is a chronic inflammatory disorder of the esophagus. This real-world study used patient and physician surveys to describe the clinical characteristics and disease burden of eosinophilic esophagitis—overall and in a subgroup of patients with dysphagia despite treatment. Methods Data analyzed in this study were collected in 2020 from US and EU patients with eosinophilic esophagitis. Eligible patients were aged ≥ 12 years with a diagnosis of eosinophilic esophagitis, had an esophageal count of ≥ 15 eosinophils/high-power field at diagnosis, and were currently prescribed treatment for eosinophilic esophagitis. Results Overall, 1001 patients were included, of whom 356 (36%) had dysphagia despite treatment. Demographics and clinical characteristics were similar in both populations. The severity of eosinophilic esophagitis was mild in more patients overall (69%) versus those with dysphagia despite treatment (48%). Patient disease history was similar in both populations, with some exceptions: common patient-reported symptoms were dysphagia (70% and 86%) and heartburn/acid reflux (55% and 49%), and common physician-reported symptoms were dysphagia (75% and 91%) and food impaction (46% and 52%). Treatment history was similar in both populations; overall, the most common treatments were proton pump inhibitors (83%) and topical corticosteroids (51%). Patients reported slightly more days with symptoms, higher impacts on activities of daily living, and slightly higher anxiety or depression in the dysphagia-despite-treatment population versus the overall population. Conclusions Eosinophilic esophagitis presents severe symptoms and comorbidities that substantially impact patients’ well-being and quality of life. Greater awareness of and novel treatments for eosinophilic esophagitis are needed.

Abstract Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with high incidence, recurrence, and metastasis rates. The emergence of immunotherapy has improved the treatment of advanced HCC, but problems such as drug resistance and immune-related adverse events still exist in clinical practice. The immunosuppressive tumor microenvironment (TME) of HCC restricts the efficacy of immunotherapy and is essential for HCC progression and metastasis. Therefore, it is necessary to elucidate the mechanisms behind immunosuppressive TME to develop and apply immunotherapy. This review systematically summarizes the pathogenesis of HCC, the formation of the highly heterogeneous TME, and the mechanisms by which the immunosuppressive TME accelerates HCC progression and metastasis. We also review the status of HCC immunotherapy and further discuss the existing challenges and potential therapeutic strategies targeting immunosuppressive TME. We hope to inspire optimizing and innovating immunotherapeutic strategies by comprehensively understanding the structure and function of immunosuppressive TME in HCC.

Abstract Background Lung cancer is a common cause of brain metastases, approximately 40% of patients with lung cancer will develop brain metastases at some point during their disease. Hypofractionated stereotactic radiotherapy (HSRT) has been demonstrated to be effective in controlling limited brain metastases. However, there is still no conclusive on the optimal segmentation of HSRT. The aim of our study was to explore the correlation between the HSRT dosage and its treatment effect and toxicity. Methods A retrospective analysis was conducted on patients with non-small cell lung cancer (NSCLC) brain metastasis at Hangzhou Cancer Hospital from 1 January 2019 to 1 January 2021. The number of brain metastases did not exceed 10 in all patients and the number of fractions of HSRT was 5. The prescription dose ranges from 25 to 40 Gy. The Kaplan–Meier method was used for estimation of the localised intracranial control rate (iLC). Adverse radiation effects (AREs) were evaluated according to CTCAE 5.0. This study was approved by the Institutional Ethics Review Board of the Hangzhou Cancer Hospital (#73/HZCH-2022). Results Forty eligible patients with a total of 70 brain metastases were included in this study. The 1-year iLC was 76% and 89% in the prescribed dose ≤ 30 Gy and > 30 Gy group, respectively (P

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the digestive system, and the exact mechanism of HCC is still unclear. Transcription factor 7 like 2 (TCF7L2) plays a pivotal role in cell proliferation and stemness maintenance. However, the exact mechanism of TCF7L2 in HCC remains unclear. Methods Clinical samples and public databases were used to analyze the expression and prognosis of TCF7L2 in HCC. The function of TCF7L2 in HCC was studied in vitro and in vivo. ChIP and luciferase assays were used to explore the molecular mechanism of TCF7L2. The relationship between TCF7L2 and NEDD9 was verified in HCC clinical samples by tissue microarrays. Results The expression of TCF7L2 was upregulated in HCC, and high expression of TCF7L2 was associated with poor prognosis of HCC patients. Overexpression of TCF7L2 promoted the metastasis of HCC in vitro and in vivo, while Knockdown of TCF7L2 showed the opposite effect. Mechanically, TCF7L2 activated neural precursor cell expressed developmentally downregulated protein 9 (NEDD9) transcription by binding to the -1522/-1509 site of the NEDD9 promoter region, thereby increasing the phosphorylation levels of AKT and mTOR. The combination of TCF7L2 and NEDD9 could distinguish the survival of HCC patients. Conclusions This study demonstrated that TCF7L2 promotes HCC metastasis by activating AKT/mTOR pathway in a NEDD9-dependent manner, suggesting that potential of TCF7L2 and NEDD9 as prognostic markers and therapeutic targets for HCC.

Hepatocellular carcinoma (HCC) is one of the cancers with the highest incidence and mortality rates in China and often presents with insidious early clinical manifestations. This frequency results in the majority of patients being diagnosed at middle and advanced stage of the disease, thereby missing the opportunity for potentially curative surgical interventions. For patients who are ineligible for radical surgical resection, a variety of therapeutic approaches, including systemic antitumor therapy, local radiotherapy, interventional treatment, and liver transplantation, have been employed. Moreover, neoadjuvant therapies have transformed a subset of initially unresectable HCC cases into operable ones. Nevertheless, many patients fail to benefit from these treatments, underscoring the urgent need for novel therapeutic targets. Cancer-associated fibroblasts (CAFs), a principal component of the solid tumor microenvironment, play a pivotal role in the proliferation, migration, invasion, and treatment resistance of cancer cells. This review delineates the origins of CAFs and their mechanisms of action in the pathogenesis and progression of HCC and discusses potential therapeutic strategies targeting CAFs.

Objective To compare the differences in gut microbiota between cirrhosis patients receiving transjugular intrahepatic portosystemic shunt (TIPS) and those not, and explore the relationship between TIPS surgery and gut microbiota in order to provide new ideas for improving the prognosis of cirrhosis patients after TIPS surgery based on gut microbiota. Methods Those who had received TIPS surgery previously were assigned into the operation group, and those without the surgery served as the control group. Their stool samples were collected for 16S rRNA sequencing, and the correlation between gut microbiota and clinical indicators was analyzed. Results There were no significant differences in gender, age, body mass index (BMI), etiology and other baseline data between the 2 groups (P>0.05), but obvious differences were observed in clinical serological indicators between them, including INR, APTT, RBC and PT counts, and HGB, ALP, ALB, total bilirubin (TBIL), and URE levels (P0.05), but beta diversity was obviously different (P

Abstract Hepatic ischemia–reperfusion injury (HIRI) is a critical pathophysiological process during liver transplantation (LT). Multiple genes and signal pathways are dysregulated during HIRI. This study aims to identify genes as potential therapeutic targets for ameliorating HIRI. Datasets containing samples from the human donor liver (GSE151648) and mouse HIRI model (GSE117066) were analyzed to determine differentially expressed genes (DEGs). The selected DEGs were confirmed by real-time PCR and western blot in the hepatocyte hypoxia-reoxygenation (HR) model, mouse HIRI model, and human liver samples after transplantation. Genetic inhibition was used to further clarify the underlying mechanism of the gene in vitro and in vivo. Among the DEGs, CSRNP1 was significantly upregulated (|log FC|= 2.08, P

The regenerative capability of the liver is remarkable, but further research is required to understand the role that neutrophils play in this process. In the present study, we reanalyzed single‐cell RNA sequencing data from a mouse partial hepatectomy (PH) model to track the transcriptional changes in hepatocytes and non‐parenchymal cells. Notably, we unraveled the regenerative capacity of hepatocytes at diverse temporal points after PH, unveiling the contributions of three distinct zones in the liver regeneration process. In addition, we observed that the depletion of neutrophils reduced the survival and liver volume after PH, confirming the important role of neutrophils in liver regeneration. CellChat analysis revealed an intricate crosstalk between neutrophils and macrophages promoting liver regeneration and, using weighted gene correlation network analysis, we identified the most significant genetic module associated with liver regeneration. Our study found that hepatocytes in the periportal zone of the liver are more active than in other zones, suggesting that the crosstalk between neutrophils and macrophages might be a potential target for liver regeneration treatment.

Aim: This systematic review and meta-analysis aimed to assess the safety and efficacy of Baduanjin, a traditional Chinese exercise (TCM), for reducing depression and anxiety in individuals suffering from coronavirus disease 2019 (COVID-19). Methods: Nineteen databases were searched from their inception through August 2024 to gather data for this study. The focus of this study was randomized controlled trials (RCTs) in which Baduanjin was administered for the treatment of COVID-19 patients with depression and anxiety. The study included various types of Baduanjin exercise, whether used alone or in conjunction with other treatment modalities, for the control group. The comparators included a waitlist control, usual care, health education and supportive counseling, psychosocial support therapy, pharmacotherapies, and other common exercises. The exclusion criteria for trials were trials comparing different treatment durations, different treatment frequencies, and different types of Baduanjin exercise. Moreover, other traditional Chinese medicine (TCM) therapeutic methods applied in either the intervention or control group were also excluded. Throughout the entire study, the selection process, data extraction and quantitative analysis were carried out in strict adherence to all relevant guidelines. The Cochrane criteria for risk of bias were used to assess the methodological quality of the trials. In our review, a meta-analysis was performed using the software STATA MP14. Results: After conducting a meta-analysis, eight RCTs were found to have satisfied the inclusion criteria. The effects of Baduanjin exercise on self-rating anxiety scale (SAS) scores were investigated in five RCTs comprising a total of 228 patients. Analysis of the results revealed that the combination of Baduanjin exercises and conventional therapies led to a statistically significant reduction in SAS scores [MD=-3.21 (95 % CI= −3.64, −2.79), P< 0.001] compared to conventional therapies alone. Moreover, this systematic review explored the effect of Baduanjin exercise on self-rating depression scale (SDS) scores (three RCTs involving 83 participants), Hamilton Anxiety Rating Scale (HAM-A) scores (one RCT involving 103 participants), Patient Health Questionnaire (PHQ-9) scores (one RCT involving 70 participants) and Generalized Anxiety Disorder-7 (GAD-7) scores (one RCT involving 59 participants) for patients with COVID-19. The results showed that, in addition to conventional therapies, Baduanjin exercise had a more favorable impact on reducing the SDS score [mean difference (MD) =-2.86 (95 % CI=4.11, −1.61), P=0.025], PHQ-9 score [MD=-5.31, 95 % CI=-8.73, −1.89), P=0.002] and HAM-A score [MD=-3.00, 95 % CI=-5.33, −0.67], P=0.010] in patients with COVID-19 than did the use of conventional therapies alone. Furthermore, the combination of Baduanjin exercise and conventional therapies effectively decreased the number of patients who experienced severe or moderate anxiety according to the GAD-7 score compared to that of patients who experienced severe or moderate anxiety according to conventional therapies alone [Relative Risk (RR) =0.03, 95 % CI=0.00, 0.51); P=0.020]. However, the included clinical trials lacked a detailed description of the randomization process, and only a small portion of the studies reported proper allocation concealment procedures, which may introduce selection bias. Moreover, owing to the nature of Baduanjin exercise, it is difficult to blind participants and practitioners, which may lead to performance bias. Furthermore, the lack of blinding may lead to subjective influences of assessors on the results, thereby causing detection bias. These methodological shortcomings and potential biases should be addressed in future studies. Conclusions: It is difficult to draw firm conclusions on whether Baduanjin exercise is an effective intervention for reducing depression and anxiety in COVID-19 patients because of the high risk of bias among the available RCTs. Further rigorous RCTs are warranted but need to overcome the methodological shortcomings of the existing evidence.

Abstract Aim To investigate and analyse the current situation of clinical nurses' sense of organisational support, emotional intelligence and work engagement in different departments and their correlation, in order to provide guidance for enhancing the sense of organisational support, improving nurses' emotional intelligence and mobilising nurses' work engagement and to promote the development of nursing teams. Methods Clinical nurses from three hospitals in eastern and western China were selected by convenience sampling method from September to October 2023 and were surveyed using a general information questionnaire, organisational support questionnaire, emotional intelligence scale and work engagement scale. We investigated the correlation between nurses' sense of organisational support, emotional intelligence and work engagement in clinical units. Results The clinical nurses investigated in this study had moderate levels of perceived organisational support and emotional intelligence and high levels of work engagement. The total score of the nurses' sense of organisational support questionnaire was positively correlated with the total score of the emotional intelligence scale, the total score of the work engagement scale and the scores of all dimensions (all p

Abstract Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer and its prognosis remains poor. Although growing numbers of studies have verified the involvement of circular RNAs (circRNAs) in various cancer types, their specific functions in ICC remain elusive. Herein, a circRNA, circUGP2 is identified by circRNA sequencing, which is downregulated in ICC tissues and correlated with patients’ prognosis. Moreover, circUGP2 overexpression suppresses tumor progression in vitro and in vivo. Mechanistically, circUGP2 functions as a transcriptional co‐activator of PURB over the expression of ADGRB1. It can also upregulate ADGRB1 expression by sponging miR‐3191‐5p. As a result, ADGRB1 prevents MDM2‐mediated p53 polyubiquitination and thereby activates p53 signaling to inhibit ICC progression. Based on these findings, circUGP2 plasmid is encapsulated into a lipid nanoparticle (LNP) system, which has successfully targeted tumor site and shows superior anti‐tumor effects. In summary, the present study has identified the role of circUGP2 as a tumor suppressor in ICC through regulating ADGRB1/p53 axis, and the application of LNP provides a promising translational strategy for ICC treatment.

Research on the functional traits of twigs is of great significance to clarify the plant life-history strategies, especially for endangered plants. However, little attention has been given to the environmental adaptation strategy of different age twigs. The dove tree (Davidia involucrata Baill.), a relict and critically endangered Chinese species, was employed as a model species. Total lamina mass and area, stem mass and length, total bract mass and area, and total petiole mass were measured for 100 current-year terminal twigs (50 per age group) from old and young dove trees in Pingwu County, Sichuan, southwest China. Then, the scaling relationships within the twig were determined using the standardized major axis (SMA) regression method. Our results showed that the significantly positive correlations among traits of D. involucrata twigs, and scaling relationships between these traits are different between the two age groups. At the twig level, isometric scaling relationships exist between stem mass and lamina size (or bract size) and between total lamina mass and total lamina area (or total petiole mass). In contrast, allometric scaling relationships exist between lamina size (total mass and area) and stem length (with a common slope > 1), and between total lamina mass and total petiole mass (with a common slope < 1). For a given stem mass, stem length and bract area, young trees have larger total lamina mass and total bract mass, larger total lamina mass and area, and larger total bract mass than old trees, respectively. The results suggest that young trees tend to have more vegetative and reproductive organ mass per unit of supporting organ mass than old trees to meet their rapid growth needs.

The advancements in intelligent action recognition can be instrumental in developing autonomous robotic systems capable of analyzing complex human activities in real-time, contributing to the growing field of robotics that operates in dynamic environments. The precise recognition of basketball players' actions using artificial intelligence technology can provide valuable assistance and guidance to athletes, coaches, and analysts, and can help referees make fairer decisions during games. However, unlike action recognition in simpler scenarios, the background in basketball is similar and complex, the differences between various actions are subtle, and lighting conditions are inconsistent, making action recognition in basketball a challenging task. To address this problem, an Adaptive Context-Aware Network (ACA-Net) for basketball player action recognition is proposed in this paper. It contains a Long Short-term Adaptive (LSTA) module and a Triplet Spatial-Channel Interaction (TSCI) module to extract effective features at the temporal, spatial, and channel levels. The LSTA module adaptively learns global and local temporal features of the video. The TSCI module enhances the feature representation by learning the interaction features between space and channels. We conducted extensive experiments on the popular basketball action recognition datasets SpaceJam and Basketball-51. The results show that ACA-Net outperforms the current mainstream methods, achieving 89.26% and 92.05% in terms of classification accuracy on the two datasets, respectively. ACA-Net's adaptable architecture also holds potential for real-world applications in autonomous robotics, where accurate recognition of complex human actions in unstructured environments is crucial for tasks such as automated game analysis, player performance evaluation, and enhanced interactive broadcasting experiences.

Abstract Despite the success of immunotherapy in treating hepatocellular carcinoma (HCC), HCC remains a severe threat to health. Here, a crucial transcription factor, SOX12, is revealed that induces the immunosuppression of liver tumor microenvironment. Overexpressing SOX12 in HCC syngeneic models increases intratumoral regulatory T‐cell (Treg) infiltration, decreases CD8+T‐cell infiltration, and hastens HCC metastasis. Hepatocyte‐specific SOX12 knockout attenuates DEN/CCl4‐induced HCC progression and metastasis, whereas hepatocyte‐specific SOX12 knock‐in accelerates these effects. Mechanistically, SOX12 transcriptionally activates C‐C motif chemokine ligand 22 (CCL22) expression to promote the recruitment and suppressive activity of Tregs. Moreover, SOX12 transcriptionally upregulates CD274 expression to suppress CD8+T‐cell infiltration. Either knockdown of CCL22 or PD‐L1 dampens SOX12‐mediated HCC metastasis. Blocking of CC chemokine receptor 4 (CCR4), a receptor for CCL22, by inhibitor C‐021 or Treg‐specific knockout of CCR4 inhibits SOX12‐mediated HCC metastasis. Transforming growth factor‐β1 (TGF‐β1)/TGFβR1‐Smad2/3/4 is identified as a key upstream signaling for SOX12 overexpression in HCC cells. Combining C‐021 or TGFβR1 inhibitor galunisertib with anti‐PD‐L1 exhibits an enhanced antitumor effect in two HCC models. Collectively, the findings demonstrate that SOX12 contributes to HCC immunosuppression through the CCL22/CCR4‐Treg and PD‐L1‐CD8+T axes. Blocking of CCR4 or TGFβR1 improves the efficacy of anti‐PD‐L1 in SOX12‐mediated HCC.

Abstract Tumor recurrence is a life‐threatening complication after liver transplantation (LT) for hepatocellular carcinoma (HCC). Precise recurrence risk stratification before transplantation is essential for the management of recipients. Here, we aimed to establish an inflammation‐related prediction model for posttransplant HCC recurrence based on pretransplant peripheral cytokine profiling. Two hundred and ninety‐three patients who underwent LT in two independent medical centers were enrolled, and their pretransplant plasma samples were sent for cytokine profiling. We identified four independent risk factors, including alpha‐fetoprotein, systemic immune‐inflammation index, interleukin 6, and osteocalcin in the training cohort (n = 190) by COX regression analysis. A prediction model named inflammatory fingerprint (IFP) was established based on the above factors. The IFP effectively predicted posttransplant recurrence (area under the receiver operating characteristic curve [AUROC]: 0.792, C‐index: 0.736). The high IFP group recipients had significantly worse 3‐year recurrence‐free survival rates (37.9 vs. 86.9%, p

Liver transplantation (LT) is the standard therapy for individuals afflicted with end-stage liver disease. Despite notable advancements in LT technology, the incidence of early allograft dysfunction (EAD) remains a critical concern, exacerbating the current organ shortage and detrimentally affecting the prognosis of recipients. Unfortunately, the perplexing hepatic heterogeneity has impeded characterization of the cellular traits and molecular events that contribute to EAD. Herein, we constructed a pioneering single-cell transcriptomic landscape of human transplanted livers derived from non-EAD and EAD patients, with 12 liver samples collected from 7 donors during the cold perfusion and portal reperfusion stages. Comparison of the 75 231 cells of non-EAD and EAD patients revealed an EAD-associated immune niche comprising mucosal-associated invariant T cells, granzyme B+ (GZMB+) granzyme K+ (GZMK+) natural killer cells, and S100 calcium binding protein A12+ (S100A12+) neutrophils. Moreover, we verified this immune niche and its association with EAD occurrence in two independent cohorts. Our findings elucidate the cellular characteristics of transplanted livers and the EAD-associated pathogenic immune niche at the single-cell level, thus, offering valuable insights into EAD onset.

Abstract Charge loss at grain boundaries of kesterite Cu2ZnSn(S, Se)4 polycrystalline absorbers is an important cause limiting the performance of this emerging thin-film solar cell. Herein, we report a Pd element assisted reaction strategy to suppress atomic vacancy defects in GB regions. The Pd, on one hand in the form of PdSe x compounds, can heterogeneously cover the GBs of the absorber film, suppressing Sn and Se volatilization loss and the formation of their vacancy defects (i.e. VSn and VSe), and on the other hand, in the form of Pd(II)/Pd(IV) redox shuttle, can assist the capture and exchange of Se atoms, thus contributing to eliminating the already-existing VSe defects within GBs. These collective effects have effectively reduced charge recombination loss and enhanced p-type characteristics of the kesterite absorber. As a result, high-performance kesterite solar cells with a total-area efficiency of 14.5% (certified at 14.3%) have been achieved.

Abstract Background To improve patient outcomes and provider team practice, the California Perinatal Quality Care Collaborative (CPQCC) created the Simulating Success quality improvement program to assist hospitals in implementing a neonatal resuscitation training curriculum. This study aimed to examine the costs associated with the design and implementation of the Simulating Success program. Methods From 2017–2020, a total of 14 sites participated in the Simulating Success program and 4 of them systematically collected resource utilization data. Using a micro-costing approach, we examined costs for the design and implementation of the program occurring at CPQCC and the 4 study sites. Data collection forms were used to track personnel time, equipment/supplies, space use, and travel (including transportation, food, and lodging). Cost analysis was conducted from the healthcare sector perspective. Costs incurred by CPQCC were allocated to participant sites and then combined with site-specific costs to estimate the mean cost per site, along with its 95% confidence interval (CI). Cost estimates were inflation-adjusted to 2022 U.S. dollars. Results Designing and implementing the Simulating Success program cost $228,148.36 at CPQCC, with personnel cost accounting for the largest share (92.2%), followed by program-related travel (6.1%), equipment/supplies (1.5%), and space use (0.2%). Allocating these costs across participant sites and accounting for site-specific resource utilizations resulted in a mean cost of $39,210.69 per participant site (95% CI: $34,094.52-$44,326.86). In sensitivity analysis varying several study assumptions (e.g., number of participant sites, exclusion of design costs, and useful life span of manikins), the mean cost per site changed from $35,645.22 to $39,935.73. At all four sites, monthly cost of other neonatal resuscitation training was lower during the program implementation period (mean = $1,112.52 per site) than pre-implementation period (mean = $2,504.01 per site). In the 3 months after the Simulating Success program ended, monthly cost of neonatal resuscitation training was also lower than the pre-implementation period at two of the four sites. Conclusions Establishing a multi-site neonatal in situ simulation program requires investment of sufficient resources. However, such programs may have financial and non-financial benefits in the long run by offsetting the need for other neonatal resuscitation training and improving practice.

Objective: Sex-specific differences are observed in various liver diseases, but the influence of sex on the outcomes of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains to be determined. This study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with HCC. Methods: Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were analyzed. The associations between donor, recipient, or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching (PSM). The survival associated with different sex-based donor-recipient transplant patterns was further studied. Results: Among 3,769 patients enrolled in this study, the 1-, 3-, and 5-year overall survival (OS) rates of patients with HCC after LT were 96.1%, 86.4%, and 78.5%, respectively, in female recipients, and 95.8%, 79.0%, and 70.7%, respectively, in male recipients after PSM ( P = 0.009). However, the OS was comparable between recipients with female donors and male donors. Multivariate analysis indicated that male recipient sex was a risk factor for post-LT survival (HR = 1.381, P = 0.046). Among the donor-recipient transplant patterns, the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival ( P < 0.05). Conclusions: Our findings highlighted that the post-LT outcomes of female recipients were significantly superior to those of male recipients, and the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival. Livers from male donors may provide the most benefit to female recipients. Our results indicate that sex should be considered as a critical factor in organ allocation.

● Objective based county-level AGD evaluation index system was established.● A typical agricultural county of Quzhou County in the North China Plain was use as a representative study.● Unbalanced development was revealed as well as large gaps relative to targets.● Spearman rank correlation analysis revealed more synergistic effect than trade-off effect.● Trade-off existed between eco-environment and both food production and socioeconomic dimensions.Agriculture green development (AGD) has become an unavoidable choice to address the unique national circumstances of China. This study established a county-level AGD evaluation index system, comprised three dimensions, food production, ecological environment and socioeconomic development, using 20 indicators. The assessment delved into historical trend and current situation, utilizing Spearman rank correlation analysis to analyze trade-off and synergy relationships, using Quzhou County, Hebei Province as a case study. The main findings were in four areas. Firstly, the index for AGD in Quzhou County increased by 58.9% from 1978 to 2019. The major contribution were the social economy (65.8%) and food production (53.5%), whereas the ecological environment was found to have had a negative impact. Secondly, in 2019, the AGD index was only 56.4, indicating substantial potential for improvement relative to the target value. A notable difference in scores existed between the three dimensions, with the order being ecological environment (66.3) > food production (61.7) > socioeconomic (41.3). Also, 90% of the indicators did not reach the target value. Thirdly, relationship analysis of the indicators revealed that the synergistic effect exceeded the trade-off effect. Specifically, 46.3% of the indicators had no significant relationship, 35.3% had a synergistic relationship, and 18.4% had a trade-off relationship. Finally, interdimensional indicator relationships exhibited a trade-off effect between the ecological environment and both food production and socioeconomic dimensions. However, a positive trend of synergy between production and ecology has emerged since 2015. In conclusion, the quantitative evaluation index system exposed the unbalanced development and significant potential relative to the target value of AGD in Quzhou County, despite notable progress.

The liver has a strong regenerative capacity that ensures patient recovery after hepatectomy and liver transplantation. The portal system plays a crucial role in the dual blood supply to the liver, making it a significant factor in hepatic function. Several surgical strategies, such as portal vein ligation, associating liver partition and portal vein ligation for staged hepatectomy, and dual vein embolization, have highlighted the portal system's importance in liver regeneration. Following hepatectomy or liver transplantation, the hemodynamic properties of the portal system change dramatically, triggering regeneration via shear stress and the induction of hypoxia. However, excessive portal hyperperfusion can harm the liver and negatively affect patient outcomes. Furthermore, as the importance of the gut–liver axis has gradually been revealed, the effect of metabolites and cytokines from gut microbes carried by portal blood on liver regeneration has been acknowledged. From these perspectives, this review outlines the molecular mechanisms of the portal system's role in liver regeneration and summarizes therapeutic strategies based on the portal system intervention to promote liver regeneration.

The bank slope rock mass below the flood control restricted water level (145 m) in the Three Gorges Reservoir area has experienced long-term immersion in the process of reservoir water lifting and lowering; the water level changes lead to the rock mass being subjected to two working conditions, tangential loading shearing and normal unloading shearing. The difference in rock shearing characteristics directly affects the stability evaluation of bank slopes in different reservoir operation stages. Tangential loading and normal unloading shear tests were carried out on the typical feldspar quartz sandstone after different soaking days; then the characteristics changes of sandstone shear under the two stress conditions were obtained. The microscopic mechanism of the differences was revealed by solution test, SEM test, and nuclear magnetic resonance test. The results show that: (1) compared with the initial sample, after soaking for 80 days, the cohesion loss of the sample is greater than the loss of internal friction angle. The cohesion of the sample under tangential loading is reduced by 40.5%, and the internal friction Angle is only reduced by 2%, while the cohesion of the sample under normal unloading shear is reduced by 31%, and the internal friction Angle is reduced by 8%. (2) The long-term immersion of the sample results in the dissolution of the cement minerals, the gradual development and penetration of the secondary pores, and the increase of porosity. After 60 days of immersion, basically， the water content, porosity, and pore structure of the sample reach a stable state; the particle skeleton overcoming the shear action is almost no longer affected by the soaking water. This is the reason why the shear properties of the samples with long-term water saturation gradually weaken and become stable. (3) Under normal unloading shear conditions, the deviation between the main crack surface and the theoretical shear surface increases; the fracture surface is more inclined to form “S” and “M” types. The increase of the actual shear plane increases the peak shear stress that the rock can bear. Because the biggest contribution to the rock is the skeleton particle, the internal friction angle is larger, and the filling cementing material that provides cohesion makes less contribution to the tensile shear failure. The cohesion obtained by normal unloading is also lower. This study can provide basic information for the stability evaluation of wading slope in reservoir area with the fluctuation of water level and the selection of test method considering the actual working conditions.

Abstract Sirolimus is a regularly applied immunosuppressant for patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC). Sirolimus not only significantly inhibits HCC recurrence but also protects renal function. However, the improvement effect of sirolimus on nontumour-related death in patients is still unknown. The aim of our study was to investigate the therapeutic effect of sirolimus on nontumour-related deaths. In this study, we retrospectively enrolled 403 LT patients with HCC from January 1, 2015, to December 31, 2018. The median follow-up time was 47.1 months. The patients were divided into the sirolimus group (N = 184) and the sirolimus-free group (N = 219). There were no significant differences between the sirolimus group and the sirolimus-free group in survival (P = 0.054). In transplant patients who exceeded the Milan or Hangzhou criteria, the sirolimus group achieved higher survival than the sirolimus-free group (P = 0.005; P = 0.02). Moreover, multivariate analysis showed that sirolimus strongly reduced the hazard ratio (HR) for nontumour-related death in LT patients who exceeded the Milan (HR: 0.42; 95% CI: 0.18–1; P = 0.05) or Hangzhou criteria (HR: 0.26; 95% CI: 0.08–0.89; P = 0.032). HCC recurrence increased the risk of nontumour-related death. In conclusion, sirolimus-based immunosuppression can significantly reduce nontumour-related death in LT patients who exceed the criteria for transplantation. In addition, this finding will further promote the application of sirolimus after liver transplantation for hepatocellular carcinoma.

Malignant tumors of the digestive system have had a notoriously dismal prognosis throughout history. Immunotherapy, radiotherapy, surgery, and chemotherapy are the primary therapeutic approaches for digestive system cancers. The rate of recurrence and metastasis, nevertheless, remains elevated. As one of the immunotherapies, chimeric antigen receptor T cell (CAR-T) therapy has demonstrated a promising antitumor effect in hematologic cancer. Despite undergoing numerous clinical trials, the ineffective antitumor effect and adverse effects of CAR-T cell therapy in the treatment of digestive system cancers continue to impede its clinical translation. It is necessary to surmount the restricted options for targeting proteins, the obstacles that impede CAR-T cell infiltration into solid tumors, and the limited survival time in vivo. We examined and summarized the developments, obstacles, and countermeasures associated with CAR-T therapy in digestive system cancers. Emphasis was placed on the regulatory functions of potential antigen targets, the tumor microenvironment, and immune evasion in CAR-T therapy. Thus, our analysis has furnished an all-encompassing comprehension of CAR-T cell therapy in digestive system cancers, which will generate tremendous enthusiasm for subsequent in-depth research into CAR-T-based therapies in digestive system cancers.

Manganese (Mn) is necessary for various biological processes, yet its function in innate immunity has been less studied, especially in fish. Stimulator of interferon (IFN) genes (STING) is an essential factor for IFN induction in virus infection. Our study demonstrated that Mn2+ increases the ability of zebrafish to resist spring viraemia of carp virus (SVCV) infection by enhancing the expression of STING. Further mechanistic studies indicated that Mn2+ promotes the expression of STING by increasing its ubiquitination. Furthermore, Mn2+treatment promoted STING-mediated activation of IFN and reversed the decrease in STING protein induced by SVCV. Collectively, our findings showed the vital involvement and necessity of Mn2+ in protecting fish against SVCV infection.

BackgroundMore than 1 million women have their labor induced in the United States each year, and synthetic oxytocin infusion is the most common method used. However, compared to spontaneous labor, medical induction is resource intensive, has increased obstetric risks, and is associated with less successful breastfeeding. In contrast to the endogenous oxytocin hormone, which is released in a pulsatile fashion in the brain, synthetic oxytocin is continuously infused intravenously, resulting in important limitations related to efficacy, safety, and cost. Akin to spontaneous labor contractions, infant suckling of the breast nipple is known to stimulate the pulsatile release of endogenous oxytocin from the posterior pituitary gland. Nipple stimulation therapy via an electric breast pump similarly stimulates endogenous oxytocin release and may be a favorable inpatient method for patients undergoing labor induction. ObjectiveThis study aims to examine whether inpatient nipple stimulation therapy is an efficacious labor induction method that increases the likelihood of spontaneous vaginal delivery and sustained breastfeeding and determine whether it is a cost-effective approach. MethodsThis is a multicenter, pragmatic, open-label, parallel-group randomized controlled trial of nulliparous patients with singleton gestations ≥36 weeks undergoing labor induction. This trial compares inpatient nipple stimulation therapy via an electric breast pump versus immediate synthetic oxytocin infusion without nipple stimulation. This trial including 988 nulliparas will provide adequate statistical power to detect clinically meaningful differences in delivery mode and breast milk as the sole source of nutrition for newborns at hospital discharge or 72 hours after birth. ResultsThe project received pilot funding in 2021 and full funding in 2023. Enrollment for this study began in November 2021 at a single site, and as of May 2024, recruitment is underway at 3 study sites. It is anticipated that enrollment will be completed by late 2026. ConclusionsSuccessful completion of this trial will provide rigorous data to determine whether inpatient nipple stimulation therapy with an electric breast pump can improve the way we induce labor and positively impact breastfeeding success and early infant nutrition through lactation. Trial RegistrationClinicalTrials.gov NCT05079841; https://clinicaltrials.gov/study/NCT05079841 International Registered Report Identifier (IRRID)DERR1-10.2196/63463

ObjectiveWe conducted this meta-analysis to comprehensively explore the prognostic value of the preoperative plasma fibrinogen in Asian patients diagnosed with urothelial cancer (UC).MethodsAfter a systematic search of Web of Science, PubMed, and Embase before May 2024, we included 10 studies in our meta-analysis. The hazard ratios (HRs) with 95% confidence interval (CI) for overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression free survival (PFS) were estimated using fixed effect model.ResultsThis meta-analysis included a total of 2875 patients. UC patients with an elevated preoperative plasma fibrinogen had worse OS (pooled HR: 2.13, 95% CI: 1.81-2.51; P

Objectives: Celastrol has widespread therapeutic applications in various pathological conditions, including chronic inflammation. Previous studies have demonstrated the potent cardioprotective effects of celastrol. Nevertheless, limited attention has been given to its potential in reducing ventricular arrhythmias (VAs) following myocardial infarction (MI). Hence, this study aimed to elucidate the potential mechanisms underlying the regulatory effects of celastrol on VAs and cardiac electrophysiological parameters in rats after MI. Methods: Sprague-Dawley rats were divided at random: the sham, MI, and MI + celastrol groups. The left coronary artery was occluded in the MI and MI + Cel groups. Electrocardiogram, heart rate variability (HRV), ventricular electrophysiological parameters analysis, histology staining of ventricles, Enzyme-linked immunosorbent assay (ELISA), western blotting and Quantitative real-time polymerase chain reaction (qRT-PCR) were performed to elucidate the underlying mechanism of celastrol. Besides, H9c2 cells were subjected to hypoxic conditions to create an in vitro model of MI and then treated with celastrol for 24 hours. Nigericin was used to activate the NLRP3 inflammasome. Results: Compared with that MI group, cardiac electrophysiology instability was significantly alleviated in the MI + celastrol group. Additionally, celastrol improved HRV, upregulated the levels of Cx43, Kv.4.2, Kv4.3 and Cav1.2, mitigated myocardial fibrosis, and inhibited the NLRP3 inflammasome pathway. In vitro conditions also supported the regulatory effects of celastrol on the NLRP3 inflammasome pathway. Conclusions: Celastrol could alleviate the adverse effects of VAs after MI partially by promoting autonomic nerve remodeling, ventricular electrical reconstruction and ion channel remodeling, and alleviating ventricular fibrosis and inflammatory responses partly by through inhibiting the NLRP3/Caspase-1/IL-1β pathway.

BackgroundCuproptosis is copper-induced cell death. Copper metabolism related genes (CMRGs) were demonstrated that used to assess the prognosis out of tumors. In the study, CMRGs were tested for their effect on TME cell infiltration in Ewing’s sarcoma (ES).MethodsThe GEO and ICGC databases provided the mRNA expression profiles and clinical features for downloading. In the GSE17674 dataset, 22prognostic-related copper metabolism related genes (PR-CMRGs) was identified by using univariate regression analysis. Subsequently, in order to compare the survival rates of groups with high and low expression of these PR-CMRGs,Kaplan-Meier analysis was implemented. Additionally, correlations among them were examined. The study employed functional enrichment analysis to investigate probable underlying pathways, while GSVA was applied to evaluate enriched pathways in the ES (Expression Set). Through an unsupervised clustering algorithm, samples were classified into two clusters, revealing significant differences in survival rates and levels of immune infiltration.ResultsUsing Lasso and step regression methods, five genes (TFRC, SORD, SLC11A2, FKBP4, and AANAT) were selected as risk signatures. According to the Kaplan-Meier survival analysis, the high-risk group had considerably lower survival rates than the low-risk group(p=6.013e-09). The area under the curve (AUC) values for the receiver operating characteristic (ROC) curve were 0.876, 0.883, and 0.979 for 1, 3, and 5 years, respectively. The risk model was further validated in additional datasets, namely GSE63155, GSE63156, and the ICGC datasets. To aid in outcome prediction, a nomogram was developed that incorporated risk levels and clinical features. This nomogram’s performance was effectively validated through calibration curves.Additionally, the study evaluated the variations in immune infiltration across different risk groups, as well as high-expression and low-expression groups. Importantly, several drugs were identified that displayed sensitivity, offering potential therapeutic options for ES.ConclusionThe findings above strongly indicate that CMRGs play crucial roles in predicting prognosis and immune status in ES.

Background: To assess the alterations in gingival thickness and the occurrence gingival recession subsequent to orthodontic-orthognathic treatment of mandibular incisors in skeletal Class III and identify risk factors associated with gingival recession. Methods: In this retrospective cohort study, we enrolled 33 patients exhibiting skeletal Class III malocclusion, totaling 131 mandibular incisors, who were undergoing orthodontic- orthognathic treatment that did not involve extraction of mandibular teeth. The subjects were categorized into surgery group (S; n = 17; ANB = −5.55 ± 3.26; IOFTN = 4.60 ± 0.51, scores ranging: 4.3–5.3) and non-surgery group (NS; n = 16; ANB = −3.00 ± 4.08; IOFTN = 4.63 ± 0.50, scores ranging: 4.3–5.4), based on if they had history of Periodontally Accelerated Osteogenic Orthodontics surgery (S) or not (NS). Patients in S group received orthognathic surgery about 1–1.5 years after Periodontally Accelerated Osteogenic Orthodontics surgery. Alterations in gingival thickness, gingival recession, and keratinized gingival width were compared before and after orthodontic-orthognathic treatment. Logistic regression analysis was used to construct a gingival recession prediction model and draw nomograms. Results: After orthodontic-orthognathic treatment, the gingival thickness and keratinized gingival width in NS group decreased by 0.15 ± 0.21 mm and 0.74 ± 0.91 mm, whereas those in the S group increased by 0.32 ± 0.28 mm and 2.09 ± 1.51 mm (P

Background: Approximately 50% of patients harbor the T790M mutation after developing first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance. Evidence has showed the major treatment failure is local relapses and limited metastases. Several studies have demonstrated the value of radiotherapy in metastatic non-small cell lung cancer (NSCLC) with the EGFR T790M mutation after the development of TKI resistance. The aim of this study was to explore the role of radiation in T790M-mutant NSCLC and the value of early radiotherapy for NSCLC with T790M-mediated EGFR-TKI resistance. Methods: Gefitinib-resistant NSCLC cell lines were established via stepwise exposure to increasing concentrations of gefitinib (PC-9-GR). Droplet digital PCR was used to determine the relative T790M subclone abundance. In vitro and in vivo models were established using different mixtures of PC-9-GR and PC-9 cells. Differentially expressed genes were identified using RNA sequencing. Two research models were constructed (salvage and prophylactic radiotherapy) to determine the effects of early radiotherapy on gefitinib-resistant cells. Results: PC-9-GR cells exhibited higher radiosensitivity than PC-9 cells (sensitivity enhancement ratio = 1.5). Salvage radiation reduced the number of T790M-mutant subclones, and the relative T790M abundance was significantly lower than that without radiation at 90 days (10.94% vs. 21.54%). Prophylactic radiation prevented the development of T790M subclones. These results were also confirmed in vivo. qRT-PCR revealed threefold elevation of miR-1243 in PC-9-GR cells, and the increased radiosensitivity of PC-9-GR cells was inhibited when miR-1243 was knocked down. RNA sequencing revealed that SPOCK1 was downregulated in PC-9-GR cells. Interestingly, bioinformatic analysis showed that SPOCK1 was a target gene of miR-1243. SPOCK1 knockdown markedly increased the radiosensitivity of PC-9 cells. Conclusion: Gefitinib-resistant NSCLC with the T790M mutation had higher radiosensitivity than that without the mutation, possibly mediated by SPOCK1. Early radiotherapy can eliminate T790M subclones, providing evidence for the benefit of early local treatment in patients with TKI-resistant NSCLC.

Abstract Objective To further comprehend the phenotype of multiple mitochondrial dysfunction syndrome type 3 (MMDS3:OMIM#615330) caused by IBA57 mutation. We present a case involving a patient who experienced acute neurological regression, and the literature was reviewed. Methods Clinical data and laboratory test results were collected; early language and development progress were tested; and genetic testing was performed. Bioinformatics analysis was performed using Mutation Taster and PolyPhen‐2, and the literature in databases such as PubMed and CNKI was searched using MMDS3 and IBA57 as keywords. Results The child, aged 1 year and 2 months, had motor decline, unable to sit alone, limited right arm movement, hypotonia, hyperreflexia of both knees, and Babinski sign positivity on the right side, accompanied by nystagmus. Blood lactate levels were elevated at 2.50 mmol/L. Brain MR indicated slight swelling in the bilateral frontoparietal and occipital white matter areas and the corpus callosum, with extensive abnormal signals on T1 and T2 images, along with the semioval center and occipital lobes bilaterally. The multiple abnormal signals in the brain suggested metabolic leukoencephalopathy. Whole‐exome sequencing analysis revealed that the child had two heterozygous mutations in the IBA57 gene, c.286T>C (p.Y96H) (likely pathogenic, LP) and c.992T>A (p.L331Q) (variant of uncertain significance, VUS). As of March 2023, a literature search showed that 56 cases of MMDS3 caused by IBA57 mutation had been reported worldwide, with 35 cases reported in China. Among the 35 IBA57 mutations listed in the HGMD database, there were 28 missense or nonsense mutations, 2 splicing mutations, 2 small deletions, and 3 small insertions. Conclusion MMDS3 predominantly manifests in infancy, with primary symptoms including feeding difficulties, neurological functional regression, muscle weakness, with severe cases potentially leading to mortality. Diagnosis is supported by elevated lactate levels, multisystem impairment (including auditory and visual systems), and distinctive MRI findings. Whole‐exome sequencing is crucial for diagnosis. Currently, cocktail therapy offers symptomatic relief.