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Abstract Background Camellia nitidissima is a rare, prized camellia species with golden-yellow flowers. It has a high ornamental, medicinal, and economic value. Previous studies have shown substantial flavonol accumulation in C. nitidissima petals during flower formation. However, the mechanisms underlying the golden flower formation in C. nitidissima remain largely unknown. Results We performed an integrative analysis of the transcriptome, proteome, and metabolome of the petals at five flower developmental stages to construct the regulatory network underlying golden flower formation in C. nitidissima. Metabolome analysis revealed the presence of 323 flavonoids, and two flavonols, quercetin glycosides and kaempferol glycosides, were highly accumulated in the golden petals. Transcriptome and proteome sequencing suggested that the flavonol biosynthesis-related genes and proteins upregulated and the anthocyanin and proanthocyanidin biosynthesis-related genes and proteins downregulated in the golden petal stage. Further investigation revealed the involvement of MYBs and bHLHs in flavonoid biosynthesis. Expression analysis showed that flavonol synthase 2 (CnFLS2) was highly expressed in the petals, and its expression positively correlated with flavonol content at all flower developmental stages. Transient overexpression of CnFLS2 in the petals increased flavonol content. Furthermore, correlation analysis showed that the jasmonate (JA) pathways positively correlated with flavonol biosynthesis, and exogenous methyl jasmonate (MeJA) treatment promoted CnFLS2 expression and flavonol accumulation. Conclusions Our findings showed that the JA-CnFLS2 module regulates flavonol biosynthesis during golden petal formation in C. nitidissima.

Abstract Background Ball thrombus is rare and life-threatening. The correct diagnosis and timely management are key to improving patient prognosis. Here, we present a case report and literature review of ball thrombus. Case presentation A 75-year-old woman presented to our outpatient clinic because of palpitations and chest distress for 8 months. She was diagnosed mitral stenosis, and transthoracic echocardiography (TTE) showed a round mass attached to the left atrial (LA) wall. Before anesthesia induction, TTE found that the mass has dropped from the LA wall, and was spinning in the LA causing intermittent obstruction of the valve. Anesthesia induction was then carried out under TTE monitoring, and transesophageal echocardiograph found another mass in the LA appendage after intubation. She underwent LA mass removal and mitral valve replacement, and was discharged uneventfully. Histopathology confirmed the diagnosis of thrombus. Our literature review identified 19 cases of ball thrombus between 2015 and 2024. The average age was 54.8 (range 3–88) years. Heart failure was present as the initial symptom in 11 cases, and most patients had mitral valve disease or concomitant with atrial fibrillation. 12 cases received surgery, and 7 received medical treatment only. 2 deaths occurred, one due to the obstruction of left ventricular inflow tract and the other due to the worsening of heart failure. Conclusion Ball thrombus is rare in clinical settings. Urgent thrombectomy should be performed as soon as possible, and echocardiography can be used for real-time monitoring during surgery.

Abstract Background The number and proportion of HIV/AIDS patients among older people are continuously and rapidly increasing in China. We conducted a detailed molecular epidemiological analysis of HIV-1 epidemic strains in a developed city in eastern China and found that elderly people play a crucial role in the transmission of subtypes and high pretreatment drug resistance (PDR). Methods A total of 1048 samples were obtained from 1129 (92.8%) newly confirmed HIV-1-positive and treatment-naive patients between 2019 and 2023. The 1316 bp target fragment of the pol gene was amplified by reverse transcription polymerase chain reaction (RT‒PCR) and nested PCR, and Maximum-likelihood (ML) phylogenetic trees and molecular transmission network were constructed to analyse the subtypes and transmission clusters. Molecular transmission network was visualized using Cytoscape with the distance threshold of 0.0075. PDR-associated mutations were determined according to the Stanford University HIV Drug Resistance Database. Results A total of 933 pol sequences (89.0%, 933/1048) were successfully obtained, and twelve HIV-1 subtypes were detected. CRF07_BC was the predominant subtype, accounting for 48.1% (449/933) of sequences, followed by CRF01_AE (29.4%, 274/933). A total of 398 individuals (42.7%, 398/933) formed 89 clusters in the network. Multivariable logistic regression analysis revealed that age, nationality, subtype, and PDR were the most significant factors associated with clustering in the transmission network. The prevalence of PDR was 14.6% (136/933).PDR associated with non-nucleoside reverse transcriptase inhibitors (10.0%, 93/933) was much more common than that associated with nucleoside reverse transcriptase inhibitors (1.8%, 17/933) and protease inhibitors (3.2%, 30/933) (χ 2 = 77.961, p

Abstract Immunotherapy confers little to no benefit in the treatment of microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Mechanistic insights suggested that epidermal growth factor receptor (EGFR) antibody plus irinotecan might augment the tumor immune response in mCRC. Therefore, we conducted a proof-of-concept, single-arm, phase 2 study (ChiCTR identifier: ChiCTR2000035642) of a combination treatment regimen including tislelizumab (anti-PD-1), cetuximab (anti-EGFR) and irinotecan in 33 patients with MSS and RAS wild-type (WT) mCRC who were previously treated with ≥2 lines of therapy. The primary endpoint was met, with a confirmed objective response rate of 33%. As secondary endpoints, the disease control rate was 79%, and the median progression-free survival and overall survival were 7.3 and 17.4 months respectively. Among the 33 patients, 32 (97.0%) had treatment-related adverse events (AEs). Three (9.1%) reported grade ≥ 3 AEs, including rash (n = 1), neutropenia (n = 2). The post-hoc evaluation of dynamic circulating tumor DNA using next generation sequencing and the analysis of peripheral immune proteomics landscape using Olink revealed that lower variant allele frequency (VAF) at baseline, greater reduction in VAF on treatment, and a hot peripheral macroenvironment were associated with the treatment response independently. Our study showed the antitumor activity of tislelizumab, cetuximab, and irinotecan combination with a tolerable safety profile in previously treated MSS and RAS WT mCRC.

Introduction: Orthodontic tooth movement (OTM) involves complex interactions between mechanical forces and periodontal tissue adaptation, mainly mediated by periodontal ligament cells, including periodontal ligament stem cells (PDLSCs), osteoblasts, and osteoclasts. Dopamine (DA), a neurotransmitter known for its critical role in bone metabolism, is investigated in this study for its potential to enhance osteogenic differentiation in PDLSCs, which are pivotal in OTM. This study examined the potential of DA to facilitate OTM by binding to DA receptors (D1R and D2R) and activating the ERK1/2 signaling pathway. We propose that DA's interaction with these receptors on PDLSCs could enhance osteogenic differentiation, thereby accelerating bone remodeling and reducing the duration of orthodontic treatments, which offering a novel approach to improve clinical outcomes in orthodontic care. Methods: This study utilized a rat OTM model, micro-CT, histological analyses, and in vitro assays to investigate dopamine's effect on osteogenesis. PDLSCs were cultured and treated with DA, and cytotoxicity, osteogenic differentiation, gene and protein expression assessed. Results: Dopamine administration significantly increased trabecular bone density and osteogenic marker expression in an OTM rat model. In vitro, DA at 10 nM optimally promoted human PDLSCs osteogenesis without affecting proliferation. Blocking DA receptors or inhibiting the ERK1/2 pathway attenuated these effects, underscoring the importance of dopaminergic signaling in tension-induced osteogenesis during OTM. Conclusion: Taken together, our study reveals that local dopamine administration at a concentration of 10 nM not only enhances tension-induced osteogenesis in vivo but also significantly promotes osteogenic differentiation of PDLSCs in vitro through D1 and D2 receptor-mediated ERK1/2 signaling pathway activation.

Abstract Cancer-associated fibroblasts (CAFs), integral components of the tumor microenvironment, play a pivotal role in tumor proliferation, metastasis, and clinical outcomes. However, its specific roles in Kidney Renal Clear Cell Carcinoma (KIRC) remain poorly understood. Employing the established Seurat single-cell analysis pipeline, we identified 21 CAFs marker genes. Subsequently, a prognostic signature consisting of 6 CAFs marker genes (RGS5, PGF, TPM2, GJA4, SEPT4, and PLXDC1) was developed in a cohort through univariate and LASSO Cox regression analyses. The model’s efficacy was then validated in an external cohort, with a remarkable predictive performance in 1-, 3-, and 5-year. Patients in the high-risk group exhibited significantly inferior survival outcomes (p

Abstract Background Data is limited on the prevalence of hypophosphatemia in general hospitalized patients, and its association with length of hospital stay (LOS) and mortality remained unclear. We aimed to investigate the prevalence of admission phosphate abnormality and the association between serum phosphate level and length of hospital stay and all-cause mortality in adult patients. Methods This was a multi-center retrospective study based on real-world data. Participants were classified into five groups according to serum phosphate level (inorganic phosphorus, iP) within 48 h after admission: G1, iP

Abstract Background Temporomandibular joint osteoarthritis (TMJOA) has a high incidence rate, but its pathogenesis remains unclear. Circadian rhythm is an important oscillation in the human body and influences various biological activities. However, it is still unclear whether circadian rhythm affects the onset and development of TMJOA. Methods We disrupted the normal rhythm of rats and examined the expression of core clock genes in the mandibular condylar cartilage of the jaw and histological changes in condyles. After isolating rat mandibular condylar chondrocytes, we upregulated or downregulated the clock gene Per1, examined the expression of cartilage matrix-degrading enzymes, tested the activation of the GSK3β/β-CATENIN pathway and verified it using agonists and inhibitors. Finally, after downregulating the expression of Per1 in the mandibular condylar cartilage of rats with jet lag, we examined the expression of cartilage matrix-degrading enzymes and histological changes in condyles. Results Jet lag led to TMJOA-like lesions in the rat mandibular condyles, and the expression of the clock gene Per1 and cartilage matrix-degrading enzymes increased in the condylar cartilage of rats. When Per1 was downregulated or upregulated in mandibular condylar chondrocytes, the GSK3β/β-CATENIN pathway was inhibited or activated, and the expression of cartilage matrix-degrading enzymes decreased or increased, which can be rescued by activator and inhibitor of the GSK3β/β-CATENIN pathway. Moreover, after down-regulation of Per1 in mandibular condylar cartilage in vivo, significant alleviation of cartilage degradation, cartilage loss, subchondral bone loss induced by jet lag, and inhibition of the GSK3β/β-CATENIN signaling pathway were observed. Circadian rhythm disruption can lead to TMJOA. The clock gene Per1 can promote the occurrence of TMJOA by activating the GSK3β/β-CATENIN pathway and promoting the expression of cartilage matrix-degrading enzymes. The clock gene Per1 is a target for the prevention and treatment of TMJOA.

Abstract Background Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally, influenced by aberrant circRNA expression. Investigating circRNA-miRNA-mRNA interactions can unveil underlying mechanisms of HCC and identify potential therapeutic targets. Methods In this study, we conducted differential analyses of mRNAs, miRNAs, and circRNAs, and established their relationships using various databases such as miRanda, miRDB, and miTarBase. Additionally, functional enrichment and immune infiltration analyses were performed to evaluate the roles of key genes. We also conducted qPCR assays and western blotting (WB) to examine the expression levels of circRNA, CCL25, and MAP2K1 in both HCC cells and clinical samples. Furthermore, we utilized overexpression and knockdown techniques for circ_0000069 and conducted wound healing, transwell invasion assays, and a tumorigenesis experiment to assess the migratory and invasive abilities of HCC cells. Results Our findings revealed significant differential expression of 612 upregulated genes and 1173 downregulated genes in HCC samples compared to normal liver tissue. Additionally, 429 upregulated circRNAs and 453 downregulated circRNAs were identified. Significantly, circ_0000069 exhibited upregulation in HCC tissues and cell lines. The overexpression of circ_0000069 notably increased the invasion and migration capacity of Huh7 cells, whereas the downregulation of circ_0000069 reduced this capability in HepG2 cells. Furthermore, this effect was counteracted by CCL25 silencing or overexpression, separately. Animal studies further confirmed that the overexpression of hsa_circ_0000069 facilitated tumor growth in xenografted nude mice, while the inhibition of CCL25 attenuated this effect. Conclusion Circ_0000069 appears to promote HCC progression by regulating CCL25, suggesting that both circ_0000069 and CCL25 can serve as potential therapeutic targets.

Abstract Resistance to chemotherapy has been a major hurdle that limits therapeutic benefits for many types of cancer. Here we systematically identify genetic drivers underlying chemoresistance by performing 30 genome-scale CRISPR knockout screens for seven chemotherapeutic agents in multiple cancer cells. Chemoresistance genes vary between conditions primarily due to distinct genetic background and mechanism of action of drugs, manifesting heterogeneous and multiplexed routes towards chemoresistance. By focusing on oxaliplatin and irinotecan resistance in colorectal cancer, we unravel that evolutionarily distinct chemoresistance can share consensus vulnerabilities identified by 26 second-round CRISPR screens with druggable gene library. We further pinpoint PLK4 as a therapeutic target to overcome oxaliplatin resistance in various models via genetic ablation or pharmacological inhibition, highlighting a single-agent strategy to antagonize evolutionarily distinct chemoresistance. Our study not only provides resources and insights into the molecular basis of chemoresistance, but also proposes potential biomarkers and therapeutic strategies against such resistance.

Abstract. Background:. Growth retardation is a common complication of chronic kidney disease in children, which can be partially relieved after renal transplantation. This study aimed to develop and validate a predictive model for growth patterns of children with end-stage renal disease (ESRD) after kidney transplantation using machine learning algorithms based on genomic and clinical variables. Methods:. A retrospective cohort of 110 children who received kidney transplants between May 2013 and September 2021 at the First Affiliated Hospital of Zhengzhou University were recruited for whole-exome sequencing (WES), and another 39 children who underwent transplant from October 2021 to March 2022 were enrolled for external validation. Based on previous studies, we comprehensively collected 729 height-related single-nucleotide polymorphisms (SNPs) in exon regions. Seven machine learning algorithms and 10-fold cross-validation analysis were employed for model construction. Results:. The 110 children were divided into two groups according to change in height-for-age Z-score. After univariate analysis, age and 19 SNPs were incorporated into the model and validated. The random forest model showed the best prediction efficacy with an accuracy of 0.8125 and an area under curve (AUC) of 0.924, and also performed well in the external validation cohort (accuracy, 0.7949; AUC, 0.796). Conclusions:. A model with good performance for predicting post-transplant growth patterns in children based on SNPs and clinical variables was constructed and validated using machine learning algorithms. The model is expected to guide clinicians in the management of children after renal transplantation, including the use of growth hormone, glucocorticoid withdrawal, and nutritional supplementation, to alleviate growth retardation in children with ESRD.

Irritable bowel syndrome (IBS) is considered a stress disorder characterized by psychological and gastrointestinal dysfunction. IBS patients not only suffer from intestinal symptoms such as abdominal pain, diarrhea, or constipation but also, experience dysthymic disorders such as anxiety and depression. Studies have found that corticotropin-releasing hormone plays a key role in IBS with comorbid dysthymic disorders. Next, we will summarize the effects of corticotropin-releasing hormone from the central nervous system and periphery on IBS with comorbid dysthymic disorders and relevant treatments based on published literatures in recent years.

Symplocos, a genus rich in endemic and keystone species in China's subtropical forests, plays a vital role in maintaining biodiversity. Climate change impacts on Symplocos trees affect ecosystem composition, dynamics, and functions. This study delves into the potential ramifications of climate change on the distribution and richness of Symplocos species across China under different climatic conditions. A comprehensive analysis was conducted using occurrence records of 29 species of Symplocos, focusing on habitat suitability modeling and spatial analysis, to demonstrate the possible effects of climate change on the distribution and diversity patterns of Symplocos species in China. Environmental data, including bioclimatic variables, were collected, and the future climate scenarios were projected using the combined average of the two global climate models. Four modeling algorithms were applied in an ensemble species distribution models to assess the distribution of Symplocos species and decipher the pattern of species richness and endemism. The results indicate high accuracy and performance of the models with a mean AUC of 0.94 and TSS of 0.77, particularly the random forest. The analysis identified key bioclimatic variables influencing Symplocos species distribution, with precipitation patterns (precipitation of driest month and precipitation of warmest quarter) and temperature variability (temperature mean diurnal range) playing significant roles. Predictions suggest a reduction in Symplocos species richness over the next six decades, particularly in southern and southwestern China, with potential gains in other regions. Overall, this study highlights the vulnerability of Symplocos species to climate change and underscores the importance of proactive conservation efforts and forest plantations to mitigate future loss in Symplocos species diversity.

In invasive lung adenocarcinoma (LUAD), patients with micropapillary (MIP) or solid (SOL) components had a significantly poorer prognosis than those with only lepidic (LEP), acinar (ACI) or papillary (PAP) components. It is interesting to explore the genetic features of different histologic subtypes, especially the highly aggressive components.Based on a cohort of 5,933 patients, this study observed that in different tumor size groups, LUAD with MIP/SOL components showed a different prevalence, and patients with ALK alteration or TP53 mutations had a higher probability of developing MIP/SOL components. To control individual differences, this research used spatial whole-exome sequencing (WES) via laser-capture microdissection of five patients harboring these five coexistent components and identified genetic features among different histologic components of the same tumor. In tracing the evolution of components, we found that titin (TTN) mutation might serve as a crucial intratumor potential driver for MIP/SOL components, which was validated by a cohort of 146 LUAD patients undergoing bulk WES. Functional analysis revealed that TTN mutations enriched the complement and coagulation cascades, which correlated with the pathway of cell adhesion, migration, and proliferation.Collectively, the histologic subtypes of invasive LUAD were genetically different, and certain trunk genotypes might synergize with branching TTN mutation to develop highly aggressive components.

Background: Dizziness often occurs after microvascular decompression (MVD), and therapeutic options are limited. The aim of this trial was to determine the potential efficacy of transcutaneous electrical acupoint stimulation (TEAS), against dizziness and its safety in patients undergoing MVD. Methods: Adult patients scheduled to undergo MVD for hemifacial spasm under total intravenous anesthesia were randomized at a 1:1 ratio to receive, after extubation, 30-min TEAS in the mastoid region as well as Fengchi acupoints (GB20) and Neiguan acupoints (PC6) or 30-min sham stimulation. The primary outcome was the incidence of dizziness at 2 h after surgery. Secondary outcomes included dizziness, postoperative nausea and vomiting (PONV) or headache severity, rescue medication, changes in intraocular pressure before and after surgery, length of stay, dizziness symptoms 4 weeks after discharge, and surgical complications. Results: A total of 86 patients (51.9 ± 9.4 years of age; 67 women) were enrolled. One patient (in the TEAS arm) was excluded from analysis due to conversion to sevoflurane anesthesia. The rate of dizziness at 2 h after surgery was 31.0 % (13/42) in the TEAS arm vs. 53.5 % (23/43) in the sham control arm (P = 0.036). TEAS was also associated with significantly lower severity of dizziness, based on a 10-point scale, during the first 24 h after surgery. None of the other secondary efficacy outcomes differed significantly between the two arms. All postoperative complications were Clavien-Dindo grade I or II. The rate of postoperative complications was 21.4 % (9/42) in the TEAS arm vs. 16.3 % (7/43) in the sham control arm (P = 0.544). Conclusions: Compared with sham control, TEAS was associated with a lower incidence of dizziness within 2 h and lower severity of dizziness within 24 h post-operatively, but no improvement in other outcomes, in adult patients undergoing MVD for hemifacial spasm.

Background/Aims: In this study, we evaluated the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with hepatic arterial infusion chemotherapy (HAIC) compared to TACE monotherapy for the treatment of unresectable hepatocellular carcinoma (HCC). Materials and Methods: Relevant studies were systematically searched in PubMed, Embase, Web of Science, and Cochrane Library databases until September 1, 2023. Our analysis included 7 cohort studies encompassing a total of 630 patients. Results: The results demonstrated that the TACE plus HAIC group exhibited significantly improved prognosis compared to the TACE alone group, as evidenced by superior rates of complete response, partial response, progressive disease, objective response rate, and disease control rate. Moreover, the TACE group displayed a lower risk of platelet reduction and vomiting when compared to the TACE plus HAIC group. None of the 7 studies reported any intervention-related mortality. Conclusion: In conclusion, the combination of TACE and HAIC may be recommended as a viable option for patients with unresectable HCC, given its evident enhancements in survival and tumor response rates without significant differences in adverse events when compared to TACE monotherapy. Nevertheless, additional randomized controlled trials and studies involving Western cohorts are warranted to further validate these findings.

Abstract Micro RNAs (miRs) have been implicated in various tumorigenic processes. Osteosarcoma (OS) is a primary bone malignancy seen in adolescents. However, the mechanism of miRs in OS has not been fully demonstrated yet. Here, miR-134-5p was found to inhibit OS progression and was also expressed at significantly lower levels in OS tissues and cells relative to normal controls. miR-134-5p was found to reduce vasculogenic mimicry, proliferation, invasion, and migration of OS cells, with miR-134-5p knockdown having the opposite effects. Mechanistically, miR-134-5p inhibited expression of the ITGB1/MMP2/PI3K/Akt axis, thus reducing the malignant features of OS cells. In summary, miR-134-5p reduced OS tumorigenesis by modulation of the ITGB1/MMP2/PI3K/Akt axis, suggesting the potential for using miR-134-5p as a target for treating OS.

Abstract Immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1) protein significantly improve survival in patients with advanced non-small-cell lung cancer (NSCLC), but its impact on early-stage ground-glass opacity (GGO) lesions remains unclear. This is a single-arm, phase II trial (NCT04026841) using Simon’s optimal two-stage design, of which 4 doses of sintilimab (200 mg per 3 weeks) were administrated in 36 enrolled multiple primary lung cancer (MPLC) patients with persistent high-risk (Lung-RADS category 4 or had progressed within 6 months) GGOs. The primary endpoint was objective response rate (ORR). T/B/NK-cell subpopulations, TCR-seq, cytokines, exosomal RNA, and multiplexed immunohistochemistry (mIHC) were monitored and compared between responders and non-responders. Finally, two intent-to-treat (ITT) lesions (pure-GGO or GGO-predominant) showed responses (ORR: 5.6%, 2/36), and no patients had progressive disease (PD). No grade 3–5 TRAEs occurred. The total response rate considering two ITT lesions and three non-intent-to-treat (NITT) lesions (pure-solid or solid-predominant) was 13.9% (5/36). The proportion of CD8+ T cells, the ratio of CD8+/CD4+, and the TCR clonality value were significantly higher in the peripheral blood of responders before treatment and decreased over time. Correspondingly, the mIHC analysis showed more CD8+ T cells infiltrated in responders. Besides, responders’ cytokine concentrations of EGF and CTLA-4 increased during treatment. The exosomal expression of fatty acid metabolism and oxidative phosphorylation gene signatures were down-regulated among responders. Collectively, PD-1 inhibitor showed certain activity on high-risk pulmonary GGO lesions without safety concerns. Such effects were associated with specific T-cell re-distribution, EGF/CTLA-4 cytokine compensation, and regulation of metabolism pathways.

Abstract The challenges associated with activating ferroptosis for cancer therapy primarily arise from obstacles related to redox and iron homeostasis, which hinder the susceptibility of tumor cells to ferroptosis. However, the specific mechanisms of ferroptosis resistance, especially those intertwined with abnormal metabolic processes within tumor cells, have been consistently underestimated. In response, we present an innovative glutathione-responsive magnetocaloric therapy nanodrug termed LFMP. LFMP consists of lonidamine (LND) loaded into PEG-modified magnetic nanoparticles with a Fe3O4 core and coated with disulfide bonds-bridged mesoporous silica shells. This nanodrug is designed to induce an accelerated ferroptosis-activating state in tumor cells by disrupting homeostasis. Under the dual effects of alternating magnetic fields and high concentrations of glutathione in the tumor microenvironment, LFMP undergoes disintegration, releasing drugs. LND intervenes in cell metabolism by inhibiting glycolysis, ultimately enhancing iron death and leading to synthetic glutathione consumption. The disulfide bonds play a pivotal role in disrupting intracellular redox homeostasis by depleting glutathione and inactivating glutathione peroxidase 4 (GPX4), synergizing with LND to enhance the sensitivity of tumor cells to ferroptosis. This process intensifies oxidative stress, further impairing redox homeostasis. Furthermore, LFMP exacerbates mitochondrial dysfunction, triggering ROS formation and lactate buildup in cancer cells, resulting in increased acidity and subsequent tumor cell death. Importantly, LFMP significantly suppresses tumor cell proliferation with minimal side effects both in vitro and in vivo, exhibiting satisfactory T2-weighted MR imaging properties. In conclusion, this magnetic hyperthermia-based nanomedicine strategy presents a promising and innovative approach for antitumor therapy. Graphical Abstract

Abstract Kaempferol (KA), an natural antioxidant of traditional Chinese medicine (TCM), is extensively used as the primary treatment for inflammatory digestive diseases with impaired redox homeostasis. Severe acute pancreatitis (SAP) was exacerbated by mitochondrial dysfunction and abundant ROS, which highlights the role of antioxidants in targeting mitochondrial function. However, low bioavailability and high dosage of KA leading to unavoidable side effects limits clinical transformation. The mechanisms of KA with poor bioavailability largely unexplored, hindering development of the efficient strategies to maximizing the medicinal effects of KA. Here, we engineered a novel thioketals (TK)-modified based on DSPE-PEG2000 liposomal codelivery system for improving bioavailability and avoiding side effects (denotes as DSPE-TK-PEG2000-KA, DTM@KA NPs). We demonstrated that the liposome exerts profound impacts on damaging intracellular redox homeostasis by reducing GSH depletion and activating Nrf2, which synergizes with KA to reinforce the inhibition of inadequate fission, excessive mitochondrial fusion and impaired mitophagy resulting in inflammation and apoptosis; and then, the restored mitochondrial homeostasis strengthens ATP supply for PAC renovation and homeostasis. Interestingly, TK bond was proved as the main functional structure to improve the above efficacy of KA compared with the absence of TK bond. Most importantly, DTM@KA NPs obviously suppresses PAC death with negligible side effects in vitro and vivo. Mechanismly, DTM@KA NPs facilitated STAT6-regulated mitochondrial precursor proteins transport via interacting with TOM20 to further promote Drp1-dependent fission and Pink1/Parkin-regulated mitophagy with enhanced lysosomal degradation for removing damaged mitochondria in PAC and then reduce inflammation and apoptosis. Generally, DTM@KA NPs synergistically improved mitochondrial homeostasis, redox homeostasis, energy metabolism and inflammation response via regulating TOM20-STAT6-Drp1 signaling and promoting mitophagy in SAP. Consequently, such a TCM’s active ingredients-based nanomedicine strategy is be expected to be an innovative approach for SAP therapy. Graphical Abstract

Abstract Introduction Chlorogenic acid, the primary active component in Chinese medicines like honeysuckle, exhibits anti-inflammatory and antiviral effects. It has been demonstrated that chlorogenic acid effectively prevents and treats Duck enteritis virus (DEV) infection. This study aims to further elucidate the mechanism by which chlorogenic acid prevents DEV infection. Methods Duck embryo fibroblast (DEF) cells were pre-treated with chlorogenic acid before being infected with DEV. Cell samples were collected at different time points for transcriptomic sequencing, while qPCR was used to detect the proliferation of DEV. Additionally, 30-day-old ducks were treated with chlorogenic acid, and their lymphoid organs were harvested for histopathological sections to observe pathological damage. The proliferation of DEV in the lymphoid organs was also detected using qPCR Based on the transcriptomic sequencing results, NF-κB1 gene was silenced by RNAi technology to analyze the effect of NF-κB1 gene on DEV proliferation. Results Compared to the viral infection group, DEF cells in the chlorogenic acid intervention group exhibited significantly reduced DEV load (P

Abstract Introduction This study aims to document and preserve the traditional medicinal knowledge of the Gelao community in Northern Guizhou, China, providing valuable insights for modern pharmacological research and the development of these traditional remedies. Methods Our methodology encompassed a blend of literature review, community interviews, and participatory observation to delve into the traditional knowledge of animal-derived medicines among the Gelao community. We employed quantitative ethnological and ecological assessment techniques to evaluate the significance of these practices. Informed consent was secured before conducting interviews, with a focus on ascertaining the types of medicines familiar to the informants, including their local names, sources, methods of preparation, application techniques, diseases treated, frequency of use, and safety considerations. Results Our research cataloged 55 varieties of animal-derived medicines utilized by the Gelao people. Out of these, 34 originate from wild animals, mainly encompassing small insects, reptiles, and aquatic species; the remaining 21 are derived from domesticated animals, largely involving their tissues, organs, and various physiological or pathological by-products. These medicines are primarily applied in treating pediatric ailments (13 types), internal disorders (11 types), gynecological issues (3 types), dermatological problems (7 types), ENT conditions (3 types), trauma-related injuries (5 types), joint and bone ailments (5 types), infections (2 types), dental issues (2 types), and urolithiasis (1 type), with three types being used for other miscellaneous conditions. Commonly utilized medicines, such as honey, Blaps beetle, chicken gallstones, and snake-based products, are preferred for their availability, edibility, and safety within the Gelao communities. Conclusion The Gelao community’s traditional medicines represent a rich diversity of animal sources, showcasing extensive expertise and knowledge in their processing and clinical applications. This wealth of traditional knowledge offers novel perspectives for the contemporary pharmacological study and development of these remedies. Additionally, our research plays a crucial role in aiding the preservation and continuation of this invaluable cultural heritage.

Abstract Background Trait compliance involves people reacting favorably to demands made by others across different situations. This may lead to susceptibility to external pressures, exploitation, and manipulation. Moreover, trait compliance was found to correlate with various mental health outcomes, such as depression and anxiety. The Gudjonsson Compliance Scale (GCS) is an efficient tool for assessing trait compliance in Western contexts. To date, no study has validated the psychometric properties of the GCS in Chinese populations. Methods Two college student samples from China were recruited. The first sample (N = 4,276) was used to conduct exploratory factor analysis. The second (N = 4,356) was used to perform a confirmatory factor analysis. The reliability, measurement invariance, and correlational tests were conducted on the two combined samples. Results The Chinese GCS showed a 3-factor structure, with two items deleted. Reliability was supported by moderate-to-good internal consistency of the three-factor scales and good internal consistency on the full scale. Strong measurement invariance across sex, ethnicity, and group recruitment was supported. Scores of the total scale and factor scales were found to significantly associated with several mental health problems. Conclusions The Chinese version of the GCS appears to be a valid and reliable instrument for measuring trait compliance and could promote both the assessment and research on compliance in Chinese population.

Background Prolonged postoperative ileus (PPOI) is a major complication of colorectal surgery. Increased opioid consumption has been proposed to increase the risk of PPOI. This study aimed to test the hypothesis that an increased total postoperative opioid dose (TPOD) is associated with the increased incidence of PPOI. Methods For this matched case-control study, patients who underwent elective laparoscopic colorectal procedures at the Peking University People’s Hospital between January 2018 and June 2020 were retrospectively reviewed. Patients with PPOI were assigned to the ileus group, while patients without PPOI (control group) were matched at a 1:1 ratio to the ileus group according to age, American Society of Anesthesiologists physical status score, and type of surgical procedure. The primary outcome was the TPOD between the ileus and control groups. The secondary outcome was risk factors of PPOI. Results A total of 267 participants were included in the final analysis. No differences in baseline or operative factors were found between the two groups. The TPOD, intravenous sufentanil dose on postoperative day 1 (POD1), and the use of patient-controlled analgesia with basal infusion were associated with PPOI (P < 0.05). Multivariate logistic regression analysis revealed that an increased TPOD was an independent risk factor for developing PPOI after laparoscopic colorectal procedures (Odd ratio: 1.67, 95% CI [1.03, 2.71], P = 0.04). Conclusions The TPOD is an independent risk factor for PPOI after laparoscopic colorectal surgery. We need to explore new strategies of postoperative analgesia to reduce the dosage of TPOD.

In Singapore, an ageing population with increasing chronic disease burden and complex social circumstances have strained the healthcare system. For the health system to run more efficiently, patients should be appropriately sited according to their medical needs. In Singapore, community hospitals serve as an intermediate inpatient facility managing patients with sub-acute and rehabilitation care needs. Our policy brief uncovers the gaps in transforming community hospital care models and offers actionable steps to unlock the community hospital chokepoints in Singapore's health system. The future community hospitals can accommodate higher acuity but medically stable patients, while patients who do not require inpatient rehabilitation care can be appropriately sited to community partners, if policy, resourcing and technology factors are addressed. An evidence-based, stepwise approach involving all stakeholders will be required to pilot and evaluate new models before large-scale change.

The aim of this study was to investigate the effects of fermented sweet potato residue (FSP) on growth performance, immune organ morphology, antioxidant capacity and nonspecific immunity in common carp. One hundred and twenty healthy and disease-free common carp with an initial body weight of (408.36±26.12) g were randomly divided into four groups, FSP0, FSP10, FSP20 and FSP30, and their base diet was supplemented with 0, 10%, 20% and 30% FSP, respectively.There were with 10 common carp in each tank, and the experiment was replicated three times. The results showed that the weight gain rate and specific growth rate of the FSP10 and FSP20 groups were significantly greater (p

ObjectivesThe objective of this study was to investigate the biomechanical effects of different tooth movement patterns and aligner thicknesses on teeth and periodontal tissues during maxillary arch expansion with clear aligners, to facilitate more precise and efficient clinical orthodontic treatments.MethodsThree-dimensional models including teeth, maxilla, periodontal ligament, and aligner were constructed and subjected to finite element analysis. Tooth displacement trends and periodontal ligament stresses were measured for seven tooth displacement patterns (divided into three categories including overall movement of premolars and molars with gradually increasing molar expansion in each step; distributed movement of premolars and molars; and alternating movement between premolars and molars at intervals) and two aligner thicknesses (0.5 mm and 0.75 mm) during maxillary arch expansion with clear aligners.ResultsWhen expanding the maxillary arch with clear aligners, the effective expansion of the target teeth mainly showed a tilting movement trend. Increasing the amount of molar expansion increased the buccal displacement of the first molar but decreased the buccal displacement of the premolars. The mean buccal displacement of the target teeth was greater in the posterior teeth interval alternating movement group (0.026 mm) than in the premolar/molar distributed movement group (0.016 mm) and the overall movement group (0.015 mm). Increasing aligner thickness resulted in greater buccal displacement of the crowns and increased stress on the periodontal ligaments.ConclusionIncreasing the amount of molar expansion reduces the efficiency of premolar expansion. Alternating movement of premolars and molars at intervals achieves a higher arch expansion efficiency, but attention should be paid to the anchorage of adjacent teeth. Increasing the thickness of the aligner increases the expansion efficiency but may also increase the burden on the periodontal tissues.

BackgroundDespite extensive research on hyperuricemia (HUA) in adults, there remains a dearth of studies examining this condition in youth. Consequently, our objective was to investigate the prevalence of HUA among youth in the United States, as well as identify the corresponding risk factors.MethodsThis study employed a nationally representative subsample of 1,051 youth aged 13–20 from the US National Health and Nutrition Examination Survey (NHANES) conducted between January 2017 and March 2020. Univariate and multivariate techniques were utilized to examine the association between HUA and obesity, dietary nutrients, liver and kidney function, glucose and lipid metabolism, inflammation, and other indicators in the adolescent population.ResultsThe study encompassed a cohort of 1,051 youth aged 13–20 years, comprising 538 boys and 513 girls. The overall prevalence of HUA was found to be 7% (74 out of 1,051). Univariate analysis revealed that the HUA group exhibited greater age, body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR). Additionally, the prevalence of obesity was significantly higher in the HUA group compared to the non- HUA group (all p 0.05).ConclusionHigh BMI remains a major risk factor for HUA in US youth aged 13–20 years, and ALT and Cr levels should be closely monitored along with serum uric acid.

Geometric information of molecules is closely related to their properties, and vibrational spectroscopy, as a common and powerful analytical tool for determining molecular structure, can assist in gaining precise geometric information. Traditional methods used to delineate spectrum-structure correlations are often expensive, time-consuming, and require extensive professional expertise. In this work, we used a machine learning protocol to construct a map from spectra to molecular geometric structures, and employed Grad-CAM, a convolutional network interpretation technology, to analyze which kinds of chemical information are important for determining our model’s results. The results obtained for six small molecules of differing structures demonstrate that the model is capable of (1) extracting the crucial spectral features that are vital to downstream tasks without necessitating any manual preprocessing, and (2) enabling retrieval of molecular structural information with high precision.

Alzheimer's disease (AD) comprises a group of neurodegenerative disorders with some changes in the brain, which could lead to the deposition of certain proteins and result in the degeneration and death of brain cells. Patients with AD manifest primarily as cognitive decline, psychiatric symptoms, and behavioural disorders. Short-chain fatty acids (SCFAs) are a class of saturated fatty acids (SFAs) produced by gut microorganisms through the fermentation of dietary fibre ingested. SCFAs, as a significant mediator of signalling, can have diverse physiological and pathological roles in the brain through the gut-brain axis, and play a positive effect on AD via multiple pathways. Firstly, differences in SCFAs and microbial changes have been stated in AD cases of humans and mice in this paper. And then, mechanisms of three main SCFAs in treating with AD have been summarized, as well as differences of gut bacteria. Finally, functions of SCFAs played in regulating intestinal flora homeostasis, modulating the immune system, and the metabolic system, which were considered to be beneficial for the treatment of AD, have been elucidated, and the key roles of gut bacteria and SCFAs were pointed out. All in all, this paper provides an overview of SCFAs and gut bacteria in AD, and can help people to understand the importance of gut-brain axis in AD.

Osteosarcoma (OS), a malignant tumor, originates from the bone marrow. Currently, treatment for OS remains limited, making it urgent to understand the immune response in the tumor microenvironment of patients with OS. A comprehensive bioinformatics analysis was performed, including cell clustering subgroups, differential expression genes screening, proposed temporal order, and genomic variant analysis on single-cell RNA-sequencing data, from ten pre-chemotherapy patients and eleven post-chemotherapy patients. Subsequently, we analyzed the differentiation trajectories of osteoblasts, osteoclasts, fibroblasts, myeloid cells, and tumor-infiltrating lymphocytes (TILs) in detail to compare the changes in cell proportions and differential genes pre- and post-chemotherapy. The nine cell types were identified, including fibroblasts, myeloid cells, osteoblasts, TILs, osteoclasts, proliferative osteoblasts, pericytes, endothelial cells, and B cells. Post-chemotherapy treatment, the proportions of myeloid cells and TILs in OS were declined, while the number of osteoblasts was elevated. Besides, a decrease was observed in CD74, FTL, FTH1, MT1X and MT2A, and an increase in PTN, COL3A1, COL1A1, IGFBP7 and FN1. Meanwhile, EMT, DNA repair, G2M checkpoint, and E2F targets were highly enriched post-chemotherapy. Furthermore, there was a down-regulation in the proportions of CD14 monocytes, Tregs, NK cells and CD1C-/CD141-DCs, while an up-regulation was observed in the proportions of SELENOP macrophages, IL7R macrophages, COL1A1 macrophages, CD1C DCs, CD4+ T cells and CD8+ T cells. Overall, these findings revealed changes in the tumor microenvironment of OS post-chemotherapy treatment, providing a new direction for investigating OS treatment.

Introduction It is appealing to accurately predict postoperative delirium (POD) before surgeries. In this study, it was hypothesized that a novel electroencephalogram-derived index, the delirium index (DELi), could extract latent information regarding the predisposing factors of POD preoperatively. This study was aimed at developing a concise model that incorporated this DELi score to predict the early POD of elderly patients after hip surgeries. Materials and Methods Elderly patients scheduled for elective hip fracture surgeries were prospectively enrolled in a tertiary care hospital from November 2020 to June 2022. DELi scores and patient characteristics (age, sex, types of fracture and surgery, the time interval between fracture and surgery, cognitive function assessed using the Montreal Cognitive Assessment (MoCA), and frailty status assessed using the FRAIL scale) were collected preoperatively as candidate predictors. POD diagnosed using the confusion assessment method (CAM) was the outcome. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to select predictors. Then, these predictors were entered into a backward logistical regression analysis to develop a prediction model. Discrimination, calibration and clinical utility were validated using the bootstrapping method. Results All data (144 qualified patients of 170) were used for development. POD was observed in 71 patients (49.3%). Preoperative DELi scores predicted early POD (the area under the curve (AUC) = .786, 95% confidence interval (CI): .712, .860, in internal validation). A nomogram with MoCA, FRAIL scale and DELi score was constructed with excellent discrimination (AUC = .920, 95% CI: .876, .963, in internal validation), accredited calibration ( P = .733, Hosmer‒Lemeshow test), and a wide range of threshold probabilities (5% to 95%). Conclusions Preoperative DELi scores predicted the early POD of elderly patients after hip surgeries. A concise prediction model was developed and demonstrated excellent discrimination.

Introduction Radical mastoidectomy is a common procedure for chronic suppurative otitis media, typically performed under a microscope. The smooth operation is closely related to the clarity of the operative field. Our trial is designed to investigate whether the intravenous administration of tranexamic acid (TXA) can improve the clarity of the operative field, reduce the operative time, and increase surgeon satisfaction.Methods and analysis This study is a prospective, randomised, double-blinded, controlled trial that aims to investigate the effects of TXA on patients with otitis media. The trial will include patients between the ages of 18 and 65 who will be randomly assigned to either the TXA group or the control group. In the TXA group, patients will receive 1 g of TXA diluted to 20 mL of normal saline before anaesthesia induction while the control group will receive 20 mL of normal saline. The primary outcome measure will be the Modena Bleeding Score, which will assess the clarity of the surgical field. Secondary outcomes will include the surgeon’s satisfaction with surgical conditions, operation time, laboratory measurements (prothrombin time, activated partial thromboplastin time, fibrin degradation products, D-dimer) and levels of inflammatory factors (such as IL-6) at 24 hours postoperatively. In addition, the incidence of general adverse reactions such as postoperative nausea, vomiting and dizziness; serious adverse events such as arterial and venous thromboembolism, myocardial infarction and epilepsy within 90 days will be compared between the two groups.Ethics and dissemination The protocol was approved by the Ethics Committee of Peking University People’s Hospital (2021PHB173-001), on 19 July 2021. The trial results will be submitted for publication in a peer-reviewed journal.Trial registration number ChiCTR2100049183.

Recently, pressure-sensing mats have been widely used to capture static and dynamic pressure over sleep for posture recognition. Both a full-size mat with a low-density sensing array for figuring out the structure of the whole body and a miniature scale mat with a high-density sensing array for identifying the local characteristics around the chest have been investigated. However, both of the mat systems may face the challenge in the trade-off between the computational complexity (involving the size, density, etc. of the mat) and the performance of sleep posture recognition, where high performance may requires overcomplex computation and result in time latency in real-time sleep posture monitoring. In this paper, a lightweight neural network named ConcatNet, is proposed to realize sleep postures (supine, left, right, and prone) recognition in real time while maintaining a favorable performance. In ConcatNet, the inception module is proposed to extract the image features under multiple receptive fields, while the multi-layer feature fusion module is utilized to fuse deep and shallow features to enhance the model performance. To further improve the efficiency of the model, the depthwise convolution is adopoted. ConcatNet models in 3 different scales (ConcatNet-S, ConcatNet-M, and ConcatNet-L) are built to explore the impact of the sensor density on sleep posture recognition performance. Experimental results exhibit that ConcatNet-M corresponding to medium sensor density ( ${16}\times {16}$ ) achieved the best comprehensive performance, with short-term data cross-validation accuracy at 95.56% and overnight data testing accuracy at 94.68%. The model size is 7.91KB, FLOPs is 56.47K, and the inference time is only 0.38ms, which shows an outstanding performance of real-time sleep posture recognition with minimum consumption, indicating the potential to be deployed in mobile devices.

Abstract Background Studies have investigated how adults with severe depressive symptoms are more likely to attempt suicide, and these adults often have traumatic experiences and chaotic sleep/wake rhythms. Thus, this study using Latent class analysis aimed to investigate the relationship between childhood trauma class, chronotype, and suicide attempts among emerging adults with severe depressive symptoms. Methods This study was conducted among emerging adults with severe depressive symptoms covering 63 Universities in Jilin Province, China. A total of 1,225 emerging adults (mean age = 19.6 ± 1.78) constructed the final sample. In addition to measuring socio-demographic characteristics, the Childhood Trauma Questionnaire-Short Form, the Single-Item Chronotyping, and a single item for suicide attempts were used to evaluate childhood trauma, chronotype, and suicide attempts, respectively. Latent class analysis was applied to identify the classes of childhood trauma within emerging adults who had severe depressive symptoms. Hierarchical logistic regression models were run to investigate the effects of socio-demographic characteristics, chronotype, and childhood trauma class on suicide attempts. Results Three latent classes were identified: the Low-risk for childhood trauma class, the Neglect class, and the High-risk for childhood abuse class. Those who suffered sexual, emotional, and physical abuse at the same time were divided into the High-risk for childhood abuse class, and were significantly more likely to experience suicide attempts than those in the Neglect class (OR = 1.97, 95%CI = 1.34–2.89, p < 0.001) and the Low-risk for childhood trauma class (OR = 2.28, 95% CI = 1.50-3.46, p

Objective: A biological system's internal morphological structure or function can be changed as a result of the mechanical effect of focused ultrasound. Pulsed low-intensity focused ultrasound (LIFU) has mechanical effects that might induce follicle development with less damage to ovarian tissue. The potential development of LIFU as a non-invasive method for the treatment of female infertility is being considered, and this study sought to explore and confirm that LIFU can activate ovarian follicles. Results: We found a 50% increase in ovarian weight and in the number of mature follicles on the ultrasound-stimulated side with pulsed LIFU and intraperitoneal injection of 10 IU PMSG in 10-day-old rats. After ultrasound stimulation, the PCOS-like rats had a decrease in androgen levels, restoration of regular estrous cycle and increase in the number of mature follicles and corpora lutea, and the ratio of M1 and M2 type macrophages was altered in antral follicles of PCOS-like rats, consequently promoting further development and maturation of antral follicles. Conclusion: LIFU treatment could trigger actin changes in ovarian cells, which might disrupt the Hippo signal pathway to promote follicle formation, and the mechanical impact on the ovaries of PCOS-like rats improved antral follicle development.

This article proposes an event-triggered resilient control algorithm for cigarette weight control systems to defend against denial of service attacks (DoS) attacks and false data injection (FDI) attacks. First, the mathematical model of the system is derived by considering its physical and electromagnetic characteristics. Then, an attack detection mechanism is designed to identify potential FDI attacks. A predictive compensation algorithm is also developed to mitigate the influence of these attacks, incorporating an observer to estimate unknown compensation signals. Due to limited network resources, we employ an event-based model-free adaptive control (MFAC) framework, where data is transmitted only when specific conditions are violated. Throughout the entire control process, only the input and output data of the system are used. Finally, simulation comparisons are provided to demonstrate the effectiveness and superiority of our method.

Abstract Otto Warburg described tumour cells as displaying enhanced aerobic glycolysis whilst maintaining defective oxidative phosphorylation (OXPHOS) for energy production almost 100 years ago [1, 2]. Since then, the ‘Warburg effect’ has been widely accepted as a key feature of rapidly proliferating cancer cells [3–5]. What is not clear is how early “Warburg metabolism” initiates in cancer and whether changes in energy metabolism might influence tumour progression ab initio. We set out to investigate energy metabolism in the HRASG12V driven preneoplastic cell (PNC) at inception, in a zebrafish skin PNC model. We find that, within 24 h of HRASG12V induction, PNCs upregulate glycolysis and blocking glycolysis reduces PNC proliferation, whilst increasing available glucose enhances PNC proliferation and reduces apoptosis. Impaired OXPHOS accompanies enhanced glycolysis in PNCs, and a mild complex I inhibitor, metformin, selectively suppresses expansion of PNCs. Enhanced mitochondrial fragmentation might be underlining impaired OXPHOS and blocking mitochondrial fragmentation triggers PNC apoptosis. Our data indicate that altered energy metabolism is one of the earliest events upon oncogene activation in somatic cells, which allows a targeted and effective PNC elimination.

Abstract Background Minimally invasive direct coronary artery bypass (MIDCAB) surgery offers an effective option for coronary artery disease (CAD) patients with the avoidance of median sternotomy and fast postoperative recovery. However, MIDCAB is still associated with significant postoperative pain which may lead to delayed recovery. The erector spinae plane block (ESPB) is a superficial fascial plane block. There have not been randomized controlled trials evaluating the effects of ESPB on analgesia and patient recovery following MIDCAB surgery. We therefore designed a double-blind prospective randomized placebo-controlled trial, aiming to prove the hypothesis that ESPB reduces postoperative pain scores in patients undergoing MIDCAB surgery. Methods The study protocol has been reviewed and approved by the Ethical Review Committee of Peking University People’s Hospital. Sixty adult patients of either sex scheduled for MIDCAB surgery under general anesthesia (GA) will be included. Patients will be randomly allocated to receive either a preoperative single-shot ESPB with 30 mL of ropivacaine 0.5% (ESPB group) or normal saline 0.9% (control group). The primary outcomes are the difference between the two groups in numeric rating scale (NRS) scores at rest at different time points (6, 12, 18, 24, 48 h) after surgery. The secondary outcomes include NRS scores on deep inspiration within 48 h, postoperative hydromorphone consumption, and quality of patient recovery at 24 h and 48 h, using the Quality of Recovery-15 (QoR-15) scale. The other outcomes include intraoperative fentanyl requirements, the need for additional postoperative rescue analgesics, time to tracheal extubation and chest tube removal after surgery, incidence of postoperative nausea and vomiting (PONV) and postoperative cognitive dysfunction (POCD), intensive care unit (ICU) length of stay (LOS), hospital discharge time, and 30-day mortality. Adverse events will be also evaluated. Discussion This is a novel randomized controlled study evaluating a preoperative ultrasound-guided single-shot unilateral ESPB on analgesia and quality of patient recovery in MIDCAB surgery. The results of this study will characterize the degree of acute postoperative pain and clinical outcomes following MIDCAB. Our study may help optimizing analgesia regimen selection and improving patient comfort in this specific population. Trial registration The study was prospectively registered with the Chinese Clinical Trial Registry (trial identifier: ChiCTR2100052810). Date of registration: November 5, 2021.

Objective: Postpartum weight retention (PPWR) is a common problem among women after childbirth. The main objectives of this study are to understand the changes in body weight of breastfeeding mothers during long-term follow-up and preliminarily explore the relationship between maternal body weight and human milk composition, including macronutrients, leptin, and adiponectin. Methods: The study included a longitudinal cohort (122 mothers), and a cross-sectional cohort (37 mothers). The human milk, maternal weight, and dietary surveys were collected in the longitudinal cohort at different follow-up time points (1−14 days postpartum, 2−4 months postpartum, 5−7 months postpartum, and 12−17 months postpartum). The maternal body weight was analyzed using the responses in the survey questionnaires. A milk analyzer based on the mid-infrared spectroscopy (MIRS) was used to determine milk composition, and nutrition analysis software evaluated dietary intakes. In the cross-sectional cohort, participating mothers were asked to provide blood and human milk samples and pertinent information related to maternal body composition. Maternal body composition was measured by bioelectrical impedance analysis (BIA), while ELISA analyzed leptin and adiponectin in milk and serum. Results: At 5−7 months postpartum, the PPWR of breastfeeding mothers was (2.46 ± 3.59) kg. At 12−17 months postpartum, the PPWR was (0.98 ± 4.06) kg. PPWR was found to be negatively correlated with milk fat content within 14 days postpartum and positively correlated at 2−4 months postpartum. In addition, the maternal weight and body muscle mass were positively correlated with leptin and adiponectin in milk. Plasma leptin was positively correlated with the mother's body weight, body mass index (BMI), FAT percentage, and body fat mass, while plasma adiponectin did not correlate with any parameter. The results also indicate that the PPWR did not correlate with leptin and adiponectin in plasma or milk. Conclusions: Breastfeeding mothers may retain considerable weight gain one year after delivery. Human milk composition may be related to changes in maternal body weight. Leptin and adiponectin in breast milk and leptin in plasma are associated with the maternal body composition. This study supports the notion that maternal nutritional status may affect offspring health through lactation, and future research should focus on exploring weight management of postpartum mothers.

Abstract Introduction Duck enteritis virus (DEV) mainly causes infectious diseases characterized by intestinal haemorrhage, inflammation and parenchymal organ degeneration in ducks and other poultry. However, the mechanism by which it causes intestinal damage in ducks is not well understood. Metabolomics can provide an in-depth understanding of the full complexity of the disease. Methods In this study, 24 clinically healthy green-shell ducks (weight 1.5 kg ± 20 g) were randomly divided into 2 groups (experimental group, 18; control group, 6). The experimental group was intramuscularly injected with 0.2 mL of DEV virus in solution (TCID50 3.16 × 108 PFU/mL), and the control group was injected with 0.2 mL of sterile normal saline. Duck duodenum and ileum tissue samples were collected at 66 h, 90 h and 114 h post-injection (12 h of fasting before killing), and metabolomics analysis of duck duodenum and ileum tissues at the three time points (66, 90, 114 h) was performed by liquid chromatography–mass spectrometry (LC–MS) to screen for and analyse the potential differentiated metabolites and related signalling pathways. Results Screening was performed in the positive/negative mode (Pos: Positive ion mode; the ionization of substances at the ion source with positive ions such as H+, NH4 +, Na+ and K+; Neg: Negative ion mode; the ionization of substances at the ion source with negative ions such as Cl−, OAc−), and compound abundance was compared to that in the control group. The total number of differentially abundant compounds in the duodenum at 66 h, 90 h and 114 h of DEV infection gradually increased, and metabolites such as cytidine, 2′-deoxyriboside and 4-guanidinobutyric acid were differentially abundant metabolites common to all three time periods. The metabolic pathways related to inflammatory response and immune response were tryptophan acid metabolism, cysteine-methionine metabolism, histidine metabolism and other amino acid metabolism and fat metabolism. Among them, the metabolic pathways with more differentially abundant metabolites were amino acid biosynthesis, cysteine and methionine metabolism, tryptophan metabolism, unsaturated fatty acid biosynthesis and purine metabolism, and the metabolic pathways with more enrichment factors were the IgA-related intestinal immune network pathway and lysosome pathway. Compared with the control group, there were 16 differentially abundant metabolites in the ileum tissue of DEV-infected ducks at 66 h of infection, 52 at 90 h of infection, and 40 at 14 h of infection with TD114. The metabolic pathways with more enriched differentially abundant metabolites were pyrimidine metabolism, tyrosine metabolism, phenylalanine metabolism and tryptophan biosynthesis. The metabolic pathways with the most enrichment factors were the mTOR signalling pathway, ferroptosis pathway, tryptophan metabolism pathway and caffeine metabolism pathway. Conclusion Comparative analysis showed that the number of differentially abundant metabolites in the duodenum and ileum differed to some extent after DEV infection, with significantly more differentially abundant metabolites in duodenal tissues and fewer in ileal tissues; after DEV infection, the highest number of differentially abundant metabolites was obtained at 114 h of DEV infection, followed by the second highest at 90 h of infection and the lowest at 66 h of infection. The common differentially abundant metabolites in duodenal and ileal tissues were prostaglandins, arachidonic acid, and arachidonic ethanolamine. The main metabolic pathways in the duodenum were the IgA-associated intestinal immune network pathway and the lysosomal pathway, and the metabolic pathways with more enriched factors in the ileum were the mTOR signalling pathway, the ferroptosis pathway, and the tryptophan metabolism pathway.

Abstract Background It is commonly accepted that surgical treatment is an essential component of the comprehensive management of metastatic spinal malignancies. However, up until now, the clinical classification of metastatic spinal malignancies has not been well-structured. Methods After IRB approval, 86 patients with metastatic spinal malignancies were adopted. According to the vascular distribution, stability of vertebrae, and degree of nerve compression, metastatic spinal malignancies can be classified into five types. Tumors classified as type I typically appear in the vertebral body. Type II tumors are those that develop in the transverse processes, superior and inferior articular processes, and spinal pedicles. Type III denotes malignancies that are present in the spinous process and vertebral plate. Types IVa and IVb are included in type IV. Type IVa combines type I and type II, whereas type IVb combines type II and type III. Type V tumors are those of types I, II, and III that co-occur and spread in different directions into the spinal canal. 20 of included 86 patients who did not receive segmental arterial embolization were set as the non-embolization group. The embolization group included 24 patients who received segmental arterial embolization on both sides of the diseased vertebrae. 42 patients were included in the offending embolization group after receiving responsible arterial embolization. A surgical intervention was performed within 24 h following an embolization. Surgical intervention with the purpose of removing as much of the tumor as possible and providing an effective reconstruction of the spinal column. Results In comparison with the non-embolization group and embolization group, the offending embolization group presented unique advantages in terms of bleeding volume (p

Abstract Objectives To evaluate the prevention efficacy of scaling up HIV/AIDS antiretroviral therapy (ART) on HIV transmission at the population level and determine associated factors of HIV secondary transmission. Methods We used HIV longitudinal molecular networks to assess the genetic linkage between baseline and newly diagnosed cases. A generalized estimating equation was applied to determine the associations between demographic, clinical characteristics and HIV transmission. Results Patients on ART had a 32% lower risk of HIV transmission than those not on ART. A 36% reduction in risk was also seen if ART-patients maintained their HIV viral load lower than 50 copies/mL. A 71% lower risk occurred when patients sustained ART for at least 3 years and kept HIV viral load less than 50 copies/mL. Patients who discontinued ART had a similar HIV transmission risk as those not on ART. Patients who were older, male, non-Han, not single, retired, infected via a heterosexual route of transmission and those who possessed higher CD4 counts had a higher risk of HIV transmission. HIV-1 subtype of CRF01_AE was less transmissible than other subtypes. Conclusions The efficacy of ART in a real-world setting was supported by this longitudinal molecular network study. Promoting adherence to ART is crucial to reduce HIV transmission.

Abstract Objective There are many injectable treatments for knee osteoarthritis with different characteristics and effects, the aim is to understand which one can lead to better and safer results. Methods The PRISMA principles were followed when doing the literature search. Web of Science databases, Embase, the Cochrane Library, PubMed, and the Wanfang database were searched to identified randomized controlled trials that assessed the efficacy of corticosteroids (CSC), platelet-rich plasma (PRP), hyaluronic acid (HA), and combination therapy in treating KOA. Risk of bias was assessed using the relevant Cochrane tools (version 1.0). The outcome measure included the visual analog scale (VAS) score, the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score, and treatment-related adverse events. The network meta-analysis was performed using STATA17 software and a Bayesian stratified random effects model. Results Network meta-analysis using the Bayesian random-effects model revealed 35 studies with 3104 participants. PRP showed the best WOMAC score at a 3-month follow-up, followed by PRP + HA, HA, placebo, and CSC; PRP + HA scored the highest VAS, followed by PRP, CSC, HA, and placebo. PRP, CSC, HA, and placebo had the highest WOMAC scores six months following treatment; PRP + HA showed the best VAS scores. PRP showed the best WOMAC score at 12 months, followed by PRP + HA, HA, placebo, and CSC; The best VAS score was obtained with PRP, followed by PRP + HA, HA, and CSC. No therapy demonstrated a rise in adverse events linked to the treatment in terms of safety. Conclusions The current study found that PRP and PRP + HA were the most successful in improving function and alleviating pain after 3, 6, and 12 months of follow-up. CSC, HA, PRP, and combination therapy did not result in an increase in the incidence of treatment-related side events as compared to placebo.

BackgroundKidney transplantation is considered the most effective treatment for end-stage renal failure. Recent studies have shown that the significance of the immune microenvironment after kidney transplantation in determining prognosis of patients. Therefore, this study aimed to conduct a bibliometric analysis to provide an overview of the knowledge structure and research trends regarding the immune microenvironment and survival in kidney transplantation.MethodsOur search included relevant publications from 2013 to 2023 retrieved from the Web of Science core repository and finally included 865 articles. To perform the bibliometric analysis, we utilized tools such as VOSviewer, CiteSpace, and the R package “bibliometrix”. The analysis focused on various aspects, including country, author, year, topic, reference, and keyword clustering.ResultsBased on the inclusion criteria, a total of 865 articles were found, with a trend of steady increase. China and the United States were the countries with the most publications. Nanjing Medical University was the most productive institution. High-frequency keywords were clustered into 6 areas, including kidney transplantation, transforming growth factor β, macrophage, antibody-mediated rejection, necrosis factor alpha, and dysfunction. Antibody mediated rejection (2019-2023) was the main area of research in recent years.ConclusionThis groundbreaking bibliometric study comprehensively summarizes the research trends and advances related to the immune microenvironment and survival after kidney transplantation. It identifies recent frontiers of research and highlights promising directions for future studies, potentially offering fresh perspectives to scholars in the field.

Background: Breast cancer (BC) is the primary cause of cancer mortality. Herein, we aimed to establish and verify a prognostic model consisting of endoplasmic reticulum stress and apoptosis related genes (ERAGs) to predict patient survival. Methods: The Cancer Genome Atlas (TCGA) database was used to download gene expression and clinical data to identify the differentially expressed genes (DEGs). Using univariate Cox regression analysis and the Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox proportional hazards regression analysis, the prognostic ERAGs were screened. The predictive performance was evaluated using Kaplan-Meier (KM) survival and receiver operating characteristic (ROC) curve analysis. Furthermore, a nomogram model incorporating clinical parameters and risk scores was constructed and subsequently evaluated using ROC and KM analysis. The correlation analysis, mutation analysis, functional enrichment analysis, and immune infiltration analysis were employed to investigate the specific mechanism of ERAGs. We also used Quantitative Real-Time PCR (RT-qPCR) to verify the differential expression of DE-ERAGs between the breast cancer cell line and mammary epithelial cell line. Results: We constructed a prognostic signature comprising 16 ERAGs. ROC, KM analysis and the nomogram model demonstrated high effectiveness in accurately predicting the overall survival (OS) of BRCA patients. The results of these analysis could provide reference for further mechanism exploration. Conclusion: We developed and assessed a novel molecular predictive model for breast cancer that focuses on endoplasmic reticulum stress and apoptosis in this study. It is a valuable complement to the existing prognostic prediction models for breast cancer.

PurposeThe purpose of this study was to explore the factors influencing PRL levels in patients with prolactinoma and to investigate the correlations between anxiety, depression, sleep, self-efficacy, and PRL levels.MethodsThis retrospective study included 176 patients with prolactinoma who received outpatient treatment at the Affiliated Hospital of Zunyi Medical University from May 2017 to August 2022. The general information questionnaire, Hospital Anxiety and Depression Scale (HADS), Athens Insomnia Scale (AIS), and General Self-Efficacy Scale (GSES) were used for data collection. A generalized estimating equation (GEE) model was used to analyze the factors influencing PRL levels in patients with prolactinoma. GEE single-effect analysis was used to compare PRL levels at different time points between anxiety group and nonanxiety group, between insomnia group and normal group, and between low, medium, and high self-efficacy groups.ResultsThe median baseline PRL level and the PRL levels at 1, 3, 6, and 12 months of follow-up were 268.50 ng/ml, 122.25 ng/ml, 21.20 ng/ml, 19.65 ng/ml, and 16.10 ng/ml, respectively. Among patients with prolactinoma, 59.10% had anxiety (HADS-A score = 7.35 ± 3.34) and 28.98% had depression (HADS-D score = 5.23 ± 3.87), 9.10% had sleep disorders (AIS score = 6.10 ± 4.31) and 54.55% had low self-efficacy (GSES score = 2.13 ± 0.83). Educational level, tumor size, number of visits, sleep quality, anxiety level, and self-efficacy level were found to be factors influencing PRL levels in patients with prolactinoma (P

Background Gender dysphoria is associated with suicidality among transgender and gender-diverse (TGD) people. Gender dysphoria also results in a stress on appearance. Aims The objectives of this study were to examine: (a) whether appearance anxiety mediates the effect of gender dysphoria on suicidality; and (b) whether gender identity moderates the mediating effect of appearance anxiety. Method A total of 117 769 college and university students were recruited in this cross-sectional study from Jilin Province, China. After screening based on participants’ gender identity, 2352 TGD young people (aged from 15 to 25 years) were divided into three subgroups: female to male (FTM), male to female (MTF) and non-binary. Self-report inventories measured gender dysphoria, suicidality and appearance anxiety. A structural equation model was run to examine the relationships among TGD gender identity, gender dysphoria, appearance anxiety and suicidality. Results Among TGD young people, gender dysphoria was significantly positively associated with suicidality (β = 0.15, 95% CI = 0.11–0.18, P < 0.001). Appearance anxiety partially mediated the association between gender dysphoria and suicidality (β = 0.07, 95% CI = 0.05–0.08, P < 0.001). Gender identity moderated the mediating effects: compared with individuals with FTM identity, among those with MTF and non-binary identities, gender dysphoria showed stronger positive effects on appearance anxiety, and appearance anxiety showed greater effects in mediating the association between gender dysphoria and suicidality. Conclusions Among TGD young people, gender dysphoria is significantly associated with suicidality via appearance anxiety, with gender identity moderating the mediating effects. Diverse treatments should consider the heterogeneity of TGD subgroups, with the aim of limiting the tendency of gender dysphoria to trigger appearance anxiety, thus further buffering against the risk of suicide.

Dual-frequency ultrasound has been widely employed to enhance and regulate acoustic droplet vaporization (ADV) but the role of ultrasonic nonlinear effects on it remains unclear. The main objective of this study is to investigate the influence of nonlinear effects on the control of ADV nucleation under different dual-frequency focused ultrasound conditions. ADV nucleation of PFC nanodroplets activated by nonlinear dual-frequency ultrasound was modeled and parametric studies were conducted to investigate the influence of dual-frequency ultrasound frequency and acoustic power on the degree of nonlinearity (DoN), nucleation rates and dimensions of the nucleation region in a wide parameter range. The results showed that the ultrasonic nonlinearity caused a significant decrease in peak negative pressure due to waveform distortion, which leads to a lower nucleation rate in the nonlinear model compared to that in the linear model. Furthermore, the distributions of nucleation regions were also affected by the interaction between waves of different frequencies and cloud-like spatial distributions were produced, which could be modulated by the dual-frequency ultrasound parameters and have great potentials in the spatial regulation of the ADV and customized treatment protocols in clinical applications. In addition, represented by 1.5 MHz + 3 MHz, such a dual-frequency combination of fundamental and second harmonic could effectively enhance ultrasonic nonlinear effects with relatively lower peak negative pressure and higher DoN. Therefore, nonlinear effect of the dual-frequency ultrasound plays an important role in the ADV regulation, which should be considered in the numerical model and practical applications.

ABSTRACT CRF01_AE strains have been shown to form multiple transmission clusters in China, and some clusters have disparate pathogenicity in Chinese men who have sex with men. This study focused on other CRF01_AE clusters prevalent in heterosexual populations. The CD4+ T-cell counts from both cross-section data in National HIV Molecular Epidemiology Survey and seropositive cohort data were used to evaluate the pathogenicity of the CRF01_AE clusters and other HIV-1 sub-types. Their mechanisms of pathogenicity were evaluated by co-receptor tropisms, predicted by genotyping and confirmed with virus isolate phenotyping, as well as inflammation parameters. Our research elucidated that individuals infected with CRF01_AE clusters 1 and 2 exhibited significantly lower baseline CD4+ T-cell counts and greater CD4+ T-cell loss in cohort follow-up, compared with other HIV-1 sub-types and CRF01_AE clusters. The increased pathogenesis of cluster 1 or 2 was associated with higher CXCR4 tropisms, higher inflammation/immune activation, and increased pyroptosis. The protein structure modeling analysis revealed that the envelope V3 loop of clusters 1 and 2 viruses is favorable for CXCR4 co-receptor usage. Imbedded with the most mutating reverse transcriptase, HIV-1 is one of the most variable viruses. CRF01_AE clusters 1 and 2 have been found to have evolved into more virulent strains in regions with predominant heterosexual infections. The virulent strains increased the pressure for early diagnosis and treatment in HIV patients. To save more lives, HIV-1 surveillance systems should be upgraded from serology and genotyping to phenotyping, which could support precision interventions for those infected by virulent viruses.IMPORTANCERetroviruses swiftly adapt, employing error-prone enzymes for genetic and phenotypic evolution, optimizing survival strategies, and enhancing virulence levels. HIV-1 CRF01_AE has persistently undergone adaptive selection, and cluster 1 and 2 infections display lower counts and fast loss of CD4+ T cells than other HIV-1 sub-types and CRF01_AE clusters. Its mechanisms are associated with increased CXCR4 tropism due to an envelope structure change favoring a tropism shift from CCR5 to CXCR4, thereby shaping viral phenotype features and impacting pathogenicity. This underscores the significance of consistently monitoring HIV-1 genetic evolution and phenotypic transfer to see whether selection bias across risk groups alters the delicate balance of transmissible versus toxic trade-offs, since virulent strains such as CRF01_AE clusters 1 and 2 could seriously compromise the efficacy of antiviral treatment. Only through such early warning and diagnostic services can precise antiviral treatments be administered to those infected with more virulent HIV-1 strains.