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BaCe0.8Fe0.1Ni0.1O3−δ (BCFN) in a perovskite structure is impregnated consecutively by BCFN solution and BCFN suspension into a phase-inversion prepared NiO–Gd0.1Ce0.9O2−δ (GDC) scaffold as an anode for solid oxide fuel cells (SOFCs) with on-cell dry reforming of methane (DRM). The whole pore surface of the scaffold is covered by small BCFN particles formed by BCFN solution impregnation; the large pores near the scaffold surface are filled by BCFN aerogels with a high specific surface area produced by BCFN suspension impregnation, which act as a catalytic layer for on-cell DRM. After reduction, the anode consists of a Ni–GDC scaffold and BCFN particles with exsolved FeNi3 nanoparticles. This BCFN-impregnated Ni–GDC anode has higher electrical conductivity, electrochemical activity, and resistance to carbon deposition, with which the cell shows maximum power densities between 1.44 and 0.92 W·cm−2 when using H2 and between 1.09 and 0.50 W·cm−2 when using CO2–CH4 at temperatures ranging from 750 to 600 °C. A stable performance at 400 mA·cm−2 and 700 °C is achieved using 45% CO2–45% CH4–10% N2 for more than 400 h without carbon deposition, benefiting from the impregnated BCFN aerogel with a high specific surface area and water adsorbability.

Abstract The bioactivity of interferon-γ (IFN-γ) in cancer cells in the tumor microenvironment (TME) is not well understood in the current immunotherapy era. We found that IFN-γ has an immunosuppressive effect on colorectal cancer (CRC) cells. The tumor volume in immunocompetent mice was significantly increased after subcutaneous implantation of murine CRC cells followed by IFN-γ stimulation, and RNA sequencing showed high expression of B7 homologous protein 4 (B7H4) in these tumors. B7H4 promotes CRC cell growth by inhibiting the release of granzyme B (GzmB) from CD8+ T cells and accelerating apoptosis in CD8+ T cells. Furthermore, interferon regulatory factor 1 (IRF1), which binds to the B7H4 promoter, is positively associated with IFN-γ stimulation-induced expression of B7H4. The clinical outcome of patients with CRC was negatively related to the high expression of B7H4 in cancer cells or low expression of CD8 in the microenvironment. Therefore, B7H4 is a biomarker of poor prognosis in CRC patients, and interference with the IFN-γ/IRF1/B7H4 axis might be a novel immunotherapeutic method to restore the cytotoxic killing of CRC cells.

Abstract Host survival depends on the elimination of virus and mitigation of tissue damage. Herein, we report the modulation of D-mannose flux rewires the virus-triggered immunometabolic response cascade and reduces tissue damage. Safe and inexpensive D-mannose can compete with glucose for the same transporter and hexokinase. Such competitions suppress glycolysis, reduce mitochondrial reactive-oxygen-species and succinate-mediated hypoxia-inducible factor-1α, and thus reduce virus-induced proinflammatory cytokine production. The combinatorial treatment by D-mannose and antiviral monotherapy exhibits in vivo synergy despite delayed antiviral treatment in mouse model of virus infections. Phosphomannose isomerase (PMI) knockout cells are viable, whereas addition of D-mannose to the PMI knockout cells blocks cell proliferation, indicating that PMI activity determines the beneficial effect of D-mannose. PMI inhibition suppress a panel of virus replication via affecting host and viral surface protein glycosylation. However, D-mannose does not suppress PMI activity or virus fitness. Taken together, PMI-centered therapeutic strategy clears virus infection while D-mannose treatment reprograms glycolysis for control of collateral damage.

Excessive local movement and inflammation are common problems in the process of wound repair, which lead to failure of later repair. In order to solve this problem, inspired by the octopus sucker structure, we successfully developed a photocrosslinked hydrogel that can adsorb skin surface fascia. In addition, extracellular vesicles from human bone marrow mesenchymal stem cells are encapsulated in the octopus like sucker structure. The morphology and structure of extracellular vesicles in bone marrow mesenchymal stem cells were detected by scanning electron microscopy and particle size analysis. Through iTRAQ, we tested the expression of angiogenesis related proteins contained in extracellular vesicles. Design small interfering RNA to verify its impact on angiogenic related genes and proteins. Macrophage polarization was detected by immunofluorescence. The expression of new blood vessels was detected by constructing a skin defect model and injecting microfil contrast agent into the heart. When the sucker is firmly adsorbed on the damaged wound, the sucker will slowly degrade. Using its delivery system, it is observed that the extracellular vesicles are released in the wound. Through iTRAQ, it was found that the angiogenesis regulator (angiopoietin-like 4, angiopoietin-like 3 and aminopeptidase N) released in the extracellular vesicles regulates collagen deposition, angiogenesis, and inhibits macrophage aggregation. In addition, the slowly released extracellular vesicles will further inhibit the polarization of proinflammatory macrophages. This biological behavior can provide an adaptive microenvironment for skin regeneration at an early stage. This new bionic octopus sucker structure gel creates a good microenvironment for wound repair and shortens the wound healing time. Therefore, this hydrogel inspired by the octopus sucker structure may provide a good strategy and commercial value for promoting wound repair treatment in clinical practice.

Abstract Objective The aim of the study was to investigate the 3.0 Tesla magnetic resonance imaging (MRI) features of Madelung’s deformity. Materials and methods The wrist MRI scans of 19 patients clinically diagnosed with Madelung’s deformity and 20 patients without deformity were consecutively selected from Beijing Jishuitan Hospital between April 2019 and December 2022 for observation, in the case group and control group, respectively. Multiple linear regression was used to analyze the factors affecting tilting angle and width of central disc (CD, also termed as triangular fibrocartilage, the main component of triangular fibrocartilage complex), while the chi-square test was used to compare the occurrences of CD (radial) attachment displacement, VL, and RTL. p

Anticoagulant treatment is an important strategy for secondary stroke prevention in non⁃valvular atrial fibrillation and acute ischemic stroke patients. However, the optimal timing for anticoagulation initiation after acute ischemic stroke has remained uncertain. In recent years, new clinical evidence has identified the benefit of early anticoagulation initiation rather than delayed anticoagulation initiation after acute ischemic stroke. This article reviews the literature on the topic of anticoagulation initiation in non⁃valvular atrial fibrillation with acute ischemic stroke patients. It helps physicians making decision to initiate anticoagulation at a more reasonable time point after balancing the risk of stroke recurrence and hemorrhagic transformation.

Objectives The objective of this study was to quantify the morphology, composition, and asymmetry of the paravertebral extensor muscles (PSEMs) in patients with cervical ossification of the posterior longitudinal ligament (OPLL) who had different modified K‐line (mK‐line) and the minimum interval between the mK‐line and OPLL (INTmin) values and to investigate the relationship between PSEMs and symptoms and outcomes following laminoplasty. These original findings elucidated that the atrophy of PSEMs could predict decompression outcomes and provided a theoretical basis for paraspinal muscle rehabilitation. Methods A total of 94 consecutive patients who underwent laminoplasty for OPLL between January 2020 and January 2022 were enrolled in this retrospective study. The relative cross‐sectional areas (rCSA), functional cross‐sectional areas (rFCSA), and FCSA/CSA ratio of the multifidus (MF), semispinalis cervicalis (SSCe), semispinalis capitis (SSCa), and splenius capitis (SpCa) were measured at the C3–C7 segments on cervical magnetic resonance imaging (MRI). This study compared the differences between the mK‐line (+) group and the mK‐line (−) group, as well as between the INTmin

BackgroundPueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) and Schisandra sphenanthera Rehder & E.H. Wilson are traditional edible and medicinal hepatoprotective botanical drugs. Studies have shown that the combination of two botanical drugs enhanced the effects of treating acute liver injury (ALI), but the synergistic effect and its action mechanisms remain unclear. This study aimed to investigate the synergistic effect and its mechanism of the combination of Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) (PM) and Schisandra sphenanthera Rehder & E.H. Wilson (SS) in the treatment of ALI.MethodsHigh performance liquid chromatography (HPLC) were utilized to conduct the chemical interaction analysis. Then the synergistic effects of botanical hybrid preparation of PM-SS (BHP PM-SS) against ALI were comprehensively evaluated by the CCl4 induced ALI mice model. Afterwards, symptom-oriented network pharmacology, transcriptomics and metabolomics were applied to reveal the underlying mechanism of action. Finally, the key target genes were experimentally by RT-qPCR.ResultsChemical analysis and pharmacodynamic experiments revealed that BHP PM-SS was superior to the single botanical drug, especially at 2:3 ratio, with a better dissolution rate of active ingredients and synergistic anti-ALI effect. Integrated symptom-oriented network pharmacology combined with transcriptomics and metabolomics analyses showed that the active ingredients of BHP PM-SS could regulate Glutathione metabolism, Pyrimidine metabolism, Arginine biosynthesis and Amino acid sugar and nucleotide sugar metabolism, by acting on the targets of AKT1, TNF, EGFR, JUN, HSP90AA1 and STAT3, which could be responsible for the PI3K-AKT signaling pathway, MAPK signaling pathway and Pathway in cancer to against ALI.ConclusionOur study has provided compelling evidence for the synergistic effect and its mechanism of the combination of BHP PM-SS, and has contributed to the development and utilization of BHP PM-SS dietary supplements.

Abstract Background Tandem C2 domains, nuclear (TC2N) is a C2 domain-containing protein that belongs to the carboxyl-terminal type (C-type) tandem C2 protein family, and acts as an oncogenic driver in several cancers. Previously, we preliminarily reported that TC2N mediates the PI3K-Akt signaling pathway to inhibit tumor growth of breast cancer (BC) cells. Beyond that, its precise biological functions and detailed molecular mechanisms in BC development and progression are not fully understood. Methods Tumor tissues of 212 BC patients were subjected to tissue microarray and further assessed the associations of TC2N expression with pathological parameters and FASN expression. The protein levels of TC2N and FASN in cell lines and tumor specimens were monitored by qRT-PCR, WB, immunofluorescence and immunohistochemistry. In vitro cell assays, in vivo nude mice model was used to assess the effect of TC2N ectopic expression on tumor metastasis and stemness of breast cancer cells. The downstream signaling pathway or target molecule of TC2N was mined using a combination of transcriptomics, proteomics and lipidomics, and the underlying mechanism was explored by WB and co-IP assays. Results Here, we found that the expression of TC2N remarkedly silenced in metastatic and poorly differentiated tumors. Function-wide, TC2N strongly inhibits tumor metastasis and stem-like properties of BC via inhibition of fatty acid synthesis. Mechanism-wise, TC2N blocks neddylated PTEN-mediated FASN stabilization by a dual mechanism. The C2B domain is crucial for nuclear localization of TC2N, further consolidating the TRIM21-mediated ubiquitylation and degradation of FASN by competing with neddylated PTEN for binding to FASN in nucleus. On the other hand, cytoplasmic TC2N interacts with import proteins, thereby restraining nuclear import of PTEN to decrease neddylated PTEN level. Conclusions Altogether, we demonstrate a previously unidentified role and mechanism of TC2N in regulation of lipid metabolism and PTEN neddylation, providing a potential therapeutic target for anti-cancer.

Abstract Due to the existence of the magnetic pole edge effect, the actual cogging torque of the existing segmented step skew motor does not reach the theoretical minimum. Thus, a method for suppressing cogging torque of permanent magnet synchronous motor considering the magnetic pole edge effect is proposed. The magnetic pole edge effect is creatively converted into the amplitude and phase offset of the cogging torque generated by each pole segment. On this basis, an optimization problem is constructed in which the fundamental component of cogging torque is zero and the total harmonics is minimum. The optimal magnetic pole length and skew angle parameters of each segment are obtained by solving the optimization problem quantitatively. The results can provide theoretical guidance for motor design, which can minimize the cogging torque of step skew structures. The effectiveness of the proposed method in weakening the cogging torque of the step skew motor is demonstrated by theoretical calculation, 3D finite element analysis, and experimental results.

Abstract DPY30 belongs to the core subunit of components of the histone lysine methyltransferase complex, which is implicated in tumorigenesis, cell senescence, and other biological events. However, its contribution to colorectal carcinoma (CRC) progression and metastasis has yet to be elucidated. Therefore, this study aimed to investigate the biological function of DPY30 in CRC metastasis both in vitro and in vivo. Herein, our results revealed that DPY30 overexpression is significantly positively correlated with positive lymph nodes, epithelial-mesenchymal transition (EMT), and CRC metastasis. Moreover, DPY30 knockdown in HT29 and SW480 cells markedly decreased EMT progression, as well as the migratory and invasive abilities of CRC cells in vitro and lung tumor metastasis in vivo. Mechanistically, DPY30 increased histone H3K4me3 level and promoted EMT and CRC metastasis by upregulating the transcriptional expression of ZEB1. Taken together, our findings indicate that DPY30 may serve as a therapeutic target and prognostic marker for CRC. Graphical Abstract

Objective To explore the effectiveness of a refined three-scene medication simulation teaching in nursing pharmacology course for nursing undergraduates. Methods Undergraduates of four-year curriculum in School of Nursing, Peking Union Medical College enrolled in 2020 and 2021 were selected as objects in control group and experimental group, respectively. Students in control group learned medication knowledge in a patient case simulation scene, while a refined three-scene medication process (before, during and after medication) simulation was applied in experimental group. The learning outcome was evaluated in forms of both test of key knowledge points and a questionnaire survey at the end of the semester. Results The scores of nursing pharmacology in experimental group were significantly higher than in control group (P＜0.001). The rates of right answer for knowledge associated with the refined class in experimental group were also significantly higher than in control group (P＜0.001). However, for knowledge that has not been adjusted for instructional design, there is no significant difference in answer accuracy between two groups. The survey by questionnaire showed that the students believed the three-scene medication simulation as good learning method and may support to strengthen professional quality of clinical performance. Conclusions Compared with the unrefined simulation class, the three-scene (before, during and after medication) class further simulated the real work flow, connected the knowledge points more reasonably, and enhanced the knowledge mastery and professional responsibility awareness.

The aim of the study was to evaluate the potential diagnostic and prognostic value of gene, Poly A-Binding Protein Interacting Protein 2B (PAIP2B) in pancreatic cancer. We used the gene expression data and clinical information of pancreatic adenocarcinoma patients from The Cancer Genome Atlas database and Gene Expression Omnibus database to analyze the expression of PAIP2B in pancreatic cancer samples, and validated the expression of PAIP2B in tumor tissue, using bioinformatics technology to explore the prognostic value of PAIP2B and its possible biological function. A significantly lower level of PAIP2B was observed in pancreatic cancer patients than in controls, and validated by immunohistochemistry. PAIP2B reduced the proliferation and invasion of cancer cells and had a significantly high expression in early stage. Patients with lower levels of PAIP2B had a significantly shorter median survival time than those with higher levels. DNA demethylation played an important role in PAIP2B expression. In addition, PAIP2B expression was significantly associated with the tumor-infiltrating immune cells, especially T cells CD8, T cells CD4 memory resting, macrophages M0, and dendritic cells resting. Our study also found that PAIP2B regulated miRNA function leading to disease progression in pancreatic cancer patients. Our study explored the potential value of PAIP2B as a biological link between prognosis and pancreatic cancer, and provided reference for the follow-up study on the role of PAIP2B in pancreatic cancer.

Abstract The application of a semi‐definite programming (SDP) approach to the Alternating Current Optimal Power Flow problem has attracted significant attention in recent years. However, the SDP relaxation of optimal power flow (OPF) can be computationally intensive and lead to memory issues when dealing with large‐scale power systems. To overcome these challenges, we have developed APD–SDP, an optimisation solver based on a first‐order primal–dual algorithm. This framework incorporates various acceleration techniques, such as rescaling, step size decay and reset, adaptive line search, and restart, to improve efficiency. To further speed up computations, we have developed a customised eigenvalue decomposition component by exploiting the 3 × 3 block structure in the dual SDP formulation. Experimental results demonstrate that APD–SDP outperforms other commercial and open‐source SDP solvers on large‐scale and high‐dimensional PGLib‐OPF datasets.

AIM: To investigate the effects of diquafosol sodium (DQS) for dry eye model induced with povidone-iodine (PI) solution. METHODS: Ten Sprague Dawley rats as the control group. Thirty Sprague Dawley rats were used to establish the dry eye model with stimulation of 10 g/L PI for 14d, then divided rats into three groups: dry eye group with no treatment (DED group, n=10); phosphate buffer saline treated group (PBS group, n=10); diquafosol treated group (DQS group, n=10). Clinical changes were observed by tear production test, fluorescein staining, tear break-up time (TBUT) test, corneal confocal microscope and ocular surface comprehensive analyzer. Eyeballs were collected on day 10 of treatment for hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and alcian blue staining. TUNEL assay, polymorphonuclear (PMN) and mucin 1 (MUC1) immunofluorescence were performed and corneal ultrastructural changes were detected by electron microscopy. RESULTS: Compared with DED and PBS groups, tear production (7.26±0.440 vs 4.07±0.474 mm; 7.26±0.440 vs 3.74±0.280 mm; all P

Abstract We compared the protective effects of inactivated SARS-CoV-2 vaccines derived from the ancestral and the currently circulating BA.5.2 strains against infection with multiple variants in Syrian golden hamsters. Vaccination with BA.5.2 effectively protected against infection with the Omicron subvariants including XBB.1, but not the Alpha or Delta variant. In contrast, hamsters vaccinated with the ancestral strain demonstrated decent neutralization activity against both the Omicron and non-Omicron variants. Our findings might instruct future design and formulation of SARS-CoV-2 vaccines.

Abstract Background and aim Liver failure, which is predominantly caused by hepatitis B (HBV) can be improved by an artificial liver support system (ALSS). This study investigated the phenotypic heterogeneity of immunocytes in patients with HBV-related acute-on-chronic liver failure (HBV-ACLF) before and after ALSS therapy. Methods A total of 22 patients with HBV-ACLF who received ALSS therapy were included in the study. Patients with Grade I according to the ACLF Research Consortium score were considered to have improved. Demographic and laboratory data were collected and analyzed during hospitalization. Immunological features of peripheral blood in the patients before and after ALSS were detected by mass cytometry analyses. Results In total, 12 patients improved and 10 patients did not. According to the immunological features data after ALSS, the proportion of circulating monocytes was significantly higher in non-improved patients, but there were fewer γδT cells compared with those in improved patients. Characterization of 37 cell clusters revealed that the frequency of effector CD8+ T (P = 0.003), CD4+ TCM (P = 0.033), CD4+ TEM (P = 0.039), and inhibitory natural killer (NK) cells (P = 0.029) decreased in HBV-ACLF patients after ALSS therapy. Sub group analyses after treatment showed that the improved patients had higher proportions of CD4+ TCM (P = 0.010), CD4+ TEM (P = 0.021), and γδT cells (P = 0.003) and a lower proportion of monocytes (P = 0.012) compared with the non-improved patients. Conclusions Changes in effector CD8+ T cells, effector and memory CD4+ T cells, and inhibitory NK cells are associated with ALSS treatment of HBV-ACLF. Moreover, monocytes and γδT cells exhibited the main differences when patients obtained different prognoses. The phenotypic heterogeneity of lymphocytes and monocytes may contribute to the prognosis of ALSS and future immunotherapy strategies.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors in the contemporary era, representing a significant global health concern. Early HCC patients have mild symptoms or are asymptomatic, which promotes the onset and progression of the disease. Moreover, advanced HCC is insensitive to chemotherapy, making traditional clinical treatment unable to block cancer development. Sorafenib (SFB) is a first-line targeted drug for advanced HCC patients with anti-angiogenesis and anti-tumor cell proliferation effects. However, the efficacy of SFB is constrained by its off-target distribution, rapid metabolism, and multi-drug resistance. In recent years, nanoparticles based on a variety of materials have been demonstrated to enhance the targeting and therapeutic efficacy of SFB against HCC. Concurrently, the advent of joint drug delivery systems has furnished crucial empirical evidence for reversing SFB resistance. This review will summarize the application of nanotechnology in the field of HCC treatment over the past five years. It will focus on the research progress of SFB delivery systems combined with multiple therapeutic modalities in HCC treatment.

Objective: To develop a model combining clinical and radiomics features from CT scans for a preoperative noninvasive evaluation of Huvos grading of neoadjuvant chemotherapy in patients with HOS. Methods: 183 patients from center A and 42 from center B were categorized into training and validation sets. Features derived from radiomics were obtained from unenhanced CT scans.Following dimensionality reduction, the most optimal features were selected and utilized in creating a radiomics model through logistic regression analysis. Integrating clinical features, a composite clinical radiomics model was developed, and a nomogram was constructed. Predictive performance of the model was evaluated using ROC curves and calibration curves. Additionally, decision curve analysis was conducted to assess practical utility of nomogram in clinical settings. Results: LASSO LR analysis was performed, and finally, three selected image omics features were obtained.Radiomics model yielded AUC values with a good diagnostic effect for both patient sets (AUCs: 0.69 and 0.68, respectively). Clinical models (including sex, age, pre-chemotherapy ALP and LDH levels, new lung metastases within 1 year after surgery, and incidence) performed well in terms of Huvos grade prediction, with an AUC of 0.74 for training set. The AUC for independent validation set stood at 0.70. Notably, the amalgamation of radiomics and clinical features exhibited commendable predictive prowess in training set, registering an AUC of 0.78. This robust performance was subsequently validated in the independent validation set, where the AUC remained high at 0.75. Calibration curves of nomogram showed that the predictions were in good agreement with actual observations. Conclusion: Combined model can be used for Huvos grading in patients with HOS after preoperative chemotherapy, which is helpful for adjuvant treatment decisions.

ABSTRACTSARS-CoV-2, the causative agent of COVID-19, has been intensely studied in search of effective antiviral treatments. The immunosuppressant cyclosporine A (CsA) has been suggested to be a pan-coronavirus inhibitor, yet its underlying mechanism remained largely unknown. Here, we found that non-structural protein 1 (Nsp1) of SARS-CoV-2 usurped CsA-suppressed nuclear factor of activated T cells (NFAT) signaling to drive the expression of cellular DEAD-box helicase 5 (DDX5), which facilitates viral replication. Nsp1 interacted with calcineurin A (CnA) to displace the regulatory protein regulator of calcineurin 3 (RCAN3) of CnA for NFAT activation. The influence of NFAT activation on SARS-CoV-2 replication was also validated by using the Nsp1-deficient mutant virus. Calcineurin inhibitors, such as CsA and VIVIT, inhibited SARS-CoV-2 replication and exhibited synergistic antiviral effects when used in combination with nirmatrelvir. Our study delineated the molecular mechanism of CsA-mediated inhibition of SARS-CoV-2 replication and the anti-SARS-CoV-2 action of calcineurin inhibitors.IMPORTANCECyclosporine A (CsA), commonly used to inhibit immune responses, is also known to have anti-SARS-CoV-2 activity, but its mode of action remains elusive. Here, we provide a model to explain how CsA antagonizes SARS-CoV-2 through three critical proteins: DDX5, NFAT1, and Nsp1. DDX5 is a cellular facilitator of SARS-CoV-2 replication, and NFAT1 controls the production of DDX5. Nsp1 is a viral protein absent from the mature viral particle and capable of activating the function of NFAT1 and DDX5. CsA and similar agents suppress Nsp1, NFAT1, and DDX5 to exert their anti-SARS-CoV-2 activity either alone or in combination with Paxlovid.

BackgroundHemorrhagic transformation (HT) after intravenous thrombolysis (IVT) might worsen the clinical outcomes, and a reliable predictive system is needed to identify the risk of hemorrhagic transformation after IVT.MethodsRetrospective collection of patients with acute cerebral infarction treated with intravenous thrombolysis in our hospital from 2018 to 2022. 197 patients were included in the research study. Multivariate logistic regression analysis was used to screen the factors in the predictive nomogram. The performance of nomogram was assessed on the area under the receiver operating characteristic curve (AUC-ROC), calibration plots and decision curve analysis (DCA).ResultsA total of 197 patients were recruited, of whom 24 (12.1%) developed HT. In multivariate logistic regression model National Institute of Health Stroke Scale (NIHSS) (OR, 1.362; 95% CI, 1.161–1.652; p = 0.001), N-terminal pro-brain natriuretic peptide (NT-pro BNP) (OR, 1.012; 95% CI, 1.004–1.020; p = 0.003), neutrophil to lymphocyte ratio (NLR) (OR, 3.430; 95% CI, 2.082–6.262; p

Trilobolide-6-O-isobutyrate exhibits significant antitumor effects on cholangiocarcinoma (CCA) cells by effectively inhibiting the JAK/STAT3 signaling pathway. This study aims to investigate the mechanisms underlying the antitumor properties of trilobolide-6-O-isobutyrate, and to explore its potential as a therapeutic agent for CCA. This study illustrates that trilobolide-6-O-isobutyrate efficiently suppresses CCA cell proliferation in a dose- and time-dependent manner. Furthermore, trilobolide-6-O-isobutyrate stimulates the production of reactive oxygen species, leading to oxidative stress and initiation of apoptosis via the activation of the mitochondrial pathway. Data from xenograft tumor assays in nude mice confirms that TBB inhibits tumor growth, and that there are no obvious toxic effects or side effects in vivo. Mechanistically, trilobolide-6-O-isobutyrate exerts antitumor effects by inhibiting STAT3 transcriptional activation, reducing PCNA and Bcl-2 expression, and increasing P21 expression. These findings emphasizes the potential of trilobolide-6-O-isobutyrate as a promising therapeutic candidate for the treatment of CCA.

Objective: To investigate the stability of Acorus tatarinowii and Atractylodes lancea essential oils (ATaAL-EO) under a hot environment at 60 °C, and to analyze the differences in component, quantity, and quality changes, as well as variations in the main components, under different treatment methods of crude oil, β-cyclodextrin inclusion of ATaAL-EO, and Pickering emulsion, to improve the stability and quality of ATaAL-EO. Methods: The stability of the ATaAL-EO group, the β-cyclodextrin inclusion ATaAL-EO group, and the Pickering emulsion group were investigated under a 60 °C heat environment. Volatile oil retention rate and peroxide value were collected and measured. The volatile oil components of each group were determined by GC-MS, and t-tests were used to screen for differential components. PCA plots for each group were constructed using the OmicShare online platform. Line plots were generated using the Rmisc and reshape2 packages. Upset Venn diagrams under different hot environments were created using the OmicShare online platform to identify quantitative and qualitative changing components and heat map stack plots for newly generated compounds and connected line plots for disappearing compounds were produced for each group. Boxplots for the main component compounds under different hot environments were generated using the reshape2 and ggplot2 packages. Results: In a hot environment of 60 °C, the β-cyclodextrin inclusion ATaAL-EO and Pickering emulsion group with 1, 3, and 8 h of placement showed higher retention and lower oxidation degree compared to the stability of the ATaAL-EO group. GC-MS analysis results showed that the stability of volatile components in the Pickering emulsion group and β-cyclodextrin inclusion ATaAL-EO group was significantly improved compared to the crude oil group. Conclusion: β-cyclodextrin inclusion complexes with ATaAL-EO, as well as Pickering emulsions, can significantly enhance the stability and quality of ATaAL-EO. Pickering emulsions have more advantages.

Summary: Background: Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising. Methods: A total of 4367 LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage Ⅰ cohort (510 HCCs and 2074 LCs) and Stage Ⅱ cohort (2293 LCs) according to their enrollment time and underwent Tri-phasic CT/enhanced MRI, US, AFP, and cell-free DNA (cfDNA). A screening model called PreCar Score was established based on five features of cfDNA using Stage Ⅰ cohort. Surveillance performance of PreCar Score alone or in combination with US/AFP was evaluated in Stage Ⅱ cohort. Findings: PreCar Score showed a significantly higher sensitivity for the detection of early/very early HCC (Barcelona stage A/0) in contrast to US (sensitivity of 51.32% [95% CI: 39.66%–62.84%] at 95.53% [95% CI: 94.62%–96.38%] specificity for PreCar Score; sensitivity of 23.68% [95% CI: 14.99%–35.07%] at 99.37% [95% CI: 98.91%–99.64%] specificity for US) (P

Background: There is currently no consensus regarding the optimal perioperative antiplatelet strategy for carotid artery surgery. This multicentre study aimed to analyse the association between preoperative aspirin monotherapy following postoperative dual antiplatelet therapy (DAPT) and the risk for stroke and death after carotid endarterectomy (CEA). Methods: This cohort study included 821 patients with carotid artery stenosis who underwent CEA. Primary outcomes included any stroke or death up to the one-month postoperative follow-up. Multilevel multivariate regression analyses and descriptive statistics were performed. Results: Patients were predominantly male (53 %), with a mean age of 66.2 years. The primary outcome occurred in 1.6 % of patients. Univariate and multivariate analyses revealed that patients with chronic obstructive pulmonary disease (COPD) exhibited a high risk for stroke or death (P = 0.011). The occurrence of any local complications in the neck was accompanied by an increase in diastolic blood pressure (DBP) (P = 0.007). Patients with a high systolic blood pressure (SBP) (P = 0.002) experienced a longer operative duration. The length of hospital stay was longer in the patients with COPD (P = 0.020), minor stroke (P = 0.011), and major stroke (P = 0.001). A positive linear correlation was found between SBP and operative duration in the overall population (β 0.4 [95 % confidence interval (CI) 0.1–0.7]; P = 0.002). The resultant curve for DBP and any local complications in the neck exhibited a two-stage change and one breakpoint in the entire population (k = 68 mmHg,

Objective: This study was designed to delve into the complexities involved in diagnosing of benign and malignant bone tumors and to assess the potential of AI technologies like ChatGPT in improving diagnostic accuracy and efficiency. The study also explores the few-shot learning as a method to optimize ChatGPT's performance in specialized medical domains such as benign and malignant bone tumors diagnosis. Methods: A total of 1366 benign and malignant bone tumors-related imaging reports were collected and diagnosed by 25 experienced physicians. The gold standard of diagnosis was established by combining clinical, imaging and pathological principles.These reports were then input into the ChatGPT model which underwent a few-shot learning method to generate diagnostic results. The diagnostic results of the physicians and the AI model were compared to evaluate the performance of ChatGPT. An experiment was conducted to assess the influence of different radiologist's reporting styles on the model's diagnostic performance. Furthermore, in-depth analysis of misdiagnosed cases was carried out, categorizing diagnostic errors and exploring possible causes. Results: The diagnostic results generated by ChatGPT showed an accuracy of 0.73, sensitivity of 0.95, and specificity of 0.58. After few-shot learning, ChatGPT demonstrated significant improvement, achieving an accuracy of 0.87, sensitivity of 0.99, and specificity of 0.73, bringing it much closer to the level of physician diagnostics. In an experiment analyzing the influence of the radiologist's reporting style, the model demonstrated higher sensitivity when interpreting reports written by high-level radiologists. In 56 benign cases, ChatGPT misdiagnosed them as malignant. Among these, 35 benign lesions- fibrous dysplasia and osteofibrous dysplasia- were incorrectly identified as metastatic tumors or osteosarcomas; 8 cases of myositis ossificans were wrongly diagnosed as extraosseous osteosarcoma. 7 cases of giant cell tumor of bone at the end of long bone were misdiagnosed as osteosarcoma by intermediate doctors. Chondroblastoma was misdiagnosed as malignant tumor in 6 cases −2 osteosarcoma and 4 chondrosarcoma-In this study, 23 osteosarcoma cases were misdiagnosed by ChatGPT as osteomyelitis; Chondrosarcoma was misdiagnosed as fibrous dysplasia or aneurysmal bone cyst in 8 cases. Four cases of spinal chordoma were misdiagnosed as spinal tuberculosis. Conclusion: Our findings highlight the potential of ChatGPT in the diagnosis of benign and malignant bone tumors, offering advantages like enhanced efficiency and a reduction in missed diagnoses. However, the necessity of collaborative interactions between physicians and ChatGPT in practical settings was underscored. With an examination into AI's capacity in benign and malignant bone tumors diagnosis, this study lays the groundwork for future AI advancements in medicine. Additionally, the benefits of few-shot learning in fine-tuning ChatGPT applications in specialized fields were also demonstrated.