ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

ObjectiveTo screen suitable packaging and storage conditions for small packaged Alismatis Rhizoma decoction pieces， laying the foundation for developing standardized storage， maintenance techniques and determining shelf life. MethodsUsing the accelerated stability test method， the small packaged decoction pieces of Alismatis Rhizoma were placed in polyethylene plastic bags， aluminum foil polyethylene composite bags， and cowhide coated paper bags under temperature of （40±2） ℃ and relative humidity of （75±5）% conditions， the quality testing was conducted at the end of the 0^th， 1^st， 2^nd， 3^rd， and 6^th month， respectively. Using long-term stability test method， an orthogonal experiment was designed to investigate storage conditions， packaging materials， and packaging methods. At the end of the 0^th， 1^st， 3^rd， 6^th， 9^th， 12^th， 18^th， and 24^th month， the quality of small packaged Alismatis Rhizoma decoction pieces was tested under different packaging and storage conditions（including 2 packaging methods：vacuum packaging and sealed packaging， 3 storage conditions：room temperature， cool， and modified atmosphere， 3 packaging materials：cowhide coated paper bag， aluminum foil polyethylene composite bag， and polyethylene plastic bag）. Then， the G1-entropy weight method combined with orthogonal experiment was used to analyze the quality changes of the decoction pieces under different packaging and storage conditions to identify optimal packaging and storage conditions. The quality testing indicators for Alismatis Rhizoma decoction pieces were expanded beyond those specified in the 2020 edition of the Pharmacopoeia of the People's Republic of China. In addition to the existing indicators（characteristics， moisture content， extractives， and the total content of 23-acetyl alisol B and 23-acetyl alisol C）， new indicators including color value， water activity， total triterpenoid content， and alisol B content have been added. ResultsThe accelerated stability test results indicated that the quality of small packaged Alismatis Rhizoma decoction pieces was more stable when packaged in aluminum foil-polyethylene composite materials compared to cowhide-coated paper bags and polyethylene plastic bags. Analysis of the long-term stability test results using the G1-entropy weight method combined with orthogonal experiment revealed that storage conditions had the greatest impact on both raw and salt-processed products， followed by packaging materials， while the packaging method had the least influence. For both types of small packaged Alismatis Rhizoma decoction pieces， modified atmosphere storage demonstrated superior efficacy compared to cool storage or room temperature storage. Storage in aluminum foil-polyethylene composite bags was superior to polyethylene plastic bags or cowhide-coated paper bags. However， the stability of sealed raw products was better than vacuum-packed ones， whereas vacuum-packed salt-processed products exhibited greater stability than their sealed counterparts. ConclusionBased on the results of the quality changes of small packaged Alismatis Rhizoma decoction pieces under different storage conditions， it is recommended that the suitable storage packaging conditions for small packaged raw products are sealed packaging with aluminum foil polyethylene composite bags and controlled atmosphere storage， and the suitable storage and packaging conditions for small packaged salt-processed products are vacuum packaging with aluminum foil polyethylene composite bags and controlled atmosphere storage.

Background: and Purpose Accurately predicting long-term functional outcomes of basilar artery occlusion (BAO) remains challenging. We compared the predictive performance of the baseline, 24-hour, and 72-hour National Institutes of Health Stroke Scale (NIHSS) scores for 90-day BAO functional outcomes using the Acute Basilar Artery Occlusion: Endovascular Thrombectomy versus Standard Medical Treatment (ATTENTION) trial data. We identified the optimal assessment time point, determined treatment-specific NIHSS cutoff values, and explored the role of early neurological function in treatment effects. Methods: This retrospective post hoc analysis included 324 patients with acute BAO with baseline NIHSS scores ≥10 and complete NIHSS assessments at each time point. The primary outcome was a favorable 90-day functional outcome (modified Rankin Scale score, 0–3). Receiver operating characteristic curve analysis was used to assess the predictive ability of NIHSS scores. The optimal 72-hour NIHSS predictive cutoff values were determined for the endovascular treatment (EVT) and best medical management (BMM) subgroups. Results: The 72-hour NIHSS score showed the highest predictive accuracy for the primary outcome (area under the receiver operating characteristic curve [AUC]: 0.954), outperforming the 24-hour (AUC: 0.903) and baseline (AUC: 0.688) scores; its optimal predictive cut-off value was ≤11 in the EVT group (sensitivity: 85.6%, specificity: 92.9%, positive predictive value [PPV]: 91.8%, negative predictive value [NPV]: 87.4%) and ≤9 in the BMM group (sensitivity: 84.6%, specificity: 95.1%, PPV: 84.6%, NPV: 95.1%). Conclusions The 72-hour NIHSS score outperformed the baseline and 24-hour scores in predicting 90-day functional outcomes and mediating the effects of EVT. Treatment-specific 72-hour NIHSS cut-off values may guide early risk stratification and prognostic assessments.

ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

Electroencephalogram (EEG) is a non-invasive, high temporal-resolution technique for monitoring brain activity. However, affected by the volume conduction effect, EEG has a low spatial resolution and is difficult to locate brain neuronal activity precisely. The surface Laplacian (SL) technique obtains the Laplacian EEG (LEEG) by estimating the second-order spatial derivative of the scalp potential. LEEG can reflect the radial current activity under the scalp, with positive values indicating current flow from the brain to the scalp (“source”) and negative values indicating current flow from the scalp to the brain (“sink”). It attenuates signals from volume conduction, effectively improving the spatial resolution of EEG, and is expected to contribute to breakthroughs in neural engineering. This paper provides a systematic overview of the principles and development of SL technology. Currently, there are two implementation paths for SL technology: current source density algorithms (CSD) and concentric ring electrodes (CRE). CSD performs the Laplace transform of the EEG signals acquired by conventional disc electrodes to indirectly estimate the LEEG. It can be mainly classified into local methods, global methods, and realistic Laplacian methods. The global method is the most commonly used approach in CSD, which can achieve more accurate estimation compared with the local method, and it does not require additional imaging equipment compared with the realistic Laplacian method. CRE employs new concentric ring electrodes instead of the traditional disc electrodes, and measures the LEEG directly by differential acquisition of the multi-ring signals. Depending on the structure, it can be divided into bipolar CRE, quasi-bipolar CRE, tripolar CRE, and multi-pole CRE. The tripolar CRE is widely used due to its optimal detection performance. While ensuring the quality of signal acquisition, the complexity of its preamplifier is relatively acceptable. Here, this paper introduces the study of the SL technique in resting rhythms, visual-related potentials, movement-related potentials, and sensorimotor rhythms. These studies demonstrate that SL technology can improve signal quality and enhance signal characteristics, confirming its potential applications in neuroscientific research, disease diagnosis, visual pathway detection, and brain-computer interfaces. CSD is frequently utilized in applications such as neuroscientific research and disease detection, where high-precision estimation of LEEG is required. And CRE tends to be used in brain-computer interfaces, that have stringent requirements for real-time data processing. Finally, this paper summarizes the strengths and weaknesses of SL technology and envisages its future development. SL technology boasts advantages such as reference independence, high spatial resolution, high temporal resolution, enhanced source connectivity analysis, and noise suppression. However, it also has shortcomings that can be further improved. Theoretically, simulation experiments should be conducted to investigate the theoretical characteristics of SL technology. For CSD methods, the algorithm needs to be optimized to improve the precision of LEEG estimation, reduce dependence on the number of channels, and decrease computational complexity and time consumption. For CRE methods, the electrodes need to be designed with appropriate structures and sizes, and the low-noise, high common-mode rejection ratio preamplifier should be developed. We hope that this paper can promote the in-depth research and wide application of SL technology.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Objective To explore the latent profile analysis of oral frailty in elderly patients with multiple chronic conditions and to analyze the influencing factors of different potential profiles in order to provide a theoretical basis for constructing clinical intervention programs.Methods Convenience sampling method was used to select elderly patients with multiple chronic conditions in a tertiary hospital in Hefei City from July to December 2024 as the survey subjects.General information questionnaire,the Chinese version of the Oral Frailty Index-8,Mini-Nutritional Assessment Short-Form,Consumer Health Activation Index and Family APGAR Index Questionnaire were used to conduct the survey,and multivariate logistic regression was used to analyze the influencing factors.Results A total of 418 elderly patients with multiple chronic conditions were included,with a total oral frailty score of(7.21±2.83).Oral frailty in elderly patients with multiple chronic conditions can be classified into 3 potential profiles,namely severe oral frailty-low oral functioning group(60.53％),moderate oral frailty-high social behaviors group(8.85％),mild oral frailty-high oral health behavior group(30.62％).Age,family care,type of chronic disease,type of oral medication,and consumer health activation index were influential factors for different potential profiles(P＜0.05).Conclusion The oral frailty in elderly patients with multiple chronic conditions was heterogeneous.Caregivers should focus on the severe oral frailty-low oral functioning group and the moderate oral frailty-high social behavior group,and develop targeted interventions according to the patients'different profile characteristics and influencing factors to prevent and delay the occurrence of oral frailty.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To explore the effect of recombinant human brain natriuretic peptide(rhBNP)combined with dopamine on cystatin C(CysC),homocysteine(Hcy)and cardiac function in patients with severe heart failure(HF).Methods:This randomized controlled study enrolled 110 severe HF patients admitted in Aerospace Center Hospital between December 2021 and December 2022.They were divided into control group(n=55,nitroglycerin combined dopamine)and combined treatment group(n=55,rhBNP combined dopamine).Each group received corresponding therapy based on basic treatment for one week.Therapeutic effect,levels of CysC,Hcy,left ventric-ular end-systolic diameter(LVESd),left ventricular end-diastolic diameter(LVEDd),left ventricular ejection fraction(LVEF),and incidence of adverse reactions were compared between two groups.Results:Compared with patients in control group,those in combined treatment group had significant higher total effective rate(81.82％vs.58.18％)and LVEF[(54.68±4.59)％vs.(44.79±4.37)％],and significant lower CysC[(1.02±0.19)mg/L vs.(1.40±0.21)mg/L],Hcy[(15.98±2.17)μmol/L vs.(21.05±2.82)μmol/L],LVESd[(35.13±3.51)mm vs.(41.71±3.28)mm]and LVEDd[(41.33±4.26)mm vs.(50.51±4.37)mm](P＜0.01 all).There was no significant difference in total incidence of adverse reactions between two groups(16.36％vs.7.27％,P=0.180).Conclusion:rhBNP combined with dopamine could significantly improve the clinical therapeutic effect,im-prove levels of CysC,Hcy and cardiac function with good safety in the treatment of severe HF.

Background and purpose:Human papilloma virus(HPV)infection status is crucial for diagnosing cervical precancerous lesions and classifying cervical cancer.High-risk(HR)HPV is often linked to P16 protein overexpression,so P16 detection via immunohistochemistry(IHC)is commonly used to assess HPV infection.However,the differences between HPV status and P16 expression remains unclear.An in-depth study of the correlation between HPV and P16 is essential for clinical guidance.Methods:We retrospectively collected clinical and pathological data of cervical lesions from 618 patients diagnosed at the Department of Pathology,Fudan University Shanghai Cancer Center from January 2020 to December 2023(Ethical number:050432-4-2307E).Polymerase chain reaction(PCR)reverse dot hybridization was used to detect HPV including HR and low-risk(LR)subtypes,and immunohistochemistry was used to detect P16 for comparative analysis.Based on different clinical and pathological diagnoses,the sensitivity and specificity of P16 expression in evaluating HPV infection were evaluated.Among the 618 cases of cervical lesions,there were 92 cases of cervical squamous cell carcinoma,257 cases of cervical adenocarcinoma,79 cases of high-grade squamous intraepithelial lesions(HSIL),105 cases of low-grade squamous intraepithelial lesions(LSIL),and 85 cases of chronic cervical inflammation.Results:According to clinical diagnosis,the HR-HPV positive rate in cervical squamous cell carcinoma was 88.0%(81/92),the P16 positive rate was 91.3%(84/92),and the overall consistency rate between P16 and HPV detection was 90.2%(88/92);for HR-HPV infection,the sensitivity and specificity of P16 were 96.3%and 45.5%.The positive rate of HR-HPV in adenocarcinoma was 54.5%(140/257),the positive rate of P16 was 58.8%(151/257),and the overall consistency rate between P16 and HPV detection was 82.5%(212/257);for HR-HPV infection,the sensitivity and specificity of P16 were 87.9%and 76.1%.In HSIL,the HR-HPV positive rate was 75.9%(60/79),the positive rate of P16 was 70.9%(56/79),and the overall consistency rate between P16 and HR-HPV detection was 82.2%(65/79);for HR-HPV infection,the sensitivity and specificity of P16 were 85.0%and 73.7%.In LSIL,the HR-HPV positive rate was 73.3%(77/105),the positive rate of P16 was 8.5%(9/105),and the overall consistency rate between P16 and HR-HPV detection was 33.3%(35/105);for HR-HPV infection,the sensitivity and specificity of P16 were 10.4%and 96.4%.In chronic cervical inflammation,the HR-HPV positive rate was 20%(17/85),the positive rate of P16 was 0.0%(0/85);for HR-HPV infection,the sensitivity and specificity of P16 were 0.0%and 100.0%.There was a significant positive correlation between P16 positivity and HPV16/18 in cervical squamous cell carcinoma,adenocarcinoma,and HSIL(P=0.000),while there was no significant correlation in LSIL and chronic cervical inflammation(P＞0.05).Conclusion:In cervical squamous cell carcinoma and adenocarcinoma,the consistency of P16 expression and HPV DNA positivity are high,especially in HPV16/18 subtype.There is a good concordance between HR-HPV positivity and P16 protein overexpression.The positive expression of P16 in HSIL may initially reflect HPV infection status.However,in LSIL and chronic cervicitis,P16 expression may not accurately correlate with HPV infection.The inconsistency between P16 and HPV DNA testing could be influenced by multiple factors,including HPV subtypes,histopathological categories,specimen quality,and technical limitations.In clinical practice,it is recommended to conduct comprehensive analysis or employ multiple diagnostic methods to confirm HPV infection status for precise evaluation.