Acute-on-chronic liver failure （ACLF） is an acute and critical illness with a high short-term mortality rate， and current therapies mainly focus on elimination of causes， organ support， and prevention of complications. Although liver transplantation is the most effective treatment modality， its clinical application is limited， and traditional Chinese medicine has shown significant advantages and characteristics in the treatment of ACLF. In traditional Chinese medicine， ACLF is classified into the same category as diseases such as “jaundice”， and unlike traditional jaundice which is mostly characterized by excess and heat syndromes， the syndrome of ACLF has gradually transformed from Yang jaundice to Yin jaundice due to the changing disease spectrum of ACLF. With reference to the pathogenesis of ACLF in Western medicine and traditional Chinese medicine theories， this article discusses the essential pathogenesis of ACLF in traditional Chinese medicine， explores the evolution of ACLF syndromes， and reviews the research advances in the clinical efficacy and mechanisms of traditional Chinese medicine based on the three-factor differentiation-based treatment of damp-heat， blood stasis-heat， and spleen deficiency， as well as the safety of spleen-strengthening and Yang-warming drugs in the clinical treatment of ACLF， in order to provide ideas， methods， and evidence for the application of traditional Chinese medicine in ACLF.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

OBJECTIVE: To systematically search and integrate the best evidence for early rehabilitation of ICU-acquired swallowing dysfunction (ICU-ASD) using evidence-based medicine methods, providing high-quality evidence-based support for intensive care unit (ICU) healthcare professionals in implementing early rehabilitation assessment and intervention strategies for ICU-ASD. METHODS: The systematic search was conducted according to the "6S" pyramid evidence model. Multiple authoritative databases and resources were comprehensively searched, including: National Guideline Clearinghouse (NGC), National Institute for Health and Care Excellence (NICE), Canadian Medical Association Clinical Practice Guidelines Library (CMACPGL), New Zealand Guidelines Group (NZGG), Guidelines International Network (GIN), Registered Nurses' Association of Ontario (RNAO), Scottish Intercollegiate Guidelines Network (SIGN), PubMed/Medline, Cochrane Library, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, JBI Evidence-Based Health Care Database, Physiotherapy Evidence Database (PEDro), Chinese Medical Pulse Guidelines Website, SinoMed, CNKI, Wanfang Data, UpToDate, BMJ Best Practice, and professional association websites. The search encompassed guidelines, expert consensus statements, original studies [including cohort studies, quasi-experimental studies, and randomized controlled trials (RCT)], systematic reviews, and evidence summaries related to the prevention and management of ICU-ASD. The search period was limited from the inception of each database to November 30, 2024. The best evidence for early rehabilitation of ICU-ASD was summarized. The quality assessment of the literature and the extraction and synthesis of evidence were independently performed by two researchers with expertise in evidence-based medicine methodology. RESULTS: A total of 16 articles were included, consisting of 1 clinical decision-making study, 1 cohort study, 2 guidelines, 2 RCTs, 6 systematic reviews, 1 evidence summary, 2 expert consensuses, and 1 expert opinion. Following quality assessment, all 16 articles were incorporated into the analysis. For the early rehabilitation of ICU-ASD, five major themes were ultimately identified and 25 best evidence items were summarized, focusing on: multidisciplinary collaboration, swallowing screening and assessment, rehabilitation interventions, dietary and nutritional management, and oral hygiene. CONCLUSIONS The evidence summary provides individualized rehabilitation strategies for ICU-ASD patients, but their implementation still needs to be adapted to China's clinical practice context and patient preferences.
Humans ; Deglutition Disorders/etiology* ; Intensive Care Units ; Evidence-Based Medicine

Bio-mineralization has emerged as a promising strategy to enhance vaccine immunogenicity. This study optimized the calcium phosphate (CaP) mineralization process of foot-and-mouth disease virus-like particles (FMD VLPs) to achieve high mineralization efficiency and scalability. Key parameters, including concentrations of Ca²⁺, HPO₄^2-, NaCl, and VLPs, as well as stirring speed, were systematically optimized. Stability of the scaled-up reaction system and immunogenicity of the mineralized vaccine were evaluated. Optimal conditions [25.50 mmol/L Ca(NO₃)₂, 15 mmol/L Na₂HPO₄, 300 mmol/L NaCl, 0.75 mg/mL VLPs, and 1 500 r/min] yielded CaP-mineralized VLPs (VLPs-CaP) with high mineralization efficiency, uniform morphology, and a favorable particle size. Scaling up the reaction by 25 folds maintained consistent mineralization efficiency and particle characteristics. Immunization in mice demonstrated that VLPs-CaP induced higher titers of specific antibodies and neutralizing antibodies than unmineralized VLPs (P < 0.05). Higher IgG2a/IgG1 ratio and enhanced IFN-γ secretion (P < 0.05) further indicated robust cellular immune responses. We establish a stable and scalable protocol for VLPs-CaP, providing a theoretical and technical foundation for developing high-efficacy VLPs-CaP vaccines.
Vaccines, Virus-Like Particle/immunology* ; Immunogenicity, Vaccine ; Calcium Phosphates/chemistry* ; Foot-and-Mouth Disease Virus ; Biomineralization ; Particle Size ; Animals ; Mice ; Antibodies, Neutralizing/blood* ; Antibodies, Viral/blood* ; Immunity, Cellular

Vaccination is a crucial strategy for the prevention and control of infectious diseases. Virus-like particles (VLPs), composed of structural proteins, have garnered significant attention as a novel type of vaccine due to their excellent safety and immunogenicity. However, similar to most vaccine antigens, VLPs exhibit insufficient thermal stability, which not only restricts the widespread application of vaccines but also increases the risk of vaccine inactivation. This study aims to enhance the stability and shelf life of VLPs derived from type A foot-and-mouth disease virus (FMDV) by employing vacuum freeze-drying technology. The optimal lyoprotectant formulation was determined through single-factor and combinatorial screening. Subsequently, the correlation between the immunogenicity of the freeze-dried vaccine and the content of FMDV VLPs was evaluated via a mouse model. The stability of FMDV VLPs before and after freeze-drying was further assessed by storing them at 4, 25, and 37 ℃ for varying time periods. Results indicated that the lyoprotectant formulation No.1, composed of 7.5% trehalose, 0.1% Tween 80, 50 mmol/L glycine, 1% sodium glutamate, and 3% polyvinylpyrrolidone (PVP), effectively preserved the content of FMDV VLPs during the vacuum freeze-drying process. The immunization trial in mice revealed that the levels of specific antibodies, immunoglobulin G1 (IgG1), interleukin-4 (IL-4), and neutralizing antibodies induced by freeze-dried FMDV VLPs were comparable to those induced by non-freeze-dried FMDV VLPs. The heat treatment results showed that the storage periods of freeze-dried FMDV VLPs at 4, 25, and 37 ℃ were significantly longer than those of non-freeze-dried FMDV VLPs. In conclusion, the selected lyoprotectant formulation effectively improved the stability of FMDV VLPs vaccines. This study provides valuable insights for enhancing the stability of novel subunit vaccines.
Freeze Drying/methods* ; Animals ; Foot-and-Mouth Disease Virus/immunology* ; Mice ; Vaccines, Virus-Like Particle/chemistry* ; Foot-and-Mouth Disease/immunology* ; Vacuum ; Drug Stability ; Mice, Inbred BALB C ; Viral Vaccines/immunology*

Objective To assess the role of the ferroptosis-associated gene GLS2 in the prognosis of pan-cancer and immunity using bioinformatics methods. Methods GLS2 expression levels in pan-cancer were profiled using publicly available databases: The Cancer Genome Atlas, GTEx, Cancer Cell Line Encyclopedia and the International Cancer Genome Consortium. The aim was to explore the role of GLS2 gene expression, gene variation survival analysis, immune infiltration, immune checkpoint related genes, TMB, and MSI in different tumors. Results Difference in GLS2 expression levels between cancer and paraneoplastic tissues was statistically significant in most cancer types, and the expression level was correlated with survival in these cancer types. A positive correlation was found between GLS2 expression and immune cell infiltration in multiple cancer types, and GLS2 expression level was positively correlated with TMB, MSI, and methylation, and its expression is an indicator for potential therapeutic response. Conclusion Pan-cancer analysis shows that the ferroptosis-related gene GLS2 can be used as a diagnostic and prognostic marker of clear cell carcinoma of kidney, adrenocortical carcinoma, lung adenocarcinoma, and pancreatic cancer.

Objective To explore the effect of individualized positive end expiratory pressure guided by driving pressure on lung protection after laparoscopic radical gastrectomy for elderly patients.Methods A total of 64 patients underwent elective laparoscopic radical gastrectomy for gastric cancer in the Second Affiliated Hospital of Anhui Medical University were selected.According to the random number table method,patients were divided into the driving the pressure guided individualized positive end-expiratory pressure(PEEP)group(experimental group)and the fixed PEEP group(control group),32 cases in each group.In the control group,PEEP = 5 cmH2O.In the experimental group,PEEP titration was performed according to the increasing method,and the PEEP corresponding to the lowest driving pressure was selected until extubation.Peak airway pressure(Ppeak),plateau airway pressure(Pplat)and PEEP were recorded at 5 min after intubation(T1),immediately after PEEP titration(T2),1 h after operation(T3),2 h after operation(T4),and 10 min after pneumoperitoneum release(T5).Driving pressure(ΔP)and lung dynamic compliance(Cdyn)were calculated.Arterial blood was collected at T1-5 for blood gas analysis,arterial partial pressure of oxygen(PaO2)was recorded,and oxygenation index(OI)was calculated.The occurrence of pulmonary complications(PPCs)within 7 days after operation was recorded.Modified clinical pulmonary infection score(mCPIS)was recorded on the second day after operation.The pulmonary function was evaluated before operation,1 day,3 days and 5 days after operation.Results Compared with T1,Ppeak,Pplat and ΔP were increased and Cdyn was decreased at T2-5,while OI was decreased at T4 in control group(P＜0.05).Compared with the control group,Ppeak,Pplat and Cdyn in the experimental group were increased at T2-5,ΔP was decreased,and OI was increased at T3-5(P＜0.05).Compared with the preoperative results,FVC at 1,3 and 5 days after surgery was decreased,and FEV1 and maximum expiratory flow(PEF)were decreased 1 and 3 days after surgery in the experimental groups(P＜0.05).Compared with the control group,FVC,FEV1 and PEF were higher 1 day after operation in the experimental group(P＜0.05).Compared with the preoperative results,mCPIS scores of the two groups were higher on the second day after surgery(P＜0.05).Compared with the control group,the mCPIS score was lower on day 2 after surgery in the experimental group(P＜0.05).The incidence of PPCs within 7 days after surgery was lower in the experimental group than that in the control group(15.6%vs.40.6%).Conclusion Individualized PEEP guided by drive pressure can improve lung compliance,reduce drive pressure,improve oxygenation function and early postoperative lung function,reduce the incidence of postoperative lung complications,and has a certain lung protection effect.

Objective:To establish a mouse model of breast cancer lung metastasis with miR-155 knockout(miR155-/-)mice,and to compare the difference of peripheral blood immune cell typing between miR155-/-mice and C57BL/6J wide-type(WT)mice.Methods:Bioinformatics analysis was used to explore the expression level of miR-155 in breast cancer tissues and peripheral serum,and its relationship with prognosis.Mouse model of lung metastasis of breast cancer was established by tail vein injection;peripheral blood was collected for flow cytometry,and the immune cell typing was analyzed;the lung tissues were collected for immunohisto-chemical detection to observe the tumor metastasis.Results:Percentage of T lymphocytes and monocytes in peripheral blood of miR155-/-mice was significantly decreased compared with WT mice(P<0.05),percentage of myeloid inhibitory cells(MDSCs)was increased significantly(P<0.05),in which the proportion of monocyte subsets(M-MDSC)was significantly decreased(P<0.05),while the proportion of granulocyte subsets(G-MDSC)was significantly increased(P<0.05).In lung metastasis model of breast can-cer,percentage of T lymphocytes in peripheral blood of miR155-/-mice was significantly higher compared with WT mice,while per-centage of NK cells was decreased significantly(P<0.05),percentage of neutrophil was significantly decreased(P<0.001),propor-tion of Th cells in T lymphocytes was significantly decreased(P<0.05),proportion of M-MDSCs was significantly decreased(P<0.01),while proportion of G-MDSCs was significantly increased(P<0.01).Conclusion:Deletion of miR-155 gene leads to significant differences in peripheral immune cell typing,making mice more susceptible to lung metastasis of breast cancer.

Since the first operational definition of cognitive frailty was proposed by the expert consensus group of the International Academy of Nutrition and Aging and the International Association of Gerontology and Geriatrics in 2013, frailty and neurocognitive assessment has become the standard diagnostic tool.Since then, the reported prevalence in the literature for cognitive frailty in community-dwelling elderly people vary by dozens of times, as a result of different scales and diagnostic cut-off points, seriously affecting health decision-making.This article reviewed the current literature with a focus on the re-recognition of the clinical significance of cognitive frailty, the limitations of existing assessment tools for diagnosis, and possible solutions in the future.