Background and aims:Advanced hepatocellular carcinoma(HCC)with pulmonary metastasis(PM)has a poor prognosis,and optimal treatment strategies remain controversial.This study aimed to compare the long-term outcomes of patients with advanced HCC with PM who were treated with resection of pul-monary metastases versus those treated with targeted therapies combined with immunotherapy.Methods:A retrospective analysis was conducted on the medical records of HCC patients with PM who underwent either pulmonary metastasectomy or immunotherapy combined with targeted therapies at the Eastern Hepatobiliary Surgery Hospital,Changhai Hospital of Shanghai,Fujian Provincial Hospital,and West China Hospital of Sichuan University from September 2013 to October 2022.One-to-one propensity score matching(PSM)was employed to control the influence of potential confounders,and the survival outcomes were compared.Results:A total of 119 HCC patients with PM were included in this study.The overall survival(OS)of patients who underwent pulmonary metastasectomy was significantly longer than that of patients who received immunotherapy targeted combinations(OS:1-year,80.0％vs.59.3％;2-year,31.7％vs.20.3％;3-year,20.0％vs.0;P＜0.001).After PSM,the long-term prognosis of the pulmonary metastasectomy group remained significantly better than that of the immunotherapy combination group(OS:1-year,87.0％vs.69.6％;2-year,34.8％vs.30.4％;3-year,21.7％vs.0;P=0.005).Multivariate analysis revealed that treat-ment allocation(hazard ratio(HR)=2.177,95％confidence interval(CI)=1.068-4.439)and hepatic tumor T stage(HR=2.342,95％CI=1.209-4.538)were independent risk factors for OS.Conclusions:Pulmonary metastasectomy was associated with improved survival compared to immu-notherapy combined with targeted therapies and may represent an optimal treatment option for highly selected HCC patients with resectable PM.

Myocardial fibrosis(MF)is the leading cause of car-diac insufficiency.Its complex pathogenesis and lack of effective treatment are key issues to be addressed in the cardiovascular field.Mitochondrial quality control system(MQC)is an impor-tant mechanism for eukaryotic cells to maintain the stability of mitochondrial form,quantity and quality.MQC disorders,which are characterized by low level of mitochondrial biogenesis,exces-sive mitochondrial oxidative stress,mitochondrial autophagy de-fect and mitochondrial dynamics disorder,play a crucial role in mediating the pathophysiological process of MF.Consequently,this article reviews the role of MQC in MF pathogenesis and the latest research,in order to better understand the molecular mech-anism of MF and provide reference for the development of more natural drugs in the future.

Objective:To investigate the neuroprotective effect of non-invasive vagus nerve stimulation(nVNS)on traumatic brain injury(TBI).Methods:Male SD rats were used to prepare controlled cortical impact(CCI)rat mod-el.nVNS treatment was performed.The motor function of rats was detected by beam walking test.The water content of rats was evaluated by the dry-wet ratio of rat brain tissue.The content of lactate dehydrogenase(LDH)in cerebrospinal fluid was detected by commercial kit.The expression of bain-derived neurotrophic factor(BDNF)and nerve growth fac-tor(NGF)mRNA in rat cortex was detected by RT-qPCR.Results:After nVNS stimulation,CCI rats significantly im-proved the neurological function deficit,improved the motor ability,decreased the cerebral water content,decreased the level of LDH in cerebrospinal fluid,and upregulated the expression of BDNF and NGF mRNA in cortex.Conclusion:nVNS has a neuroprotective effect on TBI rats,and its mechanism may be related to the increased expression of BDNF and NGF.

With the continuous advancement of medical research, it is increasingly recognized that the human body functions as a highly coordinated complex system, and the development of diseases often involves intricate interactions among multiple subsystems, including organs, tissues, and cells. Conventional pharmacological research, which primarily focuses on isolated subsystems, tends to emphasize direct interactions between drugs and the molecular targets in diseased organs. However, this approach often falls short in addressing the multifaceted challenges posed by complex diseases such as metabolic disorders, autoimmune diseases, cancers, and aging. In recent years, inter-organ cross-talk and its role in diseases progression, as well as cross-organ effects of drug intervention, have gained significant attention. This has highlighted the potential for treating complex diseases through holistic regulation of multiple organs. Traditional Chinese medicine(TCM) has long embraced a holistic and systemic approach for treatment, with concepts such as the interdependence and mutual restraint of the five Zang organs, the interconnection of Zang organs and Fu organs, treating the Zang organ diseases by regulating the Fu organs, treating the child organ diseases to cure the parent organs, and treating upper organ diseases by regulating lower organs. These concepts provide valuable insights into exploring the pathways and molecular mechanisms underlying inter-organ cross-talk. Building on our previous work on indirect actions of TCM, this paper introduces the concept of indirect pharmacology mediated by intermediate substances, as a new extension of classical pharmacology. This approach aims to offer new perspectives and innovative ideas for understanding inter-organ cross-talk and discovering cross-organ therapeutic strategies.
Humans ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology* ; Animals

OBJECTIVES: To assess the preliminary efficacy and safety of a dose-intensified C5VD regimen (cisplatin, 5-fluorouracil, vincristine, and doxorubicin) in children with locally advanced hepatoblastoma. METHODS: This prospective study enrolled 24 children with newly diagnosed, locally advanced hepatoblastoma who received the dose-intensified C5VD regimen at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children's Hospital between January 2020 and December 2023. Clinical characteristics, treatment outcomes, and chemotherapy-related toxicities were analyzed. RESULTS: Of the 24 patients, 13 were male and 11 were female, with a median age at diagnosis of 18.7 months (range: 3.5-79.4 months). All patients achieved complete macroscopic resection of hepatic lesions without liver transplantation. Serum alpha-fetoprotein levels decreased significantly after two chemotherapy cycles. During a median follow-up of 38.4 months (range: 15.8-50.7 months), all patients maintained continuous complete remission, with 3-year event-free survival and overall survival rates of 100%. Across 144 chemotherapy cycles, the incidence rates of grade 3-4 neutropenia, thrombocytopenia, and infections were 97%, 77%, and 71%, respectively; no treatment-related deaths occurred. Notably, 5 patients (21%) developed Brock grade ≥3 hearing loss, of whom 1 required a hearing aid. CONCLUSIONS The dose-intensified C5VD regimen demonstrates significant efficacy with an overall favorable safety profile in the treatment of newly diagnosed, locally advanced pediatric hepatoblastoma. Grade 3-4 myelosuppression and infection are the predominant toxicities. However, high‑dose cisplatin-induced ototoxicity remains a concern, highlighting the need for improved otoprotective strategies.
Humans ; Hepatoblastoma/pathology* ; Male ; Female ; Infant ; Liver Neoplasms/pathology* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child, Preschool ; Prospective Studies ; Doxorubicin/adverse effects* ; Child ; Cisplatin/adverse effects* ; Vincristine/adverse effects* ; Fluorouracil/adverse effects*

OBJECTIVE: By analyzing the hormone secretion of the adenohypophysis, thyroid glands, gonads, and adrenal cortex in patients with hematological diseases before and after hematopoietic stem cell transplantation (HSCT), this study aims to preliminarily explore the effect of HSCT on patients' hormone secretion and glandular damage. METHODS: The baseline data of 209 hematological disease patients who underwent HSCT in our hospital from January 2019 to December 2023, as well as the data on the levels of hormones secreted by the adenohypophysis, thyroid glands, gonads and adrenal cortex before and after HSCT were collected, and the changes in hormone levels before and after transplantation were analyzed. RESULTS: After allogeneic HSCT, the levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3) and estradiol (E2) decreased, while the levels of luteinizing hormone (LH) and follicle- stimulating hormone (FSH) increased. The T3 level of patients with decreased TSH after transplantation was lower than that of those with increased TSH after transplantation. In female patients, the levels of prolactin (PRL), progesterone (Prog), and testosterone (Testo) decreased after HSCT. Testo and PRL decreased when there was a donor-recipient sex mismatch, and the levels of adrenocorticotropic hormone (ACTH) and cortisol (COR) decreased when the HLA matching was haploidentical. The levels of T3, FT3, and PRL decreased after autologous HSCT. In allogeneic HSCT patients, the levels of TSH, T4, T3, FT3, and ACTH in the group with graft-versus-host disease (GVHD) were significantly lower than those in the group without GVHD. Logistic regression analysis showed the changes in hormone levels after transplantation were not correlated with factors such as the patient's sex, age, or whether the blood types of the donor and the recipient are the same. CONCLUSION HSCT can affect the endocrine function of patients with hematological diseases, mainly affecting target glandular organs such as the thyroid, gonads, and adrenal glands, while the secretory function of the adenohypophysis is less affected.
Humans ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Hematologic Diseases/blood* ; Follicle Stimulating Hormone/blood* ; Triiodothyronine/blood* ; Luteinizing Hormone/blood* ; Thyroid Gland/metabolism* ; Estradiol/blood* ; Thyrotropin/blood* ; Gonads/metabolism* ; Adult ; Middle Aged ; Adrenocorticotropic Hormone/blood* ; Hormones/metabolism* ; Adrenal Cortex/metabolism* ; Prolactin

OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Objective:This study aimed to investigate the value of myocardial contrast echocardiography(MCE)in the prognostic assessment of patients undergoing revascularization for acute anterior ST-segment elevation myocar-dial infarction(STEMI).Methods:A total of 234 patients with acute anterior STEMI who underwent percutaneous coronary intervention(PCI)and completed MCE admitted in Dongguan People's Hospital between July 1st 2019 and October 1st 2021 were included.According to presence of major adverse cardiovascular events(MACE)during 6 months,patients were divided into no MACE group(n=188)and MACE group(n=46).General data and MCE indexes were compared between the two groups.Multivariate Logistic regression analysis was employed to analyze influencing factors for MACE in patients with acute anterior STEMI after PCI.Receiver operating characteristic(ROC)curve was applied to analyze predictive value of MCE indexes for MACE in patients with acute anterior STE-MI after PCI.Results:Compared with patients in no MACE group,those in MACE group had significant higher proportion of previous myocardial infarction,D-dimer,C reactive protein,B-type natriuretic peptide,creatine kinase isoenzyme MB(CK-MB),incidence of T-wave inversion and ST-segment resolution amplitude(P＜0.05 or＜0.01).MCE showed that compared with those in no MACE group,those in MACE group had significant lower left ventricular ejection fraction(LVEF)[(52.54±7.66)％ vs.(55.98±10.04)％],and significant higher wall motion score index(WMSI)[(1.22±0.13)vs.(1.17±0.15)]and contrast score index(CSI)[(1.54±0.32)％vs.(1.16±0.21)％](P＜0.05 or＜0.01).Multivariate Logistic regression analysis revealed that previous myocar-dial infarction,C-reactive protein,CSI and T-wave inversion were independent risk factors for MACE in patients with acute anterior STEMI after PCI(OR=13.790～6601.747,P＜0.05 or＜0.01).ROC curve indicated that CSI had good predictive value for MACE in patients with acute anterior STEMI after PCI,the area under curve(AUC)was 0.874(95％CI 0.825～0.914)and optimal cutoff point was 1.33％.Conclusion:Myocardial contrast echocardiography plays an important role in prognostic assessment of patients undergoing revascularization for acute anterior STEMI.