OBJECTIVE To compare the efficacy and safety of chemotherapy combined with tislelizumab or sintilimab in patients with advanced non-small cell lung cancer （NSCLC）， and to analyze the influential factors of prognostic. METHODS A retrospective study was conducted on 163 patients with advanced NSCLC who received chemotherapy combined with tislelizumab or sintilimab at the First People’s Hospital of Yunnan Province from September 1， 2021 to November 30， 2024. Among them， there were 90 patients in the tislelizumab group and 73 patients in the sintilimab group. The objective response rate （ORR）， disease control rate （DCR）， progression free survival （PFS）， and overall survival （OS） of two groups were observed， and the occurrence of adverse drug reactions in patients was evaluated. Kaplan-Meier method was used to plot PFS and OS survival curves， Log-rank test was applied for univariate analysis， and Cox regression model was used to evaluate the independent prognostic factors of PFS and OS. RESULTS The median PFS of patients in the tislelizumab group and the sintilimab group were 14.14 months （95%CI of 10.95-17.33） and 10.95 months （95%CI of 8.75-13.15）， respectively. The median OS was 25.89 months （95%CI of 22.67-29.11） and 24.25 months （95%CI of 19.34-29.16）， with ORR of 45.56% and 49.32%， DCR of 94.44% and 90.41%， and the incidence of adverse drug reactions of 84.44% and 79.45%， respectively， the differences were not statistically significant （P＞0.05）. Age ≥60 years （HR＝1.542， 95%CI of 1.044-2.278， P＝0.029） and systemic immune inflammatory nutritional index （SIINI）＞ 116.58 （HR＝1.541， 95%CI of 1.058-2.245， P＝0.024） were risk factors for PFS in NSCLC patients receiving immune checkpoint inhibitor therapy； the use of antibiotics may affect the overall survival of patients （P＝0.001）. CONCLUSIONS The efficacy and safety of chemotherapy combined with tislelizumab or sintilimab for advanced NSCLC are comparable； age≥60 years and SIINI ＞116.58 are risk factors for PFS in NSCLC patients， and the use of antibiotics may affect the patients’ OS.

Climate and land use changes may significantly impact the habitat distribution of Gastrodia elata, an endangered traditional medicinal plant. Accurately predicting its future potential suitable habitats is crucial for its conservation and sustainable development. This study integrates current distribution data of G. elata with 56 environmental variables and uses the MaxEnt model to predict changes in its suitable habitats under current climate conditions and four future climate scenarios(SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5). The results show that October precipitation and December minimum temperature are key environmental factors influencing its distribution. Under the current climate, optimal habitats for G. elata are concentrated in montane forest areas in Sichuan, Yunnan, Guizhou, and Hubei, which meet the species' requirements for understory growth. Across all future scenarios, the suitable habitat of G. elata consistently shows a stable northward shift, with a steady increase in suitable areas, extending to the middle and lower reaches of the Yangtze River and the Huang-Huai region, and even expanding into Liaoning, Jilin, and southern Heilongjiang. Land use analysis, taking into account the protection of arable land and the utilization of forest resources, indicates that by 2100, under future climate conditions, arable land in medium-to high-suitability areas is expected to increase by 30%-124%. While the conversion of non-suitable forest land into suitable habitats is projected to increase by 5%-52%, the growth of medium-to high-suitability areas within forests is relatively modest, ranging from 1% to 24%. These findings highlight the need to balance agricultural expansion with forest resource conservation to ensure the long-term sustainability of G. elata and provide scientific guidance for future suitable habitat management.
Ecosystem ; China ; Climate Change ; Gastrodia/growth & development* ; Conservation of Natural Resources ; Plants, Medicinal/growth & development*

Objective To explore the effects of Yin Yang 1(YY1)on the proliferation and migration of bladder cancer cells and investigate the underlying mechanisms,so as to provide reference for the prevention and treatment of this disease.Methods The expression patterns of YY1 in common genitourinary tumors and their associations with the prognosis were analyzed using data from The Cancer Genome Atlas(TCGA)and the Gene Expression Omnibus(GEO).The efficiency of YY1 knockdown and overexpression in bladder cancer cell lines(T24 and UM-UC-3)was confirmed with quantitative reverse transcription PCR(qRT-PCR)and Western blotting.Cell proliferation and migration were assessed using methylthiazolyldiphenyl-tetrazolium bromide(MTT)and Transwell assays.RNA sequencing followed by bioinformatics analyses,including Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG),and Gene Set Enrichment Analysis(GSEA),was conducted to predict potential mechanisms.The qRT-PCR and rescue experiments were performed to validate whether YY1 exerted its effects via the E2F1 signaling pathway.Results YY1 was significantly overexpressed in bladder cancer compared to other genitourinary tumors and was associated with higher tumor grade and poorer prognosis(P＜0.05).Functional assays demonstrated that YY1 promoted the proliferation and migration of bladder cancer cells.Transcriptome analyses revealed that YY1 might regulate these processes through the E2F signaling pathway.Moreover,overexpression of E2F1 partially reversed the inhibitory effects of YY1 knockdown on bladder cancer cell proliferation and migration.Conclusion YY1 is upregulated in bladder cancer and is closely associated with tumor grade and unfavorable prognosis.It may facilitate tumor cell proliferation and migration by modulating the E 2F1 signaling pathway.

Hepatitis B virus（HBV）infection poses a significant global health burden，with chronic infection driving progression to cirrhosis，hepatic failure，and hepatocellular carcinoma（HCC）. Mounting evidence implicates immune dysfunction and microbiota dysbiosis as core drivers of disease progression across all HBV infection stages. Gut and tissue-specific microbiota alterations disrupt innate/adaptive immunity，fueling inflammation，immunosuppression，and tumor immune evasion in chronic and end-stage disease. This review synthesizes mechanisms of immune-microbiota interplay in HBV pathogenesis and explores their translational potential for diagnostics and targeted interventions，including microbiota modulation and microbial biomarker applications.

Acute-on-chronic liver failure （ACLF） is a complex clinical syndrome， and early identification and accurate prognostic evaluation are of great importance for patient treatment and management. In recent years， with in-depth research on the pathogenesis of ACLF， multiple prognostic biomarkers have been proposed and used in clinical practice. This article systematically reviews the research advances in prognostic biomarkers for ACLF from the aspects of clinical predictive models， immunological biomarkers， metabolic biomarkers， genetic and epigenetic biomarkers， microbiome-related biomarkers， and emerging technologies such as artificial intelligence and multi-omics， and it also discusses the value and application prospects of these biomarkers in the prognostic evaluation of ACLF and proposes future research directions， in order to provide a scientific and comprehensive reference for clinicians， guide individualized treatment and management of ACLF patients， and finally improve the clinical outcomes of patients.

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

Over the past few decades, tumor immunotherapy has revolutionized the landscape of cancer clinical treatment. There is a flourishing development of combination strategies to improve the anti-tumor efficacy of mono-immunotherapy. However, instead of a straightforward combination of multiple therapeutics, it is more preferable to pursue a synergistic effect by designing rational combinations as well as administration strategies, which are based on a comprehensive understanding of the physiological and pathological features. In this case, the timing and spatial distribution of the combination drugs become essential factors in achieving improved therapeutic outcomes. Therefore, the concept of Sequential Drug Delivery System (SDDS) is proposed to define the spatiotemporally programmed drug delivery/release through triggers of internal conditions and/or external interventions, thus complying with the dynamic disease evolution and the human immunity. This review summarizes the recent advancements in biomaterial-based SDDSs used for spatiotemporally-tuned combination tumor immunotherapy. Furthermore, the rationales behind various engineering strategies are discussed. Finally, an overview of potential synergistic mechanisms as well as their prospects for combination immunotherapy is presented.

Quality marker (Q-Marker) is an innovative concept and model for quality control of Traditional Chinese medicines (TCMs), which will navigate the new direction of quality development of TCMs. Yet, how to characterize the overall quality attributes of TCMs and their biological effects is still debating. In view of this key scientific issue, this paper proposes a research method based on mass spectrometry imaging (MSI) technology for the discovery and confirmation of TCMs Q-Marker. MSI is powerful in investigating the spatial distribution of molecules in a variety of samples, and visualizing the information obtained from MS. On this basis, combine with the five principles of TCMs Q-Marker validation, i.e., specificity, transmission and traceability, testability, prescription compatibility, and validity, were applied to confirm the finalized Q-Marker. It will lead the new direction of quality development of TCMs.