e16171 Background: Triple therapy combining transarterial therapy, tyrosine kinase inhibitors (TKIs), and programmed death-1 (PD-1) inhibitors represents a promising therapeutic strategy for unresectable hepatocellular carcinoma (uHCC). This study aimed to evaluate the efficacy and safety of transarterial therapy combined with donafenib (a TKI) and PD-1 inhibitors as first-line treatment in a real-world uHCC cohort. Methods: This was a multicenter, retrospective study conducted across five medical centers in China. We analyzed patients diagnosed with uHCC who had received at least one cycle of triple combination therapy comprising transarterial therapy (hepatic arterial infusion chemotherapy [HAIC] and/or transarterial chemoembolization [TACE]), donafenib, and PD-1 inhibitors. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), surgical conversion rate, and safety. Tumor responses were assessed according to both the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and RECIST v1.1. Results: After screening, 70 patients were included in the analysis. Key baseline characteristics were as follows: median age 55 years; 92.9% male; 87.1% with HBV infection; 60.0% at BCLC stage C. Additionally, 48.6% of patients had macrovascular invasion, 22.9% had extrahepatic metastasis, and 74.2% presented with multiple tumors, with a median maximum tumor diameter of 86.5 mm. The PD-1 inhibitors administered included tislelizumab (41.4%), camrelizumab (37.1%), sintilimab (18.6%), toripalimab (2.9%). Transarterial therapy regimens consisted of TACE plus HAIC (38.6%), HAIC alone (34.3%), and TACE alone (27.1%). After a median follow-up of 27.5 months, the median PFS was 12.7 months (95% CI, 8.4-23.8) per both mRECIST and RECIST v1.1. The median OS was 29.3 months (95% CI, 22.4-NA) with 12- and 24-month OS rates of 81.7% and 57.2%, respectively. The ORR was 67.1% per mRECIST and 52.9% per RECIST v1.1, and the DCR was 87.1% by both criteria. The surgical conversion rate was 22.9%. Treatment-related adverse events (TRAEs) occurred in 87.1% of patients, with grade 3-4 events in 37.1%. The most common TRAEs included liver dysfunction (51.4%), hand-foot skin reaction (47.1%), decreased platelet count (18.6%), and decreased white blood cell count (17.1%). Conclusions: This real-world study demonstrates that transarterial therapy combined with donafenib and PD-1 inhibitors provides encouraging survival outcomes and a manageable safety profile for uHCC patients. Clinical trial information: ChiCTR2200063822.

Objective Intraoperative ultrasound (IOUS) is frequently used for real-time guidance during anatomical liver resection, which is considered to be the gold standard treatment for early-stage hepatocellular carcinoma (HCC), but manual hepatic vessel annotation continues to be challenging due to the complexity and noise in ultrasound images. Materials and Methods With an emphasis on anatomical liver resection, our research examines the practicality of using the YOLOv5 deep-learning algorithm for real-time identification of hepatic vessels in ultrasound images. The model was rained, tested, and validated using a dataset of 100 intraoperative laparoscopic ultrasound images. Also, real-time hepatic vessel recognition was performed intraoperatively in 20 patients. Results The results showed engrossing performances, with the model achieving a precision of 1 when confidence reached 0.764 in the P-curve analysis. The R-curve analysis revealed that recall dropped to 0 at a confidence threshold of 1.00. When the Intersection over Union (IoU) was set to 0.5, the mean Average Precision (mAP) was 0.941. Additionally, the optimal balance between precision and recall was observed at a confidence level of 0.202, where the F1 score reached 0.58. Conclusion These findings demonstrate that the YOLOv5 model has a major potential to enhance surgical precision, reduce duration of surgery, and reduce surgical riscks. This study highlights the potential of AI models in improving outcomes in liver surgeries and suggests broader applications in other surgical domains.

Staphylococcus aureus is a major opportunistic pathogen in humans; airborne exposure to this bacterium is associated with increased respiratory disease incidence. The airway epithelium, serving as the primary barrier against inhaled pathogens, is particularly vulnerable to bacterial invasion. However, the underlying mechanisms and relevant biomarkers for this exposure remain underexplored. In this study, we evaluated the toxic effect mechanisms and biomarkers of S. aureus aerosol exposure to human bronchial epithelial (16HBE) cells at the air-liquid interface using microRNA (miRNA) sequencing. We found that exposure to aerosols containing 3.21 × 105 to 6.54 × 106 CFU/m3S. aureus impaired cell viability and proliferation, induced mitochondrial damage, and triggered inflammation by upregulating IFN-γ expression. The bacterium secreted pore-forming toxins, coagulases, nucleases, enterotoxins, and β-hemolysins to lyse cells and induced a cytokine storm by modulating the expression of hla, coa, nuc, sea, and hlb genes. 16HBE cells primarily upregulated Toll-like receptors (TLR1 and TLR5), mucins (MUC1), and epidermal growth factor receptors (KGF7 and TEP1) to recognize invasion, activate the immune response, and protect the cell membrane. miRNA sequencing suggested that medium-concentration exposure induced more differentially expressed genes (DEGs), particularly downregulated DEGs, than other concentrations. Twelve miRNAs uniquely shared across the exposure groups were considered potential biomarkers of S. aureus aerosol exposure. Regulatory networks analysis showed that miR-19a-3p, miR-18a-5p, miR-106b-5p, and miR-142-5p could influence cancer-related pathways and the MAPK signaling pathway by targeting genes such as CRK, NCOA3, MAPK1, and TGFR2 and may serve as biomarkers of 16HBE cell damage. Overall, this study elucidates the injury mechanisms and potential biomarkers of S. aureus aerosol exposure in respiratory cells, advances the understanding of airborne pathogen-induced toxicity.

Laparoscopic anatomic hepatectomy (LAH) requires precise intraoperative navigation and spatial accuracy. We developed a multimodal image fusion system based on augmented reality (AR) and intraoperative ultrasound (IOUS), which integrates laparoscopic and ultrasound images with three-dimensional (3D) holograms into a unified visual interface, thereby facilitating intuitive comprehension of liver anatomy. Preclinical simulation experiments in porcine models demonstrated that this platform reduced surgeons’ workload, as assessed by the National Aeronautics and Space Administration Task Load Index (NASA-TLX). Corroborating these findings, this system diminished cognitive burden while enhancing surgical precision and efficiency during LAH. In a retrospective cohort study of 47 patients with hepatocellular carcinoma (HCC), system-assisted LAH was associated with shorter operative duration and inflow occlusion time, reduced intraoperative blood loss, lower postoperative aminotransferase levels and higher albumin concentrations compared with traditional methods. Notably, in indocyanine green (ICG) positive-staining LAH, the puncture success rate exhibited a significant improvement in the system-assisted group, and the resected liver volume demonstrated greater concordance with the preoperatively planned volume. These preliminary results underscore the potential clinical utility of the system in improving spatial orientation, alleviating cognitive demands, and optimizing complex surgical maneuvers during LAH, with consequent improvements in perioperative outcomes for HCC patients.

Colorectal cancer (CRC), one of the most prevalent malignancies of the digestive system, has shown a steady annual rise in incidence linked to evolving lifestyle patterns. The liver serves as the most common metastatic site for CRC, with colorectal liver metastases (CRLM) representing a leading cause of mortality among affected individuals. While the molecular pathogenesis of CRC remains incompletely understood, elucidating the mechanisms underlying CRLM holds significant potential for refining diagnostic and therapeutic approaches. In recent years, patient-derived organoids (PDOs) have emerged as a transformative research model in oncology due to their unique advantages in disease modeling, mechanistic exploration, and drug sensitivity testing. Since their inaugural successful cultivation in 2013, tumor organoid technology has undergone rapid advancement. This innovative platform utilizes three-dimensional (3D) Matrigel culture systems to propagate biopsy or surgical specimens into tissue analogs that faithfully recapitulate the architectural and functional complexity of native organs, thereby establishing a robust methodology for high-efficiency expansion of primary cells, including both normal and malignant populations. The distinctive value of PDOs lies in their preservation of tumor heterogeneity and microenvironmental interactions, enabling researchers to investigate cancer biology while maintaining critical cell-cell and cell-matrix communication networks. Particularly in CRLM research, organoid models permit longitudinal observation of metastatic processes under controlled experimental conditions, facilitating mechanistic studies of invasion, angiogenesis, and hepatic colonization. Furthermore, these systems demonstrate remarkable translational potential in personalized medicine, as drug response profiles generated from patient-specific organoids frequently correlate with clinical outcomes, offering opportunities for tailored therapeutic strategies. Current progress in organoid technology has significantly enhanced our understanding of CRLM pathogenesis. Studies utilizing this model have identified key molecular pathways involved in epithelial-mesenchymal transition (EMT), immune evasion, and metabolic reprogramming during hepatic metastasis. Notably, the integration of organoid co-culture systems with hepatic stromal components has provided novel insights into tumor-stroma crosstalk mechanisms that promote metastatic niche formation. From a clinical perspective, the establishment of organoid biobanks from CRLM patients has enabled largescale pharmacological screens, accelerating the discovery of targeted therapies and overcoming traditional limitations associated with conventional 2D cell cultures. Building upon our institutional experience, this review comprehensively examines recent advancements in CRLM pathophysiology and the expanding applications of organoid models. We highlight technical innovations in organoid generation from metastatic lesions and discuss remaining challenges in standardized protocol implementation. As the field progresses toward multi-omics integration and microphysiological system development, organoid technology promises to bridge critical gaps between bench research and clinical practice, ultimately advancing precision oncology in CRLM management.

Cholangiocarcinoma (CCA) is the second most common malignant liver tumor after hepatocellular carcinoma. It is highly aggressive, and most patients are diagnosed at an advanced stage, losing the opportunity for surgical resection. What's worse, the palliative radiotherapy and chemotherapy have limited efficacy. Photodynamic therapy (PDT), based on photosensitizers, is a new treatment modality following surgery and chemoradiotherapy for tumors. Clinically, hematoporphyrin derivative preparations are commonly chosen as photosensitizers for PDT in CCA. Although these derivatives are widely used and their efficacy has been validated by numerous clinical studies, the actual long-term outcome mostly remains unsatisfactory. This is primarily due to their low efficiency in generating reactive oxygen species (ROS) and the inherently hypoxic microenvironment of CCA, which limits their function. To address these concerns, we constructed a nanocomposite based on black phosphorus nanosheets loaded with Fe3O4 nanoparticles, assisted by electrolytic oxygen supply. The study aims to enhance the cytotoxicity against CCA by leveraging the efficient singlet oxygen generation of black phosphorus and the Fe3O4-catalyzed hydroxyl radical production from hydrogen peroxide. Additionally, it proposes to improve the hypoxic microenvironment of CCA and increase the tumor's sensitivity to PDT by using direct current electrolysis (DCE) to generate oxygen. The primary focus of this research is to explore the regulatory mechanisms of hypoxia-PDT for CCA based on ultrathin black phosphorus nanosheets, providing new insights for optimizing clinical PDT for CCA.

The proteome serves as a key source for the discovery of therapeutic targets. This study utilized proteome-wide Mendelian randomization (MR) to identify protein biomarkers potentially associated with intrahepatic cholangiocarcinoma (ICC). We derived protein quantitative trait loci (pQTLs) from the deCODE plasma proteome GWAS and genetic ICC associations from a European meta-analysis. Proteome-wide MR identified candidate proteins linked to ICC risk. Expression of MR-identified biomarkers in the plasma of ICC patients was detected by ELISA. ScRNA-seq analysis detected the specific cell type with enrichment expression. Prognostic and diagnostic evaluations in ICC of these proteins were performed using samples derived from TCGA and GTEx databases. MR analysis genetically predicted 5 proteins were associated with ICC risk (STX12, A2M, CD163, CXADR and FOXJ2). The results of the MR analysis for the five identified targets were consistent with the measured plasma concentrations of these targets in ICC patients and healthy volunteers. The differential RNA-seq analysis between tumor and adjacent normal tissues showed that STX12 was expressed at higher levels in tumor tissues, while A2M, CXADR, CD163, and FOXJ2 were expressed at higher levels in adjacent normal tissues. ScRNA-seq analysis revealed that these protein-coding genes are mainly expressed in TAMs, TEC, HPC-like cells and malignant cells in ICC tumor tissue. Prognosis analysis showed higher CXADR expression correlated with longer OS in CHOL (P = 0.041). The AUC for A2M, CD163, CXADR, FOXJ2, and STX12 were 0.975, 0.705, 0.917, 0.997, and 0.956, respectively. This study represents the first Proteome-MR analysis of ICC, revealing its complex genetic architecture and identifying five novel blood proteins with potential causal links to the disease. Through proteome-MR analysis, scRNA-seq analysis, and diagnostic-prognostic evaluation using TCGA and GTEx databases, these proteins were assessed as promising therapeutic and diagnostic targets. The findings provide a theoretical foundation for future ICC treatment strategies.

Airborne microorganisms in hospitals present significant health risks to both patients and employees. However, their pollution profiles and associated hazards in different hospital areas remained largely unknown during the extensive use of masks and disinfectants. This study investigated the characteristics of bioaerosols in an urban general hospital during the COVID-19 pandemic and found that airborne bacteria and fungi concentrations range from 87 ± 35 to 1037 ± 275 CFU/m3 and 21 ± 15 to 561 ± 132 CFU/m3, respectively, with the outpatient clinic and internal medicine ward showing the highest levels. The operating room (OR) and clinical laboratory (LA) had lower bioaerosol levels but higher microbial activities, suggesting that disinfection procedures used to clean bioaerosols may change them into a viable but non-culturable state. The dominant fungi were Cladosporium, Aspergillus, and Penicillium, while the most common viruses were human associated gemykibivirus 2 and human alpha herpesvirus 1. Besides, the dominant pathogens were Staphylococcus aureus, Salmonella enterica, and Pseudomonas aeruginosa. Bacitracin and macrolides resistance genes bacA and ermC were the most prevalent subtypes of antibiotic resistance genes. Compared to the control sample, hospital-acquired bioaerosols, particularly from the outpatient examination room and emergency room can trigger higher levels of inflammatory factors and cell toxicity but lower cell proliferation rates. Lower cell toxicity was observed in low-risk areas (intensive care unit, LA, and OR). This study provides a new method for assessing bioaerosol health risks and enhances understanding of nosocomial and opportunistic infections and their control.

e16133 Background: Based on the different anti-malignant mechanisms of tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs) and transarterial therapy, several studies have demonstrated the potential of combining these three treatments to improve outcomes in patients with unresectable hepatocellular carcinoma (uHCC). This study aimed to evaluate the efficacy and safety of transarterial therapy plus donafenib and ICIs for uHCC patients in a real-world setting. Methods: This multicenter retrospective study included patients with uHCC who had received at least one cycle of transarterial therapy (hepatic arterial infusion chemotherapy, HAIC, or transarterial chemoembolization, TACE) and donafenib and ICIs (anti-PD-1 available in China) at five cancer centers. Other key inclusion criteria were: (1) no prior systemic treatment; (2) at least one follow-up image data. The primary endpoint was progression-free survival (PFS) according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Secondary endpoints included overall survival (OS), objective response rate (ORR) and toxicity. Results: Of the 61 eligible patients enrolled, 56 (91.8%) were men, 54 (88.5%) had HBV infection, 26 (42.6%) had AFP level > 400 ng/mL, 38 (62.3%) were at BCLC stage C, 32 (52.5%) had macrovascular invasion, 14 (23.0%) had extrahepatic metastasis, 47 (77.0%) had multiple tumors and the median maximum tumor size was 86.0 mm (IQR, 61.5–122.6). Four kinds of ICIs were employed, including tislelizumab (n = 29), camrelizumab (n = 21), sintilimab (n = 9), toripalimab (n = 2). Up to the date of November 24, 2023, the median follow-up time was 13.0 months. The median PFS was 12.7 months (95%CI, 8.4–NA), with a 1-year PFS rate of 52.7% (95%CI, 37.9%–73.1%). The median OS was not reached, and 1-year OS rate was 88.4% (95%CI, 79.9%–97.8%). The ORR according to mRECIST was 70.5%. Twelve (19.7%) patients had received conversion resection, and the median conversion time was 3.1 months (95%CI, 2.37–NA). Overall, 51 (83.6%) patients experienced at least one treatment-related adverse events (TRAEs), 22 (36.1%) had grade 3 or 4 AEs, and no patients died due to AEs. The most common AEs greater than 15% were hand-foot skin reaction (47.5%), liver dysfunction (27.9%), decreased platelet count (19.7%) and hypoalbuminemia (16.4%). Conclusions: This retrospective real-world study showed that transarterial therapy combined with donafenib plus ICIs in the treatment of uHCC patients was well tolerated and comparable clinical efficacy to other triple therapies. This combination strategy may be an appropriate treatment option for uHCC patients.

Protein induced by vitamin K absence or antagonist II (PIVKA-II) plays a critical role in the diagnosis of hepatocellular carcinoma (HCC), however, studies on its efficacy in diagnosing recurrent HCC were rarely found. A multicenter, retrospective, and observational study was conducted. During the overall follow-up of 5 years, HCC patients who had curative resection were monitored every 3 months in the first year post-surgery and every 6 months thereafter if no recurrence occurred. Tumor markers were collected at the diagnosis of recurrence for those with recurrence and at the last follow-up for those without recurrence. The median serum levels of PIVKA-II and AFP in the recurrence group were significantly higher than those in the non-recurrence group (PIVKA-II: 84.62 vs. 18.76 mAU/ml, p < 0.001; AFP: 4.90 vs. 3.00 ng/ml, p < 0.001) and there is a significant correlation between PIVKA-II and AFP (R = 0.901, p < 0.001). PIVKA-II showed better accuracy than AFP in the diagnosis of overall recurrent HCC (AUC: 0.883 vs. 0.672; p < 0.0001), but also in patients with negative PIVKA-II before curative resection (AUC: 0.878 vs. 0.680, p = 0.001). Clinician should pay more attention to serum PIVKA-II values when following patients after curative HCC resection to detect early recurrence. Clinical trial registration: ChiCTR2300070874

PURPOSE:Tumor-associated macrophages (TAMs) play a critical role in hepatocellular carcinoma (HCC) progression and metastasis. Systematic investigation of the cross-talk between TAMs and HCC may help in searching for the critical target to guard against HCC metastasis. METHODS AND RESULTS:Herein, we found that TREM1 highly expressed in HCC tissue by analyzing the data obtain from GEO database. Interestingly, the results indicated that TREM1 was primarily expressed by monocytes. Immune infiltration studies further validated that TREM1 expression was positively related with increased infiltration of macrophages in HCC tissues. In vitro, we observed that TREM1 knockdown significantly abrogated the effect of TAMs in promoting the metastasis and epithelial-mesenchymal transition (EMT) of HCC cells. Additionally, cytokine array detection identified CCL7 as the main responsive cytokine following with TREM1 knockdown in TAMs. CONCLUSION:Taken together, our findings strongly suggested that high expression of TREM1 was positively associated with metastasis and poor prognosis of HCC. Furthermore, TAMs expressing TREM1 contribute to EMT-based metastasis through secreting CCL7. These results provide a novel insight into the potential development of targeting the TREM1/CCL7 pathway for preventing metastatic HCC.

Spatiotemporal downregulation of immune checkpoint provides a promising strategy to activate anti-tumor immunity. In this work, a breast cancer targeted photodynamic degrader (designated as EIpro) is constructed to activate immunotherapy through EGFR degradation mediated PD-L1 downregulation. To be specific, we develop a chimeric peptide, comprising the photosensitizer Protoporphyrin IX (PpIX) and EGFR targeting peptide (QRHKPRE), to encapsulate an EGFR inhibitor afatinib (AFA) forming nanomicelle, namely EIpro. EIpro has a favorable stability and uniform nanosize distribution, preferring to accumulate in EGFR overexpressed breast cancer cells to amplify the chemotherapeutic effect and photodynamic elimination behavior. More interestingly, photodynamic therapy (PDT) produced reactive oxygen species (ROS) is able to damage breast cancer cells and induce immunogenic cell death (ICD) to release tumor associated antigens (TAAs), thereby degrading the nearby EGFR to downregulate PD-L1 and activate anti-tumor immunity. Beneficially, the multi-synergistic effects of EIpro show a robust therapeutic efficacy against primary and metastatic breast cancer with negligible systemic toxicity. This work provides a spatiotemporal strategy for protein degradation, which might inspire the development of sophisticated nanomedicine for effective tumor treatment.

Background Photodynamic therapy (PDT) has been emerging as a promising treatment for unresectable cholangiocarcinoma (CCA). A number of experiments have demonstrated that PDT could enhance antitumor immunity significantly. However, the impact of PDT on peripheral immune system for unresectable CCA remains unclear. Methods In a clinical trial comparing the perioperative and long-term outcomes of PDT+stent treatment and stent alone treatment for unresectable CCA, we tested the levels of lymphocytes (CD4+ T cells, CD8+ T cells, NK cells, B cells and Treg cells) and immune-related cytokines (IL-4, IL-6, IL-10, TNF-α, TGF-β, perforin, GM-CSF and IFN-γ) in peripheral blood before and after PDT+stent treatment or stent alone treatment and analyzed the influence of PDT on peripheral immune system for unresectable CCA. Results Before treatment, the levels of all the immune cells and immune-related cytokines did not show significant differences between the PDT+stent group and stent alone group. The ratio of CD8+ T cells increased significantly after PDT treatment, but other kinds of lymphocytes did not show significant difference. Increased level of IL-6 and decreased level of perforin and TGF-β after PDT treatment were demonstrated, whereas no significant changes were found for other immune-related cytokines. Conclusion PDT altered the levels of immune cells and immune-related cytokines in the peripheral blood of unresectable CCA patients, potentially correlating with the therapeutic efficacy of PDT in unresectable CCA treatment. Future studies could delve deeper into this aspect to explore how PDT can be more effectively utilized in the management of unresectable CCA.

Background There lacks an effective histomorphological predictive option for dismal outcome of intrahepatic cholangiocarcinoma (iCCA). This study aims to evaluate the prognosis and anti-PD 1 therapy effect of iCCA patients with radical resection through the occurrence of homotypic cell-in-cell structure (hoCIC) phenomenon. Methods The study collected biological specimens and clinical data from iCCA patients who underwent radical resection from January 2015 to December 2023. We performed an analysis of hoCICs profiling in iCCA biopsy using "epithelium-macrophage-leukocyte" (EML) multiplex staining. Subsequently, we investigate the feasibility of utilizing hoCICs as a functional biomarker for predicting prognosis and responses to PD-1 inhibitor treatment in patients with iCCA through Kaplan-Meier plotting and Cox regression model. Results A total of 34 patients with iCCA were included in the study, with a median follow-up of 37 months. The results of multivariable Cox analysis revealed that TiT (tumor cell inside tumor cell) counts ≥ 3 were independently associated with overall survival (OS) with a hazard ratio (HR) of 3.815 (P = 0.0293) and recurrence-free survival (RFS) with a HR of 3.547 (P = 0.0290), respectively. 11 of the 34 iCCA patients received postoperative anti-PD1 treatment. The log-rank test result showed that the recurrence-free survival (RFS) of TiT counts ≥ 3 group was significantly shorter than that of the TiT counts < 3 group, revealing a HR of 4.308 (P = 0.0301). These results indicated that lower TiT level had a better response to postoperative anti-PD1 treatment. Conclusions The current study highlights hoCICs as a potential adverse prognostic biomarker in patients with iCCA. Furthermore, hoCICs may serve as predictive indicators for the treatment response to postoperative anti-PD1 therapy, based on recurrence-free survival (RFS).

BACKGROUND:Macrophages are activated in ventilator-induced lung injury (VILI), accompanied by macrophage pyroptosis. Remimazolam (Re) plays a role in inhibiting macrophage activation. In this study, we aimed to investigate the mechanism of Re in VILI. METHODS:A VILI model (20 mL/kg mechanical ventilation) was created using C57BL/6 mice. Alveolar macrophages were isolated from bronchoalveolar lavage fluid (BALF) and received mechanical stretching to simulate the mechanical ventilation in vitro. VILI model mice were treated with Re (16 mg/kg) to assess the alveolar structure, wet/dry (W/D) weight ratio, endothelial barrier antigen (EBA) permeability index, BALF protein content, inflammatory factors, macrophage pyroptosis, pyroptosis-related factors, and translocator protein (TSPO) level using a series of biological experiments. Whether Re alleviated macrophage pyroptosis by regulating TSPO was determined by rescue experiments. RESULTS:Re alleviated VILI, as evidenced by improvement of abnormal morphology of lung tissues during VILI and decreases in the lung W/D weight ratio, lung EBA permeability index, and BALF protein content. Re attenuated pulmonary inflammation and macrophage pyroptosis during VILI via down-regulation of inflammatory factors (myeloperoxidase, malondialchehyche, 8-hydroxy-2 deoxyguanosine, interleukin-6, tumor necrosis factor-α, macrophage inflammatory protein-2, interleukin-1β, and interleukin-18), and pyroptosis factors (cleaved gasdermin D (GSDMD)/GSDMD value, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), and caspase-1). Re activated TSPO in macrophages. TSPO overexpression rescued the cell stretch-inhibited macrophage viability and cell stretch-induced macrophage pyroptosis. CONCLUSION:Re alleviates VILI by activating TSPO to inhibit macrophage pyroptosis.

Abstract Aim To establish a clinically applicable organoid-based model for drug sensitivity and evaluate its predictive accuracy in determining the effectiveness of chemotherapy for secondary liver cancer arising from gastrointestinal tumors. Methods Relevant information and tumor tissue from four cases of colorectal cancer with liver metastasis (synchronous or metachronous), and a case of gastric cancer with liver metastasis, were collected at the Seventh Affiliated Hospital of Sun Yat-sen University between January 1, 2019, to December 31, 2022. Liver metastasis organoid models were established, and drug sensitivity tests for fluorouracil, oxaliplatin, and irinotecan were conducted. Drug sensitivity of liver metastatic organoids was assessed using IC50 values. Changes in tumor size in patients before and after clinical drug administration were calculated based on RECIST 1.1 criteria. The relationship between drug sensitivity scores of organoids and tumor size before and after treatment was analyzed. Results Four colorectal cancer liver metastases and one gastric cancer liver metastases were successfully cultured from patient samples. Histological staining verified the homogeneity of these models. Consistency was observed between the drug sensitivity scores of the organoids and the changes in tumor size in patients before and after clinical drug administration. Conclusion The organoid model drug sensitivity testing of secondary liver cancer originating from gastrointestinal tumors can effectively predict the efficacy of chemotherapy drugs in clinical practice and guide treatment decisions.

Abstract Tumor-infiltrating lymphocyte(TIL) therapy, an immunotherapy that uses CD8 + T as the main killer cells isolated from the patient's tumor tissue to treat the patient's tumor, has shown efficacy in solid tumors. In the tumor microenvironment, effector CD8 + T cells enter a state of impaired function known as T cell exhaustion. Therefore, how to improve their activity and rapid expansion in vitro is the key problem to be solved in TIL therapy. Combination immunotherapy has recently emerged as a potent cancer treatment strategy. And nanomaterials have shown great application value in the field of immunotherapy. We achieved optimal activation and amplification of CD8 + T cells by combining organic nanomaterial black phosphorus quantum dots(BPQDs) with immune checkpoint inhibitory molecules PD-1 and LAG3. CD8 + T cells enhanced cytotoxic function through a series of biomarkers (TNF-a and IFN-γ secretion) and targeted cell-killing measurements in vitro. It was related to the increase of CD8 + T cells, and the increased function was more than the number of cells increased, indicating that the function of CD8 + T cells was also enhanced. This work demonstrates a novel strategy for using organic nanotechnology to improve effective expansion and efficacy of tumor-infiltrating lymphocytes.

Background:Biopsy of a transplanted pancreas is sometimes necessary in patients who have undergone simultaneous pancreas-kidney (SPK) transplantation and have elevated serum lipase and amylase concentrations. However, the risks associated with pancreatic graft biopsy are high, and the best biopsy technique for different location of pancreatic graft remains unclear.Methods:Depending on the anatomical location of the transplanted pancreas, percutaneous computed tomography (CT) combined with color Doppler-guided puncture biopsy or laparoscopic biopsy was used to obtain samples of transplanted pancreatic tissue that were shallow and deep, respectively.Results:After SPK transplantation, 4 patients developed abnormal serum lipase and amylase concentrations and underwent pancreas graft biopsy, 1 patient underwent percutaneous CT combined with color Doppler-guided puncture biopsy, 2 patients underwent laparoscopic wedge biopsy, and 1 patient underwent laparoscopic and puncture biopsy. All biopsies were performed successfully, with no intra- or postoperative complications (e.g., bleeding, pancreatic leakage, intestinal leakage). Biopsy sampling was effective in 3 patients, including 1 case of acute pancreatic rejection, 1 case of pancreatitis, and 1 case of pancreatic plasmablastic lymphoma. Biopsy failed to retrieve samples in 1 patient with a deep pancreatic graft who underwent laparoscopic wedge biopsy.Conclusions:Pancreas graft biopsy is safe and feasible after SPK transplantation. In addition to the two biopsy methods mentioned, other methods can also be used. Different biopsy strategies should be formulated according to the anatomical location of the transplanted pancreas.