BACKGROUND: Pre-transplant exposure to immune checkpoint inhibitors (ICIs) significantly increases the risk of allograft rejection after liver transplantation (LT); however, whether ICI-related rejection leads to increased graft loss remains controversial. Therefore, this study aimed to investigate the association between ICI-related allograft rejection and perioperative graft loss. METHODS: This was a retrospective analysis of adult liver transplant recipients with early biopsy-proven T-cell-mediated rejection (TCMR) at Liver Transplantation Center of Sun Yat-sen Memorial Hospital from June 2019 to September 2024. The pathological features, clinical characteristics, and perioperative graft survival were analyzed. RESULTS: Twenty-eight patients who underwent early TCMR between June 2019 and September 2024 were included. Based on pre-LT ICI exposure, recipients were categorized into ICI-related TCMR (irTCMR, n = 12) and conventional TCMR (cTCMR, n = 16) groups. Recipients with irTCMR had a higher median Banff rejection activity index (RAI) (6 vs . 5, P = 0.012) and more aggressive tissue damage and inflammation. Recipients with irTCMR showed higher proportion of treatment resistance, achieving a complete resolution rate of only 8/12 compared to 16/16 for cTCMR. Graft loss occurred in 5/12 of irTCMR recipients within 90 days after LT, with no graft loss in cTCMRs recipients. Cox analysis demonstrated that irTCMR with an ICI washout period of <30 days was an independent risk factor for perioperative graft loss (hazard ratio [HR], 6.540; 95% confidence interval [CI], 1.067-40.067, P = 0.042). CONCLUSION IrTCMR is associated with severe pathological features, increased resistance to treatment, and higher graft loss in adult liver transplant recipients.
Humans ; Liver Transplantation/adverse effects* ; Male ; Female ; Middle Aged ; Retrospective Studies ; Graft Rejection/immunology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; T-Lymphocytes/drug effects* ; Graft Survival/immunology* ; Aged

Cancer immunotherapy has emerged as a promising strategy. However, low response rates and immune-related side effects have plagued immunotherapy. Metallic nanoparticles, utilizing metals as their framework, are gaining prominence in cancer immunotherapy. Metal ions have shown the ability to modulate immune status by activating the cGAS-STING pathway and inducing immunogenic cell death (ICD), thereby enabling multidimensional activation of immunotherapy. Metallic nanoparticles offer significant advantages in cancer immunotherapy, leading to their increasing use in enhancing therapeutic outcomes. In view of the ever-increasing research on metallic nanoparticles, this review presents the construction, characterization, and enhanced cancer immunotherapeutic effects of different types of metal nanosystems from the perspective of the immunoregulatory mechanisms of metal ions. We delve into the current limitations and future directions of metallic nanoparticles in this rapidly evolving field. To the best of our knowledge, this review offers the most up-to-date and systematic analysis of metallic nanoparticles in immunotherapeutic applications. It is anticipated that this review of metallic nanoparticles will inspire a more refined and intelligent design of metallic nanoparticles for future research, paving the way for advancing their clinical applications.

An ideal dermal filler should integrate filling, repair, and anti-aging effects, with immediate tissue augmentation, slow degradation, and progressive stimulation of collagen regeneration. However, commonly used hyaluronic acid (HA) hydrogels, while effective for rapid filling, suffer from limited duration of support, weak cell adhesion, and an inability to promote collagen regeneration. Silk fibroin (SF), a natural protein from silkworm cocoons, is known for its excellent cell adhesion and collagen-stimulating abilities. However, its limited gelation capability restricts its potential application as a standalone injectable hydrogel. Based on a complementary strategy, this study combines the rapid gelling properties of HA with the collagen regenerative properties of SF to create a co-crosslinked HA-SF hydrogel. The composite hydrogel merges HA's rapid filling effect with SF's strong tissue adhesion and collagen-stimulating abilities. The formulation, physicochemical properties, degradation, biocompatibility, and filling effects of the HA-SF hydrogel were systematically investigated. HA-SF hydrogel exhibits excellent mechanical properties and ensures long-term support while maintaining injectability. Interestingly, after intradermal injection in the UVB-induced photoaging model, HA-SF hydrogel not only enhances hydrogel-cell interaction but also continues to stimulate collagen regeneration, especially type III collagen. This dual action achieves the biological effects of repair and anti-aging while maintaining the filling effect. Proteomic analysis confirms that repair and anti-aging effects are enhanced by the regulation of skin fibroblasts and modulation of amino acid and lipid metabolism. This composite hydrogel holds strong promise for clinical applications, offering a safer, long-lasting, and more natural injectable filler that combines filling, repair, and anti-aging into one system.

Objective To investigate the effect of NK cells on the proliferation of four kinds of colorec-tal cancer(CRC)lines,and to explore the feasibility of adoptive NK cell immunotherapy in the treatment of CRC so as to provide an experimental basis for the diagnosis and treatment of CRC.Methods Peripheral blood mononuclear cells were isolated by the Ficoll density gradient centrifuge method,which were in vitro in-duced to activate as the NK cells and amplified.The CCK-8 method was used to detect the effect of NK cells on the proliferation of CRC cell lines RKO,HCT15,HCT116 and LoVo.The inhibition rate of NK cells on CRC cell lines was statistically analyzed and compared.Results The inhibitory rate of NK cells against the same target cells was significantly different at different effect target ratios(P＜0.05).Under different num-ber of target cells(5 × 103 vs.1 × 104),the inhibitory rate of NK cells against RKO(effect-target ratio 0.4∶1),HCT15(effect-target ratio 0.4∶1 and 0.2∶1),HCT116(effect-target ratio 3.2∶1,1.6∶1,0.8∶1,0.4∶1 and 0.2∶1)and LoVo(effect-target ratio 1.6∶1,0.8∶1,0.4∶1,0.2∶1 and 0.1∶1)were significantly different(P＜0.05),while no statistical differences were found among other groups(P＞0.05).The effect-target ratio corresponding to the maximum inhibitory rate of NK cells against four CRC cell lines was 12.8∶1 under different target cell numbers.Conclusion Adoptive NK cell immunotherapy has an impor-tant significance for the early intervention and treatment of CRC,moreover 12.8∶1 may be a safe and effec-tive effect-target ratio.

Background and aims:Despite growing evidence linking pretransplant exposure to immune checkpoint inhibitors(ICIs)to increased allograft rejection risk after liver transplantation(LT),a lack of comparative studies to definitively establish the correlation between ICI exposure and adverse short-term outcomes after LT exists.This study aimed to analyze the impact of preoperative ICI exposure on short-term post-LT prognosis and allograft rejection risk.Methods:This retrospective cohort study included 121 recipients who underwent LT for hepatocellular carcinoma(HCC)between June 2019 and March 2023.The recipients were categorized into ICI(n=35)and non-ICI(n=86)exposure groups based on pretransplant ICI exposure.Demographics,clinical characteristics,and short-term outcomes were compared between the cohorts.Kaplan-Meier analysis evaluated the impact of ICI exposure on graft survival.Univariate and multivariate logistic regression models assessed the impact of patient characteristics on allograft rejection.Results:Recipients with or without ICI exposure exhibited comparable demographic baseline charac-teristics.The incidences of early allograft dysfunction and biliary and vascular complications were similar between both groups.Post-transplant infection incidence was 37.1％and 20.9％in the ICI and non-ICI groups,respectively(P=0.064).Allograft rejection rates were significantly higher in the ICI group than in the non-ICI group(22.9％vs.5.8％,P=0.015).The ICI group exhibited a higher 90-day post-transplant mortality rate than that of the non-ICI group(14.3％vs.2.3％,P=0.034).Logistic regression analyses demonstrated that allograft rejection independently correlated with 90-day post-transplant mortality,with ICI exposure being an independent risk factor for allograft rejection.In recipients with ICI exposure,a shorter interval between ICIs and LT(washout period)was significantly associated with a higher allograft rejection risk,with the optimal washout period identified as 21 days for predicting 90-day rejection-free survival(P=0.0001).Moreover,in recipients with allograft rejection,the peripheral CD4+/CD8+T cell ratio was much lower in the ICI group than in the non-ICI group.Conclusions:Pretransplant ICI exposure was an independent risk factor for allograft rejection and was significantly associated with 90-day post-transplant mortality after LT for HCC.A ≤21-day washout period was significantly associated with allograft rejection.Future multicenter studies with larger cohorts and prospective designs are essential to validate these findings,confirm causality,and establish standardized clinical guidelines for ICI use before transplantation.Trail registration:ClinicalTrials.gov NCT05913583.

Calcium-based biomaterials have been intensively studied in the field of drug delivery owing to their excellent biocompatibility and biodegradability. Calcium-based materials can also deliver contrast agents, which can enhance real-time imaging and exert a Ca²⁺-interfering therapeutic effect. Based on these characteristics, amorphous calcium carbonate (ACC), as a brunch of calcium-based biomaterials, has the potential to become a widely used biomaterial. Highly functional ACC can be either discovered in natural organisms or obtained by chemical synthesis However, the standalone presence of ACC is unstable in vivo. Additives are required to be used as stabilizers or core-shell structures formed by permeable layers or lipids with modified molecules constructed to maintain the stability of ACC until the ACC carrier reaches its destination. ACC has high chemical instability and can produce biocompatible products when exposed to an acidic condition in vivo, such as Ca²⁺ with an immune-regulating ability and CO₂ with an imaging-enhancing ability. Owing to these characteristics, ACC has been studied for self-sacrificing templates of carrier construction, targeted delivery of oncology drugs, immunomodulation, tumor imaging, tissue engineering, and calcium supplementation. Emphasis in this paper has been placed on the origin, structural features, and multiple applications of ACC. Meanwhile, ACC faces many challenges in clinical translation, and long-term basic research is required to overcome these challenges. We hope that this study will contribute to future innovative research on ACC.

Obesity and related metabolic syndromes have been recognized as important disease risks,in which the role of adipokines cannot be ignored.Adiponectin(ADP)is one of the key adipokines with various beneficial effects,including improving glucose and lipid metabolism,enhancing insulin sensitivity,reducing oxidative stress and inflammation,promoting ceramides degradation,and stimulating adipose tissue vascularity.Based on those,it can serve as a positive regulator in many metabolic syndromes,such as type 2 diabetes(T2D),cardiovascular diseases,non-alcoholic fatty liver disease(NAFLD),sarcopenia,neurodegenerative diseases,and certain cancers.Therefore,a promising therapeutic approach for treating various metabolic diseases may involve elevating ADP levels or activating ADP receptors.The modulation of ADP genes,multimerization,and secretion covers the main processes of ADP generation,providing a comprehensive orientation for the development of more appropriate therapeutic strategies.In order to have a deeper understanding of ADP,this paper will provide an all-encompassing review of ADP.

Objective:To analyze the clinical features of 6 patients with spontaneous intracranial hypotension caused by high-flow spinal cerebrospinal fluid leaks.Methods:The clinical characteristics, auxiliary examinations, treatment, and outcomes in 6 patients of spontaneous intracranial hypotension caused by high-flow spinal cerebrospinal fluid leaks enrolled in the Xuanwu Hospital, Capital Medical University from February 2021 to April 2022 were retrospectively reviewed.Results:All the 6 patients had orthostatic headaches. Brain magnetic resonance imaging showed dural enhancement and brain sagging and magnetic resonance myelography showed longitudinal extradural collection in all the patients. The high-flow spinal cerebrospinal fluid leaks were demonstrated in upper thoracic segments by the dynamic myelography. The headache disappeared after conservative treatment in 2 patients and treatment with targeted epidural blood patch in 4 patients.Conclusions:The diagnosis of spontaneous intracranial hypotension caused by high-flow spinal cerebrospinal fluid leaks with typical orthostatic headache and brain magnetic resonance imaging and myelography findings is not difficult. However, the localization of the site of high-flow spinal cerebrospinal fluid leaks in spontaneous intracranial hypotension depends on the dynamic myelography. Targeted epidural blood patch is effective, but conservative treatment does not always work.

Objective:To summarize the clinical features, radiological characteristics, therapy, and outcome of patients with spontaneous intracranial hypotension (SIH).Methods:The general information, clinical manifestations, auxiliary examinations, treatment, and outcomes in consecutive patients of SIH hospitalized in the Xuanwu Hospital, Capital Medical University from November 2018 to October 2022 were analyzed.Results:A total of 118 patients with a female-to-male ratio of 5∶4 were included and the ages were 17.00-71.00[39.00(34.00,46.75)]years with a preponderance in the age of 30-49 years. Almost all patients had orthostatic headaches (117/118, 99.2%), accompanied by nausea (90/118, 76.3%), vomiting (70/118, 59.3%), neck stiffness (88/118, 74.6%), tinnitus (57/118, 48.3%), and ear fullness (57/118, 48.3%). Brain magnetic resonance imaging (MRI) showed dural enhancement (97/113, 85.8%), enlarged venous sinus (88/113, 77.9%), subdural fluid collection (46/113, 40.7%), decreased suprasellar cistern (86/113, 76.1%), effacement of the prepontine cistern (86/113, 76.1%), diminished mamillopontine distance (80/113, 70.8%). The cerebrospinal fluid (CSF) leaks were detected in 90.7% (107/118) of the patients by magnetic resonance myelography but 54.3% (25/46) and 52.6% (20/38) by CT myelography and magnetic resonance myelography with gadolinium. Lumber puncture found CSF pressure<60 mmH 2O (1 mmH 2O=0.009 8 kPa) in 18.4% (19/103) of patients, increased CSF red blood cell counts in 50.6% (44/87) of patients, CSF pleocytosis in 44.8% (39/87) of patients, increased CSF protein concentrations in 57.5% (50/87) of patients. The headache completely disappeared after conservative treatment in 24.6% (31/118) of patients and after a single targeted epidural blood patch in 89.7% (78/87) of patients. A rebound headache after epidural blood patch treatment occurred in 66.0% (58/87) of patients. Conclusions:The patients with SIH almost manifested with orthostatic headache, and brain MRI and magnetic resonance myelography were suggested in those patients instead of CSF pressure by lumber puncture. Targeted epidural blood patch was effective and safe in SIH patients.

Chronic obstructive pneumonia cancer transformation refers to the malignant transformation of long-term repeated chronic inflammation of the lung. Traditional Chinese Medicine believes that the etiology and pathogenesis of chronic obstructive pneumonia cancer transformation always belong to the deficiency of origin and excess of signs. Chronic obstructive pulmonary disease causes damage to the qi of the lung, spleen and kidney. Qi is yang, and qi deficiency leads to yang deficiency. Yang deficiency and abnormal warm would result in qi stagnation, phlegm coagulation and blood stasis. It is the key to the transformation of chronic obstructive pneumonia cancer. Kidney yang is the root of yang qi. Deficiency of kidney yang is the initiating factor for the transformation of chronic obstructive pneumonia cancer. Deficiency of lung yang is the fundamental factor for the transformation of chronic obstructive pneumonia cancer. Deficiency of kidney yang and deficiency of spleen yang are the driving factors for the transformation of chronic obstructive pneumonia cancer. Therefore, this article discussed the role of kidney yang in the transformation of chronic obstructive pneumonia cancer from the theory of "Qi Zhu Xu Zhi", in order to broaden the thinking of clinical diagnosis and treatment of the disease.