ObjectiveTo investigate the regulatory effect of overexpressed protein tyrosine phosphatase non-receptor type 2 （Ptpn2） on the inflammatory response of mouse alveolar macrophages （MH-S） induced by SiO₂. MethodsCells with overexpressed Ptpn2 were constructed and induced by SiO₂. The experimental groups were divided into four groups： the negative control group with an empty vector （NC）， the overexpressed Ptpn2 group （P）， the negative control group with an empty vector + SiO₂ induction （NS）， and the overexpressed Ptpn2 + SiO₂ induction group （PS）. Isobaric tags for relative and absolute quantification （iTRAQ） combined with liquid chromatography-tandem mass spectrometry （LC-MS/MS） were used to screen differential proteins， followed by Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） database analyses. Immunofluorescence staining was used to detect the expressions of Tumor necrosis factor （TNF） α， Gasdermin D （GSDMD）， and Transforming growth factor （TGF）-β1. Western blot was used to detect the protein expression levels of PTPN2， Toll-like receptor 4 （TLR4）， tumor necrosis factor-α （TNF-α）， nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3）， and proteins related to the TGF-β1 signaling pathway in the cells of each group. ResultsiTRAQ results identified 144 differential proteins among the four groups. GO analysis showed that in biological processes （BP）， these differential proteins were mainly enriched in IκB kinase/nuclear factor-κB （NF-κB） signaling， cell activation and signal transduction involved in immune responses， and regulation of receptor signaling pathways by signal transducer and activator of transcription （STAT）， etc. KEGG analysis revealed that the differential proteins were mainly enriched in Toll-like receptor signaling pathway， NF-κB signaling pathway， NOD-like receptor signaling pathway， TGF-β signaling pathway， and TNF signaling pathway. The results of immunofluorescence staining showed that compared with the NC group， the expressions of TNF α， GSDMD， and TGF-β1 in the cells of the NS group increased （P < 0.05）； compared to the NS group， the expression of the aforementioned proteins in the PS group decreased in cellular proteins（P < 0.05）. The results of Western blot showed that compared with the NC group， the protein expression levels of PTPN2， p-NF-κB，MyD88，TLR4，NLRP3，GSDMD，Caspase-1，IL-1β， TGF-βR1， TGF-βR，p-Smad2/3 in the NS group were significantly upregulated （P < 0.05）； compared with the NS group， the expression levels of the aforementioned proteins in the PS group were significantly downregulated （P < 0.05）. ConclusionOverexpression of Ptpn2 can inhibit the protein expressions of TLR4-TNF-α signaling， NLRP3 signaling， and TGF-β1 signaling closely related to inflammatory response in SiO₂-mediated MH-S macrophages.

Objective To systematically review the studies on predictive models for delayed graft function (DGF) after kidney transplantation. Methods Databases including China Biology Medicine Database, China National Knowledge Infrastructure, Wanfang Database, VIP Database, PubMed, Web of Science and CINAHL were searched to collect studies on predictive models for DGF after kidney transplantation published from the establishment of each database to June 29, 2025. Two researchers screened the literatures according to the inclusion and exclusion criteria, evaluated the quality of the literatures using the prediction model risk of bias assessment tool (PROBAST), and conducted a meta-analysis of the common predictors of the models using R software. Results A total of 12 literatures were included, involving 14 predictive models with sample sizes ranging from 103 to 24 653 cases. Donor serum creatinine level, cold ischemia time, donor age and donor body mass index were the top four common predictors. All the predictive models were at high risk of bias and low in applicability. The results of meta-analysis showed that abnormal donor body mass index, advanced donor age, prolonged cold ischemia time and elevated donor serum creatinine level were all associated with an increased risk of DGF after transplantation (all P<0.01), but there was high heterogeneity among the studies. Fixed-effect model and random-effect model were used to re-pool the effect sizes separately. The results indicated that the fixed-effect model and random-effect model had good consistency in terms of donor body mass index, donor age and cold ischemia time, while there was a significant difference in the effect sizes of the two models for donor serum creatinine level. Conclusions The predictive models for DGF risk after kidney transplantation have good predictive performance, but the overall risk of bias is high. In the future, large-sample, multicenter and high-quality prospective clinical studies should be carried out to optimize the predictive models, so as to improve their predictive ability and clinical application value.

To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

Alzheimer’s disease (AD) is pathologically characterized by cerebral amyloid β‑protein (Aβ) aggregation, neurofibrillary tangles and progressive cognitive deterioration. There is an urgent clinical demand for targeted therapeutic agents against AD, whereas the blood-brain barrier (BBB) acts as a critical physical barrier that blocks over 98% small-molecule drugs and nearly all biomacromolecules from entering brain parenchyma. Nanomedicine-based drug delivery systems (NDDSs) with tunable physicochemical properties can cross the BBB via multiple transcytosis pathways including adsorptive-mediated, receptor-mediated and transporter-mediated routes, opening a promising avenue for targeted AD treatment. A core academic viewpoint proposed herein is that robust in vitro endothelial penetration of nanocarriers cannot guarantee effective accumulation in brain target cells. Comprehensive evaluation of BBB-crossing delivery efficiency should not merely rely on in vitro permeability tests, but cover the full multi-step transcytosis cascade, cellular tropism in brain tissues and in vivo therapeutic outcomes. This review systematically sorts out diverse nanoplatforms applicable to BBB penetration for AD intervention. Inorganic nanomaterials such as gold and ceria nanoparticles possess large specific surface areas and intrinsic antioxidant capacity, which eliminate reactive oxygen species and hinder Aβ fibrillization. Liposomal formulations and solid lipid nanoparticles exhibit superior biocompatibility with biomimetic phospholipid bilayer architectures, capable of co-loading hydrophilic nucleic acids for Tau regulation and lipophilic Aβ inhibitors; relying on receptor-mediated transcytosis, they achieve sustained drug retention in the brain. Polymeric nanocarriers including nanogels and polyamidoamine dendrimers enable multi-target combinatorial therapy, and can be engineered to release cargo in response to inflammatory microenvironments, thereby suppressing excessive microglial activation and protecting neuronal mitochondria. Beyond conventional nanocarriers, this work elaborates two cutting-edge BBB-crossing delivery platforms: biomimetic nanosystems and metal-organic frameworks (MOFs). Biomimetic nanoparticles camouflaged with erythrocyte, platelet or macrophage membranes, as well as natural exosomes, evade immune clearance, prolong systemic circulation and inherently home to inflammatory lesions. Serving as “nano-decoys”, they neutralize Aβ neurotoxins and remodel cerebral inflammatory microenvironments simultaneously. MOFs feature high porosity and customizable pore channels for co-delivery of multiple therapeutics, and can be integrated with near-infrared photothermal and photooxidation modalities to facilitate focal brain lesion therapy. This review highlights a transformative paradigm shift in the field of BBB-targeted AD therapy: research focus has shifted from simply maximizing cerebral drug penetration toward active modulation and functional restoration of the BBB. Impaired BBB transporters intrinsically impede endogenous Aβ clearance. Accordingly, BBB-regulating nanocarriers are designed to remodel the low-density lipoprotein receptor-related protein 1 (LRP1) trafficking cascade, redirecting endocytic vesicles from lysosomal degradation to non-degradable transcytosis and restoring the intrinsic Aβ efflux capacity of the BBB. Distinct from conventional strategies that only exert local lesion inhibition, this systemic clearance strategy eliminates cerebral Aβ deposits by accelerating peripheral excretion.

Objective To understand the distribution, species composition, seasonal fluctuations, and presence of Dabie bandavirus in ticks in Tai'an City, providing a basis for assessing tick-borne disease risks and formulating prevention strategies. Methods Free-living ticks were monitored using the flagging method, whereas parasitic ticks were monitored through host surface examination. Reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the presence of Bandavirus dabieense in tick specimens. Results The density of free-living ticks in Tai'an City showed a continuous decreasing trend over the 3 years from 2021 to 2023, with an average tick density of 0.43 ticks/(flag·100 m). The dominant habitats were scenic areas and forests, and the seasonal fluctuations exhibited a bimodal pattern, peaking in March and August. The only free-living tick species captured was Haemaphysalis longicornis. Over the 3 years, the average tick index for parasitic ticks was 1.85, with sheep as the primary host. Seasonal fluctuations also followed a bimodal pattern, peaking in March and August. The primary parasitic tick species captured were H. longicornis and Rhipicephalus sanguineus. No Dabie bandavirus was detected in the tick specimens. Conclusions Tick density in Tai'an City remains relatively high, necessitating continued efforts to enhance tick surveillance and implement targeted prevention measures in rural environments to further reduce the health risks posed by tick-borne diseases.

AIM: To investigate the effect of interleukin-8(IL-8)on the regulation of monocyte chemotactic protein-1(MCP-1)secreted by lens epithelial cells(LEC)during cell migration in the development of posterior capsule opacification(PCO).METHODS: A rat lens capsule model was established and cultured in medium supplemented with 10% fetal bovine serum. Upon migration of LEC to 30%-50% of the posterior capsule, serum was removed. The capsule was subsequently divided into two groups: a control group and an IL-8(15 ng/mL)treatment group. LEC migration was captured at multiple time points. The secretion and mRNA expression of MCP-1 were quantified using ELISA and RT-qPCR, respectively. Immunofluorescence was used to assess MCP-1 expression in the different experimental groups. SRA01/04 cells were divided into three groups: control, IL-8(15 ng/mL), and IL-8(15 ng/mL)+200 μmol/L Bindarit(BND)groups, with migration measured by the Transwell assay. Additionally, SRA01/04 cells were divided into negative control(NC), NC+15 ng/mL IL-8, and 15 ng/mL IL-8+p65 siRNA groups, and MCP-1 secretion and mRNA expression were further analyzed by ELISA and RT-qPCR.RESULTS:LEC migration in the rat lens capsule cultured in vitro showed that the cells migration of the 15 ng/mL IL-8 group significantly increased at 48, 72 and 96 h(all P<0.05). ELISA results revealed that MCP-1 levels in SRA01/04 cells from the 15 ng/mL IL-8-treated group were markedly higher than those in the control group at both 12 and 24 h(all P<0.05). RT-qPCR analysis also demonstrated a significant increase in MCP-1 mRNA expression in the 15 ng/mL IL-8 group at both time points(all P<0.05). Immunofluorescence staining indicated greater MCP-1 expression in capsular epithelial cells of the 15 ng/mL IL-8 group at 24 h(P=0.007). Transwell assays further confirmed increased cell migration in the 15 ng/mL IL-8 group compared to the control group(P=0.001), while the migration reduced in the 15 ng/mL IL-8+200 μmol/L BND group compared to the 15 ng/mL IL-8 group(P=0.003). Moreover, ELISA and RT-qPCR results demonstrated a significant increase in MCP-1 secretion and mRNA expression in the NC+15 ng/mL IL-8 group at both 12 and 24 h compared to the NC group(all P<0.01). In contrast, MCP-1 secretion and mRNA expression were reduced in the 15 ng/mL IL-8+p65 siRNA group compared to the NC+15 ng/mL IL-8 group at both time points(all P<0.01).CONCLUSION: IL-8 promotes the migration of residual epithelial cells and regulates the secretion and expression of MCP-1 in LEC. The mechanism underlying IL-8's effects appears to be mediated through the activation of the NF-κB/p65 signaling pathway.

Pancreatic cancer is a kind of highly malignant tumor with a low survival rate and poor prognosis. The effectiveness of gemcitabine as a first-line chemotherapy drug is limited; however, it can activate dendritic cells and improve antigen presentation which increase the sensitivity of tumor cell to immunotherapy. Although immunotherapy has made some advancements in cancer treatment, the therapeutic benefit of programmed cell death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) blockade therapy remains relatively low. The chemokine C-X-C chemokine ligand 12 (CXCL12) contributes to an immunosuppressive tumor microenvironment by recruiting immunosuppressive cells. The receptor C-X-C motif chemokine receptor 4 (CXCR4), highly expressed in various tumors including pancreatic cancer, plays a crucial role in tumor development and progression. In this study, the anti-tumor immune response of human peripheral blood mononuclear cell (hPBMC) was enhanced using the combination of BsNb PX4 (anti-PD-L1&CXCR4 bispecific nanobody) and gemcitabine. In a co-culture system of gemcitabine-pretreated hPBMCs with tumor cells, the BsNb PX4 synergized gemcitabine to improve the cytotoxic activity of hPBMCs against tumor cells. Flow cytometry analysis confirmed increased ratio of CD8⁺ to CD4⁺ T cells in combination treatment. In NOD/SCID mice bearing pancreatic cancer, the combination treatment exhibited more infiltration of CD8⁺ T cells into tumor tissues, contributing to an effective anti-tumor response. This study presents potential new therapies for the treatment of pancreatic cancer. Ethical approval was obtained for collection of hPBMC samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University (authorizing number: A2024246).