Most patients with pancreatic cancer are already in the locally advanced or metastatic stage at initial diagnosis. While systemic chemotherapy provides clinical benefits for those with mid-to-late-stage pancreatic cancer, its efficacy is often limited by patient tolerance. In response to the dual clinical demands of robust antitumor activity and high targeting specificity, antibody-drug conjugate (ADC) has emerged as a promising solution. By conjugating highly selective monoclonal antibodies with potent cytotoxic small-molecule drugs, ADC achieves precise tumor-targeting while minimizing damage to healthy tissues, which thereby improves treatment tolerance. However, due to the complex pathological features of pancreatic cancer, no ADC has yet been approved for clinical use for this disease. A comprehensive evaluation of factors including ADC-specific targets, payload selection, antibody-drug linkage strategies, drug delivery mechanisms, tissue distribution variability, and tumor heterogeneity will be crucial to advancing the clinical translation of ADC for pancreatic cancer treatment.

Objective To explore the correlation and dose-response relationship between blood lipid parameters and the risk of thyroid nodules (TNs) in euthyroid women, providing references for disease prevention. Methods A case-control study was conducted, including 1 412 euthyroid women (701 in the case group and 711 in the control group). Crude and multivariable logistic regression models were used to assess the association between blood lipid parameters and the risk of TNs, and restricted cubic spline regression was applied to explore the dose-response relationship. Results Compared with women in the lowest quartile of serum triglyceride (TG; Q1, TG≤0.92 mmol/L), the risk of TNs was 45% (OR＝1.45, 95%CI 1.06-1.98) higher for those in Q2 (TG 0.93-1.24 mmol/L), 101% (OR＝2.01, 95%CI 1.47-2.77) higher for those in Q3 (TG 1.25-1.81 mmol/L), and 67% (OR＝1.67, 95%CI 1.19-2.33) higher for those in Q4 (TG>1.81 mmol/L) after adjusting for age, body mass index (BMI) and education. For each unit increase in log₁₀TG, the risk increased by 98% (OR＝1.98, 95%CI 1.14-3.45). Moreover, the correlation remained statistically significant even after further adjustment for thyroglobulin antibody (TGAb), thyroid peroxidase antibody (TPOAb) and urinary iodine (OR＝1.75, 95%CI 1.00-3.06, P＜0.05). However, correlations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) with the risk of TNs were not statistically significant. Restricted cubic spline regression analysis further demonstrated the non-linear dose-response relationship of TG levels with the risk of TNs. Specifically, the risk of TNs increased in a monotonic manner at lower TG concentrations (＜1.23 mmol/L), but appeared to plateau or even slightly decrease at higher levels of TG (≥1.23 mmol/L). Conclusions Among euthyroid women, higher serum TG level is associated with risk of TNs, and this correlation is non-linear.

Sepsis is a systemic inflammatory response triggered by infection and often leads to acute kidney injury(AKI).The pathogenesis of sepsis-associated AKI is complex,involving multiple factors such as renal ischemia,inflammation and oxidative stress.In recent years,pyroptosis,a pro-inflammatory form of programmed cell death,has gradually attracted the attention of researchers.Pyroptosis is activated by inflammasomes(e.g.,the NOD-like receptor pyrin domain-related protein 3 inflammasome,NLRP3 inflammasome),accompanied by Gas-dermin D(GSDMD)-mediated formation of cell membrane pores and release of cellular contents,which leads to exacerbation of local and systemic inflammatory responses.The mechanism of pyroptosis in sepsis-associated AKI has not been fully elucidated,but AKI is directly involved in the process of renal functional impairment by indu-cing the death of renal tubular epithelial cells and exacerbating the local inflammatory response.Blockade of key molecules in the pyroptosis pathway,such as GSDMD or NLRP3 inflammasome,can significantly alleviate renal injury,suggesting that the pyroptosis pathway may be a potential therapeutic target for sepsis-associated AKI.This review summarizes the recent research progress on pyroptosis in sepsis-associated AKI,and discuss its cen-tral role in the pathogenesis,particularly focusing on the inflammasome and GSDMD pathways.Additionally,this paper analyzes the potential of focal death inhibition as a therapeutic strategy and proposes future research direc-tions with the expectation of providing references for the treatment of sepsis-related AKI.

Objective:To compare the differences in the evaluation of hemolysis performance of cellulose hemostatic materials using different detection methods and test media,and to explore a m ore reasonable testing plan for such products.Methods:Hemolysis tests were conducted on cellulose hemostatic materials using the absorbance measurement hemolysis method and hemoglobin concentration measurement hemolysis method in accordance with YY/T 1651.1-2019 standard.We compared the changes in hemolysis rate,pH value,and osmotic pressure under different experimental media.Results:Under the same experimental method,compared to SC,the hemolysis results using PBS as the extraction medium are smaller,and the changes in pH and osmotic pressure are closer to the normal range of human body changes.Conclusions:The changes in pH and osmotic pressure may be one of the reasons for the high hemolysis rate of cellulose hemostatic materials.Choosing PBS with buffering effect as the leaching medium may be more suitable for evaluating the hemolysis performance of cellulose hemostatic materials.

Objective::To systematically study the mechanisms by which Yinzhihuang (YZH), a traditional Chinese medicine, ameliorates intrahepatic cholestasis of pregnancy (ICP), a liver disorder associated with significant maternal and fetal complications.Methods::This experimental study was conducted from January 2024 to August 2024, utilizing data from public databases (Traditional Chinese Medicine Systems Pharmacology, GeneCards, Online Mendelian Inheritance in Man, DisGeNET, Proteome Xchange) alongside in vitro cell culture experiments. Network pharmacology identified active components of YZH and potential therapeutic targets for ICP. Ultra-performance liquid chromatography–mass spectrometry characterized YZH oral liquid, and its effective doses were evaluated in taurocholic acid (TCA)-induced HTR-8/SVneo cells, an in vitro ICP model. ICP-related targets were gathered from multiple databases, and hub genes were selected through bioinformatics and previously identified differentially expressed proteins. Functional annotation and pathway enrichment analyses were conducted, with validation in TCA-induced cells treated with various YZH concentrations (0.1%–5.0%) compared to controls. Molecular docking confirmed predicted interactions.Results::Using network pharmacology, 104 active compounds and 241 potential targets of YZH were identified. Integration of multiple databases yielded 1897 YZH-related therapeutic targets and 3783 ICP-associated genes. Proteomic analysis identified 227 differentially expressed proteins, from which 10 hub genes were selected; among these, APOA2, COL1A1, and ADIPOQ were significantly upregulated in ICP samples. UPLC-ESI-MS/MS detected 2022 compounds, predominantly flavonoids (25.07%, 507/2022) and phenolic acids (14.44%, 292/2022). Molecular docking demonstrated strong binding affinities between several active compounds and the hub genes. In TCA-induced HTR-8/SVneo cells, 0.5% YZH treatment significantly enhanced cell viability and modulated hub gene expression, supporting a potential multi-target mechanism.Conclusion::This study systematically explored the active components and potential targets of YZH in ICP through network pharmacology, proteomics, and in vitro validation. The findings suggest that YZH may act via the PPAR signaling pathway by modulating genes such as PPARA, PPARG, ADIPOQ, and APOA2.

Objective:To explore the difference of type 2 innate lymphoid cell(ILC2),IL-9 and related cytokines between chronic lymphocytic leukemia(CLL)patients and normal individuals,as well as the correlation between ILC2 and IL-9 and other cytokines in CLL patients.Methods:Flow cytometry was used to detect the expression of ILC2 and regulatory T cells(Tregs)in peripheral blood of 26 CLL patients at initial diagnosis and 10 healthy controls.RT-qPCR was used to detected IFN-γ,TGF-β,IL-9 and IL-10 mRNA in peripheral blood mononuclear cell(PBMC).ELISA was used to detect serum IFN-γ,TNF-α,TGF-β,IL-9,IL-10 and IL-21.ILC2 and IL-9 were observed in the cervical lymph node of 12 CLL patients at initial diagnosis and 12 patients with reactive lymphoid hyperplasias by multiplex indirect immunofluorescence staining.Spearman test was used to analyze the correlation between peripheral blood ILC2 and IL-9,IL-9 and IL-21,IFN-γ mRNA and IL-10 mRNA in CLL patients.Pearson test was used to analyze the correlation between TNF-α and TGF-β in CLL patients.Results:Compared with control group,the proportions of ILC2 and Tregs were significantly increased in CLL group(both P＜0.05).The mRNA expressions of IFN-γ,IL-9,IL-10 and TGF-β in PBMCs of CLL patients were significantly increased(all P＜0.05).In CLL patients,the expressions of IFN-γ,TNF-α,TGF-β,IL-9 and IL-10 in serum were significantly increased(all P＜0.01),while IL-21 slightly increased without statistical difference(P＞0.05).In CLL patients,the peripheral blood ILC2 was positively related to IL-9(r=0.56),IL-9 was positively related to IL-21(r=0.397),IFN-γ mRNA was positively related to IL-10 mRNA(r=0.623),and TNF-α was positively related to TGF-β(r=0.577).Compared with reactive lymphoid hyperplasias patients,the mean fluorescence intensities of GAT A3 and CRTH2 representing ILC2 and IL-9 in cervical lymph nodes were significantly increased in the CLL group(all P＜0.001),and showed colocalization.Conclusion:In CLL patients,the proportions of ILC2 and IL-9 in peripheral blood and lymph nodes increase,and ILC2 and IL-9 show colocalization in lymph nodes.There is a positive correlation between ILC2 and IL-9 in the peripheral blood of CLL patients,the ability of ILC2 to secrete IL-9 is increased,and ILC2 may affect the occurrence and development of CLL through IL-9.

Sepsis is a systemic inflammatory response triggered by infection and often leads to acute kidney injury(AKI).The pathogenesis of sepsis-associated AKI is complex,involving multiple factors such as renal ischemia,inflammation and oxidative stress.In recent years,pyroptosis,a pro-inflammatory form of programmed cell death,has gradually attracted the attention of researchers.Pyroptosis is activated by inflammasomes(e.g.,the NOD-like receptor pyrin domain-related protein 3 inflammasome,NLRP3 inflammasome),accompanied by Gas-dermin D(GSDMD)-mediated formation of cell membrane pores and release of cellular contents,which leads to exacerbation of local and systemic inflammatory responses.The mechanism of pyroptosis in sepsis-associated AKI has not been fully elucidated,but AKI is directly involved in the process of renal functional impairment by indu-cing the death of renal tubular epithelial cells and exacerbating the local inflammatory response.Blockade of key molecules in the pyroptosis pathway,such as GSDMD or NLRP3 inflammasome,can significantly alleviate renal injury,suggesting that the pyroptosis pathway may be a potential therapeutic target for sepsis-associated AKI.This review summarizes the recent research progress on pyroptosis in sepsis-associated AKI,and discuss its cen-tral role in the pathogenesis,particularly focusing on the inflammasome and GSDMD pathways.Additionally,this paper analyzes the potential of focal death inhibition as a therapeutic strategy and proposes future research direc-tions with the expectation of providing references for the treatment of sepsis-related AKI.

Early correction of childhood malocclusion is timely managing morphological, structural, and functional abnormalities at different dentomaxillofacial developmental stages. The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion. This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence, aiming to provide general guidance on appropriate imaging examination selection, comprehensive and accurate imaging assessment for early orthodontic treatment patients.
Humans ; Malocclusion/diagnostic imaging* ; Child ; Consensus

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*