Objective To develop and validate a nomogram model that integrates systemic inflammatory markers to predict the likelihood of pelvic lymph node metastasis(PLNM)in prostate cancer patients prior to surgery.Methods This study retrospectively analyzed the clinical data and preoperative inflammatory markers—including neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),systemic immune-inflammation index(SII),and monocyte-to-lymphocyte ratio(MLR)—of patients diagnosed with prostate cancer.Univariate and multi-variate logistic regression analyses were conducted to identify markers that were significantly associated with PLNM.Based on the results of the multivariate analysis,a nomogram was developed and its predictive accuracy was assessed using receiver operating characteristic curves(ROC)and calibration plots.Results Among the 334 enrolled patients with prostate cancer,107 were identified with PLNM.Univariate analysis revealed statistically significant differences in free prostate-specific antigen(fPSA),Gleason score,NLR,PLR,MLR,and SII between the PLNM and non-pelvic lymph node metastasis(NPLNM)groups(P<0.05).Multivariate analysis confirmed that fPSA,Gleason score,and SII were independent predictors of PLNM(P<0.05).A nomogram incorporating these predic-tors exhibited strong discriminative ability,with an area under the ROC curve(AUC)of 0.79(95%CI:0.73～0.84).Calibration analysis further demonstrated good consistency between the predicted and observed probabilities of PLNM.Conclusions This study successfully developed a nomogram model based on systemic inflammatory markers for preoperative prediction of pelvic lymph node metastasis in prostate cancer.Owing to its user-friendly design and high predictive accuracy,this tool may serve as a valuable complementary method to conventional imaging techniques,thereby supporting personalized treatment decision-making.

The aging demographic in China raises significant concerns, as advanced age has been identified as an independent risk factor for the onset and progression of prostate cancer among the elderly population.Patients with prostate cancer in this age group often exhibit reduced physical functionality and a higher prevalence of comorbidities, leading to notable differences in their diagnosis and treatment compared to younger patients.A comprehensive understanding of the unique characteristics, as well as the clinical diagnostic and treatment protocols for elderly prostate cancer patients, is essential for standardizing and enhancing the quality of care.This consensus, informed by the current state of diagnosis and treatment for elderly prostate cancer patients in China, along with relevant guidelines from both domestic and international sources, outlines methods for assessing the general health status of these patients.It also provides guidance on the management of localized and advanced prostate cancer, in addition to supportive care for elderly patients.The consensus aims to assist healthcare professionals in accurately evaluating the health status of elderly prostate cancer patients and implementing effective interventions and management strategies.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

OBJECTIVE: To investigate the clinical characteristics and prognostic of venetoclax (VEN) combined targeted therapy in acute leukemia (AL) patients with PICALM∷MLLT10 fusion gene positivity. METHODS: A retrospective analysis was conducted on 16 PICALM∷MLLT10-positive AL patients treated at the First Affiliated Hospital of Soochow University from January 2021 to August 2024. These patients were diagnosed by targeted RNA sequencing (RNA-seq) or reverse transcription multiplex PCR, including newly diagnosed and relapsed/refractory (R/R) cases. The immunophenotypes, genetic features, gene mutations, and the efficacy of VEN combination targeted therapy of patients were evaluated. RESULTS: Among the 16 cases, 3 were confirmed by reverse transcription multiplex PCR, and 13 were detected through targeted RNA-seq among 528 AL patients, with a detection rate of 2.46%. The averge age of patients was (28.0±8.58) years. Patients exhibited diverse immunophenotypes, including 7 cases of acute myeloid leukemia, 5 of acute T-lymphoblastic leukemia, 1 of acute B-lymphoblastic leukemia, 1 of acute undifferentiated leukemia, and 2 of mixed-phenotype acute leukemia. Among them, 11 had extramedullary disease (EMD), 14 expressed CD7, and 12 expressed CD33. Major co-occurring mutations included PHF6 (6 cases), NOTCH1 (5 cases), and 7 cases with complex karyotypes. Of the 12 patients who received standard induction therapy, 7 did not achieve remission (PR+NR). All 4 patients treated with VEN combination therapy achieved complete remission (CR). Among the 7 induction failure cases, 4 achieved CR upon re-induction with VEN, while the remaining 3 re-induced with standard therapy, did not achieve CR. Thirteen patients received allogeneic hematopoietic stem cell transplantation, including 6 who received maintenance therapy with hypomethylating agents (HMA) alone or in combination with VEN, and seven were followed up. Survival analysis showed that the overall survival was better in the maintenance therapy group (P =0.044). CONCLUSION PICALM∷MLLT10-positive AL involves multiple lineages and demonstrates poor response to conventional chemotherapy. VEN combination therapy shows promising efficacy in both newly diagnosed and R/R patients. Post-transplant maintenance therapy with HMA alone or combined with VEN may extend survival; however, further clinical validation is required.
Humans ; Sulfonamides/therapeutic use* ; Retrospective Studies ; Prognosis ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Adult ; Male ; Female ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Oncogene Proteins, Fusion/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*

Objective This study aimed to investigate whether Trichinella spiralis Ts87 protein can facilitate immune evasion by degrading the mouse neutrophil extracellular traps(NETs).Methods First,we used bioinformatics tools to analyze the physicochemical properties of Ts87 and,through sequence homology alignment,confirmed its classification within the nuclease family.Molecular cloning and protein purification techniques were then employed to obtain high-purity Ts87 protein,and its nuclease activity was confirmed.Additionally,we compared the primary sequence of Ts87 with known active sites from human lysosomal DNase IIα and the structurally characterized Burkholderia thailandensis DNase II.This enabled us to predict potential active sites.Ts87 enzymatic mutants were generated using site-directed mutagenesis,and their functions were confirmed through enzymatic activity experiments.The extracellular nucleic acid content of mouse bone marrow neutrophils and the immunofluorescence staining of mouse NETs were assessed in vitro to verify whether the Ts87 protease mutants exhibited a decreased ability to degrade NETs.Finally,after immunizing mice with Ts87,calculated larvae burden and the degradation of NETs in vivo were observed by immunostaining the MPO and CitH3 expression in the intestinal NETs of the mice.Results High-purity Ts87 protein was successfully obtained and confirmed to possess nuclease activity,capable of degrading NETs in vitro.The Ts87 mutants exhibited reduced capacity in degrading NETs.In vivo experiments in mice demonstrated that the production of anti-Ts87 antibodies in immunized mice reduced the degradation of NETs,facilitating NET-mediated attack on the parasites and resulting in decreased larvae burden in the mice.Conclusions Trichinella spiralis can utilize Ts87 nuclease to evade capture by NETs,providing potential vaccine and drug targets for the prevention and treatment of trichinellosis.

Objective Aedes albopictus is the primary vector of the dengue virus.Screening and the analysis of immune-related genes in DENV2-infected Ae.albopictus provides a scientific basis for further research on blocking the extrinsic incubation period of the dengue virus.Methods Through the approach of literature mining,thirty-three potential immune-related genes were screened from species such as Aedes aegypti and Anopheles gambiae,which have a close genetic relationship with Ae.albopictus.The protein—protein interaction(PPI)analysis is employed to explore the interaction relationship of the proteins encoded by genes.The alterations in mRNA expression levels of the relevant genes in DENV2-infected Ae.albopictus midgut were detected using the qRT-PCR method.Results The PPI results indicates that TLR and Spz of Ae.albopictus;Rel1,Rel2,DefC,Spz,PIWI,Ago2,DOME and HOP of Ae.aegypti;and Rel1,Rel2,CACT,STAT and DOME of An.gambiae exhibit PPI relationships.After Ae.albopictus was infected with DENV2,10 genes showed significant difference in expression.Ago3(7.39,P<0.05),DOMEa(1.63,P<0.01),DOMEb(21.29,P<0.001),and TLRb(1.61,P<0.05)were significantly up-regulated.Rel1(0.62,P<0.001),CACTl(0.65,P<0.001),Rel2a(0.65,P<0.01),Rel2b(0.24,P<0.001),GATAa(0.64,P<0.01)and DefC(0.28,P<0.05)were significantly down-regulated.Conclusions The concordance of Ae.albopictus with Ae.aegypti was higher than that with An.gambiae.DOMEb,Ago3,Rel2b and DefC,can serve as the preferred target genes for subsequent studies on DENV2 immune blockade.

Objective: To elucidate the molecular mechanism by which prohibitin 2(PHB2) mediates periodontitis-induced bone tissue inflammation through regulating the nuclear factor kappa B(NF-κB) signaling pathway and its role in irreversible alveolar bone resorption. Methods: Quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR) and immunohistochemistry(IHC) were used to detect the expression differences of inflammatory factors and PHB2 in healthy and inflamed alveolar bone tissues of mice in vivo. In vitro, an inflammatory model was established using lipopolysaccharide(LPS)-induced a mouse calvaria-derived preosteoblastic cell line, subclone E1(MC3T3-E1) cells. Western blot and qRT-PCR were used to clarify the regulatory relationship between PHB2 and inflammatory factors, and immunofluorescence staining was performed to observe changes in PHB2 subcellular localization. PHB2 overexpression plasmids were constructed using molecular cloning, and RNA interference was employed to knock down PHB2 expression to assess its regulatory role in inflammation. Based on RNA-seq data, differential expression analysis based on the negative binomial distribution, version 2(DESeq2) was used for differential expression analysis, and kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment along with gene ontology(GO) functional annotation were performed to identify key signaling pathways and differentially expressed genes. Results: In the mouse periodontitis model, PHB2 expression was significantly upregulated in alveolar bone tissues. In the in vitro inflammatory cell model, PHB2 levels positively correlated with interleukin(IL)-6, IL-1β, and tumor necrosis factor-alpha(TNF-α) levels, and its subcellular localization shifted during inflammation. RNA-seq data and the detection of the level of phosphorylation of p65 protein(p-p65) demonstrated that PHB2 exacerbated inflammatory responses through the NF-κB signaling pathway and was mechanistically linked to upregulation of the upstream chemokine C-X-C motif chemokine ligand 10(CXCL10). Conclusion PHB2 aggravates LPS-induced periodontitis inflammation via the NF-κB signaling pathway, providing new insights into the molecular mechanisms underlying the development of periodontitis.

Sustained inflammatory responses are closely related to various severe diseases,and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment.Natural products have garnered considerable concern for the treatment of inflammation.Huanglian-Wumei decoction(HLWMD)is a classic prescription used for treating inflammatory diseases,but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated.Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory,we successfully obtained berberine(BBR)-chlorogenic acid(CGA)supramolecular(BCS),which is an herbal pair from HLWMD.Using a series of characterization methods,we confirmed the self-assembly mechanism of BCS.BBR and CGA were self-assembled and stacked into amphiphilic spherical supra-molecules in a 2:1 molar ratio,driven by electrostatic interactions,hydrophobic interactions,and π-πstacking;the hydrophilic fragments of CGA were outside,and the hydrophobic fragments of BBR were inside.This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules.Compared with free molecules,BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide(LPS)-induced pyroptosis.Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB(NF-κB)p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.

COMPERA 2.0 risk stratification has been demonstrated to be useful in patients with precapillary pulmonary hypertension (PH). However, its suitability for patients at risk for post-capillary PH or PH associated with left heart disease (PH-LHD) is unclear. To investigate the use of COMPERA 2.0 in patients with severe aortic stenosis (SAS) undergoing transcatheter aortic valve replacement (TAVR), who are at risk for post-capillary PH, a total of 327 eligible SAS patients undergoing TAVR at our institution between September 2015 and November 2020 were included in the study. Patients were classified into four strata before and after TAVR using the COMPERA 2.0 risk score. The primary endpoint was all-cause mortality. Survival analysis was performed using Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression model. The study cohort had a median (interquartile range) age of 76 (70‒80) years and a pulmonary arterial systolic pressure of 33 (27‒43) mmHg (1 mmHg=0.133 kPa) before TAVR. The overall mortality was 11.9% during 26 (15‒47) months of follow-up. Before TAVR, cumulative mortality was higher with an increase in the risk stratum level (log-rank, both P<0.001); each increase in the risk stratum level resulted in an increased risk of death (hazard ratio (HR) 2.53, 95% confidential interval (CI) 1.54‒4.18, P<0.001), which was independent of age, sex, estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and valve type (HR 1.76, 95% CI 1.01‒3.07, P=0.047). Similar results were observed at 30 d after TAVR. COMPERA 2.0 can serve as a useful tool for risk stratification in patients with SAS undergoing TAVR, indicating its potential application in the management of PH-LHD. Further validation is needed in patients with confirmed post-capillary PH by right heart catheterization.
Humans ; Aortic Valve Stenosis/complications* ; Aged ; Hypertension, Pulmonary/mortality* ; Male ; Female ; Transcatheter Aortic Valve Replacement ; Aged, 80 and over ; Risk Assessment/methods* ; Proportional Hazards Models ; Kaplan-Meier Estimate ; Retrospective Studies