Objective To explore the impact of number of positive regional lymph nodes (nPRLN) in N1 stage on the prognosis of non-small cell lung cancer (NSCLC) patients. Methods Patients with TxN1M0 stage NSCLC who underwent lobectomy and mediastinal lymph node dissection from 2010 to 2015 were screened from SEER database (17 Regs, 2022nov sub). The optimal cutoff value of nPRLN was determined using X-tile software, and patients were divided into 2 groups according to the cutoff value: a nPRLN≤optimal cutoff group and a nPRLN>optimal cutoff group. The influence of confounding factors was minimized by propensity score matching (PSM) at a ratio of 1 : 1. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate overall survival (OS) and lung cancer-specific survival (LCSS) of patients. Results A total of 1316 patients with TxN1M0 stage NSCLC were included, including 662 males and 654 females, with a median age of 67 (60, 73) years. The optimal cutoff value of nPRLN was 3, with 1165 patients in the nPRLN≤3 group and 151 patients in the nPRLN>3 group. After PSM, there were 138 patients in each group. Regardless of before or after PSM, OS and LCSS of patients in the nPRLN≤3 group were superior to those in the nPRLN>3 group (P<0.001). N1 stage nPRLN>3 was an independent prognostic risk factor for OS [HR=1.52, 95%CI (1.22, 1.89), P<0.001] and LCSS [HR=1.72, 95%CI (1.36, 2.18), P<0.001]. Conclusion N1 stage nPRLN>3 is an independent prognostic risk factor for NSCLC patients in TxN1M0 stage, which may provide new evidence for future revision of TNM staging N1 stage subclassification.

Objective:To investigate effective strategies to reduce the high risk of recurrence after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in patients with minimal residual disease(MRD)-positive B-lineage acute lymphoblastic leukemia(B-ALL).Methods:A retrospective analysis was performed for ten B-ALL patients with positive MRD before transplantation at our center from November 2022 to November 2024.There were four male patients and six female patients,with a median age of 30(7-56)years.Of all patients,four received transplantation from unrelated donors,and six received haploidentical transplantation from relatives.All ten patients received blinatumomab(28 μg/day for 14 days for patients≥45 kg;5 μg/m2/day for 14 days for patients<45 kg)and were bridged to the conditioning regimen for allo-HSCT within 7 days.Results:After treatment with blinatumomab,all ten patients achieved the clearance of MRD.After allo-HSCT,100%of the patients achieved donor hematopoietic reconstitution.The median time to neutrophil reconstitution was 12(9-22)days,and the median time to platelet reconstitution was 13.5(9-22)days.As of January 2025,the median observation time was 14(2-26)months;of all patients,two experienced recurrence,and one had positive MRD again,with a recurrence rate of 20%.Among the ten patients,nine survived and one died of disease recurrence.One patient achieved complete re-mission again after chimeric antigen receptor T-cell(CAR-T)therapy following recurrence,and the patient with positive MRD achieved the clearance of MRD again after interleukin-2 treatment;both patients were currently alive.During treatment,one patient developed cytokine release syndrome,one patient was comorbid with SARS-CoV-2 infection,one patient had herpes zoster and viral encephalitis,three patients developed grade Ⅰ-Ⅱ acute graft-versus-host disease,and four patients developed chronic graft-versus-host disease;no transplantation-associated thrombotic microangiopathy was observed.Conclusion:For patients with MRD-positive B-ALL,blinatumomab as a bridge therapy for allo-HSCT can significantly reduce recurrence after transplantation,with fewer complica-tions that are easy to control.Multicenter randomized controlled clinical studies can be performed to further verify its efficacy and safety.

Objective To explore the application value of stage rehabilitation intervention under the Health action process approach(HAPA)model(SRI-HAPAM)combined with tranexamic acid(TXA)in elderly patients with femoral neck fracture(FNF)undergoing total hip arthroplasty(THA).Methods Elderly FNF patients with unilateral THA in the First Affiliated Hospital of Wenzhou Medical University from December 2022 to June 2023 were enrolled.According to the random number table method,the patients were divided into routine nursing(RN)group and TXA+SRI-HAPAM group.The RN group received conventional treatment after surgery,and the TXA+SRI-HAPAM group received TXA combined with SRI-HAPAM after surgery.The bleeding indexes[hidden blood loss(HBL),explicit blood loss(EBL)and blood transfusion volume(BTV)],and the levels of hemoglobin(Hb),C-reactive protein(CRP)and D-dimer(DD)were compared between the two groups at 24 h after surgery.The hip function[joint deformity(JD),joint function(JF),joint pain(JP),joint motion(JM)and total hip function(THF)],anxiety and depression[self-rating anxiety scale and self-rating depression scale],satisfaction with care,and complications were compared between the two groups at 3 months after surgery.Results A total of 100 elderly patients with unilateral THA due to FNF were included in the study,including 54 in the TXA+SRI-HAPAM group and 46 in the RN group.Before operation,there was no significant difference in Hb,CRP,DD,JD,JF,JP,JM,THF and SAS between the two groups(P>0.05).At 24 hours after operation,Hb decreased in the two groups,while CRP and DD increased(P<0.05),and the decrease in Hb and the increase in CRP and DD,as well as HBL,EBL and BTV in the TXA+SRI-HAPAM group,were lower than those in the RN group(P<0.05).At 3 months after operation,JD,JF,JP,JM and THF in both groups increased compared with those before operation,while SAS and SDS decreased compared with those before operation(P<0.05),and the functional scores of JD,JF,JP,JM and THF in the TXA+SRI-HAPAM group were significantly higher than those in the RN group,and the scores of SAS and SDS were lower than those in the RN group(P<0.05).3 months after surgery,the nursing satisfaction of the TXA+SRI-HAPAM group was significantly higher than that of the RN group,and the total complication rate was lower than that of the RN group(P<0.05).Conclusion Compared the Routine nursing,TXA combined with SRI-HAPAM more effectively promotes postoperative recovery in patients with THA.

Evidence-based medicine (EBM) is a science that uses the best available research data to make decisions, and the core is that clinical decision-making is supported by the best research evidence. Incorporating EBM into traditional standardized residency training in hematology can foster residents' professional theoretical knowledge and clinical skills, improve the quality of standardized training, and provide ideas and methods for standardized training of hematology residents, which is worthy of further research and exploration.

Objective To explore the comparison of the clinical efficacy of laparoscopic cholecystectomy based on propensity score matching through the umbilical single hole method and three holes method in the treatment of acute cholecystitis.Methods 106 patients with acute cholecystitis who underwent laparoscopic cholecystectomy in our hospital from January 2020 to December 2022 were selected as research subjects.According to different treatment methods,they were divided into the study group(n=64)and the control group(n=42).The patients in the study group were treated with single port via umbilical laparoscopic cholecystectomy,while the control group was treated with three port laparoscopic cholecystectomy.Compare the surgical related indicators,postoperative recovery,and postoperative complications between the two groups of patients.Results Comparing the general information of the two groups of patients,there was no significant difference in body mass index(BMI),BMI,and gallbladder ultrasound results(P＞0.05),but the average age of the study group patients was greater than that of the control group patients(P＜0.05).By comparing the general data of the two groups of patients after propensity score matching,it was found that there was no significant difference in gender,age,BMI,and gallbladder ultrasonography results between the two groups(P＞0.05).The surgical time for the study group patients was(61.48±10.24)minutes,while for the control group,it was(40.42±8.35)minutes;And the visual analog scale(VAS)scores at 6 and 24 hours after surgery were(5.63±1.04)and(3.42±0.65)for the study group,respectively,while(7.22±1.61)and(5.48±1.02)for the control group.The pain sensation was more pronounced(P＜0.05);However,there was no statistically significant difference in blood loss during surgery between the two groups of patients(P＞0.05).The hospitalization time and gastrointestinal function recovery time of the study group patients were(2.05±0.42)days and(33.46±4.30)hours,respectively,while the control group was(3.95±1.02)days and(47.58±7.62)hours,respectively;And the satisfaction score of the study group patients with incision scars was(4.58±0.42)points,while the control group was(3.02±0.38)points(P＜0.05).The total incidence of complications in the study group was 2.78％,while in the control group it was 16.67％,significantly lower in the study group(P＜0.05).Conclusion Patients with acute cholecystitis treated with the umbilical single hole method have significantly lower postoperative pain,shorter hospital stay,and recovery time of gastrointestinal function compared to the three hole method.Patients also have higher scores of satisfaction with incision scars,and the overall incidence of postoperative complications is also lower.

Japan is one of the main trading partners for the import and export of experimental animals in China,and its quarantine and supervision policies for the import and export of experimental animals are very detailed and strict.This article takes experimental dogs,cats,and monkeys as examples to provide an in-depth analysis of the quarantine and supervision policies for the main experimental animals exported to Japan.At the same time,it reflects on the current laws and regulations,import and export management method,standards,biosafety,breeding and management status,as well as the import and export business status of experimental animals in China.Suggestions are provided in improving the laws and regulations,import and export management method,ensuring national biosafety,improving the management level of experimental animal breeding,and promoting the import and export trade of experimental animals,in order to provide reference for comprehensively improving the production,use,and breeding management level of experimental animals in China and strengthening the trade between China and Japan.

Diabetes mellitus (DM) is a major metabolic disease endangering global health, with diabetic nephropathy (DN) as a primary complication lacking curative therapy. Sporoderm-broken spores of Ganoderma lucidum (GLP), an herbal medicine, has been used for the treatment of metabolic disorders. In this study, DN was induced in Sprague-Dawley rats using streptozotocin (STZ) and a high-fat diet (HFD), and the protective mechanisms of GLP were investigated through transcriptomic, metabolomic, and network pharmacology (NP) analyses. Our results demonstrated that GLP intervention ameliorated renal damage and inflammation levels in DN rats. Integrative metabolomic and transcriptomic analysis revealed that GLP treatment modulated glucose and cellular energy metabolisms by regulating relevant genes. GLP significantly suppressed the inflammations by impacting glucose and energy metabolism-related gene expression (Igfbp1 and Angptl4) and enhanced metabolic biomarkers of 4-Aminocatechol. In addition, NP analysis further indicated that GLP may efficiently alleviate DN via immune-related pathways. In conclusion, this study provides supportive evidence of the anti-inflammatory effects of GLP supplements, highlighting their potential for promising clinical applications in treating DN.

Diabetes mellitus(DM)is a major metabolic disease endangering global health,with diabetic ne-phropathy(DN)as a primary complication lacking curative therapy.Sporoderm-broken spores of Ganoderma lucidum(GLP),an herbal medicine,has been used for the treatment of metabolic disorders.In this study,DN was induced in Sprague-Dawley rats using streptozotocin(STZ)and a high-fat diet(HFD),and the protective mechanisms of GLP were investigated through transcriptomic,metabolomic,and network pharmacology(NP)analyses.0ur results demonstrated that GLP intervention ameliorated renal damage and inflammation levels in DN rats.Integrative metabolomic and transcriptomic analysis revealed that GLP treatment modulated glucose and cellular energy metabolisms by regulating relevant genes.GLP significantly suppressed the inflammations by impacting glucose and energy metabolism-related gene expression(Igfbp1 and Angptl4)and enhanced metabolic biomarkers of 4-Aminocatechol.In addition,NP analysis further indicated that GLP may efficiently alleviate DN via immune-related pathways.In conclusion,this study provides supportive evidence of the anti-inflammatory effects of GLP supplements,highlighting their potential for promising clinical applications in treating DN.

Gaining a better understanding of autoprotection against drug-induced liver injury(DILI)may provide new strategies for its prevention and therapy.However,little is known about the underlying mechanisms of this phenomenon.We used single-cell RNA sequencing to characterize the dynamics and functions of hepatic non-parenchymal cells(NPCs)in autoprotection against DILI,using acetaminophen(APAP)as a model drug.Autoprotection was modeled through pretreatment with a mildly hepatotoxic dose of APAP in mice,followed by a higher dose in a secondary challenge.NPC subsets and dynamic changes were identified in the APAP(hepatotoxicity-sensitive)and APAP-resistant(hepatotoxicity-resistant)groups.A chemokine(C-C motif)ligand 2+endothelial cell subset almost disappeared in the APAP-resistant group,and an R-spondin 3+endothelial cell subset promoted hepatocyte proliferation and played an important role in APAP autoprotection.Moreover,the dendritic cell subset DC-3 may protect the liver from APAP hepatotoxicity by inducing low reactivity and suppressing the autoimmune response and occurrence of inflammation.DC-3 cells also promoted angiogenesis through crosstalk with endothelial cells via vascular endothelial growth factor-associated ligand-receptor pairs and facilitated liver tissue repair in the APAP-resistant group.In addition,the natural killer cell subsets NK-3 and NK-4 and the Sca-1-CD62L+natural killer T cell subset may promote autoprotection through interferon-y-dependent pathways.Furthermore,macrophage and neutrophil subpopulations with anti-inflammatory phenotypes promoted tolerance to APAP hepatotoxicity.Overall,this study reveals the dynamics of NPCs in the resistance to APAP hepatotoxicity and provides novel insights into the mechanism of autoprotection against DILI at a high resolution.

BACKGROUND: Exploring the underlying mechanism of rituximab resistance is critical to improve the outcomes of patients with diffuse large B-cell lymphoma (DLBCL). Here, we tried to identify the effects of the axon guidance factor semaphorin-3F (SEMA3F) on rituximab resistance as well as its therapeutic value in DLBCL. METHODS: The effects of SEMA3F on the treatment response to rituximab were investigated by gain- or loss-of-function experiments. The role of the Hippo pathway in SEMA3F-mediated activity was explored. A xenograft mouse model generated by SEMA3F knockdown in cells was used to evaluate rituximab sensitivity and combined therapeutic effects. The prognostic value of SEMA3F and TAZ (WW domain-containing transcription regulator protein 1) was examined in the Gene Expression Omnibus (GEO) database and human DLBCL specimens. RESULTS: We found that loss of SEMA3F was related to a poor prognosis in patients who received rituximab-based immunochemotherapy instead of chemotherapy regimen. Knockdown of SEMA3F significantly repressed the expression of CD20 and reduced the proapoptotic activity and complement-dependent cytotoxicity (CDC) activity induced by rituximab. We further demonstrated that the Hippo pathway was involved in the SEMA3F-mediated regulation of CD20. Knockdown of SEMA3F expression induced the nuclear accumulation of TAZ and inhibited CD20 transcriptional levels via direct binding of the transcription factor TEAD2 and the CD20 promoter. Moreover, in patients with DLBCL, SEMA3F expression was negatively correlated with TAZ, and patients with SEMA3F low TAZ high had a limited benefit from a rituximab-based strategy. Specifically, treatment of DLBCL cells with rituximab and a YAP/TAZ inhibitor showed promising therapeutic effects in vitro and in vivo . CONCLUSION Our study thus defined a previously unknown mechanism of SEMA3F-mediated rituximab resistance through TAZ activation in DLBCL and identified potential therapeutic targets in patients.
Humans ; Animals ; Mice ; Rituximab/therapeutic use* ; Hippo Signaling Pathway ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Prognosis ; Semaphorins/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Membrane Proteins/genetics* ; Nerve Tissue Proteins/genetics*