Abstract:Objective To explore the effect of modified Buzhong Yiqi decoction(MBZYQ)on thyroid function in rats with Hashimoto's thyroiditis(HT)by regulating the Toll-like receptor 2(TLR2)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)signaling pathway.Methods The HT rat model was constructed.The successfully modeled rats were divided into the HT group,L-MBZYQ,M-MBZYQ,H-MBZYQ(intragastric administration of 11.35,22.70,and 45.40 g/kg MBZYQ granules,respectively),and the MBZYQ+Pam3CSK4 group(intragastric administration of 45.40 g/kg MBZYQ granules+intraperitoneal injection of 20 μg TLR2 agonist Pam3CSK4),with 10 rats in each group.Another 10 normally raised rats were selected as the control group.The pathological changes of thyroid tissues and the apoptosis of thyroid tissue cells in each group were observed by HE staining and TUNEL staining respectively.The expressions of serum thyroglobulin antibody(TGAb),thyroid peroxidase antibody(TPOAb),free triiodothyronine(FT3),free thyroxine(FT4),thyroid stimulating hormone(TSH),interleukin-17(IL-17),and interleukin-10(IL-10)were detected by enzyme-linked immunosorbent assay(ELISA).Western blot was used to detect the protein expression of TLR2,MyD88 and NF-κB in thyroid tissues.Results The pathological damage of thyroid tissues in the L-MBZYQ,M-MBZYQ and H-MBZYQ groups was alleviated.The apoptosis rate of cells,the expressions of TGAb,TPOAb,TSH,IL-17,TLR2,MyD88 and NF-κB were lower than those in the HT group,while the expressions of FT3,FT4 and IL-10 were higher than those in the HT group.Moreover,the degree of decrease or increase in the M-MBZYQ and H-MBZYQ groups was greater than that in the L-MBZYQ group,and the changes in the H-MBZYQ group were greater than those in the M-MBZYQ group(P<0.05).The pathological damage of thyroid tissue in the MBZYQ+Pam3CSK4 group was further aggravated.The apoptosis rate of cells,the expressions of TGAb,TPOAb,TSH,IL-17,TLR2,MyD88 and NF-κB were higher than those in the H-MBZYQ group,while the expressions of FT3,FT4 and IL-10 were lower than those in the H-MBZYQ group(P<0.05).Conclusion MBZYQ can protect the thyroid function of HT rats,and its mechanism of action may be achieved by inhibiting the TLR2/MyD88/NF-κB signaling pathway.

Abstract:The incidence of thyroid cancer has significantly increased in the past decade or so.The tumor tissues,stromal cells and immune cells that exist in thyroid cancer itself constitute the dynamic and changing tumor microenvironment of thyroid cancer.The tumor microenvironment plays a decisive role in the occurrence,development and treatment of thyroid cancer,among which B lymphocytes have received increasing attention.This review systematically summarizes the latest research progress of B lymphocytes in the tumor microenvironment of thyroid cancer,to better explore the characteristics of the tumor microenvironment of thyroid cancer.

Abstract:Objective To analyze the therapeutic effect and mechanism of Neferine(Nef)on psoriasis mice based on the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway.Methods A mouse model of psoriasis was constructed.The 50 mice with successful modeling were divided into the model group,the L-Nef group,the M-Nef group,the H-Nef group,and the H-Nef+ML385 group,with 10 mice in each group according to random number table method.Additionally,10 normal mice were selected as the control group.The L-Nef group,M-Nef group and H-Nef group were respectively administered 5,10 and 20 mg/kg Nef by gavage.The H-Nef+ML385 group was administered 20 mg/kg Nef by gavage and intraperitoneally injected with 30 mg/kg Nrf2/HO-1 signaling pathway inhibitor ML385.The control group and the model group were given the same amount of normal saline.The changes of skin lesions in each group of mice were observed and the psoriasis area and severity index(PASI)scoring was conducted.HE staining and toluidine blue staining were used to observe the pathological changes of the skin and the number of mast cells in each group,and immunohistochemical staining was used to observe the expression of Ki-67 in the lesion sites of mice in each group.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of inflammation and oxidative stress factors in the skin lesion tissues of mice in each group,and Western blot was used to detect the expression of Nrf2/HO-1 signaling pathway-related proteins in the skin lesion tissues of mice in each group.Results Compared with the control group,the mice in the model group presented symptoms such as skin erythema and scales,and the pathological changes of the skin lesion tissue were severe.The PASI score,the number of mast cells,Ki-67,tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),interleukin-6(IL-6),interleukin-17A(IL-17A),and malondialdehyde expressions were increased,while the expressions of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),Nrf2 and HO-1 were decreased(P<0.05).Compared with the model group,the symptoms such as skin erythema and scales and the pathological changes of skin lesion tissues in mice of the L-Nef group,M-Nef group and H-Nef group were alleviated,and the PASI score,the number of mast cells,the expressions of Ki-67,TNF-α,IFN-γ,IL-6,IL-17A and malondialdehyde were significantly reduced;however,the expressions of SOD,GSH-Px,Nrf2 and HO-1 were significantly increased(P<0.05).Compared with the H-Nef group,the symptoms such as skin erythema and scales and the pathological changes of skin lesion tissues in the H-Nef+ML385 group of mice were more severe.The PASI score,the number of mast cells,and the expressions of Ki-67,TNF-α,IFN-γ,IL-6,IL-17A,and malondialdehyde were significantly increased.while the expressions of SOD,GSH-Px,Nrf2 and HO-1 were significantly decreased(P<0.05).Conclusion Nef may have therapeutic effects by activating the Nrf2/HO-1 signaling pathway to improve the inflammation and oxidative stress responses in the lesion tissues of mice with psoriasis.

Abstract:Objective To analyze the effect of Midazolam(MID)on visceral pain in diarrheal irritable bowel syndrome(IBS-D)rats based on the forkhead box protein O1/forkhead box transcription factor O3a(FoxO1/FoxO3a)pathway.Methods An IBS-D rat model was constructed,and successfully modeled rats were randomly assigned into IBS-D group,low MID(MID-L)group,high MID(MID-H)group,and MID-H+AS1842856 group,with 12 rats in each group.Additionally,12 normal healthy rats were included as the Control group.The Control group and the IBS-D group were intraperitoneally injected with an equal volume of 0.9%sodium chloride.The MID-L and MID-H groups were intraperitoneally injected with 30 and 90 mg/kg MID respectively,while the MID-H+AS1842856 group was intraperitoneally injected with 90 mg/kg MID and given 50 mg/kg AS1842856 by gavage.Rats in each group were evaluated for abdominal wall withdrawal response(AWR)score.Enzyme-linked immunosorbent assay(ELISA)was applied to detect the levels of oxidative stress and pain factors in serum,and HE staining was applied to detect pathological changes in colonic tissue.Immunohistochemistry was applied to detect the expression of glial fbrillary acidic protein(GFAP)and nerve growth factor(NGF)in colon tissue,and Western Blot method was applied to detect the expression of proteins related to the FoxO1/FoxO3a pathway.Results The pathological damage in the colonic tissue in the IBS-D group was more severe than that in the Control group,and the AWR score,malondialdehyde(MDA),substance P(SP),5-hydroxytryptamine(5-HT),and GFAP and NGF expression elevated,while the superoxide dismutase(SOD)level and the expression of FoxO1 and FoxO3a decreased(P<0.05).The colonic tissue damage in the MID-L and MID-H groups was less severe compared with the IBS-D group,and the AWR score,MDA,SP,5-HT,and GFAP and NGF expression decreased,while SOD level and the expression of FoxO1,FoxO3a increased;the changes were more significant in the MID-H group(P<0.05).The colonic tissue damage in the MID-H+AS1842856 group was more severe than that in the MID-H group,and the AWR score,MDA,SP,5-HT,and GFAP and NGF expression increased,while SOD level level and the expression of FoxO1,FoxO3a decreased(P<0.05).Conclusion MID can improve visceral pain in IBS-D rats,and its mechanism of action is related to the activation of the FoxO1/FoxO3a pathway.

Abstract:Objective To explore the mechanism by which the early growth response protein 1(EGR1)/AMP-activated protein kinase(AMPK)/nuclear factor erythroid 2-related factor 2(Nrf2)pathway improves Neuro-2a cell injury via Mendelian randomization(MR),bioinformatics and in vitro models of ischemic stroke(IS).Methods The blood proteins associated with genetic susceptibility to IS were identified based on MR analysis.Then,the GSE22255 dataset was comprehensively analyzed,including GSEA,immunoinfiltration and differential expression analysis.The transcription factors closely related to the occurrence and development of IS were identified after joint analysis with MR results,and the biological functions of key genes were further verified by in vitro experiments.Results A total of 712 proteins related to IS susceptibility were identified by MR analysis.A total of 2357 differentially expressed genes were identified from the GSE22255 dataset,and 75 intersection genes and 34 transcription factors were identified after combined analysis with MR results.In vitro experiments showed that knockdown of EGR1 expression could significantly inhibit oxygen-glucose deprivation/reperfusion(OGD/R)-induced Neuro-2a cell damage,and the mechanism might be related to the up-regulation of p-AMPK and Nrf2 protein expression.Conclusion This study integrates MR analysis,transcriptomics and in vitro experiments to reveal the potential role of 75 IS susceptibility genes and transcription factor EGR1 in the pathogenesis of IS,which provides theoretical basis for the development of therapeutic drugs for IS.

Abstract:Knee osteoarthritis(KOA)is a chronic joint disease characterized by degeneration of articular cartilage and joint pain.Its pathogenesis is complex,involving cell death,inflammatory responses and the interaction of various signaling pathways.Apoptosis is activated by Caspase family proteins and DNA endonucleases,leading to cellular dysfunction and promoting the degeneration of articular cartilage.Pyroptosis is a form of programmed cell death triggered by inflammasome activation,involving the activation of nucleotide-binding oligomeric domain-like receptor protein 3 inflammasome,which leads to the release of pro-inflammatory cytokines such as interleukin(IL)-6,IL-1 β and tumor necrosis factor-α.This release intensifies local inf/lammation and accelerates the progression of the disease.Ferroptosis is driven by iron-catalyzed lipid peroxidation,which induces the rupture of chondrocyte cell membranes and the degradation of matrix,thereby promoting joint degeneration.In addition,autophagy plays a dual role in KOA:moderate autophagy supports chondrocyte repair,while excessive autophagy may promote joint destruction,cartilage matrix degradation and subchondral bone sclerosis.The PI3K/AKT,NF-κB,Wnt/β-catenin and Hedgehog signaling pathways can regulate the growth,differentiation,proliferation,migration and apoptosis of articular chondrocytes.Single-cell RNA sequencing technology has provided new insights into the cellular heterogeneity and molecular mechanisms in the pathogenesis of KOA.This review explores the mechanisms of cell death in KOA,with a focus on the roles of pro-inflammatory cytokines,signaling pathway,and single-cell RNA sequencing techniques in the occurrence and progression of KOA.

Abstract:Erectile Dysfunction(ED)is a relatively common clinical condition characterized by male sexual dysfunction.Macrophages,as key components of the immune and inflammatory response systems,play crucial roles in immune surveillance,tissue repair,and the maintenance of tissue homeostasis in processes related to erectile function.Immune inflammation is recognized as one of the pathological factors contributing to ED,and inflammatory markers—including macrophages—are widely believed to be closely associated with the onset of the disorder.This review summarizes the multifaceted roles of macrophages in vascular injury,neural repair,hormonal balance,and immune microenvironment remodeling in the context of erection.It aims to provide a theoretical foundation for further investigation into the involvement of macrophages in ED and discusses the potential of macrophage-targeted therapies for treating ED.

Abstract:Objective To explore the mechanism of Glaucocalyxin A(GLA)in inhibiting ovalbumin(OVA)-induced airway remodeling in asthmatic mice through the topoisomerase Ⅱ α(TOP2A)/cyclin-dependent kinase 1(CDK1)signaling pathway.Methods Forty Balb/c mice were randomly divided into 5 groups:the control group,the model group,the low-dose GLA group,the high-dose GLA group and the Dexamethasone group,with 8 mice in each group.The effect of GLA on airway remodeling was examined by immunohistochemical staining,ELISA and other methods,and bioinformatics methods were used to predict new targets of GLA.The action targets of TOP2A were screened using the STRING database,and the interaction relationship between the two was verified by co-immunoprecipitation.In vitro,GLA and siRNA were used to interfere with interleukin-4(IL-4)-stimulated human airway epithelial cells BEAS-2B.The expressions of TOP2A,epidermal growth factor receptor(EGFR),Integrin β1,focal adhesion kinase(FAK),β-catenin,CDK1 and DRP1 were detected by Western Blot.Results GLA intervention could significantly reduce OVA-induced asthma airway remodeling,airway smooth muscle thickening,collagen deposition around the airway,the number of eosinophils in alveolar lavage fluid,the expression of pro-inflammatory cytokines such as IL-4,and the level of serum IgE.The new target of GLA screened out was TOP2A,which was highly expressed in the lung tissue of the asthma airway remodeling model.GLA intervention could down-regulate its expression.In vitro,intervention with GLA and si-TOP2A could significantly down-regulate the expressions of IL-4-induced TOP2A,EGFR,Integrin β1,FAK and β-catenin.Further studies have found that TOP2A had an interaction relationship with CDK1.si-TOP2A could downregulate the expression of CDK1,and knockdown of CDK1 could significantly down-regulate the expression of phosphorylated DRP1.Conclusion GLA may alleviate asthma airway remodeling by targeting the TOP2A/CDK1 signaling pathway,providing experimental evidence for the clinical diagnosis and treatment of asthma airway remodeling in asthma.

Abstract:Objective Objective To investigate the expression levels of long non-coding RNA HCG11(LncHCG11)and miR-214-5p in pancreatic cancer tissues and their potential molecular regulatory mechanisms.Methods Ten patients with pancreatic cancer admitted between January 2022 and January 2025 were included,and post-operative cancer tissue and paired adjacent tissue samples were collected.Real-time quantitative PCR technology was used to detect the transcription levels of LncHCG11 and miR-214-5p,and the expression level of sirtuin 2(SIRT2)protein was measured by Western blot.The relationship of miR-214-5p with LncHCG11 and SIRT2 was predicted through a biological database.Results Compared with the adjacent non-cancerous tissues,the expression of LncHCG11 and SIRT2 was significantly reduced in pancreatic cancer tissues,while the level of miR-214-5p was significantly increased(P<0.01).In vitro experiments showed that overexpression of LncHCG11 in the Panc1 cell line could upregulate the expression of SIRT2 protein and simultaneously inhibit the proliferative activity of Panc1 cells(P<0.05).Both miR-214-5p and LncHCG11,SIRT2 had binding sites.Conclusion LncHCG11 may act as a competing endogenous RNA to sponge miR-214-5p,releasing its transcriptional inhibition on SIRT2,thereby inhibiting the progression of pancreatic cancer.

Abstract:Objective To analyze the value of peripheral blood helper T cell 17(Th17)/regulatory T cell(Treg),programmed death receptor-1(PD-1)+CD3+,miR-146a,miR-122 and serum C-reactive protein(CRP)in the diagnosis of postoperative infection of endometrial cancer,and to explore the influencing factors of postoperative infection for endometrial cancer.Methods A total of 289 patients with endometrial cancer who underwent surgery from January 2021 to August 2024 were selected and divided into the infection group(n=53)and the non-infection group(n=236)according to the postoperative infection of the patients.Clinical data of two groups were collected and compared.The levels of Th17,Treg and PD-1+CD3+in peripheral blood of the two groups were detected by flow cytometry,and the ratio of Th17/Treg was calculated.The levels of miR-146a and miR-122 in peripheral blood of the two groups were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).The serum CRP levels of the two groups were detected by enzyme-linked immunosorbent assay(ELISA),and the influencing factors of postoperative infection in endometrial cancer were analyzed by multivariate Logistic regression.The receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of peripheral blood Th17/Treg,PD-1+CD3+,miR-146a,miR-122 and serum CRP for postoperative infection of endometrial cancer.Results Compared with the non-infection group,the infection group had higher proportions of diabetes,anemia,adjuvant chemoradiotherapy,open abdominal surgery,drainage and catheterization time≥7 d,as well as higher levels of Th17,Th17/Treg,PD-1+CD3+,miR-122,and serum CRP(P<0.01),while the levels of Treg and miR-146a in peripheral blood were lower(P<0.01).Multivariate Logistic regression analysis showed that combined diabetes,anemia,adjuvant chemoradiotherapy,open abdominal surgery,drainage and catheterization time≥7 d,peripheral blood Th17/Treg,PD-1+CD3+,miR-122 and serum CRP levels were all risk factors for postoperative infection of endometrial cancer(P<0.05,P<0.01),while miR-146a in peripheral blood was its protective factor(P<0.05).ROC curve analysis showed that the area under the curve of the combined detection of Th17/Treg,PD-1+CD3+,miR-146a,miR-122 in peripheral blood and serum CRP was higher than that of the individual detection of Th17/Treg,PD-1+CD3+,miR-146a,miR-122 and serum CRP in peripheral blood(P<0.01).Conclusion Postoperative infection of endometrial cancer is closely related to the patients'combined diabetes,anemia,adjuvant chemoradiotherapy,open surgery,and drainage and catheterization time≥7 d.Moreover,Th17/Treg,PD-1+CD3+,miR-122 in peripheral blood and serum CRP are highly expressed in patients with postoperative infection of endometrial cancer,while miR-146a in peripheral blood is expressed at a low level.The combined detection of the five has more advantages in evaluating postoperative infection of endometrial cancer.

Abstract:Objective To investigate the therapeutic effect and potential mechanisms of allogeneic renal subcapsular transplantation of CD24+renal epithelial cells for the treatment of acute kidney injury(AKI)induced by ischemia-reperfusion(I/R).Methods CD24+renal epithelial cells were isolated from mouse kidneys using flow cytometric sorting and expanded by passaging.C57BL/6N mice were randomly divided into three groups:the normal control group(n=8,sham surgery only),the model control group(n=8,unilateral kidney I/R plus contralateral nephrectomy),and the CD24+cell treatment group(n=8,AKI model followed by renal subcapsular transplantation of CD24+cells).Mice were euthanized at 24 h after modeling and serum was collected to measure biochemical markers[serum creatinine(Scr),blood urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)].Renal tissues were subjected to pathological evaluation and macrophage staining.An M1-polarized macrophage model was established using mouse bone marrow-derived macrophages co-cultured with CD24+renal epithelial cells.The polarization state of macrophages was assessed by quantitative real-time polymerase chain reaction(qPCR)and flow cytometry.Results CD24+renal epithelial cells were successfully isolated and passaged stably.Compared with the normal control group,the model control group exhibited significantly elevated Scr and BUN levels and renal pathological damage.In contrast,the CD24+cell treatment group showed significant reduction in serum biochemical markers and pathological injury compared with the model control group,along with reduction in M1 macrophage infiltration in the kidneys(P<0.05,P<0.01).In vitro co-culture experiments demonstrated that in the CD24+co-culture group,the expression of M1 polarization-related markers in macrophages was significantly lower than that in the non-co-culture group,and the proportion of CD80+M1 macrophages in the co-culture group decreased(P<0.05,P<0.01).Conclusion Allogeneic renal subcapsular transplantation of CD24+renal epithelial cells can alleviate I/R-induced AKI by inhibiting M1 macrophage polarization through paracrine mechanisms.

Abstract:Objective To investigate expression of MAPK1(p38)in patients with refractory asthma and its association with immune abnormalities,so as to provide a new target for the treatment of refractory asthma.Methods A total of 60 asthma patients were enrolled,including 30 patients with refractory asthma and 30 with non-refractory asthma,and another 30 healthy physical examinees were enrolled as the control group.RT-qPCR and Western blot were used to detect the gene and protein expression of MAPK1 in peripheral blood samples.Additionally,flow cytometry was employed to assess the proportions of immune cells related to MAPK1,such as dendritic cells,neutrophils,macrophages,and CD8+T cells.Results RT-qPCR and Western blot results indicated that ERK1/2,JNK,MEK1/2 and p38 expression levels were significantly higher in both non-refractory asthma and refractory asthma patients compared with the healthy controls(P<0.01).Flow cytometry analysis revealed that patients with refractory asthma had significantly elevated levels of dendritic cells,neutrophils,M0 and M1 macrophages compared with non-refractory asthma patients,while CD8+T cell and M2 macrophage levels were significantly lower(P<0.05,P<0.01).Conclusion MAPK1 is highly expressed in patients with refractory asthma and is associated with the changes in immune cell populations.These findings suggest that the MAPK1 signaling pathway plays a critical role in the pathogenesis of refractory asthma and may serve as a potential therapeutic target.

Abstract:Objective Objective To explore the effects of Propofol on neuronal autophagy,memory function,and the classical protein kinase Cγ(cPKCγ)-related pathway in the offspring of rats during the second trimester of pregnancy.Methods Thirty-six SD rats at 14 d of gestation were randomly divided into the control group,the Propofol group and the Propofol+cPKCγ inhibitor group,with 12 rats in each group.Ten pregnant mice were randomly selected from each group.The pregnancy continued until the offspring mice were born.The Morris water maze test was performed on the offspring mice at 30-34 d after birth.Western blotting was used to detect microtubule-associated protein light chain 3Ⅱ/Ⅰ(LC3 Ⅱ/LC3 Ⅰ),Beclin-1,cPKCγ and growth-associated protein-43(GAP-43)expression levels in hippocampal tissue,and immunofluorescence was used to determine the expression of autophagy-related protein ATG7 in hippocampal tissue.Results Compared with the control group,the Propofol group and the propofol+cPKCγ inhibitor group showed increased escape latency at 31,32,33 and 34 d after birth(P<0.05),while there was significantly decreased escape latency in the Propofol+cPKCγ inhibitor group,compared with the Propofol group(P<0.05).Compared with the control group,the Propofol group and the Propofol+cPKCγ inhibitor group had significantly decreased number of platform crossings(P<0.05),while there was significantly increased number of platform crossings in the Propofol+cPKCγ inhibitor group,compared with the Propofol group(P<0.05).Compared with the control group,the Propofol group and the Propofol+cPKCγ inhibitor group had increased time spent in quadrant I and decreased time spent in quadrant Ⅱ(P<0.05),while there was decreased time spent in quadrant Ⅰ and increased time spent in quadrant Ⅱ in the Propofol+cPKCγ inhibitor group,compared with the Propofol group(P<0.05).Compared with the control group,the LC3 Ⅱ/LC3 Ⅰratio,and the expression of Beclin-1,cPKCγ,and GAP-43 protein in the hippocampal tissue of offspring rats in the Propofol group and the Propofol+cPKCγ inhibitor group were significantly increased(P<0.05).Compared with the Propofol group,the LC3Ⅱ/LC3Ⅰ ratio,and the expression of Beclin-1,cPKCγ,and GAP-43 protein in the hippocampal tissue of offspring rats in the Propofol+cPKCγ inhibitor group was significantly decreased(P<0.05).Compared with the control group,the expression of ATG7 in the hippocampal tissue of offspring rats in both the Propofol group and the Propofol+cPKCγ inhibitor group was significantly increased(P<0.05).Compared with the propofol group,the expression of ATG7 in the hippocampal tissue of offspring rats in the Propofol+cPKCγ inhibitor group was significantly decreased(P<0.05).Conclusion Propofol can cause cognitive impairment in the offspring of rats during the second trimester of pregnancy,promote neuronal autophagy,and inhibit activation of the cPKCγ/GAP-43 pathway in the hippocampus,which may improve cognitive impairment in the offspring rats.

Abstract:Hepatocellular carcinoma(HCC)is one of the most common malignant tumors.Tyrosine kinase inhibitors have been used in the mainstream treatment of HCC for many years,but their therapeutic efficacy is limited and the prognosis of patients is very poor.In recent years,the rapid rise of immunotherapy has provided a new direction for tumor treatment.In particular,immune checkpoint inhibitors have shown excellent clinical effect in the treatment of various solid tumors,including HCC.This article reviews various immune checkpoint inhibitors related to HCC and their clinical practice and research progress,aiming to provide a relevant reference and theoretical basis for the immunotherapy of HCC.

Abstract:Objective To investigate the effect and safety of Sintilimab combined with Endostar injection in the treatment of programmed cell death ligand-1(PD-L1)positive lung squamous cell carcinoma(LSCC)in elderly patients.Methods A total of 94 elderly patients with PD-L1 positive LSCC diagnosed and treated from November 2019 to November 2021 were selected as the research subjects,and they were divided into the observation group(n=47)and the control group(n=47)by random number table method.The observation group was treated with Sintilimab combined with Endostar injection,and the control group was treated with Sintilimab.Twenty-one days constituted one treatment cycle,and they were treated for 3 consecutive cycles.The clinical efficacy and improvement rate of Karnofsky performance status(KPS)score in the two groups were statistically analyzed,as well as the tumor markers[carcinoembryonic antigen(CEA),cancer antigen 125(CA125),cytokeratin 19 fragment(CYFRA21-1)],angiogenesis factors[endostatin,insulin-like growth factor-1(IGF-1),vascular endothelial growth factor(VEGF),basic fibroblast growth factor(bFGF),and platelet-derived growth factor(PDGF)],apoptosis factor[B-cell lymphoma-2 gene(Bcl-2),Bcl-2-associated X protein(Bax),Livin protein,programmed cell death 5(PDCD5)]before and after treatment.The toxic and side effects during treatment,progression-free survival(PFS)and median survival time at 2-year follow-up were compared between the two groups.Results After treatment,the objective remission rate and disease control rate of the observation group were higher than those of the control group(P<0.01);after treatment,the improvement rate of KPS score in the observation group was higher than that in the control group(P<0.01).After treatment,the levels of serum CEA,CA125,and CYFRA21-1 in both groups decreased,and which were lower in the observation group than in the control group(P<0.05,P<0.01).After treatment,the levels of endostatin increased in both groups,while IGF-1,VEGF,bFGF,and PDGF decreased;the levels of endostatin in the observation group were higher than those in the control group,while the levels of IGF-1,VEGF,bFGF,and PDGF were lower than those in the control group(P<0.05,P<0.01).After treatment,the levels of Bcl-2 and Livin decreased in both groups,while Bax and PDCD5 increased;the levels of Bcl-2 and Livin in the observation group were lower than those in the control group,while the levels of Bax and PDCD5 were higher than those in the control group(P<0.05,P<0.01).There was no significant difference in toxic and side effects between the two groups during treatment(P>0.05).The 2-year survival rate and median survival time of the observation group were higher or longer than those of the control group(P<0.05).Conclusion The treatment of PD-L1 positive LSCC in elderly patients with Sintilimab combined with Endostar injection can improve the therapeutic effect and the survival status of patients,inhibit tumor angiogenesis,induce tumor apoptosis,prolong the survival time of patients,and has good safety.

Abstract:Tumor immunotherapy,recognized as the fourth major treatment modality alongside surgery,radiotherapy,and chemotherapy,fundamentally relies on mobilizing and enhancing the body's intrinsic immune system to achieve the precise targeting and elimination of neoplastic lesions.In this therapeutic framework,macrophages derived from blood monocyte differentiation serve as critical components of the innate immune defense system and exert profound impacts within the tumor microenvironment(TME).As the dominant inflammatory cell population infiltrating the TME,tumor-associated macrophages(TAMs)not only perform a key function in immune regulation but also serve as a paradigm for the connection between inflammation and tumors.Therapeutic strategies targeting TAMs aim to reverse the immunosuppressive milieu of the TME through multifaceted regulatory mechanisms,including cellular depletion or functional reprogramming,thereby effectively impeding tumor progression.This review systematically analyzes the intricate immune regulatory mechanisms of macrophages in tumor immunotherapy and synthesizes research advancements in major therapeutic agents targeting TAMs,aiming to provide researchers in the field of tumor immunotherapy and developers of macrophage-modulating pharmaceuticals with novel theoretical insights and practical guidelines.

Abstract:Objective To investigate the effects of Tongyangxiao(TYX)lotion on the healing of infected wounds and the expression of interleukin(IL)-1β and inhibitor of nuclear factor κBα(IκBα)/p65 in rats.Methods Fifty rats were randomly assigned to the model group,potassium permanganate(PP)group,and low-,medium-,and high-dose(TYX-L,TYX-M,TYX-H)groups,with 10 rats in each group.An open infection model of full-thickness skin defects was established,and the rats in each group were treated with the corresponding medicinal solution for dressing changes once a day for a total of 14 days.The wound healing of rats was observed,and immunofluorescence,immunohistochemistry,and Western blotting were used to detect the nuclear translocation rate of p65 and the expression levels of IL-1β,p-IκBα/IκBα,and p-p65/p65 proteins in the granulation tissue.Results Compared with the model group,the wound healing rates of both the TYX-M group and the TYX-H group increased on the 7th day of treatment(P<0.05).Compared with the model group and the PP group,the wound healing rates of the TYX-L group,the TYX-M group and the TYX-H group increased on the 14th day of treatment(P<0.05).On the 7th day of treatment,the expression of IL-1β in the TYX-M group was lower than that in the PP group and the Model group(P<0.05),and the p-IκBα/IκBα ratio in the TYX-H group was lower than that in the PP group and the model group(P<0.05).The nuclear translocation rates of p65 in the TYX-L group,TYX-M group and TYX-H group were lower than those in the PP group and model group(P<0.05).On the 14th day of treatment,the p-p65/p65 ratio in the TYX-H group and the TYX-M group was lower than that in the model group(P<0.05),and the IL-1β in the TYX-L group,the TYX-M group,and the TYX-H group and p-IκBα/IκBα ratio in the TYX-H group were lower than those in the PP group and the model group(P<0.05).Conclusion The mechanism of TYX lotion in promoting the healing of infected wounds was associated with the suppression of the activation of NF-κB signaling pathway and alleviation of inflammatory responses.