Objectives:Photodynamic therapy(PDT)is a minimally invasive method used in the treatment of various cancers and skin diseases,but it is not widely used in bone cancer,where the current therapy is often not effective a...Objectives:Photodynamic therapy(PDT)is a minimally invasive method used in the treatment of various cancers and skin diseases,but it is not widely used in bone cancer,where the current therapy is often not effective and accompanied by side effects.Alternative and more effective therapies like PDT are needed.In this in-vitro study,the effect of the photosensitizer(PS)chlorin e6(Ce6)on cancerous bone tumor cells using PDT was examined.Methods:A total of 27 tissue specimens from patients with primary bone cancers or bone metastases of different origins were genetically characterized and treated with PDT.Following a 24-h incubation,cell viability was determined,and the effect of PDT on cell migration was analyzed over 48 h.Results:We could demonstrate that the effect on proliferation of PDT in combination with the PS Ce6 was best in cells isolated from primary osteosarcoma and in bone metastases from mammary carcinomas.Besides proliferation,PDT was also effective in inhibiting the migration of these cells.A statistically significant correlation between the PDT effect and CD164 gene expression was detected,indicating that a high expression of this gene could result in a higher effectiveness of the photodynamic treatment.Conclusion:This study analyzes for the first time the effect of PDT in bone cancers and metastases and shows the potential of treating these cancer types with Ce6 PDT.展开更多
Objectives:Gastric cancer(GC)remains a major global health concern,and Phosphoinositide-3-Kinase Regulatory Subunit 1(PIK3R1),a regulatory subunit of the PI3K signaling pathway,may play a critical yet underexplored ro...Objectives:Gastric cancer(GC)remains a major global health concern,and Phosphoinositide-3-Kinase Regulatory Subunit 1(PIK3R1),a regulatory subunit of the PI3K signaling pathway,may play a critical yet underexplored role in GC progression.This study aimed to investigate the prognostic significance of PIK3R1 in GC and its association with the tumor immune microenvironment.Methods:PIK3R1 expression and its clinical relevance were analyzed using datasets from GC patients who underwent gastrectomy,including cohorts from The Cancer Genome Atlas(TCGA)and the Sun Yat-sen University Cancer Center(SYSUCC).Prognostic models integrating PIK3R1 expression with clinical parameters were constructed for both cohorts.The immune microenvironment associated with PIK3R1 expression was assessed through immunohistochemistry and single-cell RNA sequencing.In vitro assays were conducted to evaluate the effects of PIK3R1 on GC cell proliferation and migration.Results:PIK3R1 was significantly overexpressed in GC tissues and was closely associated with aggressive tumor characteristics and poor clinical outcomes.A nomogram combining PIK3R1 expression with clinicopathological features effectively predicted patient prognosis.Knockdown of PIK3R1 in GC cells reduced proliferation and migration in vitro.Immunological profiling revealed that high PIK3R1 expression correlated with increased infiltration of forkhead box protein P3(Foxp3^(+))and cluster of differentiation 73(CD73^(+))T cells.Patients with low PIK3R1 expression and low CD73^(+)T cell infiltration had significantly better survival.Conclusions:PIK3R1 overexpression is linked to poor prognosis in GC and influences the extent of immune cell infiltration within the tumor microenvironment.A novel prognostic model integrating PIK3R1 and CD73 expression with clinical parameters was established to stratify GC patients into distinct risk groups,offering potential value for personalized therapeutic strategies.展开更多
BACKGROUND Dermatofibrosarcoma protuberans(DFSP)is a rare,low-grade,locally aggressive cutaneous sarcoma.DFSP in the periocular region is exceedingly rare,leading to diagnostic and surgical challenges due to anatomica...BACKGROUND Dermatofibrosarcoma protuberans(DFSP)is a rare,low-grade,locally aggressive cutaneous sarcoma.DFSP in the periocular region is exceedingly rare,leading to diagnostic and surgical challenges due to anatomical constraints in the periocular region.Precise diagnosis is essential to guide appropriate surgical management and prevent recurrence.CASE SUMMARY A 32-year-old female presented with a recurrent tumor in the medial canthus,previously diagnosed as a solitary fibrous tumor in an outside institution.After complete radiological and systemic workup,she was scheduled for a wide local excision followed by reconstruction after getting tumor clear margins on frozen section.Histopathology confirmed DFSP,characterized by storiform spindle cell proliferation,diffuse cluster of differentiation 34 positivity,and signal transducer and activator of transcription 6 negativity.CONCLUSION This case highlights the challenges in the diagnostic and surgical management of DFSP in periocular tumors.Comprehensive surgical excision with appropriate reconstruction is critical for achieving oncological control while preserving aesthetics and function.展开更多
BACKGROUND The decision to administer adjuvant chemotherapy to patients with local stage depends on specific high-risk features that are T4 tumor stage,presence of perineural invasion,lymphovascular invasion,poorly di...BACKGROUND The decision to administer adjuvant chemotherapy to patients with local stage depends on specific high-risk features that are T4 tumor stage,presence of perineural invasion,lymphovascular invasion,poorly differentiated tumor histology,inadequate lymph node sampling(fewer than 12 lymph nodes),and evidence of tumor perforation or obstruction.Tumor-stroma ratio,tumor infiltrating lymphocytes(TIL),Crohn-like reaction(CLR),desmoid reaction,poorly differentiated clusters(PDC)are new pathological markers that are being studied.AIM To examine the relationship between new pathological markers and defined high METHODS We evaluated 155 patients with the diagnosis stage I and II colorectal cancer between the years 2007 and 2021 who were treated at Trakya University Hospital,Department of Medical Oncology.We divided those with and without high-risk factors into two groups.We examined the relationship of new pathological markers with these groups and with pathological markers in risk factors.RESULTS There was no statistically significant correlation between presence of TIL,presence of PDC,presence of tumor budding,presence of CLR,presence of desmoid reaction and low and high-risk groups according to the degree of those with PDC(P=0.82,P=0.51,P=0.77,P=0.37,P=0.83,respectively).In addition,no statistically significant correlation was found between the tumor-stroma ratio and low and high risk groups(P=0.80).We found a statistically significant correlation between the presence of PDC and the presence of PDC grade 3 and T stage(P=0.001,P=0.001,respectively).It was determined that the presence of PDC and the frequency of grade 3 PDC increased with the advanced T stage.CONCLUSION No relationship was found between the presence of new pathological markers and high-low risk groups.When we examined the relationship between new and old pathological markers,only the frequency of detection of PDC and PDC grade 3 was found to be correlated with advanced T stage.展开更多
BACKGROUND Primary liver cancer(PLC)is characterized by high malignancy,rapid disease progression,and persistent high incidence and mortality rates,posing a significant public health challenge worldwide.Early diagnosi...BACKGROUND Primary liver cancer(PLC)is characterized by high malignancy,rapid disease progression,and persistent high incidence and mortality rates,posing a significant public health challenge worldwide.Early diagnosis and assessment of PLC are of great significance for guiding clinical treatment and improving patient prognosis.Alpha fetoprotein(AFP)and gamma-glutamyl transpeptidase(GGT)are commonly utilized tumor markers for the clinical diagnosis of PLC.They are ideal indicators for the detection of metastasis and recurrence after LC surgery.Nevertheless,not all patients with PLC secrete large amounts of AFP and GGT,which affects the accuracy of evaluating PLC by monitoring these two tumor markers alone.Cluster of differentiation 3 and 161 double-positive natural killer T(CD3^(+)CD161^(+)NKT)cell subsets are a class of molecules inextricably related to immune function and tumor occurrence and development.This research seeks to explore the clinical significance of CD3^(+)CD161^(+)NKT cell subsets combined with tumor markers AFP and GGT in the diagnosis of patients with PLC.AIM To probe the clinical significance of CD3^(+)CD161^(+)NKT cell subsets and AFP and GGT changes in the peripheral blood of individuals with PLC.METHODS The PLC group comprised 30 patients diagnosed with PLC who were admitted to our hospital between July 2022 and December 2023,whereas the control group consisted of 30 healthy individuals undergoing routine physical examinations at our hospital.Peripheral blood samples were harvested from both cohorts of patients.The levels of CD4^(+)NKT,CD8^(+)NKT,CD3^(+)CD56^(+)NKT,CD8^(+)CD56^(+)NKT,CD3^(+)CD161^(+)NKT,and CD3-CD161^(+)NKT were measured by flow cytometry.Serum AFP content was determined using a fully automatic immunoassay analyzer,and serum GGT content was ascertained by a fully automatic biochemical analyzer.The diagnostic value of CD3^(+)CD161^(+)NKT cell subsets and AFP and GGT level alterations for PLC was evaluated by receiver operating characteristic curve analysis.RESULTS No significant disparities were observed in the counts of white blood cells,neutrophils,and platelets,as well as the levels of blood urea nitrogen and serum creatinine between the two groups(P>0.05).Lymphocytes,red blood cells,hemoglobin,total protein,albumin,and globulin were more attenuated in the PLC group than in the control group,while glutamic-pyruvic transaminase,glutamic oxalacetic transaminase,and carcinoembryonic antigen levels were increased in the PLC cohort compared with the control cohort,with statistical significance(P<0.05).No substantial difference was discovered in peripheral blood CD4^(+)NKT,CD8^(+)NKT,and CD3^(+)CD56^(+)NKT cells between the two cohorts(P>0.05).The percentage of CD8^(+)CD56^(+)NKT cells(8.35%±1.01%),CD3^(+)CD161^(+)NKT cells(14.36%±1.55%),and CD3-CD161^(+)NKT cells(12.08%±1.34%)in the PLC group was higher than that in the control group(P<0.05).The levels of AFP(335.71±20.89 ng/mL)and GGT(136.87±15.62 U/mL)in the PLC cohort were elevated within the PLC cohort compared with the control cohort(P<0.05).The sensitivity of CD8^(+)CD56^(+)NKT,CD3^(+)CD161^(+)NKT,CD3-CD161^(+)NKT,AFP,and GGT alone for diagnosing PLC was 70.00%,83.33%,80.00%,56.67%,and 53.33%,respectively(P<0.05),with specificity rates of 66.67%,80.00%,76.67%,76.67%,and 66.67%,respectively(P<0.05).The area under the curve for combined detection was 0.898,with a sensitivity of 86.67%and a specificity of 80.00%(P<0.05).CONCLUSION The levels of CD8^(+)CD56^(+)NKT,CD3^(+)CD161^(+)NKT,CD3-CD161^(+)NKT,AFP,and GGT in the peripheral blood of patients with PLC were markedly elevated.The combined detection of these five indicators can improve the sensitivity and specificity of PLC diagnosis,providing solid evidence for the early clinical diagnosis of PLC.展开更多
BACKGROUND Sepsis-associated encephalopathy(SAE)is a common complication of sepsis,characterized by cognitive impairment,altered consciousness,and psychiatric symptoms,including anxiety and depression.These psychiatri...BACKGROUND Sepsis-associated encephalopathy(SAE)is a common complication of sepsis,characterized by cognitive impairment,altered consciousness,and psychiatric symptoms,including anxiety and depression.These psychiatric symptoms often exacerbate the overall prognosis and quality of life of affected patients.However,the underlying metabolic and proteomic features associated with SAE-induced psychiatric symptoms remain poorly understood.AIM To investigate the clinical manifestations of anxiety and depression in patients with sepsis and SAE and to explore their associated metabolic and proteomic characteristics.METHODS A total of 88 patients were enrolled,comprising 30 healthy controls,29 patients with sepsis,and 29 with SAE.Anxiety and depression symptoms were evaluated using the Hamilton anxiety rating scale(HAM-A)and Hamilton depression rating scale(HAM-D)in sepsis and SAE.Cognitive function was assessed using the Montreal Cognitive Assessment(MoCA),and quality of life was measured using the 36-Item Short Form Health Survey.Plasma samples were analyzed for metabolomic and proteomic profiling.Metabolic alterations were identified through liquid chromatography-mass spectrometry,while protein expression was assessed using Olink targeted proteomics.RESULTS Compared to the sepsis group,patients with SAE exhibited significantly higher levels of anxiety(HAM-A:15.2±4.0 vs 10.4±3.0,P=0.012)and depression(HAM-D:16.0±3.5 vs 9.1±2.3,P=0.003).Cognitive function,as measured by MoCA,was notably impaired in the SAE group(MoCA:18.5±4.0 vs 24.5±3.2,P=0.007).Quality of life scores,particularly in physical functioning,emotional well-being,and mental health,were significantly lower in patients with SAE.Metabolomic and proteomic analyses revealed substantial alterations in oxidative stress and nicotinamide adenine dinucleotide(NAD+)metabolism pathways,with cluster of differentiation(CD)38 emerging as a potential biomarker associated with psychiatric symptoms in SAE.Further validation in an independent cohort confirmed the diagnostic relevance of CD38.CONCLUSION This study highlights the significant psychological burden of SAE,manifested as anxiety and depression.Multiomics analysis identified distinct metabolic alterations,particularly in NAD+metabolism,that may contribute to psychiatric symptom development and progression.Furthermore,CD38 was identified as a promising biomarker for the early detection of SAE,providing potential avenues for early intervention and therapeutic targeting.展开更多
BACKGROUND Small blood vessels in the eyes are more susceptible to injury,which can lead to complications.However,since diabetic retinopathy is often a serious clinical condition,most of this study focuses on the vasc...BACKGROUND Small blood vessels in the eyes are more susceptible to injury,which can lead to complications.However,since diabetic retinopathy is often a serious clinical condition,most of this study focuses on the vascular system of the choroid.As part of this study,we looked at how gymnemic acid(from Gymnema sylvestre)and glabridin(from Glycyrrhiza glabra,or licorice)might help diabetic rats’choroid structural change and blood vessels.AIM To explore the effects of glabridin and gymnemic acid on the structural changes of the choroidal layer and choriocapillaris as well as the expression of vascular endothelial growth factor(VEGF)and cluster of differentiation(CD)31 in diabetic rat’s eye.METHODS The male Wistar rats were separated into five groups:The control group(control),the diabetic group(DM),the diabetic rats treated with glabridin 40 mg/kg body weight(DM+GB),the diabetic rats treated with gymnemic acid 400 mg/kg body weight(DM+GM),and the diabetic rats treated with glyburide 4 mg/kg body weight(DM+GR).RESULTS There was an increase in the thickness of both the choroid layer and the wall of the arteries in the DM.A decrease in vascularity and choroidal impairment was found in DM rats.After eight weeks of experimentation,the choroidal thickness increased,and the walls of choroid arteries.The choroidal thickness in the DM+GB was 15.69±1.54μm,DM+GM was 14.84±1.31,and DM+GR groups was 16.45±1.15 when compared with DM group(27.22±2.05),the walls thickness of choroid arteries in the DM+GB was 10.23±1.11,DM+GM was 10.41±1.44,and DM+GR was 9.80±1.78 when compared with DM group(16.35±5.01),The expression of VEGF and CD31 was lower compared to the DM group.CONCLUSION In diabetic choroidopathy,hyperglycemia and inflammation cause damage to the neurovascular unit and bloodretinal barrier.Anti-VEGF treatments can slow or reverse the progression of the disease.According to current research findings,glabridin and gymnemic acid can reduce damage to the choroid,which is a factor that can sometimes result in vision loss.展开更多
Cluster of differentiation 47(CD47),an immune checkpoint commonly referred to as the“don’t eat me”signal,plays a pivotal role in tumor immune evasion by inhibiting phagocytosis through interaction with signal regul...Cluster of differentiation 47(CD47),an immune checkpoint commonly referred to as the“don’t eat me”signal,plays a pivotal role in tumor immune evasion by inhibiting phagocytosis through interaction with signal regulatory protein alpha(SIRPα)on macrophages and dendritic cells(DCs).Although early enthusiasm drove broad clinical development,recent discontinuations of major CD47-targeted programs have prompted re-evaluation of its therapeutic potential.The purpose of this commentary is to contextualize the setbacks observed with first-generation CD47 inhibitors and to highlight strategies aimed at overcoming their limitations.Clinical challenges,including anemia,thrombocytopenia,suboptimal pharmacokinetics,and limited single-agent efficacy,underscore the need to develop safer,more selective approaches.Emerging next-generation strategies,such as SIRPα-directed agents,bispecific antibodies,and conditionally active therapeutics,are designed to enhance safety and tumor selectivity and reduce systemic toxicity.In addition,spatial profiling and biomarker-driven patient selection are advancing toward guiding rational therapeutic combinations,including with“eat-me”signals(e.g.,calreticulin[CALR])orDNA damage response therapies(e.g.,poly(ADP-ribose)polymerase[PARP]inhibitors).Rather than signaling failure,these developments underscore the need for precision,context-specific applications,and adaptive trial designs to realize the durable therapeutic promise of CD47 blockade in cancer immunotherapy.展开更多
BACKGROUND Gestational diabetes mellitus(GDM)is a metabolic disorder causing hyperglycemia during pregnancy.Insulin resistance and decreased insulin secretion are linked to altered lipid metabolism that leads to progr...BACKGROUND Gestational diabetes mellitus(GDM)is a metabolic disorder causing hyperglycemia during pregnancy.Insulin resistance and decreased insulin secretion are linked to altered lipid metabolism that leads to progression of GDM.CD36 is a membrane glycoprotein involved in lipid metabolism and insulin sensitivity.Studies indicate that the CD36 gene is substantially linked to type 2 diabetes mellitus(T2DM)and could also influence GDM susceptibility.Insulin resistance and decreased insulin secretion are the hallmarks of T2DM,which is thought to have a similar genetic pathophysiology in GDM.AIM To investigate the impact of CD36 gene polymorphisms[rs1761667(G/A)and rs75326924(C/T)]and mRNA expression in GDM women.METHODS The case-control study involved a total of 400 pregnant women,(200 healthy controls and 200 GDM cases).The study of CD36 gene polymorphisms G/A(rs1761667)and C/T(rs75326924))were determined by polymerase chain reaction-restriction fragment length polymorphism.The mRNA expression study of CD36 gene was analyzed by quantitative polymerase chain reaction/quantitative real-time polymerase chain reaction followed by statistical analysis done using GraphPad Prism8 software(ver.8.0).RESULTS The study revealed statistically significant association(P<0.05)in anthropometric/biochemical parameters(age,gestational age,body mass index,fasting prandial glucose,post-prandial glucose,triglyceride,low-density lipoprotein)between GDM cases and healthy controls.CD36 G/A(rs1761667)and CD36 C/T(rs75326924)polymorphisms were significantly associated with GDM cases.The heterozygous genotypes(GA and CT)of both variants showed significant association(P=0.0001 and P=0.0025,odds ratio=2.683 and 2.022 respectively).Allele frequency of‘T’allele in CD36 C/T(rs75326924)polymorphism was also found to be significant(P=0.0046).CD36 gene was upregulated in individuals with GDM as compared to healthy controls(P=0.0001).However,the upregulation of gene expression was not significantly associated with the genotypes of CD36 G/A(rs1761667)and CD36 C/T(rs75326924)polymorphisms.CONCLUSION Heterozygous genotypes GA and CT of CD36 gene variants and expression are linked to GDM,potentially serving as predictive biomarkers for GDM susceptibility;further exploration needed in diverse ethnic communities.展开更多
Objective:The tumor microenvironment plays a pivotal role in prostate cancer progression and may differ across metastatic sites.This study aimed to evaluate and compare the primary and metastatic prostate adenocarcino...Objective:The tumor microenvironment plays a pivotal role in prostate cancer progression and may differ across metastatic sites.This study aimed to evaluate and compare the primary and metastatic prostate adenocarcinoma tumor microenvironment.Methods:A total of 27 formalin-fixed paraffin-embedded tissue samples derived from 17 patients diagnosed with prostate adenocarcinoma,including the primary tumors,and the corresponding metastatic lymphatic and hematogenous lesions from various anatomical sites.Immunohistochemical labeling was performed using antibodies against Cluster of Differentiation 3 epsilon chain(CD3e),CD8 alpha chain(CD8a),Cluster of Differentiation 68(CD68),Cluster of Differentiation 163(CD163),Forkhead box P3(FOXP3),Cytotoxic T-Lymphocyte–Associated protein 4(CTLA-4),B7 homolog 3(B7-H3),Programmed cell death protein 1(PD-1),and Marker of proliferation Ki-67(Ki-67).Comparisons were made between primary and metastatic tumors to assess differences in immune cell infiltration,checkpoint expression,and proliferative indices.Results:Sampleswere classified into three groups:Primary Tumor n=12,Lymphatic Metastasis n=7,and Hematogenous Metastasis n=10.FOXP3(p=0.0017)and CD163(p=0.0316)expression levels were significantly higher in the Hematogenous Metastasis compared to both the Primary Tumor and Lymphatic Metastasis.PD-1 showed a clear trend(p=0.0577)toward higher levels in the Primary Tumor compared to both the HematogenousMetastasis and LymphaticMetastasis groups,suggesting distinct immunological landscapes depending on tumor location and progression.Conclusion:Diverse PD-1,CD163,and FOXP3 profiles were observed in primary and metastatic microenvironments of prostate cancer.These findings may contribute to the development of personalized therapeutic strategies and novel prognostic tools beyond conventional histological and TNM staging.展开更多
在肿瘤微环境中,CD38(cluster of differentiation 38)不仅能够影响烟酰胺腺嘌呤二核苷酸(nicotinamide adenine dinucleotide,NAD^(+))代谢途径,还与程序性死亡受体1(programmed cell death 1,PD-1)及其配体细胞程序性死亡-配体1(progr...在肿瘤微环境中,CD38(cluster of differentiation 38)不仅能够影响烟酰胺腺嘌呤二核苷酸(nicotinamide adenine dinucleotide,NAD^(+))代谢途径,还与程序性死亡受体1(programmed cell death 1,PD-1)及其配体细胞程序性死亡-配体1(programmed cell death ligand 1,PD-L1)存在协同作用,从而影响恶性肿瘤进展。NAD^(+)代谢与PD-1/PD-L1同样存在相关性,使得CD38、NAD^(+)、PD-1/PD-L1三者之间直接或间接发生相互作用。鉴于CD38独特的生理特性,提示其可能是备选免疫检查点。目前,关于CD38在抗肿瘤应用及作用机制方面的研究尚不完全,CD38多功能、高表达的特性及应用尚有探索潜力。本文基于肿瘤微环境对CD38作为备选免疫检查点及其与NAD^(+)、PD-1/PD-L1间的相互作用进行综述,以期为CD38相关恶性肿瘤治疗方案的研究、挖掘CD38潜力提供一定思路。展开更多
BACKGROUND Irreversible electroporation(IRE)represents an innovative localized technique for tumor ablation,possessing the capacity to activate the immune response of the host.However,this method alone is inadequate t...BACKGROUND Irreversible electroporation(IRE)represents an innovative localized technique for tumor ablation,possessing the capacity to activate the immune response of the host.However,this method alone is inadequate to halt cancer progression,necessitating the integration of additional strategies to achieve effective immuno-therapy.AIM To investigate the effects and underlying mechanisms of antitumor immunity derived from the synergistic application of IRE and anti-programmed cell death protein 1(PD-1)therapy within a murine model of hepatocellular carcinoma.METHODS C57BL-6 mice with tumor growth were divided into four separate cohorts:Control group;IRE group;Anti-PD-1 group;And IRE+anti-PD-1 group.The infiltration levels of T,B,and natural killer cells within the tumors,as well as the plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-β),were evaluated.Real-time polymerase chain reaction was utilized to quantify the expression of cluster of differentiation(CD)8(a marker indicative of CD8+T cells)in the tumor specimens of the mice at various temporal intervals.Tumor growth trajectories were charted.RESULTS The results indicated that the IRE+anti-PD-1 group exhibited significantly heightened percentages of T lymphocyte infiltration,particularly CD4+and CD8+T cells,when compared to the control cohort.Additionally,this group displayed increased infiltration of natural killer and B cells,augmented cytokine levels,and elevated CD8 messenger RNA expression.A marked decrease in tumor volume was noted in the IRE+anti-PD-1 group,indicating enhanced therapeutic efficacy.CONCLUSION The combined application of IRE and checkpoint blockade elicits an antitumor immune response,leading to a more substantial reduction in tumor volume and improved therapeutic outcomes,thereby establishing a novel avenue for the ablation and immunotherapy of hepatocellular carcinoma.展开更多
AIM: To evaluate the relation of cluster of differentiation 44 (CD44) expression with clinicopathological features of gastric adenocarcinoma, and also its effect on prognosis with an emphasis on the differences betwee...AIM: To evaluate the relation of cluster of differentiation 44 (CD44) expression with clinicopathological features of gastric adenocarcinoma, and also its effect on prognosis with an emphasis on the differences between intestinal and diffuse types. METHODS: From 2000 to 2006, 100 patients with gastric adenocarcinoma, who had undergone total or subtotal gastrectomy without any prior treatment, were studied. Haematoxylin & eosin (HE) staining was used for histological evaluation, including the type (Lauren's classifi cation) and grading of the tumor. The expression of CD44 in the gastric adenocarcinoma mucosa and the adjacent mucosa were determined by immunohistochemistry. The survival analysis was obtained using the Kaplan-Meier test. RESULTS: Of 100 patients, 74 (74%) patients were male. The tumors were categorized as intestinal type (78%) or diffuse type (22%). Sixty-five percent of patients were CD44-positive. CD44 expression was not detected in normal gastric mucosa. Rather, CD44 was more commonly expressed in the intestinal subtype (P = 0.002). A signifi cant relation was seen between the grade of tumor and the expression of CD44 (P = 0.014). The survival analysis showed a poor prognosis of patients with CD44-positive tumors (P = 0.008); and this was more prominent in the intestinal (P = 0.001) rather than diffuse type. CONCLUSION: Cell adhesion molecule CD44 is highly expressed in gastric adenocarcinoma. CD44 expression is correlated with a poor prognosis in patients with the intestinal type of gastric adenocarcinoma. CD44 can, therefore, be utilized as a prognostic marker for this group of patients.展开更多
AIM: To explore the associations of polymorphisms of lipopolysaccharide binding protein (LBP), cluster of differentiation 14 (CD14), toll-like receptor 4 (TLR-4), interleukin-6 (IL-6) and tumor necrosis factor α (TNF...AIM: To explore the associations of polymorphisms of lipopolysaccharide binding protein (LBP), cluster of differentiation 14 (CD14), toll-like receptor 4 (TLR-4), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) with the colorectal carcinoma (CRC) risk in Han Chinese. METHODS: Polymorphisms of LBP (rs1739654, rs223 2596, rs2232618), CD14 (rs77083413, rs4914), TLR-4 (rs5030719), IL-6 (rs13306435) and TNF-α (rs35131721) were genotyped in 479 cases of sporadic colorectal carcinoma and 486 healthy controls of Han Chinese in a case-control study. Single-nucleotide polymorphisms (SNPs) between cases and controls were analyzed by unconditional logistic regression. RESULTS: GA and GG genotypes of LBP rs2232596 were associated with a significantly increased risk ofCRC [odds ratio (OR) = 1.51, 95% confidence interval (CI) 1.15-1.99, P = 0.003; OR = 2.49, 95% CI 1.16-5.38, P = 0.016, respectively]. A similar association was also observed for the CG genotype of CD14 rs4914 (OR= 1.69, 95% CI 1.20-2.36, P = 0.002). In addition, a combination of polymorphisms in LBP rs2232596 and CD14 rs4914 led to a 3.4-fold increased risk of CRC (OR = 3.44, 95% CI 1.94-6.10, P = 0.000). CONCLUSION: This study highlights the LBP rs2232596 and CD14 rs4914 polymorphisms as biomarkers for elevated CRC susceptibility in the Chinese Han population.展开更多
Glaucoma is an eye disease that usually occurs with the increased Intra-Ocular Pressure(IOP),which damages the vision of eyes.So,detecting and classifying Glaucoma is an important and demanding task in recent days.For...Glaucoma is an eye disease that usually occurs with the increased Intra-Ocular Pressure(IOP),which damages the vision of eyes.So,detecting and classifying Glaucoma is an important and demanding task in recent days.For this purpose,some of the clustering and segmentation techniques are proposed in the existing works.But,it has some drawbacks that include ineficient,inaccurate and estimates only the affected area.In order to solve these issues,a Neighboring Differential Clustering(NDC)-Intensity V ariation Making(IVM)are proposed in this paper.The main intention of this work is to extract and diagnose the abnormal retinal image by identifying the optic disc.This work includes three stages such as,preprocessing,clustering and segmentation.At first,the given retinal image is preprocessed by using the Gaussian Mask Updated(GMU)model for eliminating the noise and improving the quality of the image.Then,the cluster is formed by extracting the threshold and patterns with the help of NDC technique.In the segmentation stage,the weight is calculated for pixel matching and ROI extraction by using the proposed IVM method.Here,the novelty is presented in the clustering and segmentation processes by developing NDC and IVM algorithms for accurate Glaucoma identification.In experiments,the results of both existing and proposed techniques are evaluated in terms of sensitivity,specificity,accuracy,Hausdorff distance,Jaccard and dice metrics.展开更多
The tumor,nodes,metastasis(TNM)staging system has long been the gold standard for the classification and prognosis of solid tumors.However,the TNM staging system is not without limitations.Prognostic heterogeneity exi...The tumor,nodes,metastasis(TNM)staging system has long been the gold standard for the classification and prognosis of solid tumors.However,the TNM staging system is not without limitations.Prognostic heterogeneity exists within patients at the same stage.Therefore,the pursuit of other biomarkers with the potential to classify patients with cancer has never stopped.One of them,tumor budding(TB),has gained much success in colorectal cancer.In recent years,TB in gastric cancer has attracted much attention from researchers,beginning to reveal the molecular and biological aspects of this phenomenon in gastric cancer,and has emerged as a promising prognostic biomarker in gastric cancer,predicting disease progression and unfavorable survival.Therefore,it is time and essential to provide a holistic overview of TB in gastric cancer,which has not been achieved and is the aim of this review.展开更多
BACKGROUND Solitary fibrous tumor(SFT)is a rare fibroblastic mesenchymal neoplasm that affects spindle cell soft tissues with broad-spectrum biological behavior;it is predominantly benign,and rarely metastasizes.SFT o...BACKGROUND Solitary fibrous tumor(SFT)is a rare fibroblastic mesenchymal neoplasm that affects spindle cell soft tissues with broad-spectrum biological behavior;it is predominantly benign,and rarely metastasizes.SFT occurs mainly in the tissue structure of the serosa in the pleura and the thorax,and can be found throughout the body,though extra-thoracic localization,including the cephalic region,is uncommon.We reported the first case of intracranial malignant SFT metastasized to the chest wall.CASE SUMMARY An 81-year-old Japanese man was referred to our hospital due to progressive gait disturbance and appetite loss.His medical history included partial resection due to brain tumor,four times,and 50-Gray radiation therapy at another hospital,starting when he was 74 years old.An unenhanced head computed tomography(CT)scan revealed an 8 cm×5.1 cm×6.5 cm mixed-density mass at the left frontal lobe,accompanying a midline shift,and an unenhanced chest-abdomen CT scan revealed a 6 cm×4.1 cm×6.5 cm low-density mass in the left chest wall.A CT-guided percutaneous lung biopsy was performed,and the pathological findings were SFT corresponding to brain tumor.Finally,the correct diagnosis of his brain tumor in history of past illness revealed to be SFT,and the unremovable tumor,namely present brain lesions enlarged and metastasized to the chest wall.We established a definitive diagnosis of intracranial malignant SFT metastasized to the chest wall.We notified him and his family of the disease,and offered palliative care.He passed away on the 29 th hospital day.CONCLUSION This case suggests the need for careful,detailed examination,and careful followup when encountering patients presenting with a mass.展开更多
Objective： Airway inflammation and airway hyper-responsiveness（AHR） are principle pathological manifestations of asthma. Cluster of differentiation 69（CD69） is a well-known co-stimulatory factor associated with t...Objective： Airway inflammation and airway hyper-responsiveness（AHR） are principle pathological manifestations of asthma. Cluster of differentiation 69（CD69） is a well-known co-stimulatory factor associated with the activation, proliferation as well as apoptosis of immune cells. This study aims to examine the effect of anti-CD69 monoclonal antibody（m Ab） on the pathophysiology of a mouse model of asthma. Methods： A murine model of ovalbumin（OVA）-induced allergic airway inflammation was used in this study. Briefly, mice were injected with 20 μg chicken OVA intraperitoneally on Days 0 and 14, followed by aerosol provocation with 1%（0.01 g/ml） OVA on Days 24, 25, and 26. Anti-CD69 m Ab or isotype Ig G was injected intraperitoneally after OVA challenge; dexamethasone（DXM） was administrated either before or after OVA challenge. AHR, mucus production, and eosinophil infiltration in the peribronchial area were examined. The levels of granulocyte-macrophage colony-stimulating factor（GM-CSF） and interleukin-5（IL-5） in bronchoalveolar lavage fluid（BALF） were also assayed as indices of airway inflammation on Day 28 following OVA injection. Results： Pretreatment with DXM together with anti-CD69 m Ab treatment after OVA provocation completely inhibited AHR, eosinophil infiltration and mucus overproduction, and significantly reduced BALF IL-5. However, treatment with DXM alone after OVA challenge only partially inhibited AHR, eosinophil infiltration and mucus overproduction, and did not diminish BALF IL-5. Treatment with either DXM or anti-CD69 m Ab did not alter the concentration of BALF GM-CSF. Conclusions： Anti-CD69 m Ab treatment inhibits established airway inflammation as effectively as DXM pretreatment. This study provides a potential alternative therapeutic opportunity for the clinical management of asthma and its exacerbation.展开更多
The biocompatibility of silicone rubber （SR） based electrodes coating with poly （vinyl alcohol） （PVA） films after implanted in the brain of rats was investigated. Twenty-two Wistar rats were used and implanted w...The biocompatibility of silicone rubber （SR） based electrodes coating with poly （vinyl alcohol） （PVA） films after implanted in the brain of rats was investigated. Twenty-two Wistar rats were used and implanted with SR electrodes and PVA/PAA films coated electrodes in left and right cerebral cortex respectively. After 4 and 8 weeks, the expression of glial fibrillary acidic protein （GFAP, a specific marker of astrocytes） and cluster of differentiation 68 （CD68, a specific marker of macrophages） were evaluated by immunohistochemistry. After 8 weeks, GFAP and CD68 expressions around PVA electrodes were significantly lower than those around SR electrodes in every stratified area （0-50 μm, 50-100 μm, 100 μm from further up to the electrode-tissue interface）. The resuits show that PVA coating can reduce the expressions of GFAP and CD68, suggesting the PVA coating can improve the biocompatibility of the SR while it is implanted in brain.展开更多
BACKGROUND Advanced glycation end products(AGEs)are diabetic metabolic toxic products that cannot be ignored.Nε-(carboxymethyl)lysine(CML),a component of AGEs,could increase macrophage lipid uptake,promote foam cell ...BACKGROUND Advanced glycation end products(AGEs)are diabetic metabolic toxic products that cannot be ignored.Nε-(carboxymethyl)lysine(CML),a component of AGEs,could increase macrophage lipid uptake,promote foam cell formation,and thereby accelerate atherosclerosis.The receptor for AGEs(RAGE)and cluster of differentiation 36(CD36)were the receptors of CML.However,it is still unknown whether RAGE and CD36 play key roles in CML-promoted lipid uptake.AIM Our study aimed to explore the role of RAGE and CD36 in CML-induced macrophage lipid uptake.METHODS In this study,we examined the effect of CML on lipid uptake by Raw264.7 macrophages.After adding 10 mmol/L CML,the lipid accumulation in macrophages was confirmed by oil red O staining.Expression changes of CD36 and RAGE were detected with immunoblotting and quantitative real-time polymerase chain reaction.The interaction between CML with CD36 and RAGE was verified by immunoprecipitation.We synthesized a novel N-succinimidyl-4-18Ffluorobenzoate-CML radioactive probe.Radioactive receptor-ligand binding assays were performed to test the binding affinity between CML with CD36 and RAGE.The effects of blocking CD36 or RAGE on CML-promoting lipid uptake were also detected.RESULTS The study revealed that CML significantly promoted lipid uptake by macrophages.Immunoprecipitation and radioactive receptor-ligand binding assays indicated that CML could specifically bind to both CD36 and RAGE.CML had a higher affinity for CD36 than RAGE.ARG82,ASN71,and THR70 were the potential interacting amino acids that CD36 binds to CML Anti-CD36 and anti-RAGE could block the uptake of CML by macrophages.The lipid uptake promotion effect of CML was significantly attenuated after blocking CD36 or RAGE.CONCLUSION Our results suggest that the binding of CML with CD36 and RAGE promotes macrophage lipid uptake.展开更多
文摘Objectives:Photodynamic therapy(PDT)is a minimally invasive method used in the treatment of various cancers and skin diseases,but it is not widely used in bone cancer,where the current therapy is often not effective and accompanied by side effects.Alternative and more effective therapies like PDT are needed.In this in-vitro study,the effect of the photosensitizer(PS)chlorin e6(Ce6)on cancerous bone tumor cells using PDT was examined.Methods:A total of 27 tissue specimens from patients with primary bone cancers or bone metastases of different origins were genetically characterized and treated with PDT.Following a 24-h incubation,cell viability was determined,and the effect of PDT on cell migration was analyzed over 48 h.Results:We could demonstrate that the effect on proliferation of PDT in combination with the PS Ce6 was best in cells isolated from primary osteosarcoma and in bone metastases from mammary carcinomas.Besides proliferation,PDT was also effective in inhibiting the migration of these cells.A statistically significant correlation between the PDT effect and CD164 gene expression was detected,indicating that a high expression of this gene could result in a higher effectiveness of the photodynamic treatment.Conclusion:This study analyzes for the first time the effect of PDT in bone cancers and metastases and shows the potential of treating these cancer types with Ce6 PDT.
基金supported by the National Natural Science Foundation of China(grant no.81602426).
文摘Objectives:Gastric cancer(GC)remains a major global health concern,and Phosphoinositide-3-Kinase Regulatory Subunit 1(PIK3R1),a regulatory subunit of the PI3K signaling pathway,may play a critical yet underexplored role in GC progression.This study aimed to investigate the prognostic significance of PIK3R1 in GC and its association with the tumor immune microenvironment.Methods:PIK3R1 expression and its clinical relevance were analyzed using datasets from GC patients who underwent gastrectomy,including cohorts from The Cancer Genome Atlas(TCGA)and the Sun Yat-sen University Cancer Center(SYSUCC).Prognostic models integrating PIK3R1 expression with clinical parameters were constructed for both cohorts.The immune microenvironment associated with PIK3R1 expression was assessed through immunohistochemistry and single-cell RNA sequencing.In vitro assays were conducted to evaluate the effects of PIK3R1 on GC cell proliferation and migration.Results:PIK3R1 was significantly overexpressed in GC tissues and was closely associated with aggressive tumor characteristics and poor clinical outcomes.A nomogram combining PIK3R1 expression with clinicopathological features effectively predicted patient prognosis.Knockdown of PIK3R1 in GC cells reduced proliferation and migration in vitro.Immunological profiling revealed that high PIK3R1 expression correlated with increased infiltration of forkhead box protein P3(Foxp3^(+))and cluster of differentiation 73(CD73^(+))T cells.Patients with low PIK3R1 expression and low CD73^(+)T cell infiltration had significantly better survival.Conclusions:PIK3R1 overexpression is linked to poor prognosis in GC and influences the extent of immune cell infiltration within the tumor microenvironment.A novel prognostic model integrating PIK3R1 and CD73 expression with clinical parameters was established to stratify GC patients into distinct risk groups,offering potential value for personalized therapeutic strategies.
文摘BACKGROUND Dermatofibrosarcoma protuberans(DFSP)is a rare,low-grade,locally aggressive cutaneous sarcoma.DFSP in the periocular region is exceedingly rare,leading to diagnostic and surgical challenges due to anatomical constraints in the periocular region.Precise diagnosis is essential to guide appropriate surgical management and prevent recurrence.CASE SUMMARY A 32-year-old female presented with a recurrent tumor in the medial canthus,previously diagnosed as a solitary fibrous tumor in an outside institution.After complete radiological and systemic workup,she was scheduled for a wide local excision followed by reconstruction after getting tumor clear margins on frozen section.Histopathology confirmed DFSP,characterized by storiform spindle cell proliferation,diffuse cluster of differentiation 34 positivity,and signal transducer and activator of transcription 6 negativity.CONCLUSION This case highlights the challenges in the diagnostic and surgical management of DFSP in periocular tumors.Comprehensive surgical excision with appropriate reconstruction is critical for achieving oncological control while preserving aesthetics and function.
文摘BACKGROUND The decision to administer adjuvant chemotherapy to patients with local stage depends on specific high-risk features that are T4 tumor stage,presence of perineural invasion,lymphovascular invasion,poorly differentiated tumor histology,inadequate lymph node sampling(fewer than 12 lymph nodes),and evidence of tumor perforation or obstruction.Tumor-stroma ratio,tumor infiltrating lymphocytes(TIL),Crohn-like reaction(CLR),desmoid reaction,poorly differentiated clusters(PDC)are new pathological markers that are being studied.AIM To examine the relationship between new pathological markers and defined high METHODS We evaluated 155 patients with the diagnosis stage I and II colorectal cancer between the years 2007 and 2021 who were treated at Trakya University Hospital,Department of Medical Oncology.We divided those with and without high-risk factors into two groups.We examined the relationship of new pathological markers with these groups and with pathological markers in risk factors.RESULTS There was no statistically significant correlation between presence of TIL,presence of PDC,presence of tumor budding,presence of CLR,presence of desmoid reaction and low and high-risk groups according to the degree of those with PDC(P=0.82,P=0.51,P=0.77,P=0.37,P=0.83,respectively).In addition,no statistically significant correlation was found between the tumor-stroma ratio and low and high risk groups(P=0.80).We found a statistically significant correlation between the presence of PDC and the presence of PDC grade 3 and T stage(P=0.001,P=0.001,respectively).It was determined that the presence of PDC and the frequency of grade 3 PDC increased with the advanced T stage.CONCLUSION No relationship was found between the presence of new pathological markers and high-low risk groups.When we examined the relationship between new and old pathological markers,only the frequency of detection of PDC and PDC grade 3 was found to be correlated with advanced T stage.
文摘BACKGROUND Primary liver cancer(PLC)is characterized by high malignancy,rapid disease progression,and persistent high incidence and mortality rates,posing a significant public health challenge worldwide.Early diagnosis and assessment of PLC are of great significance for guiding clinical treatment and improving patient prognosis.Alpha fetoprotein(AFP)and gamma-glutamyl transpeptidase(GGT)are commonly utilized tumor markers for the clinical diagnosis of PLC.They are ideal indicators for the detection of metastasis and recurrence after LC surgery.Nevertheless,not all patients with PLC secrete large amounts of AFP and GGT,which affects the accuracy of evaluating PLC by monitoring these two tumor markers alone.Cluster of differentiation 3 and 161 double-positive natural killer T(CD3^(+)CD161^(+)NKT)cell subsets are a class of molecules inextricably related to immune function and tumor occurrence and development.This research seeks to explore the clinical significance of CD3^(+)CD161^(+)NKT cell subsets combined with tumor markers AFP and GGT in the diagnosis of patients with PLC.AIM To probe the clinical significance of CD3^(+)CD161^(+)NKT cell subsets and AFP and GGT changes in the peripheral blood of individuals with PLC.METHODS The PLC group comprised 30 patients diagnosed with PLC who were admitted to our hospital between July 2022 and December 2023,whereas the control group consisted of 30 healthy individuals undergoing routine physical examinations at our hospital.Peripheral blood samples were harvested from both cohorts of patients.The levels of CD4^(+)NKT,CD8^(+)NKT,CD3^(+)CD56^(+)NKT,CD8^(+)CD56^(+)NKT,CD3^(+)CD161^(+)NKT,and CD3-CD161^(+)NKT were measured by flow cytometry.Serum AFP content was determined using a fully automatic immunoassay analyzer,and serum GGT content was ascertained by a fully automatic biochemical analyzer.The diagnostic value of CD3^(+)CD161^(+)NKT cell subsets and AFP and GGT level alterations for PLC was evaluated by receiver operating characteristic curve analysis.RESULTS No significant disparities were observed in the counts of white blood cells,neutrophils,and platelets,as well as the levels of blood urea nitrogen and serum creatinine between the two groups(P>0.05).Lymphocytes,red blood cells,hemoglobin,total protein,albumin,and globulin were more attenuated in the PLC group than in the control group,while glutamic-pyruvic transaminase,glutamic oxalacetic transaminase,and carcinoembryonic antigen levels were increased in the PLC cohort compared with the control cohort,with statistical significance(P<0.05).No substantial difference was discovered in peripheral blood CD4^(+)NKT,CD8^(+)NKT,and CD3^(+)CD56^(+)NKT cells between the two cohorts(P>0.05).The percentage of CD8^(+)CD56^(+)NKT cells(8.35%±1.01%),CD3^(+)CD161^(+)NKT cells(14.36%±1.55%),and CD3-CD161^(+)NKT cells(12.08%±1.34%)in the PLC group was higher than that in the control group(P<0.05).The levels of AFP(335.71±20.89 ng/mL)and GGT(136.87±15.62 U/mL)in the PLC cohort were elevated within the PLC cohort compared with the control cohort(P<0.05).The sensitivity of CD8^(+)CD56^(+)NKT,CD3^(+)CD161^(+)NKT,CD3-CD161^(+)NKT,AFP,and GGT alone for diagnosing PLC was 70.00%,83.33%,80.00%,56.67%,and 53.33%,respectively(P<0.05),with specificity rates of 66.67%,80.00%,76.67%,76.67%,and 66.67%,respectively(P<0.05).The area under the curve for combined detection was 0.898,with a sensitivity of 86.67%and a specificity of 80.00%(P<0.05).CONCLUSION The levels of CD8^(+)CD56^(+)NKT,CD3^(+)CD161^(+)NKT,CD3-CD161^(+)NKT,AFP,and GGT in the peripheral blood of patients with PLC were markedly elevated.The combined detection of these five indicators can improve the sensitivity and specificity of PLC diagnosis,providing solid evidence for the early clinical diagnosis of PLC.
基金the Shanghai Municipal Health Commission Medical New Technology Research and Translation Seed Program,No.2024ZZ2052Scientific Research Project funded by Shanghai Fifth People’s Hospital,Fudan University,No.2023WYRH03 and No.2025GZRFY05+2 种基金Shanghai Putuo District Health System Clinical Medicine Discipline Construction Project,No.2024tszk01Shanghai Health System Key Discipline,No.2024ZDXK0005Shanghai Minhang District Health and Family Planning Commission,No.2024MWDXK01.
文摘BACKGROUND Sepsis-associated encephalopathy(SAE)is a common complication of sepsis,characterized by cognitive impairment,altered consciousness,and psychiatric symptoms,including anxiety and depression.These psychiatric symptoms often exacerbate the overall prognosis and quality of life of affected patients.However,the underlying metabolic and proteomic features associated with SAE-induced psychiatric symptoms remain poorly understood.AIM To investigate the clinical manifestations of anxiety and depression in patients with sepsis and SAE and to explore their associated metabolic and proteomic characteristics.METHODS A total of 88 patients were enrolled,comprising 30 healthy controls,29 patients with sepsis,and 29 with SAE.Anxiety and depression symptoms were evaluated using the Hamilton anxiety rating scale(HAM-A)and Hamilton depression rating scale(HAM-D)in sepsis and SAE.Cognitive function was assessed using the Montreal Cognitive Assessment(MoCA),and quality of life was measured using the 36-Item Short Form Health Survey.Plasma samples were analyzed for metabolomic and proteomic profiling.Metabolic alterations were identified through liquid chromatography-mass spectrometry,while protein expression was assessed using Olink targeted proteomics.RESULTS Compared to the sepsis group,patients with SAE exhibited significantly higher levels of anxiety(HAM-A:15.2±4.0 vs 10.4±3.0,P=0.012)and depression(HAM-D:16.0±3.5 vs 9.1±2.3,P=0.003).Cognitive function,as measured by MoCA,was notably impaired in the SAE group(MoCA:18.5±4.0 vs 24.5±3.2,P=0.007).Quality of life scores,particularly in physical functioning,emotional well-being,and mental health,were significantly lower in patients with SAE.Metabolomic and proteomic analyses revealed substantial alterations in oxidative stress and nicotinamide adenine dinucleotide(NAD+)metabolism pathways,with cluster of differentiation(CD)38 emerging as a potential biomarker associated with psychiatric symptoms in SAE.Further validation in an independent cohort confirmed the diagnostic relevance of CD38.CONCLUSION This study highlights the significant psychological burden of SAE,manifested as anxiety and depression.Multiomics analysis identified distinct metabolic alterations,particularly in NAD+metabolism,that may contribute to psychiatric symptom development and progression.Furthermore,CD38 was identified as a promising biomarker for the early detection of SAE,providing potential avenues for early intervention and therapeutic targeting.
基金Supported by the Prince of Songkla University Research Fund,No.SCI6302040S。
文摘BACKGROUND Small blood vessels in the eyes are more susceptible to injury,which can lead to complications.However,since diabetic retinopathy is often a serious clinical condition,most of this study focuses on the vascular system of the choroid.As part of this study,we looked at how gymnemic acid(from Gymnema sylvestre)and glabridin(from Glycyrrhiza glabra,or licorice)might help diabetic rats’choroid structural change and blood vessels.AIM To explore the effects of glabridin and gymnemic acid on the structural changes of the choroidal layer and choriocapillaris as well as the expression of vascular endothelial growth factor(VEGF)and cluster of differentiation(CD)31 in diabetic rat’s eye.METHODS The male Wistar rats were separated into five groups:The control group(control),the diabetic group(DM),the diabetic rats treated with glabridin 40 mg/kg body weight(DM+GB),the diabetic rats treated with gymnemic acid 400 mg/kg body weight(DM+GM),and the diabetic rats treated with glyburide 4 mg/kg body weight(DM+GR).RESULTS There was an increase in the thickness of both the choroid layer and the wall of the arteries in the DM.A decrease in vascularity and choroidal impairment was found in DM rats.After eight weeks of experimentation,the choroidal thickness increased,and the walls of choroid arteries.The choroidal thickness in the DM+GB was 15.69±1.54μm,DM+GM was 14.84±1.31,and DM+GR groups was 16.45±1.15 when compared with DM group(27.22±2.05),the walls thickness of choroid arteries in the DM+GB was 10.23±1.11,DM+GM was 10.41±1.44,and DM+GR was 9.80±1.78 when compared with DM group(16.35±5.01),The expression of VEGF and CD31 was lower compared to the DM group.CONCLUSION In diabetic choroidopathy,hyperglycemia and inflammation cause damage to the neurovascular unit and bloodretinal barrier.Anti-VEGF treatments can slow or reverse the progression of the disease.According to current research findings,glabridin and gymnemic acid can reduce damage to the choroid,which is a factor that can sometimes result in vision loss.
文摘Cluster of differentiation 47(CD47),an immune checkpoint commonly referred to as the“don’t eat me”signal,plays a pivotal role in tumor immune evasion by inhibiting phagocytosis through interaction with signal regulatory protein alpha(SIRPα)on macrophages and dendritic cells(DCs).Although early enthusiasm drove broad clinical development,recent discontinuations of major CD47-targeted programs have prompted re-evaluation of its therapeutic potential.The purpose of this commentary is to contextualize the setbacks observed with first-generation CD47 inhibitors and to highlight strategies aimed at overcoming their limitations.Clinical challenges,including anemia,thrombocytopenia,suboptimal pharmacokinetics,and limited single-agent efficacy,underscore the need to develop safer,more selective approaches.Emerging next-generation strategies,such as SIRPα-directed agents,bispecific antibodies,and conditionally active therapeutics,are designed to enhance safety and tumor selectivity and reduce systemic toxicity.In addition,spatial profiling and biomarker-driven patient selection are advancing toward guiding rational therapeutic combinations,including with“eat-me”signals(e.g.,calreticulin[CALR])orDNA damage response therapies(e.g.,poly(ADP-ribose)polymerase[PARP]inhibitors).Rather than signaling failure,these developments underscore the need for precision,context-specific applications,and adaptive trial designs to realize the durable therapeutic promise of CD47 blockade in cancer immunotherapy.
基金Supported by Maulana Azad National Fellowship,University Grants Commission,New Delhi,Department of Biotechnology,New Delhi,No.AS[82-27/2019(SA III)]DBT-BUILDER-University of Lucknow Interdisciplinary Life Science Programme for Advance Research and Education(Level II),No.TG(BT/INF/22/SP47623/2022)Department of Science and Technology-SERB Power Grant Scheme,No.SPG/2021/00545.
文摘BACKGROUND Gestational diabetes mellitus(GDM)is a metabolic disorder causing hyperglycemia during pregnancy.Insulin resistance and decreased insulin secretion are linked to altered lipid metabolism that leads to progression of GDM.CD36 is a membrane glycoprotein involved in lipid metabolism and insulin sensitivity.Studies indicate that the CD36 gene is substantially linked to type 2 diabetes mellitus(T2DM)and could also influence GDM susceptibility.Insulin resistance and decreased insulin secretion are the hallmarks of T2DM,which is thought to have a similar genetic pathophysiology in GDM.AIM To investigate the impact of CD36 gene polymorphisms[rs1761667(G/A)and rs75326924(C/T)]and mRNA expression in GDM women.METHODS The case-control study involved a total of 400 pregnant women,(200 healthy controls and 200 GDM cases).The study of CD36 gene polymorphisms G/A(rs1761667)and C/T(rs75326924))were determined by polymerase chain reaction-restriction fragment length polymorphism.The mRNA expression study of CD36 gene was analyzed by quantitative polymerase chain reaction/quantitative real-time polymerase chain reaction followed by statistical analysis done using GraphPad Prism8 software(ver.8.0).RESULTS The study revealed statistically significant association(P<0.05)in anthropometric/biochemical parameters(age,gestational age,body mass index,fasting prandial glucose,post-prandial glucose,triglyceride,low-density lipoprotein)between GDM cases and healthy controls.CD36 G/A(rs1761667)and CD36 C/T(rs75326924)polymorphisms were significantly associated with GDM cases.The heterozygous genotypes(GA and CT)of both variants showed significant association(P=0.0001 and P=0.0025,odds ratio=2.683 and 2.022 respectively).Allele frequency of‘T’allele in CD36 C/T(rs75326924)polymorphism was also found to be significant(P=0.0046).CD36 gene was upregulated in individuals with GDM as compared to healthy controls(P=0.0001).However,the upregulation of gene expression was not significantly associated with the genotypes of CD36 G/A(rs1761667)and CD36 C/T(rs75326924)polymorphisms.CONCLUSION Heterozygous genotypes GA and CT of CD36 gene variants and expression are linked to GDM,potentially serving as predictive biomarkers for GDM susceptibility;further exploration needed in diverse ethnic communities.
基金National Council for Scientific and Technological Development,CNPq,Research Productivity,grant numbers:304747/2018-1,310135/2022-2,INCT-UROGEN#408576/2024-3(Leonardo O.Reis)and CAPES 88887.508226/2020-00-code 001,and 88887.974845/2024-00.
文摘Objective:The tumor microenvironment plays a pivotal role in prostate cancer progression and may differ across metastatic sites.This study aimed to evaluate and compare the primary and metastatic prostate adenocarcinoma tumor microenvironment.Methods:A total of 27 formalin-fixed paraffin-embedded tissue samples derived from 17 patients diagnosed with prostate adenocarcinoma,including the primary tumors,and the corresponding metastatic lymphatic and hematogenous lesions from various anatomical sites.Immunohistochemical labeling was performed using antibodies against Cluster of Differentiation 3 epsilon chain(CD3e),CD8 alpha chain(CD8a),Cluster of Differentiation 68(CD68),Cluster of Differentiation 163(CD163),Forkhead box P3(FOXP3),Cytotoxic T-Lymphocyte–Associated protein 4(CTLA-4),B7 homolog 3(B7-H3),Programmed cell death protein 1(PD-1),and Marker of proliferation Ki-67(Ki-67).Comparisons were made between primary and metastatic tumors to assess differences in immune cell infiltration,checkpoint expression,and proliferative indices.Results:Sampleswere classified into three groups:Primary Tumor n=12,Lymphatic Metastasis n=7,and Hematogenous Metastasis n=10.FOXP3(p=0.0017)and CD163(p=0.0316)expression levels were significantly higher in the Hematogenous Metastasis compared to both the Primary Tumor and Lymphatic Metastasis.PD-1 showed a clear trend(p=0.0577)toward higher levels in the Primary Tumor compared to both the HematogenousMetastasis and LymphaticMetastasis groups,suggesting distinct immunological landscapes depending on tumor location and progression.Conclusion:Diverse PD-1,CD163,and FOXP3 profiles were observed in primary and metastatic microenvironments of prostate cancer.These findings may contribute to the development of personalized therapeutic strategies and novel prognostic tools beyond conventional histological and TNM staging.
文摘在肿瘤微环境中,CD38(cluster of differentiation 38)不仅能够影响烟酰胺腺嘌呤二核苷酸(nicotinamide adenine dinucleotide,NAD^(+))代谢途径,还与程序性死亡受体1(programmed cell death 1,PD-1)及其配体细胞程序性死亡-配体1(programmed cell death ligand 1,PD-L1)存在协同作用,从而影响恶性肿瘤进展。NAD^(+)代谢与PD-1/PD-L1同样存在相关性,使得CD38、NAD^(+)、PD-1/PD-L1三者之间直接或间接发生相互作用。鉴于CD38独特的生理特性,提示其可能是备选免疫检查点。目前,关于CD38在抗肿瘤应用及作用机制方面的研究尚不完全,CD38多功能、高表达的特性及应用尚有探索潜力。本文基于肿瘤微环境对CD38作为备选免疫检查点及其与NAD^(+)、PD-1/PD-L1间的相互作用进行综述,以期为CD38相关恶性肿瘤治疗方案的研究、挖掘CD38潜力提供一定思路。
基金Supported by the Science and Technology Program of Guangzhou,No.202201020024.
文摘BACKGROUND Irreversible electroporation(IRE)represents an innovative localized technique for tumor ablation,possessing the capacity to activate the immune response of the host.However,this method alone is inadequate to halt cancer progression,necessitating the integration of additional strategies to achieve effective immuno-therapy.AIM To investigate the effects and underlying mechanisms of antitumor immunity derived from the synergistic application of IRE and anti-programmed cell death protein 1(PD-1)therapy within a murine model of hepatocellular carcinoma.METHODS C57BL-6 mice with tumor growth were divided into four separate cohorts:Control group;IRE group;Anti-PD-1 group;And IRE+anti-PD-1 group.The infiltration levels of T,B,and natural killer cells within the tumors,as well as the plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-β),were evaluated.Real-time polymerase chain reaction was utilized to quantify the expression of cluster of differentiation(CD)8(a marker indicative of CD8+T cells)in the tumor specimens of the mice at various temporal intervals.Tumor growth trajectories were charted.RESULTS The results indicated that the IRE+anti-PD-1 group exhibited significantly heightened percentages of T lymphocyte infiltration,particularly CD4+and CD8+T cells,when compared to the control cohort.Additionally,this group displayed increased infiltration of natural killer and B cells,augmented cytokine levels,and elevated CD8 messenger RNA expression.A marked decrease in tumor volume was noted in the IRE+anti-PD-1 group,indicating enhanced therapeutic efficacy.CONCLUSION The combined application of IRE and checkpoint blockade elicits an antitumor immune response,leading to a more substantial reduction in tumor volume and improved therapeutic outcomes,thereby establishing a novel avenue for the ablation and immunotherapy of hepatocellular carcinoma.
基金Supported by A research grant offered by Mashhad University of Medical Sciences, No. 85017
文摘AIM: To evaluate the relation of cluster of differentiation 44 (CD44) expression with clinicopathological features of gastric adenocarcinoma, and also its effect on prognosis with an emphasis on the differences between intestinal and diffuse types. METHODS: From 2000 to 2006, 100 patients with gastric adenocarcinoma, who had undergone total or subtotal gastrectomy without any prior treatment, were studied. Haematoxylin & eosin (HE) staining was used for histological evaluation, including the type (Lauren's classifi cation) and grading of the tumor. The expression of CD44 in the gastric adenocarcinoma mucosa and the adjacent mucosa were determined by immunohistochemistry. The survival analysis was obtained using the Kaplan-Meier test. RESULTS: Of 100 patients, 74 (74%) patients were male. The tumors were categorized as intestinal type (78%) or diffuse type (22%). Sixty-five percent of patients were CD44-positive. CD44 expression was not detected in normal gastric mucosa. Rather, CD44 was more commonly expressed in the intestinal subtype (P = 0.002). A signifi cant relation was seen between the grade of tumor and the expression of CD44 (P = 0.014). The survival analysis showed a poor prognosis of patients with CD44-positive tumors (P = 0.008); and this was more prominent in the intestinal (P = 0.001) rather than diffuse type. CONCLUSION: Cell adhesion molecule CD44 is highly expressed in gastric adenocarcinoma. CD44 expression is correlated with a poor prognosis in patients with the intestinal type of gastric adenocarcinoma. CD44 can, therefore, be utilized as a prognostic marker for this group of patients.
基金Supported by The Nationgal Natural Science Foundation of China,No.30571924
文摘AIM: To explore the associations of polymorphisms of lipopolysaccharide binding protein (LBP), cluster of differentiation 14 (CD14), toll-like receptor 4 (TLR-4), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) with the colorectal carcinoma (CRC) risk in Han Chinese. METHODS: Polymorphisms of LBP (rs1739654, rs223 2596, rs2232618), CD14 (rs77083413, rs4914), TLR-4 (rs5030719), IL-6 (rs13306435) and TNF-α (rs35131721) were genotyped in 479 cases of sporadic colorectal carcinoma and 486 healthy controls of Han Chinese in a case-control study. Single-nucleotide polymorphisms (SNPs) between cases and controls were analyzed by unconditional logistic regression. RESULTS: GA and GG genotypes of LBP rs2232596 were associated with a significantly increased risk ofCRC [odds ratio (OR) = 1.51, 95% confidence interval (CI) 1.15-1.99, P = 0.003; OR = 2.49, 95% CI 1.16-5.38, P = 0.016, respectively]. A similar association was also observed for the CG genotype of CD14 rs4914 (OR= 1.69, 95% CI 1.20-2.36, P = 0.002). In addition, a combination of polymorphisms in LBP rs2232596 and CD14 rs4914 led to a 3.4-fold increased risk of CRC (OR = 3.44, 95% CI 1.94-6.10, P = 0.000). CONCLUSION: This study highlights the LBP rs2232596 and CD14 rs4914 polymorphisms as biomarkers for elevated CRC susceptibility in the Chinese Han population.
文摘Glaucoma is an eye disease that usually occurs with the increased Intra-Ocular Pressure(IOP),which damages the vision of eyes.So,detecting and classifying Glaucoma is an important and demanding task in recent days.For this purpose,some of the clustering and segmentation techniques are proposed in the existing works.But,it has some drawbacks that include ineficient,inaccurate and estimates only the affected area.In order to solve these issues,a Neighboring Differential Clustering(NDC)-Intensity V ariation Making(IVM)are proposed in this paper.The main intention of this work is to extract and diagnose the abnormal retinal image by identifying the optic disc.This work includes three stages such as,preprocessing,clustering and segmentation.At first,the given retinal image is preprocessed by using the Gaussian Mask Updated(GMU)model for eliminating the noise and improving the quality of the image.Then,the cluster is formed by extracting the threshold and patterns with the help of NDC technique.In the segmentation stage,the weight is calculated for pixel matching and ROI extraction by using the proposed IVM method.Here,the novelty is presented in the clustering and segmentation processes by developing NDC and IVM algorithms for accurate Glaucoma identification.In experiments,the results of both existing and proposed techniques are evaluated in terms of sensitivity,specificity,accuracy,Hausdorff distance,Jaccard and dice metrics.
基金the Health Commission of Mianyang City and the Science and Education Department of the Third Hospital of Mianyang for their support
文摘The tumor,nodes,metastasis(TNM)staging system has long been the gold standard for the classification and prognosis of solid tumors.However,the TNM staging system is not without limitations.Prognostic heterogeneity exists within patients at the same stage.Therefore,the pursuit of other biomarkers with the potential to classify patients with cancer has never stopped.One of them,tumor budding(TB),has gained much success in colorectal cancer.In recent years,TB in gastric cancer has attracted much attention from researchers,beginning to reveal the molecular and biological aspects of this phenomenon in gastric cancer,and has emerged as a promising prognostic biomarker in gastric cancer,predicting disease progression and unfavorable survival.Therefore,it is time and essential to provide a holistic overview of TB in gastric cancer,which has not been achieved and is the aim of this review.
文摘BACKGROUND Solitary fibrous tumor(SFT)is a rare fibroblastic mesenchymal neoplasm that affects spindle cell soft tissues with broad-spectrum biological behavior;it is predominantly benign,and rarely metastasizes.SFT occurs mainly in the tissue structure of the serosa in the pleura and the thorax,and can be found throughout the body,though extra-thoracic localization,including the cephalic region,is uncommon.We reported the first case of intracranial malignant SFT metastasized to the chest wall.CASE SUMMARY An 81-year-old Japanese man was referred to our hospital due to progressive gait disturbance and appetite loss.His medical history included partial resection due to brain tumor,four times,and 50-Gray radiation therapy at another hospital,starting when he was 74 years old.An unenhanced head computed tomography(CT)scan revealed an 8 cm×5.1 cm×6.5 cm mixed-density mass at the left frontal lobe,accompanying a midline shift,and an unenhanced chest-abdomen CT scan revealed a 6 cm×4.1 cm×6.5 cm low-density mass in the left chest wall.A CT-guided percutaneous lung biopsy was performed,and the pathological findings were SFT corresponding to brain tumor.Finally,the correct diagnosis of his brain tumor in history of past illness revealed to be SFT,and the unremovable tumor,namely present brain lesions enlarged and metastasized to the chest wall.We established a definitive diagnosis of intracranial malignant SFT metastasized to the chest wall.We notified him and his family of the disease,and offered palliative care.He passed away on the 29 th hospital day.CONCLUSION This case suggests the need for careful,detailed examination,and careful followup when encountering patients presenting with a mass.
基金Project supported by the National Natural Science Foundation of China(No.30600266)the Zhejiang Provincial Science and Technology Project(No.2011C37073)+2 种基金the Zhejiang Provincial Natural Science Foundation(No.LQ12H16012)the National Key Clinical Project of Allergy of Chinathe National Key Clinical Specialist Construction Programs of China
文摘Objective： Airway inflammation and airway hyper-responsiveness（AHR） are principle pathological manifestations of asthma. Cluster of differentiation 69（CD69） is a well-known co-stimulatory factor associated with the activation, proliferation as well as apoptosis of immune cells. This study aims to examine the effect of anti-CD69 monoclonal antibody（m Ab） on the pathophysiology of a mouse model of asthma. Methods： A murine model of ovalbumin（OVA）-induced allergic airway inflammation was used in this study. Briefly, mice were injected with 20 μg chicken OVA intraperitoneally on Days 0 and 14, followed by aerosol provocation with 1%（0.01 g/ml） OVA on Days 24, 25, and 26. Anti-CD69 m Ab or isotype Ig G was injected intraperitoneally after OVA challenge; dexamethasone（DXM） was administrated either before or after OVA challenge. AHR, mucus production, and eosinophil infiltration in the peribronchial area were examined. The levels of granulocyte-macrophage colony-stimulating factor（GM-CSF） and interleukin-5（IL-5） in bronchoalveolar lavage fluid（BALF） were also assayed as indices of airway inflammation on Day 28 following OVA injection. Results： Pretreatment with DXM together with anti-CD69 m Ab treatment after OVA provocation completely inhibited AHR, eosinophil infiltration and mucus overproduction, and significantly reduced BALF IL-5. However, treatment with DXM alone after OVA challenge only partially inhibited AHR, eosinophil infiltration and mucus overproduction, and did not diminish BALF IL-5. Treatment with either DXM or anti-CD69 m Ab did not alter the concentration of BALF GM-CSF. Conclusions： Anti-CD69 m Ab treatment inhibits established airway inflammation as effectively as DXM pretreatment. This study provides a potential alternative therapeutic opportunity for the clinical management of asthma and its exacerbation.
基金Funded by the "863" Program of China (No.2006AA02Z4E6)the National Nature Science Foundation of China (No.30570516)
文摘The biocompatibility of silicone rubber （SR） based electrodes coating with poly （vinyl alcohol） （PVA） films after implanted in the brain of rats was investigated. Twenty-two Wistar rats were used and implanted with SR electrodes and PVA/PAA films coated electrodes in left and right cerebral cortex respectively. After 4 and 8 weeks, the expression of glial fibrillary acidic protein （GFAP, a specific marker of astrocytes） and cluster of differentiation 68 （CD68, a specific marker of macrophages） were evaluated by immunohistochemistry. After 8 weeks, GFAP and CD68 expressions around PVA electrodes were significantly lower than those around SR electrodes in every stratified area （0-50 μm, 50-100 μm, 100 μm from further up to the electrode-tissue interface）. The resuits show that PVA coating can reduce the expressions of GFAP and CD68, suggesting the PVA coating can improve the biocompatibility of the SR while it is implanted in brain.
基金Supported by The National Natural Science Foundation of China,No.82070455Natural Science Foundation of Jiangsu Province,No.BK20201225Medical Innovation Team Project of Jiangsu Province,No.CXTDA2017010。
文摘BACKGROUND Advanced glycation end products(AGEs)are diabetic metabolic toxic products that cannot be ignored.Nε-(carboxymethyl)lysine(CML),a component of AGEs,could increase macrophage lipid uptake,promote foam cell formation,and thereby accelerate atherosclerosis.The receptor for AGEs(RAGE)and cluster of differentiation 36(CD36)were the receptors of CML.However,it is still unknown whether RAGE and CD36 play key roles in CML-promoted lipid uptake.AIM Our study aimed to explore the role of RAGE and CD36 in CML-induced macrophage lipid uptake.METHODS In this study,we examined the effect of CML on lipid uptake by Raw264.7 macrophages.After adding 10 mmol/L CML,the lipid accumulation in macrophages was confirmed by oil red O staining.Expression changes of CD36 and RAGE were detected with immunoblotting and quantitative real-time polymerase chain reaction.The interaction between CML with CD36 and RAGE was verified by immunoprecipitation.We synthesized a novel N-succinimidyl-4-18Ffluorobenzoate-CML radioactive probe.Radioactive receptor-ligand binding assays were performed to test the binding affinity between CML with CD36 and RAGE.The effects of blocking CD36 or RAGE on CML-promoting lipid uptake were also detected.RESULTS The study revealed that CML significantly promoted lipid uptake by macrophages.Immunoprecipitation and radioactive receptor-ligand binding assays indicated that CML could specifically bind to both CD36 and RAGE.CML had a higher affinity for CD36 than RAGE.ARG82,ASN71,and THR70 were the potential interacting amino acids that CD36 binds to CML Anti-CD36 and anti-RAGE could block the uptake of CML by macrophages.The lipid uptake promotion effect of CML was significantly attenuated after blocking CD36 or RAGE.CONCLUSION Our results suggest that the binding of CML with CD36 and RAGE promotes macrophage lipid uptake.
