Hepatitis C virus in human B lymphocytes transformed by Epstein-Barr virus in vitro by in situ reverse transcriptase-polymerase chain reaction

AIM: To study persistence and replication of hepatitis C virus (HCV) in patients' peripheral blood mononuclear cells (PBMC) cultured in vitro. METHODS: Epstein Barr virus (EBV) was used to transform the hepatitis C virus from a HCV positive patient to permanent lymphoblastoid cell lines (LCL). Positive and negative HCV RNA strands of the cultured cells and growth media were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) each month. Core and NS5 proteins of HCV were further tested using immunohistochemical SP method and in situ RT-PCR. RESULTS: HCV RNA positive strands were consistently detected the cultured cells for one year. The negative-strand RNA in LCL cells and the positive-strand RNA in supernatants were observed intermittently. Immunohistochemical results medicated expression of HCV NS3 and C proteins in LCL cytoplasm mostly. The positive signal of PCR product was dark blue and mainly localized to the LCL cytoplasm. The RT-PCR signal was eliminated by overnight RNase digestion but not DNase digestion. CONCLUSION: HCV may exist and remain functional in a cultured cell line for a long period.

Mesenteric adipose tissue B lymphocytes promote intestinal injury in severe acute pancreatitis by mediating enteric pyroptosis

Background:Visceral adipose tissue(VAT)has been linked to the severe acute pancreatitis(SAP)prognosis,although the underlying mechanism remains unclear.It has been reported that pyroptosis worsens SAP.The present study aimed to verify whether mesenteric adipose tissue(MAT,a component of VAT)can cause secondary intestinal injury through the pyroptotic pathway.Methods:Thirty-six male Sprague Dawley(SD)rats were divided into six different groups.Twelve rats were randomly divided into the SAP and control groups.We monitored the changes of MAT and B lymphocytes infiltration in MAT of SAP rats.Twelve SAP rats were injected with MAT B lymphocytes or phosphate buffer solution(PBS).The remaining twelve SAP rats were first injected with MAT B lymphocytes,and then with MCC950(NLRP3 inhibitor)or PBS.We collected blood and tissue samples from pancreas,gut and MAT for analysis.Results:Compared to the control rats,the SAP group showed inflammation in MAT,including higher expression of tumor necrosis factor(TNF-α)and interleukin-6(IL-6),lower expression of IL-10,and histological changes.Flow cytometry analysis revealed B lymphocytes infiltration in MAT but not T lymphocytes and macrophages.The SAP rats also exhibited intestinal injury,characterized by lower expression of zonula occludens-1(ZO-1)and occludin,higher levels of lipopolysaccharide and diamine oxidase,and pathological changes.The expression of NLRP3 and n-GSDMD,which are responsible for pyroptosis,was increased in the intestine of SAP rats.The injection of MAT B lymphocytes into SAP rats exacerbated the inflammation in MAT.The upregulation of pyroptosis reduced tight junction in the intestine,which contributed to the SAP progression,including higher inflammatory indicators and worse histological changes.The administration of MCC950 to SAP+MAT B rats downregulated pyroptosis,which subsequently improved the intestinal barrier and ameliorated inflammatory response of SAP.Conclusions:In SAP,MAT B lymphocytes aggravated local inflammation,and promoted the injury to the intestine through the enteric pyroptotic pathway.

Competition between TRAF2 and TRAF6 Regulates NF-κB Activation in Human B Lymphocytes

Objective To investigate the role of TNF receptor-associated factor 2 (TRAF-2) and TRAF6 in CD40-induced nuclear factor-κB (NF-κB) signaling pathway and whether CD40 signaling requires TRAF2. Methods Human B cell lines were transfected with plasmids expressing wild type TRAF2 or dominant negative TRAF2,TRAF2-shRNA,or TRAF6-shRNA. The activation of NF-κB was detected by Western blot,kinase assay,transfactor enzyme-linked immunosorbent assay (ELISA),and fluorescence resonance energy transfer (FRET). Analysis of the role of TRAF-2 and TRAF-6 in CD40-mediated NF-κB activity was examined following stimulation with recombinant CD154. Results TRAF2 induced activity of IκB-kinases (IKKα,IKKi/ε),phosphorylation of IκBα,as well as nuclear translocation and phosphorylation of p65/RelA. In contrast,TRAF6 strongly induced NF-κB activation and nuclear translocation of p65 as well as p50 and c-Rel. Engagement of CD154-induced nuclear translocation of p65 was inhibited by a TRAF6-shRNA,but conversely was enhanced by a TRAF2-shRNA. Examination of direct interactions between CD40 and TRAFs by FRET documented that both TRAF2 and TRAF6 directly interacted with CD40. However,the two TRAFs competed for CD40 binding. Conclusions These results indicate that TRAF2 can signal in human B cells,but it is not essential for CD40-mediated NF-κB activation. Moreover,TRAF2 can compete with TRAF6 for CD40 binding,and thereby limit the capacity of CD40 engagement to induce NF-κB activation.

Immunotherapy in pancreatic cancer:Unleash its potential through novel combinations

Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States,with poor response to current standard of care,short progression-free and overall survival.Immunotherapies that target cytotoxic T lymphocyte antigen-4,programmed cell death protein-1,and programmed death-ligand 1 checkpoints have shown remarkable activities in several cancers such as melanoma,renal cell carcinoma,and nonsmall cell lung cancer due to high numbers of somatic mutations,combined with cytotoxic T-cell responses.However,single checkpoint blockade was ineffective in pancreatic cancer,highlighting the challenges including the poor antigenicity,a dense desmoplastic stroma,and a largely immunosuppressive microenvironment.In this review,we will summarize available clinical results and ongoing efforts of combining immune checkpoint therapies with other treatment modalities such as chemotherapy,radiotherapy,and targeted therapy.These combination therapies hold promise in unleashing the potential of immunotherapy in pancreatic cancer to achieve better and more durable clinical responses by enhancing cytotoxic T-cell responses.

Identification of the epitopes on HCV core protein recognized by HLA-A2 restricted cytotoxic T lymphocytes

AIM: To identify hepatitis C virus(HCV) core protein epitopes recognized by HLA-A2 restricted cytotoxic T lymphocyte (CTL). METHODS: Utilizing the method of computer prediction followed by a 4h(51)Cr release assay confirmation. RESULTS: The results showed that peripheral blood mononuclear cells (PBMC) obtained from two HLA-A2 positive donors who were infected with HCV could lyse autologous target cells labeled with peptide "ALAHGVRAL (core 150-158)". The rates of specific lysis of the cells from the two donors were 37.5% and 15.8%, respectively. Blocking of the CTL response with anti-CD4 mAb caused no significant decrease of the specific lysis. But blocking of CTL response with anti-CD8 mAb could abolish the lysis. CONCLUSION: The peptide (core 150-158) is the candidate epitope recognized by HLAA2 restricted CTL.

Activation-induced cell death in B lymphocytes

Upon encountering the antigen (Ag), the immune system can either develop a specific immune response or enter a specific state of unresponsiveness, tolerance. The response of B cells to their specific Ag can be activation and proliferation, leading to the immune response, or anergy and activation-induced cell death (AICD), leading to tolerance. AICD in B lymphocytes is a highly regulated event initiated by crosslinking of the B cell receptor (BCR). BCR engagement initiates several signaling events such as activation of PLCr, Ras, and PI3K, which generally speaking, lead to survival. However, in the absence of survival signals (CD40 or IL-4R engagement), BCR crosslinking can also promote apoptotic signal transduction pathways such as activation of effector caspases, expression of pro-apoptotic genes, and inhibition of pro-survival genes. The complex interplay between survival and death signals determines the B cell fate and, consequently, the immune response.

SUBTYPES OF B LYMPHOCYTES IN PATIENTS WITH AUTOIMMUNE HEMOCYTOPENIA

Objective To investigate the quantities of bone marrow CD5+ B lymphocytes in the patients with autoimmune hemocytopenia and the relationship between quantities of CD5+ B lymphocytes and clinical or laboratorial parameters. Methods Quantities of CD5+ B lymphocytes in the bone marrow of 14 patients with autoimmune hemolytic anemia (AIHA) or Evans syndrome, 22 immunorelated pancytopenia (IRP) patients, and 10 normal controls were assayed by flow cytometry. The correlation between their clinical or laboratorial parameters and CD5+ B lymphocytes was analyzed. Results The quantity of CD5+ B lymphocytes of AIHA/Evans syndrome (34.64%±19.81%) or IRP patients (35.81%±16.83%) was significantly higher than that of normal controls (12.00%±1.97%, P<0.05). However, there was no significant difference between AIHA/Evans syndrome and IRP patients (P>0.05). In all hemocytopenic patients, the quantity of bone marrow CD5+ B lymphocytes showed significantly negative correlation with serum complement C3 level (r=-0.416, P<0.05). In the patients with AIHA/Evans syndrome, the quantity of bone marrow CD5+ B lymphocytes showed significantly positive correlation with serum indirect bilirubin level (r=1.00, P<0.05). In Evans syndrome patients, the quantity of CD5+ B lymphocytes in bone marrow showed significantly positive correlation with platelet-associated immunoglobulin G (r=0.761, P<0.05) and platelet-associated immunoglobulin M (r=0.925, P<0.05). The quantity of CD5+ B lymphocytes in bone marrow of all hemocytopenic patients showed significantly negative correlation with treatment response (tau-b=-0.289, P<0.05), but had no correlation with colony forming unit-erythroid (r=-0.205, P>0.05) or colony forming unit-granulocyte-macrophage colonies (r=-0.214, P>0.05). Conclusions The quantity of bone marrow CD5+ B lymphocytes in the patients with autoimmune hemocytopenia significantly increases and is correlated with disease severity and clinical response, which suggest that CD5+ B lymphocytes might play an important role in the pathogenesis of autoimmune hemocytopenia.

Bystanders or not?Microglia and lymphocytes in aging and stroke

As the average age of the world population increases,more people will face debilitating aging-associated conditions,including dementia and stroke.Not only does the incidence of these conditions increase with age,but the recovery afterward is often worse in older patients.Researchers and health professionals must unveil and understand the factors behind age-associated diseases to develop a therapy for older patients.Aging causes profound changes in the immune system including the activation of microglia in the brain.Activated microglia promote T lymphocyte transmigration leading to an increase in neuroinflammation,white matter damage,and cognitive impairment in both older humans and rodents.The presence of T and B lymphocytes is observed in the aged brain and correlates with worse stroke outcomes.Preclinical strategies in stroke target either microglia or the lymphocytes or the communications between them to promote functional recovery in aged subjects.In this review,we examine the role of the microglia and T and B lymphocytes in aging and how they contribute to cognitive impairment.Additionally,we provide an important update on the contribution of these cells and their interactions in preclinical aged stroke.

In vitro and in vivo analyses of a genetically-restricted antigen specific factor from mixed cell cultures of macrophage, T and B lymphocytes

An immunostimulatory factor was identified to be secreted by antigen-pulsed maorophages. This factor was able to induce the generation of antigen specific T helper lymphocytes in vitro as well as in vivo. Further in vitro experiments testing for the genetic restriction of this factor indicated that it is a genetically-restricted antigen specific factor (ASF). The Cunningham plaque assay was used to quantify the generation of T helper lymphocytes by measuring the number of plaque forming cells after sequential incubations of antigen-pulsed maorophages with T lymphocytes, and then spleen cells, and finally the TNP-coated sheep red blood cells.

Costimulation of resting B lymphocytes alters the IL-4-activated IRS2 signaling pathway in a STAT6 independent manner: implications for cell survival and proliferation

IL-4 is an important B cell survival and growth factor. IL-4 induced the tyrosine phosphorylation of IRS2 in resting B lymphocytes and in LPS- or CD40L-activated blasts. Phosphorylated IRS2 coprecipitated with the p85 subunit of PI 3’ kinase in both resting and activated cells. By contrast, association of phosphorylated IRS2 with GRB2 was not detected in resting B cells after IL-4 treatment although both proteins were expressed. However, IL-4 induced association of IRS2 with GRB2 in B cell blasts. The pattern of IL-4- induced recruitment of p85 and GRB2 to IRS2 observed in B cells derived from STAT6 null mice was identical to that observed for normal mice. While IL-4 alone does not induce activation of MEK, a MEKI inhibitor suppressed the IL-4-induced proliferative response of LPS-activated B cell blasts. These results demonstrate that costimulation of splenic B cells alters IL-4-induced signal transduction independent of STAT6 leading to proliferation. Furthermore, proliferation induced by IL-4 in LPS-activated blasts is dependent upon the MAP kinase pathway.

Donor-Derived CD19-Targeted T Cell Infusion Eliminates B Cell Acute Lymphoblastic Leukemia Minimal Residual Disease with No Response to Donor Lymphocytes after Allogeneic Hematopoietic Stem Cell Transplantation

Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with BALL after allo-HSCT have a very short median survival. Minimal residual disease (MRD) is predictive of forthcoming hematological relapse after hematopoietic stem cell transplantation (HSCT);furthermore, eliminating MRD effectively prevents relapse. Donor lymphoblastic infusion (DLI) is the main established approach to treat B-ALL with MRD after allo-HSCT. However, about one-third of patients with MRD are non-responsive to DLI and their prognosis worsens. Although donor-derived cluster of differentiation (CD)19-directed chimeric antigen receptor-modified (CAR) T cells (CART19s) can potentially cure leukemia, the efficiency and safety of infusions with these cells have not yet been investigated in patients with MRD after HSCT. Between September 2014 and February 2018, six patients each received one or more infusions of CART19s from HSCT donors. Five (83.33%) achieved MRD-negative remission, and one case was not responsive to the administration of CAR T cells. Three of the six patients are currently alive without leukemia. No patient developed acute graft-versus-host disease (aGVHD), and no patient died of cytokine release syndrome. Donor-derived CAR T cell infusions seem to be an effective and safe intervention for patients with MRD in B-ALL after allo-HSCT and for those who were not responsive to DLI.

Guben Tongluo Formula Protects LPS-induced Damage in Lamina Propria B Lymphocytes Through TLR4/MyD88/NF-κB Pathway

Objective The main pathological feature of immunoglobulin A nephropathy(IgAN),an autoimmune kidney disease,is the deposition of IgA immune complexes,accompanied by mesangial cell proliferation and elevated urine protein.The Guben Tongluo formula(GTF)is a traditional Chinese medicine prescription,which has predominant protective effects on IgAN.However,the therapeutic mechanism of the GTF in IgAN remains elusive.The present study aimed to determine the effects of GTF in treating IgAN via regulating the TLR4/MyD88/NF-κB pathway.Methods In the present study,lamina propria B lymphocytes were treated with different concentrations of lipopolysaccharide(LPS)(0,1,5,10 and 20 ng/mL).Flow cytometry was used to define positive CD86+CD19+cells.CCK-8 assay was used to examine cell proliferation.RNAi was used to induce TLR4 silencing.qRT-PCR and Western blotting were used to determine gene expression.Results It was found that the LPS dose-dependently increased the content of IgA and galactose-deficient IgA1(Gd-IgA),the levels of TLR4,Cosmc,MyD88 and phosphorylated(p)-NF-κB,and the ratio of CD86+CD19+and IgA-producing B cells.However,the TLR4 knockdown reversed the role of LPS.This suggests that TLR4 mediates the effects of LPS on lamina propria B lymphocytes.Furthermore,the GTF could dose-dependently counteract the effects of LPS and TLR4 overexpression on lamina propria B lymphocytes through the TLR4/MyD88/NF-κB pathway.Conclusion Collectively,these results demonstrate that the GTF can regulate the TLR4/MyD88/NF-κB pathway to treat IgAN model lamina propria B lymphocytes stimulated by LPS.

RNA polymerases in plasma cells trav-ELL2 the beat of a different drum

There is a major transformation in gene expression between mature B cells （including follicular, marginal zone, and germinal center cells） and antibody secreting cells （ASCs）, i.e. , ASCs, （including plasma blasts, splenic plasma cells, and long-lived bone marrow plasma cells）. This signifcant change-over occurs to accommodate the massive amount of secretory-specific immunoglobulin that ASCs make and the export processes itself. It is well known that there is an up-regulation of a small number of ASC-specific transcription factors Prdm1 （B-lymphocyte-induced maturation protein 1）, interferon regulatory factor 4, and Xbp1, and the reciprocal down-regulation of Pax5, Bcl6 and Bach2, which maintain the B cell program. Less well appreciated are the major alterations in transcription elongation and RNA proce-ssing occurring between B cells and ASCs. The three ELL family members ELL1, 2 and 3 have different protein sequences and potentially distinct cellular roles in transcription elongation. ELL1 is involved in DNA repair and small RNAs while ELL3 was previously described as either testis or stem-cell specifc. After B cell stimulation to ASCs, ELL3 levels fall precipitously while ELL1 falls off slightly. ELL2 is induced at least 10-fold in ASCs relative to B cells. All of these changes cause the RNA Polymerase Ⅱ in ASCs to acquire different properties, leading to differences in RNA processing and histone modifcations.

Primary duodenal T/histiocyte-rich large B-cell lymphoma complicated with obstructive jaundice:A case report and review of literature

BACKGROUND T/histiocyte-rich large B-cell lymphoma(T/HRBCL)is a highly aggressive subtype of diffuse large B-cell lymphoma characterized histologically by the presence of a few neoplastic large B cells amidst an abundant background of reactive T lymphocytes and/or histiocytes.T/HRBCL commonly affects the lymph nodes,followed by extranodal sites,such as the spleen,liver,and bone marrow,with rare occurrences in the gastrointestinal tract.Primary gastrointestinal T/HRBCL lacks specific clinical and endoscopic manifestations,and it is difficult to differentiate from inflammatory diseases,nodular lymphocyte predominant Hodgkin lymphoma,and other diseases on a histological basis,thereby hindering early diagnosis.CASE SUMMARY A 63-year-old man was hospitalized with a one-month history of jaundice and weight loss of approximately 3 kg.Laboratory tests revealed increased hepatic parameters in a cholestatic pattern and elevated carbohydrate antigen 19-9 levels.An abdominal computed tomography scan revealed a low-density mass within the descending duodenum and dilation of the bile and pancreatic ducts.He was clinically diagnosed with a duodenal tumor.During surgery,a 7.0 cm×8.0 cm mass was identified within the descending duodenum,so pancreaticoduodenectomy and cholecystectomy were performed.Following operative biopsy,the tumor was diagnosed as primary duodenal T/HRBCL.The patient refused postoperative chemotherapy and died four months after surgery.CONCLUSION Primary duodenal T/HRBCL is an extremely rare and highly aggressive malignancy.The initial treatment strategies should be based on the original site of the tumor,the disease stage,and the patient's physical condition.Chemotherapy-based comprehensive treatment is still the main treatment method for primary gastrointestinal T/HRBCL.

Effect of Bifidobacterium triple live bacteria on inflammatory factors, oxidative stress and T lymphocyte subsets in patients with ulcerative colitis

Objective: To explore the effect of Bifidobacterium triple live bacteria on inflammatory factors, oxidative stress and T lymphocyte subsets in patients with ulcerative colitis (UC). Method: A total of 90 patients with UC treated in our hospital were selected and randomly divided into the observation group and the control group each with 45 cases. The control group was given Mesalazin Enteric-coated Tablets 1 g/times, 4 times/d, continuous treatment for 1 months:when the clinical symptoms were stable, switched to 500 mg/times, 3 times/d, continuous treatment for 3 months. The observation group on the basis of conventional treatment to give Bifidobacterium triple live bacteria scattered adjuvant therapy (Bifico capsule), 0.84 g/time, 2 times/d, continuous treatment for 3 months. In the two groups, the levels of inflammatory factors (IL-6, IL-10, CRP, TNF-α), oxidative stress markers (MDA, SOD) and T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+) were compared pre and post treatment. Results: The levels of IL-6, CRP, MDA, TNF-α, CD8+ in both two groups were significantly decreased compared with treatment before;the levels of IL-10, SOD, CD3+, CD4+ and CD4+/CD8+were significantly increased compared with treatment before. After treatment, the levels of serum IL-6, CRP, TNF-α, MDA and CD8+ in observation group with the data (72.17±15.18) pg/mL, (21.52±10.21) mg/mL, (15.98±4.12) pg/mL respectively were decreased more significantly than those data in control group which were (86.55±17.26) pg/mL, (43.02±12.27) mg/L, (22.35±3.67) pg/mL, MDA level (5.89±0.56) nmol/mL in observation group was decreased more significantly than the level in the control group (6.75±0.68) nmol/mL;CD8+level (17.24±3.06)% in observation group was decreased more significantly than the level (19.01±2.62)% in the control group. After treatment, IL-10 level (70.21±6.03) pg/mL in observation group was increased more significantly than the level in the control group (56.48+ 8.67) pg/mL;SOD level (1.84±0.06) U/mL in observation group was increased more significantly than the level in the control group (1.32±0.05) U/mL;the levels of CD3+, CD4+, CD4+/CD8+ in the observation group (57.84±6.07)%;(36.78±4.32)%;(1.92±0.29) were increased more significantly than the level in the control group (54.93±6.87)%;(35.42±5.27)%;(1.89±0.12). Conclusion: Bifidobacterium triple live bacteria scattered adjuvant treatment of ulcerative colitis helps regulate oxidative stress and inflammatory cytokines inhibiting inflammatory reaction and improving enhance function, and can effectively improve the clinical symptoms of patients with UC.

The Role of T Lymphocytes in Bone Remodeling

Bone remodeling is a tightly regulated resorption and formation of bone matrix for physiological processes or to maintain bone function. Bone remodeling involves the synchronized differentiation and activity of bone-related cell types including bone matrix-depositing osteoblasts, bone matrix-resorbing osteoclasts, collagen/extracellular matrix-producing chondrocytes, and the progenitors of these cell types. T and B cells are adaptive immune cells that can influence bone remodeling by directly regulating the function of bone-related cells under normal and pathophysiological conditions. The specific mechanisms through which T cells control remodeling are not well defined. Here, we review the impact and influence of T cells and their products on the differentiation and function of bone cells during bone remodeling. Synthesizing new connections and highlighting potential mechanisms may promote additional avenues of study to elucidate the full role that immune cells play in regulating bone homeostasis.

Costimulatory blockade:A novel approach to the treatment of glomerular disease?

Costimulatory pathways(Cluster of differentiation 28,tumor necrosis factor-related,adhesion and T Cell Ig-and mucin-domain molecules) regulating the interactions between receptors on the T cells andtheir ligands expressed on several cell types,have a key role in controlling many immunological and non immunological processes.Indeed,accumulating evidence indicate that these molecules are involved in the pathogenesis of numerous conditions,such as allograft rejection,atherosclerosis,rheumatoid arthritis,psoriasis and renal diseases,including glomerulonephritis.Primary or secondary(i.e.,associated with infections,drugs or systemic diseases,such as systemic lupus erythematosus,diabetes,etc.) glomerulonephritis represent a group of heterogeneous diseases with different pathogenic mechanisms.Since costimulatory molecules,in particular CD80 and CD40,have been found to be expressed on podocytes in the course of different experimental and clinical glomerulonephritis,costimulation has been thought as a new therapeutic target for patients with glomerular diseases.However,although experimental data suggested that the blockade of costimulatory pathways is effective and safe in the prevention and treatment of glomerular diseases,clinical trials reported contrasting results.So,at this moment,there is not a strong evidence for the general use of costimulatory blockade as an alternative treatment strategy in patients with primary or secondary glomerulonephritis.Here,we critically discuss the current data and the main issues regarding the development of this innovative therapeutic approach.

Impact of oxaliplatin and trastuzumab combination therapy on tumor markers and T lymphocyte subsets for advanced gastric cancer

BACKGROUND Advanced gastric cancer(AGC)remains a challenging malignancy with poor prognosis.The combination of oxaliplatin and trastuzumab has shown promising results in AGC treatment.This study aimed to investigate the effects of oxaliplatin and trastuzumab combination therapy on serum tumor markers and T lymphocyte subsets in patients with AGC and to explore their potential as predictive biomarkers for treatment response.AIM To investigate the impact of oxaliplatin and trastuzumab combination therapy on serum markers and T cell subsets in patients with AGC.METHODS This prospective study enrolled 60 patients with AGC.All patients received oxaliplatin(130 mg/m^(2),every 3 weeks)and trastuzumab(8 mg/kg loading dose,followed by 6 mg/kg every 3 weeks)for six cycles.Serum carcinoembryonic antigen(CEA),cancer antigen 19-9(CA19-9),and cancer antigen 72-4(CA72-4)were measured before and after treatment.T-lymphocyte subsets,including CD3+,CD4+,CD8+,and CD4+/CD8+ratios,were also evaluated.The clinical response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1.RESULTS After six cycles of treatment,the CEA,CA19-9,and CA72-4 serum levels significantly decreased compared to baseline levels(P<0.001).The percentages of CD3+and CD4+T lymphocytes increased significantly(P<0.05),whereas the percentage of CD8+T lymphocytes decreased(P<0.05).The CD4+/CD8+ratio also significantly increased after treatment(P<0.05).Patients with a higher decrease in serum tumor markers(≥50%reduction)and a higher increase in CD4+/CD8+ratio(≥1.5-fold)showed better clinical response rates(P<0.05).CONCLUSION Oxaliplatin and trastuzumab combination therapy effectively reduced serum tumor marker levels and modulated T lymphocyte subsets in patients with AGC.Combination therapy not only has a direct antitumor effect,but also enhances the immune response in patients with AGC.Serum tumor markers and T lymphocyte subsets may serve as potential predictive biomarkers for treatment response in patients with AGC receiving combination therapy.

Is the neutrophil to lymphocyte ratio associated with liver fibrosis in patients with chronic hepatitis B?

AIM: To determine the association between the neutrophil to lymphocyte(N/L) ratio and the degree of liver fibrosis in patients with chronic hepatitis B(CHB) infection. METHODS: Between December 2011 and February 2013, 129 consecutive CHB patients who were admitted to the study hospitals for histological evaluation of chronic hepatitis B-related liver fibrosis were included in this retrospective study. The patients were divided into two groups based on the fibrosis score: individuals with a fibrosis score of F0 or F1 were included in the "no/minimal liver fibrosis" group, whereas patients with a fibrosis score of F2, F3, or F4 were included in the "advanced liver fibrosis" group. The Statistical Package for Social Sciences 18.0 for Windows was used to analyze the data. A P value of < 0.05 was accepted as statistically significant.RESULTS: Three experienced and blinded pathologists evaluated the fibrotic status and inflammatory activity of 129 liver biopsy samples from the CHB patients. Following histopathological examination, the "no/minimal fibrosis" group included 79 individuals, while the "advanced fibrosis" group included 50 individuals. Mean(N/L) ratio levels were notably lower in patients with advanced fibrosis when compared with patients with no/minimal fibrosis. The mean value of the aspartate aminotransferase-platelet ratio index was markedly higher in cases with advanced fibrosis compared to those with no/minimal fibrosis.CONCLUSION: Reduced levels of the peripheral blood N/L ratio were found to give high sensitivity, specificity and predictive values in CHB patients with significant fibrosis. The prominent finding of our research suggests that the N/L ratio can be used as a novel noninvasive marker of fibrosis in patients with CHB.

自拟补肾潜阳汤联合阿仑膦酸钠维D3治疗骨质疏松症疗效及对骨代谢和TMAO-NF-κB/NFATc1通路影响分析

【目的】分析自拟补肾潜阳汤联合阿仑膦酸钠维D3治疗骨质疏松症(osteoporosis,OP)的疗效及其对骨代谢和氧化三甲胺(TMAO)-核因子κB(NF-κB)/活化T细胞核因子c1(NFATc1)通路的影响。【方法】将2021年1月至2023年1月在台州市中西医结合医院就诊的102例脾肾阳虚型OP患者按随机数字表法随机分为观察组和西药组,每组各51例。西药组给予阿仑膦酸钠维D3治疗,观察组在西药组的基础上给予自拟补肾潜阳汤治疗,疗程为12周。观察2组患者治疗前后中医证候积分、Oswestry功能障碍指数(ODI)评分、疼痛程度视觉模拟量表(VAS)评分、骨代谢指标及TMAO-NF-κB/NFATc1通路相关因子水平的变化情况,评价2组患者的临床疗效和用药安全性。【结果】(1)治疗12周后,观察组的总有效率为96.08%(49/51),西药组为78.43%(40/51),组间比较(χ^(2)检验),观察组的疗效明显优于西药组(P<0.01)。(2)治疗后,2组患者的腰背冷痛、酸软乏力、少气懒言、头昏目眩等中医证候积分均较治疗前降低(P<0.05),且观察组的降低幅度均明显优于西药组(P<0.01)。(3)治疗后,2组患者的ODI评分和疼痛程度VAS评分均较治疗前降低(P<0.05),且观察组的降低幅度均明显优于西药组(P<0.01)。(4)治疗后,2组患者的血清骨钙素(BGP)水平均较治疗前升高(P<0.05),血清总Ⅰ型原胶原氨基端延长肽(PINP)、β胶原降解产物(β-CTX)水平均较治疗前降低(P<0.05),且观察组对血清BGP水平的升高幅度及对血清PINP、β-CTX水平的降低幅度均明显优于西药组(P<0.01)。(5)治疗后,2组患者的血清TMAO、NF-κB、NFATc1水平均较治疗前降低(P<0.05),且观察组的降低幅度均明显优于西药组(P<0.01)。(6)观察组的不良反应总发生率为5.88%(3/51),西药组为9.80%(5/51),组间比较,差异无统计学意义(P>0.05)。【结论】自拟补肾潜阳汤联合阿仑膦酸钠维D3治疗脾肾阳虚型OP患者疗效确切,可有效缓解腰背冷痛等症状,减轻功能障碍程度,改善骨代谢,抑制血清TMAO、NF-κB、NFATc1高表达,且未引发严重不良反应,具有较高的安全性。