Inactivation of FOXO1 induces T follicular cell polarization and involves angioimmunoblastic T cell lymphoma

Objective:Angioimmunoblastic T cell lymphoma(AITL)is an aggressive form of non-Hodgkin lymphoma derived from mature T cells.However,the underlying pathogenesis of AITL remains unresolved.We aimed to explore the role of FOXO1-mediated signaling in the tumorigenesis and progression of AITL.Methods:FOXO1 expression was assessed using immunohistochemistry on a total of 46 AITL tissue samples.Retroviruses encoding FOXO1 shRNA were used to knockdown FOXO1 expression in CD4^+T cells.Flow cytometric assays analyzed the proliferation and survival of FOXO1 knockdown CD4^+T cells.Furthermore,we performed adoptive T-cell transfer experiments to identify whether inactivation of FOXO1 induced neoplastic follicular-helper T(Tfh)cell polarization and function.Results:Patients with low FOXO1 protein levels were prone to have an advanced tumor stage(P=0.049),higher ECOG ps(P=0.024),the presence of bone marrow invasion(P=0.000),and higher IPI(P=0.035).Additionally,the survival rates of patients in the FOXO1 high-expression group were significantly better than those in the FOXO1 low-expression group(χ^2=5.346,P=0.021).We also observed that inactivation of FOXO1 increased CD4^+T cell proliferation and altered the survival and cell-cycle progression of CD4^+T cells.Finally,we confirmed that inactivation of FOXO1 induces Tfh cell programing and function.Conclusions:Inactivation of FOXO1 in AITL plays a key role in the tumorigenesis and progression of AITL.We propose that FOXO1 expression could be a useful prognostic marker in AITL patients to predict poor survival,and to design appropriate therapeutic strategies.

SENP3 Promotes Mantle Cell Lymphoma Development through Regulating Wnt10a Expression

Objective SUMO-specific protease 3(SENP3),a member of the SUMO-specific protease family,reverses the SUMOylation of SUMO-2/3 conjugates.Dysregulation of SENP3 has been proven to be involved in the development of various tumors.However,its role in mantle cell lymphoma(MCL),a highly aggressive lymphoma,remains unclear.This study was aimed to elucidate the effect of SENP3 in MCL.Methods The expression of SENP3 in MCL cells and tissue samples was detected by RT-qPCR,Western blotting or immunohistochemistry.MCL cells with stable SENP3 knockdown were constructed using short hairpin RNAs.Cell proliferation was assessed by CCK-8 assay,and cell apoptosis was determined by flow cytometry.mRNA sequencing(mRNA-seq)was used to investigate the underlying mechanism of SENP3 knockdown on MCL development.A xenograft nude mouse model was established to evaluate the effect of SENP3 on MCL growth in vivo.Results SENP3 was upregulated in MCL patient samples and cells.Knockdown of SENP3 in MCL cells inhibited cell proliferation and promoted cell apoptosis.Meanwhile,the canonical Wnt signaling pathway and the expression of Wnt10a were suppressed after SENP3 knockdown.Furthermore,the growth of MCL cells in vivo was significantly inhibited after SENP3 knockdown in a xenograft nude mouse model.Conclusion SENP3 participants in the development of MCL and may serve as a therapeutic target for MCL.

Early gastric composite tumor comprising signet-ring cell carcinoma and mucosa-associated lymphoid tissue lymphoma:A case report

BACKGROUND Composite tumors are neoplasms comprising two distinct,yet intermingling,cell populations.This paper reports a rare phenomenon where early gastric signet-ring cell carcinoma(SRCC)and gastric mucosa-associated lymphoid tissue(MALT)lymphoma coexist within the same lesion.CASE SUMMARY A 40-year-old woman presented to the West China Hospital for examination,which revealed a whitish,shallow,and uneven mucosal lesion in the stomach.The lesion was diagnosed as a poorly differentiated adenocarcinoma,including SRCC with atypical lymphoid hyperplasia associated with Helicobacter pylori infection,based on histopathological examination of the biopsy specimen.The lesion was excised using segmental gastrectomy.However,histological exami-nation of the surgical specimen confirmed that it was a poorly differentiated gastric adenocarcinoma with features of SRCC and MALT lymphoma.These two entities were stage I and coexisted in the same lesion.CONCLUSION It is uncommon for gastric SRCC and MALT lymphoma to coexist without distinct borders.Surgical resection is effective for these lesions.

Monomorphic epitheliotropic intestinal T-cell lymphoma with bone marrow involved: A case report

BACKGROUND Monomorphic epithelial intestinal T-cell lymphoma(MEITL)is a rare type of peripheral T-cell lymphoma.The clinical manifestations are diarrhea,abdominal pain,perforation and an abdominal mass.CASE SUMMARY We present a 52-year-old female patient who was diagnosed with MEITL.Further disease progression was observed after multiline chemotherapy.Eventually,the patient died of a severe infection.CONCLUSION MEITL is a rare intestinal primary T-cell lymphoma with aggressive behavior,a high risk of severe life-threatening complications,and a poor prognosis.

Diagnostic and management challenges in primary cutaneous anaplastic large cell lymphoma with necrosis,inflammation,and surgical intervention:A case report

BACKGROUND Primary cutaneous anaplastic large cell lymphoma(PC-ALCL)poses significant diagnostic difficulties due to its similarity in the appearance of skin lesions with chronic inflammatory disorders and other dermatological conditions.This study aims to investigate these challenges by conducting a comprehensive analysis of a case presenting with PC-ALCL,emphasizing the necessity of accurate differentiation for appropriate management.CASE SUMMARY An 89-year-old female patient with diabetes and hypertension presented with arm and abdominal ulcerated mass lesions.Diagnostic procedures included skin biopsies,histopathological assessments,and immunohistochemistry,complemented by advanced imaging techniques to confirm the diagnosis.The patient’s lesions were determined as PC-ALCL,characterized by necrosis,chronic inflammation,and a distinct immunophenotypic profile,including CD30,CD3,CD4,and EBER,CD56,MUM-1,Ki 67-positive in>80%of tumor cells,CD10,but negative for anaplastic lymphoma kinase,CD5,CD20,PAX-5,Bcl-2,Bcl-6,CD8,and CD15.Recurrence was not reported at the 6-month follow-up.CONCLUSION Accurate PC-ALCL differentiation from similar conditions is crucial for effective management and requires a multidisciplinary approach.

NUCLEOLAR ORGANIZER REGIONS IN CUTANEOUS T CELL LYMPHOMAS

The present work studied the application of AgNOR count to differential diagnosis between cutaneous T cell lymphoma (CTCL) and cutaneous pseudolymphoma (CPL). Paraffin sections from 50 mycosis fungoides (22 MFI-Premycotic stage, 24 MF Ⅰ infiltrative stage and 4 MF Ⅲ - tumor stage), 2 nonepidermotropic cutaneous T cell lymphoma (NECTCL) and 9 CPL were investigated. In each case, 200 cells randomly selected were examined using a × 100 oil immersion lens. The mean number, standard deviation and standard error of the mean of AgNOR counts were as follows: MFⅠ 1.17±0.09, SEM = 0.01; MⅡ 1.17±0.01, SEM = 0.01; MF Ⅲ. 3.55±0.87, SEM = 0.43; NECTCL 4.5±0.28, SEM -0.199; CPL 1.17±0.1, SEM ± 0.03. The results revealed a highly significant difference between CTCL (MFⅢ+NECTCL) and CPL (t = 4.75, P<0.001), tumor stage (MF Ⅲ) and pretumor stage (MFI, MF Ⅱ) of mycosis fungoides (t = 4.75, P<0.001). Thus. AgNOR count is valuable in differential diagnosis.

Programmed cell death protein-1 inhibitor combined with chimeric antigen receptor T cells in the treatment of relapsed refractory non- Hodgkin lymphoma: A case report

BACKGROUND Chimeric antigen receptor T cell(CART)therapy has benefited many refractory lymphoma patients,but some patients experience poor effects.Previous studies have shown that programmed cell death protein-1(PD-1)inhibitors can improve and prolong the therapeutic effect of CAR-T cell treatment.CASE SUMMARY A 61-year-old male presented with 15-d history of diarrhea and lower-limb edema.A large mass was detected in the pelvis,and pathology indicated non-Hodgkin diffuse large B-cell lymphoma.After three cycles of the R-CHOP chemotherapeutic regimen,the patient showed three subcutaneous nodules under the left armpit and both sides of the cervical spine.Pathological examination of the nodules indicated DLBCL again.The patient was diagnosed with relapsed and refractory diffuse large B-cell lymphoma.We recommended CAR-T cell treatment.Before treatment,the patient’s T cell function and expression of immune detection points were tested.Expression of PD-1 was obviously increased(52.7%)on cluster of differentiation(CD)3+T cells.The PD-1 inhibitor(3 mg/kg)was infused prior to lymphodepleting chemotherapy with fludarabine and cyclophosphamide.CAR-CD19 T cells of 3×10^(6)/kg and CAR-CD22 T cells 1×10^(6)/kg were infused,respectively.The therapeutic effect was significant,and the deoxyribonucleic acid copy numbers of CAR-CD19 T cells and CAR-CD22 T cells were stable.Presently,the patient has been disease-free for more than 12 mo.CONCLUSION This case suggests that the combination of PD-1 inhibitors and CAR-T cellsimproved therapeutic efficacy in B-cell lymphoma.

Refractory lymphoma treated with chimeric antigen receptor T cells combined with programmed cell death-1 inhibitor:A case report

BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is a common aggressive non-Hodgkin's lymphoma(NHL),accounting for 30%-40%of adult NHL.Primary testicular(PT)lymphoma is an uncommon extranodal disease representing approximately 1%-2%of lymphoma.Approximately 30%–40%of patients are refractory to frontline therapy or relapse after complete remission.Refractory DLBCL responds poorly to other lines of chemotherapy,and experiences short-term survival.CASE SUMMARY We present a 41-year-old male patient who was diagnosed with PT-DLBCL.Further disease progression was observed after multiline chemotherapy.Chimeric antigen receptor T cells(CAR-T)therapy salvaged the patient.Unfortunately,a new mass was observed in the right adrenal area after six months.The patient was administered programmed cell death protein-1(PD-1)inhibitor therapy and maintained progression-free survival at more than 17 mo of follow-up.CONCLUSION Our findings support the potential benefit of CAR-T combined with PD-1 inhibitor therapies in this type of relapsed and refractory PT-DLBCL.

Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography evaluation of subcutaneous panniculitis-like T cell lymphoma and treatment response

Subcutaneous panniculitis-like T cell lymphoma(SPTCL) is a very rare variant of non-Hodgkin's lymphoma. Currently, there is no standard imaging method for staging of SPTCL nor for assessment of treatment response. Here, we describe our use of fluorine-18 fluorodeoxyglucose(FDG) positron emission tomography/computed tomography(PET/CT) for staging and monitoring of treatment response in 3 cases of SPTCL. Primary staging by PET/CT showed that all 3 patients had multiple foci in the subcutaneous fat tissue, with SUVmax from 10.5 to 14.6. Involvement of intra-abdominal fat with high SUVmax was identified in 2 of the patients. Use of the triple drug regimen of gemcitabine, cisplatin and methylprednisolone(commonly known as "GEM-P") as first-line therapy or second-line therapy facilitated complete metabolic response for all 3 cases. FDG PET/CT provides valuable information for staging and monitoring of treatment response and can reveal occult involvement of the intraabdominal visceral fat. High FDG uptake on pre-treatment PET can identify patients with aggressive disease and help in selection of first-line therapy.

Chidamide based combination regimen for treatment of monomorphic epitheliotropic intestinal T cell lymphoma following radical operation:Two case reports

BACKGROUND Monomorphic epitheliotropic intestinal T cell lymphoma(MEITL)is a rare extranodal T-cell lymphoma that has uniformly aggressive features with a poor prognosis.No standardized treatment protocols have been established.Previous experience has demonstrated favorable outcomes with combination chemotherapy followed by autologous hematopoietic stem cell transplant.However,many patients are unable to tolerate the toxicities.Chidamide is a new histone deacetylase inhibitor that has shown preferential efficacy in mature T-cell lymphoma.CASE SUMMARY We herein present two cases of MEITL who were both intermediate risk according to enteropathy-associated T cell lymphoma prognostic index.Case one was a 61-year-old man.He complained of upper abdominal pain and intermittent black stool for 2 mo.Imaging examination revealed that the intestinal wall was thickened.He received a partial excision of the small intestine.A chidamidebased combination regimen was given postoperatively.Eleven months later,he presented with recurrence in the bilateral lungs.He passed away 15 mo after his diagnosis.Case two was a 35-year-old woman who complained of abdominal distention for 1 mo.Positron emission tomography/computed tomography demonstrated wall thickening of the small intestine and upper sigmoid colon.Colon perforation and septic shock occurred on the fourth day of her admission.She was treated by sigmoid colostomy.Chidamide-based combination therapy was then provided.She was recurrence-free for 6 mo until lesions were found in the bilateral brain and lived for 17 mo since her diagnosis.Compared to historical data,chidamide seems to improve the prognosis of MEITL slightly.CONCLUSION MEITL is a type of aggressive lymphoma.Chidamide is a new promising approach for the treatment of MEITL.

Imbalance of Circulating Follicular Regulatory and Follicular Helper T Cell Subpopulations Is Associated with Disease Progression and Serum CYFRA 21-1 Levels in Patients with Non-small Cell Lung Cancer

Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their significance.Methods Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy controls.Flow cytometry was used to detect TFH cell subpopulation based on programmed death 1(PD-1)and inducible co-stimulator(ICOS),and TFR cell subpopulation based on cluster determinant 45RA(CD45RA)and forkhead box protein P3(FoxP3).The levels of interleukin-10(IL-10),interleukin-17a(IL-17a),interleukin-21(IL-21),and transforming growth factor-β(TGF-β)in the plasma were measured,and changes in circulating B cell subsets and plasma IgG levels were also analyzed.The correlation between serum cytokeratin fragment antigen 21-1(CYFRA 21-1)levels and TFH,TFR,or B cell subpopulations was further explored.Results The TFR/TFH ratio increased significantly in NSCLC patients.The CD45RA^(+)FoxP3^(int) TFR subsets were increased,with their proportions increasing in stages Ⅱ to Ⅲ and decreasing in stage IV.PD-1^(+)ICOS+TFH cells showed a downward trend with increasing stages.Plasma IL-21 and TGF-β concentrations were increased in NSCLC patients compared with healthy controls.Plasmablasts,plasma IgG levels,and CD45RA^(+)FoxP3^(int) TFR cells showed similar trends.TFH numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages Ⅰ-Ⅲ and negatively correlated with CYFRA 21-1 in stage IV.Conclusion Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC,which is associated with serum CYFRA 21-1 levels and reflects disease progression.

Sustained Remission with Mogamulizumab in Peripheral T Cell Lymphoma with Aberrant CD20 Expression: Case Report and Literature Review

A 82-year-old man presented with an enlarged multiple superficial lymph nodes. The histological diagnosis of lymph node was peripheral T cell lymphoma, not otherwise specified (PTCL-NOS), with an aberrant expression of CD20. Generally, PTCL lacks B cell antigen such as CD19 or CD20, however, rare cases have been reported in the literature that showed PTCL patients expressing the B cell antigens. It is considered that the prognosis of CD20 positive PTCL is poor, however, standard therapy has not been established. He was treated with eight cycles of CHOP regimen, but the enlargement of a part of lymph nodes still remained. Recently, it is reported that C-C Chemokine receptor type 4 (CCR4) is known to be expressed about 50% case of PTCL and CCR4 target therapy is effective. Our case was positive for CCR4 so mogamulizumab (anti-CCR4 antibody) was administered. Consequently, dramatic response was obtained and its combination of these therapy resulted in complete remission for 24 months. This is the first case of sustained remission by administration of mogamulizumab against CCR4/CD20 double positive PTCL. This strategy may be benefit to obtain the good prognosis.

Primary Cutaneous Gamma Delta T Cell Lymphoma: A Clinicopathological Analysis

Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) is a very uncommon and extremely aggressive tumor, and is described in the newly re-vised World health organization for research and treatment of cancer classification of cutaneous lymphomas. A 43-year-old male patient presented with a 4 months history of cutaneous lesion over upper lip, without plaque and any constitutional symptom. Histopathological examination of skin biopsy revealed infiltration of atypical lymphocytes with hyperchromatic irregular nuclei. Immunophenotyping pattern of skin biopsy was compatible with PCGD-TLC. It is a highly aggressive tumor resistant to chemotherapy, immunotherapy, and radiation therapy. The GDTCL is characterized by a worse prognosis with a median survival of 15 months. Early diagnosis is essential and aggressive therapy is necessary.

Primary cutaneous anaplastic large cell lymphoma with overexpressed Ki-67 transitioning into systemic anaplastic large cell lymphoma:A case report

BACKGROUND Primary cutaneous anaplastic large cell lymphoma(PC-ALCL)differs from systemic anaplastic large cell lymphoma(sALCL)in cell biological behavior,clinical features,treatment,and outcome.PC-ALCL has been reported to rarely transition into sALCL,but the underlying mechanism is not clear.Here we report such a case with certain characteristics that shed light on this.CASE SUMMARY Herein,we report a 43-year-old male with symptoms of a skin nodule and histologically confirmed PC-ALCL with high expression of Ki-67.After three months of observation,two skin nodules re-appeared with muscle layer involvement and was histologically confirmed as sALCL.Seventeen months after receiving six cycles of CHOP regimen,the patient had pain in the chest and back,cough,shortness of breath,and night sweats.This was confirmed as relapse of sALCL by immunohistochemistry and several organs,such as the lung were involved as shown by positron emission tomography/computed tomography.After four cycles of DICE plus chidamide regimens followed by auto-hematopoietic stem cell transplantation(ASCT),complete remission(CR)duration was achieved for twelve months while the patient was on maintenance with chidamide(20 mg)pills.CONCLUSION This case had significantly high expression of Ki-67 when diagnosed as PC-ALCL initially and then transitioned into sALCL,which is rare.Auto-ASCT combined with demethylation drugs effectively maintained CR and prolonged progression free survival.

Diffuse large B-cell lymphoma successfully treated with amplified natural killer therapy alone: A case report

BACKGROUND The prognosis of patients with advanced diffuse large B-cell lymphoma(DLBCL)is poor,with a 5-year survival rate of approximately 50%.The mainstay of treatment is multidrug combination chemotherapy,which has been associated with serious side effects.Amplified natural killer(ANK)cell therapy amplifies and activates natural killer(NK)cells to attack only malignant tumors.As ANK cells attack programmed death ligand 1(PD-L1)-positive tumor cells,ANK therapy is considered effective against adult T-cell lymphoma and malignant lymphoma.CASE SUMMARY Herein,we report a case of an older patient with advanced DLBCL who was successfully treated with ANK immunotherapy.A 91-year-old female visited our hospital with sudden swelling of the right axillary lymph node in April 2022.The patient was diagnosed with stage II disease,given the absence of splenic involvement or contralateral lymphadenopathy.ANK therapy was administered.Six rounds of lymphocyte sampling were performed on July 28,2022.To reduce the occurrence of side effects,the six samples were diluted by half to obtain 12 samples.Cultured NK cells were administered twice weekly.The treatment efficacy was evaluated by performing computed tomography and serological tests every 1 or 2 mo.The treatment suppressed lesion growth,and the antitumor effect persisted for several months.The patient experienced mild side effects.PD-L1 immunostaining was positive,indicating that the treatment was highly effective.CONCLUSION ANK therapy can be used as a first-line treatment for malignant lymphoma;the PD-L1 positivity rate can predict treatment efficacy.

Synchronous rectal adenocarcinoma and intestinal mantle cell lymphoma:A case report

BACKGROUND Mantle cell lymphoma(MCL)of the gastrointestinal tract is a rare malignancy,accounting for about 0.2%of malignant colorectal tumors.MCL synchronous with rectal adenocarcinoma is extremely rare.We know of only a few cases reported in the literature.We describe the case of a patient with synchronous rectal adenocarcinoma and intestinal MCL.CASE SUMMARY A 63-year-old man was admitted to our hospital due to abdominal pain and hematochezia over the past month.The patient was diagnosed with middle rectal cancer cT2N0M0 and underwent surgery.However,we found a large tumor in the small intestine during surgery.The patient underwent total mesorectal excision for rectal cancer and resectioning of the ileal segment containing the large mass.Pathology and immunohistochemistry revealed the presence of both rectal adenocarcinoma and pathognomonic MCL stage IIE presenting as multiple lymphomatous polyposis.The patient subsequently underwent RDHAP/RCHOP chemotherapy and was maintained with rituximab.A Positron Emission Tomography and Computed Tomography(PET/CT)scan showed that the disease responded well to treatment without tumor-increased metabolism in the gastrointestinal tract.CONCLUSION Synchronous rectal adenocarcinoma and intestinal MCL presenting as multiple lymphomatous polyposis are extremely rare.MCL is often discovered fortuitously when rectal cancer is diagnosed.The coexistence of these tumors poses treatment challenges.

Subpopulations of regulatory T cells are associated with subclinical atherosclerotic plaques,levels of LDL,and cardiorespiratory fitness in the elderly

Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early interventions.There is evidence that regulatory T cells(Tregs)are involved in the development of atherosclerosis.Therefore,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated signatures.Methods:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking medication.Ultrasound of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed.Additionally,tests were conducted to assess blood lipids and determine glucose levels.Immunophenotyping of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow cytometry.Participants were categorized according to atherosclerotic plaque status.Linear and logistic regression models were used to analyze associations between parameters.Results:SAP was detected in a total of 29 participants.The participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(OR)=1.20(95%confidence interval(95%CI):1.011.42))and mTregs(OR=1.05(95%CI:1.021.10))as independent risk factors for SAP.Stepwise linear regression could reveal an association of peak oxygen uptake(β=0.441),low-density lipoprotein(LDL)(β=0.096),and SAP(β=6.733)with mTregs and LDL(β=0.104)with rTregs.Conclusion:While at an early stage of SAP,the total proportion of Tregs gives no indication of vascular changes,this is indicated by a shift in the Treg subgroups.Factors such as serum LDL or cardiopulmonary fitness may be associated with this shift and may also be additional diagnostic indicators.This could be used to initiate lifestyle-based preventive measures at an early stage,which may have a protective effect against disease progression.

Milk fat globule membrane supplementation protects againstβ-lactoglobul-ininduced food allergy in mice via upregulation of regulatory T cells and enhancement of intestinal barrier in a microbiota-derived short-chain fatty acids manner

Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.

Endoscopic features and prognoses of mantle cell lymphoma with gastrointestinal involvement

AIM: To evaluate the endoscopic manifestations and prognoses of gastrointestinal (GI) mantle cell lymphoma (MCL). METHODS: A database search at the Department of Pathology of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences revealed 57 MCL patients with GI involvement. Clinical records were available for 35 of the 57 patients from 21 institutions, and those 35 patients were enrolled in this study. We summarized the gross types of endoscopic features, event-free survival (EFS), and overall survival (OS) of those patients.RESULTS: Of the 35 patients, GI involvement in the esophagus, stomach, and duodenum was found in 2 (5.7%), 26 (74.3%), and 12 (34.3%) patients, respectively. Twenty-one of the 35 patients underwent colonoscopy; among them, GI involvement in the ileum, cecum, colon, and rectum was found in 10 (47.6%), 3 (14.3%), 12 (57.1%), and 10 (47.6%), respectively. Various lesions, such as superficial, protruded, fold thickening, or ulcerative, were found in the stomach, whereas multiple lymphomatous polyposis (MLP) was dominant from the duodenum to the rectum. Twelve patients were treated with a hyper-CVAD/MA regimen, and they had better OS (3-year rate, 88.3% vs 46.4%, P < 0.01) and better EFS (3-year rate, 66.7% vs 33.8%, P < 0.05) than the remaining 23 patients who were not treated with this regimen. CONCLUSION: MLP was a representative form of intestinal involvement, whereas a variety of lesions were found in the stomach. The hyper-CVAD/MA regimen may improve survival in these patients.

The Value of γδ T Cells in Lung Infections and Advances in Diagnosis and Treatment

Lung infections are usually caused by pathogenic microorganisms and are a disease with high morbidity and mortality. In clinical practice, the use of broad-spectrum antibiotics has become increasingly common, but this has also led to the problem of antibiotic abuse and irrational use, which in turn has spawned the emergence of multidrug-resistant bacteria, making the treatment of lung infections more complex and difficult. In the human immune system, γδ T cells play a crucial role in defense against foreign pathogens and regulation of autoimmune responses. These cells act as a bridge between innate and adaptive immunity and can be rapidly activated in the early stages of infection to produce inflammatory factors and chemokines that attract other immune cells to the site of infection. Recent advances have shown that γδ T cells not only play a direct role in the innate immunity of pathogen infection, but are also involved in regulating the subsequent adaptive immune response. The aim of this review is to explore the mechanism of γδ T cells in lung infections and to summarize the current progress of clinical research, with the aim of providing new scientific basis and therapeutic strategies for the treatment of lung infections.