Lymph Node Research Articles

Clinicopathological features and prognosis of mucinous breast carcinoma with a micropapillary structure.

To conduct a comparative analysis of clinicopathological data between mucinous micropapillary breast carcinoma (MUMPC) and pure mucinous carcinoma (PMC) without a micropapillary structure to elucidate the distinctive clinicopathological characteristics of MUMPC and their impact on prognosis. This retrospective analysis included 325 patients diagnosed with mammary mucinous carcinoma admitted to Tianjin Cancer Hospital between July 2014 and December 2019, including 197 patients with MUMPC and 128 patients with PMC without a micropapillary structure. Clinicopathological features were compared, and factors influencing the prognosis of MUMPC were analyzed. Survival analysis was conducted using the Kaplan-Meier method, and univariate and multivariate prognostic analyses for MUMPC were performed using the Cox proportional hazard regression model. The median follow-up period was 76 months. In the MUMPC and PMC groups, the disease-free survival (DFS) rates at 3, 5, and 7 years were 95.4%, 90.4%, 89.8%, and 100%, 98.4%, and 96.9%, respectively, with a statistically significant difference between the two groups (p = 0.009). Tumor, node, and metastasis (TNM) stage, lymph node metastasis, and endocrine treatment were significant factors influencing the prognosis of the MUMPC group (p < 0.001). Multivariate analysis revealed that lymph node metastasis and endocrine therapy were independent prognostic factors in patients with MUMPC (p < 0.001). Compared with PMC, the MUMPC group exhibited a higher prevalence of HER2 (11.2% vs. 3.1%, p = 0.009) and Ki-67 overexpression (79.7% vs. 60.2%, p < 0.001). The lymph node stage is the most crucial clinicopathological feature of MUMPC. Endocrine treatment strategy is an independent risk factor affecting the prognosis of MUMPC.

Mycophenolate Mofetil, an Inhibitor of Inosine Monophosphate Dehydrogenase, and Tofacitinib, a Janus Kinase Inhibitor, Attenuate Airway Inflammation and Hyperresponsiveness in a Mouse Model of Allergic Asthma

Treatment-resistant asthma remains an unresolved clinical problem and a challenge for current medical science. Consequently, there is a growing and urgent need to develop novel or alternative therapeutic options for the treatment of asthma. The research problem raised in this study was to assess and compare mycophenolate mofetil (MMF), an inhibitor of inosine monophosphate dehydrogenase, and tofacitinib (TFB), a Janus kinase inhibitor, for anti-asthmatic properties, and consequently to determine whether these agents may have potential as alternative options for treatment of allergic asthma. For this purpose, we assessed the effect of administration of MMF and TFB on the development of a mouse model of allergic airway inflammation (AAI) and accompanying CD4+ (cluster of differentiation 4) T-cell immune response in the lung-draining mediastinal lymph nodes (MLNs) and lungs, i.e., in the inductive and effector sites, respectively, of the immune response underlying the development of allergic asthma. The results from a histopathological scoring system demonstrated that the administration of MMF and TFB did not prevent or abolish ovalbumin-induced AAI, but strongly attenuated its severity. The pulmonary function tests revealed that the treatment with MMF and TFB significantly reduced methacholine-induced bronchoconstriction. These results indicate that the treatment with TFB and MMF attenuated the development of ovalbumin-induced AAI. The magnitude of the anti-asthmatic effect was comparable between both agents. The study revealed that the impairment of the clonal expansion of effector CD4+ T cells in the MLNs is a critical event in the mechanism underlying the anti-asthmatic effect of MMF and TFB. Apart from this, the findings of the study strongly suggest that the suppression of the interleukin-33/suppression of tumorigenicity-2 signaling pathway may constitute an additional mechanism responsible for producing this effect. In turn, the results indicate that the anti-asthmatic action induced by the studied agents is not mediated by the generation of forkhead box protein 3-expressing CD4+ regulatory T cells. Clinical implication of the results: the results suggest that MMF and TFB may exert anti-asthmatic action, and thus they may be considered therapeutic options for the treatment of allergic asthma cases resistant to conventional/existing treatment.

Immunohistochemical Status Predicts Pathologic Complete Response to Neoadjuvant Therapy in HER2-Overexpressing Breast Cancers.

Human epidermal growth factor receptor 2 (HER2) overexpression (HER2+) is defined by immunohistochemistry (IHC) and in situ hybridization (ISH) as IHC3+ or IHC2+/ISH+. Response differences to neoadjuvant anti-HER2 therapy (NT) in IHC3+ versus IHC2+/ISH+ breast cancer patients are poorly characterized. We explored whether pathologic complete response (pCR) varies by HER2 IHC status. Patients with stage I-III HER2+ breast cancer undergoing NT and surgery between 2013 and 2020 were identified from the National Cancer Database and stratified by IHC status. Breast and nodal pCR were analyzed. Of 40,711 HER2+ patients, 83% were IHC3+ and 17% were IHC2+/ISH+. IHC3+ patients were more likely to be hormone receptor (HR)-negative (33 vs. 21%), have cT3/4 tumors (24 vs. 21%), and be cN+ (52 vs. 47%; all p < 0.0001). Breast conservation rates were similar (each 43%, p = 0.32), although IHC3+ axillary lymph node dissection rates were lower (41 vs. 45%, p < 0.0001). Among all patients, breast pCR was 49%, while nodal pCR was 64%. Compared with IHC2+/ISH+, IHC3+ had higher unadjusted breast (54 vs. 22%, p < 0.0001) and nodal (69 vs. 37%, p < 0.0001) pCR rates. When stratified by HR status, pCR was lower for HR+ disease but remained higher among IHC3+ patients. Analysis of T1cN0 primaries mirrored these trends. In multivariable analysis, IHC3+ remained an independent predictor of breast (odds ratio [OR] 3.91, confidence interval [CI] 3.65-4.19, p < 0.0001) and nodal (OR 3.40, CI 3.12-3.71, p < 0.0001) pCR. HER2 IHC status predicts pCR and may help select breast cancer patients who derive the greatest benefit from NT. These findings provide further evidence that revision of HER2 classification may improve clinical management.

Engineered Immune Constructs Alter Antigen-Specific Immune Tolerance and Confer Durable Protection in Myelin-Driven Autoimmunity.

Autoimmune diseases are broadly characterized as a failure in immune tolerance. In multiple sclerosis (MS), autoreactive immune cells attack the protective myelin sheath lining neurons in the central nervous system. Therapeutic strategies that selectively and durably restore immune tolerance without broad immunosuppression are urgently needed for MS. Our lab has developed assemblies of immune constructs built entirely from myelin antigen (MOG35-55 or PLP139-151) and regulatory innate immune cues (GpG) using layer-by-layer self-assembly. Here, we present mechanistic and translational data showing these assemblies confer therapeutic benefits in a range of clinically relevant disease contexts, including progressive disease in male mice and in relapsing-remitting disease that mimics the intermittent bouts of disease and remission most MS patients initially experience. Here, the antigen component in the complexes is matched to the disease-causing antigen, resulting in a decrease in paralysis in these models. We show that subcutaneous delivery of assemblies durably prevents diseases and drives tolerance by regulatory remodeling of the draining lymph node. Importantly, we show that subcutaneously delivered assemblies recruit and expand antigen-specific regulatory T cells (TREGS) in draining lymph nodes. Finally, we find a shift of these recruited TREGS from a resting to an activated phenotype. Taken together, these data inform the design of therapeutics for antigen-specific tolerance that could combat autoimmunity by exploiting the role of innate pathways in a disease.

How to Do Laparoscopic D3 Lymph Node Dissection with Left Colic Artery and First Sigmoid Artery Preservation in Rectal Cancer

How to Do Laparoscopic D3 Lymph Node Dissection with Left Colic Artery and First Sigmoid Artery Preservation in Rectal Cancer

Adult supratentorial peripheral primitive neuroectodermal tumor with multiple metastases: a case report and literature review

BackgroundIntracranial primitive neuroectodermal tumors (PNETs) are characterized by poorly differentiated, highly malignant, aggressive small round tumor cells originating from the central and peripheral nervous systems.Case presentationA 25-year-old Chinese woman experienced sudden onset headache, vomiting, and severe anemia. Imaging examinations revealed a mass in the left parietal occipital lobe. Following microsurgery, histological confirmation revealed the tumor to be pPNET. Postoperative computed tomography (CT) showed multiple metastases in the lung, liver, and retroperitoneal lymph node. Unfortunately, she died of tumor cachexia 1 month after chemotherapy.ConclusionsDue to the rare presentation of pPNET, pPNET would be misdiagnosed without the histological diagnosis. Here, we aimed to provide clinicians with information about the treatment and relevant literature of pPNET.

Predictors of tolerability for postoperative adjuvant S1 plus docetaxel chemotherapy for gastric cancer: a multicenter retrospective study.

Adjuvant docetaxel plus S1 (DS) chemotherapy after gastrectomy with D2 lymph node dissection is the standard treatment for stage III gastric cancer in Japan; however, some patients are unable to receive adequate drug administration because of the deterioration of their conditions. This study aimed to investigate the correlation between tolerability for postoperative adjuvant DS chemotherapy and prognosis, and the factors affecting tolerability. This retrospective study involved patients with stage III gastric cancer who underwent curative resection between 2018 and 2021 from a multicenter database. Patients with a cumulative dose of docetaxel and S1 greater than 120 and 8400mg/m2, respectively, were considered tolerable. The prognostic impact and factors predicting tolerability were analyzed. Of the 103 patients, the tolerable group comprised of 63 (61%) patients and had a significantly better 3-year recurrence-free survival than the intolerable group (83% vs. 64%, P = 0.02). Among the preoperative factors, only performance status (PS, P = 0.04) was significantly correlated with tolerability in the univariate analysis. Among the postoperative factors, PS (P = 0.001) and perioperative weight loss rate (P = 0.02) were significantly correlated with tolerability in the univariate analysis. The multivariate analysis showed significant differences in the PS (odds ratio [OR]: 4.94, 95% confidence interval [CI] 1.79-14.98, P = 0.002) and weight loss rate (OR: 1.10, 95% CI 1.01-1.21, P = 0.03). Tolerance to postoperative adjuvant DS chemotherapy has a significant prognostic impact. Postoperative PS and perioperative weight loss rates were independent predictors of tolerability.

Case report: Benign lateral neck ectopic thyroid tissue mimicking cervical lymph node metastasis

AbstractWe herein report a rare case of benign lateral neck ectopic thyroid tissue that presentation micmicked cerivcal lymph node metastasis of follicular thyroid cancer and discuss its management pearl.

Lymphadenectomy and chemotherapy are effective treatments for patients with 2023 international federation of gynecology and obstetrics stage IIC-high risk endometrial cancer in Japan.

In early-stage endometrial cancer (EC), the treatment of aggressive histological subtypes (endometrioid carcinoma grade 3, serous carcinoma, clear-cell carcinoma, undifferentiated carcinoma, mixed carcinoma, and carcinosarcoma) is controversial. We aimed to investigate the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stage IC and stage IIC EC according to the 2023 classification. We retrospectively identified patients with FIGO 2023 stage IC, IIC-intermediate risk (IIC-I), and IIC-high risk (IIC-H) EC who underwent adjuvant therapy or observation after surgery at eight medical institutions from 2004 to 2023. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier estimates and univariate and multivariate analyses. The PFS and OS were significantly worse in patients with FIGO 2023 stage IIC-H EC than in those with FIGO 2023 stage IIC-I EC (PFS: p = 0.008 and OS: p = 0.006). According to the FIGO 2023 stage IIC-H classification, lymphadenectomy and chemotherapy resulted in better prognoses regarding both PFS and OS (p < 0.001 for both) than other treatments. Our findings suggest that lymphadenectomy and chemotherapy effectively reduced vaginal stump and lymph node metastases in FIGO 2023 stage IIC-H EC (p < 0.001 and p = 0.008, respectively). Furthermore, in the multivariate analysis, not undergoing lymphadenectomy or chemotherapy were independent predictors of recurrence and poor prognoses in patients with FIGO 2023 stage IIC-H EC (p < 0.001 and p = 0.031, respectively). Lymphadenectomy and chemotherapy resulted in better prognoses regarding both recurrence and survival in patients with FIGO 2023 stage IIC high-risk EC.

Evaluation of prognostic significance of histopathological characteristics and tumor-infiltrating lymphocytes for pancreatic cancer survival

With a 5-year survival of ˂ 10%, pancreatic cancer is one of the leading causes of cancer-related deaths. Given the role of the distribution of tumor-infiltrating lymphocyte (TILs) subtypes in the tumor and its microenvironment in predicting prognosis, the development of new targeted therapies based on T-cell adaptive response has gained considerable attention. This study aimed to examine the peritumoral spread of TILs and its relationship with other prognostic parameters and survival. This study included 60 patients with pancreatic cancer who had undergone surgery with follow-up between 2011 and 2021. Demographic characteristics, tumor histopathological features, peritumoral TILs counts, and intratumoral programmed cell death protein-1 (PD-1) and programmed death ligand − 1 (PD-L1) positivity were evaluated. Furthermore, overall survival and their efficacy in predicting survival according to TNM stage were analyzed. The number of cluster differentiation-3 positive (CD3 P) TILs increased with advancing pathological T stage. CD3 P and CD8 P TIL counts were higher in patients with peripancreatic fatty tissue invasion. Patients with PD-L1 positivity and higher TIL counts had better survival rates. PD-L1-negative patients with a low CD8 positive/total lymph node count (P/T) ratio had a longer survival. Moreover, patients with poorly differentiated tumors with low CD3 P/T and CD8 P/T ratios had a longer survival. The CD3 P/T and CD8 P/T ratios were compatible with the automatic and manual measurements. Age, tumor differentiation, N stage, and peritumoral TIL count and subtype, when evaluated together with the presence of PD-L1 in the tumor tissue, may have prognostic significance for survival in patients with pancreatic cancer.

Bladder Adenocarcinoma in a Constellation of Multiple Site Malignancies: An Unusual Case and Systematic Review

Background and Objectives: Multiple primary malignant tumors represent a small percentage of the total number of oncological cases and can involve either metachronous or synchronous development and represent challenges in diagnosis, staging, and treatment planning. Our purpose is to present a rare case of bladder adenocarcinoma in a female patient with multiple primary malignant tumors and to provide systematic review of the available literature. Materials and Methods: A 67-year-old female patient was admitted with altered general condition and anuria. The past medical history of the patient included malignant melanoma (2014), cervical cancer (2017), colon cancer (2021), obstructive anuria (2023), and liver metastasectomy (2023). Transurethral resection of bladder tumor was performed for bladder tumors. Results: Contrast CT highlighted multiple pulmonary metastases, a poly nodular liver conglomerate, retroperitoneal lymph node, II/III grade left ureterohydronephrosis, and no digestive tract tumor masses. The pathological result of the bladder resection showed an infiltrative adenocarcinoma. Conclusions: The difference between primary bladder adenocarcinoma tumor and metastatic colorectal adenocarcinoma is the key for the future therapeutic strategy. Identification and assessment of risk factors such as viral infection, radiotherapy, chemotherapy, smoking, and genetics are pivotal in understanding and managing multiple primary malignant tumors. Personalized prevention strategies and screening programs may facilitate the early detection of these tumors, whether synchronous or metachronous. The use of multicancer early detection (MCED) blood tests for early diagnosis appears promising. However, additional research is needed to standardize these techniques for cancer detection.

Determining optimal clinical target volume margins based on microscopic extracapsular extension of metastatic nodes in patients with non-small-cell lung cancer after chemotherapy or chemotherapy combined with immunotherapy

BackgroundNo standard has been established for the clinical target volume (CTV) margins of lymph nodes (LNs) in patients with non-small-cell lung cancer (NSCLC) receiving chemotherapy or chemotherapy combined with immunotherapy followed by radiotherapy. This study aimed to discuss the CTV range of NSCLC after chemotherapy or chemotherapy combined with immunotherapy by observing the microscopic extent of tumor spread beyond the LN capsule.MethodsWe retrospectively analyzed the data of 240 patients with stage II and III NSCLC who underwent surgery without neoadjuvant therapy, with neoadjuvant chemotherapy (NAC), or with NAC combined with immunotherapy (NACI). We measured the maximal distance of extracapsular extension (ECE) using a digital microscope, analyzed the correlation between clinicopathological features and ECE distance, and determined the CTV margins of metastatic LN under different treatment methods.ResultsThe ECE distance differed significantly among the three groups (p < 0.001). We determined appropriate margin widths based on a 5% error risk as 3.00, 2.30, and 1.40 mm for direct surgery, NAC, and NACI, respectively. Multivariate analysis revealed that the ECE of metastatic LN correlated with the treatment methods and LN size.ConclusionThe existing CTV delineation standards may increase the radiation toxicity of patients. We believe that different CTV margins should be used for LN in patients with NSCLC receiving different treatments. To ensure 95% coverage of ECE, the gross tumor volume of untreated, chemotherapy-treated, and chemotherapy combined with immunotherapy-treated patients should be expanded by 3.00, 2.30, and 1.40 mm, respectively, to obtain the CTV.

Ultrasound assessment of lymph nodes for staging of gynecological cancer: consensus opinion on terminology and examination technique.

The lymphatic pathway is an important route of metastasis in gynecological malignancy. Therefore, the examination of lymph nodes is an essential part of the ultrasound evaluation in patients with known or suspected gynecological malignancy. The lymph nodes most frequently involved in gynecological malignancy (apart from vulvar cancer) are parietal (retroperitoneal) and visceral abdominopelvic lymph nodes. In advanced disease, more distant lymph-node regions, such as the inguinal, axillary and supraclavicular lymph nodes, can also be involved. The standardized description of lymph nodes has been published previously by the Vulvar International Tumor Analysis (VITA) collaborative group. Herein, a collaborative group of gynecologists and gynecological oncologists with extensive ultrasound experience presents a systematic methodology for ultrasonographic lymph-node assessment performed as part of the locoregional and distant work-up to assess the extent of gynecological malignancy. The aim of this consensus opinion is also to describe the anatomical classification and drainage pathways of the lymphatic system as relevant to the gynecological organs. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Recurrent laryngeal nerve lymph node dissection with subcomplete sealing using advanced bipolar energy device in minimally invasive esophagectomy.

Recurrent laryngeal nerve (RLN) palsy is a complication that must be avoided during esophagectomy. While RLN injury is thought to be caused by thermal spread from electric devices, electric devices are useful to avoid bleeding. When dissecting lymph nodes around RLNs, to seal small vessels, we use subcomplete technique with advanced bipolar. We describe our surgical technique, termed the subcomplete sealing technique, in RLN lymph node dissection. The first step is to perform blunt dissection with forceps on both sides of the esophageal branch near the right RLN. A distance of at least 2 mm from the RLN was preferred. Sealing with advanced bipolar often causes tissue shrinkage, pulling the RLN near the device. To prevent this, sealing should be stopped before reaching completion. Although the sealing was not complete, it was sufficient to seal the small vessels. After subcomplete sealing, the sealed tissues were dissected using laparoscopic scissors. The lymph nodes around left RLN are dissected in the same manner. A total of 76 patients received esophagectomy with the subcomplete technique. Grade IIIa RLN palsy occurred in three cases (3.95%). Over Grade IIIb RLN palsies did not occur. This subcomplete sealing technique can assist surgeons in performing RLN lymph node dissection without bleeding and increasing the rate of RLN palsy.

Identification and Categorization of Technical Errors and Hazard-zones of Robotic versus Laparoscopic total Gastrectomy for Gastric Cancer: A Single Center Prospective Randomized Controlled Study.

The current research aimed to conduct a detailed analysis of intraoperative surgical performance, short-term outcomes, identify and categorize technical errors, and hazard-zones enacted during total gastrectomy performed robotically and laparoscopically by surgeons. Prospective research is needed to determine whether the technical advantages of robotic surgery translate to patient outcomes. Identify and process risk areas in robot-assisted total gastrectomy (RTG) and laparoscopic total gastrectomy (LTG) to get the best patient results. Patients undergoing RTG and LTG were recruited and randomized into the study. Six consultant/attending surgeons participated in this study and all surgical procedures were recorded. The unedited surgical video-recordings were handed over to third-party experts for granular analysis of the procedures using objective clinical human reliability analysis (OC-HRA) for the quality of intraoperative performance, technical errors, intraoperative complications. This study is a single center prospective randomized controlled trial. 82 patients were recruited and participated in this study with 40 cases undergoing RTG and 42 cases for LTG. RTG vs LTG. Determine whether RTG or LTG can provide the better intraoperative technical performance and identify the most hazardous zone (area) during total gastrectomy (TG). The technical errors enacted and identified in the RTG and the LTG were (46.11±5.63 VS 58.79±8.45, P＜0.001) respectively. The highest number of technical errors was identified during the dissection of the supra-pancreatic lymph nodes (Task Zones3, TZ3), including No.5, 7, 8a, 9, 11p, and 12a to complete the nodal clearance around the celiac artery and its trifurcation (7.29±1.88 VS 9.43±2.24, P <0.001) in both RTG and LTG. The number of lymph nodes harvested with RTG was higher than LTG (35.36±7.51 VS 30.54±6.95, P=0.016), especially in the upper margin of the pancreas (13.32±4.17 VS 9.36±3.81, P＜0.001). The total cost of hospitalization in the RTG group cost 3% more than LTG group ($15953.41±3533.91 VS $12198.26±2761.27, P＜0.001). This study offers compelling OC-HRA evidence demonstrating that RTG facilitates significantly superior technical performance compared to LTG. Whether examining short-term clinical outcomes or intraoperative operations, the robotic surgery system consistently outperforms laparoscopic surgery. Lymph node dissection in the supra-pancreatic region emerged as a major hazard zone in both procedures. chictr.org.cn: ChiCTR2000039193.

Combined Use of External Iliac Lymph Node Count and Bone Scintigraphy for PJI Diagnosis: A Prospective Study

Background: The reactive enlargement of external iliac lymph nodes and increased blood flow in the infected region are commonly observed in lower limb infections. We aimed to differentiate between aseptic loosening and periprosthetic joint infection (PJI) after joint replacement surgery by quantifying the number of enlarged external iliac lymph nodes and using bone scintigraphy to monitor blood flow. Methods: We recruited 124 patients undergoing revision surgery for aseptic loosening or PJI. All the patients underwent preoperative dual-energy computed tomography (DECT) imaging for external iliac lymph nodes and bone scintigraphy. The diagnostic value was evaluated using ROC curve analysis. Results: The number of enlarged external iliac lymph nodes was significantly higher in the PJI group than in the aseptic failure group (4.0 versus. 1.0, p value &lt; 0.001). The median affected/unaffected side ratio in the blood pool phase of ECT in the PJI group was 1.49, significantly higher than the aseptic failure group’s median ratio of 1.04 (p value &lt; 0.001). The AUC for diagnosing PJI using the number of enlarged lymph nodes alone was 0.91, and when using the bone scintigraphy blood pool phase alone, the AUC was 0.89. When both metrics were combined, the AUC increased to 0.95, which was higher than the AUCs for the ESR (AUC = 0.83), CRP (AUC = 0.76), and synovial fluid PMN% (AUC = 0.62). Conclusions: Combining the enlargement of the lymph node count with the bone scintigraphy blood pool phase is a promising approach for diagnosing PJI.

IMMUNE DYSREGULATION IN AUTOIMMUNE HEPATITIS: THE ROLE OF AUTOANTIBODIES, T-REG CELLS, AND NOVEL THERAPEUTIC APPROACHES

Introduction. The liver is a crucial immunological tolerogenic organ with a unique ability to generate effective immune responses against hepatotropic pathogens while maintaining both local and systemic immune tolerance to self and foreign antigens. Autoimmune hepatitis (AIH) is an immune-mediated inflammatory liver disease caused by the loss of tolerance to liver-specific antigens, leading to autoimmune liver damage.Aim – to summarize current knowledge on the immunopathogenesis of AIH based on information from open sources.Material and methods. The selection of publications was conducted using databases such as PubMed, Clinical Key Elsevier, Cochrane Library, eBook Business Collection, and Google Scholar, which covered information on the immunopathogenesis of AIH. Literature search was performed using keywords: autoimmune diseases, autoimmune hepatitis, Kupffer cells, autoantibodies to liver microsomal antibodies, and mesenchymal stem cells.Research results. Liver immune regulation is mediated by unique cell populations, including T-reg cells, Kupffer cells, and NK cells, which interact to maintain immune tolerance and regulate inflammation. Deficiency or dysfunction of T-reg cells, along with the activation of Th17 cells, contribute to the development of inflammatory processes and autoimmune liver damage. The quantitative and qualitative composition of immune cells in the liver differs significantly from that in secondary lymphoid organs, such as lymph nodes, spleen, or peripheral blood. The CD8+/CD4+ ratio (3.5:1) of liver T cells contrasts with the 1:2 ratio observed in peripheral blood, lymph nodes, and spleen.Conclusions. AIH is a complex disease with a multifaceted immunopathogenesis. T-reg and MSC-based therapies show promising results in clinical trials; however, further research is needed to optimize these methods and ensure their safe and effective application.

Comprehensive Analysis of the Potential Toxicity of Magnetic Iron Oxide Nanoparticles for Medical Applications: Cellular Mechanisms and Systemic Effects

Owing to recent advancements in nanotechnology, magnetic iron oxide nanoparticles (MNPs), particularly magnetite (Fe3O4) and maghemite (γ-Fe2O3), are currently widely employed in the field of medicine. These MNPs, characterized by their large specific surface area, potential for diverse functionalization, and magnetic properties, have found application in various medical domains, including tumor imaging (MRI), radiolabelling, internal radiotherapy, hyperthermia, gene therapy, drug delivery, and theranostics. However, ensuring the non-toxicity of MNPs when employed in medical practices is paramount. Thus, ongoing research endeavors are essential to comprehensively understand and address potential toxicological implications associated with their usage. This review aims to present the latest research and findings on assessing the potential toxicity of magnetic nanoparticles. It meticulously delineates the primary mechanisms of MNP toxicity at the cellular level, encompassing oxidative stress, genotoxic effects, disruption of the cytoskeleton, cell membrane perturbation, alterations in the cell cycle, dysregulation of gene expression, inflammatory response, disturbance in ion homeostasis, and interference with cell migration and mobility. Furthermore, the review expounds upon the potential impact of MNPs on various organs and systems, including the brain and nervous system, heart and circulatory system, liver, spleen, lymph nodes, skin, urinary, and reproductive systems.

The comparison of clinicopathological characteristics of two distinct manifestations of gastric signet ring cell carcinoma under EUS

ABSTRACT Background and Objectives There are two different endoscopic ultrasonographic manifestations of gastric signet ring cell carcinoma (GSRCC). No studies have been reported on the differences in the clinical profiles of patients based on EUS examination. We aim to study the variations in clinicopathological characteristics between two distinct endoscopic ultrasonographic manifestations of GSRCC. Methods A total of 302 patients with GSRCC confirmed by pathological examination who underwent EUS were enrolled in the study. Based on the endoscopic ultrasonographic features, patients were categorized into two groups: type 1, where the entire layer structure disappeared, and type 2, where the layer structure was still present and appeared lymphomatoid. Clinicopathologic features were collected retrospectively and analyzed. Results Compared with type 2 patients, type 1 patients tended to develop GSRCC at an older age (P = 0.033) and had higher serum levels of tumor markers and were more likely to experience anemia (P &lt; 0.001) and weight loss (P &lt; 0.001) during the disease progression. Significant increases in the tumor size (P &lt; 0.001), thickness of the affected gastric wall (P &lt; 0.001), and depth of tumor invasion (P &lt; 0.001) were observed in type 1 patients. Furthermore, type 1 patients had higher prevalence of affected blood vessels (P &lt; 0.001), nerves (P &lt; 0.001), lymph nodes (P &lt; 0.001), and peritoneal metastasis (P &lt; 0.001). However, no difference was found in the duration of disease between the two groups, and all deficient mismatch repairs were observed in type 1 patients. Conclusions The two distinct endoscopic ultrasonographic manifestations of GSRCC exhibited different clinicopathological characteristics, suggesting that they may represent different subtypes of the disease that require special attention in management strategies.

TCR-CD3 signal strength regulates plastic coexpression of IL-4 and IFN-γ in Tfh-like cells

The development of T follicular helper (Tfh) cells is an ongoing process resulting in the formation of various Tfh subsets. Despite advancements, the precise impact of T cell receptor (TCR) stimulation on this process remains incompletely understood. This study explores how TCR-CD3 signaling strength influences naive CD4+ T cell differentiation into Tfh-like cells and the concurrent expression of interleukin-21 (IL-21), interleukin-4 (IL-4), and interferon-gamma (IFN-γ). Strong TCR-CD3 stimulation induces proliferation and increased IL-21 expression in Tfh-like cells, which exhibit a characteristic phenotype expressing CXCR5 and PD1. The coexpression of IL-4 and IFN-γ in IL-21-producing Tfh-like cells is controlled by the strength TCR-CD3 stimulation; low stimulation favors IL-4, while strong stimulation enhances IFN-γ secretion. Exogenous addition of the effector cytokines IL-21 and IL-4 further modulate cytokine coexpression. These findings highlight the intricate regulatory mechanisms governing cytokine production and plasticity in Tfh-like cells, providing insights into B cell response modulation. In vivo, antigen availability may regulate Tfh cell plasticity, impacting subsequent B cell differentiation, emphasizing the need for further exploration through animal models or antigen-specific Tfh cell analyses in human lymph node biopsies