Detection of thyroglobulin for diagnosis of metastatic lateral cervical lymph nodes in papillary thyroid carcinoma: accuracy and application in clinical practice.

Background: Accurate assessment of lateral cervical lymph node metastasis (LLNM) involvement is important for treating papillary thyroid carcinoma (PTC). Thyroglobulin is associated with LLNM, but there may be differences in the diagnostic value of serum thyroglobulin (sTg) and fine needle aspiration washout fluid thyroglobulin (FNA-Tg). Herein, we investigated the optimal cutoff value (OCV) of sTg and FNA-Tg and their diagnostic performance. Methods: We enrolled 116 PTC patients who underwent radical resection of thyroid carcinoma with lateral cervical lymph node dissection at the Affiliated Hospital of Zunyi Medical University from June 2018 to July 2022. We used the receiver operating characteristic (ROC) curve analysis to determine the OCV for sTg and FNA-Tg to diagnose LLNM in PTC patients. We also evaluated the performance of FNA-Tg, sTg, fine needle aspiration cytology (FNAC), and their combinations for diagnosis. Pathological results were the gold standard. Results: We performed 125 lymph node dissections, 106 had metastasis, and 19 did not. The OCV for sTg was 17.31 ng/mL [area under the curve (AUC) =0.760, sensitivity =78.30%, specificity =73.68%, and accuracy =77.60%]. Meanwhile, the OCV for FNA-Tg was 4.565 ng/mL (AUC =0.948, sensitivity =89.62%, specificity =100%, and accuracy =91.20%). The combination of FNAC and FNA-Tg presented the greatest diagnostic performance for LLNM detection in PTC patients. Moreover, serum antithyroglobulin antibody (TgAb) was not correlated with sTg or FNA-Tg levels. Conclusions: The cutoff value for the diagnosis of LLNM in PTC are sTg >17.31 ng/mL or FNA-Tg >4.565 ng/mL. The combination method of FNA-Tg and FNAC is the most optimal choice for the diagnosis of LLNM and is highly recommended for further clinical application.

SLC26A9 promotes colorectal tumorigenesis by modulating Wnt/ß-catenin signaling.

Solute carrier family 26 member 9 (SLC26A9) is a member of the Slc26a family of multifunctional anion transporters that functions as a Cl- channel in parietal cells during acid secretion. We explored the role of SLC26A9 in colorectal cancer (CRC) and its related mechanisms through clinical samples from CRC patients, CRC cell lines and mouse models. We observed that SLC26A9 was expressed at low levels in the cytoplasm of adjacent tissues, polyps and adenomas but was significantly increased in colorectal adenocarcinoma. Moreover, increased levels of SLC26A9 were associated with a high risk of disease and poor prognosis. In addition, downregulation of SLC26A9 in CRC cells induced cell cycle arrest and apoptosis but inhibited cell proliferation and xenograft tumor growth both in vitro and in vivo. Mechanistic analysis revealed that SLC26A9 was colocalized with ß-catenin in the nucleus of CRC cells. The translocation of these two proteins from the cytoplasm to the nucleus reflected the activation of Wnt/ß-catenin signaling, and promoted the transcription of downstream target proteins, including CyclinD1, c-Myc and Snail, but inhibited the expression of cytochrome C (Cyt-c), cleaved Caspase9, cleaved Caspase3 and apoptosis-inducing factor (AIF). CRC is accompanied by alteration of epithelial mesenchymal transition (EMT) markers. Meanwhile, further studies showed that in SW48 cells, overexpressing SLC26A9 was cocultured with the ß-catenin inhibitor XAV-939, ß-catenin was downregulated, and EMT was reversed. Our study demonstrated SLC26A9 may be responsible for alterations in the proliferative ability and aggressive potential of CRC by regulating the Wnt/ß-catenin signaling pathway.

The effects of metabolism on the immune microenvironment in colorectal cancer.

Colorectal cancer (CRC) is a malignancy that is widely prevalent worldwide. Due to its unsatisfactory treatment outcome and extremely poor prognosis, many studies on the molecular mechanisms and pathological mechanisms of CRC have been published in recent years. The tumor microenvironment (TME) is an extremely important feature of tumorigenesis and one of the hallmarks of tumor development. Metabolic reprogramming is currently a hot topic in tumor research, and studies on this topic have provided important insights into CRC development. In particular, metabolic reprogramming in cancer causes changes in the composition of energy and nutrients in the TME. Furthermore, it can alter the complex crosstalk between immune cells and associated immune factors, such as associated macrophages and T cells, which play important immune roles in the TME, in turn affecting the immune escape of tumors by altering immune surveillance. In this review, we summarize several metabolism-related processes affecting the immune microenvironment of CRC tumors. Our results showed that the immune microenvironment is regulated by metabolic reprogramming and influences the development of CRC.

Chemotherapy combined with endocrine neoadjuvant therapy for hormone receptor-positive local advanced breast cancer: a case report and literature review.

Background: Early studies have revealed antagonistic effects associated with stacking chemotherapy (CT) and endocrine therapy (ET), thereby conventional wisdom does not advocate the simultaneous combination of these two treatment modalities. Limited clinical studies exist on the combined use of neoadjuvant CT (NACT) and neoadjuvant ET (NET), and there are no reported instances of concurrent neoadjuvant treatment for locally advanced breast cancer (LABC) using capecitabine and fulvestrant (FUL). Case presentation: We reported a 54-year-old woman who was diagnosed with hormone receptor-positive (HR+) LABC at our hospital. After neoadjuvant treatment involving two distinct CT regimens did not lead to tumor regression. Consequently, the patient was transitioned to concurrent capecitabine and FUL therapy. This change resulted in favorable pathological remission without any significant adverse events during treatment. Conclusions: A novel approach involving concurrent neoadjuvant therapy with CT and endocrine therapy may offer a potentially effective treatment avenue for some cases with HR+ LABC.

LCN2: Versatile players in breast cancer.

Lipocalin 2 (LCN2) is a secreted glycoprotein that is produced by immune cells, including neutrophils and macrophages. It serves various functions such as transporting hydrophobic ligands across the cellular membrane, regulating immune responses, keeping iron balance, and fostering epithelial cell differentiation. LCN2 plays a crucial role in several physiological processes. LCN2 expression is upregulated in a variety of human diseases and cancers. High levels of LCN2 are specifically linked to breast cancer (BC) cell proliferation, apoptosis, invasion, migration, angiogenesis, immune regulation, chemotherapy resistance, and prognosis. As a result, LCN2 has gained attention as a potential therapeutic target for BC. This article offered an in-depth review of the advancement of LCN2 in the context of BC occurrence and development.

Effect of metabolic reprogramming on the immune microenvironment in gastric cancer.

Gastric cancer (GC) is a malignant tumor of the gastrointestinal tract with a high mortality rate worldwide, a low early detection rate and a poor prognosis. The rise of metabolomics has facilitated the early detection and treatment of GC. Metabolism in the GC tumor microenvironment (TME) mainly includes glucose metabolism, lipid metabolism and amino acid metabolism, which provide energy and nutrients for GC cell proliferation and migration. Abnormal tumor metabolism can influence tumor progression by regulating the functions of immune cells and immune molecules in the TME, thereby contributing to tumor immune escape. Thus, in this review, we summarize the impact of metabolism on the TME during GC progression. We also propose novel strategies to modulate antitumor immune responses by targeting metabolism.

The role of HMGB1 in digestive cancer.

High mobility group box protein B1 (HMGB1) belongs to the HMG family, is widely expressed in the nucleus of digestive mucosal epithelial cells, mesenchymal cells and immune cells, and binds to DNA to participate in genomic structural stability, mismatch repair and transcriptional regulation to maintain normal cellular activities. In the context of digestive inflammation and tumors, HMGB1 readily migrates into the extracellular matrix and binds to immune cell receptors to affect their function and differentiation, further promoting digestive tract tissue injury and tumor development. Notably, HMGB1 can also promote the antitumor immune response. Therefore, these seemingly opposing effects in tumors make targeted HMGB1 therapies important in digestive cancer. This review focuses on the role of HMGB1 in tumors and its effects on key pathways of digestive cancer and aims to provide new possibilities for targeted tumor therapy.

Role of spasmolytic polypeptide-expressing metaplasia in gastric mucosal diseases.

Spasmolytic polypeptide-expressing metaplasia (SPEM) is a trefoil factor 2-expressing metaplasia in the fundic glands that resembles the fundic metaplasia of deep antral glandular cells and arises mainly from transdifferentiation of mature chief cells as well as mucous neck cells or isthmic stem cells. SPEM participates in the regulation of gastric mucosal injury, including focal and diffuse injury. This review focuses on the origin, models, and regulatory mechanisms of SPEM and on its role in the development of gastric mucosal injury. We hope to provide new prospects for the prevention and treatment of gastric mucosal diseases from the perspective of cell differentiation and transformation.

Gastric immune homeostasis imbalance: An important factor in the development of gastric mucosal diseases.

The gastric mucosal immune system is a unique immune organ independent of systemic immunity that not only maintains nutrient absorption but also plays a role in resisting the external environment. Gastric mucosal immune disorder leads to a series of gastric mucosal diseases, including autoimmune gastritis (AIG)-related diseases, Helicobacter pylori (H. pylori)-induced diseases, and various types of gastric cancer (GC). Therefore, understanding the role of gastric mucosal immune homeostasis in gastric mucosal protection and the relationship between mucosal immunity and gastric mucosal diseases is very important. This review focuses on the protective effect of gastric mucosal immune homeostasis on the gastric mucosa, as well as multiple gastric mucosal diseases caused by gastric immune disorders. We hope to offer new prospects for the prevention and treatment of gastric mucosal diseases.

Effect of metabolism on the immune microenvironment of breast cancer.

Breast cancer (BC) is a highly prevalent primary malignancy worldwide with poor prognosis. Despite the development of aggressive interventions, mortality due to BC remains high. BC cells reprogram nutrient metabolism to adapt to the energy acquisition and progression of the tumor. The metabolic changes in cancer cells are closely related to the abnormal function and effect of immune cells and immune factors, including chemokines, cytokines, and other related effector molecules in the tumor microenvironment (TME), leading to tumor immune escape, whereby the complex crosstalk between immune cells and cancer cells has been considered the key mechanism regulating cancer progression. In this review, we summarized the latest findings on metabolism-related processes in the immune microenvironment during BC progression. Our findings showing the impact of metabolism on the immune microenvironment may suggest new strategies for regulating the immune microenvironment and attenuating BC through metabolic interventions.

The mechanisms of gastric mucosal injury: focus on initial chief cell loss as a key target.

Diffuse gastric mucosal injury is a chronic injury with altered cell differentiation, including spasmolytic polypeptide expression metaplasia (SPEM) and intestinal metaplasia (IM), which are considered precancerous lesions of gastric cancer (GC). Previously, most studies have focused on how parietal cell loss causes SPEM through transdifferentiation of chief cells. In theory, alteration or loss of chief cells seems to be a secondary phenomenon due to initial partial cell loss. However, whether initial chief cell loss causes SPEM needs to be further investigated. Currently, increasing evidence shows that initial chief cell loss is sufficient to induce gastric mucosal injury, including SPEM and IM, and ultimately lead to GC. Therefore, we summarized the two main types of models that explain the development of gastric mucosal injury due to initial chief cell loss. We hope to provide a novel perspective for the prevention and treatment of diffuse gastric mucosal injury.

Gastric alarmin release: A warning signal in the development of gastric mucosal diseases.

Alarmins exist outside cells and are early warning signals to the immune system; as such, alarmin receptors are widely distributed on various immune cells. Alarmins, proinflammatory molecular patterns associated with tissue damage, are usually released into the extracellular space, where they induce immune responses and participate in the damage and repair processes of mucosal diseases.In the stomach, gastric alarmin release has been shown to be involved in gastric mucosal inflammation, antibacterial defense, adaptive immunity, and wound healing; moreover, this release causes damage and results in the development of gastric mucosal diseases, including various types of gastritis, ulcers, and gastric cancer. Therefore, it is necessary to understand the role of alarmins in gastric mucosal diseases. This review focuses on the contribution of alarmins, including IL33, HMGB1, defensins and cathelicidins, to the gastric mucosal barrier and their role in gastric mucosal diseases. Here, we offer a new perspective on the prevention and treatment of gastric mucosal diseases.

Significant efficacy of paclitaxel plus carboplatin (TP) as a neoadjuvant regimen for metaplastic squamous cell carcinoma of the breast: a rare case report and literature review.

Background: Metaplastic squamous cell carcinoma of the breast (MSCCB) is a rare and aggressive type of cancer. So far, no standard treatment regimen has been established due to the absence of clinical data. Case Description: We report a case of a 48-year-old female admitted to our hospital as a result of a left breast mass with skin rupture. Core needle biopsy under ultrasonic guidance confirmed MSCCB. Immunohistochemistry revealed negative staining for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor type 2 (HER2/neu). After receiving 4 cycles of paclitaxel and carboplatin neoadjuvant chemotherapy, the patient was treated with modified radical mastectomy. Postoperative pathology revealed a Miller-Payne score of 4 and no metastasis in the axillary lymph nodes (0/13), indicating a good response to neoadjuvant chemotherapy. She recovered well post-surgery and was discharged to home after admission. No recurrence was identified during the 2 years post-surgery follow-up. Conclusions: MSCCB is a rare and aggressive type of cancer. However, the treatment of MSCCB has not been standardized due to its rarity. Given the observation that the majority of patients with MSCCB had ER, PR, HER2-negative neoplasms, we refer to the triple negative breast cancer (TNBC) treatment protocol. TP regimen was demonstrated to be an effective treatment for TNBC. The results of this case suggest that the TP regimen is effective in neoadjuvant chemotherapy of MSCCB.

SLC26A9 deficiency causes gastric intraepithelial neoplasia in mice and aggressive gastric cancer in humans.

BACKGROUND: Solute carrier family 26 member (SLC26A9) is a Cl- uniporter with very high expression levels in the gastric mucosa. Here, we describe morphological and molecular alterations in gastric mucosa of slc26a9-/- mice and in selective parietal cell-deleted slc26a9fl/fl/Atp4b-Cre mice and correlate SLC26A9 expression levels with morphological and clinical parameters in a cohort of gastric cancer (GC) patients. METHODS: The expression patterns of genes related to transport and enzymatic function, proliferation, apoptosis, inflammation, barrier integrity, metaplasia and neoplasia development were studied by immunohistochemistry (IHC), quantitative RT-PCR, in situ hybridization and RNA microarray analysis. SLC26A9 expression and cellular/clinical phenotypes were studied in primary human GC tissues and GC cell lines. RESULTS: We found that both complete and parietal cell-selective Slc26a9 deletion in mice caused spontaneous development of gastric premalignant and malignant lesions. Dysregulated differentiation of gastric stem cells in an inflammatory environment, activated Wnt signaling, cellular hyperproliferation, apoptosis inhibition and metaplasia were observed. Analysis of human gastric precancerous and cancerous tissues revealed that SLC26A9 expression progressively decreased from atrophic gastritis to GC, and that downregulation of SLC26A9 was correlated with patient survival. Exogenous expression of SLC26A9 in GC cells induced upregulation of the Cl-/HCO3- exchanger AE2, G2/M cell cycle arrest and apoptosis and suppressed their proliferation, migration and invasion. CONCLUSIONS: Our data indicate that SLC26A9 deletion in parietal cells is sufficient to trigger gastric metaplasia and the development of neoplastic lesions. In addition, we found that SLC26A9 expression decreases during human gastric carcinogenesis, and that exogenous SLC26A9 expression in GC cells reduces their malignant behavior.

Sentinel Lymph Node Biopsy Mapped With Carbon Nanoparticle Suspensions in Patients With Breast Cancer: A Systematic Review and Meta-Analysis.

Background: The mapping method represents a crucial factor affecting the rate of sentinel lymph node detection in breast cancer. We carried out this meta-analysis to assess the clinical utility of carbon nanoparticle suspensions (CNSs) in guiding sentinel lymph node biopsy (SLNB) for breast cancer patients. Methods: Electronic databases, which comprised the China National Knowledge Infrastructure, the Wanfang electronic database, the Cochrane Library, EMBASE, and PubMed, were explored to identify relevant studies from database inception to July 2021 that studied the detection rate of CNSs-guided SLNB. A meta-analysis was performed to generate pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), a summary receiver operator characteristic curve (SROC), and a diagnostic odds ratio (DOR). Results: A total of 33 publications that enrolled 2,171 patients were analyzed. The pooled sensitivity, specificity, PLR, and NLR were 0.93 (95% CI: 0.91-0.95, I2 = 0.0%), 0.99 (95% CI: 0.98-0.99, I2 = 56.5%), 42.85 (95% CI: 29.73-61.77, I2 = 47.0%), and 0.09 (95% CI: 0.07-0.11, I2 = 0.0%), respectively. The area under the curve (AUC) of the SROC curve was 0.98. There were no significant differences when analyzed based on the dose and site of CNS injection. There was significant publication bias among the included publications based on Deeks' funnel plot [Slope (Bias) = -7.35, P = 0.00]. Nonetheless, the sensitivity analysis identified the results to be reliable and stable. Conclusion: This meta-analysis highlights the accuracy and feasibility of using CNSs for SLNB in patients with breast cancer. Clinically, the identification and predictive values of CNSs as an optimal tracer for SLNB remains undisputed.

Expression alteration and dysfunction of ion channels/transporters in the parietal cells induces gastric diffused mucosal injury.

Gastric mucosal injuries include focal and diffused injuries, which do and do not change the cell differentiation pattern. Parietal cells loss is related to the occurrence of gastric mucosal diffused injury, with two phenotypes of spasmolytic polypeptide-expressing metaplasia and neuroendocrine cell hyperplasia, which is the basis of gastric cancer and gastric neuroendocrine tumor respectively. Multiple ion channels and transporters are located and expressed in the parietal cells, which is not only regulate the gastric acid-base homeostasis, but also regulate the growth and development of parietal cells. Therefore, alteration and dysregulation of ion channels and transporters in the parietal cells impairs the morphology and physiological functions of stomach, resulted in gastric diffused mucosal damage. In this review, multiple ion channels and transporters in parietal cells, including K+ channels, aquaporins, Cl- channels, Na+/H+ transporters, and Cl-/HCO3- transporters are described, and their roles in gastric diffused mucosal injury are discussed. We hope to drive researcher's attention to focus on the role of ion channels/transporters loss in the parietal cells induced gastric diffused mucosal injury.

An extremely dangerous case of acute massive upper gastrointestinal bleeding: a case report.

BACKGROUND: Upper gastrointestinal (GI) bleeding is a severe acute disease of gastroenterology department. Fish bone is the most common food-related foreign body. However, fish bone piercing the esophagus, causing the mediastinal abscess that corroded the left subclavian artery, resulting delayed but high-risk massive upper gastrointestinal bleeding is very rare. CASE PRESENTATION: We report a 54-year-old man who was diagnosed with delayed but high-risk massive upper GI bleeding that was the result of a fish bone piercing the esophagus, causing a mediastinal abscess that corroded the left subclavian artery. He was saved effectively by early and timely multidisciplinary collaboration. CONCLUSION: A fish bone-caused mediastinal abscess that corrodes the left subclavian artery and induces delayed but high-risk massive upper GI bleeding is very rare. In addition to routine consideration of upper GI bleeding, medical history, endoscopy and CT are helpful for achieving a diagnosis. Importantly, early and timely multidisciplinary collaboration can effectively save critically ill patients.

Pathophysiological role of ion channels and transporters in HER2-positive breast cancer.

The incidence of breast cancer (BC) has been increasing each year, and BC is now the most common malignant tumor in women. Among the numerous BC subtypes, HER2-positive BC can be treated with a variety of strategies based on targeting HER2. Although there has been great progress in the treatment of HER2-positive BC, recurrence, metastasis and drug resistance remain considerable challenges. The dysfunction of ion channels and transporters can affect the development and progression of HER2-positive BC, so these entities are expected to be new therapeutic targets. This review summarizes various ion channels and transporters associated with HER2-positive BC and suggests potential targets for the development of new and effective therapies.

Fatty acid ß-oxidation promotes breast cancer stemness and metastasis via the miRNA-328-3p-CPT1A pathway.

MicroRNAs (miRNA) have been shown to be associated with tumor diagnosis, prognosis, and therapeutic response. MiR-328-3p plays a significant role in breast cancer growth; however, its actual function and how it modulates specific biological functions is poorly understood. Here, miR-328-3p was significantly downregulated in breast cancer, especially in patients with metastasis. Mitochondrial carnitine palmitoyl transferase 1a (CPT1A) is a downstream target gene in the miR-328-3p-regulated pathway. Furthermore, the miR-328-3p/CPT1A/fatty acid ß-oxidation/stemness axis was shown responsible for breast cancer metastasis. Collectively, this study revealed that miR-328-3p is a potential therapeutic target for the treatment of breast cancer patients with metastasis, and also a model for the miRNA-fatty acid ß-oxidation-stemness axis, which may assist inunderstanding the cancer stem cell signaling functions of miRNA.

Pathophysiological role of ion channels and transporters in gastrointestinal mucosal diseases.

The incidence of gastrointestinal (GI) mucosal diseases, including various types of gastritis, ulcers, inflammatory bowel disease and GI cancer, is increasing. Therefore, it is necessary to identify new therapeutic targets. Ion channels/transporters are located on cell membranes, and tight junctions (TJs) affect acid-base balance, the mucus layer, permeability, the microbiota and mucosal blood flow, which are essential for maintaining GI mucosal integrity. As ion channel/transporter dysfunction results in various GI mucosal diseases, this review focuses on understanding the contribution of ion channels/transporters to protecting the GI mucosal barrier and the relationship between GI mucosal disease and ion channels/transporters, including Cl-/HCO3- exchangers, Cl- channels, aquaporins, Na+/H+ exchangers, and K+ channels. Here, we provide novel prospects for the treatment of GI mucosal diseases.