The pathological roles and potential mechanisms of vascular endothelial growth factor receptor-3 in gastric cancer.

OBJECTIVE: To investigate the roles and underlying mechanisms of vascular endothelial growth factor receptor-3 (VEGFR-3) in gastric cancer (GC). METHODS: VEGFR-3 gene expression profiles in human gastric adenocarcinoma (GAC) tissues were analysed using The Cancer Genome Atlas database. Human GC cell lines and were used for in vitro studies. Mouse models of GC and distant metastasis were used for in vivo studies. Silencing of VEGFR-3 gene expression was achieved using small interfering RNA. RESULTS: VEGFR-3 gene expression was significantly elevated in GAC tissues and GC cells. Higher VEGFR-3 expression was positively correlated with more advanced stages and a greater number of metastatic lymph nodes. In vitro studies in GC cells showed that knockdown of VEGFR-3 gene expression significantly suppressed cell proliferation and migration, but promoted apoptosis. In vivo investigations revealed that silencing of VEGFR-3 gene expression exhibited significant inhibition on tumour growth and metastasis. Further mechanistic studies showed that VEGFR-3 exerted its pathological roles by affecting the key molecules in the apoptotic and epithelial-mesenchymal transition pathways. CONCLUSION: The molecular pathways associated with VEGFR-3-mediated pathological effects could be targets in the development of novel approaches for the diagnosis, prognosis and treatment of GC.

Efficacy of Qingpeng ointment (a Tibetan medicine) for acute gouty arthritis: a multi-center, randomized, double-blind, placebo-controlled trial.

BACKGROUND: This study aims to assess the efficacy and safety of Qingpeng ointment (QPO), a Tibetan medicine for alleviating symptoms in individuals with acute gouty arthritis (AGA). METHODS: This study was a randomized, double-blind, placebo-controlled trial that involved individuals with AGA whose joint pain, as measured on a visual analog scale (VAS) from 0 to 10, was equal to or greater than 3. The participants were randomly assigned to either the QPO or the placebo group and received their respective treatments twice daily for seven consecutive days. In case of intolerable pain, the participants were allowed to use diclofenac sodium sustained-release tablets as a rescue medicine. The primary outcomes measured were joint pain and swelling, while the secondary outcomes included joint mobility, redness, serum uric acid levels, C-reactive protein levels, and the amount of remaining rescue medicine. Any adverse events that occurred during the trial were also recorded. RESULTS: A total of 203 cases were divided into two groups, with balanced baselines: 102 in the QPO group and 101 in the placebo group. For joint pain, differences between the groups were notable in the VAS scores [1.75 (0, 3.00) versus 2.00 (1.00, 3.50); P = 0.038], changes in VAS [5.00 (3.00, 6.00) versus 4.00 (2.00, 6.00); P = 0.036], and disappearance rate [26.47% compared to 15.84%; P = 0.046] after treatment. Concerning joint swelling, significant between-group differences were observed in the VAS scores [1.00 (0, 2.30) versus 2.00 (0.70, 3.00); P = 0.032] and disappearance rate [33.33% compared to 21.78%; P = 0.046] at treatment completion. The QPO group exhibited a statistically significant mobility improvement compared to the placebo group (P = 0.004). No significant differences were found in other secondary outcomes. Five patients, four from the QPO group and one from the other, encountered mild adverse events, primarily skin irritation. All of these cases were resolved after dosage reduction or discontinuation of the medication. CONCLUSIONS: Compared to the placebo, QPO exhibits positive effects on AGA by alleviating pain, reducing swelling, and enhancing joint mobility, without causing significant adverse effects. TRIAL REGISTRATION: ISRCTN34355813. Registered on 25/01/2021.

Primary adenomatoid tumor of the adrenal gland: A case report and literature review.

RATIONALE: Adenomatoid tumors are rare benign tumors, mainly involving the reproductive tract, such as the epididymis in men and the uterus and fallopian tubes in women. However, a few cases can occur outside the reproductive tract. Herein, we report a rare case of a primary adenomatoid tumor of the adrenal gland. PATIENT CONCERNS: A 50-year-old man underwent ultrasound examination and was found to have a right adrenal mass without elevated blood pressure, weakness after fatigue, frequent nocturnal urination urgency, pain, or a history of hematuria. The patient's general health was normal. Computed tomography revealed a polycystic mixed-density lesion in the right adrenal region, approximately 7.3 × 4.5 cm in size. DIAGNOSES: Based on the clinical information, morphological features, and immunohistochemistry results, a pathological diagnosis of primary adenomatoid tumor of the adrenal gland was made. INTERVENTION: Excision of the right adrenal gland and tumor through the 11 ribs. OUTCOMES: The patient's postoperative course was uneventful. LESSONS: Preventing misdiagnosis adenomatoid tumors with other types of adrenal gland tumors or metastatic tumors is imperative. Morphological and immunohistochemical features can help diagnose primary adenomatoid tumors of the adrenal gland.

Warthin-like papillary renal cell carcinoma: A case report.

BACKGROUND: Warthin-like papillary renal cell carcinoma (WPRCC) has been described as a rare pathological subtype of papillary renal cell carcinoma in the 2022 World Health Organization Classification of the Urinary and Male Reproductive System. Herein we report a case of WPRCC in the left kidney. CASE SUMMARY: Physical examination of a previously healthy 47-year-old woman revealed a lump in her left kidney, 4.5 cm × 3.5 cm × 3.5 cm in size. Based on the clinical information, imaging data, histmorphological features, and immunohistochemistry results, the pathological diagnosis was WPRCC in left kidney. CONCLUSION: Resection of the mass in the left kidney was performed and her postoperative course was uneventful.

Primary acinic cell carcinoma of the trachea: A case report and literature review.

RATIONALE: Salivary gland-type acinic cell carcinoma (ACC) is a low-grade malignancy. Primary ACC of the trachea and lungs is rare; here, we describe 1 such case. The histological morphology of tracheal ACC was similar to that of its salivary gland-associated equivalent. Because of its rarity, it is easily misdiagnosed as another type of tracheal or lung tumor. Microscopic analysis of pathological features and immunohistochemistry help diagnose primary ACC of the trachea and lungs. PATIENT CONCERNS: A 33-year-old female complained of shortness of breath and hemoptysis for 2 years, and reported the symptoms to have aggravated over the last 4 months. The patient was admitted to our hospital for further treatment. Enhanced computed tomography revealed a soft tissue density nodule shadow in the trachea, which was approximately 1.3 × 1.2 cm in size. DIAGNOSES: Based on the clinical information, morphological features, and immunohistochemistry, the pathological diagnosis was primary ACC of the trachea. INTERVENTION: The tracheal lesion was resected with an electric snare, electrotomy, freezing, and an argon knife using a rigid bronchoscope. OUTCOMES: The patient's postoperative course was uneventful. LESSONS: It is important to prevent misdiagnosis of this type of tumor as another type of lung tumor. Morphological and immunohistochemical features can be useful in diagnosing primary ACC of the trachea and lungs.

Epithelial-myoepithelial carcinoma of the nasopharynx: A case report and review of the literature.

Background: Epithelial-myoepithelial carcinoma (EMCa) is a rare low-grade malignant tumor that most commonly occurs in the salivary glands, with approximately 320 cases having been reported worldwide. Here, we report the third case of EMCa occurring in the nasopharynx. Rare cases in the breast, pituitary gland, lacrimal gland, nose, paranasal sinus, nasal cavity, trachea and bronchus, lung, and even the pleura mediastinalis have also been reported. Histopathology and immunohistochemistry are useful for confirming the diagnosis of EMCa, which is characterized by biphasic tubular structures composed of inner ductal and outer clear myoepithelial cells and stains for different markers in each layer. However, because of the rarity of EMCa, the clinicopathological characteristics and treatment of these patients remain unclear. Case presentation: We report a rare case of EMCa of the nasopharynx. A 51-year-old man presented with a 5-month history of pain while swallowing and aggravation accompanied by right ear tinnitus lasting for 1 month. Nasopharyngoscopy and magnetic resonance imaging (MRI) of the nasopharynx and neck revealed a 5.6 cm × 3.4 cm × 3.1 cm mass in the nasopharyngeal space, invasion of the right cavernous sinus, and lymph node enlargement in the right retropharyngeal space. On 17 April 2019, based on the histopathological and immunohistochemical features, a final diagnosis of EMCa of the right nasopharynx was made. The patient underwent concurrent chemoradiotherapy (CCRT), and his symptoms were relieved after treatment. On 10 January 2022, nasopharynx MRI and biopsy revealed local recurrence, but chest and abdominal computed tomography (CT) showed no obvious signs of metastasis. The local recurrence-free survival (LRFS) period was 33 months. Conclusion: To the best of our knowledge, this is the third reported case of EMCa in the nasopharynx and the only case of EMCa in the nasopharynx treated with CCRT, and a partial response was achieved. Therefore, to improve the quality of life and prognosis of patients with unresectable tumors, we believe that CCRT is a suitable option. Further clinical observations are required to elucidate the pathophysiology and prognosis of EMCa.

The Prognostic Value of Deficient Mismatch Repair in Stage II-IVa Nasopharyngeal Carcinoma in the Era of IMRT.

In the era of intensity-modulated radiotherapy (IMRT), it is important to analyse the prognostic value of deficient mismatch repair (dMMR) in nasopharyngeal carcinoma (NPC). In this study, in pretreatment biopsies of 69 patients with stage II-IVa NPC, the expression levels of MMR proteins, including MLH1, MSH2, MSH6 and PMS2, were assessed by immunohistochemistry (IHC). The median follow-up time was 37.5 months (3.1-87.4 months). 50.7% of cases (35/69) showed preserved expression of all 4 MMR proteins, which was interpreted as proficient mismatch repair (pMMR). Only 1.5% of cases (1/69) lost expression of all 4 MMR proteins, 26.1% of cases (18/69) have PMS2 loss alone and 21.7% of cases (15/69) lost expression of both PMS2 and MLH1. Thus, 49.3% of cases (34/69) lost expression of one or more MMR proteins, which was interpreted as dMMR. There was no significant difference (P > 0.05) in terms of sex, age, clinical stage, T category, N category or therapy regimens between the dMMR and pMMR groups. The multivariate Cox regression analysis revealed that dMMR was an independent significant prognostic factor for distant metastasis-free survival (DMFS) (dMMR vs pMMR: P = 0.01, HR = 0.25, 95% CI: 0.09~0.75). Therefore, NPC patients with dMMR had significantly superior DMFS compared with patients with pMMR. It can be expected that dMMR will become a new independent prognostic factor for NPC.

Association between red blood cell distribution width and long-term mortality among patients undergoing percutaneous coronary intervention with previous history of cancer.

Background: The number of patients suffering from coronary heart disease with cancer is rising. There is scarce evidence concerning the biomarkers related to prognosis among patients undergoing percutaneous coronary intervention (PCI) with cancer. Thus, the aim of this study was to investigate the association between red blood cell distribution width (RDW) and prognosis in this population.Methods: A total of 172 patients undergoing PCI with previous history of cancer were enrolled in this retrospective study. The endpoint was long-term all-cause mortality. According to tertiles of RDW, the patients were classified into three groups: Tertile 1 (RDW <12.8%), Tertile 2 (RDW ≥12.8% and <13.5%) and Tertile 3 (RDW ≥13.5%).Results: During an average follow-up period of 33.3 months, 29 deaths occurred. Compared with Tertile 3, mortality of Tertile 1 and Tertile 2 was significantly lower in the Kaplan-Meier analysis. In multivariate Cox regression analysis, RDW remained an independent risk factor of mortality (HR: 1.938, 95% CI: 1.295-2.655, p < 0.001). The all-cause mortality in Tertile 3 was significantly higher than that in Tertile 1 (HR: 5.766; 95% CI: 1.426-23.310, p = 0.014).Conclusions: An elevated RDW level (≥13.5%) was associated with long-term all-cause mortality among patients undergoing PCI with previous history of cancer.

Correlation among VEGFR3 gene promoter methylation, protein overexpression, and clinical pathology in early gastric cancer.

BACKGROUND: The occurrence and development of gastric cancer is a multi-factor, multi-stage, multi-gene abnormal accumulation process. Both genetic and epigenetic mechanisms play an important role in the molecular mechanism of gastric cancer. DNA methylation is one of the most studied epigenetic expression mechanisms. To study the correlation between gene promoter methylation status and protein expression of vascular endothelial growth factor receptor 3 (VEGFR3), as well as their association with clinicopathological features in early gastric cancer (EGC) cases. METHODS: Immunohistochemical analysis and methylation-specific PCR (MSP) were used to detect the expression of VEGFR3 protein and methylation status of the VEGFR3 promoter in 50 cases of EGC and their paired normal gastric mucosa tissues. The level of DNA methylation of the VEGFR3 promoter, in situ VEGFR3 protein expression, and the clinicopathological characteristics of EGC patients were statistically analyzed. RESULTS: The positive rate of VEGFR3 protein expression in EGC tumor tissue (60%) was significantly higher than that in the normal gastric mucosa (10%). The detectable methylation frequency of VEGFR3 promoter in EGC tumor tissue (48%) was significantly lower than that in the normal gastric mucosa (85%). As anticipated, the methylation level of the VEGFR3 gene promoter was negatively associated with the overexpression of VEGFR3 protein. In addition, methylation status of the VEGFR3 gene promoter was positively correlated with lymph node metastasis in EGC patients (P<0.05), but was not linked to patients' gender, age, tumor size, degree of differentiation, or tumor invasion depth (P>0.05). CONCLUSIONS: Hypomethylation of the VEGFR3 gene promoter is one of the major mechanisms underlying VEGFR3 gene overexpression in EGC tumor tissues and is related to lymph node metastasis in EGC patients. DNA methylation of VEGFR3 is expected to become a molecular diagnostic and prognostic biomarker for EGC.

Erratum to correlation among VEGFR3 gene promoter methylation, protein overexpression, and clinical pathology in early gastric cancer.

[This corrects the article DOI: 10.21037/tcr.2020.03.74.].

Identification of Sphaeroma terebrans via morphology and the mitochondrial cytochrome c oxidase subunit I (COI) gene.

Sphaeroma terebrans, a wood-boring isopoda, is distributed worldwide in tropical and subtropical mangroves. The taxonomy of S. terebrans is usually based on morphological characteristics, with its molecular identification still poorly understood. The number of teeth on the uropodal exopod and the length of the propodus of the seventh pereopod are considered as the major morphological characteristics in S. terebrans, which can cause difficulty in regards to accurate identification. In this study, we identified S. terebrans via molecular and morphological data. Furthermore, the validity of the mitochondrial cytochrome c oxidase subunit I (COI) gene as a DNA barcode for the identification of genus Sphaeroma, including species S. terebrans, S. retrolaeve, and S. serratum, was examined. The mitochondrial COI gene sequences of all specimens were sequenced and analysed. The interspecific Kimura 2-parameter distances were higher than intraspecific distances and no intraspecific-interspecific distance overlaps were observed. In addition, genetic distance and nucleotide diversity (π) exhibited no differences within S. terebrans. Our results revealed that the mitochondrial COI gene can serve as a valid DNA barcode for the identification of S. terebrans. Furthermore, the number of teeth on the uropodal exopod and the length of the propodus of the seventh pereopod were found to be unreliable taxonomic characteristics for S. terebrans.

Qualitative and quantitative analysis of the major constituents in traditional Chinese medicine Danmu injection using LC-ESI-MS(n) and LC-DAD.

BACKGROUND: Danmu injection, a traditional Chinese medicine (TCM) preparation made from Nauclea officinalis, has been commonly used for the treatment of cold, fever, swelling of throat in China. However, the chemical constituents in Danmu injection have not been clarified yet. OBJECTIVE: a HPLC/DAD/ESI-MS(n) method was developed for qualitative and quantitative analysis of the components in Danmu injection. MATERIALS AND METHODS: The chromatographic separation was performed on a Welch Material XB-C18 (4.6mm × 250mm, 5µm) using gradient elution with acetonitrile (A) and water containing 0.1% formic acid (B) as mobile phase at a flow rate of 1.0 ml/min. RESULTS: Twenty-five compounds, including phenolic acid and phenol glycoside, iridous glycoside and glycoalkaloid were identified or tentatively deduced on the base of their retention behaviors, UV absorption, MS and MS(n) data with those elucidated references or literature. In addition, eleven compounds were simultaneously determined by HPLC-DAD, which was validated and successfully applied for determination of major components in Danmu injection. CONCLUSION: The results suggested that the established qualitative and quantitative method would be a powerful and reliable analytical tool for the characterization of multi-constituent in complex chemical system and quality control of Danmu injection.

[Multi-dimensional structure quality control technology system of Danmu injection based on component structural theory].

Danmu is one of common medicines in folks of Li nationality, with such effects in clearing heat and removing toxicity, antisepsis and anti-inflammation. Danmu injection, which is developed with Danmu herbs, has been clinically applied for years and showed curative efficacy. Currently, though many studies have been conducted to analyze chemical constituents in Danmu in details, its pharmacodynamic material basis related to disease prevention and treatment has not been defined. Furthermore, as the quality control methods for Danmu and its preparations remain restricted to single index component and irrational to some extent, it fails to ensure their inherent quality. On the basis of the summary of previous study results, as well as the "component structural theory" of the material basis, we established a "multi-dimensional structure quality control technology system" that is capable of reflecting the integrity of effects of Danmu injection and component structure hierarchy, and performed a dynamic monitoring over the whole process from medicinal materials and preparation products, so as to ensure the inherent quality of Danmu injection.

Functional coupling reactions of human amylin receptor and nicotinic acetylcholine receptors in rat brain neurons.

Human amylin (hAmylin) is co-released with insulin from pancreatic B-cells and the actions of this peptide on its target tissues maintain the cell excitability and glucose homeostasis. Inappropriate control of hAmylin secretion may result in human disease, particularly Alzheimer's disease (AD). It's unknown that which kind of receptor is activated by human amylin, leading to the neurotoxicity in neurons of brain. Nicotinic acetylcholine receptors (nAChRs) are known to play a critical role in a variety of nervous diseases. In the present study, we sought to determine the inter-relationships between these two receptors by examining the actions of hAmylin and nicotine on whole-cell currents and membrane potential in basal forebrain neurons. Whole cell patch-clamp recordings were performed on enzymatically dissociated neurons of the diagonal band of Broca (DBB), a cholinergic basal forebrain nucleus. The results showed that either hAmylin or nicotine individually caused a dose-dependent (1 nmol/L-20 µmol/L) membrane depolarization and an increase in firing frequency of DBB neurons. Application of AC253, an amylin receptor antagonist, blocked the excitatory effects of not only hAmylin but also nicotine; dihydro-ß-erythroidine (DHßE), a nAChR antagonist, also blocked the effects of nicotine and hAmylin. These electrophysiological results suggest that hAmylin receptor and nAChRs on DBB neurons are coupled and may function in a co-operative manner to influence the excitability of DBB neurons. This finding is important for us to understand the cause and mechanisms of AD.