Fruquintinib plus oxaliplatin combined with S-1 (SOX) as neoadjuvant therapy for locally advanced gastric cancer (GC) or gastro-oesophageal junction adenocarcinoma (GEJ): a multicentre, phase II, single-arm, open-label clinical trial (FRUTINEOGA) protocol.

INTRODUCTION: Curing locally advanced gastric cancer (GC) or gastro-oesophageal junction adenocarcinoma (GEJ) with surgery alone is challenging. Neoadjuvant chemotherapy (NCT) has become the standard treatment for patients with locally advanced GC/GEJ, and SOX is the most common neoadjuvant regimen in China. The generally good tolerability in patients and fruquintinib's low potential for drug-drug interaction suggest that it may be highly suitable for combinations with other antineoplastic therapies. A combination of fruquintinib, S-1 and oxaliplatin can be a promising neoadjuvant treatment for locally advanced GC/GEJ. In this phase II study, we aim to investigate the efficacy and toxicity of fruquintinib plus SOX as neoadjuvant treatment for locally advanced GC/GEJ. METHODS AND ANALYSIS: The FRUTINEOGA trial is a prospective, multicentre, phase II, single-arm, open-label clinical trial that will enrol 54 patients. Eligible patients will be registered, enrolled and receive 2-4 cycles of fruquintinib plus SOX, after which surgery will be performed and tumour regression will be evaluated. The primary endpoint is the pathological remission rate, and the secondary endpoints are disease-free survival, overall survival, objective response rate, major pathological response rate and R0 resection rate. ETHICS AND DISSEMINATION: Written informed consent will be required from all patients enrolled, and it will be provided by them. The study protocol received approval from the independent ethical review committee of Guangxi Medical University Cancer Hospital, Wuming Hospital of Guangxi Medical University and Wuzhou Red Cross Hospital, Wuzhou Gongren Hospital (approval number: CS2021(96)). We will submit the finalised paper for publication on completing the analyses. This study will provide valuable insights to clinicians regarding the safety and efficacy of incorporating fruquintinib into SOX as neoadjuvant treatment for locally advanced GC/GEJ. The findings have the potential to inform future research proposals and may guide the use of fruquintinib in the neoadjuvant setting for locally advanced GC/GEJ. TRIAL REGISTRATION NUMBER: NCT05122091.

Advances in diagnosis, treatment and prognostic factors of gastrointestinal DLBCL.

Gastrointestinal diffuse large B-cell lymphoma (GI-DLBCL) is an extremely aggressive form of B-cell non-Hodgkin lymphoma (BNHL) which has complex histological characteristics and manifests a high degree of heterogeneity in terms of clinical, morphological, immunological, and genetic features. GI-DLBCL mainly spreads by infiltrating neighboring lymph nodes, and common gastrointestinal complications (GICS) such as obstruction, perforation, or bleeding, frequently arise during the progression of the disease, posing significant challenges in both diagnosing and treating the condition. Meanwhile, the incidence of GI-DLBCL has been gradually increasing in recent years, and its strong invasiveness makes it prone to being misdiagnosed or completely missed. In clinical practice, over half of the patients diagnosed with the disease are in stage III or stage IV. What makes it worse is that certain patients may not exhibit a favorable response to chemotherapy. All these lead to intricacies in management of this disease. Unfortunately, there is currently no large prospective study or evidence-based medical evidence to provide clear guidance on treatment decisions for this specific type of lymphoma. Neither do physicians have a consensus regarding the optimal approach to address this condition. Recent studies have identified the presence of various prognostic factors that significantly impact survival in GI-DLBCL, which demonstrates the unique particularity of GI-DLBCL, and could help optimize the clinical decision.

Clinical Features of Trousseau Syndrome With Cerebral Infarction as the Initial Manifestation.

OBJECTIVE: There are few reports of Trousseau syndrome with cerebral infarction as the initial manifestation before the discovery of the tumor, which is often missed and misdiagnosed, and there is no unified therapy. To explore the clinical features of the Trousseau syndrome and, among those features, the risk factors for cerebral infarction as the initial manifestation. METHODS: This was a retrospective study of 416 consecutive patients with cerebral infarction and malignant tumor admitted at The First Affiliated Hospital of Xinxiang Medical University between January 2015 and December 2017. The patients were grouped as: (1) cerebral infarction as the initial manifestation; and (2) tumor as the initial manifestation. A multivariable logistic regression analysis was used to analyze the relationship between the clinical features (age, sex, characteristics of the infarction, characteristics of the tumors, treatments, depression, coagulopathy, The National Institute of Health stroke scale score, platelet count, red cell count, hemoglobin, atherosclerosis, and coagulation parameters) and the hypercoagulable state. RESULTS: A total of 416 patients met the criteria were included: 212 (51.0%) in the group with cerebral infarction as the initial manifestation and 204 (49.0%) in the group with tumor as the initial manifestation. The multivariable analysis showed that metastatic cancer (odds ratio=2.517; 95% confidence interval, 1.193-5.311; P=0.015) and depressive state (odds ratio=3.158; 95% confidence interval, 1.522-6.551; P=0.002) were independently associated with the Trousseau syndrome with cerebral infarction as the main manifestation. CONCLUSIONS: Trousseau syndrome with cerebral infarction as the initial manifestation was associated with metastatic cancer and depressive state. There was no difference in coagulation status between the 2 groups.

Intracerebral Hemorrhage Induced Brain Injury Is Mediated by the Interleukin-12 Receptor in Rats.

BACKGROUND: IL-12 inhibition of the endothelial cell functions and angiogenesis is mediated by the cross-talk between the lymphocyte and the endothelial cells, which plays a key role in inhibiting the process of angiogenesis in the eyeballs and in malignant tumors. METHODS: We established the intracerebral hemorrhage (ICH) rat model, and IL-12 receptor beta monoclonal antibody was injected into the ICH rats. Western blot, immunofluorescence and RT-qPCR were used to detect the gene expression. Brain water content, EB staining, Garcia test, Beam walking test and wire hanging test were used to assess the injury of brain in ICH rats. RESULTS: IL-12 gene was significantly increase in hematoma border tissue of ICH rats, and IL-12 protein mainly localized in monocytes. Anti-IL-12 treatment with IL-12 monoclonal antibodies could not only significantly decrease the brain water content and EB content in brain tissues of ICH rats, but also significantly increase the score of the Garcia, Beam balance and the Wire hanging test in ICH rats. Moreover, anti-IL-12 treatment significantly decrease the expression of pro-inflammatory gene, inflammatory gene, p-JAK2/JAK2 and p-STAT4/STAT4 protein, but significantly increase the expression anti-inflammatory gene and CD31 protein, and M2 macrophage ratio in hematoma border tissues of ICH rats. In vitro, rmIL-12 inhibited the tube formation of brain microvascular endothelial cells (BMVES) in BMVES and bone marrow-derived monocytes (BMDM) co-culture systems, but not work in a separately cultured BMVES system. In addition, Fedratinib not only reduced p-JAK2/JAK2 and p-STAT4/STAT4 protein expression in BMDM after treating with b-FGF and rmIL-12, but also significantly increased the tube formation of BMVES in BMVES and BMDM co-culture systems after treating with b-FGF and rmIL-12. CONCLUSION: Blockade of IL-12 receptor attenuated brain injury after ICH in rat by promoting angiogenesis, and the mechanism might be related to blocking IL-12 could inhibit M2 cell activation via the JAK2/STAT4 pathway.

Neuroprotective Effects of Umbilical Cord-Derived Mesenchymal Stem Cells on Radiation-Induced Brain Injury in Mice.

OBJECTIVE: To investigate the neuroprotective effects of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on radiation-induced brain injury (RIBI). METHODS: Thirty female C57BL/6 mice were randomly divided into three groups: control (CON), whole brain irradiation (WBI), and the cell therapy (MSC) group. Mice in the WBI and MSC groups received a single, whole brain irradiation treatment with 15 Gy of 60Co. Learning and memory were evaluated in the mice using the step-down avoidance test. The neuronal changes in the hippocampal cornu ammonis (CA) 1 region were observed using hematoxylin eosin (H&E) staining. The changes in astrocytes were visualized with glial fibrillary acidic protein immunohistochemistry, and the expression of TNF-α, IL-6, and IL-10 was detected by quantitative polymerase chain reaction (qPCR) along with Enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with mice in the WBI group, learning and memory in the MSC mice were significantly increased (P<0.05), neuronal degeneration and necrosis were significantly decreased (P<0.05), and the number of astrocytes was significantly increased (P<0.05). The levels of the in˙ammatory cytokines, TNF-α and IL-6, were significantly decreased (P<0.05), however, the inhibitory factor IL-10 was significantly increased (P<0.05). CONCLUSIONS: UC-MSCs play a neuroprotective role by inhibiting brain cell injury and neuroinflammation.

Polyphenols from blueberries modulate inflammation cytokines in LPS-induced RAW264.7 macrophages.

Polyphenols including 3-glucoside/arabinoside/galactoside-based polymers of delphinidins, petunidins, peonidins, malvidins and cyanidins are one type of biological macromolecules, which are extraordinarily rich in blueberries. Anti-inflammatory activity of blueberry polyphenols (BPPs) was investigated by using lipopolysaccharide (LPS) induced RAW264.7 macrophages. The results showed that BPPs suppressed the gene expression of IL-1ß (interleukin-1ß), IL-6 and IL-12p35. The inhibition effect on IL-1ß and IL-6 mRNA was most obvious at the concentration of 10-200µg/mL BPPs. But the inhibition effect on IL-12p35 mRNA was increased with the increasing concentration of BPPs. When fixed at 100µg/mL BPPs, the most significant inhibition on IL-1ß, IL-6 and IL-12p35 mRNA expression was detected at 12-48h. In conclusion, BPPs exhibit anti-inflammation activity by mediating and modulating the balances in pro-inflammatory cytokines of IL-1ß, IL-6, and IL-12.

Associations of genetic polymorphisms of SAA1 with cerebral infarction.

BACKGROUND: Serum amyloid A protein (SAA) is both an inflammatory factor and an apolipoprotein. However, the relation between genetic polymorphisms of SAA and cerebral infarction (CI) remains unclear. METHODS AND RESULTS: The previously reported 4 Single Nucleotide Polymorphisms (rs12218, rs4638289, rs7131332, and rs11603089) of SAA1 gene were genotyped by TaqMan method in a case-control study including 287 cerebral infarction patients and 376 control subjects. We found rs12218 CC genotype and rs7131332 AA genotype were more frequent among CI patients than among controls (9.76% versus 3.19%, P = 0.001; 32.75% versus 24.20%; p = 0.017; respectively). After adjustment of confounding factors such as sex, age, smoking, drinking, hypertension, diabetes, and lipids profile, the difference remained significant in rs12218 (P < 0.01, OR = 2.106, 95% CI: 1.811-7.121). CONCLUSION: Genetic polymorphism of SAA1 may be a genetic maker of cerebral infarction in Chinese.