Microsatellite stable (MSS) gastric cancer (GC) is largely unresponsive to immunotherapy, presenting a persistent and formidable challenge in the field. Patients with advanced GC and Helicobacter pylori (H. pylori) infection have shown benefits from immunotherapy. However, it remains unreported whether neoadjuvant immunotherapy is beneficial for H. pylori-positive MSS GC patients. This retrospective cohort study analyzed data from GC patients treated at three medical centers in China between January 1, 2014, and July 1, 2024. Patients with gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction underwent testing for H. pylori infection prior to receiving neoadjuvant therapy. In this retrospective analysis, those positive for H. pylori had a higher objective response rate of 63.77

BACKGROUND: Hepatic ischemia-reperfusion(I/R) injury is a major challenge in liver surgery and transplantation. Bromodomain protein 4(BRD4) has emerged as a promising target due to its role in oxidative stress and inflammation. JQ-1, a specific BRD4 inhibitor, has shown protective effects on organs suffering I/R injury. This study aims to investigate the expression of BRD4 in liver tissues after I/R injury and to explore its role in this process using JQ-1 both in vivo and in vitro.METHODS: Our study established a mouse model of hepatic I/R injury and investigated the protective effect of JQ-1. We compared the histological features, BRD4 expression, and liver enzyme levels between JQ-1-treated and untreated groups. Additionally, the antioxidant properties of JQ-1 were analyzed in RAW 264.7 cells by evaluating cytokine expression, NLRP3 inflammasome activity, and reactive oxygen species production.RESULTS: BRD4 was abundantly expressed in liver tissues after hepatic I/R injury, while JQ-1 treatment had antioxidant and hepatoprotective effects. JQ-1 also suppressed pro-inflammatory cytokine release in vitro. Furthermore, we clarified the mechanism by which JQ-1 enhances liver injury recovery through Kupffer cells by blocking the NOD-like receptor thermal protein domain-associated protein 3(NLRP3)/caspase-1 pathway. CONCLUSION: JQ-1 has potential as a pre-clinical emergency therapy for hepatic I/R injury. Its ability to inhibit BRD4 and modulate the inflammatory response in Kupffer cells offers a promising avenue for future clinical intervention.

Abstract Purpose The totally implanted venous access port (TIVAP) is widely applied to chemotherapy. The traditional approach is to implant the port by directly cutting skin at the chest wall, but surgical scarring on the chest wall may bring permanent psychological trauma to patients and affect the port once the incision is infected. In this study, the effect and safety of an improved port implantation (noninvasive chest wall implantation) via the axillary approach on breast cancer patients were evaluated. Methods This study discusses the surgical steps of the improved port implantation. The incidences of complication, comfort, convenience, aesthetics, and privacy from the improved operation were analyzed and compared with the traditional operation. Results All patients successfully presented improved infusion port implantation through the axillary access (noninvasive chest wall implantation). Two cases had a hemorrhage during the operation. One case had a postoperative subcutaneous hemorrhage, and one case had a folded catheter. Nevertheless, the patients did not need a secondary operation for adjustment. The average operation time of the improved infusion port implantation was 51.85 min (range: 37–69 min). The improved operation was significantly better than the traditional operation in terms of aesthetics and privacy. In terms of comfort and convenience, the difference between the two operations was not significant. Conclusions This study described the specific steps and particular aspects of the improved operation. The effectiveness and safety of the improved operation were reported for the first time. The improved operation has been proven safe and reliable, and it entails only a few intraoperative and postoperative complications.

This case report describes about a young patient with right lower quadrant pain initially considered acute appendicitis by imaging scans, which was finally diagnosed as EBV infection. Appendicitis is the most common surgical emergency and is typically accompanied by pain in the right lower quadrant of the abdomen and localized tenderness at McBurney’s point. A 21-year-old male patient was admitted to the hospital with fever and stomach ac he for 2 days. The patient had a high value of infection index, but there was no obvious tenderness in the appendix; therefore, appendicitis could not be diagnosed. Surgical investigation was inevitable, but lesions could not be detected during the procedure; nevertheless, the patient’s family consented to the surgical procedure. Hence, laparoscopic examination and appendectomy were performed under general anesthesia.

Dear editor, Epstein-Barr virus (EBV) infection is common, and more than 90％ of adults develop serum EBV antibodies over the course of life.[1] After the first EBV infection, a long-term latent infection develops, which is followed by B-cell infections in instances when the function of the resistance mechanisms of the body weakens. As a result, clinical manifestations of EBV infection are fever, pharyngitis, lymphadenopathy, and hepatosplenomegaly.[2] EBV rarely causes abdominal pain, but when it does, it often caused mesenteric lymphadenitis, lymphoepithelioma-like carcinoma,[3] or spleen and/or liver involvement and very rarely causes acute appendicitis. Appendicitis caused by EBV has previously been reported as infectious mononucleosis.[4] Appendicitis is the most common surgical emergency and is typically accompanied by pain in the right lower quadrant of the abdomen and localized tenderness at McBurney's point.[5] This case report describes a young patient with right lower quadrant pain initially considered acute appendicitis by imaging scans, which was finally diagnosed as EBV infection.

Background Despite being a common malignant tumor, the molecular mechanism underlying the initiation and progression of triple-negative breast cancers (TNBCs) remain unclear. Tumor-associated macrophages (TAMs) are often polarized into a pro-tumor phenotype and are associated with a poor prognosis of TNBCs. Exosomes, important mediators of cell-cell communication, can be actively secreted by donor cells to reprogram recipient cells. The functions and molecular mechanisms of tumor cell-derived exosomes in TNBCs progression and TAMs reprogramming urgently need to be further explored. Results We demonstrated that tumor cell-derived exosomes enriched with miR-184-3p were taken up by macrophages to inhibit JNK signaling pathway by targeting EGR1, thereby inducing M2 polarization of macrophages and synergistically promoting tumor progression. Nanoparticles loaded with oncogene c-Myc inhibitor JQ1 could suppress the polarization process by reducing Rac1-related exosome uptake by macrophage. More importantly, it was found for the first time that tumor-suppressive miR-184-3p was actively sorted into exosomes by binding to RNA-binding protein heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1), thus facilitating tumor cell proliferation and metastasis by relieving the inhibitory effect of miR-184-3p on Mastermind-like 1 (MAML1). Overexpressing miR-184-3p in tumor cells and simultaneously knocking down hnRNPA2B1 to block its secretion through exosomes could effectively inhibit tumor growth and metastasis. Conclusions Our study revealed that hnRNPA2B1-mediated exosomal transfer of tumor-suppressive miR-184-3p from breast cancer cells to macrophages was an important mediator of TNBCs progression, providing new insights into TNBCs pathogenesis and therapeutic strategies. Graphical Abstract

Bromodomain and extraterminal domain protein inhibitors have shown therapeutic promise in hepatocellular carcinoma. However, resistance to bromodomain and extraterminal domain protein inhibitors has emerged in preclinical trials, presenting an immense clinical challenge, and the mechanisms are unclear. In this study, we found that overexpression of SIRT1 induced by JQ-1, a bromodomain and extraterminal domain protein inhibitor, may confer resistance to JQ-1 in hepatocellular carcinoma. SIRT1 protein expression was higher in hepatocellular carcinoma tissues than in normal tissues, and this phenotype was correlated with a poor prognosis. Cotreatment with JQ-1 and the SIRT1 inhibitor EX527 synergistically suppressed proliferation and blocked cell cycle progression in hepatocellular carcinoma cells. Combined administration of JQ-1 and EX527 successfully reduced the tumor burden in vivo. In addition, JQ-1 mediated AMPK/p-AMPK axis activation to upregulate SIRT1 protein expression and enhanced autophagy to inhibit cell apoptosis. Activation of AMPK could alleviate the antitumor effect of the combination of JQ-1 and EX527 on hepatocellular carcinoma cells. Furthermore, inhibition of SIRT1 further enhanced the antitumor effect of JQ-1 by blocking protective autophagy in hepatocellular carcinoma. Our study proposes a novel and efficacious therapeutic strategy of a BET inhibitor combined with a SIRT1 inhibitor for hepatocellular carcinoma.

Ferroptosis is a unique cell death modality triggered by iron-dependent lipid peroxidation, with cysteine metabolism and glutathione-dependent antioxidant defence responses as the primary triggering mechanisms. Ferroptosis is an independent tumour suppression mechanism and has been implicated in various disorders. In tumourigenesis, ferroptosis plays a dual role in promoting and inhibiting tumours. P53, NFE2L2, BAP1, HIF, and other tumour suppressor genes regulate ferroptosis, releasing damage-associated molecular patterns or lipid metabolites to influence cellular immune responses. Ferroptosis is also involved in tumour suppression and metabolism. The combination of amino acid, lipid, and iron metabolism is involved in the initiation and execution of ferroptosis, and metabolic regulatory mechanisms also play roles in malignancies. Most investigations into ferroptosis in gastric cancer are concentrated on predictive models, not the underlying processes. This review investigates the underlying mechanisms of ferroptosis, tumour suppressor genes, and the tumour microenvironment.

Liver cancer ranks fifth leading malignancy in incidence and third in mortality worldwide. Recently, its comprehensive treatment has greatly progressed; however, the prognosis is still poor due to difficulties in early diagnosis, high recurrence and metastasis rates, and lack of specific treatment. The search for new molecular biological factors that target the early diagnosis of cancer, predict recurrence, evaluate treatment efficacy, and identify high-risk individuals and specific therapeutic targets during follow-up becomes a great urgent task. circSOX4 is upregulated in lung cancer and plays the role of oncogene. This study attempted to assess circSOX4’s role in hepatocellular carcinoma (HCC). HCC tissues and cells were collected to measure circSOX4 level by qRT-PCR, cell behaviors by CCK-8 assay and Transwell assay, and relationship between circSOX4 and downstream targets by dual-luciferase gene assay and RIP. circSOX4 was upregulated in HCC tissue and cell lines, and its level was correlated with reduced patient survival. Interestingly, circSOX4 knockdown reduced HCC behaviors, glucose consumption, and lactate production. Furthermore, circSOX4 knockdown resulted in decreased in vivo tumor growth. circSOX4 was confirmed to target miR-218-5p, and the effect of circSOX4 downregulation on inhibiting tumor growth was diminished after miR-218-5p inhibition or YY1 overexpression in HCC cells. circSOX4 expression is closely associated with HCC through miR-218-5p and YY1-dependent pathways and may be a target and marker for HCC.

Background and purpose: Neutrophil extracellular traps (NETs) are special web-like structures that can be generated in both infectious and noninfectious diseases. Previous studies showed that reactive oxygen species (ROS) were crucial in the formation of NETs (NETosis). The purpose of this study is to evaluate the effect of (+)-borneol, an antioxidant, on NETosis. Methods: Human neutrophils were stimulated with phorbol-12-myristate-13-acetate (PMA) to induce NETosis in vitro . Neutrophils treated with (+)-borneol at three different time points (−30 min, 0, and 30 min) associated with PMA stimulation were used to examine the effect of (+)-borneol on the formation of NETs. The ROS generation of neutrophils was also measured to explore the potential mechanism of the inhibitory effect of (+)-borneol on NETosis. Results: (+)-Borneol pretreatment inhibited NETosis induced by PMA. Immunofluorescence staining visualized and confirmed the inhibitory effect. (+)-Borneol inhibited the burst of ROS in neutrophils caused by PMA. Suppressing NADPH oxidase or protein kinase C (PKC) eliminated the effect of (+)-borneol on NETosis. Moreover, inhibiting Toll-like receptor 2 (TLR2) led to increased NETosis which can be inhibited by (+)-borneol. Conclusion: (+)-Borneol decreases the ROS level in activated neutrophils and inhibits NETosis triggered by PMA stimulation in vitro . (+)-Borneol therapy may be effective in some NET-dependent conditions.

Different components of the mulberry tree (fruits, leaves, twigs, and roots) are rich in active compounds, and have been reported to possess potent beneficial properties, including antioxidative, anti-inflammatory, antimicrobial, anticancer, anti-allergenic, antihypertensive, and neuroprotective. The mulberry and its extracts can effectively improve the growth performance and fitness of animals. They not only possess the properties of being safe and purely natural, but also they are not prone to drug resistance. According to the literature, the supplemental level of the mulberry and its extracts in animal diets varies with different species, physiological status, age, and the purpose of the addition. It has been observed that the mulberry and its extracts enhanced the growth performance, the quality of animal products (meat, egg, and milk), the antioxidant and the anti-inflammatory responses of animals. Furthermore, the mulberry and its extracts have antibacterial properties and can effectively moderate the relative abundance of the microbial populations in the rumen and intestines, thus improving the immunity function of animals and reducing the enteric methane (CH4) production in ruminants. Furthermore, the mulberry and its extracts have the potential to depurate tissues of heavy metals. Collectively, this review summarizes the nutrients, active compounds, and biological functions of mulberry tree products, as well as the application in livestock production with an aim to provide a reference for the utilization of the mulberry and its extracts in animal production.

Sepsis-associated encephalopathy is a common brain diseases, presenting severe diffuse brain dysfunction. The umbilical cord mesenchymal stem cells have been reported to have protective role for treating diseases, while its role in sepsis-associated encephalopathy remained elusive. This brief report investigated the therapeutic effect of umbilical cord mesenchymal stem cells on sepsis-associated encephalopathy in mice model and uncovering the underlying mechanism. The sepsis-associated encephalopathy mice were injected with 3 mg/kg lipopolysaccharide. An enzyme-linked immunosorbent assay was carried out to determine the production of inflammatory cytokines. Morris water maze test was used to evaluate mice's neurological dysfunction. Cell apoptosis and tissue injury of the cerebral cortex were assessed using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and HE staining. Evans Blue leakage detection was used to examine the blood-brain barrier integrity. The protein levels were determined using Western blot. Results showed that the productions of inflammatory cytokines including interleukin 6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), and high mobility group box protein 1 (HMGB1) and activated NF-κB were increased in sepsis-associated encephalopathy mice, which were decreased by umbilical cord mesenchymal stem cells treatment. Besides, umbilical cord mesenchymal stem cells inhibited lipopolysaccharide-induced cell apoptosis and neuron injury of the cerebral cortex in sepsis-associated encephalopathy mice. Moreover, cognitive dysfunction was observed in sepsis-associated encephalopathy mice, which was alleviated by umbilical cord mesenchymal stem cells. Furthermore, umbilical cord mesenchymal stem cells activated PI3K/AKT signaling pathway. In conclusion, umbilical cord mesenchymal stem cells alleviated inflammation, cell apoptosis and neuron injury of the cerebral cortex, and cognitive dysfunction in sepsis-associated encephalopathy animal model in a PI3K/AKT dependent pathway, making them to be a promising therapeutic strategy for treating sepsis-associated encephalopathy.

It is crucial to identify potential molecular targets and their interaction involved in myocardial infarction (MI). In our study, we obtained microarray data of MI from GEO database and identify differentially expressed mRNAs and microRNAs (miRNAs). Compared with normal tissues, 686 mRNAs and 16 miRNAs were differentially expressed in MI. Subsequently, function enrichment analysis was performed to further investigate their biological functions. Also, gene set enrichment analysis indicated they were enriched into Pathway in cancer. Besides, protein-protein interaction analysis was performed to assess the interactions of the differentially expressed mRNAs. Finally, we constructed an mRNA-miRNA interaction network based on the overlapping genes between the differentially expressed mRNAs and predicted target genes of dysregulated miRNAs. The network demonstrated three MI-associated miRNAs, miR-498, miR-181a, and miR-612, and 45 novel target genes, as well as their interaction involved in MI. What is more, in vitro and in vivo quantitative real-time PCR confirmed our results were consistent. In conclusion, miR-498, miR-181a, and miR-612 may participate in the pathogenesis of MI and may serve as the potential therapeutic targets or biomarkers.

目的:评估血清生长和分化因子15(GDF-15)与营养状态的相关性,为胃癌术后患者发生营养不良的临床诊疗提供新的临床思路和治疗靶点.方法:收集2019年3月—2020年3月收治的胃癌患者78例,根据TNM分期分为早期胃癌组和进展期胃癌组,分别在术前、术后14 d、术后30 d时收集两组患者的营养状态指标及GDF-15水平.用NRS-2002评分和PG-SGA评分评估患者的营养状态.结果:术后14 d时两组总白蛋白、白蛋白、前白蛋白均较术前降低(<0.05),而GDF-15、NRS-2002评分和PG-SGA评分均显著高于术前(<0.05).术后30 d时早期胃癌组的营养状态较术后14 d有所恢复,但进展期胃癌组总白蛋白、白蛋白、前白蛋白仍低于术后14 d(<0.05),GDF-15、NRS-2002评分和PG-SGA评分均显著高于术后14 d(<0.05).相关性分析结果显示术后14 d和术后30 d的GDF-15与前白蛋白显著负相关(=-0.872、-0.895,<0.05),与NRS-2002评分、PG-SGA评分正相关(=0.262、0.401和0.551、0.436,<0.05),在术后30 d时GDF-15与总蛋白质和白蛋白也表现出负相关性(=-0.598、-0.503,<0.05).结论:胃癌术后患者GDF-15水平与前白蛋白和PG-SGA评分密切相关,营养状态越差,GDF-15水平越高,因此GDF-15可以作为评估胃癌患者术后营养状态的潜在生物标志物.

Tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) play an important role in the development of tumors by secreting a variety of cytokines or directly communicating with tumor cells, making TAMs-targeted therapeutic strategies very attractive. It has been reported that oncogene c-Myc is related to every aspect of the oncogenic process of tumor cells and the alternative activation of macrophages. Hence, we constructed a glycolipid nanocarrier containing ROS-responsive peroxalate linkages (CSOPOSA) for ROS-triggered release of drugs and further modified it with Ex 26 (Ex 26-CSOPOSA), a selective sphingosine 1-phosphate receptor 1 (S1PR1) antagonist, to achieve the dual-targeted delivery of the c-Myc inhibitor JQ1 via S1PR1, which is overexpressed on both tumor cells and TAMs, thereby inducing apoptosis of tumor cells, and blocking M2 polarization of macrophages. More strikingly, our studies found that JQ1 could effectively inhibit the migration of tumor cells induced by M2 macrophages-derived exosomes via blocking Caveolin-1 related intercellular exosome exchange through lncRNA H19 and miR-107. The in vivo results revealed that this dual-targeted delivery strategy effectively inhibited tumor growth and metastasis with less systemic toxicity, providing a potential method for effective tumor treatment.

OBJECTIVE:Hypoxic/ischemic brain damage (HIBD) results in increased neonatal mortality and serious neurologic morbidity. Long noncoding RNAs (lncRNAs) are shown as essential modulators of various neurological diseases. Here, we determined the mechanisms of lncRNA GAS5 in mitochondrial apoptosis in HIBD rats.METHODS:The HIBD neonatal rat model was established and treated with shRNA-GAS5 or antagomir miR-128-3p. The morphological changes and apoptosis rate were observed by histological staining. Expressions of GAS5, miR-128-3p, and Bax mRNA in brain tissues of HIBD neonatal rats were determined. The binding relationships between GAS5 and miR-128-3p, and miR-128-3p and Bax were confirmed by dual-luciferase assay. Subsequently, the mitochondrial membrane potential and apoptosis-related factors in brain tissues of HIBD neonatal rats were detected. Western blot analysis was performed to detect the expression of Akt/GSK3β pathway-associated proteins.RESULTS:The neurons in the brain tissue of HIBD neonatal rats decreased with disordered arrangement, and showed vacuolization and nuclear pyknosis, obvious brain damage, increased neuronal apoptosis, and enhanced mitochondrial apoptotic pathway. Downregulated miR-128-3p and upregulated GAS5 and Bax mRNA were found in HIBD neonatal rats. There were binding relationships between GAS5 and miR-128-3p, and miR-128-3p and Bax mRNA. Inhibition of lncRNA GAS5 in HIBD neonatal rats suppressed mitochondrial apoptosis. miR-128-3p knockdown annulled the inhibitory effect of inhibiting lncRNA GAS5 on mitochondrial apoptosis. Silencing GAS5 increased the phosphorylation levels of Akt and GSK3β.CONCLUSION:Downregulation of lncRNA GAS5 prevents mitochondrial apoptosis in neonatal HIBD rats by regulating the miR-128-3p/Bax/Akt/GSK-3β axis.

A bee sting can lead to an extremely rare case of visual loss caused by central retinal artery occlusion (CRAO). In this study, we report a 66-year-old healthy woman who was referred to our Eye Center because of visual loss, which had occurred after bee sting 2 days earlier. The visual acuity was no light perception (NLP). Examination revealed left eyelid edema, conjunctiva congestion, a 6-mm fixed pupil, scattered retinal hemorrhage, and white-appearing ischemic retina with one small area of the normal-appearing retina temporal to the optic disk. Fundus fluorescein angiography revealed CRAO with one cilioretinal artery sparing. Her systemic workup revealed hypersensitivity, hypercoagulable state, myocardial damage, and hepatic damage. After topical and systemic treatments, the visual acuity was still NLP with improved systemic workup. In brief, CRAO may occur after bee sting, and visual acuity should be monitored for early diagnosis.

Abstract Objective This investigation was carried out with an aim of exploring neuroprotection by naringin (Nar) in rats with cerebral ischemia-reperfusion (CI/R) injury and its mechanism. Methods Rats were grouped into ischemia-reperfusion (I/R), sham operation (Sham), nimodipine control (NIM), and different doses of Nar (Nar-L, Nar-M, Nar-H) groups. With Zea Longa score for assessment of neurological deficits, dry and wet method for measurement of brain tissue water content, and (2,3,5-triphenyltetrazolium chloride) TTC staining for determination of cerebral infarction volume, the related parameters were obtained and compared. Subsequently, ELISA was introduced to detect levels of proinflammatory cytokines (TNF-α, IL-8) and anti-inflammatory cytokine (IL-10) in the serum as well as superoxide dismutase (SOD) and malondialdehyde (MDA) activities in brain tissue. Western blot was applied to evaluate endoplasmic reticulum stress (ERS)-related proteins expression, including glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), caspase-12, and activating transcription factor 6 (ATF-6). Results Nar significantly alleviated nerve injury and decreased brain tissue water content and brain infraction volume in CI/R injury rats in a concentration-dependent manner. Reduction of TNF-α, IL-8 as well as MDA content and elevation of IL-10 as well as SOD activity were confirmed to be caused by Nar treatment in a concentration-dependent manner. Meanwhile, ERS-related proteins also markedly decreased in the Nar groups. Conclusion Nar may achieve neuroprotection and alleviation of CI/R injury by anti-inflammation, anti-oxidation, and inhibiting ERS, and its efficacy is concentration-dependent.

Epidemiologic studies have shown that in the aging society, a person dies from stroke every 3 minutes and 42 seconds, and vast numbers of people experience depression around the globe. The high prevalence and disability rates of stroke and depression introduce enormous challenges to public health. Accumulating evidence reveals that stroke is tightly associated with depression, and both diseases are linked to oxidative stress (OS). This review summarizes the mechanisms of OS and OS-mediated pathological processes, such as inflammation, apoptosis, and the microbial-gut-brain axis in stroke and depression. Pathological changes can lead to neuronal cell death, neurological deficits, and brain injury through DNA damage and the oxidation of lipids and proteins, which exacerbate the development of these two disorders. Additionally, aging accelerates the progression of stroke and depression by overactive OS and reduced antioxidant defenses. This review also discusses the efficacy and safety of several antioxidants and antidepressants in stroke and depression. Herein, we propose a crosstalk between OS, aging, stroke, and depression, and provide potential therapeutic strategies for the treatment of stroke and depression.