Comparison of vonoprazan and proton pump inhibitors for the treatment of gastric endoscopic submucosal dissection-induced ulcer: an updated systematic review and meta-analysis.

BACKGROUND: Both vonoprazan and proton pump inhibitors (PPIs) are currently used to treat artificial ulcers after gastric endoscopic submucosal dissection. However, evidence-based medicine proving the efficacy of vonoprazan is still lacking. Therefore, this meta-analysis aimed to compare the efficacy of vonoprazan and PPIs for the treatment of artificial ulcers after gastric endoscopic submucosal dissection. METHODS: The PubMed, EMBASE and Cochrane Library databases were searched up to September 2023 for related randomized controlled trials (RCTs). RCTs that compared the efficacy of vonoprazan and PPIs in treating artificial gastric ulcers after gastric endoscopic submucosal dissection were included. Two independent reviewers screened the included studies, extracted the data and assessed the risk of bias. The following outcomes were extracted for comparison: ulcer healing rate, ulcer shrinkage rate, delayed postoperative bleeding rate, and ulcer perforation rate. RESULTS: Nine randomized controlled trials involving 926 patients were included. The pooled results showed that vonoprazan had a significantly lower rate of delayed postoperative bleeding than did PPIs (RR = 0.46; 95% CI = 0.23-0.91; P = 0.03). No significant differences were found in terms of ulcer healing, shrinkage rates, or ulcer perforation rates between vonoprazan and PPIs. CONCLUSIONS: Compared with PPIs, vonoprazan is superior at reducing delayed postoperative bleeding after endoscopic submucosal dissection. However, further studies are needed to prove the efficacy of vonoprazan. SYSTEMATIC REVIEW REGISTRATION: Identifier CRD42024509227.

Obliteration of portal venules contributes to portal hypertension in biliary cirrhosis.

The effects of the obliteration of portal venules (OPV) in cirrhotic portal hypertension are poorly understood. To investigate its contribution to portal hypertension in biliary cirrhosis and its underlying mechanism, we evaluated OPV using two-dimensional (2D) histopathology in liver explants from patients with biliary atresia (BA, n = 63), primary biliary cholangitis (PBC, n = 18), and hepatitis B-related cirrhosis (Hep-B-cirrhosis, n = 35). Then, three-dimensional (3D) OPV was measured by X-ray phase-contrast CT in two parallel models in rats following bile duct ligation (BDL) or carbon tetrachloride (CCl4) administration, representing biliary cirrhosis and post-necrotic cirrhosis, respectively. The portal pressure was also measured in the two models. Finally, the effects of proliferative bile ducts on OPV were investigated. We found that OPV was significantly more frequent in patients with biliary cirrhosis, including BA (78.57 ± 16.45%) and PBC (60.00 ± 17.15%), than that in Hep-B-cirrhotic patients (29.43 ± 14.94%, p < 0.001). OPV occurred earlier, evidenced by the paired liver biopsy at a Kasai procedure (KP), and was irreversible even after a successful KP in the patients with BA. OPV was also significantly more frequent in the BDL models than in the CCl4 models, as shown by 2D and 3D quantitative analysis. Portal pressure was significantly higher in the BDL model than that in the CCl4 model. With the proliferation of bile ducts, portal venules were compressed and irreversibly occluded, contributing to the earlier and higher portal pressure in biliary cirrhosis. OPV, as a pre-sinusoidal component, plays a key role in the pathogenesis of portal hypertension in biliary cirrhosis. The proliferated bile ducts and ductules gradually take up the 'territory' originally attributed to portal venules and compress the portal venules, which may lead to OPV in biliary cirrhosis. © 2024 The Pathological Society of Great Britain and Ireland.

The association between cholecystectomy and the risk of colorectal cancer: an updated systematic review and meta-analysis of cohort studies.

Background: The effect of cholecystectomy on the development of colorectal cancer (CRC) has prompted a large number of population-based studies. However, the results of these studies are debatable and inconclusive. Our aim in the present study was to conduct an updated systematic review and meta-analysis to explore the causality between cholecystectomy and CRC. Methods: Cohort studies published in the PubMed, Web of Science, Embase, Medline, and Cochrane databases up to May 2022 were retrieved. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were analyzed using a random effects model. Results: Eighteen studies, involving 1,469,880 cholecystectomy and 2,356,238 non-cholecystectomy cases, were eligible for the final analysis. Cholecystectomy was not associated with the development of CRC (P=0.109), colon cancer (P=0.112), or rectal cancer (P=0.184). Subgroup analysis of sex, lag period, geographic region, and study quality revealed no significant differences in the relationship between cholecystectomy and CRC. Interestingly, cholecystectomy was significantly associated with right-sided colon cancer (RR =1.20, 95% CI: 1.04-1.38; P=0.010), especially in the cecum, the ascending colon and/or the hepatic flexure (RR =1.21, 95% CI: 1.05-1.40; P=0.007) but not in the transverse, descending, or sigmoid colon. Conclusions: Cholecystectomy has no effect on the risk of CRC overall, but a harmful effect on the risk of right-sided colon cancer proximally.

Highly Sensitive Imaging of Tumor Metastasis Based on the Targeting and Polarization of M2-like Macrophages.

Tumor-associated macrophages, especially M2-like macrophages, are extensively involved in tumor growth and metastasis, suppressing the innate immunity to help tumor cells escape and reshaping the microenvironment to help metastatic cells grow. However, in vivo, real-time visualized migration of M2-like macrophages has never been explored to monitor the tumor metastasis process. Herein, we prepared an M2-like macrophage-targeting nitric oxide (NO)-responsive nanoprobe (NRP@M-PHCQ) consisting of an amphiphilic block copolymer with mannose and hydroxychloroquine (HCQ) moieties (denoted as M-PHCQ) and a NO-responsive NIR-II probe (denoted as NRP). The mannose moieties provided M2-like macrophage-targeting capacity, and the HCQ moieties polarized M2-like macrophages to M1-like ones with enhanced NO secretion. Consequently, NRP@M-PHCQ was lit up by the secreted NO to visualize the migration and polarization of M2-like macrophages in real time. In vivo metastasis imaging with NRP@M-PHCQ successfully tracked early tumor metastasis in the lymph nodes and the lungs with high sensitivity, even superior to Luci-labeled bioluminescence imaging, suggesting the extensive distribution and critical role of M2-like macrophages in tumor metastasis. In general, this work provided a new strategy to sensitively image metastatic tumors by tracking the polarization of M2-like macrophages and visually disclosed the critical role of M2-like macrophages in early tumor metastasis.

A ROS-responsive synergistic delivery system for combined immunotherapy and chemotherapy.

Immune checkpoint blockade (ICB) therapies that target programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway are currently used for the treatment of various cancer types. However, low response rates of ICB remain the major issue and limit their applications in clinic. Here, we developed a ROS-responsive synergistic delivery system (pep-PAPM@PTX) by integrating physically-encapsulated paclitaxel (PTX) and surface-modified anti-PD-L1 peptide (pep) for combined chemotherapy and ICB therapy. Pep-PAPM@PTX could bind the cell surface PD-L1 and drive its recycling to lysosomal degradation, thus reverting PTX-induced PD-L1 upregulation and downregulating PD-L1 expression. As a result, pep-PAPM@PTX significantly promoted T cell infiltration and increased tumor immunoactivating factors, synergizing PTX chemotherapy to achieve enhanced anticancer potency in a triple-negative breast cancer (TNBC) model.

A case of primary intestinal lymphangiectasia with non-Hodgkin lymphoma.

BACKGROUND: Primary intestinal lymphangiectasia (PIL) is a rare protein-losing enteropathy characterized by the loss of proteins, lymphocytes, and immunoglobulins into the intestinal lumen. Increasing evidence has demonstrated an association between PIL and lymphoma. CASE PRESENTATION: A 54-year-old man with a 20-year history of abdominal distension and bilateral lower limb edema was admitted. Laboratory investigations revealed lymphopenia, hypoalbuminemia, decreased triglyceride and cholesterol level. Colonoscopy showed multiple smooth pseudo polyps in the ileocecal valve and terminal ileum and histological examination showed conspicuous dilation of the lymphatic channels in the mucosa and submucosa. A diagnosis of PIL was made. Three years later colonoscopy of the patient showed an intraluminal proliferative mass in the ascending colon and biopsy examination confirmed a malignant non-Hodgkin lymphoma. Then the patient was been underwent chemotherapy, and his clinical condition is satisfactory. CONCLUSION: Our report supports the hypothesis that PIL is associated with lymphoma development.

Vanadyl nanocomplexes enhance photothermia-induced cancer immunotherapy to inhibit tumor metastasis and recurrence.

Conventional photothermal therapy (PTT) is insufficient to induce a strong and potent anti-tumor immune response. Herein, we present a vanadyl nanocomplex, which simultaneously serves as a photothermal agent (PTA) and an immunogenic cell death (ICD) inducer to enhance the anti-tumor immunity of PTT. The vanadyl nanocomplex (STVN) is constructed via facile one-step coordination assembly under ambient conditions. STVN not only has a strong and stable photothermal effect under near-infrared (NIR) irradiation, but also can cause severe endoplasmic reticulum (ER) stress by itself, leading to ICD and activating the systemic immune responses. In the absence of any adjuvants, NIR-irradiated STVN almost completely ablates primary tumors and simultaneously inhibits distant tumors in mice bearing bilateral melanoma. Meanwhile, the intratumorally injected STVN combined with NIR effectively suppressed melanoma lung metastasis as well as tumor recurrence, displaying that local STVN-mediated PTT could trigger a systemic anti-tumor immunity. Therefore, STVN, as a novel immunogenicity-enhanced PTA, affords a "one stone two birds" strategy for improved photothermia-induced cancer immunotherapy.

Glutathione-Responsive Magnetic Nanoparticles for Highly Sensitive Diagnosis of Liver Metastases.

Liver metastasis (LM) occurs in various cancers, and its early and accurate diagnosis is of great importance. However, the detection of small LMs is still a great challenge because of the subtle differences between normal liver tissue and small metastases. Herein, we prepare glutathione (GSH)-responsive hyaluronic acid-coated iron oxide nanoparticles (HIONPs) for highly sensitive diagnosis of LMs through a facile one-pot method. HIONPs greatly enhance the signal of MRI in tumor metastases as T1 contrast agent (CA), whereas they substantially decrease the signal of liver as T2 CA as they aggregate into clusters upon the high GSH in liver. Consequently, MRI contrasted by HIONPs clearly distinguishes metastatic tumors (bright) from surrounding liver tissues (dark). HIONPs with superior LM contrasting capability and facile synthesis are very promising for clinical translation and indicate a new strategy to develop an ultrasensitive MRI CA for LM diagnosis that exploits high GSH level in the liver.

Progress and perspective of microneedle system for anti-cancer drug delivery.

Transdermal drug delivery exhibited encouraging prospects, especially through superficial drug administration routes. However, only a few limited lipophilic drug molecules could cross the skin barrier, those are with low molecular weight and rational Log P value. Microneedles (MNs) can overcome these limitations to deliver numerous drugs into the dermal layer by piercing the outermost skin layer of the body. In the case of superficial cancer treatments, topical drug administration faces severely low transfer efficiency, and systemic treatments are always associated with side effects and premature drug degradation. MN-based systems have achieved excellent technical capabilities and been tested for pre-clinical chemotherapy, photothermal therapy, photodynamic therapy, and immunotherapy. In this review, we will focus on the features, progress, and opportunities of MNs in the anticancer drug delivery system. Then, we will discuss the strategies and advantages in these works and summarize challenges, perspectives, and translational potential for future applications.

Improving safety of cancer immunotherapy via delivery technology.

Breakthroughs in molecular mechanisms underlying immune-suppressive tumor microenvironment and paradigm shifts in the cancer-immunity response cycle have profoundly changed the landscape of cancer immunotherapy. However, one of the challenges is to mitigate the serious side effects caused by systemic autoimmunity and autoinflammatory responses following immunotherapy. Thus, restraining the activation of the immune system in healthy tissues is highly desirable to address this problem. Bioengineering and delivery technologies provide a solution to the issue. In this Review, we first introduce immune-related adverse effects of main immunotherapies and the underlying mechanisms, summarize strategies of designingde bioengineering and delivery systems to reduce their immunotoxicities, and highlight the importance of the development of immunotoxicity-related animal models.

Vanadium-based nanomaterials for cancer diagnosis and treatment.

In the past few decades, various vanadium compounds have displayed potential in cancer treatment. However, fast clearness in the body and possible toxicity of vanadium compounds has hindered their further development. Vanadium-based nanomaterials not only overcome these limitations, but take advantage of the internal properties of vanadium in photics and magnetics, which enable them as a multimodal platform for cancer diagnosis and treatment. In this paper, we first introduced the basic biological and pharmacological functions of vanadium compounds in treating cancer. Then, the synthesis routes of three vanadium-based nanomaterials were discussed, including vanadium oxides, 2D vanadium sulfides, carbides and nitrides: VmXn (X = S, C, N) and water-insoluble vanadium salts. Finally, we highlighted the applications of these vanadium-based nanomaterials as tumor therapeutic and diagnostic agents.

Self-stabilized silk sericin-based nanoparticles: In vivo biocompatibility and reduced doxorubicin-induced toxicity.

A variety of colloid stabilizers and cryoprotectants confer improved nanoparticle (NP) colloidal stability and redisperability. However, discounted tumor targetability, delivery efficacy and possible side effects limit the application in vascular delivery of NPs. Here we present water-soluble silk sericin (SS) not only as a material for the preparation of NPs, but also both a dispersion stabilizer and a cryoprotectant. In the absence of any stabilizers, SS-based NPs (SSC@NPs) can resist the adsorption of serum proteins, preventing the formation of particle agglomerates. Following freeze-drying without addition of cryoprotectants, SSC@NPs powder can be easily resuspended into NP dispersion with a nearly monodispersed distribution. Additionally, SSC@NPs do not result in acute toxicity in mice at a dose of 400 mg/kg with a slow injection. Moreover, doxorubicin (DOX)-loaded SSC@NPs (DOX-SSC@NPs) diminish the biodistribution of DOX in the heart, mitigating DOX-induced cardiotoxicity of mice without compromising therapeutic efficacy. Our results suggest that the self-stabilized SSC@NPs could be a secure and effective drug carrier for intravenous administration when deprived of protective agents. STATEMENT OF SIGNIFICANCE: During manufacturing process such as freeze-drying, or interaction with complex fluids like blood, NPs for systemic drug delivery need to be highly dispersible and structurally intact. In this work, we have demonstrated the self-stability of SSC@NPs subjected to biological media and freeze-drying. This study represents the first work showing water-soluble SS could both act as a dispersion stabilizer and a cryoprotectant due to its hydrophilicity. Plus, good in vivo biocompatibility of SSC@NPs has been confirmed. Therefore, it may be promising that water-soluble SS can be generally used as a safe biomaterial against serum adsorption.