Pancreatic cancer encompasses a heterogeneous group of malignancies, primarily divided into endocrine and exocrine types, with pancreatic ductal adenocarcinoma representing approximately 90% of cases. While the incidence of pancreatic cancer is relatively low, accounting for about 3% of all cancers in the United States, it has a disproportionately high mortality rate, responsible for around 7% of cancer-related deaths. In 2024, it is estimated that there will be 66,440 new diagnoses and 51,750 fatalities associated with this disease. The overall five-year survival rate remains alarmingly low at just 13%, primarily due to late-stage diagnosis; over 80% of pancreatic ductal adenocarcinoma patients present with unresectable tumors and metastases at the time of diagnosis. This review aims to highlight recent advancements in imaging and laboratory tests that are paving the way for innovative screening and diagnostic approaches. Some of the modalities discussed in detail include endoscopic ultrasound (EUS) and its modifications, such as EUS elastography, EUS contrast-enhanced, and EUS Fine Needle Aspiration, as well as multi-detector computed tomography scans, magnetic resonance imaging, and positron emission tomography scans. Furthermore, laboratory tests, such as multi-marker analysis and circulating tumor DNA, alongside traditional markers like carcinoembryonic antigen, carbohydrate antigen 19-9, and carbohydrate antigen 125, are explored. The role of radiomics and proteomics in the early detection of pancreatic cancer is also discussed. These developments hold the promise of improving early detection, which is crucial for enhancing patient outcomes in pancreatic cancer. On the treatment front, conventional therapies, including platinum-based therapies and monoclonal antibodies, are reviewed, alongside innovative therapies such as immunotherapies, chimeric antigen receptor T-cell therapy, and cancer vaccines. It has been increasingly recognized that the intricate patho-mechanisms underlying tumorigenesis in pancreatic cancers necessitate a deeper understanding to facilitate targeted therapeutic strategies. We also explore various newer therapies currently in clinical trials, assessing their practicality and effectiveness in real-world settings.

Despite the large number of cancer chemotherapeutics, cancer treatment is still not very satisfactory. Immune checkpoint inhibition has emerged as a new ray of hope in the immunotherapy approach for cancer treatment. Immune checkpoint inhibitors are molecules located on the surface of immune cells that regulate unnecessary immune responses and keep autoimmune reactions in check. Immune checkpoint inhibitors (ICIs), such as anti-programmed cell death protein-1 and anti-programmed cell death ligand-1, have been employed to activate receptors on immune cells like T-cells, which can deactivate the immune checkpoint and thus reactivate them against cancer cells. However, ICI therapy has limitations, including resistance development in patients, its suitability for all patients, multiple organ disorders, and hyper-progression. Therefore, understanding the chemical structures of small molecule ICIs may aid in designing and developing novel ICIs with improved efficacy and efficiency for cancer chemotherapy. This review’s novelty lies in its summary of the U.S. Food and Drug Administration-approved drugs, repurposed drugs, candidate drugs used alone or in combination with monoclonal antibodies, and novel potential lead molecules under preclinical investigation, which may be useful for designing new chemical entities as ICIs. The review describes 10 different drugs approved by the U.S. Food and Drug Administration that have demonstrated immune checkpoint inhibition targeting the programmed cell death ligand-1/programmed cell death protein-1 signaling, CTLA-4/CD28, TIGIT/PVR, and CD47/SIRPα pathways, as well as three repurposed drugs, 11 candidate drugs, and nine drugs in combination with monoclonal antibodies that are in various phases of clinical trials.

Colorectal cancer (CRC) is the second most commonly diagnosed cancer in China. Early detection and diagnosis of CRC are essential for improving survival rates. However, socioeconomic factors such as regional disparities, economic conditions, and varying levels of awareness impact the uptake of screening programs. Recently, rapid advancements in non-invasive tests, including high-quality fecal immunochemical tests and the emergence of stool and blood biomarkers for CRC, have facilitated improvements in early detection and diagnosis. Additionally, image-enhanced endoscopy, a group of advanced imaging technologies, has been developed to assist in the early identification of colorectal lesions, including narrow band imaging and linked-color imaging. The emergence of artificial intelligence also offers promising opportunities to improve early diagnosis and treatment of CRC. This review mainly introduces screening technologies and the current status of CRC screening in China, provides an overview of CRC early detection and diagnosis, and discusses the limitations and future prospects.

Yersinia pseudotuberculosis (Yptb) causes intestinal infection and can spread to the liver, where the bacterium induces hemosiderosis, abscesses, and hepatitis. To evade the immune response of the host organism, Yptb expresses at least six plasmid-encoded Yersinia outer proteins belonging to the Type III secretion system, which suppress phagocytic activity. Recently, evidence has accumulated that chromosome-encoded protein toxins are also involved in the anti-phagocytic defense of Yptb. Most of these toxins have been found in isolates from patients with Far East scarlet-like fever, often accompanied by liver pathology. Yersinia proteins contribute to bacterial colonization of lymphoid organs through their effects on immune cells. A thorough understanding of the immunomodulatory effects of these toxic proteins on bacterial dissemination and colonization in the liver will contribute to the development of novel approaches to cure hepatic pathology during Yptb infection. The review aimed to summarize the current data on the mechanisms of effects of Yptb plasmid- and chromosome-encoded toxins on bacterial colonization in the liver. The review highlights the fine-tuning of immune system activity by toxins encoded by both a 70-kb plasmid and chromosomes, through various mechanisms of action of individual proteins and their interactions. The focus is on mechanisms that promote bacterial survival in macrophages, including those that facilitate bacterial-induced macrophage polarization towards the M2 phenotype. The role of a type of phagocyte death in bacterial dissemination and colonization in the organs is also discussed.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with difficulties in early diagnosis, poor prognosis, and limited effective therapies. Early detection and effective treatment offer the optimal chance to improve survival rates. Various studies have shown that gut microbiota dysbiosis is closely related to PDAC, with potential mechanism involving immune regulation, metabolic process impact, and reshaping the tumor microenvironment. A comprehensive understanding of the microbiota in PDAC might lead to the establishment of screening or early-stage diagnosis methods, implementation of cancer bacteriotherapy such as fecal microbiota transplantation, creating new opportunities and fostering hope for desperate PDAC patients.

Drug-induced liver injury (DILI) is a harmful reaction to medications, herbs, and dietary supplements that results in liver dysfunction. Based on the distinct clinical patterns of liver damage, DILI can be categorized into hepatocellular, cholestatic, and mixed types. Hepatocellular DILI is linked to inflammation, apoptosis, and necrosis, while cholestatic DILI is commonly associated with bile plugs and, in rare cases, ductopenia. Ursodeoxycholic acid (UDCA) is the therapeutic agent most widely used for the treatment of cholestatic hepatopathies of diverse etiologies and has been mainly used as a supportive treatment in cholestatic DILI. In this review, we presented a more structured and systematic framework for the potential application of this hepatoprotective agent across a broader range of DILI scenarios. A MEDLINE search of the literature from 1995 to the present retrieved 41 preliminary clinical studies suggesting that UDCA may offer curative and preventive benefits for hepatocellular DILI as well. This aligns with preclinical studies in rodents, showing beneficial effects of UDCA in experimental DILI irrespective of the clinical patterns of injury involved. This could be due to the broad range of potentially beneficial effects of UDCA, which may address the various types of liver damage with different causes and mechanisms seen in all forms of DILI. UDCA’s beneficial properties include anticholestatic, antioxidant, anti-inflammatory, anti-apoptotic, anti-necrotic, mitochondrial protective, endoplasmic reticulum stress-relieving, and immunomodulatory effects. Controlled studies with systematic use of standardized causality assessments are eagerly awaited to properly validate the use of UDCA in DILI. Meanwhile, we hope this article helps clarify and systematize the use of this versatile and safe hepatoprotective medication for different types of liver toxicity.

Information on the survival of urothelial cancer (UCa) patients with brain metastases (BM) is largely unreliable due to the rarity of such cases. Previous studies that have attempted to capture the prevalence and survival of these patients are limited to case series and retrospective studies with small cohort sizes. This study aimed to explore patient characteristics and treatment outcomes based on treatment modalities from a large sample of patients with UCa and BM.

In this retrospective study, we utilized the TriNetX Research Network, a real-world and in-house database with longitudinal electronic medical records from 92 institutions. The database was queried for patients with UCa who also had BM. Kaplan–Meier plots were used to assess overall survival (OS). Log-rank tests were applied for stratified outcomes. The Cox proportional hazards model was used for continuous data.

We identified 357 patients with UCa and BM, representing 4.7% of the 7,521 patients diagnosed with primary UCa. The mean age at diagnosis was 65.6 years, with a predominance of male patients (67%). The median OS from BM diagnosis was 18.6 months. For patients treated solely with stereotactic radiosurgery (SRS), the median OS was 20.8 months. For those treated with both SRS and surgical resection, the median OS was 18.6 months. There was no significant difference in survival between patients treated with SRS alone and those treated with both SRS and surgical resection (p = 0.875). For patients treated only with gemcitabine chemotherapy, the median OS was 15.4 months.

This study represents the largest known retrospective analysis of UCa patients with BM. Survival trends for patients treated with surgical resection, SRS, and systemic therapies are described in detail.

Hepatic encephalopathy (HE) is a brain disorder secondary to cirrhosis, characterized by cognitive deficits, psychiatric manifestations, and motor impairments. It is associated with frequent hospitalizations, high mortality rates, and poor quality of life in cirrhotic patients. Additionally, ammonia and inflammation are key contributors to the onset of HE. Rifaximin is minimally absorbed in the intestine and is considered a locally acting, semi-synthetic antibiotic with broad-spectrum antibacterial activity. The pharmacological effects of rifaximin include reducing plasma ammonia levels, decreasing proinflammatory cytokine levels, and modulating gut microbiota and their functions. Currently, both Chinese and EASL clinical practice guidelines recommend rifaximin (800–1,200 mg/d) as a first-line treatment for HE for up to six months. However, the efficacy and safety of long-term (≥six months) use of rifaximin for HE remain debated. This review aimed to analyze the long-term (≥six months) use and dose-effect relationships of rifaximin treatment for HE. Long-term, low-dose use of rifaximin (600–800 mg/d) may offer potential benefits in terms of efficacy, safety, and cost-effectiveness.

Free radicals are produced in the body during normal cellular metabolic activities, and their excessive accumulation can overwhelm the natural antioxidant mechanisms. This leads to oxidative stress, which is associated with the development and progression of non-communicable diseases (NCDs) such as liver and kidney diseases, cardiovascular diseases, neurodegenerative diseases, cancer, and diabetes. Enzymes play a significant role in maintaining a balance between antioxidants and free radicals by either enhancing the production of antioxidants or slowing down the generation of free radicals in the body. There is no up-to-date review on how antioxidant-enzyme interactions modulate the development and progression of NCDs. This review, therefore, discusses the mechanisms of antioxidant-enzyme interactions in the control of oxidative stress, as well as the implications and prospects of these interactions in the management of NCDs. Therapeutic strategies targeting antioxidant-enzyme interactions in the natural defense mechanisms of the body against oxidative stress can provide targeted benefits in the management of various NCDs. The mechanisms of interaction of some antioxidants with catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase, glutathione S-transferases, thioredoxin protein, and thioredoxin reductase suggest their strong involvement in mitigating the development and progression of NCDs. Moreover, understanding the specific interactions and signaling pathways involved in antioxidant-enzyme interactions could facilitate the emergence of novel and effective therapeutic strategies for the management of NCDs and should be considered a primary goal of future studies. This study provides the necessary template, encourages discussion, and creates more opportunities for the next stage in the development of antioxidant therapies.

Over the past decade, significant progress has been made in managing acute myeloid leukemia (AML). However, refractory disease and relapse continue to pose major challenges. These issues highlight the need for innovative therapeutic options to achieve deeper remission and effectively treat refractory and relapsed diseases, thereby improving survival rates. Natural killer (NK) cell-based therapies have emerged as a promising option. NK cells, a specialized population of innate lymphoid cells, exhibit inherent anti-viral and anti-cancer capabilities. Unlike T cells, NK cells do not require prior antigen sensitization to eliminate their target cells, enhancing their potential as immunotherapeutic agents. However, NK cells often exhibit dysfunction in patients with hematological malignancies. Revitalizing these cells represent another immunotherapeutic strategy. Various NK cell-based therapies have been explored in recent decades, particularly in managing AML. These therapies include chimeric antigen receptor-NK cell therapy, bispecific and trispecific NK cell engagers (bi-specific killer cell engager (BiKEs) and tri-specific killer cell engager (TriKEs), and cytokine-induced memory-like NK cells. These therapies are also associated with fewer adverse events, such as neurotoxicity. Despite their potential for clinical cancer management, challenges such as the in vivo expansion of NK cells remain unresolved. This review summarizes the biology of NK cells and the diverse NK cell-based therapies being developed for the potential management of AML, as evidenced in preclinical studies and clinical trials.