Inflammatory bowel disease (IBD) is a chronic, relapsing intestinal disorder driven by multiple factors including genetics, immunity, and environment, and is clinically classified into ulcerative colitis and Crohn's disease. Currently, mice and zebrafish are the primary experimental animals used in IBD research, among which zebrafish have emerged as an ideal model due to their unique advantages. Compared with rodent models, zebrafish serve as an effective and convenient model, offering advantages such as a short life cycle, robust reproductive capacity, small size, and transparent embryos. These characteristics make zebrafish highly suitable for dynamic tracking of continuous pathological progression and high-throughput drug screening. Zebrafish share over 70% genetic homology with humans, and their intestinal cellular composition and ontogeny closely resemble those of humans. Moreover, the structure and characteristics of their gut microbiota are similar to the human intestinal microbiome, providing a solid foundation for studying the relationship between gut microbiota and IBD. With advances in biotechnology, zebrafish IBD models generated by chemical induction or genetic engineering can accurately simulate the core pathological features of human IBD, such as intestinal wall thickening, inflammatory cell infiltration, and elevated expression of pro-inflammatory factors. These models have played a significant role in revealing the pathogenesis of IBD as well as the development of targeted therapeutic drugs. This article first outlines the intestinal characteristics of zebrafish and features of zebrafish IBD models, then provides an in-depth analysis of their application in IBD pathogenesis research from multiple aspects, including genetics, immunity, environment and diet, and infection. It also reviews research progress on the application of zebrafish in the development of anti-inflammatory drugs, probiotics, and traditional Chinese medicine therapies, aiming to provide researchers with references for the rational use of zebrafish models at all stages of preclinical research, to advance fundamental IBD research and accelerate breakthroughs in this field.

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

In recent years, immune checkpoint inhibitors (ICIs) have been widely used in malignant solid tumors with remarkable efficacy. However, in colorectal cancer (CRC), ICIs have shown significant therapeutic effects only in patients with highly microsatellite unstable/mismatch repair-deficient metastatic CRC and these patients are only a minority of all CRC patients. In contrast, the majority of patients, those with microsatellite stable (MSS)/mismatch repair-complete (pMMR)-type metastatic CRC, could hardly benefit from ICI monotherapies, and immune combination therapies have become the key to solveing this clinical challenge. This article introduces the common patterns and possible mechanisms of immune-combination therapies for MSS/pMMR-type CRC, the exploration and progress made in the application of immune-combination therapies, as well as the possible predictive markers of efficacy of immune therapies. The prospects and directions of ICIs in the treatment of MSS/pMMR-type CRC are also discussed.

Colorectal cancer(CRC)ranks in third place in terms of incidence but second in terms of mortality.Cancer vaccine,as a novel immunotherapy,presents tumor antigens to human immune system and further elicits anti-tumor immune response,leading to long-term immune memory.This review summarized representative research progress in both clinical and basic scenario of past five years,and prospected the future of CRC vaccine.

Colorectal cancer is one of the common malignant tumors of the digestive tract.With the popularization of screening methods and advancement of endoscopic technology,an increasing number of T1 stage colorectal cancers can be discovered.Accurately predicting lymph node metastasis risk is significantly important for guiding clinical treatment decisions,reducing complications and mortality.Current research on risk factors for lymph node metastasis in T1 stage colorectal cancer covers multiple aspects including clinical pathological features,molecular phenotypes and genetic characteristics.Some studies have built prediction models by integrating these factors,which show higher sensitivity,specificity and accuracy compared to current clinical guidelines.These models provide valuable experience for clinical practice.

In January 2024,Cancer Statistics,2024 was published in CA:A Cancer Journal for Clinicians.This report estimated cancer cases and deaths in 2024 and described the secular trends of major cancers over recent decades.We summarized the report and integrated the latest data on the cancer burden in China to compare the prevalence cancer between two countries.We also comprehensively interpreted the underlying reasons for these trends to provide insights for cancer prevention and control strategies in China.

In recent years, immune checkpoint inhibitors (ICIs) have been widely used in malignant solid tumors with remarkable efficacy. However, in colorectal cancer (CRC), ICIs have shown significant therapeutic effects only in patients with highly microsatellite unstable/mismatch repair-deficient metastatic CRC and these patients are only a minority of all CRC patients. In contrast, the majority of patients, those with microsatellite stable (MSS)/mismatch repair-complete (pMMR)-type metastatic CRC, could hardly benefit from ICI monotherapies, and immune combination therapies have become the key to solveing this clinical challenge. This article introduces the common patterns and possible mechanisms of immune-combination therapies for MSS/pMMR-type CRC, the exploration and progress made in the application of immune-combination therapies, as well as the possible predictive markers of efficacy of immune therapies. The prospects and directions of ICIs in the treatment of MSS/pMMR-type CRC are also discussed.

Polycystic ovary syndrome(PCOS)is characterized by high heterogeneity and heredity,and its exact pathogenesis is still not clear.Some studies have shown that epigenetic disorders,such as hyperandrogen-induced methyla-tion or acetylation of lysine at different sites(K4,K9,and K27)in histone H3,methylation and demethylation modifica-tion of genes related to steroids,hormone receptors and follicular development,and transcriptional control of microRNA or long noncoding RNA,play a central role in the occurrence and development of PCOS.This article reviews the research ad-vances in epigenetic mechanisms(histone modifications,DNA methylation,and noncoding RNA)of PCOS,in order to provide a reference for the prediction and early prevention of PCOS.

There is an accumulating body of evidence implicating the muscarinic acetylcholine receptor 4 (M₄) in schizophrenia and dementia with Lewy bodies, however, a clinically validated M₄ positron emission tomography (PET) radioligand is currently lacking. As such, the aim of this study was to develop a suitable M₄ PET ligand that allows the non-invasive visualization of M₄ in the brain. Structure-activity relationship studies of pyrazol-4-yl-pyridine derivates led to the discovery of target compound 12 - a subtype-selective positive allosteric modulator (PAM). The radiofluorinated analogue, [¹⁸F] 12, was synthesized in 28 ± 10% radiochemical yield, >37 GBq/μmol and an excellent radiochemical purity >99%. Initial in vitro autoradiograms on rodent brain sections were performed in the absence of carbachol and showed moderate specificity as well as a low selectivity of [¹⁸F] 12 for the M₄-rich striatum. However, in the presence of carbachol, a significant increase in tracer binding was observed in the rat striatum, which was reduced by >60% under blocking conditions, thus indicating that orthosteric ligand interaction is required for efficient binding of [¹⁸F] 12 to the allosteric site. Remarkably, however, the presence of carbachol was not required for high specific binding in the non-human primate (NHP) and human striatum, and did not further improve the specificity and selectivity of [¹⁸F] 12 in higher species. These results pointed towards significant species-differences and paved the way for a preliminary PET study in NHP, where peak brain uptake of [¹⁸F] 12 was found in the putamen and temporal cortex. In conclusion, we report on the identification and preclinical development of the first radiofluorinated M₄ PET radioligand with promising attributes. The availability of a clinically validated M₄ PET radioligand harbors potential to facilitate drug development and provide a useful diagnostic tool for non-invasive imaging.

Glaucoma is one of the most common optic neuropathies, featuring progressive retinal ganglion cell damage and visual field loss (Tham et al., 2014; Xu et al., 2020). Currently, the only effective treatment for this condition is the reduction of intraocular pressure (IOP) (Palmberg, 2001; Heijl et al., 2002). Canaloplasty is a proven bleb-independent surgery with good efficacy and safety profiles in primary open-angle glaucoma (POAG) (Gołaszewska et al., 2021). However, early transient postoperative IOP elevation has been reported in up to 30% of cases (Riva et al., 2019), similar to that commonly observed in other internal drainage glaucoma surgeries such as implantation using iStent (0%-21.0%), CyPass (10.8%), and Hydrus (4.8%-6.5%) (Lavia et al., 2017). This complication may be a predictor of poor reserve in the outflow system and is potentially associated with surgical failure. Nonetheless, the exact pathophysiology of glaucoma remains unknown, and studies clarifying the risk factors for postoperative IOP elevation have been scarce.
Humans ; Intraocular Pressure ; Glaucoma, Open-Angle/surgery* ; Incidence ; Treatment Outcome ; Risk Factors