Gastric cancer (GC) is a malignant tumor with one of the lowest five-year survival rates. Traditional first-line treatment regimens, such as platinum drugs, have limited therapeutic efficacy in treating advanced GC and significant side effects, greatly reducing patient quality of life. In contrast, trastuzumab and other immune checkpoint inhibitors, such as nivolumab and pembrolizumab, have demonstrated consistent and reliable efficacy in treating GC. Here, we discuss the intrinsic characteristics of GC from a molecular perspective and provide a comprehensive review of classification and treatment advances in the disease. Finally, we suggest several strategies based on the intrinsic molecular characteristics of GC to aid in overcoming clinical challenges in the development of precision medicine and improve patient prognosis.

With the explosion research on the gut microbiome in the recent years, much insight has been accumulated in comprehending the crosstalk between the gut microbiota community and host health. Acute pancreatitis (AP) is one of the gastrointestinal diseases associated with significant morbidity and subsequent mortality. Studies have elucidated that gut microbiota are engaged in the pathological process of AP. Herein, we summarize the major roles of the gut microbiome in the development of AP. We then portray the association between dysbiosis of the gut microbiota and the severity of AP. Finally, we illustrate the promises and challenges that arise when seeking to incorporate the microbiome in acute pancreatitis treatment.

Background: Acute respiratory distress syndrome (ARDS) is the most common cause of organ failure in acute pancreatitis (AP) patients, which associated with high mortality. Specific changes in the gut microbiota have been shown to influence acute pancreatitis progression. This study was aimed to determine whether early alterations in the gut microbiota is related to and could predict ARDS occurrence in AP patients. Method: In the present study, we performed 16S rRNA sequencing analysis in 65 AP patients and 20 healthy volunteers. The AP patients were further divided into two groups: 26 AP-ARDS patients and 49 AP-nonARDS patients according to ARDS occurrence during the following hospitalization. We also conducted a combination analysis using lung microbiota data between ICU-ARDS patients and ICU-nonARDS patients with publically available data. Finding: Our results showed that the AP-ARDS patients exhibited specific changes in gut microbiota composition and function as compared to subjects of AP-nonARDS group. Higher abundances of Proteobacteria phylum, Enterobacteriaceae family, Escherichia-Shigella genus, and Klebsiella pneumoniae, but lower abundances of Bifidobacterium genus were found in AP-ARDS group compared with AP-nonARDS groups. Random forest modelling analysis revealed that the Escherichia-shigella genus was effective to distinguish AP-ARDS from AP-nonARDS, which could predict ARDS occurrence in AP patients. Higher abundance of Escherichia-shigella genus was also found in the lung of ICU-ARDS patients compared with ICU-nonARDS patients. Interpretation: Our study revealed that alterations of gut microbiota in AP patients on admission were associated with ARDS occurrence after hospitalization, indicating a potential predictive and pathogenic role of gut microbiota in the development of ARDS complication in AP patients. Funding Information: This study was supported by grants from Chinese Natural Science Foundation, grant number 82270405 and 32170788, National Key Clinical Specialty Construction Project, grant number ZK108000, Beijing Natural Science Foundation, grant number 7202152, and National High Level Hospital Clinical Research Funding, grant number 2022-PUMCH-A-026. Declaration of Interests: The authors declare no conflict of interest for this article. Ethics Approval Statement: The study was conducted according to the Declaration of Helsinki and was approved by the Ethics Committee of PUMCH (JS1826). Informed consent was obtained from all subjects involved in the study.

Pancreatic repair after acute pancreatitis (AP) is essential for restoring tissue integrity, but the intrinsic mechanisms coordinating acinar plasticity and regeneration remain poorly understood. Aberrant Ca ^{2 +} signaling drives acinar injury, but whether Ca ^{2 +} ‐responsive effectors regulate post‐injury repair remains unclear. This study identifies calcium/calmodulin‐dependent protein kinase II δ (CaMKIIδ) as a repair‐associated regulator of pancreatic regeneration. Global Camk2d deletion delays repair after caerulein‐induced AP without altering initial injury severity. Bone marrow chimeras and pancreas‐specific Camk2d deletion further demonstrate that pancreatic, rather than bone marrow‐derived, CaMKIIδ is required for efficient tissue repair. Transcriptomic and ultrastructural analyses reveal that Camk2d deficiency disrupts endoplasmic reticulum (ER) homeostasis and enhances PERK‐dependent unfolded protein response activation. Camk2d ‐deficient pancreas shows impaired acinar‐to‐ductal metaplasia (ADM) programs in vivo and defective ADM formation in ex vivo 3D culture. Integrated proteomic and phosphoproteomic profiling of acinar‐derived ADM identifies ancient ubiquitous protein 1 (AUP1), an ER‐associated degradation regulator, as a previously unrecognized CaMKIIδ‐dependent substrate candidate. Functional analyses show that phosphorylation of the AUP1 S280‐containing serine‐rich region promotes K48‐linked ubiquitination and restrains PERK‐dependent ER stress under pancreatic stress conditions. These findings define a CaMKIIδ–AUP1 axis linking Ca ^{2 +} ‐responsive kinase activity to ER proteostasis, ADM formation and pancreatic repair.