By analyzing the current application of multi-modal data in the diagnosis of gastric "inflammation-cancer" transformation， this study explored the feasibility and strategies for constructing a disease-syndrome integrated diagnosis and treatment system. Based on traditional Chinese medicine （TCM） phenomics， we proposed utilizing multi-modal data from literature research， cross-sectional studies， and cohort follow-ups， combined with artificial intelligence technology， to establish a multi-dimensional diagnostic and treatment index system. This approach aims to uncover the complex pathogenesis and transformation patterns of gastric "inflammation-cancer" progression. Additionally， by dynamically collecting TCM four-diagnostic information and modern medical diagnostic information through a long-term follow-up system， we developed three major modules including information extraction， multi-modal phenotypic modeling， and information output， to make it enable real-world clinical data-driven long-term follow-up and treatment of chronic atrophic gastritis. This system can provide technical support for clinical diagnosis， treatment evaluation， and research， while also offering insights and methods for intelligent TCM diagnosis.

Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I ( 1, 4- 11), and two known ones ( 2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.

Objective:To investigate the consistency between the iodine-unstained area and the pathological size of endoscopic submucosal dissection (ESD) specimens of superficial esophageal cancer.Methods:A retrospective study was performed on data of 32 patients with superficial esophageal cancer who accepted ESD from May 2019 to April 2020 in the First Affiliated Hospital, Zhejiang University School of Medicine. The maximum transverse diameter and maximum longitudinal diameter of the iodine-unstained area were compared with the tumor pathological area. A size difference no more than 0.5 cm was considered as conformity, any difference between 0.5 and 1.0 cm was considered as non-conformity, and any difference no less than 1.0 cm was considered as serious non-conformity. At the same time, pink sign after spraying Lugo solution and the consistency of pink sign area with the iodine free area were observed.Results:A total of 32 patients with 33 lesions were enrolled in this study, including 23 males and 9 females and the age of the patients was 59.5±7.3 years. There were 19 (57.6%) lesions whose size of iodine-unstained area was consistent with the tumor pathological area. These 19 lesions were all positive for the pink sign, and the pink sign area overlapped with the iodine-unstained area. In addition, 4 (12.1%) iodine-unstained areas of the lesions did not match the size of the pathological area, and 10 (30.3%) iodine-unstained areas of the lesions were seriously inconsistent with the size of the pathological area. These 14 (42.4%) lesions were all positive for pink sign, and the pink sign area was significantly smaller than the iodine-unstained area. Among the 14 discordant lesions, 2 lesions underwent ESD according to the iodine-unstained area, which resulted in excessive resection and postoperative stenosis.Conclusion:Determining the extent of superficial esophageal cancer by iodine-unstained areas before ESD may lead to excessive resection of the lesions, which is related to the fact that the iodine-unstained areas of the lesions are sometimes significantly larger than the pink sign areas. Therefore, in order to achieve precise treatment, endoscopists can choose the iodine-unstained area with positive pink sign as the first choice for resection.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

Carotid artery stenosis is an important cause of ischemic stroke, and its mechanism is mainly associated with the formation of atherosclerotic plaques. Head and neck radiotherapy may accelerate plaque formation, leading to carotid artery stenosis. In addition, radiotherapy can also cause the damage to the intima and adventitia of blood vessels, exacerbating the degree of carotid artery stenosis. This carotid artery stenosis caused by radiotherapy is different from atherosclerotic carotid artery stenosis in etiology, pathogenesis, prevention and treatment. Therefore, a thorough understanding of the pathogenic mechanism is crucial for selecting appropriate prevention and treatment methods.

Objective:To automatically synthesize Al 18F-fibroblast activation protein inhibitor (FAPI)-74, and explore its value of clinical application. Methods:Al 18F-FAPI-74 was synthesized automatically by the commercial synthesis module CFN-MPS-100, and its yield, radiochemical purity and stability were determined. Sixteen normal Kunming (KM) mice were randomly divided into 4 groups and euthanized at 10, 30, 60 and 90 min after Al 18F-FAPI-74 injection, and the biodistribution was measured. MicroPET/CT dynamic scanning (60 min) was performed in 5 rat pancreatic tumor-bearing BALB/c nude mice to observe the tumor uptake. Al 18F-FAPI-74 PET/CT imaging was performed on 3 volunteers (1 male, 2 females; age: 37, 41, 43 years) to evaluate the clinical application value of Al 18F-FAPI-74. Results:The automated synthesis time of Al 18F-FAPI-74 was about 35 min, with the synthesis yield of (21.34±3.86)% (without attenuation correction, n=5) and the radiochemical purity more than 99%. The radiochemical purity was still more than 96% after placement at 37 ℃ for 6 h. Biodistribution in normal mice and microPET/CT dynamic scanning in tumor-bearing nude mice showed that consistently high uptake in the kidneys and bladder, and the tumor uptake was the highest at 20 min, and the maximum tumor-to-muscle ratio was 3.16±0.01 at 60 min. PET/CT imaging on volunteers showed that there was a small amount of uptake in myocardium, most organs such as the liver and lung had background uptake, and the maximum SUV max of persistent high uptake of tumor was 17.08. Conclusions:Al 18F-FAPI-74 has the advantages of simple synthesis, high yield, stable quality and good imaging performance in mice and volunteers. It is a kind of imaging agent that meets the requirements of clinical diagnosis.

Cyclin-dependent kinase 9 (CDK9) activity is correlated with worse outcomes of triple-negative breast cancer (TNBC) patients. The heterodimer between CDK9 with cyclin T1 is essential for maintaining the active state of the kinase and targeting this protein-protein interaction (PPI) may offer promising avenues for selective CDK9 inhibition. Herein, we designed and generated a library of metal complexes bearing the 7-chloro-2-phenylquinoline CˆN ligand and tested their activity against the CDK9-cyclin T1 PPI. Complex 1 bound to CDK9 via an enthalpically-driven binding mode, leading to disruption of the CDK9-cyclin T1 interaction in vitro and in cellulo. Importantly, complex 1 showed promising anti-metastatic activity against TNBC allografts in mice and was comparably active compared to cisplatin. To our knowledge, 1 is the first CDK9-cyclin T1 PPI inhibitor with anti-metastatic activity against TNBC. Complex 1 could serve as a new platform for the future design of more efficacious kinase inhibitors against cancer, including TNBC.

Blast injury of the chest injury is the most common wound in modern war trauma and terrorist attacks, and is also the most fatal type of whole body explosion injury. Most patients with severe blast injury of the chest die in the early stage before hospitalization or during transportation, so first aid is critically important. At present, there exist widespread problems such as non-standard treatment and large difference in curative effect, while there lacks clinical treatment standards for blast injury of the chest. According to the principles of scientificity, practicality and advancement, the Trauma Society of Chinese Medical Association has formulated the guidance of classification, pre-hospital first aid, in-hospital treatment and major injury management strategies for blast injury of the chest, aiming to provide reference for clinical diagnosis and treatment.

Objective To investigate the effect of fecal microbiota transplantation (FMT) on a rat model of hypertriglyceridemic acute pancreatitis (HLAP). Methods A total of 72 male Sprague-Dawley rats were randomly divided into sham-operation group, model group, Rheum officinale group, and fecal microbiota group, with 18 rats in each group. After 8 weeks of feeding with high-fat diet, the rats in the sham-operation group were given sham operation, and those in the other three groups were given retrograde pancreaticobiliary injection of 5% sodium taurocholate to induce acute pancreatitis; after modeling, the rats in the Rheum officinale group were given enema with Rheum officinale , and those in the fecal microbiota group were given enema with fresh fecal microbiota solution. Blood, pancreatic, and terminal ileal tissue samples were collected at 6, 24, and 36 hours after surgery. HE staining was used to observe histopathological changes of the pancreas and the intestine; an automatic biochemical analyzer was used to measure the serum levels of amylase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HLD-C); ELISA was used to measure the serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and endotoxin as an index for intestinal permeability. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test or the Tamhane T2 test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Bonferroni method was used for further comparison between two groups. Results Compared with the sham-operation group, the Rheum officinale group and the fecal microbiota group had no significant increase in the pathological score of the terminal ileum at 6 and 24 hours, and there was no significant difference between the fecal microbiota group and the sham-operation group at 36 hours (all P > 0.05). At 36 hours, the Rheum officinale group and the fecal microbiota group had a significantly lower serum level of amylase than the model group (all P < 0.05). Compared with the model group, the Rheum officinale group had a significantly lower serum level of ALT at 36 hours ( P < 0.05) and a significantly lower serum level of AST at 24 hours ( P < 0.05), while the fecal microbiota group had a significantly lower level of ALT at each time point ( P < 0.05) and a significantly lower serum level of AST at 24 and 36 hours (all P < 0.05). The Rheum officinale group and the fecal microbiota group had significant reductions in the serum levels of TC and TG (all P < 0.05); compared with the Rheum officinale group, the fecal microbiota group had a significantly higher serum level of HDL-C at 24 and 36 hours (all P < 0.05), and compared with the model group, the fecal microbiota group had a significantly lower serum level of HDL-C at each time period (all P < 0.05). There were no significant differences in the inflammatory indices IL-6 and TNF-α between the fecal microbiota group and the sham-operation group at each time point (all P > 0.05), and the Rheum officinale group had significantly higher levels than the sham-operation group (all P < 0.05); both the Rheum officinale group and the fecal microbiota group had a significantly lower serum level of endotoxin than the model group (all P < 0.05), and the fecal microbiota group had a significantly lower level of endotoxin than the Rheum officinale group within 6 hours of treatment ( P < 0.05). Conclusion Both Rheum officinale and fecal microbiota transplantation can improve tissue inflammation and intestinal permeability in HLAP rats and can improve lipid metabolism and alleviate the progression of pancreatitis to a certain extent, and fecal microbiota transplantation shows a better clinical effect than Rheum officinale alone, but more randomized controlled trials are needed for further investigation.

Objective:To analyze whether there are differences and related influencing factors in liver injury associated with different strains of 2019-nCoV/SARS-CoV-2 infection.Methods:Data of epidemiology, clinical symptoms, laboratory tests, and treatment outcomes of patients with COVID-19 infection confirmed with Alpha and Delta virus strain in Zhejiang Province were retrospectively collected. Statistical analysis was performed using independent samples t-test or Mann-Whitney U test, χ2 test or Fisher's exact test, and logistic regression analysis. Results:A total of 788 and 381 cases with Alpha and Delta virus strain were included. Vaccination ratio was 0% in Alpha and 85.30% in Delta group ( P<0.001), The proportion of patients with fever (80.71% vs. 40.94%, P<0.001) was significantly higher in Alpha than Delta strain group. The proportion of critical ill patients was significantly higher in Delta group (9.90% vs. 1.57%, respectively, P<0.001). The virus negative conversion time was significantly longer in Delta than Alpha group (22 d vs. 11 d, P<0.001), but the incidence of liver injury was significantly higher in Alpha than Delta group (20.05% vs. 13.91%, P=0.011). Univariate analysis showed that Alpha virus strain infection, male sex, body mass index, chronic liver disease, fever, diarrhea, shortness of breath, severe/critical illness, elevated creatine kinase (CK), elevated international normalized ratio (INR) and an elevated neutrophil/lymphocyte ratio was significantly associated with an increased risk of liver injury occurrence, and in patients with pharyngeal pain the risk of liver injury occurrence was significantly reduced. Multivariate analysis showed that shortness of breath [ OR, 2.667 ( CI: 1.389-5.122); P=0.003], increased CK [ OR, 2.544 ( CI: 1.414-4.576); P=0.002] and increased INR [OR, 1.721] ( CI: 1.074-2.758); P=0.024] was significantly associated with an increased risk of liver injury occurrence, and in patients with pharyngeal pain the risk of liver injury occurrence was significantly reduced [ OR, 0.424 ( CI: 0.254-0.709); P=0.001]. Conclusion:Although the virulence of the Delta is stronger than Alpha strain, most patients infected with Delta strain vaccinated against COVID-19 in Zhejiang province had milder clinical symptoms and a lower incidence and degree of liver injury. Notably, the infection risk even remains after vaccination; however, symptoms and the incidence of severe and critical illness can be significantly reduced.