The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.

The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.

The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.

OBJECTIVE To provide a reference for standardizing the conduct of positron-emitting radiopharmaceuticals’ phase 0 clinical trials （hereinafter referred to as “phase 0 clinical trials”） and advancing the development of innovative drug by medical institutions. METHODS Initiated by the First Affiliated Hospital of Jinan University， a panel of experts consisting of pharmacy， clinical medicine and medical ethics from multiple institutions was established to investigate the current landscape， and discuss the necessary conditions， procedures， and other aspects for conducting phase 0 clinical trials in medical institutions by integrating relevant national policies， regulations and expert consensus. Finally， an agreement was reached to formulate this consensus. RESULTS & CONCLUSIONS Currently， most medical institutions have deficiencies in pharmaceutical care during the management of radiopharmaceuticals and the phase 0 clinical trials. In conjunction with the Expert Consensus on the Establishment of Nuclear Pharmacist Positions， this consensus explicitly defines the responsibilities of nuclear pharmacists in the phase 0 clinical trials on the basis of the Expert Consensus for the Application of Positron Emission Tomography Radioligands for Translational Study in the Phase 0 Clinical Trials （2020 edition）， providing a guidance for high-quality participation of nuclear pharmacists from medical institutions in China in phase 0 clinical research. Additionally， in consideration of some constraints imposed by current relevant regulations， this consensus also proposes strategic recommendations， such as encouraging medical institutions to form a consortium， leading to the establishment of dedicated bases or industrial parks， holding significant implications to strengthen institutional capacity for advancing radiopharmaceutical innovation through phase 0 clinical trials.

Humans ; Lupus Vasculitis, Central Nervous System/pathology* ; Magnetic Resonance Imaging/methods* ; Diffusion Tensor Imaging/methods* ; Patients ; Lupus Erythematosus, Systemic/pathology* ; Brain/pathology*

Humans ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis ; Biomarkers, Tumor/genetics* ; Mutation/genetics* ; Colorectal Neoplasms/genetics* ; Proto-Oncogene Proteins B-raf/metabolism*

OBJECTIVE To investigate and analyze the operational costs and current charging policies of pharmacy intravenous admixture service （PIVAS） in China， and provide a reference for promoting high-quality and sustainable development of PIVAS. METHODS Questionnaires were distributed in 30 provinces， autonomous regions， and municipalities across the country through the “Wenjuanxing” platform from May 6th to July 1st， 2022. The operational costs， charging status and suggestions of PIVAS were investigated and analyzed. RESULTS A total of 761 PIVAS participated in the survey nationwide， including 666 tertiary medical institutions， 93 secondary medical institutions， and 2 primary medical institutions. Approximately 60.58% of PIVAS had implemented a charging system that allowed charges. Among them， most PIVAS required inspection and evaluation before charging. The annual operating cost of PIVAS in China was approximately 2 098 100 yuan， with the integrated operating cost comprising 89.36% of the total， while the dispensing cost accounted for only 10.64%. Human costs emerged as the highest annual consumption （74.20%）， followed by decoration and facility maintenance costs （4.77%） and equipment acquisition costs （3.44%）. Regarding charges for different drugs nationwide， common drugs had an average charge standard of 4.39 yuan per bag while antibacterial drugs averaged 5.01 yuan per bag； hazardous drugs had an average charge of 23.17 yuan per bag， whereas parenteral nutrition solutions averaged 38.75 yuan per bag. However， the recommended average charges of the four drugs mentioned above were 6.71， 9.63， 38.35 and 44.03 yuan per bag， respectively. CONCLUSIONS At present， there is no unified inspection and evaluation standard and charging standard in China. Moreover， the current charging standard is lower than the recommended standard. It is necessary to combine operational costs and develop more reasonable and fair charging standards.

Objective To investigate the value of serum aquaporin 1(AQP1)level combined with extra-vascular lung water index(EVLWI)in assessing the severity and prognosis of sepsis causing acute respiratory distress syndrome(ARDS).Methods 268 patients with sepsis-induced ARDS(ARDS group)and 55 patients with sepsis alone(sepsis alone group)admitted to our hospital from January 2020 to December 2023 were selected.Patients with sepsis-induced ARDS were divided into 89 mild,109 moderate,and 70 severe groups according to the oxygenation index(OI),and 104 deaths and 164 survivors according to the 28 d prognosis.Detection of serum AQP1 levels and calculation of EVLWI.Using Spearman's method,the correlation between serum AQP1 level,EVLWI and OI in patients with sepsis-induced ARDS;the establishment of a logistic regression model to determine the factors of sepsis-induced mortality in patients with ARDS;and the plotting of ROC curves to evaluate the value of serum AQP1 level in combination with EVLWI for its assessment.Results Compared with the simple sepsis group,serum AQP1 level was reduced and EVLWI was increased in the ARDS group(P<0.05).AQP1 levels were sequentially lower and EVLWI sequentially higher in the mild,moderate,and severe groups(P<0.05).Serum AQP1 levels were positively correlated with OI in patients with sepsis-induced ARDS,and EVLWI was negatively correlated with OI in patients with sepsis-induced ARDS(P<0.05).The 28 d mortality rate in 268 patients with ARDS due to sepsis was 38.81%(104/268).The independent protective factors for death in ARDS patients with sepsis were elevated OI(OR=0.984,95%CI:0.976～0.992)and elevated AQP1(OR=0.761,95%CI:0.677～0.854),and the independent risk factors were increased SOFA score(OR=1.367,95%CI:1.142～1.636)and elevated blood lactate(OR=2.515,95%CI:1.689～3.745),and elevated EVLWI(OR=1.559,95%CI:1.290～1.885)(P<0.05).The AUC predicted by serum AQP1 level combined with EVLWI was 0.887(95%CI:0.843～0.923),which was greater than the AUC predicted by serum AQP1 level,and EVLWI alone,which was 0.792(95%CI:0.738～0.839),and 0.807(95%CI:0.754～0.852)(P<0.05).Conclusion Decreased serum AQP1 levels and elevated EVLWI were associated with increased severity and poor prognosis in patients with sepsis-induced ARDS,and serum AQP1 levels in combination with EVLWI were of high value in assessing the prognosis of patients with sepsis-induced ARDS.

Background::Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.Methods::We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.Results::The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1. The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes. Conclusion::The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1. Trial Registration::No. NCT00454519 (https://clinicaltrials.gov/)

Background::Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD.Methods::In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort.Results::In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone.Conclusion::ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE.Trial Registration::Chictr.org.cn: ChiCTR2200059599.