Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is the primary cause of mortality in sepsis, with its core pathophysiological mechanism being severe ischemia and hypoxia in critical units—composed of microcirculation and the mitochondria of functional cells—resulting from disruptions in blood flow and oxygen flow following a dysregulated host response. Due to the systemically convergent yet clinically heterogeneous nature of the host response, current understanding and management strategies for hemodynamics remain inconsistent, often leading to inadequate resuscitation or overtreatment. To improve the quality of care, based on a systematic review of the "blood flow-oxygen flow" theory, an expert panel emphasizes reevaluating septic shock from an integrated perspective of blood flow and oxygen flow, and has formulated the Expert Consensus on Blood Flow and Oxygen Delivery Phenotyping and Clinical Management of Septic Shock (2025). The consensus proposes that clinical typing of blood flow-oxygen flow should comprehensively consider cardiac function, vascular tone, oxygen flow utilization status in critical units, and disease trajectory, while optimizing subtype identification by integrating host response phenotypes and artificial intelligence technologies. It advocates establishing a continuous assessment system through multi-site oxygen flow monitoring for organ perfusion, peripheral perfusion monitoring, and critical care ultrasound. Under the framework of the "critical care triangle", the consensus promotes the implementation of individualized, bundled management strategies, providing guidance for multiple management points to restore blood flow-oxygen flow matching, reduce the risk of organ failure, and decrease patient mortality.

The construction of a training system for visiting physicians in the department of rare diseases in China is an important measure to improve the overall diagnosis and treatment capacity for rare diseases and address the critical challenge of insufficient knowledge and skills among clinicians in practice. This article systematically describes the visiting physician training system established by the Department of Rare Diseases at Peking Union Medical College Hospital. It summarizes the training objectives and positioning, design logic, and learning modules of the system, aiming to provide a reference for the construction of the specialized talent team for rare diseases in China.

Endoscopic retrograde cholangiopancreatography （ERCP）， as an advanced endoscopic diagnostic and therapeutic technique， plays an important role in clinical practice. However， due to its complex operation and high technical requirements， it may lead to a series of severe complications， among which perforation is an important issue of concern. Perforation not only increases pain and treatment difficulty， but also threatens the life of patients. In order to guarantee good clinical outcomes， it is necessary to further improve the standard processes for the prediction， diagnosis， and management of perforation due to ERCP. This article discusses the risk factors， diagnostic methods， preventive measures， and treatment strategies for ERCP-related gastrointestinal perforation， in order to provide a reference for identifying high-risk populations and developing individualized treatment regimens in clinical practice.

Objective:To investigate the temporal expression of Growth Differentiation Factor-15 (GDF15) in the serum of patients with Acute Coronary Syndrome (ACS) and explore the clinical significance of GDF15 in protecting cardiomyocytes in ACS.Methods:A retrospective study was conducted on 289 ACS patients admitted to the emergency departments from February to October 2023. Data on gender, age, troponin T (TnT), creatine kinase isoenzyme (CK-MB), GDF15, and B-type natriuretic peptide (BNP) within 30 minutes of admission were recorded. Differences in these indicators among different groups were compared. Receiver Operating Characteristic (ROC) curves were plotted to evaluate the diagnostic value of GDF15, TnT, and BNP for ACS. Among the patients, 15 exhibited a temporal expression pattern of GDF15, and their blood samples were re-measured using a GDF15 fluorescent quantitative immunochromatographic assay kit. Fifteen patients without temporal expression were randomly selected as controls, and their samples were also re-measured to exclude detection errors. Fifteen patients with temporal expression were included in the temporal expression group, and 15 without temporal expression were included in the non-temporal expression group. Laboratory indicators such as fasting blood glucose, glycated hemoglobin, triglycerides, creatinine, and uric acid were compared between the groups. Additionally, patient age, gender, body mass index (BMI), coronary angiography results, echocardiography, Gensini score, left ventricular ejection fraction (LVEF), and GRACE risk score were recorded to assess their correlation with GDF15 temporal expression. Statistical analysis was performed using SPSS 27 software, with continuous data expressed as mean ± standard deviation (Mean ± SD) and compared using t-tests and χ2 tests. Results:The overall trend in ACS patients showed a higher proportion of males than females (73.36% vs. 26.64%). The oldest group was the Unstable Angina (UA) group, with a mean age of (63.98 ± 15.19) years, while the youngest group was the non-ACS chest pain group, with a mean age of (54.29 ± 16.39) years. A higher proportion of patients in the UA, ST-segment elevation myocardial infarction (STEMI), and non-ST-segment elevation myocardial infarction (NSTEMI) groups had a history of smoking. The combination of GDF15 and TnT showed high diagnostic value for ACS, with an area under the ROC curve (AUC) of 0.843, consistent with previous studies. Among all ACS patients, 15 exhibited a temporal expression pattern of GDF15, where GDF15 levels peaked at 4 hours, gradually decreased, and peaked again at 24 hours. Patients in the temporal expression group had higher LVEF and left ventricular end-systolic diameter compared to the non-temporal expression group. The Gensini score was lower in the temporal expression group, and the GRACE risk score was significantly lower in the temporal expression group (00.7±14.72) compared to the non-temporal expression group (116.1±23.46), with a statistically significant difference ( P = 0.0115). There were no significant differences in general characteristics (age, gender, BMI) or clinical biochemical indicators (fasting blood glucose, glycated hemoglobin, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, creatinine, uric acid) between the temporal and non-temporal expression groups ( P > 0.05). Conclusions:GDF15 demonstrates significant diagnostic and prognostic predictive value in ACS. Patients with temporally dynamic expression of serum GDF15 exhibit milder myocardial injury and a lower probability of mortality. These findings provide novel therapeutic targets and research directions for further exploring the role of GDF15 in ACS management.

Background: Acetaminophen (APAP)-induced hepatotoxicity has attracted considerable attention in clinical settings due to the limited treatment options available. Liensinine stands out as a key alkaloid known for its pharmaceutical activities. However, the role of liensinine in mitigating APAP-induced liver injury remains unclear. Objective: The aim of the study was to explore the protective effects of liensinine against APAP-induced liver injury. Methods: C57BL/6 male mice were treated with a dose of 200 mg/kg N-acetylcysteine or varying doses of liensinine (10 or 20 mg/kg) for seven consecutive days. APAP (400 mg/kg, i.g.) was then administered to induce liver damage for 12 hours. Blood samples and hepatic tissues were collected for further analysis. Liver enzyme levels and histopathological analysis were employed to assess liver injury. RNA-seq was conducted to evaluate the dynamic changes in gene expression. Biochemical assays were used to measure oxidative stress and inflammation, while the TUNEL assay was performed to assess hepatocyte apoptosis. Results: The results demonstrated that the administration of liensinine mitigated serum liver enzyme levels and tissue damage resulting from APAP overdose. Transcriptome analysis revealed significant and coordinated changes in genes related to the peroxisome proliferator-activated receptor signaling pathway, mitogen-activated protein kinase signaling pathway, and apoptosis pathway in response to APAP-induced hepatotoxicity. The expression alterations of key genes within these three pathways, associated with inflammation, oxidative stress, and cell apoptosis, were reversed by liensinine, indicating its potential in alleviating APAP-induced liver damage through multiple signaling pathways. This suggests the diverse therapeutic effects of liensinine, including inflammation suppression, oxidative stress reduction, and cell apoptosis inhibition. Indeed, pretreatment with liensinine effectively reduced inflammatory cytokines, oxidative stress indicators, and apoptotic cells induced by APAP. Conclusions: Liensinine mitigates APAP-induced hepatotoxicity in mice through multifaceted pathways, providing anti-inflammatory, antioxidant, and anti-apoptotic benefits.

Background: Acetaminophen (APAP)-induced hepatotoxicity has attracted considerable attention in clinical settings due to the limited treatment options available. Liensinine stands out as a key alkaloid known for its pharmaceutical activities. However, the role of liensinine in mitigating APAP-induced liver injury remains unclear. Objective: The aim of the study was to explore the protective effects of liensinine against APAP-induced liver injury. Methods: C57BL/6 male mice were treated with a dose of 200 mg/kg N-acetylcysteine or varying doses of liensinine (10 or 20 mg/kg) for seven consecutive days. APAP (400 mg/kg, i.g.) was then administered to induce liver damage for 12 hours. Blood samples and hepatic tissues were collected for further analysis. Liver enzyme levels and histopathological analysis were employed to assess liver injury. RNA-seq was conducted to evaluate the dynamic changes in gene expression. Biochemical assays were used to measure oxidative stress and inflammation, while the TUNEL assay was performed to assess hepatocyte apoptosis. Results: The results demonstrated that the administration of liensinine mitigated serum liver enzyme levels and tissue damage resulting from APAP overdose. Transcriptome analysis revealed significant and coordinated changes in genes related to the peroxisome proliferator-activated receptor signaling pathway, mitogen-activated protein kinase signaling pathway, and apoptosis pathway in response to APAP-induced hepatotoxicity. The expression alterations of key genes within these three pathways, associated with inflammation, oxidative stress, and cell apoptosis, were reversed by liensinine, indicating its potential in alleviating APAP-induced liver damage through multiple signaling pathways. This suggests the diverse therapeutic effects of liensinine, including inflammation suppression, oxidative stress reduction, and cell apoptosis inhibition. Indeed, pretreatment with liensinine effectively reduced inflammatory cytokines, oxidative stress indicators, and apoptotic cells induced by APAP. Conclusions: Liensinine mitigates APAP-induced hepatotoxicity in mice through multifaceted pathways, providing anti-inflammatory, antioxidant, and anti-apoptotic benefits.

Background: Acetaminophen (APAP)-induced hepatotoxicity has attracted considerable attention in clinical settings due to the limited treatment options available. Liensinine stands out as a key alkaloid known for its pharmaceutical activities. However, the role of liensinine in mitigating APAP-induced liver injury remains unclear. Objective: The aim of the study was to explore the protective effects of liensinine against APAP-induced liver injury. Methods: C57BL/6 male mice were treated with a dose of 200 mg/kg N-acetylcysteine or varying doses of liensinine (10 or 20 mg/kg) for seven consecutive days. APAP (400 mg/kg, i.g.) was then administered to induce liver damage for 12 hours. Blood samples and hepatic tissues were collected for further analysis. Liver enzyme levels and histopathological analysis were employed to assess liver injury. RNA-seq was conducted to evaluate the dynamic changes in gene expression. Biochemical assays were used to measure oxidative stress and inflammation, while the TUNEL assay was performed to assess hepatocyte apoptosis. Results: The results demonstrated that the administration of liensinine mitigated serum liver enzyme levels and tissue damage resulting from APAP overdose. Transcriptome analysis revealed significant and coordinated changes in genes related to the peroxisome proliferator-activated receptor signaling pathway, mitogen-activated protein kinase signaling pathway, and apoptosis pathway in response to APAP-induced hepatotoxicity. The expression alterations of key genes within these three pathways, associated with inflammation, oxidative stress, and cell apoptosis, were reversed by liensinine, indicating its potential in alleviating APAP-induced liver damage through multiple signaling pathways. This suggests the diverse therapeutic effects of liensinine, including inflammation suppression, oxidative stress reduction, and cell apoptosis inhibition. Indeed, pretreatment with liensinine effectively reduced inflammatory cytokines, oxidative stress indicators, and apoptotic cells induced by APAP. Conclusions: Liensinine mitigates APAP-induced hepatotoxicity in mice through multifaceted pathways, providing anti-inflammatory, antioxidant, and anti-apoptotic benefits.

Endoscopic retrograde cholangiopancreatography(ERCP),as an advanced endoscopic diagnostic and therapeutic technique,plays an important role in clinical practice.However,due to its complex operation and high technical requirements,it may lead to a series of severe complications,among which perforation is an important issue of concern.Perforation not only increases pain and treatment difficulty,but also threatens the life of patients.In order to guarantee good clinical outcomes,it is necessary to further improve the standard processes for the prediction,diagnosis,and management of perforation due to ERCP.This article discusses the risk factors,diagnostic methods,preventive measures,and treatment strategies for ERCP-related gastrointestinal perforation,in order to provide a reference for identifying high-risk populations and developing individualized treatment regimens in clinical practice.

Objective To investigate the value of CT radiomics combined with CT and preoperative pathological features for predicting postoperative early recurrence(ER)of local advanced esophageal squamous cell carcinoma(LAESCC).Methods Data of 334 patients with LAESCC were retrospectively analyzed.The patients were divided into training set(n=234)and verification set(n=100)at the ratio of 7:3 and were followed up to observe ER(recurrence within 12 months after surgery)or not.Univariate and multivariate logistic regression were used to analyze clinical,CT and preoperative pathological features of LAESCC in patients with or without ER in training set.The independent risk factors of ER were screened,and a CT-preoperative pathology model was constructed.Based on venous phase CT in training set,the radiomics features of lesions were extracted and screened to establish radiomics model,and finally a combined model was established based on radiomics model and the independent risk factors.Receiver operating characteristic(ROC)curves were drawn,and the area under the curve(AUC)was calculated to evaluate the diagnostic efficacy of each model.Results Among 334 cases,168 were found with but 166 without ER.In training set,117 cases were found with while the rest 117 without ER,while in verification set,51 were found with but 49 without ER.The length of lesions,cT stage and cN stage shown on CT and tumor differentiation degree displayed with preoperative pathology were all independent risk factors for ER of LAESCC(all P＜0.05).The AUC of CT-preoperative pathology model in training set and validation set was 0.759 and 0.783,respectively.Ten best radiomics features of LAESCC were selected,and AUC of the established radiomics model in training set and validation set was 0.770 and 0.730,respectively.The AUC of combined model in training and validation set was 0.838 and 0.826,respectively.The AUC of CT radiomics combined with CT and preoperative pathological features in training set was higher than that of CT-preoperative pathologymodel and radiomics model(both P＜0.01).Conclusion CT radiomics combined with CT and preoperative pathological features could effectively predict postoperative ER of LAESCC.

OBJECTIVE To investigate the intervention effect and potential mechanism of breviscapine on hepatic fibrosis （HF） in rats based on the transforming growth factor-β（1 TGF-β1）/Smad2/extracellular signal-regulated protein kinase 1（ERK1） and Kelch-like epichlorohydrin-associated protein 1（Keap1）/nuclear factor-erythroid 2-related factor 2（Nrf2）/heme oxygenase-1（HO-1） pathways. METHODS Totally 60 rats were randomly divided into normal control group， model group， breviscapine low-dose， medium-dose and high-dose groups （5.4， 10.8， 21.6 mg/kg）， and colchicine group （positive control， 0.45 mg/kg）， with 10 rats in each group， half male and half female. Except for the normal control group， HF model of the other groups was induced by carbon tetrachloride. Subsequently， each drug group was given corresponding medicine by gavage once a day for 28 days. The liver appearance of rats in each group was observed and their liver coefficients were calculated. The levels of alanineaminotransferase （ALT） and aspartate aminotransferase （AST）in serum， those of ALT， AST， superoxide dismutase （SOD），malondialdehyde （MDA） and glutathione peroxidase （GSH- Px） in liver tissue were detected. The liver tissue inflammatory and fibrotic changes were observed. The protein and mRNA expressions of TGF-β1， Smad2， ERK1， Nrf2， Keap1 and HO-in liver tissue were detected. RESULTS Compared with the normal control group， the model group showed large areas of white nodular lesions in the liver， obvious inflammatory cell infiltration and collagen fiber deposition. The body weight， the levels of SOD and GSH-Px in liver tissue， the protein and mRNA expressions of Nrf2 and HO-1 were significantly lowered in the model group （P＜0.05）； the liver coefficient， the percentage of Masson staining positive area， ALT and AST levels of serum and liver tissue， MDA level of liver tissue， the protein and mRNA expressions of TGF-β1， Smad2， ERK1 and Keap1 were significantly increased （P＜0.05）. Compared with the model group， the liver lesions of rats in each drug group were improved， and the above quantitative indexes were generally reversed （P＜0.05）. CONCLUSIONS Breviscapine has a good intervention effect on HF rats， which may be related to inhibiting TGF-β1/Smad2/ERK1 pathway for anti-fibrosis and regulating Keap1/Nrf2/HO-1 pathway to inhibit oxidative stress.