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 harmonious doctor-patient relationship requires both doctors and patients to bear the corresponding moral responsibilities. Patients’ moral responsibilities refer to the duties that patients should take action and bear the corresponding good and bad consequences to restore their physical or mental health， as well as the good qualities that help patients adapt to and integrate into their patient roles and pursue excellence. The logical direction of patients’ moral responsibilities represents the practical vision and value orientation of patients’ moral responsibility research. Healthy bodies are the direct goal of patients’ moral responsibilities， harmonious interpersonal relationships serve as the basic goal， and good lives represent the core goal. The logical direction of patients’ moral responsibilities returns to the human being， focusing on profound care for real patients and ideal construction. Healthy bodies， harmonious interpersonal relationships， and good lives collectively achieve “good patients”， who are the logical direction of patients’ moral responsibilities.

Objective To analyze the occurrence status and risk factors of frailty in elderly patients with heart failure (HF), and improve the prognosis of elderly patients with HF. Methods Totally 306 elderly patients with HF who received treatment in the hospital were selected from April 2021 to April 2024 as the study subjects. The occurrence of frailty was counted, and the patients were divided into frailty group and non-frailty group according to occurrence status of frailty. Univariate and logistic multivariate regression analyses were adopted to analyze the risk factors of frailty in elderly HF patients. Results Among the 306 patients, there were 92 cases of frailty, with an incidence rate of 30.07%. There were obvious differences in age, HF grading, nutritional status, negative emotions, left ventricular ejection fraction, hemoglobin and creatinine between groups (P<0.05). After logistic multivariate analysis, it was found that age≥70 years old, HF grading, malnutrition, negative emotions and creatinine were the high risk factors for frailty in elderly patients with HF, and left ventricular ejection fraction and hemoglobin level were the protective factors (OR: 1.662, 95%CI: 0.845-3.268; OR: 4.586, 95%CI: 2.318-9.071; OR: 3.971, 95%CI: 1.806-8.731; OR: 3.307, 95%CI: 1.457-7.503; OR: 0.456, 95%CI: 0.255-0.816; OR: 0.525, 95%CI: 1.156-0.967, P<0.05). Conclusion The risk of frailty is high in elderly patients with HF, and is affected by age, heart failure grading, nutritional status, negative emotions, left ventricular ejection fraction, hemoglobin and creatinine. Clinically, it is necessary to take prevention and intervention measures for such patients to reduce the occurrence of frailty.

Objective By using the bibliometrics method,the literature about Yinchenhao decoction was visualized and analyzed to explore its research hot spot and frontier.Methods The related literatures on Yinchenhao decoction were retrieved from CNKI database,and CiteSpace 6.1.R6 software was used to analyze the authors,institutions and key words,and the key words were clustered to draw a visual atlas.Results A total of 856 articles were included,and the number of articles showed a fluctuating upward trend.There were 764 authors and 513 related key words,including clinical application,experimental study and signaling pathway of Yinchenhao decoction.Conclusion Although Yinchenhao decoction is a commonly used clinical prescription for liver disease,there is a lack of studies on the mechanism of action and molecular level.Future research hot spot should focus more on large sample randomized controlled clinical studies and experimental studies,so as to provide new directions for researchers.

ObjectiveTo reveal the molecular mechanism of Angong Niuhuangwan（AGNH） in improving traumatic brain injury（TBI） based on single cell sequencing. MethodSeventy-five male SD rats were randomly divided into the sham group， model group， piracetam group（3.6 g·kg^-1）， AGNH low- and high-dose groups（0.09， 0.27 g·kg^-1）， with 15 rats in each group. In addition to the sham group， the other 4 groups used the modified Feeney free-fall impact method to prepare TBI model， and the drugs were administered by gavage immediately after modeling， 24 hours later， the modified neurological deficit score（mNSS） was performed， and brain tissue was isolated to determine the degree of cerebral edema. Hematoxylin-eosin（HE） staining was used to observe the injury degree in the cortex， CA1 region and CA3 region of brain tissue. The expression levels of cyclooxygenase-2（COX-2）， interferon regulatory factor 1（IRF1）， Janus kinase 2（JAK2） and suppressor of cytokine signaling 3（SOCS3） were observed by immunofluorescence（IF） staining. The levels of interleukin（IL）-6， IL-18， IL-1β， IL-17A， tumor necrosis factor-α（TNF-α）， Caspase-1 and nucleotide binding oligomerization domain（NOD）-like receptor heat protein domain associated protein 3（NLRP3） inflammasome were determined by enzyme-linked immunosorbent assay（ELISA）. The regulation of AGNH on each cell population was analyzed by single cell sequencing， and differentially expressed genes were analyzed by Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG）， which led to construct microglia differentially expressed gene network to search for the key targets， and validated by ELISA and IF. ResultCompared with the sham group， the mNSS and brain water content were significantly increased in the model group（P<0.01）. Compared with the model group， mNSS and brain water content in the low and high dose AGNH groups were decreased（P<0.05，P<0.01）. HE staining results showed that compared with the sham group， the cells in the cerebral cortex and hippocampus of rats in the model group were seriously lost， and the cells were arranged loosely（P<0.01）. Compared with the model group， AGNH could significantly increase the density of neurons in the CA1 and CA3 regions of the cerebral cortex and hippocampus， making the arrangement more compact， as well as improved cell morphology（P<0.05，P<0.01）. ELISA and IF staining showed that AGNH could reduce the levels of Caspase-1， IL-17A， TNF-α， NLRP3 and COX-2 in brain tissue of TBI rats（P<0.05， P<0.01）. A total of 13 cell subsets were identified by single cell sequencing， among which microglia played an important role in neuroimmunity. The results of GO enrichment analysis of differentially expressed genes in microglia showed that AGNH improved TBI in response to inflammation and TNF-α. KEGG enriched IL-17 signaling pathway， TNF signaling pathway， Toll-like receptor signaling pathway， etc. The results of network analysis showed that the key targets of AGNH in regulating TBI might be IL-6， IL-1β， JAK2， SOCS3， IRF1. IF and ELISA verification results showed that compared with the sham group， SOCS3 expression in microglia was decreased in the model group， and the expressions of IL-6， IL-1β， JAK2 and IRF1 were increased（P<0.01）. Compared with the model group， AGNH could increase the expression of SOCS3， decrease the expression of IL-6， IL-1β， JAK2， IRF1 （P<0.05， P<0.01）. ConclusionAGNH can reduce the degree of brain edema and brain injury， decrease the expression of inflammatory factors， and inhibit the expression of NLRP3 and its downstream Caspase-1 in TBI rats， which may act on the targets of IL-6， IL-1β， JAK2， IRF1 and SOCS3 in microglia.

Acute ST-segment elevation myocardial infarction with multivessel disease is one of the high-risk types of coronary heart disease.Early opening of infarct-related artery and reperfusion of myocardium could significantly reduce the mortality in acute phase.However,the presence of non-culprit lesions in non-infarct-related arteries is still at risk and has an important impact on the long-term prognosis of patients.It remains controversial on how to precisely evaluate the clinical significance and revascularization value of non-culprit lesions.This article aims to review the research status and progress of guidance strategies of non-culprit lesion revascularization in patients with ST-segment elevation myocardial infarction and multivessel disease.

Objective:To make an individual phantom that was printed by using three dimension(3D)technique,which could reflect the real situation of patient,and to analyze the computed tomography(CT)value and dose distribution of radiotherapy on each organ of the inside of the 3D-printed individual phantom.Methods:According to the localization of CT image of the patient,the empty shell of 3D structure of each organ were reconstructed and printed by using 3D technique.The CT value was used as basis to select the equivalent material of each organ to perform fill,which could obtain the individual phantom of chest that could appear the structural characteristics of patient.The treatment plan of patients were included in treatment plan group,and the plans which were transplanted to 3D-printed individual phantom from treatment plan of patients were included in phantom plan group.The dosimetric parameters of the plans of two groups were compared.Results:The average CT values of left and right lung,soft tissue,cancellous bone,compact bone and heart of the phantom plan group were respectively-709,-737,14,144,760 and 28 HU.The errors of the all CT values between phantom images and located images of patients were less than 16.7%.The exposure doses of normal tissues of radiotherapy plans on the images of two groups could meet the clinical requirements.The minimum dose(Dmin),mean dose(Dmean),the corresponding doses of 98%,50% and 2% target volumes(D98%,D50% and D2%),conformity index(CI),homogeneity index(HI),monitor unit(MU)of dosimetric parameters of the target region could meet the clinical requirements without statistically significant differences.There was significant differences in the maximum dose(Dmax)of the target region(t=2.678,P＜0.05).Among of these Dmax values,the Dmax value of phantom plan group was larger,which was(56.97±0.32)Gy.Conclusion:The CT value,tissue structure and spatial distribution of the phantom,which is finally designed,can emulate the chest of human body in radiotherapy.It has verified the feasibility that 3D-printed phantom is applied in measuring dose in the quality assurance of radiotherapy.

OBJECTIVE To comprehensively evaluate the three oral Janus kinase inhibitors （JAKi） such as upadacitinib， abrocitinib and baricitinib in the treatment of atopic dermatitis. METHODS The six dimensions of safety， efficacy， economy， appropriateness， accessibility and innovativeness were used for evaluation. Meta-analysis was conducted to evaluate the safety and efficacy of three oral JAKi； pharmacoeconomic studies were searched， and the treatment costs were calculated to evaluate the economy of each JAKi. Appropriateness was described based on literature review and drug labels. Accessibility of three oral JAKi was assessed by using a questionnaire survey. The innovation of JAKi was elucidated from the perspective of its mechanism of action. RESULTS In terms of safety， the incidence of upper respiratory tract infection （OR＝1.47， 95%CI of 1.04-2.08， P＝0.03） and nasopharyngitis （OR＝1.44， 95%CI of 1.06-1.95， P＝0.02） in the upadacitinib 30 mg group was significantly higher than that in the placebo group； the incidence of nasopharyngitis in baricitinib 4 mg group was significantly higher than that in the placebo group （OR＝2.24， 95%CI of 1.39-3.61， P＝0.000 8） and baricitinib 2 mg group （OR＝0.48， 95%CI of 0.31-0.74，P＝0.001）. In terms of efficacy， regardless of the dosage， all three JAKi groups were superior to the placebo group， and the high-dose groups of upadacitinib and abrocitinib were superior to the low-dose groups （P＜0.000 1）. In terms of economy， the annual treatment cost of baricitinib was the lowest （13 870.0 yuan）， but it has not been approved for atopic dermatitis indication in China； next was upadacitinib （27 192.5 yuan）. In terms of appropriateness， the overall appropriateness of the three JAKis was good， but none of them was suitable for patients with severe liver injury. In terms of accessibility， baricitinib had the highest availability rate （59.4%）， but the affordability of upadacitinib was relatively good under China’s medical insurance system. In terms of innovation， among the three types of JAKi， upadacitinib and abrocitinib had better innovation. CONCLUSIONS Three oral JAKi treatments for atopic dermatitis have controllable safety and good efficacy. Considering the issue of medical insurance reimbursement， it is recommended that Chinese patients use upadacitinib.

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.

Objective To explore the correlation of CPNE3 expression with long-term prognosis of patients with gastric cancer(GC)and the possible mechanism.Methods We retrospectively collected the data of 104 GC patients undergoing radical surgery in our hospital from February,2013 to October,2017.TCGA database and immunohistochemistry were used to analyze CPNE3 expression level in GC tissues and its effects on tumor progression and long-term prognosis of the patients.GO analysis was performed to predict the biological role of CPNE3 in GC.We also conducted cell experiments with MGC803 cells and observed the effects of CPNE3 knockdown,CPNE3 overexpression and LY294002(a PI3K/AKT inhibitor)treatment on cell apoptosis and cellular expressions of apoptotic proteins using flow cytometry and Western blotting.Results TCGA analysis and immunohistochemistry both showed high expressions of CPNE3 in GC(P<0.05).The patients with high CPNE3 expressions had a reduced 5-year survival(P<0.01),and a high CPNE3 expression,CEA level≥5 μg/L,CA19-9 level≥37 kU/L,T3-T4 stage,and N2-N3 stage were all independent risk factors for a lowered 5-year survival rate after surgery.The sensitivity and specificity of CPNE3 for predicting 5-year mortality was 79.59%and 74.55%,respectively(P<0.05).GO analysis predicted that CPNE3 negatively regulated GC cell apoptosis.In MGC803 cells,CPNE3 knockdown significantly increased cell apoptosis,enhanced Bax and Cleaved Caspase-3 expressions and decreased Bcl-2 expression,while CPNE3 overexpression produced the opposite results(P<0.05).The cellular expressions of p-PI3K and p-AKT were significantly decreased following CPNE3 knockdown and increased following CPNE3 overexpression(P<0.05).Treatment with LY294002 obviously attenuated the inhibitory effect of CPNE3 overexpression on apoptosis of MGC803 cells(P<0.05).Conclusion CPNE3 is highly expressed in GC tissues and affects the long-term prognosis of the patients possibly by inhibiting GC cell apoptosis through activation of PI3K/AKT signaling.