Objective:To investigate the value of habitat radiomic features based on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI in establishing a predictive model for cytokeratin 19 (CK19) expression in hepatocellular carcinoma (HCC) and to evaluate its role in prognostic risk stratification.Methods:This multicenter case-control study retrospectively enrolled 489 patients with pathologically confirmed HCC who underwent Gd-EOB-DTPA-enhanced MRI between June 2016 and June 2024. Among them, 346 patients from the First Affiliated Hospital of Soochow University were divided into a training cohort ( n=245) and an internal test cohort ( n=101) via stratified sampling at a 7∶3 ratio. And 143 patients from Nantong Third Hospital Affiliated to Nantong University served as an external validation cohort. The training cohort included 53 CK19-positive and 192 CK19-negative patients. The internal test cohort included 21 CK19-positive and 80 CK19-negative patients. The external validation cohort included 30 CK19-positive and 113 CK19-negative patients. Univariate logistic regression analysis was performed to identify potential factors associated with CK19 expression, and a clinical-radiologic model was constructed. The k-means clustering algorithm was applied to segment target HCC lesions into 3 subregions. Radiomic features were extracted and selected from these habitat subregions. Habitat radiomics models were constructed for the arterial phase (AP), portal venous phase, hepatobiliary phase (HBP), and combined phases (CP). Multivariate logistic regression analysis identified independent clinical and radiologic predictors of CK19 expression, and the optimal habitat model score was integrated to build a clinical-radiologic-habitat combined model. The area under the receiver operating characteristic curve (AUC) was used to evaluate model predictive performance. Recurrence-free survival (RFS) was analyzed using the Kaplan-Meier method and the differences in survival curves were compared with the log-rank test. Results:Univariate logistic regression analysis revealed that alpha-fetoprotein (AFP) ( OR=2.629, 95% CI 1.412-4.896, P=0.002), AP enhancement ( OR=3.636, 95% CI 1.642-8.052, P=0.001), AP peritumoral enhancement ( OR=2.219, 95% CI 1.084-4.542, P=0.029), and HBP peritumoral hypointensity ( OR=2.010, 95% CI 1.004-4.021, P=0.049) were potential factors associated with CK19 expression, which were incorporated into the clinical-radiologic model. In the internal and external validation cohorts, the AUC of the clinical-radiologic model was 0.690 (95% CI 0.590-0.778) and 0.650 (95% CI 0.565-0.727), respectively. The habitat radiomics model based on CP images demonstrated the highest performance. It achieved AUC of 0.729 (95% CI 0.622-0.836) and 0.725 (95% CI 0.607-0.842) in the internal and external validation cohorts, respectively. Multivariate analysis identified AFP ( OR=2.494, 95% CI 1.163-5.348, P=0.019), AP enhancement ( OR=5.230, 95% CI 1.868-14.643, P=0.002) and habitat radiomics model score ( OR=4.105, 95% CI 2.643-6.368, P<0.001) as independent predictors of CK19 positivity. Based on these factors, a combined clinical-radiologic-habitat combined model was established. The clinical-radiologic-habitat combined model achieved AUCs of 0.767 (95% CI 0.671-0.846) and 0.730 (95% CI 0.649-0.801) in the internal and external validation cohorts, respectively. Significant differences in RFS were observed between the CK19-positive group (25.1 month) and CK19-negative group (51.0 month) as predicted by the clinical-radiologic-habitat model ( χ2=4.17, P=0.041). Conclusion:The clinical-radiologic-habitat combined model based on Gd-EOB-DTPA-enhanced MRI habitat radiomics demonstrates good predictive performance for CK19 expression in HCC and offers valuable prognostic stratification for clinical practice.

Acute lung injury (ALI) is a significant complication of sepsis, characterized by high morbidity, mortality, and poor prognosis. Neutrophils, as critical intrinsic immune cells in the lung, play a fundamental role in the development and progression of ALI. During ALI, neutrophils generate neutrophil extracellular traps (NETs), and excessive NETs can intensify inflammatory injury. Research indicates that Taohe Chengqi decoction (THCQD) can ameliorate sepsis-induced lung inflammation and modulate immune function. This study aimed to investigate the mechanisms by which THCQD improves ALI and its relationship with NETs in sepsis patients, seeking to provide novel perspectives and interventions for clinical treatment. The findings demonstrate that THCQD enhanced survival rates and reduced lung injury in the cecum ligation and puncture (CLP)-induced ALI mouse model. Furthermore, THCQD diminished neutrophil and macrophage infiltration, inflammatory responses, and the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Notably, subsequent experiments confirmed that THCQD inhibits NET formation both in vivo and in vitro. Moreover, THCQD significantly decreased the expression of peptidyl arginine deiminase 4 (PAD4) protein, and molecular docking predicted that certain active compounds in THCQD could bind tightly to PAD4. PAD4 overexpression partially reversed THCQD's inhibitory effects on PAD4. These findings strongly indicate that THCQD mitigates CLP-induced ALI by inhibiting PAD4-mediated NETs.
Extracellular Traps/immunology* ; Acute Lung Injury/immunology* ; Animals ; Sepsis/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neutrophils/immunology* ; Male ; Protein-Arginine Deiminase Type 4/genetics* ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; Cytokines/metabolism*

INTRODUCTION: The primary objective of this guideline is to establish evidence-based recommendations for the clinical use of parenteral nutrition (PN) in adult patients within the acute hospital setting in Singapore. METHOD: An expert workgroup, consisting of healthcare practitioners actively involved in clinical nutrition support across all public health institutions, systematically evaluated existing evidence and addressed clinical questions relating to PN therapy. RESULTS: This clinical practice guideline developed 30 recommendations for PN therapy, which cover these key aspects related to PN use: indications, patient assess-ment, titration and formulation of PN bags, access routes and devices, and monitoring and management of PN-related complications. CONCLUSION This guideline provides recommendations to ensure appropriate and safe clinical practice of PN therapy in adult patients within the acute hospital setting.
Humans ; Singapore ; Parenteral Nutrition/adverse effects* ; Adult

OBJECTIVES: To evaluate the clinical efficacy of hospital-prepared Chinese medicine Feigan granules for influenza patients. This study has been registered at the International Traditional Medicine Clinical Trial Registry platform (ITMCTR2025000162). METHODS: A prospective observational study was conducted on influenza patients who visited the Fever Clinic of the First Affiliated Hospital, Zhejiang University School of Medicine between February and March 2024. Patients were divided into the observation group (Feigan granules combined with conventional Western medicine) and the control group (conventional Western medicine). Main symptoms (including fever, cough and sore throat) and secondary symptoms (including chest tightness, poor appetite, muscle soreness and dry mouth) were evaluated with traditional Chinese medicine (TCM) symptom scale on the first day of the patient's visit and the third day after treatment. The degrees of improvement in the TCM symptom scores before and after treatment were compared using paired rank-sum test, and the differences in the overall symptom efficacy index between two groups were compared using the Wilcoxon test. RESULTS: A total of 217 influenza patients were included. After treatment, the TCM symptom scores of both groups were significantly improved compared with those before treatment (all P<0.01). The median differences in the main symptom score before and after treatment in the observation and the control groups were 7 points (95%CI: 6.0-8.0) and 6 points (95%CI: 6.0-8.0), respectively. The median difference in the secondary symptom score was 3 points (95%CI: 2.0-4.0) in both groups. The median differences in the total score were 9 points (95%CI: 8.0-10.5) and 8 points (95%CI: 7.0-10.0) in the observation and control groups, respectively. In the subgroup with an initial cough score >2, the improvement rates of total score (97.06% vs. 92.59%) and secondary symptoms (92.31% vs. 85.11%) in observation group were significantly higher than those in the control group (P<0.05); while there was no significant difference in the improvement rate of the main symptoms (95.59% vs. 90.74%, P>0.05). CONCLUSIONS Feigan granules can improve the TCM syndromes of influenza patients, especially for patients with more severe cough.
Humans ; Prospective Studies ; Influenza, Human/drug therapy* ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Male ; Middle Aged ; Adult ; Aged ; Adolescent ; Young Adult ; Treatment Outcome

With the continuous advancement of internet technology and the improvement of internet literacy among the general population, the concept of online-offline integration in internet hospitals has gradually gained acceptance and has been applied and developed both domestically and internationally. In thoracic surgery, the applicability of this model lies in enhancing efficiency and delivering comprehensive, diversified, and personalized medical services to address complex and severe conditions. However, challenges such as hardware limitations and diagnostic/treatment risks persist during the implementation of internet hospitals. Through future in-depth and localized research, the online-offline integration of internet hospitals is expected to undergo further development and refinement. This progress will facilitate its integration into clinical practice in thoracic surgery, ultimately providing patients with improved medical care services.

Objective To explore the alteration and function of TIMM8A during gefitinib-induced growth inhibition of lung cancer cell line PC-9.Methods TIMM8A siRNA transfection experiment was used to inhibit the expression of TIMM8A in PC-9 and gefitinib resistant PC-9 cells(PC-9-MTAC).CCK-8 assay was carried out to assess PC-9 and PC-9-MTAC cell viability after gefitinib treatment or TIMM8A siRNA transfection.qPCR was used to determine TIMM8A expression in PC-9 or PC-9-MTAC cells.Results Gefitinib inhibited PC-9 cell growth in a dose-depend-ent manner.The expression of TIMM8 A was inhibited during this process,and more than 50％TIMM8 A expression had been inhibited by 25 nmol/L gefitinib,while knockdown of TIMM8 A enhanced inhibitory effects of gefitinib on PC-9 cell proliferation(P＜0.05).Compared with the sensitive cells,treatment of the gefitinib-resistant PC-9-MTAC with 100 nmol/L gefitinib for 48 h only inhibited approximately 30％of TIMM8A expression.Furthermore,inhibition of TIMM8A expression enhanced the sensitivity of PC-9-MTAC cells to gefitinib(P＜0.05).Conclusions Low expression of TIMM8A improves anti-tumor effects of gefitinib in lung cancer cell line PC-9.

Objective To construct nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)knockout mice in order to investigate the effects of NLRP3 knockout on radiation-induced acute pneumonitis and pulmonary fibrosis.Methods Nlrp3+/+and Nlrp3-/-mice were randomly divided into the control group and irradiation group.To induce radiation-caused acute pneumonitis,the control group was exposed to sham irradiation while the irradiation group was exposed to 60Co γ-rays at a dose of 22 Gy at a dose rate of 184.30 R/min.At 14 days post-irradiation,the body weight of each mouse and the wet weight of its lung tissue were measured separately using an analytical balance to calculate the lung coefficient.Quantitative real-time PCR(qPCR)and cytometric bead array(CBA)were used to detect inflammatory responses in lung tissues and serum.Hematoxylin-eosin(HE)staining and F4/80 immunohistochemical staining were used to assess pathological changes and inflammatory cell infiltration in lung tissues.Cysteinyl aspartate specific proteinase-1(caspase-1)activation was analyzed by Western blotting.To establish a model of radiation-induced pulmonary fibrosis,mice were irradiated with 60Co γ-rays at a dose of 18 Gy at a dose rate of 174.67 R/min.At 24 weeks post-irradiation,HE staining and Masson staining were performed to evaluate pulmonary fibrosis.Results NLRP3 knockout inhibited caspase-1 activation,reduced inflammatory responses in lung tissues and serum,suppressed macrophage infiltration,alleviated pulmonary edema,and thereby protected against acute radiation-induced lung injury.Additionally,NLRP3 knockout significantly ameliorated late-stage radiation-induced pulmonary fibrosis.Conclusion NLRP3 knockout can mitigate both early radiation-induced pneumonia and lateradiation-induced pulmonary fibrosis.

ObjectiveTo explore the feasibility， evaluation methods and metabolic differences of high-fat diet（HFD） combined with myocardial ischemia-reperfusion injury（MIRI） to establish a rat model of myocardial ischemia-reperfusion with phlegm and blood stasis blocking collaterals syndrome（PBSBCS）. MethodsThirty-two SD rats were randomly divided into the sham operation， HFD， MIRI， and MIRI+HFD groups. Rats in the sham operation and MIRI groups were fed a standard diet（regular chow）， while the HFD and MIRI+HFD groups received a HFD for 10 weeks. Rats in the MIRI and MIRI+HFD groups underwent myocardial ischemia-reperfusion surgery， while the sham operation group underwent only thread placement without ligation. Cardiac function was assessed via small-animal echocardiography， including left ventricular ejection fraction（EF）， left ventricular fractional shortening（FS）， cardiac output（CO）， and stroke volume（SV）. Serum levels of creatine kinase（CK）， CK-MB， triglyceride（TG）， total cholesterol（TC）， high-density lipoprotein cholesterol（HDL-C）， low-density lipoprotein cholesterol（LDL-C）， lactate dehydrogenase（LDH）， endothelin-1（ET-1）， endothelial nitric oxide synthase（eNOS）， tumor necrosis factor-α（TNF-α）， interleukin-18（IL-18）， oxidized LDL（ox-LDL）， and cardiac troponin T（cTnT） were measured by biochemical assays and enzyme-linked immunosorbent assay（ELISA）. Myocardial histopathology was evaluated via hematoxylin-eosin（HE） staining， while myocardial infarction and no-reflow area were assessed using 2，3，5-triphenyltetrazolium chloride（TTC）， Evans blue， and thioflavin staining. Changes in syndrome characteristics［body weight， tongue surface red-green-blue ［RGB］ values， and pulse amplitude］ of PBSBCS were recorded. Serum differential metabolites were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）. ResultsCompared with the sham operation group， the HFD and MIRI+HFD groups showed significant increases in body weight（P<0.01）， RGB values and pulse amplitude decreased in the HFD， MIRI and MIRI+HFD groups， TC， TG， LDL-C and ox-LDL levels increased in the HFD and MIRI+HFD groups， while HDL-C decreased. Blood perfusion peak time and myocardial no-reflow area increased， serum eNOS level decreased， and CK-MB， LDH， and cTnT activities increased in the HFD， MIRI and MIRI+HFD groups（P<0.05， P<0.01）. Whole blood viscosity was increased in the HFD group at medium shear rate， and in the MIRI and MIRI+HFD groups at low， medium and high shear rates（P<0.05， P<0.01）. Platelet aggregation rate increased in the MIRI and MIRI+HFD groups， accompanied by elevated ET-1， TNF-α， and IL-18 levels， reduced cardiac function indices， expanded myocardial no-reflow and infarction areas， and increased serum CK， CK-MB， LDH， and cTnT activities（P<0.05， P<0.01）. Compared with the MIRI group， the HFD and MIRI+HFD groups showed significant increase in body weight， TC， TG， LDL-C and ox-LDL levels， and significant decrease in HDL-C content（P<0.01）. The MIRI+HFD group showed decrease in RGB values and pulse amplitude， and an increase in whole blood viscosity， platelet aggregation， blood perfusion peak time， myocardial no-reflow and infarction areas， elevated ET-1， TNF-α and IL-18 levels， decreased eNOS content， EF and SV， increased serum CK， CK-MB and cTnT activities， and worsened myocardial pathology（P<0.05）. Compared with the HFD group， the MIRI+HFD group showed similar aggravated trends（P<0.05， P<0.01）. Metabolomics results showed that 34 potential biomarkers involving 13 common metabolic pathways were identified in the MIRI+HFD group compared with the sham operation group. ConclusionThe MIRI group resembles blood stasis syndrome in hemodynamics and myocardial injury， and the HFD group mirrors phlegm-turbidity syndrome in lipid profiles and tongue characteristics. While the MIRI+HFD group aligns with PBSBCS in comprehensive indices， effectively simulating clinical features of coronary heart disease（CHD）， which can be used for the evaluation of the pathological mechanism and pharmacodynamics of CHD with PBSBCS.

ObjectiveTo explore the feasibility， evaluation methods and metabolic differences of high-fat diet（HFD） combined with myocardial ischemia-reperfusion injury（MIRI） to establish a rat model of myocardial ischemia-reperfusion with phlegm and blood stasis blocking collaterals syndrome（PBSBCS）. MethodsThirty-two SD rats were randomly divided into the sham operation， HFD， MIRI， and MIRI+HFD groups. Rats in the sham operation and MIRI groups were fed a standard diet（regular chow）， while the HFD and MIRI+HFD groups received a HFD for 10 weeks. Rats in the MIRI and MIRI+HFD groups underwent myocardial ischemia-reperfusion surgery， while the sham operation group underwent only thread placement without ligation. Cardiac function was assessed via small-animal echocardiography， including left ventricular ejection fraction（EF）， left ventricular fractional shortening（FS）， cardiac output（CO）， and stroke volume（SV）. Serum levels of creatine kinase（CK）， CK-MB， triglyceride（TG）， total cholesterol（TC）， high-density lipoprotein cholesterol（HDL-C）， low-density lipoprotein cholesterol（LDL-C）， lactate dehydrogenase（LDH）， endothelin-1（ET-1）， endothelial nitric oxide synthase（eNOS）， tumor necrosis factor-α（TNF-α）， interleukin-18（IL-18）， oxidized LDL（ox-LDL）， and cardiac troponin T（cTnT） were measured by biochemical assays and enzyme-linked immunosorbent assay（ELISA）. Myocardial histopathology was evaluated via hematoxylin-eosin（HE） staining， while myocardial infarction and no-reflow area were assessed using 2，3，5-triphenyltetrazolium chloride（TTC）， Evans blue， and thioflavin staining. Changes in syndrome characteristics［body weight， tongue surface red-green-blue ［RGB］ values， and pulse amplitude］ of PBSBCS were recorded. Serum differential metabolites were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）. ResultsCompared with the sham operation group， the HFD and MIRI+HFD groups showed significant increases in body weight（P<0.01）， RGB values and pulse amplitude decreased in the HFD， MIRI and MIRI+HFD groups， TC， TG， LDL-C and ox-LDL levels increased in the HFD and MIRI+HFD groups， while HDL-C decreased. Blood perfusion peak time and myocardial no-reflow area increased， serum eNOS level decreased， and CK-MB， LDH， and cTnT activities increased in the HFD， MIRI and MIRI+HFD groups（P<0.05， P<0.01）. Whole blood viscosity was increased in the HFD group at medium shear rate， and in the MIRI and MIRI+HFD groups at low， medium and high shear rates（P<0.05， P<0.01）. Platelet aggregation rate increased in the MIRI and MIRI+HFD groups， accompanied by elevated ET-1， TNF-α， and IL-18 levels， reduced cardiac function indices， expanded myocardial no-reflow and infarction areas， and increased serum CK， CK-MB， LDH， and cTnT activities（P<0.05， P<0.01）. Compared with the MIRI group， the HFD and MIRI+HFD groups showed significant increase in body weight， TC， TG， LDL-C and ox-LDL levels， and significant decrease in HDL-C content（P<0.01）. The MIRI+HFD group showed decrease in RGB values and pulse amplitude， and an increase in whole blood viscosity， platelet aggregation， blood perfusion peak time， myocardial no-reflow and infarction areas， elevated ET-1， TNF-α and IL-18 levels， decreased eNOS content， EF and SV， increased serum CK， CK-MB and cTnT activities， and worsened myocardial pathology（P<0.05）. Compared with the HFD group， the MIRI+HFD group showed similar aggravated trends（P<0.05， P<0.01）. Metabolomics results showed that 34 potential biomarkers involving 13 common metabolic pathways were identified in the MIRI+HFD group compared with the sham operation group. ConclusionThe MIRI group resembles blood stasis syndrome in hemodynamics and myocardial injury， and the HFD group mirrors phlegm-turbidity syndrome in lipid profiles and tongue characteristics. While the MIRI+HFD group aligns with PBSBCS in comprehensive indices， effectively simulating clinical features of coronary heart disease（CHD）， which can be used for the evaluation of the pathological mechanism and pharmacodynamics of CHD with PBSBCS.