OBJECTIVE To study the mechanisms and effect of sufentanil(SUF)on protection of sepsis-induced myocardial injury.METHODS The in vitro experimental models of sepsis-induced myocardial injury were estab-lished by using lipopolysaccharide(LPS).The myocardial H9C2 cells were divided into the Control group,the LPS group,the SUF-L group,the SUF-M group,the SUF-H group,the SUF-H-ComC group and the SUF-H-ML385 group;the LPS group,the SUF-L group,the SUF-M group,the SUF-H group,the SUF-H-ComC group and the SUF-H-ML385 group were the experimental groups.The cells from the experimental groups were respec-tively inoculated and incubated in culture media containing 25 mg/L of LPS,and the culture media were respec-tively added SUF with the terminal dose of 0,5,10,20,20 and 20 μmol/L;the culture media of the SUF-H-ComC was added ComC with the terminal dose of 10 μmol/L,and the culture media of the SUF-H-ML385 was added ML385 with the terminal dose of 5 μmol/L.The cells from the Control group were incubated in normal cul-ture media.The same amount of culture media and CCK-8 reagent without containing myocardial H9C2 cells were assigned as the blank group.The cell viability was determined by CCK-8 method,the levels of reactive oxygen species(ROS),malondialdehyde(MDA),lactate dehydrogenase(LDH),superoxide dismutase(SOD)and gluta-thione peroxidase(GSH-Px)were detected.The Fe2+level of the cells was detected by iron ion colorimetric meth-od.The levels of interleukin(IL)-1β,IL-6 and tumor necrosis factor-α(TNF-α)in supernatant fluid of the culture media were detected with the use of enzyme-linked immunosorbent assay.The expression levels of adenosine 5'-monophosphate-activated protein kinas(AMPK),phosphorylated-AMPK(p-AMPK),nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)were detected by means of Western Blot.RESULTS The cell viability of the LPS group was lower than that of the Control group;the levels of ROS,MDA,LDH,Fe2+,IL-1β,IL-6 and TNF-α of the LPS group were higher than those of the Control group;the levels of SOD and GSH-Px of the LPS group were lower than those of the Control group;the expression levels of p-AMPK/AMPK,Nrf2 and HO-1 proteins of the LPS group were lower than those of the Control group(P＜0.05).As compared with the LPS group,the cell viability of the SUF-L group,the SUF-M group and the SUF-H group was succes-sively increased,the levels of ROS,MDA,LDH,Fe2+,IL-1β,IL-6 and TNF-α were successively reduced,the levels of SOD and GSH-Px were successively elevated,and the expression levels of p-AMPK/AMPK,Nrf2 and HO-1 proteins were successively increased(P＜0.05).AMPK pathway inhibitor and Nrf2 pathway inhibitor could reverse the viability of SUF-affecting LPS-induced myocardial H9C2 cells,levels of ROS,MDA,LDH,Fe2+,SOD,GSH-Px,IL-1β,IL-6 and TNF-α and downregulated the expression levels of p-AMPK/AMPK,Nrf2 and HO-1 proteins(P＜0.05).CONCLUSION SUF can improve the sepsis-induced myocardial injury,and the mecha-nism may be associated with activation of AMPK/Nrf2/HO-1 signaling pathways,inhibition of ferroptosis,oxi-dative stress injury and inflammatory reactions.

OBJECTIVE To study the mechanisms and effect of sufentanil(SUF)on protection of sepsis-induced myocardial injury.METHODS The in vitro experimental models of sepsis-induced myocardial injury were estab-lished by using lipopolysaccharide(LPS).The myocardial H9C2 cells were divided into the Control group,the LPS group,the SUF-L group,the SUF-M group,the SUF-H group,the SUF-H-ComC group and the SUF-H-ML385 group;the LPS group,the SUF-L group,the SUF-M group,the SUF-H group,the SUF-H-ComC group and the SUF-H-ML385 group were the experimental groups.The cells from the experimental groups were respec-tively inoculated and incubated in culture media containing 25 mg/L of LPS,and the culture media were respec-tively added SUF with the terminal dose of 0,5,10,20,20 and 20 μmol/L;the culture media of the SUF-H-ComC was added ComC with the terminal dose of 10 μmol/L,and the culture media of the SUF-H-ML385 was added ML385 with the terminal dose of 5 μmol/L.The cells from the Control group were incubated in normal cul-ture media.The same amount of culture media and CCK-8 reagent without containing myocardial H9C2 cells were assigned as the blank group.The cell viability was determined by CCK-8 method,the levels of reactive oxygen species(ROS),malondialdehyde(MDA),lactate dehydrogenase(LDH),superoxide dismutase(SOD)and gluta-thione peroxidase(GSH-Px)were detected.The Fe2+level of the cells was detected by iron ion colorimetric meth-od.The levels of interleukin(IL)-1β,IL-6 and tumor necrosis factor-α(TNF-α)in supernatant fluid of the culture media were detected with the use of enzyme-linked immunosorbent assay.The expression levels of adenosine 5'-monophosphate-activated protein kinas(AMPK),phosphorylated-AMPK(p-AMPK),nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)were detected by means of Western Blot.RESULTS The cell viability of the LPS group was lower than that of the Control group;the levels of ROS,MDA,LDH,Fe2+,IL-1β,IL-6 and TNF-α of the LPS group were higher than those of the Control group;the levels of SOD and GSH-Px of the LPS group were lower than those of the Control group;the expression levels of p-AMPK/AMPK,Nrf2 and HO-1 proteins of the LPS group were lower than those of the Control group(P＜0.05).As compared with the LPS group,the cell viability of the SUF-L group,the SUF-M group and the SUF-H group was succes-sively increased,the levels of ROS,MDA,LDH,Fe2+,IL-1β,IL-6 and TNF-α were successively reduced,the levels of SOD and GSH-Px were successively elevated,and the expression levels of p-AMPK/AMPK,Nrf2 and HO-1 proteins were successively increased(P＜0.05).AMPK pathway inhibitor and Nrf2 pathway inhibitor could reverse the viability of SUF-affecting LPS-induced myocardial H9C2 cells,levels of ROS,MDA,LDH,Fe2+,SOD,GSH-Px,IL-1β,IL-6 and TNF-α and downregulated the expression levels of p-AMPK/AMPK,Nrf2 and HO-1 proteins(P＜0.05).CONCLUSION SUF can improve the sepsis-induced myocardial injury,and the mecha-nism may be associated with activation of AMPK/Nrf2/HO-1 signaling pathways,inhibition of ferroptosis,oxi-dative stress injury and inflammatory reactions.

support the diagnosis.The treatment of PHCC is mainly based on surgery.Due to the characteristics of intact capsule,surgical resection is relatively easy and the cure rate is higher than that of ordinary hepatocellular carcinoma,and the postoperative survival rate is relatively ideal.For unresectable PHCC,palliative treatment based on transcatheter arterial chemoembolization can be used.This article reviews the progress on diagnosis and treatment of PHCC in order to provide reference for clinical practice.

Objective To explore the influencing factors of acute kidney injury in severe burn patients,and to construct a visual risk nomogram model.Methods A total of 390 patients with severe burn admitted to the Institute of Burn Frostbite and Tissue Function Reconstruction of Chinese People's Armed Police Force Specialty Medical Center from January 2018 to January 2022 were collected as an internal training data set,and 50 patients with severe burn admitted from February to December 2022 were collected as an external validation data set.The 390 patients of the internal training data set were divided into the acute kidney injury group and the non-acute kidney injury group according to the occurrence of acute kidney injury,and the baseline data of patients in the two groups were compared.Univariate and multivariate Logistic regression were used to analyze the risk factors of acute kidney injury in severe burn patients of the internal training data set,and a nomogram model was drawn.Subsequently,the model was verified both internally and externally.Kaplan-Meier analysis and Log-rank test were used to compare the 90-day survival rate of patients between the acute kidney injury group and the non-acute kidney injury group.Results The burn area(OR=1.18,95%CI:1.06 to 2.36,P=0.004),sequential organ failure assessment(SOFA)score(OR=1.81,95%CI:1.21 to 5.92,P<0.001),inhalation injury(OR=3.21,95%CI:1.23 to 6.35,P<0.001),neutrophil to lymphocyte ratio(NLR)(OR=1.22,95%CI:1.05 to 3.65,P<0.001)and albumin(ALB)(OR=0.78,95%CI:0.57 to 0.92,P=0.011)were the independent risk factors for the development of acute kidney injury in severe burn patients.The nomogram model was established by the above factors.The area under the receiver operating characteristic curve(AUC)of the internal training data set was 0.833(95%CI:0.752 to 0.935),the sensitivity was 81.2%,and the specificity was 83.2%.The AUC of the external validation data set was 0.842(95%CI:0.762 to 0.912),the sensitivity 87.2%,and the specificity was 78.7%.The 90-day survival rate of patients in the acute kidney injury group after burns was significantly lower than that in the non-acute kidney injury group(P<0.001).Conclusion Larger burn area,higher SOFA score,combined inhalation injury,increased NLR,and decreased ALB level are the risk factors for the occurrence of acute kidney injury in severe burn patients,which are related to the 90-day survival rate of patients after burns.The nomogram model based on the risk factors can provide certain reference for clinical individualized prevention and treatment of acute kidney injury in severe burn patients.

ObjectivePhotoacoustic pump-probe imaging can effectively eliminate the interference of blood background signal in traditional photoacoustic imaging, and realize the imaging of weak phosphorescence molecules and their triplet lifetimes in deep tissues. However, background differential noise in photoacoustic pump-probe imaging often leads to large fitting results of phosphorescent molecule concentration and triplet lifetime. Therefore, this paper proposes a novel triplet lifetime fitting method for photoacoustic pump-probe imaging. By extracting the phase of the triplet differential signal and the background noise, the fitting bias caused by the background noise can be effectively corrected. MethodsThe advantages and feasibility of the proposed algorithm are verified by numerical simulation, phantom and in vivo experiments, respectively. ResultsIn the numerical simulation, under the condition of noise intensity being 10% of the signal amplitude, the new method can optimize the fitting deviation from 48.5% to about 5%, and has a higher exclusion coefficient (0.88>0.79), which greatly improves the fitting accuracy. The high specificity imaging ability of photoacoustic pump imaging for phosphorescent molecules has been demonstrated by phantom experiments. In vivo experiments have verified the feasibility of the new fitting method proposed in this paper for fitting phosphoometric lifetime to monitor oxygen partial pressure content during photodynamic therapy of tumors in nude mice. ConclusionThis work will play an important role in promoting the application of photoacoustic pump-probe imaging in biomedicine.

Accurate prediction of drug-induced adverse drug reactions (ADRs) is crucial for drug safety evaluation, as it directly impacts public health and safety. While various models have shown promising results in predicting ADRs, their accuracy still needs improvement. Additionally, many existing models often lack interpretability when linking molecular structures to specific ADRs and frequently rely on manually selected molecular fingerprints, which can introduce bias. To address these challenges, we propose ToxBERT, an efficient transformer encoder model that leverages attention and masking mechanisms for simplified molecular input line entry system (SMILES) representations. Our results demonstrate that ToxBERT achieved area under the receiver operating characteristic curve (AUROC) scores of 0.839, 0.759, and 0.664 for predicting drug-induced QT prolongation (DIQT), rhabdomyolysis, and liver injury, respectively, outperforming previous studies. Furthermore, ToxBERT can identify drug substructures that are closely associated with specific ADRs. These findings indicate that ToxBERT is not only a valuable tool for understanding the mechanisms underlying specific drug-induced ADRs but also for mitigating potential ADRs in the drug discovery pipeline.

Metabonomics and proteomics were employed to investigate the mechanism of Yuzhi Zhixue Granules in treating polycystic ovary syndrome with insulin resistance(PCOS-IR). The disease model was established by feeding a high-fat diet and gavage of letrozole solution and it was then treated with different doses of Yuzhi Zhixue Granules. The therapeutic effect of Yuzhi Zhixue Granules was evaluated based on the body mass, homeostasis model assessment of insulin resistance and insulin sensitivity index, serum levels of adipokines, and histopathological changes of rats. Metabolomics and proteomics were employed to find the action pathways of Yuzhi Zhixue Granules. The results showed that Yuzhi Zhixue Granules reduced the body mass, improved the insulin sensitivity and aromatase activity, improved the levels of leptin, adiponectin and other adipokines, and alleviated insulin resistance, histopathological changes, and metabolic disorders in PCOS-IR rats. Metabolomics results revealed 14 metabolites with altered levels in the ovarian tissue, which were closely related to glutathione metabolism and pyruvate metabolism. Proteomics results showed that the therapeutic effect of Yuzhi Zhixue Granules was mainly related to the adipokine, adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), forkhead box protein O(FoxO), and mechanistic target of rapamycin(mTOR) signaling pathways. Western blot results showed that compared with the model group, Yuzhi Zhixue Granules treatment decreased the p-AMPK/AMPK and p-FoxO1/FoxO1 levels, increased the p-mTOR/mTOR level, and up-regulated the expression level of recombinant glucose transporter 4(GLUT4). Yuzhi Zhixue Granules can balance amino acid metabolism and pyruvate metabolism by regulating the AMPK/mTOR/FoxO/GLUT pathway to maintain the homeostasis of the ovarian environment and alleviate insulin resistance, thus treating PCOS-IR.
Animals ; Female ; Insulin Resistance ; Polycystic Ovary Syndrome/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Metabolomics ; Proteomics ; Rats, Sprague-Dawley ; Humans ; Ovary/metabolism* ; Signal Transduction/drug effects*

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.