Hepatic ischemia/reperfusion injury (IRI) remains a critical complication contributing to graft dysfunction following liver surgery. As part of an ongoing search for hepatoprotective natural products, five previously unreported homoadamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), named hyperhomanoons A-E (1-5), and one known analog, hypersampsone O (6), were isolated from Hypericum patulum. Among these, compound 6 demonstrated potent protective effects against CoCl₂-induced hypoxic injury in hepatocytes. Furthermore, in a murine model of hepatic IRI induced by vascular occlusion, pretreatment with 6 markedly alleviated liver damage and reduced hepatocyte apoptosis. This study is the first to identify PPAPs as promising scaffolds for the development of therapeutic agents targeting hepatic IRI, underscoring their potential as lead compounds in drug discovery efforts for ischemic liver diseases.
Reperfusion Injury/prevention & control* ; Animals ; Hypericum/chemistry* ; Phloroglucinol/administration & dosage* ; Mice ; Humans ; Male ; Liver/blood supply* ; Apoptosis/drug effects* ; Molecular Structure ; Protective Agents/pharmacology* ; Hepatocytes/drug effects* ; Mice, Inbred C57BL ; Liver Diseases/drug therapy*

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

Objective:To screen the key genetic,diagnostic and therapeutic targets of chronic obstructive pulmonary disease(COPD)patients by using microarray datasets and Mendelian randomization(MR)method,and to provide the evidence for clinical diagnosis and treatment of COPD.Methods:Four COPD gene expression profile datasets were obtained from the Gene Expression Omnibus(GEO)database.The data were processed and normalized using R software,and differentially expressed genes(DEGs)were screened.MR analysis was performed to explore the causal relationship between COPD and expression quantitative trait loci(eQTL),intersection with DEGs was taken to identify potential key targets.Gene Set Enrichment Analysis(GSEA),Gene Ontology(GO)functional enrichment analysis,and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were conducted to investigate the functional roles and pathways of the key targets,external datasets were used to validate their expression.Results:A total of 1 571 DEGs were screened,including 820 upregulated genes and 751 downregulated genes.MR analysis identified 286 COPD-related genes,and intersection with DEGs revealed 3 upregulated genes:diacylglycerol kinase gamma(DGKG),neurofilament heavy polypeptide(NEFH),and Fc receptor like B(FCRLB);and 6 downregulated genes:STEAP4 metalloreductase(STEAP4),pleckstrin homology domain containing family F member 2(PLEKHF2),CD3d molecule(CD3D),transgelin 2(TAGLN2),tripartite motif containing 22(TRIM22),and ribosomal protein L9(RPL9).The biological function analysis results indicated that these genes were mainly involved in pathways such as iron ion transport into the cells,oxidoreductase activity,primary immunodeficiency,and Th1 and Th2 cell differentiation.The MR analysis results confirmed the causal relationship between these targets and COPD.The external validation results showed that compared with healthy controls,the expression level of FCRLB in COPD samples was significantly increased(P<0.01),while the expression levels of CD3D and RPL9 were significantly decreased(P<0.05 or P<0.01),which was consistent with the MR analysis results,highlighting the reliability of this study.Conclusion:DGKG,NEFH,FCRLB,STEAP4,PLEKHF2,CD3D,TAGLN2,TRIM22,and RPL9 may serve as important regulatory factors and clinical diagnostic/therapeutic targets in the pathogenesis of COPD,providing clues for early screening,diagnosis,and targeted treatment of COPD.

Objective To investigate the effect of polymorphism at the-94ins/del ATTG(rs28362491)site in the promoter region of nuclear transcription factor-κB(NF-κB)1 on the lipid-lowering and anti-inflammatory efficacy of atorvastatin in patients with coronary heart disease(CHD).Methods A total of 180 patients with CHD in Jinhua People's Hospital from June 2022 to June 2024 were selected as the research objects.The genotypes of rs28362491 locus of NF-κB1 gene were detected.The levels of blood lipids and inflammatory factors before treatment,1 month and 6 months after treatment were analyzed,and the incidence of adverse reactions during treatment were observed.Results A total of 180 CHD patients underwent genetic testing and were divided into DD genotypes 46 cases,ID genotypes 76 cases,and II genotypes 58 cases.The levels of total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),interleukin(IL)-6,IL-8,and tumor necrosis factor-α(TNF-α)in DD genotypes were higher than those in ID genotypes and Ⅱ genotypes(P<0.05).After 1month and 6 months treatment,the levels of TC,LDL-C,IL-6,IL-8,and TNF-α in three groups of patients decreased significantly compared to before treatment(P<0.05).At the same time point,the change rates of TC,LDL-C,IL-6,IL-8,and TNF-α levels in ID genotypes and Ⅱgenotypes were higher than those in DD genotypes(P<0.05).Conclusion The efficacy of atorvastatin in CHD patients is associated with the rs28362491 polymorphism of the NF-κB1 gene,with II genotypes and ID genotypes showing better efficacy than DD genotypes.

Objective To investigate the effect of polymorphism at the-94ins/del ATTG(rs28362491)site in the promoter region of nuclear transcription factor-κB(NF-κB)1 on the lipid-lowering and anti-inflammatory efficacy of atorvastatin in patients with coronary heart disease(CHD).Methods A total of 180 patients with CHD in Jinhua People's Hospital from June 2022 to June 2024 were selected as the research objects.The genotypes of rs28362491 locus of NF-κB1 gene were detected.The levels of blood lipids and inflammatory factors before treatment,1 month and 6 months after treatment were analyzed,and the incidence of adverse reactions during treatment were observed.Results A total of 180 CHD patients underwent genetic testing and were divided into DD genotypes 46 cases,ID genotypes 76 cases,and II genotypes 58 cases.The levels of total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),interleukin(IL)-6,IL-8,and tumor necrosis factor-α(TNF-α)in DD genotypes were higher than those in ID genotypes and Ⅱ genotypes(P<0.05).After 1month and 6 months treatment,the levels of TC,LDL-C,IL-6,IL-8,and TNF-α in three groups of patients decreased significantly compared to before treatment(P<0.05).At the same time point,the change rates of TC,LDL-C,IL-6,IL-8,and TNF-α levels in ID genotypes and Ⅱgenotypes were higher than those in DD genotypes(P<0.05).Conclusion The efficacy of atorvastatin in CHD patients is associated with the rs28362491 polymorphism of the NF-κB1 gene,with II genotypes and ID genotypes showing better efficacy than DD genotypes.

Objective To investigate the role of triggering receptor expressed on myeloid cells-1(TREM-1)in ath-erosclerosis induced by chronic intermittent hypoxia(CIH).Methods ApoE-/-mice were randomly divided into blank group,model group and experimental group.The mice in the model group and the experimental group were kept in a hypoxic environment and fed with a high-fat diet.After 4 weeks of high-fat feeding,mice in the experi-mental group were intraperitoneally injected with TREM-1 inhibitor LR12(5 mg/kg)for 8 weeks.After 12 weeks of feeding,the level of serum total cholesterol(TC),low density lipoprotein(LDL),triglyceride(TG),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-10(IL-10)were detected.Histological analysis of aortic TREM-1 expression,plaque area and macrophage level were examined.Results Compared with blank group,the expression of TREM-1 in the aorta of the model group significantly increased(P＜0.05).Com-pared with model group,the aortic plaque,the level of lipids in serum(TC,LDL,TG)and inflammatory factors(TNF-α,IL-1β,IL-10),aortic plaque,the expression of TREM-1 and infiltrating macrophages in aortic plaque of the experimental group were all significantly reduced(P＜0.05).Conclusions TREM-1 is involved in the develop-ment of CIH-induced AS.Inhibition of TREM-1 can alleviate CIH-induced AS and its mechanism is related to the inhibition of macrophage activation.

The World Health Organization (WHO) classification serves as the internationally recognized standard for diagnosing and classifying hematopoietic and lymphoid tissue tumors(WHO-HEAM). Since 2001, it has undergone multiple upgrades and revisions, updating, clarifying, and refining previous tumor diagnostic and classification standards while incorporating numerous new genetic and molecular biological subtypes. In 2022, two classification proposals emerged due to a wealth of clinical and scientific research results: the fifth edition of the WHO hematopoietic and lymphoid tissue classification (WHO-HAEM5), published in Leukemia journal; and the International Consensus Classification (ICC), published in Blood journal. These two schemes differ in their approach to classifying hematopoietic and lymphoid tissue tumors, posing challenges for clinical laboratory diagnosis and treatment.

Objective:To investigate the influence of Kruppel-like factor 16 (KLF16) on the proliferation and migration of pancreatic cancer cells.Methods:Immunohistochemical images of KLF16 were collected from 171 pancreatic cancer tissues and their matched paracarcinoma normal pancreas tissues and 8 pancreatic cancer tissues only in GEPIA database. The expression of KLF16 protein was detected by immunohistochemical imaging software. The protein and mRNA expressions of pancreatic cancer cell lines AsPC-1 and MIA PaCa-2 KLF16 were detected by Western blot and quantitative fluorescence PCR. By knockdown or exogenous overexpression of KLF16, the two cells were divided into blank control group (NC group), negative control group (siRNA-NC group), downexpression KLF16 group (siKLF16 group), overexpression control group (OE-NC group) and ovexpression KLF16-OE group (KLF16-OE group). CCK-8 assay, colony formation assay and transwell chamber were used to detect cell proliferation and migration.Results:The KLF16 protein expression level (4.02±1.26 vs 1.73±1.07) and positive expression rate (91.6% vs 13.5%) in pancreatic cancer tissues were significantly higher than those in paracancer normal pancreas tissues, with statistical significance ( P<0.05). After downregulating KLF16 expression and culturing for 24, 48, 72, and 96 hours, the A450 values of both AsPC-1 (0.19±0.02 vs 0.23±0.03, 0.24±0.06 vs 0.36±0.06, 0.45±0.09 vs 0.78±0.10, 0.69±0.04 vs 0.88±0.07) and MIA PaCa-2 cells (0.20±0.03 vs 0.22±0.02, 0.29±0.05 vs 0.31±0.04, 0.47±0.06 vs 0.78±0.10, 0.71±0.02 vs 0.90±0.07) and colony counts [(36±4.32) per well vs (118.51±10.01) per well, (13.6±2.62) per well vs (83.1±9.11) per well], and the number of migrated cells [(16.67±2.05) vs (46.67±5.91), (19.67±1.69) vs (55±4.89)] all decreased significantly. However, after up-regulating the expression of KLF16 and culturing for 24, 48, 72 and 96 h, the A450 value of both AsPC-1 (0.21±0.05 vs 0.20±0.04, 0.48±0.03 vs 0.31±0.04, 0.91±0.09 vs 0.72±0.03, 1.28±0.10 vs 1.05±0.02) and MIA PaCa-2 cells (0.20±0.01 vs 0.19±0.05, 0.44±0.03 vs 0.30±0.04, 0.89±0.06 vs 0.72±0.03, 1.19±0.05 vs 1.01±0.10), and the number of cell colonies [(189±6.37)/per hole vs (108±9.62)/ per hole, (141±12.56)/ per hole vs (80.69±10.32)/ per hole]], migration cell numbers [(79±4.89) per hole vs (50.33±4.11) per hole, (79.66±3.85) per hole vs (51±4.08) per hole] all increased significantly. Conclusions:KLF16 is highly expressed in pancreatic cancer. The up-regulated expression of KLF16 in pancreatic cancer cell lines can promote the proliferation and migration of pancreatic cancer cells.

Objective:To explore the degree of fear of pain in bum patients and analyze the related factors of fear of pain.Methods:519 cases of bum inpatients were selected and investigated by using the Fear of Pain Ques-tionnaire(FPQ),the Medical Coping Modes Questionnaire(MCMQ)and the Family APGAR Index(APGAR).Re-sults:The score of fear of pain in burn patients was(95.5±16.3).The results of multiple linear regression analysis showed that the score of fear of pain was positively correlated with male,moderate and severe burn and hospitaliza-tion time over 4 weeks(β=0.22,0.35,0.41),and negatively correlated with the scores of family function of the Family APGAR Index and coping style of the Medical Coping Modes Questionnaire(β=-0.29,-0.16).Con-clusion:Male patients with moderate and severe bums who have been hospitalized for more than 4 weeks are more likely to have a higher level of fear of pain,and burn patients with better family function and coping style may have a lower degree of fear of pain.

Objective To investigate the mechanism by which Ginkgo biloba extract reduces myocardial injury in rats with myocardial infarction(MI).Methods Bioinformatics was used to identify key targets of Ginkgo biloba extract in the treatment of MI in rats.An MI rat model was established via coronary artery ligation.Rats were randomly assigned to the model group,Betaloc ZOK group(2.5 mg/kg),and low-,medium-,and high-dose Ginkgo biloba extract groups(50,100,and 200 mg/kg,respectively).A sham-operation group was included for comparison.Following six weeks of gavage administration,myocardial tissues were examined using hematoxylin-eosin and Sirius red staining to assess pathological changes.Wheat germ agglutinin staining was used to observe cardiomyocyte hypertrophy.Western blotting was performed to evaluate changes in the expression of MCODE core targets,including HIF1α,MAPK14,MMP9,and CXCR4.Results Compared to the sham-operation group,the model group exhibited irregular arrangement of cardiomyocytes,significant inflam-matory infiltration,and a marked increase in type Ⅰ and Ⅲ collagen fibers in the myocardial tissue(P＜0.05).Additionally,significant upregulation in the expression of MCODE core target proteins(P＜0.05)was observed.In contrast,compared to the model group,low-,medium-,and high-dose Ginkgo biloba extract groups displayed more orderly arrangement of cardiomyocytes,reduced inflammatory infil-tration,significantly decreased levels of type Ⅰ and Ⅲ collagen fibers(P＜0.05),notable downregulation in the expression of p-MAPK14,MMP9,and CXCR4 proteins(P＜0.05),and significantly increased expression of HIF1α protein(P＜0.05).Conclusion Ginkgo biloba extract may exert protective effects on myocardial cells following MI by inhibiting the formation of neutrophil extracellular traps.