(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

Objective To investigate the application value of 320-slice wide-detector multi-phase left at-rial appendage computed tomography angiography(LAA-CTA)with pulmonary artery(PA)monitoring in the preoperative evaluation of left atrial appendage closure.Methods A retrospective analysis was conducted on the clinical data of 110 patients who underwent LAA-CTA before left atrial appendage closure.Among them,47 patients underwent single-phase enhanced scanning with superior vena cava(SVC)monitoring(con-trol group),and 63 patients underwent multi-phase enhanced scanning with pulmonary artery monitoring(study group).The differences in imaging effects of the left atrial appendage under different monitoring points and phase imaging methods were compared,as well as the accuracy of comparing with the diagnostic results of transesophageal ultrasound(TEE),and the differences in the presentation of thrombus,perithrombus,and hypoperfusion areas in the left atrial appendage.Results The study group could comprehensively display the multi-phase CT value changes of different components(thrombus,peri-thrombotic viscosity,normal blood)within the left atrial appendage cavity,and its evaluation of lesion size and progression was superior to that of the control group.Using TEE as the gold standard,the study group demonstrated better diagnostic ac-curacy for different components and normal regions within the left atrial appendage cavity compared to the control group(P<0.001).Additionally,the study group improved the detection rate of peri-thrombotic vis-cosity,clearly delineated thrombus boundaries,and enhanced diagnostic accuracy(P<0.001).Conclusion Multi-phase LAA-CTA with pulmonary artery monitoring can effectively evaluate the morphological dimensions,thrombus,and peri-thrombotic CT manifestations of the left atrial appendage.It is simple to operate,with an accuracy rate close to the gold standard,providing reliable imaging evidence for preoperative evaluation of left atrial appendage closure.

Objective To explore the mechanism by which cancer-associated fibroblasts(CAFs)regulate CD13-high expression neutrophil-like myeloid-derived suppressor cell(CD13hi-nMDSC)migration in pancreatic ductal adenocarcinoma(PDAC),so as to provide potential molecular targets and experimental evidences for immunotherapy in patients.Methods CAFs were isolated and purified from pancreatic cancer tissues of 5 PDAC patients.The phenotype and purity of CAFs were identified by immunofluorescence and flow cytometry.The expression of related factors in CAF was detected by quantitative polymerase chain reaction(qPCR)and enzyme-linked immunosorbent assay(ELISA).CAF conditioned medium and myeloid-derived suppressor cell(MDSC)migration system were constructed by Transwell to observe the migration of MDSCs and to study the specific mechanisms by which the aforementioned cytokines participate in regulating the migration of MDSCs.Results The isolated primary CAFs expressed activation biomarkers fibroblast activation protein(FAP)and α-smooth muscle actin(α-SMA),while the human foreskin fibroblasts(HFFs)of control cells did not express FAP and α-SMA.qPCR results showed that the mRNA expression levels of interleukin 6(IL-6),monocyte chemotactic protein 1(MCP-1),and stromal cell-derived factor 1(SDF-1)in CAFs were higher than those in HFFs(all P＜0.01).The contents of IL-6,MCP-1,and SDF-1 in the CAF culture supernatant were significantly higher than those in the HFF culture supernatant(all P＜0.01),and the secretion content increased with the prolongation of culture time.Compared with HFF conditioned medium and regular medium(RPMI 1640),CAF conditioned medium could recruit more total MDSCs and CD13hi-nMDSCs(all P＜0.01).The addition of SDF-1 recombinant protein alone in the culture system could induce the migration of total MDSCs and CD13hi-nMDSCs,and the addition of SDF-1 neutralizing antibodies or C-X-C motif chemokine receptor 4(CXCR4)blocking antibodies could significantly reduce the migration of CD13hi-nMDSCs induced by CAF conditioned medium(all P＜0.01).Although MCP-1 alone could also induce the migration of total MDSCs and CD13hi-nMDSCs,the number of CD13hi-nMDSCs migrating was significantly less than that of the SDF-1 experimental group.The IL-6 recombinant protein did not induce the migration of total MDSCs or CD13hi-nMDSCs.Conclusion CAFs can mediate the migration of total MDSCs and CD13hi-nMDSCs in PDAC through SDF-1/CXCR4 pathway.

Objective To explore the mechanism of hydroxyl safflower flavin A(HSYA)in the treatment of sepsis-induced liver injury by using metabolomics and network pharmacology.Methods A total of 50 male C57BL/6 mice were randomly divided into sham-operation group(10 mice),sepsis group(20 mice)and HSYA group(20 mice).Cecal ligation and puncture was conducted to establish the sepsis-induced liver injury mouse model.The mice in HSYA group were subcutaneously injected with HSYA after 2 hours of modeling.The content of serum inflammatory factors and liver function were detected,and the pathological changes of liver tissue were observed with HE staining,UPLC-Q-TOF-MS metabolomics was used to analyze liver tissue,screening for differential metabolites using multivariate statistical methods,network pharmacology was used to predict potential targets for HSYA treatment of sepsis-induced liver injury,and conduct GO and KEGG pathway enrichment analysis on potential targets,Metabo Analyst 5.0 database was used to match differential metabolites and potential targets between the model group and HSYA group,a targets metabolite-metabolism pathway network was constructed.AutoDock Vina software was used to perform molecular docking between HSYA and core genes,and finally RT-qPCR was used to verify the expression of core genes.Results HSYA can reduce the contents of IL-6,IL-1β and TNF-α in serum,restore liver function,and alleviate the morphological alternation in liver induced by sepsis.A total of 26 differential metabolites identified by metabolomics were screened out,including flufenamic acid,cryptolepine,opthalmic acid,fenpropathrin etc.,which were mainly involved in 5 metabolic pathways such as biosynthesis of unsaturated fatty acids and alpha-linolenic acid metabolism.Network pharmacology identified 81 potential targets,2 735 items enriched in GO and 124 signaling pathways enriched in KEGG;a total of 5 differential metabolites were matched for joint analysis,corresponding to 14 targets including IL1B,STAT3,PTGS2,TP53,etc.,involved in the regulation of metabolic disorders in sepsis-induced liver injury by HSYA.Molecular docking results showed that HSYA had good binding activity to IL1B,STAT3,PTGS2 and TP53 targets.RT-qPCR results showed that HSYA could inhibit the expressions of IL1B,STAT3 and PTGS2 in liver tissue.Conclusions HSYA may inhibit the release of inflammatory cytokines,maintain metabolic homeostasis,and alleviate sepsis-induced liver injury through modulating the expressions of IL1B,STAT3,and PTGS2.

Objective:To evaluate the development of fetal cerebral sulci and gyrus and the blood perfusion in pregnant women with gestational diabetes mellitus(GDM) by ultrasound.Methods:A total of 1 540 pregnant women with 28-34 weeks of pregnancy who underwent systematic screening in Henan Provincial People′s Hospital from January 2022 to October 2022 were prospectively selected, 100 pregnant women with GDM were selected as the GDM group. According to the effect of blood glucose control, the GDM group was divided into 2 groups: the satisfied control group (GDM group 1), and the dissatisfied control group (GDM group 2), with 50 cases in each group. At the same period, 50 healthy pregnant women at 28-34 weeks of gestation were enrolled as the control group. The differences of the sylvian fissure, parietooccipital sulci, calcarine sulci and cinguli sulci among the 3 groups were statistically analyzed. And the correlations between the deep of the brain cerebral sulci and gyrus and controlled blood glucose levels were evaluated. The umbilical artery pulsation index(UAPI), middle cerebral artery pulsation index(MCAPI) and ductus venosus pulsation index(DVPI) among the 3 groups were compared, and the differences in fetal blood perfusion among the 3 groups were evaluated.Results:There were no significant differences in the depths of the sylvian fissure, parietooccipital sulci, calcarine sulci and cinguli sulci between the control group and the GDM group 1 (all P>0.05), and they were larger than those of the GDM group 2 (all P<0.05). The depths of lateral fissure, parieto-occipital sulcus, cingulate sulcus and calcarine sulcus were negatively correlated with fasting blood glucose, 1 h and 2 h postprandial blood glucose (all P<0.05). There were no significant differences in MCAPI, UAPI and DVPI between the control group and GDM1 group (all P>0.05). The MCAPI in GDM 2 group was lower than that in the control group and GDM 1 group, and the UAPI and DVPI values were higher than those in the control group and GDM1 group(all P<0.05). Conclusions:The maturity of fetal cerebral sulci and gyrus in GDM pregnant women is related to the blood glucose control of pregnant women. The change of blood perfusion caused by persistent hyperglycemia in pregnant women and intrauterine hypoxia may cause the development retardation of cerebral sulci and gyrus.

ObjectiveTo identify the possible health impact of the 14th five⁃year plan for the development of employment and social security in Deqing County and propose improvement measures through health impact assessment. MethodsBased on the data of Deqing County， stakeholder interviews and Delphi Consultation Method， this study described the current status of employment and social security and analyzed the potential health impacts of implementing the 14th five⁃year plan for the development of employment and social security in Deqing County. ResultsThrough a quick assessment process， the results showed that the implementation of the plan would bring mixed health impacts. Positive impacts included enhanced social security capacity， improved health levels of low-income populations and families， increased convenience of medical treatment， and improved efficiency of health services. Negative impacts included reduced accessibility of digital services for the elderly， increased gap in benefits for retirees， increased risk of discrimination against disabled individuals， increased risks of layoffs and unemployment for vulnerable groups， and increased employment instability for middle-aged and elderly populations. ConclusionThe 14th five⁃year plan for the development of employment and social security in Deqing County will bring a series of positive health impacts， but negative health impacts also warrant attention.

Tumor cells use glycolysis to provide material and energy under hypoxic conditions to meet the energy requirements for rapid growth and proliferation， namely the Warburg effect. Even under aerobic conditions， tumor cells mainly rely on glycolysis to provide energy. Therefore， glucose transporter protein 1（GLUT1）， which is involved in the process of glucose metabolism， plays an important role in tumorigenesis， development and drug resistance， and is considered to be one of the important targets in the treatment of malignant tumors. In recent years， research on tumor glucose metabolism has gradually become a hot spot. It has been shown that various factors are involved in the regulation of tumor energy metabolism， among which the role of GLUT1 is the most critical. In this paper， the authors reviewed the latest research progress of GLUT1-targeted traditional Chinese medicine（TCM） active ingredient nano-delivery system in tumor therapy， aiming to reveal the feasibility and effectiveness of this system in the delivery of chemotherapeutic drugs. The GLUT1-targeted TCM active ingredient nano-delivery system can overcome the bottleneck of the traditional targeting strategy as well as the high-permeability long retention（EPR） effect. In summary， the authors believe that the GLUT1-targeted TCM active ingredient nano-delivery system provides a new strategy for targeted treatment of tumors and has a broad application prospect in tumor prevention and treatment.

Objective:To investigate the efficacy and mechanism of canagliflozin (Cana) in the treatment of high glucose-induced human podocyte (HPC) injury.Methods:The HPCs were divided into 5 groups: normal glucose group (NG group), mannitol group (MA group), high glucose group (HG group), Cana low dose (0.3 μmol/L) group and Cana high dose (1.0 μmol/L) group. Western blotting was used to examine the protein expressions of membrane-associated guanylate kinase inverted-2 (MAGI2), podocyte-associated protein nephrin, sodium-glucose transporter 2 (SGLT2), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis- associated speck-like protein containing a CARD (ASC), and cleaved-caspase1 in podocytes. Phalloidin staining of F-actin in podocytes was used to observe cytoskeletal injury. Intracellular reactive oxygen species (ROS) level of HPC was detected by the 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) probe. Levels of interleukin (IL)-18 and IL-1β in culture medium of podocytes were detected by enzyme-linked immunosorbent assay (ELISA).Results:(1) Compared with the NG group, the protein expressions of MAGI2 and nephrin decreased (both P<0.01), the protein expression of SGLT2 increased ( P<0.01), the changes of cell morphology and cytoskeleton remodeling were obvious, intracellular ROS level increased ( P<0.01), while NLRP3, ASC and cleaved-caspase1 protein expressions decreased in the HG group (all P<0.01). The results of ELISA showed that IL-18 and IL-1β concentrations were higher in the HG group (both P<0.05). (2) Compared with the HG group, in the Cana groups, MAGI2 and nephrin expressions up-regulated (both P<0.01), the changes of cell morphology and cytoskeleton remodeling were alleviated. Meanwhile the Cana groups showed decreased SGLT2 expression ( P<0.05), lower ROS level, down- regulated NLRP3, ASC, cleaved-caspase1 expressions (all P<0.01), and decreased concentrations of IL-18 and IL-1β in culture medium of podocytes (both P<0.05). Conclusion:Cana can improve high glucose-induced injury and inflammation in human podocyte, possibly due to the repression of the ROS/NLRP3 signaling pathway.

Objective:To observe any effect of repetitive transcranial magnetic stimulation (rTMS) on sleep disorders among children with cerebral palsy (CP).Methods:A total of 102 children with CP and disordered sleep were randomly divided into an experimental group and a control group, each of 51. All were given routine rehabilitation and sleep health education, but the experimental group additionally received rTMS for two weeks. The polysomnography (PSG) results of the two groups were recorded and analyzed.Results:The PSG parameters had improved greatly in both groups after the treatment. The percentage of N2 sleep (depth of sleep during light sleep) in the severe cerebral palsy group and of N3 sleep (depth of sleep during deep sleep) in the moderate cerebral palsy group had increased significantly more than in the mild cerebral palsy group, on average. After the intervention the percentages of N2 and N3 in those with mixed cerebral palsy and of N3 in those with involuntary motor cerebral palsy had increased significantly more than in those with spastic cerebral palsy, on average.Conclusion:rTMS treatment can improve the sleep disorders of children with cerebral palsy, especially N2 sleep among children with moderate to severe cerebral palsy, N3 sleep in cases of mixed or dyskinetic CP.