Combined seawater Hf and Nd isotope compositions have been applied as reliable tracers of water mass mixing and weathering input changes.The establishment of standardized synchronous extraction methods for Fe-Mn oxyhydroxide in sediments,which serve as effective carriers for isotopic signals of ancient seawater,is a prerequisite and key for paleoceanography research.The research material of this study was the surface sediments of the Western Arctic Ocean obtained from China's 7th Arctic Scientific Expedition,and a reliable simultaneous Nd-Hf isotope extraction method in Fe-Mn oxyhydroxide fraction was established through systematic optimization of pretreatment procedures and key extraction parameters.This research focused on analyzing the effects of pretreatment(Milli-Q water pre-wash)and key extraction parameters(leaching time,solution/solid ratios,concentration of EDTA-2Na,and concentration of mixed solution of hydroxyamine hydrochloride(HH)and acetic acid(HAc))on element extraction efficiency and isotopic composition.The experimental results indicated that the Milli-Q water pre-wash was not necessary,Fe-Mn oxyhydroxide extraction could be directly performed.Nd extraction amount in Fe-Mn oxyhydroxide fraction was not sensitive to changes in extraction conditions,while the Hf extraction amount was significantly affected by leaching time,solution/solid ratios and concentration of EDTA-2Na.The optimal conditions for synchronously extracting Nd-Hf isotopes were as follows:adding 20 mL of a mixed solution of 0.005 mol/L HH+1.5%HAc+0.03 mol/L EDTA-2Na per gram of sample,and reaction at room temperature for 3 h under shaking.Through systematic verification of 87Sr/86Sr ratio,εNd value,εHf value,Al/Nd ratio and Al/Hf ratio,it was confirmed that this method could effectively avoid interferences from residual components and accurately obtain Nd-Hf isotope signals of ancient seawater preserved in sediments.The standardized method established in this work provided reliable technical support for reconstructing water mass mixing between the Arctic,North Atlantic,and North Pacific Oceans and riverine input histories.It also provided important reference for the extraction methods of Nd and Hf isotopes from marine sources in sediments from other sea areas around the world.

ObjectiveObesity has been identified as one of the most important risk factors for cognitive dysfunction. Physical exercise can ameliorate learning and memory deficits by reversing synaptic plasticity in the hippocampus and cortex in diseases such as Alzheimer’s disease. In this study, we aimed to determine whether 8 weeks of treadmill exercise could alleviate hippocampus-dependent memory impairment in high-fat diet-induced obese mice and investigate the potential mechanisms involved. MethodsA total of sixty 6-week-old male C57BL/6 mice, weighing between 20-30 g, were randomly assigned to 3 distinct groups, each consisting of 20 mice. The groups were designated as follows: control (CON), high-fat diet (HFD), and high-fat diet with exercise (HFD-Ex). Prior to the initiation of the treadmill exercise protocol, the HFD and HFD-Ex groups were fed a high-fat diet (60% fat by kcal) for 20 weeks. The mice in the HFD-Ex group underwent treadmill exercise at a speed of 8 m/min for the first 10 min, followed by 12 m/min for the subsequent 50 min, totally 60 min of exercise at a 0° slope, 5 d per week, for 8 weeks. We employed Y-maze and novel object recognition tests to assess hippocampus-dependent memory and utilized immunofluorescence, Western blot, Golgi staining, and ELISA to analyze axon length, dendritic complexity, number of spines, the expression of c-fos, doublecortin (DCX), postsynaptic density-95 (PSD95), synaptophysin (Syn), interleukin-1β (IL-1β), and the number of major histocompatibility complex II (MHC-II) positive cells. ResultsMice with HFD-induced obesity exhibit hippocampus-dependent memory impairment, and treadmill exercise can prevent memory decline in these mice. The expression of DCX was significantly decreased in the HFD-induced obese mice compared to the control group (P<0.001). Treadmill exercise increased the expression of c-fos (P<0.001) and DCX (P=0.001) in the hippocampus of the HFD-induced obese mice. The axon length (P<0.001), dendritic complexity (P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P<0.001) in the hippocampus were significantly decreased in the HFD-induced obese mice compared to the control group. Treadmill exercise increased the axon length (P=0.002), dendritic complexity(P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P=0.001) of the hippocampus in the HFD-induced obese mice. Our study found a significant increase in MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of HFD-induced obese mice compared to the control group. Treadmill exercise was found to reduce the number of MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of obese mice induced by a HFD. ConclusionTreadmill exercise led to enhanced neurogenesis and neuroplasticity by increasing the axon length, dendritic complexity, dendritic spine numbers, and the expression of PSD95 and DCX, decreasing the number of MHC-II positive cells and neuroinflammation in HFD-induced obese mice. Therefore, we speculate that exercise may serve as a non-pharmacologic method that protects against HFD-induced hippocampus-dependent memory dysfunction by enhancing neuroplasticity and neurogenesis in the hippocampus of obese mice.

Objective:To observe the clinical effect of Cangfu Daotan Decoction combined with ethinylestradiol and cyproterone acetate,metformin in patients with spleen deficiency phlegm-dampness type polycystic ovary syndrome(PCOS)accompanied by insulin resistance.Methods:80 patients with PCOS accompanied by insulin resistance who were admitted to our hospital from June 2023 to June 2024 were included.The patients were divided into control group(treated with ethinylestradiol and cyproterone acetate,metformin)and study group(treated with modified Cangfu Daotan Decoction combine with ethinylestradiol and cyproterone acetate,metformin)by the random number table method,with 40 cases in each group.The total clinical effective rate,TCM syndrome score,sex hormone levels[prolactin(PRL),estradiol(E2),follicle-stimulating hormone(FSH),testosterone(T),and luteinizing hormone(LH)],insulin resistance indicators[fasting insulin(FINS),fasting blood glucose(FBG),homeostatic model assessment of insulin resistance(HOMA-IR)],and endometrial receptivity[pulsatile index(PI),resistance index(RI),endometrial thickness(ET),ovulation rate]and the occurrence of adverse reactions were compared between the two groups.Results:Compared with the control group after treatment,the total clinical effective rate,PRL,E2,FSH level,ET and the ovulation ratein the study group were higher,while the main symptoms,secondary symptoms,total score,T,LH levels,FBG,FINS levels,HOMA-IR,PI and RI were lower(P＜0.05).There was no difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:Cangfu Daotan Decoction combined with ethinylestradiol and cyproterone acetate,metformin in patients with spleen deficiency phlegm-dampness type PCOS accompanied by insulin resistance,can improve the clinical symptoms,increase the total clinical effective rate,it may be related to the regulation of insulin resistance,sex hormone levels,and endometrial receptivity,it is safe and reliable.

Objective:To observe the clinical effect of Cangfu Daotan Decoction combined with ethinylestradiol and cyproterone acetate,metformin in patients with spleen deficiency phlegm-dampness type polycystic ovary syndrome(PCOS)accompanied by insulin resistance.Methods:80 patients with PCOS accompanied by insulin resistance who were admitted to our hospital from June 2023 to June 2024 were included.The patients were divided into control group(treated with ethinylestradiol and cyproterone acetate,metformin)and study group(treated with modified Cangfu Daotan Decoction combine with ethinylestradiol and cyproterone acetate,metformin)by the random number table method,with 40 cases in each group.The total clinical effective rate,TCM syndrome score,sex hormone levels[prolactin(PRL),estradiol(E2),follicle-stimulating hormone(FSH),testosterone(T),and luteinizing hormone(LH)],insulin resistance indicators[fasting insulin(FINS),fasting blood glucose(FBG),homeostatic model assessment of insulin resistance(HOMA-IR)],and endometrial receptivity[pulsatile index(PI),resistance index(RI),endometrial thickness(ET),ovulation rate]and the occurrence of adverse reactions were compared between the two groups.Results:Compared with the control group after treatment,the total clinical effective rate,PRL,E2,FSH level,ET and the ovulation ratein the study group were higher,while the main symptoms,secondary symptoms,total score,T,LH levels,FBG,FINS levels,HOMA-IR,PI and RI were lower(P＜0.05).There was no difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:Cangfu Daotan Decoction combined with ethinylestradiol and cyproterone acetate,metformin in patients with spleen deficiency phlegm-dampness type PCOS accompanied by insulin resistance,can improve the clinical symptoms,increase the total clinical effective rate,it may be related to the regulation of insulin resistance,sex hormone levels,and endometrial receptivity,it is safe and reliable.

Objective:To evaluate the diagnostic value of intestinal tissue metagenomic next-generation sequencing (mNGS) in severe diarrhea following haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:Sixteen patients who developed severe diarrhea or hematochezia after haploidentical allo-HSCT at the First Affiliated Hospital of Fujian Medical University (June 2023–August 2024) were enrolled. All underwent gastrointestinal endoscopy and mNGS for microbial detection. Clinical, endoscopic, pathological, and microbiological data were analyzed to evaluate the diagnostic value of mNGS and treatment outcomes following targeted therapy.Results:The study included 16 patients (12 males, 4 females; median age 32.5 years, range 3–60 years). Diarrhea occurred a median of 3.93 months post-transplant (range 1.63–10.40 months). Stool cultures were negative except for one case with Candida. One patient tested positive for Clostridium difficile antigen. Endoscopy revealed mucosal congestion, edema, erosion, and bleeding, with focal inflammation on pathology. mNGS detected pathogens in 87.5% (14/16) of cases, including mixed infections in 78.5% (11/14). Common pathogens were Klebsiella pneumoniae, Enterococcus faecium, Escherichia coli, Rhizopus microsporus, EBV, and CMV. Targeted treatment adjustments led to symptom improvement in 87.5% of patients.Conclusion:Allo-HSCT patients are prone to infectious diarrhea due to immunosuppression. Molecular analysis of endoscopic biopsy tissues using mNGS can accurately identify pathogens, guide targeted therapy, and improve clinical outcomes.

Objective:To evaluate the diagnostic value of intestinal tissue metagenomic next-generation sequencing (mNGS) in severe diarrhea following haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:Sixteen patients who developed severe diarrhea or hematochezia after haploidentical allo-HSCT at the First Affiliated Hospital of Fujian Medical University (June 2023–August 2024) were enrolled. All underwent gastrointestinal endoscopy and mNGS for microbial detection. Clinical, endoscopic, pathological, and microbiological data were analyzed to evaluate the diagnostic value of mNGS and treatment outcomes following targeted therapy.Results:The study included 16 patients (12 males, 4 females; median age 32.5 years, range 3–60 years). Diarrhea occurred a median of 3.93 months post-transplant (range 1.63–10.40 months). Stool cultures were negative except for one case with Candida. One patient tested positive for Clostridium difficile antigen. Endoscopy revealed mucosal congestion, edema, erosion, and bleeding, with focal inflammation on pathology. mNGS detected pathogens in 87.5% (14/16) of cases, including mixed infections in 78.5% (11/14). Common pathogens were Klebsiella pneumoniae, Enterococcus faecium, Escherichia coli, Rhizopus microsporus, EBV, and CMV. Targeted treatment adjustments led to symptom improvement in 87.5% of patients.Conclusion:Allo-HSCT patients are prone to infectious diarrhea due to immunosuppression. Molecular analysis of endoscopic biopsy tissues using mNGS can accurately identify pathogens, guide targeted therapy, and improve clinical outcomes.

Objective To investigate the predictive value of combined plasma gluconic acid(GA),fumaric acid(FA),and pseudouridine levels at admission for acute kidney injury(AKI)in elderly patients with acute myocardial infarction(AMI).Methods A total of 78 elderly AMI patients transferred from Emergency Department to Coronary Care Unit in Fuwai Hospital during Decem-ber 2021 and July 2022 were enrolled in this prospective study.They were divided into AKI group(40 cases)and non-AKI group(38 cases)according to whether they developed AKI during hospi-talization.Plasma levels of GA,FA and pseudouridine were quantitatively detected with liquid chromatography-tandem mass spectrometry.ROC curve was plotted to assess the predictive value of these three plasma metabolites for AKI in AMI patients.Multivariate logistic regression analy-sis was applied to analyze the clinical risk factors for AKI.Results There were no statistical differences in the plasma levels of GA,FA and pseudouridine between the AKI group and the non-AKI group(P＞0.05).ROC curve analysis revealed that the plasma levels of the three indicators had no predictive value for the development of AKI in elderly AMI patients(AUC=0.576,95％CI:0.449-0.704,P=0.246;AUC=0.595,95％CI:0.467--0.721,P=0.154;AUC=0.563,95％CI:0.435-0.692,P=0.337).Multivariate logistic regression analysis revealed that left ventricu-lar ejection fraction(LVEF)was an independent predictor for AKI development in elderly AMI patients(OR=0.923,95％CI:0.870-0.978,P=0.007).Conclusion Plasma GA,FA and pseud-ouridine cannot predict the development of AKI in elderly AMI patients,while,LVEF is an inde-pendent predictor for the development.

This study aims to study the effective substance and mechanism of Ziziphi Spinosae Semen extract in the treatment of insomnia based on serum metabolomics and network pharmacology. The rat insomnia model induced by p-chlorophenylalanine(PCPA) was established. After oral administration of Ziziphi Spinosae Semen extract, the general morphological observation, pentobarbital sodium-induced sleep test, and histopathological evaluation were carried out. The potential biomarkers of the extract in the treatment of insomnia were screened by ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS) combined with multivariate analysis, and the related metabolic pathways were further analyzed. The "component-target-pathway" network was constructed by ultra-high performance liquid chromatography coupled with quadrupole-Exactive mass spectrometry(UHPLC-Q-Exactive-MS/MS) combined with network pharmacology to explore the effective substances and mechanism of Ziziphi Spinosae Semen in the treatment of insomnia. The results of pentobarbital sodium-induced sleep test and histopathological evaluation(hematoxylin and eosin staining) showed that Ziziphi Spinosae Semen extract had good theraputic effect on insomnia. A total of 21 endogenous biomarkers of Ziziphi Spinosae Semen extract in the treatment of insomnia were screened out by serum metabolomics, and the metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and nicotinate and nicotinamide metabolism were obtained. A total of 34 chemical constituents were identified by UHPLC-Q-Exactive-MS/MS, including 24 flavonoids, 2 triterpenoid saponins, 4 alkaloids, 2 triterpenoid acids, and 2 fatty acids. The network pharmacological analysis showed that Ziziphi Spinosae Semen mainly acted on target proteins such as dopamine D2 receptor(DRD2), 5-hydroxytryptamine receptor 1 A(HTR1 A), and alpha-2 A adrenergic receptor(ADRA2 A) in the treatment of insomnia. It was closely related to neuroactive ligand-receptor interaction, serotonergic synapse, and calcium signaling pathway. Magnoflorine, N-nornuciferine, caaverine, oleic acid, palmitic acid, coclaurine, betulinic acid, and ceanothic acid in Ziziphi Spinosae Semen may be potential effective compounds in the treatment of insomnia. This study revealed that Ziziphi Spinosae Semen extract treated insomnia through multiple metabolic pathways and the overall correction of metabolic disorder profile in a multi-component, multi-target, and multi-channel manner. Briefly, this study lays a foundation for further research on the mechanism of Ziziphi Spinosae Semen in treating insomnia and provides support for the development of innovative Chinese drugs for the treatment of insomnia.
Animals ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Metabolomics ; Network Pharmacology ; Rats ; Seeds/chemistry* ; Sleep Initiation and Maintenance Disorders/drug therapy* ; Tandem Mass Spectrometry ; Ziziphus/chemistry*

This study analyzed the main chemical components of Zhuru Decoction via ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS), and then predicted the mechanism of Zhuru Decoction in clearing heat, resolving phlegm, detoxifying, and treating vomiting and alcohol-related vomiting caused by heat in stomach based on network pharmacology. The gradient elution was conducted in Agilent ZORBAX extend-C_(18) column(2.1 mm×100 mm, 1.8 μm) with the mobile phase of 0.1% formic acid aqueous solution(A)-acetonitrile(B) at a flow rate of 0.3 mL·min~(-1) and the column temperature of 35 ℃. The MS adopted the positive and negative ion mode of electrospray ionization(ESI), and the data were collected in the scanning range of m/z 100-1 500. A total of 98 compounds in Zhuru Decoction were identified via BATMAN, SYMMAP, TCMSP, and relevant literature, including 36 flavonoids, 7 triterpenoids, 8 gingerols, 20 organic acids, 5 amino acids, and 22 other compounds. On the basis of the available studies, 9 components were selected as index components, and the protein-protein interaction(PPI) network of the common targets was established with STRING 11.0. Finally, 10 core targets associated with the pharmacodynamic effect were screened out. This study established the UPLC-Q-TOF-MS/MS method for identifying the chemical components in the classic prescription Zhuru Decoction, and employed network pharmacology to explore the core targets of its efficacy, which provided a refe-rence for the quality control and the research of the pharmacodynamic substances of Zhuru Decoction.
Humans ; Tandem Mass Spectrometry ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Network Pharmacology ; Vomiting

Targeted gene therapy has become a promising approach for lung cancer treatment. In our previous work, we reported that the targeted expression of microRNA-7 (miR-7) operated by thyroid transcription factor-1 (TTF-1) promoter inhibited the growth of human lung cancer cells in vitro and in vivo; however, the intervention efficiency needed to be further improved. In this study, we identified the core promoter of TTF-1 (from -1299 bp to -871 bp) by 5' deletion assay and screened out the putative transcription factors nuclear factor-1 (NF-1) and activator protein-1 (AP-1). Further analysis revealed that the expression level of NF-1, but not AP-1, was positively connected with the activation of TTF-1 core promoter in human non-small-cell lung cancer (NSCLC) cells. Moreover, the silencing of NF-1 could reduce the expression level of miR-7 operated by TTF-1 core promoter. Of note, we optimized four distinct sequences to form additional NF-1-binding sites (TGGCA) in the sequence of TTF-1 core promoter (termed as ^optTTF-1 promoter), and verified the binding efficiency of NF-1 on the ^optTTF-1 promoter by electrophoretic mobility shift assay (EMSA). As expected, the ^optTTF-1 promoter could more effectively drive miR-7 expression and inhibit the growth of human NSCLC cells in vitro, accompanied by a reduced transduction of NADH dehydrogenase (ubiquinone) 1α subcomplex 4 (NDUFA4)/protein kinase B (Akt) pathway. Consistently, ^optTTF-1 promoter-driven miR-7 expression could also effectively abrogate the growth and metastasis of tumor cells in a murine xenograft model of human NSCLC. Finally, no significant changes were detected in the biological indicators or the histology of some important tissues and organs, including heart, liver, and spleen. On the whole, our study revealed that the optimized TTF-1 promoter could more effectively operate miR-7 to influence the growth of human NSCLC cells, providing a new basis for the development of microRNA-based targeting gene therapy against clinical lung cancer.
Animals ; Humans ; Mice ; Carcinoma, Non-Small-Cell Lung/therapy* ; Lung Neoplasms/metabolism* ; MicroRNAs/metabolism* ; Nuclear Proteins/metabolism* ; Thyroid Gland/pathology* ; Thyroid Nuclear Factor 1/genetics* ; Transcription Factors/metabolism*