ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease （AD） based on network pharmacology， molecular docking， and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and the Encyclopedia of Traditional Chinese Medicine（ETCM） databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards， Online Mendelian Inheritance in Man（OMIM）， TTD， PharmGKB， and DrugBank databases were used to obtain the relevant targets of AD. The intersection （common targets） of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken， and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction（PPI） network. The CytoNCA plugin within Cytoscape was used to screen out the core targets， and the Metascape platform was used to perform gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2， and AutoDock Vina was used for molecular docking. Scopolamine （SCOP） was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control （CON） group （0.9% NaCl， n=8）， model （SCOP） group （3 mg·kg^-1·d^-1， n=8）， positive control group （3 mg·kg^-1·d^-1 of SCOP+3 mg·kg^-1·d^-1 of Donepezil， n=8）， and Kaixinsan group （3 mg·kg^-1·d^-1 of SCOP+6.5 g·kg^-1·d^-1 of Kaixinsan， n=8）. Mice in each group were administered with 0.9% NaCl， Kaixinsan， or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin （HE） staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay（ELISA） was used to determine the serum acetylcholine （ACh） and acetylcholinesterase （AChE） contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3（STAT3） and nuclear transcription factor（NF）-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained， and 578 potential targets （common targets） of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol， gijugliflozin， etc.. Potential core targets were STAT3， NF-κB p65， et al. GO functional enrichment analysis obtained 3 124 biological functions， 254 cellular building blocks， and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways， mainly involving cancer-related pathways， TRP pathway， cyclic adenosine monophosphate（cAMP） pathway， and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65， STAT3， and other targets involved in the NF-κB signaling pathway.

To investigate the genetic relatedness between carbapenem-resistant Klebsiella pneumoniae(CRKP) strains isolated from intestinal colonization and subsequent bloodstream infections.

Metabolic dysfunction-associated steatotic liver disease (MASLD), the most prevalent chronic liver condition globally, lacks adequate and effective therapeutic remedies in clinical practice. Recent studies have increasingly highlighted the close connection between the ubiquitin-proteasome system (UPS) and the progression of MASLD. This relationship is crucial for understanding the disease's underlying mechanism. As a sophisticated process, the UPS govern protein stability and function, maintaining protein homeostasis, thus influencing a multitude of elements and biological events of eukaryotic cells. It comprises four enzyme families, namely, ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), ubiquitin-protein ligases (E3), and deubiquitinating enzymes (DUBs). This review aims to delve into the array of pathways and therapeutic targets implicated in the ubiquitination within the pathogenesis of MASLD. Therefore, this review unveils the role of ubiquitination in MASLD while spotlighting potential therapeutic targets within the context of this disease.

(±)-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 characterize the complete genome sequence and elucidate the structural features of norovirus (NoV) isolate SD20200267.Methods:The viral nucleic acid was extracted from patient samples, followed by amplification and sequencing for genotyping based on the nucleotide sequences. The metagenomic sequencing technology was utilized for whole genome sequencing, and subsequent analysis was performed on the acquired nucleotide sequences.Results:The complete genome sequence of the SD20200267 strain, spanning a total length of 7 465 nucleotides, was successfully obtained. The SD20200267 strain belongs to the GⅡ.12 and GⅡ.P16 genotypes in the VP1 and RdRp regions, respectively. The nucleotide sequence identity of SD20200267 strain with other GⅡ.12[P16] strains ranged from 96.0% to 97.3%, exhibiting 15 amino acid variations. The strain displayed evidence of recombination, with the recombination site located in the overlapping region of ORF1 and ORF2.Conclusions:SD20200267 is classified as a GⅡ.12[P16] strain, and recombination was observed in the overlapping region of ORF1 and ORF2.

Objective To investigate the effects of mindfulness-based parenting course on parenting burnout and parent-child relationship of adolescents' mothers.Methods A total of 203 mothers who volun-teered to participate in the mindfulness-based parenting course in a middle school in Chongqing City in May 2023 were recruited as the research subjects and divided into the intervention group (n=99) and control group (n=104).The intervention group attended the eight mindfulness parenting sessions twice a week,while the control group did not attended the course.The Parenting Burnout Assessment Scale,Parent-Child Relationship Self Evaluation Scale,Five Factors of Mindfulness scale and Satisfaction with Life Scale were used to evaluate the two groups before and after intervention.Results The scores of parent-child relationship and satisfaction with life had statistical difference between the two groups (P<0.05).Compared with before intervention,the parental burnout score of the intervention group was decreased,the scores of parent-child relationship,five fac-tors of mindfulness,scores of awareness,no judgment,no reaction dimensions and life satisfaction were in-creased,the differences were statistically significant (P<0.05).Compared with the control group,the scores of parent-child relationship,five factors of mindfulness,awareness dimension and life satisfaction after inter-vention in the intervention group were higher,while the score of conscious action dimension was lower,the differences were statistically significant (P<0.05).Conclusion The 4-week mindfulness-based parenting course could could decrease the parenting burnout,and improve the parent-child relationship and satisfaction with life.

Objective:To analyze the influence of E-Coaching self-management model on health behavior change in perimenopausal women.Methods:In this randomized controlled trial, 230 perimenopausal women who participated in health management prograam in the Health Management Center of Hangzhou Wuyunshan Hospital from January 2020 to October 2021 were selected as study objects by convenience sampling method. The subjects were divided into the experimental group and the control group with random number table (115 cases in each group). The experimental group was managed by health coaches with E-Coaching self-management model, and the control group was routinely managed by health managers. The intervention lasted for 6 months. Finally, 29 cases were lost to follow-up due to the failure of the subjects to comply with protocol requirements or voluntary withdrawal. So, a total of 201 subjects were included in the analysis (107 cases in the experimental group and 94 cases in the control group). χ2 test and t test were used to analyze the differences in modified Kupperman symptom score, perimenopausal knowledge and belief, regular exercise and dietary healthy behavior stage between the two groups. And the influence of E-Coaching self-management model on health behavior change in perimenopausal women was analyzed too. Results:After the intervention, the total score of modified Kupperman scale and the scores of insomnia, anxiety and fatigue in the experimental group were all lower than those in the control group [(7.36±2.91) vs (10.01±2.78) points, (0.49±1.13) vs (1.27±1.20) points, (0.80±0.99) vs (1.68±1.39) points, (0.67±0.55) vs (0.93±0.64) points]( t=6.553, 4.785, 5.219, 3.013, all P<0.05); and the total score of knowledge and belief questionnaire and the score of knowledge or belief dimension in the experimental group were significantly higher than those in control group [(25.15±1.55) vs (21.05±1.64) points, (9.61±0.56) vs (9.03±0.68) points, (15.54±1.53) vs (12.02±1.28) points] ( t=-18.238, -6.570, -17.801, all P<0.05). After the intervention, the proportions of the experimental group in the precontemplation and contemplation stage of exercise and diet were both significantly lower than those before intervention ( χ2=116.616, 139.964, both P<0.001), and were lower than those in the control group (the proportion of precontemplation stage of exercise was 7.5% vs 38.3%, and the contemplation stage of exercise was 26.2% vs 34.0%, χ2=38.330; the proportion of precontemplation stage of diet was 3.7% vs 23.4%, and the contemplation stage of diet was 18.7% vs 29.8%, χ2=25.399; all P<0.001). After the intervention, the proportion of the subjects in the preparation stage and action stage the experimental group were significantly higher than those before intervention ( χ2=116.616, 139.964, both P<0.001), and were higher than those in the control group (the proportion in preparation stage of exercise 18.7% vs 8.5%, and the action stage of exercise 47.7% vs 19.1%, χ2=38.330; the proportion in preparation stage of diet 20.6% vs 14.9%, and the action stage of diet 57.0% vs 31.9%, χ2=25.399; all P<0.001). Conclusion:E-Coaching self-management model can improve women′s perimenopausal symptoms in certain degrees, it improves their understanding of perimenopausal knowledge, enhances self-management beliefs and promotes healthy behavior changes.

Objective:To study the influence of serum triggering receptor expressed on myeloid cells 1(TREM-1)level on prognosis in elderly patients with sepsis and acute respiratory distress syndrome(ARDS).Methods:A total of 100 elderly patients with sepsis were selected as the research objects.All the patients with sepsis were divided into sepsis ARDS group and sepsis non-ARDS group.General data and TREM-1 level were compared between the two groups.The patients with sepsis ARDS were divided into death group and survival group according to the survival status during the 28-day follow-up.TREM-1 level, acute physiology and chronic health evaluation(APACHE)Ⅱ score and SOFA score were compared between the two groups.The correlation between serum TREM-1 level and procalcitonin(PCT), APACHE Ⅱ score and SOFA score was analyzed.The survival rate of high TREM-1 level group and low TREM-1 level group was compared.Results:The age, white blood cell(WBC), PCT, APACHE Ⅱ score, SOFA score and TREM-1 level of sepsis ARDS patients were significantly higher than those of non-ARDS patients( t=2.722, 6.088, 11.55, 6.889, 4.661, 6.122, all P<0.05). The incidence of sepsis ARDS patients with chronic obstructive pulmonary disease was significantly higher than that of non-ARDS patients( χ2=7.895, P<0.05). Serum TREM-1 level, APACHE Ⅱ score and SOFA score of ARDS patients in death group were significantly higher than those in survival group( t=3.293, 6.173, 4.255, all P<0.05). Serum TREM-1 level was positively correlated with PCT, APACHE Ⅱ score and SOFA score( t=0.553, 0.602, 0.636, P<0.001). The Kaplan-Meier survival curve showed that the survival rate of high TREM-1 level group was significantly lower than that of low TREM-1 level group( χ2=3.999, P=0.036). Cox regression analysis showed that TREM-1 level was a risk factor for the prognosis of ARDS patients with sepsis( HR=1.893, 95% CI: 1.049-3.414). Conclusions:Serum TREM-1 level is significantly increased in elderly patients with sepsis ARDS, which is closely related to the prognosis and can be used as a potential prognostic biomarker.

OBJECTIVE: To investigate the effects of methanol-ethyl acetate partitioned fractions from (MEDS) on the proliferation and apoptosis of human non-small cell lung cancer H1975 cells. METHODS: The systemic solvent extraction method was used to preliminary separation of the effective fractions in the methanol extract of . The cytotoxicity of each extract (5, 10, 20, 40, and 80 μg/mL) was tested using MTT assay. Colony cloning method was used to assess the effect of different concentrations of methanol-ethyl acetate partitioned fractions from MEDS (5, 10, 20, 40, and 80 μg/ mL) on the proliferation of H1975 cells. Flow cytometric analysis with Annexin V-FITC/PI staining was performed to detect the apoptosis of the cells after treatment with different concentrations of MEDS fractions (10, 20, and 40 μg/mL). Western blotting was used to evaluate the effects of MEDS fractions on the expressions of apoptosis-related proteins Akt, Bax, and Bcl-2. The anti-tumor activity of 100 mg/kg MEDS fractions was tested in a nude mouse model bearing H1975 cell xenografts. RESULTS: MTT assay and colony forming experiment showed that MEDS fractions significantly inhibited the proliferation of H1975 cells in a dose-and time-dependent manner ( < 0.05). The results of flow cytometry showed that MEDS fractions induced obvious apoptosis of H1975 cells in a concentration-dependent manner ( < 0.05). MEDS fractions also significantly decreased the expressions of Bcl-2 and Akt protein and increased the protein expression of Bax ( < 0.05). In the tumor-bearing nude mouse model, MEDS fractions showed potent anti-tumor effects with a low toxicity to affect the body weight and organs of the mice. CONCLUSIONS The methanol-ethyl acetate partitioned fractions from MEDS show potent anti-tumor activity both and , suggesting their value as promising therapeutic agents against lung cancer.
Acetates ; Animals ; Antineoplastic Agents, Phytogenic ; isolation & purification ; pharmacology ; Apoptosis ; drug effects ; Carcinoma, Non-Small-Cell Lung ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Heterografts ; Humans ; Lung Neoplasms ; pathology ; Methanol ; Mice ; Mice, Nude ; Plant Extracts ; isolation & purification ; pharmacology

Objective: To investigate serum level changes of heart-type fatty acid-binding protein(H-FABP)and S100 calcium-binding protein B(S-100B)protein in elderly patients with chronic heart failure and their clinical significance. Methods: A total of 160 patients with chronic heart failure treated at our hospital were recruited, and 80 healthy individuals receiving regular check-ups were enrolled as normal controls.Serum levels of H-FABP and S-100B and cardiac function index scores were compared between patients with different cardiac function grades.Correlations of serum H-FABP and S-100B levels with N-terminal pro-B-type natrlure tiepeptide(NT-proBNP)and with cardiac function index scores in heart failure patients were analyzed.The sensitivity, specificity and accuracy of serum H-FABP, S-100B and NT-proBNP for heart failure detection were compared. Results: Serum levels of H-FABP, S-100B and NT-proBNP in elderly patients with chronic heart failure were elevated with increased cardiac function grading(F=9.823, 11.573 and 13.056, P=0.013, 0.000 and 0.000), and serum levels of H-FABP, S-100B and NT-proBNP were higher in elderly patients with heart failure than in the control group(P<0.05). Serum levels of H-FABP and S-100B were positively correlated with serum NT-proBNP levels, cardiac function grading and left ventricular end-diastolic diameter(LVEDd)(r=0.527, 0.510 and 0.487, P=0.008, 0.003 and 0.002; r=0.604, 0.496 and 0.533, P=0.006, 0.005 and 0.003), and were negatively correlated with left ventricular ejection fraction(LVEF)(r=-0.536 and-0.528, P=0.005 and 0.008). The sensitivity, specificity and accuracy of serum H-FABP combined with S-100B for heart failure detection were 93.2%, 91.6% and 95.7%, respectively. Conclusions Serum levels of H-FABP and S-100B are high in elderly patients with heart failure, and they are correlated with serum NT-proBNP levels, cardiac function grading and LVEDd.H-FABP combined with S-100B has a high positive rate for heart failure detection.