ObjectiveTo investigate how Xiaoyao Shukun decoction （XYSKD） regulates the formation and release of neutrophil extracellular traps （NETs） via the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway， thereby reducing inflammation， inhibiting the excessive proliferation of fibroblasts in pelvic adhesion tissue， decreasing adhesion and fibrosis， and repairing the tissue damage in sequelae of pelvic inflammatory disease （SPID）. MethodsA total of 84 Wistar rats were randomly allocated into seven groups： blank， model， XYSKD （8 mg·kg^-1）， mTOR agonist （10 mg·kg^-1）， mTOR agonist + XYSKD （10 mg·kg^-1+8 mg·kg^-1）， mTOR inhibitor （2 mg·kg^-1）， and mTOR inhibitor + XYSKD （2 mg·kg^-1+8 mg·kg^-1）. The rat model of SPID was constructed by starvation， fatigue， and ascending Escherichia coli infection. After 14 days of drug intervention， the ultrastructure of fibroblasts in the pelvic adhesion tissue was observed by transmission electron microscopy. The general morphology of the uterus， fallopian tube， and ovary was observed by laparotomy. The levels of interleukin-1β （IL-1β）， interleukin-17 （IL-17）， and tumor necrosis factor-α （TNF-α） in the peritoneal flushing fluid were determined by enzyme-linked immunosorbent assay （ELISA）. The expression of myeloperoxidase （MPO） and citrullinated histone 3 （H3） in the fallopian tube was detected by immunofluorescence. Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR） were employed to determine the relative protein and mRNA levels， respectively， of neutrophil elastase （NE）， intercellular adhesion molecule-1 （CD54）， α-smooth muscle actin （α-SMA）， H3， PI3K， and Akt. ResultsCompared with the blank group， the model group presented a large number of collagen fibers in bundles， numerous cytoplasmic folds of fibroblasts， reduced or absent mitochondrial cristae， and disordered and expanded endoplasmic reticulum. By laparotomy， extensive pelvic congestion， connective tissue hyperplasia， thickening and hardening of the tubal end near the uterus， and tubal and ovarian adhesion or cyst were observed in the model group. In addition， the model group showed raised levels of IL-1β， IL-17， and TNF-α in the peritoneal flushing fluid （P<0.01）， increased average fluorescence intensities of MPO and H3 （P<0.01）， and up-regulated protein and mRNA levels of NE， H3， CD54， PI3K， and Akt （P<0.01）. Compared with the model group， the mTOR agonist group showed increased fibroblasts and cytoplasmic folds， absence of mitochondrial cristae， endoplasmic reticulum dilation， and evident collagen fiber hyperplasia. Pelvic adhesions were observed to cause aggravated damage to the uterine， fallopian tube， and ovarian tissues. The levels of IL-1β， IL-17， and TNF-α in the peritoneal lavage fluid elevated （P<0.01） and the average fluorescence intensities of MPO and H3 enhanced （P<0.01） in the mTOR agonist group. In contrast， the XYSKD group and the mTOR inhibitor group showcased decreased fibroblasts and collagen fibers， alleviated mitochondrial crista loss and endoplasmic reticulum dilation， improved morphology and appearance of the uterine， fallopian tube， and ovarian tissues， lowered levels of IL-1β， IL-17， and TNF-α in the peritoneal lavage fluid （P<0.01）， decreased average fluorescence intensities of MPO and H3 （P<0.01）， and down-regulated protein and mRNA levels of NE， H3， CD54， PI3K， and Akt （P<0.05）. Compared with the mTOR agonist group， the mTOR agonist + XYSKD group showed alleviated pathological changes in the pelvic tissue， declined levels of IL-1β， IL-17， and TNF-α （P<0.01）， decreased average fluorescence intensities of MPO and H3 （P<0.01）， and down-regulated protein levels of NE， H3， CD54， α-SMA， p-PI3K/PI3K， and p-Akt/Akt （P<0.01） and mRNA levels of NE， H3， CD54， α-SMA， PI3K， and Akt （P<0.01）. Compared with the mTOR inhibitor group， the mTOR inhibitor + XYSKD group demonstrated reduced pathological severity of the pelvic tissue， reduced levels of IL-1β， IL-17， and TNF-α （P<0.01）， decreased average fluorescence intensities of MPO and H3 （P<0.01）， and down-regulated protein and mRNA levels of NE and CD54 （P<0.05）. ConclusionXYSKD can inhibit the excessive formation and release of NETs via PI3K/Akt/mTOR to ameliorate the inflammatory environment and reduce fibrosis and adhesion of the pelvic tissue， thereby playing a role in the treatment of SPID. It may exert the effects by lowering the levels of IL-1β， IL-17， and TNF-α and down-regulating the expression of NE， H3， CD54， α-SMA， PI3K， and Akt in the pelvic adhesion tissue.

OBJECTIVES: To investigate the effects of early life intervention with Bifidobacterium bifidum BD-1 (B. bifidum BD-1) on hyperactivity in a female mouse model of attention deficit hyperactivity disorder (ADHD) and explore the underlying mechanisms. METHODS: Eight newborn female Wistar-Kyoto (WKY) rats and 6 spontaneous hypertensive rats (SHRs) were gavaged with saline and another 6 SHRs were gavaged with B. bifidum BD-1 (10⁹ CFU) daily for 3 weeks. Open field test of the rats was conducted at 7 weeks, and fecal samples were collected at weaning (3 weeks) and at 7 weeks for 16S rRNA sequencing. Immunofluorescent staining was used to detect dopamine transporter (DAT) and tyrosine hydroxylase (Th) levels in the striatum and activated microglia in the prefrontal cortex. Treg cells in the mesenteric lymph nodes, spleen and blood were analyzed using flow cytometry. RESULTS: The SHRs traveled a significantly greater distance in open fields test than WKY rats, and this behavior was significantly attenuated by B. bifidum BD-1 intervention. The expression of DAT and Th in the striatum was significantly lower in the SHRs than in WKY rats, while B. bifidum BD-1 treatment obviously increased Th levels in the SHRs. B. bifidum BD-1 intervention significantly deceased the number of activated microglia and increased Treg cell counts in the spleen of SHRs. The treatment also enhanced α diversity in gut microbiota of the SHRs and resulted in a decreased Firmicutes/Bacteroidota ratio, more active Muribaculaceae growth, and suppression of Clostridia_UCG-014 proliferation. CONCLUSIONS Early life intervention with B. bifidum BD-1 alleviates hyperactivity in female SHRs by modulating the gut microbiota and peripheral immune response, suppressing neuroinflammation and improving dopaminergic system function. These findings provide evidence for early prevention strategies and support the development and application of psychobiotics for ADHD.
Animals ; Female ; Rats ; Rats, Inbred WKY ; Rats, Inbred SHR ; Attention Deficit Disorder with Hyperactivity/therapy* ; Bifidobacterium bifidum ; Probiotics/therapeutic use* ; Dopamine Plasma Membrane Transport Proteins/metabolism* ; Tyrosine 3-Monooxygenase/metabolism* ; Gastrointestinal Microbiome ; Disease Models, Animal

Objective To explore the action targets and related mechanisms of pogostemon cablin in the treatment of glioma based on network pharmacology and cellular experiments.Methods The active ingredi-ents and action targets of pogostemon cablin were collected by using databases such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the Traditional Chinese Med-icine Comprehensive Database(TCMID).The relevant targets of glioma were collected through databases such as Gene Cards and OMIM,and the network diagrams of"drug-target"and"disease-target"were estab-lished by using Cytoscape3.7.1 software.The intersection targets of pogostemon cablin for treating glioma were obtained and STRING database was used to analyzed,and their protein-protein interaction(PPI)net-work diagram was established.Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis on key targets were performed by using the DAVID database.In vitro cell experiments on key signaling pathways were conducted,U87 glioma cells were collected and divided into the control group(added to basic culture medium)and the 60,90,120 μg/mL pog-ostemon cablin groups(added to culture medium containing 60,90,and 120 μg/mL pogostemon cablin,respec-tively).CCK-8 assay and wound healing assay were used to detect the proliferation and migration ability of each group of cells,and the protein expression levels of mitogen activated protein kinase 1(MAPK1),recom-binant V-rel reticuloendotheliosis viral oncogene homolog A(RELA)phosphatidylinositol 3-kinase(PI3K),protein kinase B(Akt),phosphorylated-PI3K(p-PI3K),and phosphorylated-Akt(p-Akt)in each group of cells were detected by Western blot.Results A total of 94 main chemical constituents of pogostemon cablin were obtained.According to the screening conditions,9 effective active ingredients,239 drug target proteins,4 526 glioma related genes and 121 drug and disease common targets were identified.Protein interaction net-works discovered that Akt1,c-Jun N-terminal kinase(JUN),MAPK1,RELA,interleukin(IL)-6 and epider-mal growth factor receptor(EGFR)may be the key targets of pogostemon cablin in the treatment of glioma.GO function enrichment analysis identified 1 819 items in biological processes,109 items of cellular compo-nents and 216 items of molecular functions,which involved various aspects such as the positive regulation of the cellular metabolic process,the activity of protein homodimers,kinase activation,and membrane rafts.KEGG pathway enrichment analysis identified 181 related signaling pathways,involving anti-cancer,inflamma-tion,cell apoptosis,endocrine,immune regulation and so on,mainly including the PI3K/Akt pathway,ad-vanced glycation advanced glycation end products(AGE)/recepter for advanced glycation end products(RAGE)pathway,IL-6 pathway,and HIF-1 pathway,TNF pathway and so on.The in vitro experimental re-sults showed that compared with the control group,with the increase of the dose of the alcohol extract of pog-ostemon cablin,the cell activity decreased,the cell migration ability decreased,and the expression levels of MAPK1,RELA,p-PI3K and p-Akt proteins decreased(P＜0.05).Conclusion Pogostemon cablin can syner-gistically inhibit the development of glioma through multiple targets and pathways,and can suppress cell pro-liferation of U87 cells through the PI3K/Akt pathway.

Objective To understand the research status,hotspots and trends of Wuzhuyu Decoction;To provide reference for relevant research.Methods The literature related to Wuzhuyu Decoction was retrieved from CNKI,VIP,Wanfang Data and CBM databases from the establishment to February 28,2023.NoteExpress 3.6 was used to merge and deduplicate,and the author,organization and keywords were mapped and interpreted by CiteSpace 6.1.R6 software.Results A total of 822 articles were included,and the number of publications showed a wave upward trend;the top journals were New Chinese Medicine,Henan Traditional Chinese Medicine and Sichuan Traditional Chinese Medicine;the main research institutions were Beijing University of Chinese Medicine,China Academy of Chinese Medical Sciences and Shandong University of Traditional Chinese Medicine;a total of 566 authors were involved,and the authors with more publications included Wang Zhimin(12),Gong Muxin(9)and Bi Kaishun(5);high-frequency keywords included"headache","Shang Han Lun","TCM therapy"and so on.Conclusion Wuzhuyu Decoction is effective in treating chronic gastritis,hypertension and other primary diseases,which is a research hotspot in this field.It is a research trend in this field to explore its active components by high performance liquid chromatography and explain its action mechanism and target at the molecular level.

Objective To understand the research status,hotspots and trends of animal medicinal materials;To provide reference for future research.Methods The literature related to animal medicinal materials was retrieved from CNKI,VIP,Wanfang Data and CBM from January 1,2000 to April 30,2023.NoteExpress 3.6 was used to merge and deduplicate,and the author,institution and keywords were mapped and interpreted by CiteSpace 6.1.R6 software.Results A total of 1 169 articles were included,and the overall publication quantity in this field showed a stable fluctuation trend;the top journals were Lishizhen Medicine and Materia Medica Research,China Journal of Chinese Materia Medica and Modern Chinese Medicine;the main research institutions were China Academy of Chinese Medical Sciences,Changchun University of Chinese Medicine and Chinese Academy of Medical Sciences;a total of 676 authors were involved,and the authors with more publications included Zhang Hui(22),Liu Rui(15),Lin Zhe and Ma Shuangcheng(14);high-frequency keywords included"identification","TCM resources","clinical application"and so on.Conclusion Resource survey of animal medicinal materials,standardized breeding of medicinal animals,development of alternatives to rare medicinal animal resources,and construction of quality standard system for animal medicinal materials are the research hotspots in this field.The basic research of pharmacodynamic substances of animal medicinal materials based on the integrated analysis strategies of proteomics,peptideomics and transcriptomics,and the revelation of the signaling pathways and targets of animal medicinal materials from the molecular biology level are the research trends in this field.

Objective To investigate the efficacy of Amplatzer duct occluder-Ⅱ device(ADO-Ⅱ)in treating ventricular septal detect(VSD)with aortic sinus prolapse(ASP)in child patients.Methods The clinical data of 94 child patients with VSD complicated by ASP,who were admitted to the Hunan Provincial Children's Hospital of China between January 2018 and September 2022,were retrospectively collected.The child patients included 60 males and 34 females with a mean age of(4.7±3.1)years.Mild-moderate ASP was seen in 83 child patients,with a mean(4.12±0.97)mm-sized VSD.Severe ASP was seen in 11 child patients,with a mean(4.95±0.51)mm-sized VSD.Perimembrane VSD was observed in 54 child patients and intracristal VSD in 40 child patients.The relationship of VSD size and degree of ASP to the selection of ADO-Ⅱ,postoperative middle period aortic valve regurgitation and residual leakage was analyzed,so as to clarify the applicability of ADO-Ⅱ to such child patients.Results In the postoperative middle period,6 child patients had mild aortic valve regurgitation,most seen in the child patients who received 4-4 mm or 5-4 mm ADO-occluder;and 10 child patients had residual leakage,mainly seen in the child patients who received 5-4 mm or 6-4 mm occluder.Conclusion In the condition when the ADO-Ⅱ occluder shows satisfactory placement pattern,this treatment is suitable for the child patient having＜6 mm VSD with ASP.Although there are some residual leakage and aortic valve regurgitation after surgery,this interventional therapy still meets the clinical requirements.(J Intervent Radiol,2024,32:17-21)

Objective To review the characteristics of animal models of sequelae of pelvic inflammatory disease(SPID)to provide a reference for standardizing the modeling process and improving the modeling rate.Methods Literature relevant to animal models of SPID from the past 40 years was searched,and animal species,modeling method,modeling cycles,modeling substances,positive control drugs,and evaluation indexes were summarized and analyzed.Results A total of 243 study manuscripts were included,most of which induced the SPID model in rats via the phenol paste or microbial infection method.The modeling cycles were typically between 14 and 16 days,and the success of the models was mostly determined by pelvic tissue morphology observation and pathological HE staining.Few research reports have focused on the traditional Chinese medicine(TCM)disease combination model.Conclusions No consistent criteria have been established for SPID animal model modeling,and thus it is recommended that researchers evaluate changes to animal behavior,pelvic histomorphology,and pathology.TCM syndrome modeling lacks effective method and evaluation standards,which need further research and development.Finally,the selection and use of positive-control drugs need to be further explored and perfected.

Objective To understand the current status and development trend of the research on Prunellae Spica;To provide reference for the subsequent research.Methods The research literature related to Prunellae Spica was searched in China Knowledge Resources Database(CNKI),Chinese Science and Technology Journal Database(VIP),Chinese Academic Journal Database(Wanfang Data),and Chinese Biomedical Literature Database(CBM)from January 1,2002 to March 23,2023.After merging and removing duplicates using NoteExpress 3.7.0.9258 software,CiteSpace 6.2.R1 software was used to visualize and analyze authors,institutions and keywords.Results Totally 3 136 articles were included,and the annual number of publications showed a fluctuating upward trend.Shaanxi Journal of Traditional Chinese Medicine had the most publications(93).The core authors included Lin Limei(34),Guo Qiaosheng(27),and Zhang Mingzhi(20),and core research institutions included Shandong University of Traditional Chinese Medicine(37),Tianjin University of Traditional Chinese Medicine(30),and Nanjing University of Chinese Medicine(28),with less cooperation among authors and institutions.The analysis of keywords showed that the research on the treatment of diseases were mainly"hypertension","breast cancer","hyperplasia of mammary glands","vertigo","insomnia".The chemical composition studies were mainly on"rosmarinic acid"and"ursolic acid".The type of literature was mainly"experience of famous doctors"and"clinical observation".Conclusion The research field of Prunellae Spica is in the rising stage of development,and the research content mainly focuses on clinical application and chemical composition research,etc.Summarizing the law of medication,exploring its mechanism of action and action target through data mining and molecular docking technology are the research trends.

Objective To understand the research hotspots and trend of Scrophulariae Radix from 2000 to 2023;To provide reference for related research.Methods The relevant literature of Scrophulariae Radix were retrieved from CNKI,VIP,Wanfang Data and CBM from January 1,2000 to June 1,2023.NoteExpress 3.7.0.9296 software was used to manage files and weight,and CiteSpace 6.2.R4 software was used for visualization analysis of authors,institutions and keywords.Results A total of 2 240 articles were included,and the annual number of publications showed a dynamic upward trend.The source journals with more publications included Shaanxi Journal of Traditional Chinese Medicine,Journal of Traditional Chinese Medicine,Shizhen Journal of Traditional Chinese Medicine Research and so on.The core authors were Zhang Ning,Liu Shumin,Liu Bin,etc;the main research institutions included Beijing University of Chinese Medicine,Nanjing University of Chinese Medicine,Guangzhou University of Chinese Medicine,etc.;high-frequency keywords were"harpagoside","quality standard","clinical observation"and so on.Conclusion The research of Scrophulariae Radix mainly focuses on chemical composition,disease treatment and compatibility application.It is a research trend in recent years to explore the medication law and mechanism of Scrophulariae Radix by using data mining,network pharmacology and molecular docking.

Objective This study aims to analyze the proteomic characteristics of peripheral blood in patients with lung cancer coexistent with pulmonary tuberculosis(LC-PTB),identify the differential proteins compared with lung cancer(LC)patients,and conduct functional analysis on these proteins.Methods The study included 8 LC-PTB patients and 10 LC patients.The LC patients were newly diagnosed and confirmed by pathology and did not receive any anti-tumor treatment before,while the PTB patients were Mycobacterium tuberculosis positive at the time of sampling.Liquid chromatography-tandem mass spectrometry(LC-MS/MS)was applied to perform proteomic mass spectrometry to assess the differential proteins,and then functional analysis was conducted via bioinformatics.Results A total of 5,185 proteins were detected between two groups.Through differential expression screening,190 proteins(58 upregulated and 132 downregulated)were identified to be differentially expressed.Subcellular localization analysis revealed that the differential proteins were mainly concentrated in the cytoplasm,nucleus,and extracellular matrix.KEGG pathway and GO analysis showed the roles of differential proteins in biological processes including immune response,metabolism,and secretion regulation.Protein interaction network analysis highlighted the importance of SORT1,SAR1B,RPS6KB1,VWF,SHC1,SRPRB,CTSD,TARDBP,RPLP0,PSMA2,RPS6,XPO1,PRKACB,and HLA-DRB1 in LC-PTB.Additionally,the expression changes in proteins like ADA2,MAP3K1,and GLS2 might be closely associated with the development of LC-PTB.Conclusions The proteomic profile comprehensively described the proteomic characteristics of LC-PTB and identified numerous differentially expressed proteins,which could provide further clues for research on biological mechanism of LC-PTB.