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 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 analyze the development status, research hotspots and development trend of Tianma Gouteng Decoction.Methods:Research literature on Tianma Gouteng Decoction in the medical field from January 1, 2002 to December 31, 2022 was retrieved from CNKI, WanFang, VIP, and SinoMed. The NoteExpress 3.7.0 software was used to merge and remove the duplicates. CiteSpace 6.1.R6 software was used to visually analyze the information such as the publication trend, authors, institutions and keywords of the included literature, and to display the cooperation network of authors and institutions, as well as the co-occurrence, clustering and burst map of keywords.Results:Totally 2 137 articles were finally included, with an overall increasing trend of annual publication. The distribution of journals was mainly in TCM, among which the Journal of Practical Traditional Chinese Internal Medicine had the most publications. Xian Shaoxiang (First Affiliated Hospital of Guangzhou University of Chinese Medicine) was the author with the most publications (17 articles). The institution with the most publications was Tianjin University of Traditional Chinese Medicine (23 articles), and the cooperation between research institutions was mainly in Chinese medicine colleges and their affiliated hospitals. The results of keyword analysis showed that the high-frequency keywords were hypertension, vertigo, hyperactivity of liver yang, clinical efficacy, migraine, etc. The keywords formed 10 clusters. The keywords with a long time span were syndrome differentiation and treatment, hypertension, experience of famous doctors, and clinical observation. In recent years, the emergent keywords were adverse reactions, blood pressure levels, vertigo, addition and subtraction treatment, and medication laws. Conclusions:The current research field of Tianma Gouteng Decoction is in a rising stage of development, and it is still necessary to strengthen academic exchanges and cooperation across regions and teams. Relevant research mainly focuses on the clinical application of cardiovascular and cerebrovascular diseases. The commonly used treatment is comprehensive therapy of TCM, focusing on blood pressure changes, adverse reactions and so on. The application of Tianma Gouteng Decoction in the treatment of vertigo, the study of adverse drug reactions and the discussion of medication rules have gradually become research hotspots.

Objective To investigate the imaging features and pathogenesis of lethal iatrogenic hemobilia(LIH)and the value of transarterial intervention in the treatment of LIH.Methods A total of 269 patients with upper gastrointestinal bleeding who were admitted to The First Affiliated Hospital of Nanjing Medical University from August 2009 to July 2023 were enrolled,among whom 24 had a confirmed diagnosis of LIH and received treatment,and a retrospective analysis was performed for the clinical data of these 24 patients,including the iatrogenic causes,angiographic findings,and arterial interventions of LIH.Among the 24 patients,23 received transarterial embolization(TAE)with gelatin sponge particles and coils,and 1 received a covered stent for isolation.The main criteria for assessing treatment outcome included the technical success rate of surgery,procedure-related complications,and long-term clinical follow-up.Results Among the 24 patients with LIH,12 had LIH caused by interventional procedures,and 12 had LIH caused by hepatobiliary and pancreatic surgery.The main clinical manifestations included a significant reduction in blood pressure or a persistent reduction in hemoglobin in 13 patients and upper gastrointestinal bleeding in 18 patients.Among the 24 patients,2 developed symptoms during surgery,4 developed symptoms within 24 hours,and 18 developed symptoms after 24 hours.Angiography showed a positive bleeding rate of 100%(24/24),and imaging findings included pseudoaneurysms in 15 patients,hepatic artery truncation in 3 patients,extravasation of contrast medium in 5 patients,and hepatic arteriobiliary fistula in 3 patients.Among the 24 patients,23 received TAE and 1 received stent implantation.Successful hemostasis was achieved for 23 patients,with a technical success rate of 95.8%(23/24).Four patients developed hepatic necrosis and abscess after TAE,and there was no rebleeding or recurrence after hemostatic treatment.Conclusion Various iatrogenic injuries may result in LIH with diverse clinical and imaging findings,and integrated diagnostic imaging combined with transarterial intervention is the best effective life-saving measure for LIH.

Objective We aimed to explore the mechanism by which Bushen Yangjing Soup improves elderly infertility based on oocyte mitochondrion.Methods C57BL/6J mice were used,including 15 young females(6-8 weeks old),45 elderly females(10 months old),and ten young males(6-8 weeks old).The female 6-8-week-old young mice were assigned to the young group,and the female 10-month-old elderly mice were randomly divided into the model group,the dehydroepiandrosterone(DHEA)group,and the Bushen Yangjing Soup group.Mice in the DHEA and Bushen Yangjing Soup groups were given DHEA[11.26 mg/(kg·d)]and Bushen Yangjing Soup[11.41 g/(kg·d)].Mice in the other groups were given normal saline.After 45 days,oocytes were collected,the number of oocytes and the proportion of mature oocytes were recorded,and in vitro fertilization(IVF)was carried out,followed by calculation of the successful fertilization rate.Real-time PCR was used to determine the copy number of mitochondrial DNA in oocytes,mito-tracker green was used to observe the distribution of mitochondria,and the mitochondrial membrane potential(MMP)of oocytes was determined using the JC-1 kit.The mRNA and protein levels of mitofusin 2(Mfn2)in oocytes were determined by real-time PCR and Western blotting,respectively.Results Compared with the young group,the number of oocytes,the proportion of mature oocytes,and the IVF rate were significantly reduced(P＜0.01),the copy number of mitochondrial DNA in oocytes was decreased,the rate of abnormal mitochondrial distribution was increased,the MMP was decreased(P＜0.01),and the mRNA and protein levels of Mfn2 were decreased(P＜0.01)in the elderly model mice.Compared with the elderly model group,the number of oocytes,the proportion of mature oocytes,and the IVF rate were significantly increased(P＜0.05),the copy number of mitochondrial DNA in oocytes was increased(P＜0.05),the rate of abnormal mitochondrial distribution was decreased,the MMP was increased(P＜0.05),and the mRNA and protein levels of Mfn2 were increased(P＜0.01)in the Bushen Yangjing Soup group.Compared with the DHEA group,the number of oocytes,the proportion of mature oocytes,and the IVF rate were increased,the copy number of mitochondrial DNA in oocytes was increased,the rate of abnormal mitochondrial distribution was decreased,the MMP was increased,the mRNA and protein levels of Mfn2 were increased in the Bushen Yangjing Soup group,and there was a significant difference in the number of oocytes and the expression of Mfn2 protein(P＜0.05).Conclusion Bushen Yangjing Soup may improve the quantity,distribution,and function of oocyte mitochondria by increasing the mRNA and protein levels of Mfn2,thereby improving oocyte quality.This is one of the possible mechanisms for clinical application of Bushen Yangjing Soup to improve ovarian function and treat elderly infertility.

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 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.