As an innovative form of combining traditional aromatherapy with modern nasal medicine delivery technology， "olfactory administration of Chinese medicine" carries the theoretical essence of traditional Chinese medicine （TCM）， which is "moving and channeling Qi and fragrance， dredging and awakening the mind". Based on the systematic records of olfactory therapies in ancient books in emergency care， disorders of consciousness， lung system， and gynecological diseases， this paper examines the historical evolution of its clinical application， and elucidates the profound historical basis and theoretical feasibility of "olfactory administration of Chinese medicine" as a new form. Combined with the innovation and precise application of modern Chinese medicine olfactory agents in multi-system diseases such as nervous， respiratory， and cardiovascular diseases， this paper further analyzes the multi-dimensional mechanism of olfactory receptor pathway， olfactory brain pathway， nasal mucosal blood vessels， and lymphatic channels， and demonstrates its advantages of rapid onset， targeted brain entry， and systemic regulation. Under the background of continuous growth in the demand for external TCM treatment， continuous breakthroughs in the technology of nasal dosage forms， and increasingly accurate drug delivery paths， Chinese medicine olfactory agents have shown significant practical applicability and development potential. This study aims to provide theoretical support and practical direction for the system construction of this form.

The nose-to-brain pathway refers to a significant drug delivery route through which substances traverse the unique anatomical structures of the nasal cavity to directly access the central nervous system， bypassing the blood-brain barrier. Its core advantage lies in utilizing the olfactory and trigeminal nerves， enabling peripheral drug administration to rapidly and efficiently reach the brain， thereby avoiding the drug loss and bioavailability reduction associated with oral or intravenous routes due to the circulatory system and blood-brain barrier limitations. In recent years， with in-depth research into the neuroanatomy of the olfactory system， nasal mucosal barrier properties， and neural regulatory mechanisms， the potential application of the nose-to-brain pathway in neurological diseases has attracted increasing attention. Traditional Chinese medicine （TCM） essential oils， characterized by strong lipophilicity， small molecular weights， volatility， and diverse chemical components， are highly compatible with the physiological characteristics of the nose-to-brain pathway， thus serving as promising carriers for brain-targeted drug delivery， enhancing drug bioavailability， and exerting neuroprotective effects. On this basis， this review systematically summarizes the anatomical and physiological bases for the delivery of TCM essential oils via the nose-to-brain pathway， the patterns of drug transport and brain distribution， clinical and animal study examples in neurological diseases， the associated molecular mechanisms and signaling pathways， and the progress in the development of novel nasal essential oil formulations. Additionally， the review analyzes the current challenges in this field and proposes strategies for future research and application. By systematically discussing the nose-to-brain pathway and the delivery mechanisms of TCM essential oils， this study aims to provide theoretical support for drug development， mechanism exploration， and formulation innovation in the treatment of neurological diseases， while also offering scientific guidance for further research and clinical applications of the nose-to-brain delivery system.

The nose-to-brain pathway refers to a significant drug delivery route through which substances traverse the unique anatomical structures of the nasal cavity to directly access the central nervous system， bypassing the blood-brain barrier. Its core advantage lies in utilizing the olfactory and trigeminal nerves， enabling peripheral drug administration to rapidly and efficiently reach the brain， thereby avoiding the drug loss and bioavailability reduction associated with oral or intravenous routes due to the circulatory system and blood-brain barrier limitations. In recent years， with in-depth research into the neuroanatomy of the olfactory system， nasal mucosal barrier properties， and neural regulatory mechanisms， the potential application of the nose-to-brain pathway in neurological diseases has attracted increasing attention. Traditional Chinese medicine （TCM） essential oils， characterized by strong lipophilicity， small molecular weights， volatility， and diverse chemical components， are highly compatible with the physiological characteristics of the nose-to-brain pathway， thus serving as promising carriers for brain-targeted drug delivery， enhancing drug bioavailability， and exerting neuroprotective effects. On this basis， this review systematically summarizes the anatomical and physiological bases for the delivery of TCM essential oils via the nose-to-brain pathway， the patterns of drug transport and brain distribution， clinical and animal study examples in neurological diseases， the associated molecular mechanisms and signaling pathways， and the progress in the development of novel nasal essential oil formulations. Additionally， the review analyzes the current challenges in this field and proposes strategies for future research and application. By systematically discussing the nose-to-brain pathway and the delivery mechanisms of TCM essential oils， this study aims to provide theoretical support for drug development， mechanism exploration， and formulation innovation in the treatment of neurological diseases， while also offering scientific guidance for further research and clinical applications of the nose-to-brain delivery system.

Objective:To investigate the effects of long intergenic non-coding RNA00894(LINC00894)on the malignant biological behaviors of gastric cancer(GC)cells via regulating the microRNA-205-5p(miR-205-5p)/glycoprotein non-metastatic melanoma protein B(GPNMB)axis.Methods:Twenty-five pairs of gastric cancer tissues and corresponding adjacent tissues were collected from patients undergoing surgical resection at the First Hospital of Hebei Medical University between November 2022 and September 2023.BGC823 cells were routinely cultured and into control,sh-NC,sh-LINC00894,sh-LINC00894+anti-NC,and sh-LINC00894+anti-miR-205-5p groups,followed by corresponding plasmids transfection using transfection reagents.The mRNA expression of LINC00894,miR-205-5p,and GPNMB in BGC823 cells and cancer tissues of each group was detected using qPCR.Dual luciferase reporter gene assay and AGO2-RNA immunoprecipitation were used to verify the targeted binding relationships between LINC00894 and miR-205-5p,as well as between miR-205-5p and GPNMB.Colony formation assay,EdU staining,wound-healing assay,and Transwell assay were performed to detect cell proliferation,migration and invasion abilities.Western blotting was used to detect the protein expression of CDK1,MMP-2 and MMP-9 in each group of cells.A nude mouse xenograft model was established to determine the effect of LINC00894 knockdown on tumor growth,and immunohistochemistry was used to detect the protein expression of GPNMB in xenograft tissues.Results:LINC00894 and GPNMB were significantly upregulated in gastric cancer tissues and cells,while miR-205-5p was downregulated(both P<0.05).LINC00894 negatively regulated miR-205-5p,while miR-205-5p negatively regulated GPNMB(all P<0.05).Knocking down LINC00894 promoted miR-205-5p expression and inhibited GPNMB expression in BGC823 cells(all P<0.05).Additionally,LINC00894 knockdown suppressed the proliferation,migration and invasion abilities of BGC823 cells,as well as the protein expression of CDK1,MMP-2,and MMP-9(all P<0.05).Inhibition of miR-205-5p reversed these effects(all P<0.05).Knocking down LINC00894 inhibited the growth of BGC823 cell-transplanted tumors,promoted miR-205-5p expression,and inhibited GPNMB protein expression(all P<0.05).Conclusion:LINC00894 is highly expressed in gastric cancer tissues and cells,while miR-205-5p is downregulated.Knockdown of LINC00894 can regulate the expression of miR-205-5p/GPNMB pathway-related proteins in BGC823 cells,thereby inhibiting their malignant biological behaviors.

The structure and potential antigenic epitopes of FliCEcN were analysed using bioinformat-ics technology.With the help of ClonExpress? homologous recombination technology,primers were designed to deletion of different structural domains in the highly variable region of FliCEcN and cloned into pET-28a(+)expression vector for expression.The expressed flagellin variants were identified by SDS-PAGE and Western blot.Endotoxin residues in the flagellin variants were detected by horseshoe crab reagent chromatography,and Caco-2 cells were stimulated with differ-ent concentrations of flagellin variants.The biological activity of each flagellin variant was assessed by detecting the secretion level of IL-8.Bioinformatic analysis showed that most of the structural domains in the highly variable region of FliCEcN were predicted to contain potential antigenic epitopes.PC R results showed that fliC△820-1 518,fliC△736-963,fliC△985-1 200,fliC △748-828,fliC△1 114-1 191,andfliC△1 225-1311 were approximately 1 095,1 566,1 578,1 713,1 716 and 1 707 bp,respectively.SDS-PAGE results showed that the sizes of the flagellin variants treated with nickel column purifi-cation and dialysis replication were about 41.36,57.06,57.50,61.97,61.95 and 61.56 kDa,respec-tively.Western blot results showed that all six flagellin variants reacted specifically with anti-His monoclonal antibody and E.coli H7 antigen diagnostic serum.The results of TLR5 activity assay showed that the flagellin variants missing different structural domains retained their TLR5 agonist function.In this study,six flagellin variants with different structural domains of FliCEcN deletion hypervariable region were successfully constructed,and all of them retained their TLR5 agonist function and showed good biological properties.This provides a reference for further research on the adjuvant effect of flagellin after deletion of different structural domains and the effect of flagel-lin antibody titer on its adjuvant effect.

OBJECTIVE To analyze the etiological and clinical characteristics of the neonates with early-onset and late-onset purulent meningitis.METHODS A total of 140 neonates who were diagnosed with purulent meningitis and were hospitalized in neonatal intensive care unit(NICU)of Xuzhou Children's Hospital Affiliated to Xuzhou Medical University from Jan.2018 to Dec.2022 were recruited as the research subjects and were divided into the early-onset group with 32 cases and the late-onset group with 108 cases according to the onset time.The clinical data were collected from the enrolled neonates and were retrospectively analyzed.The etiological and clinical char-acteristics of the neonates with purulent meningitis were observed.RESULTS Totally 140 neonates with purulent meningitis were included in the study,the total morbidity rate was 1.03％(140/13644),and it was more common among the male neonates and full-term neonates,dominated by late-onset cases.The incidence rates of perinatal infection,premature rupture of fetal membranes,lethargy/irritability,cyanosis,abnormal muscle tone and septic shock were higher in the early-onset group than in the late-onset group(P＜0.05).There were significant differ-ences in serum PCT,cerebrospinal fluid cell counts,percentage of neutrophils and proteins between the early-on-set group and the late-onset group(P＜0.05).The positive rate of etiological culture of the early-onset group was 43.75％(14/32),higher than 20.37％(22/108)of the late-onset group(P＜0.05);Escherichia coli was the pre-dominant species of pathogen isolated from the two groups.The total proportion of the neonates with abnormal imaging findings was 22.85％among the two groups of neonates;the intracranial hemorrhage,subdural effusion and ventricular enlargement/hydrocephalus were the major abnormal types;the proportion of the neonates with abnormal imaging findings of the early-onset group was 43.75％,higher than 16.67％of the late-onset group(P＜0.05).CONCLUSIONS The neonates with late-onset purulent meningitis are dominant among the neonates with purulent meningitis enrolled in the study.The neonates with early-onset purulent meningitis present with more se-vere clinical manifestations and higher proportion of abnormal imaging findings;there is significant difference in the clinical characteristics between the early-onset neonates and the late-onset neonates.The result of etiological culture shows that E.coli is the predominant species of pathogen among both the early-onset neonates and the late-onset children.

Objective To investigate the clinical effect of elastic fixation of Endobutton plate with loop in the treatment of lower tibiofibular combined injury.Methods A total of 326 patients with lower tibiofibular joint injury combined with ankle fracture underwent surgical treatment from June 2019 to June 2021 were randomly divided into experimental group(163 cases)and control group(163 cases)by using a random number table.The control group was fixed with traditional steel plate screw,and the experimental group was fixed with elastic steel plate with loop Endobutton.Hospitalization and operation related indexes were compared between the two groups.The American Association of Foot and Ankle Surgery Ankle Function Score(AOFAS)was performed on the two groups at 2 and 6 months after surgery,respectively,and the reseparation rate of the lower tibiofibular union was evaluated and compared between the two groups at 6 months after surgery.Results There were no significant differences in operation time,blood loss,incision length,getting out of bed time and hospital stay between experimental group and control group(P＞0.05).The incidence of postoperative complications in experimental group was 2.45％,lower than that in control group(7.98％),and the difference between the two groups was statistically significant(P＜0.05).The incidence of postoperative complications in experimental group was 2.45％,lower than that in control group(7.98％),and the difference was statistically significant between the two groups(P＜0.05).The AOFAS scores of control group were(74.5±9.2)and(81.3±4.3)at 2 months and 6 months,respectively,and the excellent and good rate was 76.0％.AOFAS of experimental group were(82.3±5.3)points and(91.2±3.8)points at 2 months and 6 months after surgery,respectively,and the excellent and good rate was 93.2％,the above indexes of experimental group were higher than those of control group,and the difference between the two groups was statistically significant(P＜0.05).Reexamination 6 months after surgery the reseparation rate of lower tibiofibular combination was 12.8％in the control group and 2.4％in the experimental group,and the risk of reseparation in the experimental group was lower than that in the control group,with statistical significance(P＜0.05).Conclusion Elastic fixation using Endobutton plate with loop could be used in the treatment of ankle fracture with distal tibiofibular syndesmosis injury,which has a better effect of traditional internal fixation with plate and screws.

Objective:To investigate the effects of circular RNA fascin actin-bundling protein 1(circFSCN1)on the malignant biological behaviors of gastric cancer cells by regulating the microRNA-429(miR-429)/glycoprotein nonmetastatic melanoma protein B(GPNMB)axis and its mechanisms.Methods:The gastric cancer tissues and corresponding para-cancerous tissues of 54 patients who underwent surgical resection at the First Hospital of Hebei Medical University between September 2022 and September 2023 were collected.The expressions of circFSCN1,miR-429 and GPNMB mRNA in gastric cancer tissues were detected by qPCR.Gastric cancer MGC803 cells were routinely cultured and divided into the control group,the sh-NC group,the sh-circFSCN1 group,the sh-circFSCN1+anti-NC group,and the sh-circFSCN1+anti-miR-429 group.The expressions of circFSCN1,miR-429 and GPNMB mRNA in MGC803 cells of each group were detected by qPCR.The proliferation,migration,invasion and apoptosis of MGC803 cells in each group were detected by CCK-8 method,colony formation assay,Transwell assay and flow cytometry,respectively.Immunofluorescence was used to detect the expressions of GPNMB protein in cells of each group.WB assay was used to detect the expressions of PCNA,MMP-2,GPNMB and Cleaved Caspase-3 proteins in MGC803 cells of each group.Dual luciferase reporter assay and RNA-binding protein immunoprecipitation(RIP)assay were used to verify the binding regulatory relationship between circFSCN1 and miR-429,and between miR-429 and GPNMB.Results:circFSCN1 and GPNMB mRNA were both highly expressed in gastric cancer tissues(both P<0.05),while miR-429 was lowly expressed(P<0.05).Knockdown of circFSCN1 could promote the expression of miR-429 and inhibit the expression of GPNMB mRNA.Inhibition of miR-429 could promote the expression of GPNMB mRNA.Knockdown of circFSCN1 could significantly inhibit the proliferation,migration and invasion abilities of MGC803 cells and promote their apoptosis.Inhibition of miR-429 could partially reverse the effect of circFSCN1 knockdown.Knockdown of circFSCN1 could inhibit the expressions of PCNA,MMP-2 and GPNMB proteins in MGC803 cells and inhibit the expression of cleaved caspase-3 protein.There was a targeted binding and negative regulatory relationship between circFSCN1 and miR-429 and between miR-429 and GPNMB mRNA.Conclusion:Knocking down circFSCN1 inhibits the malignant biological behaviors of gastric cancer cells through the miR-429/GPNMB axis,indicating that circFSCN1 is a potential therapeutic target for gastric cancer.

Objective To identify clinicopathological parameters that differentiate between very high-risk and ordinary high-risk gas-trointestinal stromal tumors(GISTs)to provide guidance for clinical treatment and follow-up monitoring.Methods A retrospective cohort study was conducted,collecting 174 cases of high-risk GISTs initially diagnosed and surgically resected at Tianjin Medical University Cancer Institute and Hospital between January 1st,2011,and December 31st,2019.Based on long-term follow-up data,the X-tile software was used to identify key parameters for screening very high-risk GISTs from ordinary high-risk GISTs,and the results were validated by using high-risk GIST cases from the cBioPortal database.Results Among the 174 high-risk GIST cases,the X-tile software indicat-ed that the maximum tumor diameter of 14 cm,the mitotic count of 14/5 mm2,and the Ki-67 proliferation index of 10%were the optimal cutoff values for distinguishing very high-risk GISTs from ordinary high-risk GISTs.Univariate survival analysis confirmed that these cutoff values were associated with progression free survival(PFS,all P<0.05).Multivariate survival analysis confirmed that the maximum tumor diameter≥14 cm(HR=5.727,P<0.01),mitotic count≥14/5 mm2(HR=2.454,P=0.047),and Ki-67 proliferation index≥10%(HR=2.275,P=0.047)were independent risk factors for tumor progression in high-risk GIST patients.High-risk GISTs with any one of the three parameters more than or equal to its optimal cutoff value were defined as very high-risk GISTs,and the other GISTs were defined as ordinary high-risk GISTs.Compared to very high-risk GIST patients,the ordinary high-risk GIST patients had superior PFS(P<0.01),and a trend toward better overall survival(OS,P=0.082).Stratified analysis showed that,in subgroups of patients with gastric or non-gas-tric primary tumors,those receiving or not receiving adjuvant therapy,and those with KIT proto-oncogene,receptor tyrosine kinase(KIT)gene mutations,ordinary high-risk GIST patients all exhibited superior PFS compared to very high-risk GIST patients(all P<0.05).Both PFS and OS of ordinary high-risk GIST patients in the cBioPortal database were better than those of very high-risk GIST patients(both P=0.001).Stratified analysis of the cBioPortal database data showed that,in subgroups of patients with gastric or non-gastric primary tu-mors,those who received adjuvant therapy,and those with KIT gene mutations,ordinary high-risk GIST patients all exhibited superior PFS compared to very high-risk GIST patients(all P<0.05);conversely,among patients who did not receive adjuvant therapy,very high-risk GIST patients showed a trend toward poorer PFS(P=0.366).Conclusions This study has established a method utilizing commonly used clinical parameters to distinguish very high-risk GISTs in clinical practice.However,further validation through multicenter studies with larger sample sizes is still required.

The 16S rRNA sequencing,whole genome sequencing and drug sensitivity tests were used to identify the isolates molecularly and to detect and analyse their virulence genes,resistance genes and drug resistance.The results showed that the isolate was highly homologous to Klebsiella pneumoniae X4 and located on the same branch by 16S rRNA sequence analysis,and it was named as KLKp10.Whole genome sequencing results showed that the KLKp10 genome was 5 342 841 bp in length,containing 5 138 genes,346 repetitive segments,6 rRNAs and 81 tRNAs,with a GC con-tent of 57.30％.MLST analysis showed that KLKp10 belongs to the ST-4263 type.The functions of 4 097 of the genes encoding proteins were classified and annotated by COG,and there were also 382 genes with unknown functions.A total of 50 functional classifications were involved in the an-notation results based on the GO database;33 kinds of signaling pathways were covered based on the signaling pathway annotations in the KEGG database.A total of 443 virulence genes were screened in the VFDB database,of which 339 belonged to the Set A database and could encode 124 virulence factors.The 101 resistance genes were predicted by comparing with the CARD database,among which there were more resistance genes against β-lactam antibiotics.The results of drug sensitivity test showed that KLKp10 was highly sensitive to ceftazidime,gentamicin,azithro-mycin,chloramphenicol,norfloxacin,ofloxacin,and enrofloxacin;moderately sensitive to ceftriax-one,neomycin,kanamycin,and streptomycin;and resistant to ciprofloxacin,tetracycline,amoxicil-lin,and penicillin.In this study,we systematically revealed the gene-wide characterization,virulence factors and drug resistance of Klebsiella pneumoniae KLKp10 of Kole pig origin,which provides important data support for the study of Klebsiella pneumoniae at the overall level of its genome.