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.

ObjectiveTo investigate the effects of mitotically-associated long non-coding RNA （lncRNA MANCR） on the proliferation，migration， and epithelial mesenchymal transition （EMT） of gastric cancer （GC） cells by regulating the microRNA-50-5p （miR-150-5p）/non-metastatic melanoprotein B （GPNMB） axis. MethodsThe mRNA expressions of lncRNA MANCR，miR-150-5p， and GPNMB in 42 cases of GC tissue and adjacent tissue resected during surgery in the First Hospital of Hebei Medical University from June 2022 to September 2023 were detected by Real-time PCR. Human gastric mucosal epithelial cells GES-1 and human GC cells BGC-823 were cultured in vitro， and their lncRNA MANCR expression was detected. BGC-823 cells were randomly separated into control group （routine culture），sh-NC group （with sh-NC transfected），sh-MANCR group （with sh-MANCR transfected），sh-MANCR + anti-NC group （with sh-MANCR and anti-NC both transfected），and sh-MANCR + anti-miR-150-5p group （with sh-MANCR and anti-miR-150-5p both transfected）. The mRNA expressions of lncRNA MANCR，miR-150-5p， and GPNMB in the BGC-823 cells of all groups were analyzed. EdU staining was used to detect the proliferation of BGC-823 cells. Transwell assay was used to detect the migration and invasion of BGC-823 cells. The expressions of EMT-related proteins E-cadherin，N-cadherin，Vimentin， and GPNMB were detected by Western blot. The interactions between lncRNA MANCR and miR-150-5p and between miR-150-5p and GPNMB were analyzed by dual luciferase reporter assay. ResultsThe mRNA expressions of lncRNA MANCR and GPNMB in GC tissue were higher than those in adjacent tissue，and the expression of miR-150-5p was lower than that in adjacent tissue （P<0.05）. Compared with that in GES-1，lncRNA MANCR expression in BGC-823 cells was increased （P<0.05）. Compared with those in the sh-NC group and control group，the EdU-positive cell rate，migration number，invasion number，the mRNA expressions of lncRNA MANCR and GPNMB， and the expressions of protein，N-cadherin protein， and Vimentin protein in the BGC-823 cells in the sh-MANCR group were lower ，and the protein expressions of miR-150-5p and E-cadherin were higher （P<0.05）. Compared with those in the sh-MANCR group and the sh-MANCR + anti-NC group，the protein expressions of miR-150-5p and E-cadherin in the sh-MANCR + anti-miR-150-5p group were decreased. The EdU-positive cell rate，migration number，invasion number，mRNA expressions of GPNMB， and expressions of protein，N-cadherin protein， and Vimentin protein were increased （P<0.05）. lncRNA MANCR could target the negative regulation of miR-150-5p，and miR-150-5p could target the negative regulation of GPNMB. ConclusionKnockout of lncRNA MANCR can inhibit the proliferation，migration， and EMT of GC cells by regulating the miR-150-5p/GPNMB axis.

Objective: To investigate the effects of Zuogui Jiangtang Jieyu Formula (ZGJTJYF) on histone H3 lysine 18 lactylation (H3K18la) in the hippocampus of rats with diabetes mellitus complicated with depression (DD) and predict the regulatory genes of H3K18la. Methods: Male Sprague-Dawley rats were divided into control, model, and positive drug (metformin [0.18 g/kg] and fluoxetine [1.8 mg/kg]) groups, and the three groups were treated with high, medium, and low ZGJTJYF doses (20.52, 10.26, and 5.13 g/kg, respectively), with 10 rats per group. After treatment, the forced swimming and water maze tests were performed to assess depressive-like behaviors and cognitive function. An enzyme-linked immunosorbent assay was used to measure blood insulin, glycosylated hemoglobin, lactate levels, and lactate content in the hippocampus. Western blotting was used to detect H3K18la expression in the hippocampus. Cleavage Under Targets and lagmentation(CUT&Tag) experiments targeted hippocampal H3K18la epigenetic modification regions to analyze the transcription factors bound by H3K18la. Kyoto Encyclopedia of Genes and Genomes and Protein-Protein Interaction networks were constructed to identify key pathways and target genes regulated by H3K18la. Results: Compared with the normal group, the model group rats showed prolonged immobility time in the forced swim test, increased escape latency in the water maze experiment, decreased target quadrant distance ratio (P<0.01), increased serum lactate content, and decreased lactate content in hippocampal homogenate (P<0.01), as well as decreased H3K18la protein expression in the hippocampus (P<0.01). Compared with the model group, ZGJTJYF reduced the immobility time in the forced swim test and the escape latency in the water maze test (P<0.01), while the distance ratio in the target quadrant increased (P<0.01) in model rats. Lowered fasting blood glucose, insulin, and glycosylated hemoglobin levels (P<0.05, P<0.01) were also observed. ZGJTJYF also increased the lactate content and H3K18la protein expression in hippocampal homogenate (P<0.05, P<0.01). The DNA sequences bound by H3K18la were predominantly enriched at the transcription start sites. ZGJTJYF modulated H3K18la-associated pathways, including cell adhesion junctions, tumor growth factor-beta (TGF-β) signaling, stem cell pluripotency regulation, mitogen-activated protein kinase(MAPK) signaling pathway, and insulin resistance, leading to the identification of 12 target genes. Conclusion ZGJTJYF enhances hippocampal lactate levels and H3K18la modification in DD rats, which may regulate neural cell interactions, neurogenic stem cell function, TGF-β signaling, MAPK signaling, and insulin resistance pathways.

Aging is an inevitable, physiological process of the human body, leading to deterioration in bodily function and increased susceptibility to various diseases. Effective endogenous therapeutic strategies for anti-aging and related diseases remain limited. Exercise confers multifaceted benefits to physical health by augmenting osteogenic and myogenic processes, enhancing cardiovascular and nervous system function, and attenuating chronic inflammation. Angiogenesis and lymphangiogenesis play pivotal roles in anti-aging, tissue repair, and immune response modulation, underscoring their potential as therapeutic targets for age-related diseases. Modulating angiogenic and lymphangiogenic pathways may provide a promising strategy for mitigating vascular decline and immune system dysfunction associated with aging. Exercise-induced endogenous angiogenesis and lymphangiogenesis can exert beneficial effects on physiological function, thereby representing a potential therapeutic paradigm for combating age-related decline and diseases. This review offers a thorough summary of the present knowledge regarding angiogenesis and lymphangiogenesis induced by exercise, encompassing the underlying mechanisms and the effects in different organs. In addition, it explores the potential of physical activity as a non-pharmacological intervention for anti-aging strategies and disease management, offering novel insights into the intersection of physical activity, aging, and disease progression.
Humans ; Lymphangiogenesis/physiology* ; Aging/physiology* ; Exercise/physiology* ; Animals ; Neovascularization, Physiologic/physiology* ; Angiogenesis

ObjectiveTo investigate the effects of mitotically-associated long non-coding RNA （lncRNA MANCR） on the proliferation，migration， and epithelial mesenchymal transition （EMT） of gastric cancer （GC） cells by regulating the microRNA-50-5p （miR-150-5p）/non-metastatic melanoprotein B （GPNMB） axis. MethodsThe mRNA expressions of lncRNA MANCR，miR-150-5p， and GPNMB in 42 cases of GC tissue and adjacent tissue resected during surgery in the First Hospital of Hebei Medical University from June 2022 to September 2023 were detected by Real-time PCR. Human gastric mucosal epithelial cells GES-1 and human GC cells BGC-823 were cultured in vitro， and their lncRNA MANCR expression was detected. BGC-823 cells were randomly separated into control group （routine culture），sh-NC group （with sh-NC transfected），sh-MANCR group （with sh-MANCR transfected），sh-MANCR + anti-NC group （with sh-MANCR and anti-NC both transfected），and sh-MANCR + anti-miR-150-5p group （with sh-MANCR and anti-miR-150-5p both transfected）. The mRNA expressions of lncRNA MANCR，miR-150-5p， and GPNMB in the BGC-823 cells of all groups were analyzed. EdU staining was used to detect the proliferation of BGC-823 cells. Transwell assay was used to detect the migration and invasion of BGC-823 cells. The expressions of EMT-related proteins E-cadherin，N-cadherin，Vimentin， and GPNMB were detected by Western blot. The interactions between lncRNA MANCR and miR-150-5p and between miR-150-5p and GPNMB were analyzed by dual luciferase reporter assay. ResultsThe mRNA expressions of lncRNA MANCR and GPNMB in GC tissue were higher than those in adjacent tissue，and the expression of miR-150-5p was lower than that in adjacent tissue （P<0.05）. Compared with that in GES-1，lncRNA MANCR expression in BGC-823 cells was increased （P<0.05）. Compared with those in the sh-NC group and control group，the EdU-positive cell rate，migration number，invasion number，the mRNA expressions of lncRNA MANCR and GPNMB， and the expressions of protein，N-cadherin protein， and Vimentin protein in the BGC-823 cells in the sh-MANCR group were lower ，and the protein expressions of miR-150-5p and E-cadherin were higher （P<0.05）. Compared with those in the sh-MANCR group and the sh-MANCR + anti-NC group，the protein expressions of miR-150-5p and E-cadherin in the sh-MANCR + anti-miR-150-5p group were decreased. The EdU-positive cell rate，migration number，invasion number，mRNA expressions of GPNMB， and expressions of protein，N-cadherin protein， and Vimentin protein were increased （P<0.05）. lncRNA MANCR could target the negative regulation of miR-150-5p，and miR-150-5p could target the negative regulation of GPNMB. ConclusionKnockout of lncRNA MANCR can inhibit the proliferation，migration， and EMT of GC cells by regulating the miR-150-5p/GPNMB axis.

Objective:To investigate the preventive and therapeutic effects and mechanisms of Dachaihu decoction(DCD)on dextran sodium sulfate(DSS)-induced ulcerative colitis(UC)and liver injury in mice,as well as the association between DCD benefits and gut microbiota modulation.Methods:Mice were treated with DCD(20.10 and 10.05 g/kg)for 2 weeks,with free access to drinking water containing 3%DSS in the second week to induce UC.Histopathological examination,RT-qPCR and 16S rRNA sequencing were used to investigate the effect of DCD on UC mice.Results:DCD pretreatment significantly alleviated weight loss,bloody diarrhea with mucus,histopathological abnormalities of the colon,and colon shortening in mice with DSS-induced UC.In addition,DCD pretreat-ment significantly upregulated the levels of Occludin,ZO-1,and MUC-2 in the colon and protected the intestinal barrier of mice.DCD pretreatment also alleviated inflammatory cell infiltration in the colon and the liver and significantly reduced the expression levels of the proinflammatory factors such as IL-1β,IL-6,TNF-α,iNOS,COX-2,and NLRP3,thereby exerting a protective effect against UC and liver injury.It should be noted that DCD corrected gut micro-biota imbalance in UC mice by enriching probiotic bacteria such as Lactobacillus and Bifidobacterium and reducing harmful bacteria such as Norank_f_Desulfovibrionaceae and Escherichia-Shigella.Conclusion:DCD can alleviate DSS-induced UC and exert a liver-protecting effect by protecting intestinal barrier,inhibiting inflam-mation,and regulating gut microbiota.

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.

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.

Idiopathic intracranial hypertension (IIH) is a neurological disorder characterized by an unexplained increase in intracranial pressure that primarily affects obese women of childbearing age, but individuals of any age, gender, or weight may also be affected. Its signature symptoms include disc edema, headache, visual disturbance, and throbbing tinnitus. Due to potentially serious complications, such as vision loss, accurate diagnosis and appropriate treatment management are critical to improving patients' quality of life. Ophthalmologists play a key role in the treatment process, as about half of patients first visit the eye department. Diagnosis of IIH depends not only on clinical presentation, but also on the exclusion of other diseases that may cause similar symptoms, and imaging and other tests to ensure an accurate diagnosis. In order to improve diagnostic accuracy and treatment efficiency, multidisciplinary collaborative diagnosis and treatment mode is advocated, especially in the face of patients with complex trauma or systemic diseases, which can effectively shorten the treatment time and ensure patient safety. Future research directions include establishing China's IIH epidemiological database, exploring clinical diagnosis and treatment methods and basic scientific research, aiming at forming diagnosis and treatment standards suitable for China's national conditions, improving medical level and improving patient prognosis. At the same time, a deeper understanding of the different forms of IIH will better serve the affected populations.