As a commonly used clinical herb, Ligustri Lucidi Fructus is renowned for its effects in nourishing the liver and kidneys, improving vision, and darkening hair. Its preparation originated from the "steaming on rice" method in the Song Dynasty. After centuries of inheritance and development, it has evolved into the diverse processing techniques used today. Ancient methods primarily included cleaning, cutting, soaking, honey-roasting, and steaming, while baking-though documented-was not a mainstream practice. Modern techniques have inherited traditional approaches such as cleaning, steaming, and roasting, while diversifying into specifications like wine-steaming, wine-stewing, plain steaming, vinegar-steaming, salt-roasting, and ultra-fine granules. However, variations in critical parameters, such as auxiliary material ratios and steaming duration across regions, have led to inconsistencies in the quality of processed Ligustri Lucidi Fructus. Notably, region-specific methods warrant further exploration, as they may embody unique processing principles and advantages with potential value for enhancing efficacy and quality. By systematically reviewing the historical evolution and regional variations of processing techniques for Ligustri Lucidi Fructus, key issues such as inconsistent processing parameters were identified, which provided a reference for the standardization of processing procedures and the improvement of quality standards.

ObjectiveTo explore the mechanism of herbal cake-separated moxibustion using the classical formula Xiaoyaosan in alleviating neuroimmune inflammatory responses in chronic fatigue syndrome （CFS） rats， based on the regulation of the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear transcription factor-κB （NF-κB） signaling pathway. MethodsFifty SPF-grade SD rats aged 6-8 weeks were randomly divided into five groups： Normal group， model group， sham herbal cake moxibustion group， Chinese medicine intragastric administration group， and herbal cake-separated moxibustion group， with 10 rats in each group. Except for the normal group， all other groups underwent a 21-day modeling process， followed by behavioral testing. The herbal cake-separated moxibustion and sham herbal cake moxibustion groups received interventions at the Shenque （CV8）， Guanyuan （CV4）， Zusanli （ST36）， and Qimen （LR14） acupoints. The Chinese medicine intragastric administration group was treated with a Xiaoyaosan suspension via gavage. Behavioral tests were conducted after 10 days of continuous intervention. Serum levels of interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α）， as well as hippocampal levels of IL-1β， IL-6， TNF-α， and NF-κB， were detected by enzyme-linked immunosorbent assay （ELISA）. Morphological changes in the hippocampus were observed using hematoxylin-eosin （HE） staining. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression levels of TLR4， MyD88， and NF-κB in the hippocampus. Western blot analysis was performed to detect the relative expression levels of TLR4， MyD88， NF-κB， and p65 proteins in the hippocampus. ResultsCompared with the normal group， the model group showed a significant decrease in upright times during the open field test （P<0.01）， as well as significant reductions in total movement distance， resting time， and center region duration （P<0.01）. In the tail suspension test， immobility time increased （P<0.01）， and struggle times decreased （P<0.01）. Serum and hippocampal levels of IL-1β， IL-6， and TNF-α， as well as hippocampal NF-κB levels and TLR4， MyD88， and NF-κB mRNA expression， were significantly elevated （P<0.01）. After treatment， compared with the model group， the total movement distance and upright times in the open field test were significantly increased in all treatment groups （P<0.01）， while resting time and center region duration were notably prolonged （P<0.05， P<0.01）. Immobility time in the tail suspension test was significantly shortened （P<0.01）， and struggle times significantly increased （P<0.05）. Serum and hippocampal levels of IL-1β， IL-6， TNF-α， hippocampal NF-κB levels， and TLR4 and NF-κB mRNA expression were significantly reduced （P<0.05， P<0.01）. Compared with the sham herbal cake moxibustion group， the herbal cake-separated moxibustion group showed a significant extension in center region duration during the open field test （P<0.05） and a significant increase in upright times （P<0.01）. In the tail suspension test， immobility time was reduced （P<0.01）， and struggle times increased （P<0.01）. Serum TNF-α levels in the Chinese medicine intragastric administration group were significantly reduced （P<0.01）， while serum IL-6 levels， as well as hippocampal levels of IL-1β， TNF-α， NF-κB， and TLR4， MyD88， and NF-κB mRNA expression， were significantly decreased in both the Chinese medicine intragastric administration group and the herbal cake-separated moxibustion group （P<0.05， P<0.01）. Compared with the Chinese medicine intragastric administration group， the herbal cake-separated moxibustion group exhibited significantly increased upright times in the open field test （P<0.01）. In the tail suspension test， immobility time was reduced （P<0.01）， and struggle times increased （P<0.01）. Serum IL-1β， hippocampal TNF-α levels， and TLR4， MyD88， and NF-κB mRNA expression were significantly decreased （P<0.05， P<0.01）. ConclusionHerbal cake-separated moxibustion effectively improves fatigue and memory function in CFS rats， regulates neuroimmune inflammatory responses， and its mechanism may be related to the modulation of the TLR4/MyD88/NF-κB signaling pathway.

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.

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.

Objective To explore the risk factors for postpartum hemorrhage in the patients with severe preeclampsia.Methods A retrospective analysis was conducted on the data of 767 pregnant women with se-vere preeclampsia admitted and treated in this hospital from January 2021 to July 2023.Among them,80 pa-tients with severe preeclampsia who developed postpartum hemorrhage were included in the observation group,and the remaining 687 patients without PPH were included in the control group.The univariate analysis and binary logistic multivariate regression analysis were used to identify the independent risk factors for post-partum hemorrhage.The receiver operating characteristic(ROC)curve was drawn to analyze the effectiveness of these risk factors in predicting postpartum hemorrhage occurrence in the patients with severe preeclampsia.Results The univariate analysis results showed that the incidence rates of assisted reproduction,twin preg-nancy,hypoproteinemia,placenta previa,oligohydramnios,abnormal umbilical cord blood flow and nuchal cord in the observation group were significantly higher than those in the control group(P＜0.05).The binary lo-gistic regression analysis results revealed that the large neonatal birth weight,assisted reproduction,hypopro-teinemia,placenta previa and twin pregnancy were the independent risk factors for postpartum hemorrhage oc-currence in the patients with severe preeclampsia.The ROC curve analysis results indicated that the area un-der the curve(AUC)of the above factors for predicting postpartum hemorrhage in the patients with severe preeclampsia was 0.603,0.567,0.528,0.588 and 0.574,respectively.When the combined prediction,AUC was 0.735,the optimal cut-off value was 0.385,the sensitivity was67.5％and specificity was 71.0％.Conclu-sion Large neonatal birth weight,assisted reproduction,hypoproteinemia,placenta previa and twin pregnancy are the independent risk factors for postpartum hemorrhage occurrence in the patients with severe preeclampsia.

ObjectiveTo explore the mechanism of moxibustion with the classical prescription Xiaoyaosan as the herbal cake in improving cognitive function in the rat model of chronic fatigue syndrome （CFS） by regulating autophagy via phosphatidylinosiol 3-kinase （PI3K）/autophagy key molecule yeast Atg6 homologue 1 （Beclin1） signaling pathway. MethodsFifty SPF-grade SD rats aged 6-8 weeks were randomly grouped as follows： control， model， sham cake-separated moxibustion， intragastric administration with Chinese herbs， and herbal cake-separated moxibustion， each with 10 rats. The other groups except the control group were subjected to modeling by exhaustive swimming and chronic restraint stress for 21 days， and the behavioral test was performed after modeling. Herbal cake-separated moxibustion and sham cake-separated moxibustion were carried out at Shenque （CV8）， Guanyuan （CV4）， Zusanli （ST36）， and Qimen （LR14）. The rats in the intragastric administration with Chinese herbs group were treated with Xiaoyaosan suspension by gavage. After continuous intervention for 10 days， rat behaviors were observed and the levels of interleukin （IL）-4， IL-10， blood urine nitrogen （BUN）， and malondiadehyde （MDA） in the serum and hippocampal tissue of rats in each group were determined by enzyme-linked immunosorbent assay. The morphological changes of the hippocampal tissue were observed by hematoxylin-eosin staining. The relative mRNA and protein levels of PI3K and Beclin1 in the hippocampal tissue were determined by Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultsCompared with the normal group， the model group showed reduced crossings， shortened residence time in the target quadrant， and prolonged average escape latency on days 1， 2， 3， and 4 （P<0.01） in the Morris water maze test. In the new object recognition test， the model group showed decreased recognition index of exploration time and recognition index of exploration times （P<0.01）， lowered levels of IL-4 and IL-10 and elevated levels of BUN and MDA in the serum and hippocampus （P<0.01）， and down-regulated mRNA and protein levels of PI3K and Beclin1 （P<0.01）. After treatment， compared with the model group， each treatment group showed increased crossings， prolonged residence time in the target quadrant， and shortened average escape latency on days 1， 2， 3， and 4 （P<0.05， P<0.01）. In addition， the treatment elevated the levels of IL-4 and IL-10 and lowered the levels of BUN and MDA in the serum and hippocampus （P<0.05， P<0.01）， and up-regulated the mRNA and protein levels of PI3K and Beclin1 （P<0.05， P<0.01）. Compared with the sham cake-separated moxibustion group， the herbal cake-separated moxibustion group and the intragastric administration with Chinese herbs group showed increased crossings， prolonged residence time in the target quadrant （P<0.05）， elevated level of IL-4， lowered level of MDA， and up-regulated relative mRNA and protein levels of PI3K and Beclin1 in the hippocampus （P<0.05， P<0.01）. The serum levels of MDA and BUN in the intragastric administration with Chinese herbs group were significantly decreased. The average escape latency of the herbal cake-separated moxibustion group was significantly shortened on days 2 and 3 （P<0.05， P<0.01）. In addition， this group showed elevated serum level of IL-4， lowered serum level of MDA， and declined BUN level in the hippocampus （P<0.05， P<0.01）. Compared with the intragastric administration with Chinese herbs group， the herbal cake-separated moxibustion group presented risen serum level of IL-4 and up-regulated mRNA level of Beclin1 （P<0.05） and relative protein levels of PI3K and Beclin1 （P<0.05， P<0.01）. ConclusionHerbal cake-separated moxibustion can effectively alleviate fatigue and improve the memory， reduce inflammatory response and oxidative stress， and decrease autophagy of hippocampal neurons in CFS rats by regulating the PI3K/Beclin1 signaling pathway.

ObjectiveTo explore the mechanism of moxibustion with the classical prescription Xiaoyaosan as the herbal cake in improving cognitive function in the rat model of chronic fatigue syndrome （CFS） by regulating autophagy via phosphatidylinosiol 3-kinase （PI3K）/autophagy key molecule yeast Atg6 homologue 1 （Beclin1） signaling pathway. MethodsFifty SPF-grade SD rats aged 6-8 weeks were randomly grouped as follows： control， model， sham cake-separated moxibustion， intragastric administration with Chinese herbs， and herbal cake-separated moxibustion， each with 10 rats. The other groups except the control group were subjected to modeling by exhaustive swimming and chronic restraint stress for 21 days， and the behavioral test was performed after modeling. Herbal cake-separated moxibustion and sham cake-separated moxibustion were carried out at Shenque （CV8）， Guanyuan （CV4）， Zusanli （ST36）， and Qimen （LR14）. The rats in the intragastric administration with Chinese herbs group were treated with Xiaoyaosan suspension by gavage. After continuous intervention for 10 days， rat behaviors were observed and the levels of interleukin （IL）-4， IL-10， blood urine nitrogen （BUN）， and malondiadehyde （MDA） in the serum and hippocampal tissue of rats in each group were determined by enzyme-linked immunosorbent assay. The morphological changes of the hippocampal tissue were observed by hematoxylin-eosin staining. The relative mRNA and protein levels of PI3K and Beclin1 in the hippocampal tissue were determined by Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultsCompared with the normal group， the model group showed reduced crossings， shortened residence time in the target quadrant， and prolonged average escape latency on days 1， 2， 3， and 4 （P<0.01） in the Morris water maze test. In the new object recognition test， the model group showed decreased recognition index of exploration time and recognition index of exploration times （P<0.01）， lowered levels of IL-4 and IL-10 and elevated levels of BUN and MDA in the serum and hippocampus （P<0.01）， and down-regulated mRNA and protein levels of PI3K and Beclin1 （P<0.01）. After treatment， compared with the model group， each treatment group showed increased crossings， prolonged residence time in the target quadrant， and shortened average escape latency on days 1， 2， 3， and 4 （P<0.05， P<0.01）. In addition， the treatment elevated the levels of IL-4 and IL-10 and lowered the levels of BUN and MDA in the serum and hippocampus （P<0.05， P<0.01）， and up-regulated the mRNA and protein levels of PI3K and Beclin1 （P<0.05， P<0.01）. Compared with the sham cake-separated moxibustion group， the herbal cake-separated moxibustion group and the intragastric administration with Chinese herbs group showed increased crossings， prolonged residence time in the target quadrant （P<0.05）， elevated level of IL-4， lowered level of MDA， and up-regulated relative mRNA and protein levels of PI3K and Beclin1 in the hippocampus （P<0.05， P<0.01）. The serum levels of MDA and BUN in the intragastric administration with Chinese herbs group were significantly decreased. The average escape latency of the herbal cake-separated moxibustion group was significantly shortened on days 2 and 3 （P<0.05， P<0.01）. In addition， this group showed elevated serum level of IL-4， lowered serum level of MDA， and declined BUN level in the hippocampus （P<0.05， P<0.01）. Compared with the intragastric administration with Chinese herbs group， the herbal cake-separated moxibustion group presented risen serum level of IL-4 and up-regulated mRNA level of Beclin1 （P<0.05） and relative protein levels of PI3K and Beclin1 （P<0.05， P<0.01）. ConclusionHerbal cake-separated moxibustion can effectively alleviate fatigue and improve the memory， reduce inflammatory response and oxidative stress， and decrease autophagy of hippocampal neurons in CFS rats by regulating the PI3K/Beclin1 signaling pathway.

Depression and circadian rhythms exhibit bidirectional interactions,suggesting a close association with the biological clock system.The biological clock in the suprachiasmatic nucleus of the hypothalamus is regulated by circadian genes.Recent clinical and basic research has revealed multifaceted associations between depression and circadian genes.For instance,significant phase abnormalities in BMAL1,PER2,and PER3 were detected in brain tissue from depressed patients,while plasma levels of CRY1,ARNTL,and PER1 proteins showed marked reduction,demonstrating good diagnostic value.Mice with CLOCK and BMAL1 knockouts exhibited depression-like behaviors.Single nucleotide polymorphisms(SNPs)in genes such as PER1 and PER3 directly influence depression susceptibility.Methylation levels of BMAL1,PER3,and CLOCK genes correlate closely with depressive symptoms.Antidepressant mechanisms like ketamine exert their effects by downregulating PER2 and other genes.This review summarizes the differential expression patterns of circadian clock genes in depression and associated therapeutic approaches,aiming to provide new theoretical foundations for precision diagnosis and personalized treatment strategies for depression.

With the extended survival period of breast cancer patients and the increasing health demands, the concomitant diseases of breast cancer have gradually attracted the attention of both doctors and patients, and it is imperative to conduct comprehensive management of these diseases, in which the general practitioners, as the more comprehensive and complex medical talents, have not yet played their due roles. In this article, we report two cases of comprehensive management of concomitant diseases of breast cancer through collaboration of general practitioners and specialists (integrated general and specialist care). The role and function of general practitioners in this process were deeply analyzed, and the establishment of a consultation-liaison general practice model to further promote the role of integrated general and specialist care in integrated oncology care was advocated.

Parathyromegaly refers to chronic enlargement of the parathyroid glands caused by multiple etiological factors. Pathological conditions, such as hyperparathyroidism, parathyroid hyperfunction, parathyroid adenoma, parathyroid cysts, and parathyroid carcinoma may all lead to parathyromegaly. Notably, calcium intake insufficiency and/or vitamin D insufficiency (CVI), which is the predominant etiology of parathyromegaly, now has been recognized as a global public health challenge. Chronic CVI induces negative calcium balance and relative low serum calcium level, stimulating compensatory parathyroid hyperplasia and enlargement. This progression triggers parathyroid hyperfunction and secondary hyperparathyroidism, resulting in bone mass loss, height reduction, kyphosis, osteoporosis, pathological fractures, metastatic vascular calcification and systemic abnormal calcium migration and calcinosis (such as urolithiasis). During the early stages of parathyromegaly, the condition remains preventable and treatable; However, delayed intervention may lead to irreversible tertiary hyperparathyroidism. CVI-associated parathyromegaly exhibits high prevalence and heterogeneous clinical manifestations, representing a critically underrecognized clinical entity. This article will systematically discuss the etiology, pathological characteristics, clinical consequences, and prevention and control strategies for CVI-related parathyromegaly.