ObjectiveTo investigate the changes in chemical components of Gardeniae Fructus（GF） before and after being charred， providing data support for research on the material basis of GF Carbonisata（GFC）. MethodsUltra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Orbitrap MS/MS） was used to conduct a comprehensive analysis of the chemical components in GF and GFC under positive and negative ion modes with Compound Discoverer 3.3 software and online database. Then， principal component analysis and partial least squares-discriminant analysis in SIMCA14.1 software were used to analyze the MS data of each sample. Based on the principle of variable importance in the projection（VIP） value>1， differential secondary and primary metabolites before and after carbonization were screened. In addition， MetaboAnalyst website was used for pathway enrichment of Kyoto Encyclopedia of Genes and Genomes（KEGG）， so as to provide a reference for clarifying the processing mechanism. ResultsA total of 185 components were identified， including 96 secondary metabolites and 89 primary metabolites. These components were classified into nine categories， primarily including iridoid glycosides， flavonoids， and terpenoids， their fragmentation pathways were also analyzed. Simultaneously， multivariate statistical analysis was performed on the secondary and primary metabolites， identifying 70 and 59 differential metabolites， respectively. The secondary metabolites were enriched in two metabolic pathways， including C5-branched dibasic acid metabolism and flavonoid and flavonol biosynthesis， while the primary differential metabolites were enriched in seven pathways such as linoleic acid metabolism and tyrosine metabolism. ConclusionThe chemical components of GF change significantly after carbonization， with a significant decrease in the contents of iridoid glycosides and terpenoids such as hydroxyisogeniposide， crocin Ⅱ， crocetin， and jasminoside B. while the contents of 4-hydroxycoumarin， geniposidic acid， gentiopicroside， and gardenoside methyl ester increase significantly. This change is presumed to be associated with the enhanced cooling and hemostatic effects of the processed products. The identified key components provide a basis for elucidating the material basis underlying the efficacy changes before and after carbonization.

OBJECTIVE To provide a scientific basis for the quality evaluation and clinical application of Qingwen hufei granules. METHODS Fourteen batches of Qingwen hufei granules were used as samples to establish high-performance liquid chromatography （HPLC） fingerprints using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine （2012 Edition）. The chromatographic peaks were identified and the similarity was evaluated. Cluster analysis （CA）， principal component analysis （PCA）， and orthogonal partial least squares-discriminant analysis （OPLS-DA） were used to conduct chemical pattern recognition analysis on the 14 batches of samples. Meanwhile， the contents of neochlorogenic acid （NGA）， chlorogenic acid （CHA）， cryptochlorogenic acid （CGA）， forsythoside A （FTA）， 3，5-O-dicaffeoylquinic acid （3，5-O- DA）， 4，5-O-dicaffeoylquinic acid （4，5-O-DA）， and angoroside C （AGC） in the samples were determined by HPLC. RESULTS The methodological investigation results of both the fingerprint and the content determination complied with the relevant requirements. Fourteen common peaks were indicated in the HPLC fingerprints of the 14 batches of samples， and 7 of them were identified [NGA （peak 2）， CHA （peak 3）， CGA （peak 5）， FTA （peak 11）， 3，5-O-DA （peak 12）， 4，5-O-DA （peak 13）， and AGC （peak 14）]； the similarity of each sample was greater than 0.94. The results of CA and PCA showed that the samples could be classified into 3 categories； the results of OPLS-DA indicated that peak 4 （unknown）， peak 11 （FTA）， peak 8 （unknown）， peak 9 （unknown）， and peak 1 （unknown） were the differential components. The content ranges of NGA， CHA， CGA， 3，5-O-DA， FTA， 4，5-O-DA and AGC in the 14 batches of samples were 0.210 4-0.458 7， 0.269 1-0.506 3， 0.228 1-0.461 1， 0.443 9-1.044 6， 0.066 7-0.155 7， 0.062 8-0.143 8， and 0.057 4-0.105 7 mg/g， respectively. CONCLUSIONS The HPLC fingerprint and multi-component content determination methods established in this study are efficient and reliable， and can be used for the quality evaluation of Qingwen hufei granules.

Background: Parenchymal brain metastasis (BM) and its extended growth into cerebrospinal fluid(CSF) pathways or surgical spillage could result in leptomeningeal metastasis (LM). We defined BM with epipial spread or dural attachment on MRI as BM with CSF space invasion (BM-CSFi), regardless of CSF cytology results, and evaluated its clinical course after BM resection. Methods: We retrospectively reviewed 297 patients who underwent craniotomy for BM exclud-ing patients followed for <6 months or without follow-up MRI. Primary outcomes were proportion of patients progressing to overt LM and time to progression. We also evaluated clinical and radiologic variables to identify risk factors for LM progression. Results: A total of 91 patients (30.6%) developed overt LM, with median time to progressionof 7.9 months during 18.3 months follow-up after the craniotomy. On multivariable analysis, preoperative MRI evidence of dural attachment with enhancement (hazard ratio [HR], 5.59; p=0.002), primary small cell lung cancer (HR, 4.92; p=0.026), infratentorial BM location (HR, 2.14; p=0.019), and postoperative cumulative CSF cytology positive rate ≥50% (HR, 7.13; p=0.012) were independent risk factors for LM progression. The mode of resection and postoperative radiotherapy or systemic chemotherapy were not significantly associated with LM progression. Conclusion BM-CSFi, defined by preoperative MRI findings, may represent a clinically importantprecursor of LM. Our findings highlight the need for close monitoring of patients with BM-CSFi and the development of management protocols to minimize the risk of LM progression.

Objective:To analyse the clinical characteristics of 214 cases of paediatric high altitude pulmonary edema（HAPE）and the efficacy of dexamethasone in adjunctive therapy.Methods:This retrospective study analyzed 214 pediatric cases of HAPE admitted to the Department of Paediatrics of the General Hospital of Tibetan Military between June 2015 to June 2017 and June 2019 to June 2021.Patients were divided into dexamethasone-treated group and dexamethasone-untreated group.Baseline data，clinical characteristics were collected to evaluate the treatment efficacy and drug side effects.Results:There were 107 children in each of the two groups with a median age of 8（5，11）years. The median age of the dexamethasone-treated group was 9（6，12）years and the mean age of the dexamethasone-untreated group was 7（3，10）years. The proportion of male children was 69.60%（149/214）；the onset of illness was mostly concentrated within 72 hours，accounting for 97.20%（208/214）of the cases；83.18%（178/214）of the cases had symptoms of combined upper respiratory tract infection before entering the plateau. The most important clinical symptoms of the children were cough（86.92%，186/214），cyanosis（70.09%，150/214），and shortness of breath（66.36%，142/214）. The proportion of auscultatory rhonchi was 83.18%（178/214），and all cases showed positive findings on chest radiography. After the dexamethasone regimen，the overall cure rate of the children was 94.39%，the average disappearance time of the symptoms and signs was（40.52±7.85）h，and the average hospital stay was（3.60±1.90）d. After treatment with the dexamethasone-free regimen，the overall cure rate was 92.52%，the mean time to disappearance of symptoms and signs was（42.10±7.62）h，and the mean length of stay in the hospital was(3.84±2.08)d. There was no significant difference in the cure rate，the disappearance time of symptoms and signs，and the average hospitalisation days between the two groups（ P>0.05），but a total of 11 children in the dexamethasone-treated group experienced adverse drug reactions，and no children in the dexamethasone-untreated group experienced adverse drug reactions. Conclusion:Han Chinese male children，particularly those with upper respiratory infections，should be closely monitored for HAPE risk within three days of ascending to high altitudes. This study does not recommend the use of dexamethasone for pediatric HAPE due to the lack of therapeutic benefits and potential adverse effects.

Objective To explore the effects of different concentrations of simvastatin on nerve regeneration after sciatic nerve injury.Methods Rats were randomly divided into the normal group,the control group,the low-dose group and the high-dose group,with 3 rats in each group.Except for the normal group,adult rat sciatic nerve crush injury models were established in the other groups.Rats in the normal group and the control group were orally administered with water,while those in the low-dose group and high-dose group were orally administered with 98%simvastatin at dosages of 4 mg/mL and 40 mg/mL,respectively.The sciatic nerve regeneration in rats was evaluated by sciatic function index(SFI),HE staining,luxol fast blue(LFB)staining and immunofluorescence staining,etc.Results The SFI of rats in the high-dose group 7 days and 14 days after surgery were higher than those in the control group(P<0.05);there was no significant difference in SFI of rats between the low-dose group and the control group 7 days and 14 days after surgery(P>0.05).HE staining and LFB staining results showed that compared with the control group,the number of neurons of rats in the high-dose group increased,the nerve fibers and myelin were clearer and denser,and the nerve function was significantly restored;while no significant improvement was observed in the sciatic nerve of rats in the low-dose group.The immunofluorescence staining results showed that compared with the control group,the immunofluorescence intensity in the high-dose group increased,while that in the low-dose group decreased,the differences were statistically significant(P<0.05).Conclusion High-dose simvastatin can promote peripheral nerve regeneration by regulating the expression of M2 macrophages.

Tumor-associated macrophages(TAMs)are one of the key components of the tumor microenvironment(TME)in gastric cancer.Glucose metabolism reprogramming significantly impacts TAMs'polarization and immune functions,thereby regulating the onset and the progression of gastric cancer.This review summarizes glucose metabolism reprogramming in TAMs'polarization and explores its role in gastric cancer-related TAMs through aspects such as signaling regulation,transcription factors,and epigenetic modifications.This review aims to deepen the understanding of TAMs'role in gastric cancer progression and offer new perspectives for the immunotherapy in gastric cancer.

This review has introduced the Coronary Artery Tree description and Lesion EvaluaTion(CatLet or Hexu)angiographic scoring system,which,based solely on coronary angiography results,has characterized 6 types of right coronary artery,3 types of left descending artery,and 3 types of diagonal size,together resulting in 54 types of coronary circulation pattern.This novel angiographic scoring system can be utilized to account for coronary anatomy in its diversity,severity and complexity of diseased coronary arteries,and their subtended myocardial territories in jeopardy.The CatLet angiographic scoring system is unique in that the importance of a coronary artery is weighted according to its subtended myocardial segments,by which the variability of coronary artery has been accounted for and measured.Researchers at home and abroad have increasingly paid attention to its clinical utilities,which warrant further validation in the context of large sample size,prospective,and randomized controlled trials.The CatLet angiographic scoring system is accessible at www.catletscore.com.

AIM To study the effects of total flavonoids of Dracocephalum Moldavica L.(TFDM)on reducing the inflammatory response of RAW264.7 macrophages induced by ox-LDL via the nuclear factor κB(NF-κB)/NOD-like receptor 3(NLRP3)signaling pathway.METHODS The RAW264.7 macrophages cultured in vitro were divided into the normal group,the model group(50 μg/mL ox-LDL),the TFDM group(100 μg/mL TFDM+50 μg/mL ox-LDL),the NF-κB inhibitor group(10 μmol/L Bay11-7821+50 μg/mL ox-LDL)and the TFDM+NF-κB inhibitor group(100 μg/mL TFDM+10 μmol/L Bay11-7821+50 μg/mL ox-LDL).The cells had their viability assessed by CCK-8 method;their ROS expression detected by the ROS kit;their mRNA expressions of NF-κB p65,NLRP3,Caspase-1,IL-18 and IL-1β detected by RT-qPCR;their protein expressions of NF-κB p65,IκBα,NLRP3,pro-Caspase-1,Caspase-1,IL-18 and IL-1β by Western blot;their protein expressions of NF-κB p65 and NLRP3 detected using immunofluorescence method.RESULTS Compared with the normal group,the model group showed increased ROS expression(P＜0.01);increased mRNA expressions of NF-κB p65,NLRP3,Caspase-1,IL-18 and IL-1β(P＜0.05,P＜0.01);decreased protein expressions of IκBα and cytoplasmic NF-κB p65(P＜0.01);increased protein expressions of nuclear NF-κB p65,NLRP3,Caspase-1,IL-1 β and IL-18(P＜0.01);and increased fluorescence intensity of NF-κB p65 and NLRP3(P＜0.01).Compared with the model group,the groups intervened with either TFDM or TFDM+inhibitor displayed decreased ROS expression(P＜0.01);the groups administrated with TFDM or NF-κB inhibitor,or TFDM+inhibitor showed decreased mRNA expressions of NF-κB p65,NLRP3,Caspase-1,IL-18 and IL-1β(P＜0.05,P＜0.01),increased protein expressions of IκBα and cytoplasmic NF-κB p65(P＜0.05,P＜0.01),decreased protein expressions of nuclear NF-κB p65,NLRP3,Caspase-1,IL-1β and IL-18(P＜0.05,P＜0.01),and decreased fluorescence intensity of NF-κB p65 and NLRP3(P＜0.01).There existed no significant group difference between the TFDM group and the NF-κB inhibitor group(P＞0.05).The TFDM+inhibitor group demonstrated decreased mRNA expressions of IL-1βand IL-18(P＜0.05),increased IκBα protein expression(P＜0.05),decreased protein expressions of nuclear NF-κB p65,NLRP3,Caspase-1,IL-1 β and IL-18(P＜0.05),and decreased fluorescence intensity of NLRP3 protein(P＜0.05).CONCLUSION TFDM can inhibit the ox-LDL-induced inflammatory response of RAW264.7 macrophages,and the mechansism may be associated with the reduced ROS expression and inflammatory factors due to the inhibited activation of the NF-κB/NLRP3 signaling pathway.

Aim To identify the underlying target of bullatine A(BA)against rheumatoid arthritis(RA)u-sing limited proteolysis-small molecule mapping(LiP-SMap)drug target proteomics and to provide a scientif-ic basis for clinical application of Aconiti brachypodi Radix in the treatment of RA.Methods LiP-SMap drug target proteomics was employed to perform bioin-formatics analysis for comparing and validating the dif-ferential protein expression after BA intervention.A collagen-induced arthritis(CIA)model was estab-lished in DBA/1 mice using bovine type Ⅱ collagen.The mice were then divided into the CIA model group,methotrexate-positive control group(MTX group),and BA groups(10 mg·kg-1 and 20 mg·kg-1)based on their clinical scores.After drug intervention,the thera-peutic efficacy against RA was assessed by joint index scores and foot thickness measurements.Histopatholog-ical changes in the arthritic joints of CIA mice were e-valuated using hematoxylin and eosin(HE)staining.Enzyme-linked immunosorbent assay(ELISA)was employed to detect inflammatory cytokines interleukin-17(IL-17)and total IgG and IgG3 anti-collagen-spe-cific antibodies levels from the serum of CIA mice.Flow cytometry was used to detect the expression levels of intracellular Th17 cells(IL-17+CD4+T cells)and Th1 cells(IFN-γ+CD4+T cells).Fluorescent quanti-tative PCR was performed to detect the expression of genes related to differential proteins.Results The proteomic analysis identified Serpinb1a as a protein with strong binding affinity to BA,and KEGG enrich-ment analysis indicated IL-17 signaling pathway was a crucial pathway of BA in against RA.BA treatment significantly reduced clinical scores and foot thickness,improved local arthritis symptoms in CIA mice,and al-leviated inflammatory cell infiltration into arthritic joints(P＜0.05).Differential protein validation re-sults showed that BA had strong affinity with Serpinb1a(-5.92 kJ·mol-1)and downregulated the expres-sion of Serpinb1a mRNA.Furthermore,the administra-tion of BA markedly reduced serum IL-17 A levels from CIA mice,inhibited the expression of intracellular IL-17 A and IFN-γ cytokines in splenic CD4+T cells(P＜0.05),and significantly downregulated the transcrip-tional expression of IL-17F(P＜0.05).Conclusion BA exhibits therapeutic effects on collagen-induced arthritis,and its mechanism of action may involve the regulation of Serpinb1a and the IL-17 signaling path-way.

Aim To identify the underlying target of bullatine A(BA)against rheumatoid arthritis(RA)u-sing limited proteolysis-small molecule mapping(LiP-SMap)drug target proteomics and to provide a scientif-ic basis for clinical application of Aconiti brachypodi Radix in the treatment of RA.Methods LiP-SMap drug target proteomics was employed to perform bioin-formatics analysis for comparing and validating the dif-ferential protein expression after BA intervention.A collagen-induced arthritis(CIA)model was estab-lished in DBA/1 mice using bovine type Ⅱ collagen.The mice were then divided into the CIA model group,methotrexate-positive control group(MTX group),and BA groups(10 mg·kg-1 and 20 mg·kg-1)based on their clinical scores.After drug intervention,the thera-peutic efficacy against RA was assessed by joint index scores and foot thickness measurements.Histopatholog-ical changes in the arthritic joints of CIA mice were e-valuated using hematoxylin and eosin(HE)staining.Enzyme-linked immunosorbent assay(ELISA)was employed to detect inflammatory cytokines interleukin-17(IL-17)and total IgG and IgG3 anti-collagen-spe-cific antibodies levels from the serum of CIA mice.Flow cytometry was used to detect the expression levels of intracellular Th17 cells(IL-17+CD4+T cells)and Th1 cells(IFN-γ+CD4+T cells).Fluorescent quanti-tative PCR was performed to detect the expression of genes related to differential proteins.Results The proteomic analysis identified Serpinb1a as a protein with strong binding affinity to BA,and KEGG enrich-ment analysis indicated IL-17 signaling pathway was a crucial pathway of BA in against RA.BA treatment significantly reduced clinical scores and foot thickness,improved local arthritis symptoms in CIA mice,and al-leviated inflammatory cell infiltration into arthritic joints(P＜0.05).Differential protein validation re-sults showed that BA had strong affinity with Serpinb1a(-5.92 kJ·mol-1)and downregulated the expres-sion of Serpinb1a mRNA.Furthermore,the administra-tion of BA markedly reduced serum IL-17 A levels from CIA mice,inhibited the expression of intracellular IL-17 A and IFN-γ cytokines in splenic CD4+T cells(P＜0.05),and significantly downregulated the transcrip-tional expression of IL-17F(P＜0.05).Conclusion BA exhibits therapeutic effects on collagen-induced arthritis,and its mechanism of action may involve the regulation of Serpinb1a and the IL-17 signaling path-way.