ObjectiveTo observe the intervention effect of Fufang Kangjiaolv capsules on anxiety-like behaviors in the rat model of chronic restraint stress （CRS） and explore the mechanism underlying the anti-anxiety effect via the microbiota-gut-brain axis. MethodsRats were assigned into blank， model， positive drug （diazepam， 1 mg·kg^-1）， and low-， medium-， and high-dose （0.75， 1.5， 3 g·kg^-1， respectively） Fufang Kangjiaolv capsules groups. After 14 days of administration， the elevated plus maze test， open field test， light and dark box test， and marble burying test were performed. Hematoxylin-eosin staining was employed to observe the pathological changes in the hippocampus and colon of rats， and Nissl staining was conducted to observe the damage of hippocampal neurons. The gut microbiota was analyzed by 16S rRNA gene sequencing. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of zonula occludens-1 （ZO-1） and occludin in the colon of rats. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in the colon， serum， and hippocampus were determined by enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of ZO-1， occludin， nuclear factor-κB p65 （NF-κB p65） in the colon tissue and NF-κB p65 and brain-derived neurotrophic factor （BDNF） in the hippocampal tissue. ResultsCompared with the blank group， the model group showed reductions in the time and frequency ratio of rats entering the elevated plus maze， the time and frequency of rats entering the central area of the open field， the time of entering the open box， the times of passing through the light and dark box， and the number of unburied beads （P<0.05， P<0.01）. Compared with the model group， Fufang Kangjiaolv capsules ameliorated the anxiety of the model rats to varying degrees， and the high-dose group had the best effect， with increases in the proportions of time and frequency of rats entering the open arm in the elevated plus maze （P<0.05）， the number of rats entering the central area in the open field （P<0.05）， the time of entering the open box， the times of passing through the light and dark boxes， and the number of unburied beads （P<0.01）. Moreover， the high-dose group showed alleviated pathological damage of hippocampal neurons and colon. The results of 16S rRNA gene sequencing showed that the model group had increased relative abundance of Firmicutes， Deferribacterota， Romboutsia， and Phascolarctobacterium， while it had decreased relative abundance of Bavcteroidota and Lactobacillus. The drug administration groups showed increased relative abundance of Bavcteroidota， Bacteroides， norank f norank o Clostridia UCG-014， and Blautia and decreased relative abundance of Firmicutes and Deferribacterota. Compared with the blank group， the model group showed down-regulated protein and mRNA levels of ZO-1 and occludin in the colon （P<0.01）， elevated levels of TNF-α， IL-6， and IL-β in the colon， serum， and hippocampus （P<0.01）， up-regulated protein level of NF-κB p65 in the colon and hippocampus （P<0.01）， and down-regulated protein level of BDNF in the hippocampus （P<0.05）. Compared with the model group， high-dose Fufang Kangjiaolv capsules up-regulated the mRNA levels of ZO-1 and occludin in the colon （P<0.01）， lowered the levels of TNF-α， IL-6， and IL-β in the colon， serum， and hippocampus （P<0.01）， up-regulated the protein levels of ZO-1 （P<0.01） and occludin （P<0.05） in the colon， down-regulated the protein level of NF-κB p65 in the colon and hippocampus （P<0.05）， and up-regulated the protein level of BDNF in the hippocampus. ConclusionFufang Kangjiaolv capsules can reduce the anxiety-like behaviors in the rat model of CRS by regulating the gut microbiota disturbance， up-regulating the expression of tight junction proteins in the colon， repairing intestinal mucosal mechanical barrier， and down-regulating NF-κB/BDNF signaling pathway， thereby reducing peripheral and central inflammation. This study proves the hypothesis that Fufang Kangjiaolv capsules play an anti-anxiety role via the microbiota-gut-brain axis， providing a new idea for further research.

ObjectiveTo explore the changes in volatile components， total polysaccharides， enzyme activity， and chromaticity value of Myristicae Semen Koji（MSK） during the fermentation process， and conduct correlation analysis. MethodsBased on gas chromatography-mass spectrometry（GC-MS）， the changes of volatile components in MSK at different fermentation times were identified. The phenol sulfuric acid method， dinitrosalicylic acid method（DNS）， and carboxymethyl cellulose sodium salt method（CMC-Na） were used to investigate the total polysaccharide content， amylase activity， and cellulase activity during the fermentation process. Visual analysis technology was used to explore the changes in chromaticity values， revealing the fermentation process of MSK and the dynamic changes of various measurement indicators， partial least squares-discriminant analysis（PLS-DA） was used to explore the differential compounds of MSK at different fermentation degrees， and Pearson correlation analysis was used to explore the correlation between volatile components of MSK and total polysaccharides， enzyme activity， and chromaticity values. ResultsA total of 60 volatile compounds were identified from MSK， the relative contents of components such as （+）-α-pinene， β-phellandrene， β-pinene， （+）-limonene， and p-cymene obviously increased， while the relative contents of components such as safrole， methyl isoeugenol， methyleugenol， myristicin， and elemicin significantly decreased. During the fermentation process， the total polysaccharide content showed an upward trend， while the activities of amylase and cellulase showed an initial increase followed by a decrease， and reached their maximum value at 40 h. the overall brightness（L^*） and total color difference（ΔE^*） gradually increased， while the changes in red-green value（a^*） and yellow-blue value（b^*） were not obvious. PLS-DA results showed that MSK could be clearly distinguished at different fermentation times， and 13 differential biomarkers were screened out. Pearson correlation analysis results showed that the contents of α-terpinene， β-phellandrene， methyleugenol， β-cubebene and myristic acid had an obvious correlation with chromaticity values. ConclusionAfter fermentation， the volatile components， total polysaccharides， amylase activity， and cellulase activity of MSK undergo significant changes， and there is a clear correlation between them and chromaticity values， which reveals the dynamic changes in the fermentation process and related indicators of MSK， laying a foundation for the quality control.

Objective : To explore the effect and mechanism of CD151 on vascular permeability by regulating vesicle internalization and recycling. Methods: Wild-type mice and CD151 knockout mice were divided into WT-con group, WT-model group, KO-con group and KO-model group, with 6 mice in each group. WT-model group and KO-model group were intraperitoneally injected with LPS to prepare sepsis ALI model, and WT-con group and KO-con group were intraperitoneally injected with phosphate buffer saline(PBS) as a control. 24 h after modeling, pulmonary vascular permeability was measured by Miles test. The siRNA silencing CD151 expression(si-CD151) and negative control si-NC were transfected into EA.hy 926 cells. The permeability of endothelial cell layer to FITC-dextran at different time points was observed under basic conditions and vascular endothelial growth factor-A(VEGF-A) stimulation conditions. Transcriptome sequencing of endothelial cells in si-CD151 group and si-NC group; the distribution and internalization of CD151 in each group were measured using immunofluorescence. Western blot and real-time quantitative RT-qPCR were used to detect the expression of VE-cadherin in si-CD151 groupand other groups. The distribution and internalization of VE-cadherin in each group were measured using immunofluorescence. Results : Miles experiment results indicated that dye exudation in lung tissue of WT-model group was significantly higher than that of WT-con group(P<0.01). The dye exudation in the lung tissue of KO-model group increased compared with WT-model group(P<0.05). The results of endothelial cell layer permeability test showed that the permeability of FITC-dextran in si-CD151 group was significantly higher than that in control group after VEGF-A stimulation for 30, 60 and 120 min(P<0.05). Transcriptome sequencing results suggested that CD151 in endothelial cells was closely related to vesicle-mediated transport. Compared with other groups, protein and mRNA levels of VE-cadherin in CD151 knockdown endothelial cells was significantly lower(allP<0.01). The immunofluorescence assay demonstrated that after VEGF-A stimulation, the decrease of CD151 expression significantly impaired the expression of VE-cadherin at cell-cell contacts and reduced the CD151-VE-cadherin colocalization in the perinuclear region compared with other groups. Conclusion The absence of CD151 affects the internalization and recycling of endothelial cell vesicles, affects the expression and internalization of VE-cadherin, and then influences vascular permeability.

Objective To investigate the changes and diagnostic value of serum hypoxia inducible factor 1 subunit alpha(HIF-1α)and Toll-like receptor 4(TLR4)levels in patients with chronic obstructive pulmonary disease(COPD)complicated with pulmonary Aspergillosis infection.Methods A total of 240 COPD patients who visited Xi'an Qinhuang Hospital(hereinafter referred to as the hospital)from December 2020 to Decem-ber 2023 were selected as the study subjects in the study,and another 218 volunteers who underwent physical examinations at the hospital were selected as the control group.The COPD patients were separated into an in-fected group(124 cases)and an uninfected group(116 cases)based on whether they had pulmonary Aspergil-losis infection.Enzyme-linked immunosorbent assay was applied to detect the levels of HIF-1α and TLR4 in patients.Fully automated biochemical analyzer was applied to detect lactate dehydrogenase(LDH)and albu-min(ALB)levels.Multivariate Logistic regression was applied to analyze the influencing factors of infection in COPD patients.Pearson correlation was applied to analyze the correlation between HIF-1α and TLR4 levels in the infected group.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic val-ue of HIF-1α and TLR4 levels for the occurrence of infection in COPD patients.Results Compared with the control group,the COPD group showed an increase in HIF-1α and TLR4 levels(P＜0.05).Compared with the uninfected group,the proportion of dyspnea,antibiotics＞3 types,the duration of antibiotic use ≥ 14 days,mechanical ventilation procedures,the longer glucocorticosteroid(GC)use time,and levels of LDH,HIF-1α,TLR4 in the infected group were higher(P＜0.05),while the level of ALB was lower(P＜0.05).The types of antibiotics＞3 types,the duration of antibiotic use ≥ 14 days,the duration of GC use,and elevat-ed levels of LDH,HIF-1α,and TLR4 were independent risk factors for infection in COPD patients(P＜0.05),while elevated level of ALB was an independent protective factor for infection in COPD patients(P＜0.05).The levels of HIF-1α and TLR4 in the infected group were positively correlated(r=0.453,P＜0.001).The area under the curve(AUC)of HIF-1α and TLR4 in diagnosing infection in COPD patients alone was 0.816 and 0.813,and the AUC of their combined diagnosis was 0.930,which was better than their indi-vidual diagnoses(Zcombination-HIF-1α=4.923,Z combination-TLR4=5.192,P＜0.001,P＜0.001).Conclusion The levels of HIF-1α and TLR4 increase in COPD patients,and further increase after infection with pulmonary Aspergil-lus.They are independent risk factors for infection in patients,and the two are positively correlated.The combined di-agnosis of pulmonary aspergillosis has certain value and provides a theoretical basis for clinical diagnosis.

Objective To investigate the correlation between serum galectin-3(Gal-3),fibroblast growth factor-21(FGF-21)and the lung function and and the Modified British Medical Research Council dyspnea in-dex(mMRC)score in invalids with chronic obstructive pulmonary disease(COPD).Methods A total of 79 patients with COPD who received treatment in the hospital from April 2021 to April 2023 were selected as the observation group,and 60 healthy individuals in the hospital during the same period were selected as control group.The expressions of Gal-3 and FGF-21 in serum were detected and compared.The first second forced ex-piratory volume(FEV1),FEV1/forced vital capacity(FVC)and mMRC score in two groups were compared,and the correlation between the expression levels of Gal-3 and FGF-21 and FEV1,FEV1/FVC and mMRC score in COPD patients was analyzed.Results The expression levels of serum Gal-3 and FGF-21 in the obser-vation group were higher than those in the control group(P＜0.05).The pulmonary function indexes in ser-um of observation group were higher than those in the control group,while the mMRC score was lower than that in the control group(P＜0.05).The expression levels of Gal-3 and FGF-21 were positively correlated with FEV1 and FEV1/FVC(P＜0.05),was negatively correlated with mMRC score(P＜0.05).Conclusion The expression of serum Gal-3 and FGF-21 in COPD invalids is abnormal,and the expression levels of serum Gal-3 and FGF-21 in COPD patients were correlated with FEV1,FEV1/FVC and mMRC score,which could be used as important reference indicators for diagnosis and disease evaluation of COPD.

Objective To discuss the significance and feasibility of infodemiology researches in hospital library.Methods This paper analyzed the background,significance,advantages,constraints,research direction and themes of the hospital library's researches on infodemiology.Results Hospital library had the advantages of disciplinary background and convenient resources to carry out researches on infodemiology,and can carry out researches in many aspects such as network health information evaluation,network health information monitoring,medical intervention measures evaluation,public opinion analysis and management.Conclusion It is feasible for hospital libraries to carry out infodemiology researches to promote their own transformation and to help hospital make decisions.

Objective Exploring the antidiarrhea effect of new Ershen pills composed of nutmeg koji based on the spleen and kidney yang deficiency diarrhea mouse model.Methods KM mice were randomly divided into normal,model,Ershen pills Ⅰ(salt psoralen+bran-stewed nutmeg),Ershen pills Ⅱ(salt psoralen+nutmeg koji),Ershen pills Ⅲ(salt psoralen+nutmeg raw product),salt psoralen,and nutmeg koji groups.The combined modeling method of hydrocortisone+senna leaf was used to establish the diarrhea mouse model with spleen-kidney yang deficiency.General signs and pathological changes of each organ were observed.Various organ indexes,the small intestine propulsion rate,gastric residual rate,serum motilin(MTL),gastrin(GAS),adrenal ketone(CORT),thyroid stimulating hormone(TSH),testosterone(T),tumor necrosis factor-α(TNF-α),and interleukin 1β(IL-1β)were assessed.16S rDNA sequencing and data analysis were conducted for fecal microorganisms.Results After modeling,compared with the normal group,the weight and activity of mice in the model group were reduced,the small intestine propulsion rate was significantly increased,the gastric residual rate and organ indexes were significantly decreased,serum GAS,CORT,TSH,and T levels were significantly decreased,MTL,TNF-α,and IL-1β levels were significantly increased,and intestinal flora species diversity was decreased.After administration,the above indexes and symptoms were improved by various degrees in each administration group,and the Ershen pills Ⅱ group was better than Ershen pills Ⅰ,Ershen pills Ⅲ,salt-psoralea,and nutmeg koji groups.Conclusions Combined use of nutmeg koji and salt psoralen has a remarkable effect on diarrhea of spleen-kidney yang deficiency.Fermented nutmeg reduces its toxicity risk and enhances its effect of warming the spleen and preventing diarrhea,which facilitates the development of nutmeg koji.

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

Objective:To investigate the clinical characteristics of patients with myocardial infarction with non-obstructive coronary arteries(MINOCA)and the risk factors of major adverse cardiovascular events(MACE)within 1 year of follow-up.Methods:A total of 1 866 patients who met the diagnosis of acute myocardial infarction and underwent coronary angiography in the Department of Cardiovascular Medicine of our hospital from Sep 2018 to Sep 2021 were selected.According to the results of coronary angiography,the patients were divided into MINOCA group and myocardial infarction with obstructive coronary artery disease(MI-CAD)group.The clinical characteristics and the occurrence of MACE in the two groups were compared.According to the occurrence of MACE,patients in MINOCA group were divided into MACE group and non-MACE group.Binary logistic regression analysis was used to explore the risk factors for MACE in MINOCA patients.Results:The age of patients in MINOCA group was lower than that in MI-CAD group,and more patients were female(P＜0.05).The risk factors of cardiovascular diseases in MINOCA group were less than those in MI-CAD group(P＜0.05).Some indexes of laboratory were lower than those in MI-CAD group(P＜0.05).Left ventricular ejection fraction(LVEF)were higher than that in MI-CAD group(P＜0.05).Left ventricular end-diastolic inner diameter(LVEDD)was lower than that in MI-CAD group,and the proportion of patients with abnormal ventricular wall motion and high cardiac function grade was lower than that in MI-CAD group,and the difference was statistically significant(P＜0.05).The 1-year follow-up showed no significant difference in the incidence of MACE between the two groups(P=0.115).Binary logistic regression analysis showed that smoking(OR=13.095,95%CI:1.799-7.398)and low LVEF(OR=0.036,95%CI:0.012-0.679)were independent risk factors for MACE in MIONCA patients.Conclusions:MINOCA patients are more common in women,with lower age and fewer cardiovascular risk factors,but the incidence of MACE is not less than that of MI-CAD patients.Smoking and low LVEF are independent risk factors for MACE in MINOCA patients.

Objective To evaluate iron deposition in gray matter nuclei in patients with cerebral small vessel disease(CSVD)based on quantitative susceptibility mapping(QSM)and to analyze its correlation with cognitive function.Methods Patients with CSVD attending the outpatient clinic in the Department of Neurology at Xuanwu Hospital of Capital Medical University from December 2016 to November 2022,and healthy controls recruited from previous studies in the Department of Radiology and Nuclear Medicine at Xuanwu Hospital of Capital Medical University from September 2022 to November 2022 were retrospectively consecutively collected.Baseline data of CSVD patients and healthy controls was collected and compared,including age,sex,past history(hypertension,diabetes,hyperlipidemia),smoking history,alcohol consumption history and Montreal cognitive assessment(MoCA)scale score.MRI of all CSVD patients and healthy controls were collected,including three-dimensional T1 weighted imaging,QSM,T2 weighted imaging,and fluid attenuated inversion recovery(FLAIR)sequence imaging.According to the MRI-related imaging features and CSVD total burden score,the patients were divided into mild CSVD(CSVD-m)group and severe CSVD(CSVD-s)group,and healthy controls were the control group.QSM was used to obtain the susceptibility values of gray matter nuclei for all CSVD patients and controls.One-way covariance analysis and Bonferroni correction were used to compare the gray matter nuclei susceptibility values among the three groups.Spearman correlation analysis was performed between susceptibility values of gray matter nuclei with statistically significant differences in susceptibility values and cognitive function.Results A total of 61 cases of CSVD patients were included,including 29 cases in the CSVD-s group and 32 cases in the CSVD-m group;32 healthy controls were included in the control group.(1)There was no statistically significant difference in age,sex,hypertension,diabetes,hyperlipidemia,smoking,and alcohol consumption between the CSVD-s group,CSVD-m group and control group(all P＞0.05).The MoCA scale scores of the CSVD-s group and CSVD-m group were lower than those of the control group(25.0[22.5,27.5]points,27.0[25.0,29.0]points than 28.0[27.0,29.0]points,H=15.006,P＜0.01).The difference in the imaging features distribution of cerebral microbleeds,white matter hyperintensity,and perivascular space among the CSVD-s group and the CSVD-m group was statistically significant(all P＜0.05).(2)The differences in susceptibility values of the left putamen(F=4.790),pallidus(F=12.896),hippocampus(F=3.904)and the right putamen(F=36.278),pallidus(F=39.449),caudate nucleus(F=6.797),and thalamus(F=6.525)were statistically significant among the three groups(all P＜0.05).After Bonferroni correction,the susceptibility values of the left putamen and pallidus and the right putamen,pallidus,caudate nucleus,and thalamus in the CSVD-s group were higher than those of the control group(all P＜0.05);the susceptibility values of the left pallidus and the right pallidus,putamen,and thalamus in the CSVD-m group were higher than those of the control group(all P＜0.01),and the left hippocampus was lower than that of the control group(P=0.045).(3)The susceptibility values of the bilateral putamen were significantly negatively correlated with MoCA scale score(left putamen:rs=-0.316,P=0.015;right putamen:rs=-0.316,P=0.014).Conclusion Abnormal iron metabolism occurs in gray matter nuclei of CSVD patients,and iron deposition in the putamen correlate with cognitive dysfunction.