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.

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.

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 pollution levels and influencing factors of polybrominated diphenyl ethers (PBDEs) in household dust in five cities in northern China.Methods:Based on the "Chinese Indoor Environment and Health Surveillance" project carried out by the National Institute of Environmental Health, Chinese Center for Disease Control and Prevention in 2018-2019, during the warm season (April 2018 to September 2018) and the cold season (November 2018 to March 2019), Lanzhou in Northwest China, Shijiazhuang in North China, Panjin in Northeast China, Luoyang in Central China, and Qingdao in East China were selected as the research sites. A total of 87 families were recruited to study residences in real-life scenarios. At the same time, dust samples were collected to detect the concentration of PBDEs. The level of household environmental indicators was measured, and the residential building characteristics and family behavior habits were collected through questionnaires. A total of 142 valid dust samples and 140 valid questionnaires were obtained. The differences in PBDE concentrations across seasons, wind zones, residential building characteristics, and family habits were analyzed. The exploratory factor analysis was performed to investigate the possible sources of PBDEs, and multivariate linear regression was used to explore the factors influencing PBDEs in household dust.Results:The M ( Q1,Q3) of total PBDE concentrations in 142 household dust samples in five cities was 144.51 (106.61, 222.65) ng/g in the warm season and 145.10 (98.57, 180.65) ng/g in the cold season, respectively. There were seasonal differences in the concentration of ∑ 12PBDEs in Luoyang and Shijiazhuang ( P<0.01). The concentration of BDE-71 was highest among PBDE homologues, followed by BDE-66 and BDE-47. Three factors were extracted by exploratory factor analysis in the warm season, and the cumulative variance contribution rate was 67.90%. The multivariate linear regression showed that the house completion less than ten years [ β (95% CI): 0.186 (0.013, 0.359)], infrequent home cooking [ β (95% CI):-0.342 (-0.570, -0.114)], and increased residential PM 10 concentration [ β (95% CI): 0.001 (0.000, 0.002)] during the warm season, as well as the house far from driveway [ β (95% CI): 0.093 (0.013, 0.172)], house area less than 90 m 2 [ β (95% CI):-0.138 (-0.264, -0.013)], and lower residential xylene concentration [ β (95% CI):-0.006 (-0.011, -0.001)] during the cold season might be related to the elevated concentrations of ∑ 12PBDEs in household dust. Conclusion:The pollution of PBDEs in household dust in five northern cities is at a medium to high level. Years of house completion, frequency of cooking at home, residential PM 10 concentration, distance from house to driveway, house area, and residential xylene concentration may influence household PBDE concentrations.

Objective:To investigate the pollution levels and influencing factors of polybrominated diphenyl ethers (PBDEs) in household dust in five cities in northern China.Methods:Based on the "Chinese Indoor Environment and Health Surveillance" project carried out by the National Institute of Environmental Health, Chinese Center for Disease Control and Prevention in 2018-2019, during the warm season (April 2018 to September 2018) and the cold season (November 2018 to March 2019), Lanzhou in Northwest China, Shijiazhuang in North China, Panjin in Northeast China, Luoyang in Central China, and Qingdao in East China were selected as the research sites. A total of 87 families were recruited to study residences in real-life scenarios. At the same time, dust samples were collected to detect the concentration of PBDEs. The level of household environmental indicators was measured, and the residential building characteristics and family behavior habits were collected through questionnaires. A total of 142 valid dust samples and 140 valid questionnaires were obtained. The differences in PBDE concentrations across seasons, wind zones, residential building characteristics, and family habits were analyzed. The exploratory factor analysis was performed to investigate the possible sources of PBDEs, and multivariate linear regression was used to explore the factors influencing PBDEs in household dust.Results:The M ( Q1,Q3) of total PBDE concentrations in 142 household dust samples in five cities was 144.51 (106.61, 222.65) ng/g in the warm season and 145.10 (98.57, 180.65) ng/g in the cold season, respectively. There were seasonal differences in the concentration of ∑ 12PBDEs in Luoyang and Shijiazhuang ( P<0.01). The concentration of BDE-71 was highest among PBDE homologues, followed by BDE-66 and BDE-47. Three factors were extracted by exploratory factor analysis in the warm season, and the cumulative variance contribution rate was 67.90%. The multivariate linear regression showed that the house completion less than ten years [ β (95% CI): 0.186 (0.013, 0.359)], infrequent home cooking [ β (95% CI):-0.342 (-0.570, -0.114)], and increased residential PM 10 concentration [ β (95% CI): 0.001 (0.000, 0.002)] during the warm season, as well as the house far from driveway [ β (95% CI): 0.093 (0.013, 0.172)], house area less than 90 m 2 [ β (95% CI):-0.138 (-0.264, -0.013)], and lower residential xylene concentration [ β (95% CI):-0.006 (-0.011, -0.001)] during the cold season might be related to the elevated concentrations of ∑ 12PBDEs in household dust. Conclusion:The pollution of PBDEs in household dust in five northern cities is at a medium to high level. Years of house completion, frequency of cooking at home, residential PM 10 concentration, distance from house to driveway, house area, and residential xylene concentration may influence household PBDE concentrations.

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.

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 safety of tocilizumab (TCZ) in the treatment of children with systemic juvenile idiopathic arthritis (sJIA).Methods:Data of children aged 2 to 18 years with the diagnosis of sJIA and treated with TCZ from June 1, 2017 to June 30, 2022 at our hospital were retrospectively collected. The clinical medication characteristics, incidence, severity and outcome of adverse drug reactions (ADR) were statistically analyzed. Univariate and multivariate analysis were used to analyze the risk factors of TCZ-induced ADR. Univariate comparison between groups were compared to the measured data followed by t test for normal distribution, and the counting data were paired with Chi-square test. Binary logistic regression analysis was used for multivariate analysis. Results:A total of 83 eligible children were enrolled. The age at TCZ initiation was (8.5±3.7) years old. Most of the children received oral glucocorticoid (86.8%) and/or methotrexate (72.3%) prior to TCZ treatment. The mean time of TCZ duration was (1.2±0.9) years, the total TCZ exposure was 92.70 patient years. Fifty-five (66.3%) children reported 123 ADR, with a rate of 132.69/100 patient years. Forty-two (50.6%) children reported 103 general ADR, with a rate of 111.11/100 patient years. Eighteen (21.7%) children reported 20 serious ADR, with a rate of 21.57/100 patient years. The results of univariate analysis showed that the dosage of glucocorticoid in ADR group was higher than that in non-ADR group [(0.76±0.50) mg·kg -1·d -1vs. (0.52±0.41) mg·kg -1·d -1, t=2.27, P=0.026], and the difference was statistically significant. However, there were no significant differences in gender [(male 23, female 32) cases vs. (male 9, female 19) cases, χ2=0.73, P=0.392], age at TCZ initiation [(8.5±3.8) years old vs. (9.0±3.1) years old, t=-0.65, P=0.516], duration of TCZ treatment [(1.24±1.00) years vs. (1.05±0.90) years, t=0.87, P=0.385], methotrexate doses weekly [(8.0±5.2) mg/m 2vs. (7.6±5.1) mg/m 2, t=0.39, P=0.696], and history of drug or food allergy (11 cases vs. 5 cases, χ2=0.06, P=0.815) between the two groups. The results of binary logistic regression analysis showed that the combined use of oral glucocorticoids was an independent risk factor for TCZ-induced ADR [ OR (95% CI) =3.05 (1.11, 8.36), P=0.030]. The risk of ADR was 3.05 times higher in the combined daily dose of glucocorticoids ≥0.76 mg/kg prednisone equivalent than that of < 0.76 mg/kg. Common general ADR to TCZ include infections (38.83/100 patient years) and abnormalities in laboratory parameters (37.76/100 patient years) such as elevated glutamic-pyrupiane transaminase (18.34/100 patient years), dyslipidemia (12.94/100 patient years), and hemocytopenia (5.39/100 patient years). The serious ADR included serious infection (9.71/100 patient years) and serious infusion reaction(7.55/100 patient years). All ADR were improved after drug withdrawal or symptomatic treatment, and no deaths occurred. Conclusion:TCZ has a good safety profile in the treatment of sJIA. Serious infections and severe infusion reactions often lead to discontinuation of the drug. The combination of glucocorticoids≥0.76 mg/kg prednisone equivalent is an independent risk factor for TCZ-induced ADR. Monitoring should be strengthened during the application of TCZ, and ADR should be detected and treated as early as possible to reduce the risk of medication related adverse reactions.

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.

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.