Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

Objective To evaluate the inhibitory activity of fluoxetine alone and in combination with fluconazole on Candida albicans.Methods This study used standard strains of Candida albicans,clinical isolates of Candida albicans,and drug-resistant strains of Candida albicans for experiments to prepare the planktonic and biofilm states of Candida albicans,respectively.The effect of fluoxetine on Candida albicans was detected by XTT reduction method.Pharmacodynamic properties of fluoxetine against Candida albicans biofilm were determined by improved time-kill test.The morphological changes of fluoxetine on Candida albicans biofilm were observed by scanning electron microscopy,and the synergistic effect of fluoxetine combined with fluconazole on Candida albicans biofilms was detec-ted by the checkerboard dilution method.Results Fluoxetine had inhibitory effects on three types of Candida albicans biofilms.The minimum drug concentration that inhibited 50%activity(SMIC50)of biofilms of standard strains of Candida albicans and drug-resistant strains was 32 μg/mL;the SMIC50 of clinical strains of Candida albicans biofilm was 64 μg/mL.Time-kill test displayed that the bio-film activity of three types of Candida albicans significantly decreased compared to the control group at the fluoxetine concentration of 1×SMIC50 and 2×SMIC50.Scanning electron microscopy observation showed that compared with the control group,the number of fungal hyphae in the biofilm of Candida albicans treated with fluoxetine decreased and their morphology wrinkled.The checkerboard microdilu-tion method showed that the combination of fluoxetine and fluconazole exhibited a synergistic effect on the standard strain of Candida al-bicans bioflim,while showing no or antagonistic effects on the other two strains.Conclusion Fluoxetine alone has inhibitory effects on biofilms of different types of Candida albicans and has a synergistic inhibitory effect on biofilms of standard strains of Candida albicans combined with fluconazole.

Objective To evaluate the effects of chloroquine alone and in combination with traditional antifungal agents on the Candi-da albicans biofilms and its drug resistance.Methods This study used standard strains of Candida albicans,and drug-resistant strains of Candida albicans.The inhibitory effects of chloroquine alone and in combination with antifungal drugs on biofilms of Candida albi-cans were detected by XTT reduction method and chessboard dilution method respectively.The morphological characteristics of biofilms were observed under scanning electron microscopy.Results Chloroquine at the concentration of 50 μmol/L or above showed a direct inhibitory effect and increased with concentration.Chloroquine combined with amphotericin B had a synergistic inhibitory effect.Results of the time-killing curve showed that the growth trends of biofilms treated with chloroquine alone and combined with amphotericin B var-ied in different time periods during the experimental culture.Morphological observation also revealed that chloroquine alone and in com-bination with amphotericin B could reduce the ability of Candida albicans to form hyphae and biofilms.Conclusion Chloroquine has an inhibitory effect on Candida albicans biofilms and can reduce its drug resistance.Furthermore,chloroquine shows a synergistic anti-fungal effect when combined with amphotericin B.

Objective To investigate the changes of coagulation,fibrinolysis and platelet indexes in ovarian cancer patients before and after neoadjuvant chemotherapy,and to analyze the risk relationship between relevant indexes before treatment and the effect of neoadjuvant chemotherapy(NACT).Methods Patients with ovarian cancer admitted to Xi'an Fengcheng Hospital,from March 2020 to March 2023 were included as the ovarian cancer group,and female patients who underwent physical examination in the same period were selected as the control group according to a 2∶1 ratio.Prothrombin time(PT),thrombin time(TT),activated partial thromboplastin time(APTT),fibrinogen(FIB),platelet distribution width(PDW),platelet hematocrit(PCT),platelet(PLT)and mean platelet volume(MPV)were compared between the two groups.The changes of these indexes were compared before and after NACT,at different clinical stages and before and after NACT with different efficacy effects.Moreover,they were divided into effective and ineffective groups according to their treatment efficacy.Logistic regression was used to explore the relationship between the parameters and NACT efficacy;receiver operating characteristic curve was drawn to predict the value of NACT efficacy.Results A total of 144 patients were included,with 96 cases in the ovarian cancer group and 48 in the control group.The FIB,PLT and MPV of patients in the ovarian cancer group were higher than those in the control group(P<0.05).The PT,TT,APTT,FIB and PLT of ovarian cancer patients after NACT were lower than those before NACT(P<0.05).FIB and PLT of stage Ⅱ patients were lower than those of stage Ⅲ before and after NACT,and the PT,TT,APTT,FIB and PLT of the effective group were lower than those of the ineffective group before and after NACT,and the PT,TT,APTT,FIB and PLT of the two groups after NACT were lower than those before NACT(P<0.05).Multivariate Logistic regression analysis indicated that high PT,TT,APTT,FIB and PLT before NACT were independent risk factors for NACT ineffectiveness(P<0.05).The area under the curve of PT,TT,APTT,FIB and PLT before NACT to predict the effect of NACT were 0.713(sensitivity of 80.95%,specificity of 69.33%),0.756(sensitivity of 71.43%,specificity of 82.67%)and 0.787(sensitivity of 76.19%,specificity of 70.67%),0.727(sensitivity of 71.43%,specificity of 84.00%),0.794(sensitivity of 80.95%,specificity of 76.00%),respectively.Conclusion Changes in coagulation and fibrinolytic function and platelet parameters in ovarian cancer patients after NACT are associated with clinical stages and NACT effect.High levels of PT,TT,APTT,FIB and PLT before NACT are important reasons affecting NACT effect.Constructing the risk prediction model of NACT efficacy in ovarian cancer patients based on the above five parameters can provide a reference for clinical practice.

AIM To study the secondary metabolites from the endophytic fungi Candida sp.of Berberis atrocarpa Schneid.METHODS The ethyl acetate fraction and petroleum ether fraction from the secondary metabolites of Candida sp.fermentation extract were separated and purified by silica gel,Sephadex LH-20 and preparative liquid chromatography,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Eighteen compounds were isolated and identified as 1-phenyl-1,2-ethanediol(1),4-hydroxyphenethyl alcohol(2),4-hydroxybenzoic acid(3),4-hydroxyphenylacetic acid(4),3-hydroxyphenylacetic acid(5),3-methylsulfinyl propionic acid(6),phenylacetic acid(7),(S)-N-nitroso-1-amino-p-hydroxy phenylethanol(8),2-phenylacetamide(9),p-hydroxybenzaldehyde(10),ethyl 2-(4-hydroxyphenyl)acetate(11),dibutyl phthalate(12),5,5'-dimethoxybiphenyl-2,2'-diol(13),3-indolealdehyde(14),N-acetyl-L-phenylalanine(15),9-hydroxy-10E,12Z-octadecadienoic acid(16),9-hydroxy-10E,12E-octadecadienoic acid(17),(6E)-5-methylene-6-tetradecenoic acid(18).CONCLUSION Compounds 1,3-8 and 10-18 are isolated from Candida sp for the first time.

Objective:To determine the expression of Brahma-related gene 1 (BRG1) in cutaneous squamous cell carcinoma (cSCC) tissues and cells, and to investigate molecular mechanisms underlying the regulatory effect of its interaction with activating transcription factor 2 (ATF2) on the proliferation, migration and invasion of cSCC cells.Methods:From 2015 to 2021, 66 paraffin-embedded actinic keratosis (AK) tissue samples and 80 paraffin-embedded cSCC (including squamous cell carcinoma in situ) tissue samples were collected from the Department of Dermatology, Affiliated Hospital 2 of Nantong University, and the diagnoses of all the cases were confirmed histopathologically; at the same time, 35 paraffin-embedded normal skin tissue samples obtained by cosmetic surgery served as normal control group. Immunohistochemical staining was performed to determine the BRG1 expression in cSCC, AK, and normal skin tissues, and correlations between BRG1 expression and clinicopathological parameters of cSCC patients were analyzed. Fresh tissue samples were collected from 12 cSCC patients and 12 healthy controls, and cSCC cell lines A431 and Scl-1 and a human immortalized keratinocyte cell line HaCaT were routinely cultured; real-time fluorescence-based quantitative PCR (qRT-PCR) was performed to determine the mRNA expression of BRG1 in tissues and cells, and co-immunoprecipitation assay and cellular immunofluorescence staining were conducted to analyze the interaction between BRG1 and ATF2. The expression of BRG1 (BRG1 siRNA1 - 5 groups) and ATF2 (ATF2-shRNA group) in A431 and Scl-1 cells was knocked down by RNA interference, and cells transfected with negative control siRNA or shNC served as controls (control siRNA group and shNC group, respectively), cell counting kit-8 (CCK8) assay, colony formation assay, cell scratch assay, and Transwell assay were conducted to evaluate effects of knocking down BRG1 and ATF2 on the proliferation, migration, and invasion of cSCC cells. Comparisons of measurement data among multiple groups were conducted using one-way analysis of variance, and multiple comparisons were conducted using Dunnett- t test. Results:Immunohistochemical staining showed that the expression intensity of BRG1 protein was significantly lower in the cSCC and AK tissues than in the normal skin tissues ( χ2 = 44.40, P < 0.001). qRT-PCR showed that the mRNA expression level of BRG1 was significantly lower in the cSCC tissues (1.345 ± 0.956) than in the normal skin tissues (2.499 ± 1.501, t = 2.25, P = 0.035), and also significantly lower in A431 and Scl-1 cells (0.041 ± 0.002, 0.026 ± 0.003, respectively) than in HaCaT cells (0.135 ± 0.033, t = 4.95, 5.73, P = 0.008, 0.005, respectively). The low expression of BRG1 was associated with tumors at sun-exposed sites ( P = 0.041), low tumor differentiation ( P = 0.001), and high Broder′s grade ( P < 0.001) in the cSCC patients. In both A431 cells and Scl-1 cells, the BRG1 siRNA1 group and BRG1 siRNA2 group showed significantly increased numbers of cell colonies, migratory cells and invasive cells, as well as cell migration rates compared with the control siRNA group (all P < 0.05). Co-immunoprecipitation assay showed that BRG1 protein could bind to ATF2 protein in A431 and Scl-1 cells, and immunofluorescence staining showed that the two proteins were co-localized; compared with the control siRNA group, the BRG1 siRNA1 group (both A431 and Scl-1 cells) and BRG1 siRNA2 group (A431 cells) both showed increased phosphorylation and activation of ATF2 (all P < 0.05) ; in both A431 cells and Scl-1 cells, the shATF2 group showed significantly decreased numbers of cell colonies (both P = 0.001), cellular proliferative activity at 24 - 96 hours (all P < 0.001), and numbers of migratory cells and invasive cells compared with the shNC group (all P ≤ 0.001) . Conclusion:BRG1 was lowly expressed in the cSCC and AK tissues, and could inhibit the proliferation, migration, and invasion of cSCC cells; ATF2 could promote the proliferation, migration, and invasion of cSCC cells; BRG1 may exert an anti-tumor effect by interacting with ATF2 protein and inhibiting phosphorylation-dependent activation of ATF2.

A quantitative proton nuclear magnetic resonance(qHNMR) method was established to determine the glucose content in commercially available Massa Medicata Fermentata(MMF) products and explore the variations of glucose content in MMF products during processing. The qHNMR spectrum of MMF in deuterium oxide was obtained with 2,2,3,3-d_4-3-(trimethylsilyl) propionate sodium salt as the internal standard substance. With the doublet peaks of terminal hydrogen of glucose with chemical shift at δ 4.65 and δ 5.24 as quantitative peaks, the content of glucose in MMF samples was determined. The glucose content showed a good linear relationship within the range of 0.10-6.44 mg·mL~(-1). The relative standard deviations(RSDs) of precision, stability, repeatability, and recovery for determination were all less than 2.3%. The glucose content varied in different commercially available MMF samples, which were associated with the different fermentation days, wheat bran-to-flour ratios, and processing methods. The glucose content in MMF first increased and then decreased over the fermentation time. Compared with the MMF products fermented with wheat bran or flour alone, the products fermented with both wheat bran and flour had increased glucose. The glucose content of bran-fried MMF was slightly lower than that of raw MMF, while the glucose content in charred MMF was extremely low. In conclusion, the qHNMR method established in this study is simple, fast, and accurate, serving as a new method for determining the glucose content in MMF. Furthermore, this study clarifies the variations of glucose content in MMF during processing, which can not only indicate the processing degree but also provide a scientific basis for revealing the fermentation mechanism and improving the quality control of MMF.
Protons ; Drugs, Chinese Herbal/chemistry* ; Dietary Fiber ; Magnetic Resonance Spectroscopy

UPLC-Q-Exactive-MS/MS and network pharmacology were employed to preliminarily study the active components and mechanism of Jinwugutong Capsules in the treatment of osteoporosis. Firstly, UPLC-Q-Exactive-MS/MS was employed to characterize the chemical components of Jinwugutong Capsules, and network pharmacology was employed to establish the "drug-component-target-pathway-disease" network. The key targets and main active components were thus obtained. Secondly, AutoDock was used for the molecular docking between the main active components and key targets. Finally, the animal model of osteoporosis was established, and the effect of Jinwugutong Capsules on the expression of key targets including RAC-alpha serine/threonine-protein kinase(AKT1), albumin(ALB), and tumor necrosis factor-alpha(TNF-α) was determined by enzyme-linked immunosorbent assay(ELISA). A total of 59 chemical components were identified from Jinwugutong Capsules, among which coryfolin, 8-prenylnaringenin, demethoxycurcumin, isobavachin, and genistein may be the main active components of Jinwugutong Capsules in treating osteoporosis. The topological analysis of the protein-protein interaction(PPI) network revealed 10 core targets such as AKT1, ALB, catenin beta 1(CTNNB1), TNF, and epidermal growth factor receptor(EGFR). The Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment showed that Jinwugutong Capsules mainly exerted the therapeutic effect by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, neuroactive ligand-receptor interaction, mitogen-activated protein kinase(MAPK) signaling pathway, Rap1 signaling pathway and so on. Molecular docking showed that the main active components of Jinwugutong Capsules well bound to the key targets. ELISA results showed that Jinwugutong Capsules down-regulated the protein levels of AKT1 and TNF-α and up-regulated the protein level of ALB, which preliminarily verified the reliability of network pharmacology. This study indicates that Jinwugutong Capsules may play a role in the treatment of osteoporosis through multiple components, targets, and pathways, which can provide reference for the further research.
Animals ; Tumor Necrosis Factor-alpha/genetics* ; Network Pharmacology ; Capsules ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Reproducibility of Results ; Tandem Mass Spectrometry