Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

Objective To determine the chemical constituents in BSLYT by ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS/MS),and to establish a high-performance liquid chromatographic fingerprint of the material basis of BSLYT and the content determination of its six main constituents,mononoside,loganin,oroxin A,oroxin B,baicalein and astilbin,providing a reference for the quality control.Methods The mass spectrometry data were used to establish the fingerprints.The content of the main components in the BSLYT samples was calculated by using the external method,and the discrepency between different batches of samples were analyzed by combining with chemometric methods.Results A total of 69 compounds were identified by mass spectrometry,and 13 compounds were identified after comparison with high-performance liquid chromatography(HPLC).The similarity of the baseline characterization profiles of the 15 batches of BSLYT substances was above 0.90,and a total of 27 common peaks were identified.Cluster analysis(CA)classified the substance benchmarks into 2 classes,S1,S2,S5,S8,S9,S13,and S15 were clustered into one class,and S3,S4,S6,S7,S10-S12,and S16 were clustered into one class.By combining PCA and OPLS-DA,the chemical components affecting the baseline classification of the substances were screened and attributed to wood butterfly,cornelian cherry and cocos nigra,respectively.The contents of six components were determined by MICS,which ranged from 0.31%-0.51%,0.12%-0.22%,0.09%-0.19%,0.09%-0.24%,0.07%-0.18%,and 0.08%-0.29%for mononoside,loganin,oroxin A,oroxin B,baicalein and astilbin respectively.Conclusion The fingerprint and multi-indicator content determination method established in this paper are accurate and stable,which provide a basis for the quality control of the material benchmark of Kidney and Pharynx Formula and its related preparations.

Methods: The median sagittal diameter and transverse diameter of the spinal canal from C2 to C7 were measured on CT images. The ratio of the median sagittal diameter to the transverse diameter was calculated. Accordingly, the spinal canal shape of each segment was classified into four, and the specific criteria of lunar phase classification were determined through linear discriminant analysis based on the ratio of the median sagittal diameter to the transverse diameter. The inter-rater reliability of the classification was explored using Kappa coefficients. Finally, the morphology of the different segments of the cervical spinal canal in healthy volunteers was revised and compared. Results: According to the ratio of the median sagittal diameter and the transverse diameter of the cervical spinal canal, the lunar phase classification of the cervical bony spinal canal was determined as follows: full-moon >0.65, 0.55< convex-moon ≤0.65, 0.46≤ quarter-moon ≤0.55, and residual-moon <0.46. The Kappa values of C2–C7 were 0.851, 0.958, 0.823, 0.927, 0.793, and 0.946, and the Kappa value of all C2–C7 segments was 0.854 that mainly presented two forms of full-moon (76.5%) and convex-moon (23.0%). A quarter-moon spinal canal was mainly distributed in C3, C4, C5, and C6; a residual-moon spinal canal was mainly distributed in C4 and C5; and the morphological distribution of C4 and C5 were similar (p>0.05). The frequency of the spinal canal of the residual-moon type was the highest, and the full-moon (6.5%) and residual-moon (7.5%) types of C7 were rare. Conclusions The morphological classification of the cervical spinal canal was established to present anatomical variations. The classification showed good inter-rater reliability.

Currently, the first-line drugs for invasive fungal infections (IFI), such as amphotericin B, fluconazole and itraconazole, have drawbacks including poor water solubility, low bioavailability, and severe side effects. Using drug delivery systems is a promising strategy to improve the efficacy and safety of traditional antifungal therapy. Synthetic and biomimetic carriers have greatly facilitated the development of targeted delivery systems for antifungal drugs. Synthetic carrier drug delivery systems, such as liposomes, nanoparticles, polymer micelles, and microspheres, can improve the physicochemical properties of antifungal drugs, prolong their circulation time, enhance targeting capabilities, and reduce toxic side effects. Cell membrane biomimetic drug delivery systems, such as macrophage or red blood cell membrane-coated drug delivery systems, retain the membrane structure of somatic cells and confer various biological functions and specific targeting abilities to the loaded antifungal drugs, exhibiting better biocompatibility and lower toxicity. This article reviews the development of antifungal drug delivery systems and their application in the treatment of IFI, and also discusses the prospects of novel biomimetic carriers in antifungal drug delivery.
Antifungal Agents/therapeutic use* ; Drug Delivery Systems ; Amphotericin B/therapeutic use* ; Liposomes/chemistry* ; Nanoparticles ; Drug Carriers

As a typical human pathogenic fungus,

Objective:To analyze the practice and experience of " patient-centered, popularizing multi-disciplinary team(MDT) mode" in medical institutions, and to put forward reasonable suggestions and opinions for medical institutions to further improve and popularize MDT mode.Methods:Based on the evaluation of China Healthcare Improvement Initiative, 40 typical cases of MDT in medical institutions were collected, and descriptive analysis and textual analysis were carried out on the cases.Results:There were more specialized hospitals carrying out MDT, the application scope of MDT services was constantly expanding, and the management system and diagnosis and treatment process were constantly optimized.Conclusions:The mode of MDT in China is in the stage of exploration and development. In the promotion process, it is necessary to give full play to the role of information means, establish scientific and reasonable cost measurement and charge standard, and improve the enthusiasm of medical institutions and medical personnel to participate in MDT.

Objective:To investigate the effects of decorin (DCN) on the proliferation, migration and invasion of bladder cancer cells.Methods:Bladder cancer T24 cell line was used as the research object. MTT assay was used to detect the inhibitory effect of DCN at different concentrations (0, 5, 10, 20, 30, 40, 50 mg/L) on T24 cell proliferation at 24, 48, 72 and 96 h. The effects of DCN on T24 cell cycle and apoptosis were analyzed by flow cytometry. MTT assay, Transwell migration and invasion experiments were used to detect the effects of DCN on the adhesion, migration and invasion ability of T24 cells. The effects of DCN on TGF-β1 and P21 protein expression were detected by ELISA and Western blotting.Results:T24 cells were treated with 0, 5, 10, 20, 30, 40 and 50 mg/L DCN at 24, 48, 72 and 96 h, and there were statistically significant diffe-rences in cell proliferation activity ( F=168.64, P<0.001; F=165.81, P<0.001; F=291.02, P<0.001; F=148.93, P<0.001). T24 cells were treated with 0, 5, 10, 20, 30, 40 and 50 mg/L DCN for 72 h, and the cell proliferation activities were (60.71±3.03)%, (40.82±2.09)%, (37.24±1.63)%, (25.65±2.55)%, (23.00±2.67)%, (10.78±1.17)%, (11.04±0.96)%, respectively, and there was a statistically significant difference. At the concentration of 40 mg/L, the proliferation activity reached the lowest level, and the inhibitory effect on cell proliferation was the strongest. At concentrations of 40 and 50 mg/L, the cells in G 1 phase reached the peak value, while the cells in S phase reached the lowest value, and the cells in G 2 phase remained unchanged throughout the treatment process. T24 cells were treated with 0, 5, 10, 20, 30, 40 and 50 mg/L DCN for 72 h, and the apoptosis rates of cells were (12.18±1.17)%, (21.24±1.05)%, (19.80±1.20)%, (26.52±1.40)%, (30.86±1.40)%, (52.99±1.22)%, (43.04±2.16)%, respectively, and there was a statistically significant difference ( F=178.54, P<0.001). The differences between 5, 10, 20, 30, 40, 50 mg/L DCN and 0 mg/L DCN were all statistically significant (all P<0.001). When T24 cells were treated with 0, 40 mg/L DCN for 72 h, the cell adhesion rates were (37.14±1.35)% and (59.86±1.95)%, the numbers of migrated cells were 53.86±3.18 and 12.86±1.35, and there were statistically significant differences ( t=25.25, P<0.001; t=31.36, P<0.001). When DCN was applied to T24 cells for 48 h, the numbers of invasion at 0, 40 mg/L were 235.14±3.44 and 160.86±3.13, and there was a statistically significant difference ( t=2.27, P<0.001). When T24 cells were treated with 0, 5, 10, 20, 30, 40 and 50 mg/L DCN for 72 h, the relative expression levels of TGF-β1 were 85.67±3.35, 45.51±1.19, 49.93±4.15, 47.64±3.53, 46.05±3.18, 25.54±2.25, 33.44±4.05, and there was a statistically significant difference ( F=324.58, P<0.001). Compared with 0 mg/L DCN, 5, 10, 20, 30, 40 and 50 mg/L DCN could significantly inhibited the expression of TGF-β1 (all P<0.001). Compared with 0 mg/L DCN, P21 protein was upregulated 72 h after treatment with 40 mg/L DCN. Conclusion:DCN can inhibit proliferation and induce apoptosis of T24 cells in vitro, and has the effect of anti-metastasis of T24 cells.

Objective:This study uses two markers of resting-state functional MRI (r-fMRI) to investigate changes in spontaneous neural activity and their correlation with postpartum depression (PPD) severity.Methods:A total of 15 individuals with PPD, who met the diagnostic criteria for DSM-5 unipolar depression, 24-Item Hamilton Depression Scale (HAMD 24) scores greater than 20, Edinburgh Postnatal Depression Scale (EPDS) score≥12, and 16 postpartum healthy mothers (control group) matched with age and education were examined using r-fMRI. Two-sample t-test was used to compare the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values between groups. Pearson correlation analysis was used to determine the correlation between the ALFF and ReHo of the abnormal brain region and the HAMD 24 and EPDS scores. Results:Compared with the healthy control (HC), PPD showed increased ALFF in the right cerebellum anterior lobe culmen and the left dorsolateral prefrontal cortex (DLPFC), and decreased ALFF in the right parietal lobe (individual voxel P<0.005, cluster size >10 voxels, Alphasim correction). PPD had increased ReHo values in the left superior?frontal?gyrus,?orbital?part, inferior?frontal?gyrus,?orbital?part, middle?frontal?gyrus, precuneus, inferior?parietal lobule than HC. Decreased ReHo values were found in the right inferior?occipital?gyrus, inferior?frontal?gyrus, frontal lobule and left cerebellum inferior semi-lunar lobule (individual voxel P<0.005, cluster size>10 voxels, Alphasim correction). The ALFF value of the left DLPFC was positively correlated with the HAMD 24 score in PPD ( r=0.585, P=0.022). Age, body mass index and education years of each subject was included as covariates, partial correlation coefficient was still statistically significant ( r = 0.561, P = 0.046). Conclusion:This r-fMRI study suggested that changes in the spontaneous neural activity of these regions were related to emotional responses. PPD cases with high ALFF values in the left DLPFC had severe depression.

Objective:This study uses two markers of resting-state functional MRI (r-fMRI) to investigate changes in spontaneous neural activity and their correlation with postpartum depression (PPD) severity.Methods:A total of 15 individuals with PPD, who met the diagnostic criteria for DSM-5 unipolar depression, 24-Item Hamilton Depression Scale (HAMD 24) scores greater than 20, Edinburgh Postnatal Depression Scale (EPDS) score≥12, and 16 postpartum healthy mothers (control group) matched with age and education were examined using r-fMRI. Two-sample t-test was used to compare the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values between groups. Pearson correlation analysis was used to determine the correlation between the ALFF and ReHo of the abnormal brain region and the HAMD 24 and EPDS scores. Results:Compared with the healthy control (HC), PPD showed increased ALFF in the right cerebellum anterior lobe culmen and the left dorsolateral prefrontal cortex (DLPFC), and decreased ALFF in the right parietal lobe (individual voxel P<0.005, cluster size >10 voxels, Alphasim correction). PPD had increased ReHo values in the left superior?frontal?gyrus,?orbital?part, inferior?frontal?gyrus,?orbital?part, middle?frontal?gyrus, precuneus, inferior?parietal lobule than HC. Decreased ReHo values were found in the right inferior?occipital?gyrus, inferior?frontal?gyrus, frontal lobule and left cerebellum inferior semi-lunar lobule (individual voxel P<0.005, cluster size>10 voxels, Alphasim correction). The ALFF value of the left DLPFC was positively correlated with the HAMD 24 score in PPD ( r=0.585, P=0.022). Age, body mass index and education years of each subject was included as covariates, partial correlation coefficient was still statistically significant ( r = 0.561, P = 0.046). Conclusion:This r-fMRI study suggested that changes in the spontaneous neural activity of these regions were related to emotional responses. PPD cases with high ALFF values in the left DLPFC had severe depression.

OBJECTIVE: To explore clinical efficacy of bridge-link combined fixation system for adult mid-shaft clavicle fractures. METHODS: From January 2016 to August 2016, 28 patients with mid-shaft clavicle fractures were treated by bridge-link combined fixation system, including 15 males and 13 females, aged from 27 to 82 years old with an average of(48.50±15.34) years old; the courses of disease was for 13 to 15 months with an average of (14.17±0.77) months. Fracture healing time and complication were observed, postoperative and postoperative Constant function score of shoulder joint at 1, 3 and 13 months and were compared. RESULTS: All patients were followed up for 13 to 15 months with an average of (14.17±0.77) months. Twenty-eight patients achieved clinical fracture healing without infection, bone un-union, delayed union, breakage of internal fixation and re-fracture after removing of the internal fixation occurred. Fracture healing time ranged from 2.5 to 4 months with (3.05±0.44) months. Postoperative Constant score at 1, 3 and 13 months were 76.57±4.70, 90.75±3.62, 96.07±2.40 respectively, and had significant difference compared with before operation(58.36±4.98). CONCLUSIONS Bridge-link combined fixation system could be used as a new internal fixation for adult mid-shaft clavicle fractures, which has advantages of rapid recovery, less complications, and could reduce incidence of breakage of internal fixation, osteoporosis, re-fractures after removing the internal fixation.
Adult ; Aged ; Aged, 80 and over ; Bone Plates ; Clavicle ; Female ; Fracture Fixation, Internal ; Fracture Healing ; Fractures, Bone ; surgery ; Humans ; Male ; Middle Aged ; Treatment Outcome