This study identified 8 members including NjBIN2 of the GSK3 family in Nardostachys jatamansi by bioinformatics analysis. Moreover, the phylogenetic tree revealed that the GKS3 family members of N. jatamansi had a close relationship with those of Arabidopsis. RT-qPCR results showed that NjBIN2 presented a tissue-specific expression pattern with the highest expression in roots, suggesting that NjBIN2 played a role in root growth and development. In addition, the application of epibrassinolide or the brassinosteroid(BR) synthesis inhibitor(brassinazole) altered the expression pattern of NjBIN2 and influenced the photomorphogenesis(cotyledon opening) and root development of N. jatamansi, which provided direct evidence about the functions of NjBIN2. In conclusion, this study highlights the roles of BIN2 in regulating the growth and development of N. jatamansi by analyzing the expression pattern and biological function of NjBIN2. It not only enriches the understanding about the regulatory mechanism of the growth and development of N. jatamansi but also provides a theoretical basis and potential gene targets for molecular breeding of N. jatamansi with improved quality in the future.
Brassinosteroids/metabolism* ; Steroids, Heterocyclic/metabolism* ; Gene Expression Regulation, Plant/drug effects* ; Plant Proteins/metabolism* ; Phylogeny ; Nardostachys/metabolism* ; Plant Growth Regulators/pharmacology* ; Plant Roots/drug effects*

The antidepressant activity and molecular mechanisms of Yueju Wan volatile oil were investigated. The Yueju Wan volatile oil was extracted by using supercritical CO_2. Gas chromatography-mass spectrometry(GC-MS) combined with network pharmacology identified 28 chemical constituents in Yueju Wan volatile oil, primarily terpenes and lactones. A total of 123 overlapping targets were associated with depression, including core targets of interleukin-1β(IL-1β), signal transducer and activator of transcription 3(STAT3), and caspase-3(CASP3). These targets were mainly involved in the prolactin, advanced glycation end products/receptor(AGE/RAGE), and phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) signaling pathways. A reserpine-induced depression mouse model was established to evaluate the therapeutic effects and mechanisms of Yueju Wan volatile oil. The effects of Yueju Wan volatile oil on depression-like behavior in mice were evaluated by analyzing body mass, body temperature index, tail suspension immobility time, forced swimming immobility time, and sucrose preference. Hematoxylin-eosin(HE) staining revealed neuronal protection of Yueju Wan volatile oil in the brain of mice. Enzyme-linked immunosorbent assay(ELISA) and Western blot were employed to detect the protein expression of AGEs, IL-1β, phosphorylated PI3K(p-PI3K), Akt, phosphorylated Akt(p-Akt), nuclear factor κB(NF-κB), and brain-derived neurotrophic factor(BDNF). Behavioral evaluation showed that Yueju Wan volatile oil could effectively control the decline of body mass and body temperature of depressed mice, reduce tail suspension and swimming immobility time, and enhance their preference for sucrose. Histopathological examination showed that Yueju Wan volatile oil could alleviate the neuronal damage in CA1 and dentate gyrus(DG) of the hippocampus of mice. ELISA and Western blot results showed that Yueju Wan volatile oil could significantly increase the protein expression levels of PI3K, Akt, and BDNF and significantly decrease the protein expression levels of AGEs, IL-1β, p-PI3K, p-Akt, and NF-κB in the hippocampus of mice. Furthermore, the p-PI3K/PI3K and p-Akt/Akt ratios were significantly decreased at medium and high doses. These findings suggest that the aromatherapy of Yueju Wan volatile oil can significantly improve reserpine-induced depression-like behavior in mice, which may be related to reducing the expression of neuronal membrane protein AGEs, reducing the phosphorylation levels of PI3K and Akt, inhibiting NF-κB entry into the nucleus, and alleviating the release of pro-inflammatory factors and nerve injury.
Animals ; Antidepressive Agents/chemistry* ; Mice ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/immunology* ; Oils, Volatile/chemistry* ; Male ; Drugs, Chinese Herbal/chemistry* ; Signal Transduction/drug effects* ; Depression/metabolism* ; Glycation End Products, Advanced/immunology* ; Humans

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To establish and optimize a method for the detection of recombinant human midkine (rhMK) activity and verify its methodology, cell counting kit-8 (cck-8) method was used to measure the proliferation activity of rat knee chondrocytes. The specificity, accuracy, precision, linearity and robustness of the method were also verified in this study. The established method was proven to have good specificity because the buffer of rhMK and recombinant human interleukin-1 receptor antagonist have no obvious active effect; the recoveries of the samples with relative activities of 50%, 75%, 100%, 125%, 150% were in the range of 80.0% to 124.0% by statistical analysis, the relative standard deviations (RSD) of relative potency were all within 20%, the linear correlation coefficient, R² ≥ 0.98, suggesting that the accuracy, precision and linearity of the method were good; the robustness correlation coefficient, R² ≥ 0.92 and the ratio of maximum to minimum of sigmoidal dose-response were no less than 1.5, indicating that robustness of the methods was good. In conclusion, a bioactivity measurement method for rhMK was established and fully validated in this study and it provides a reliable method for the bioactivity analysis of rhMK routine samples during the development. This study was approved by the Animal Care and Use Committee of Shanghai Model Organisms Center, Inc. (approval number: 2019-0008-06).

This study explored a new model of Prostate Imaging Reporting and Data System (PIRADS) and adjusted prostate-specific antigen density of peripheral zone (aPSADPZ) for predicting the occurrence of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). The demographic and clinical characteristics of 853 patients were recorded. Prostate-specific antigen (PSA), PSA density (PSAD), PSAD of peripheral zone (PSADPZ), aPSADPZ, and peripheral zone volume ratio (PZ-ratio) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The calibration and discrimination abilities of new nomograms were verified with the calibration curve and area under the ROC curve (AUC). The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves. The AUCs of PSA, PSAD, PSADPZ, aPSADPZ, and PZ-ratio were 0.669, 0.762, 0.659, 0.812, and 0.748 for PCa diagnosis, while 0.713, 0.788, 0.694, 0.828, and 0.735 for csPCa diagnosis, respectively. All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of PCa or csPCa. The new model significantly improved the diagnostic accuracy of PCa (0.945 vs 0.830, P < 0.01) and csPCa (0.937 vs 0.845, P < 0.01) compared with the base model. In addition, the number of patients with PCa and csPCa predicted by the new model was in good agreement with the actual number of patients with PCa and csPCa in high-risk threshold. This study demonstrates that aPSADPZ has a higher predictive accuracy for PCa diagnosis than the conventional indicators. Combining aPSADPZ with PIRADS can improve PCa diagnosis and avoid unnecessary biopsies.
Male ; Humans ; Prostate/pathology* ; Prostate-Specific Antigen/analysis* ; Prostatic Neoplasms/diagnostic imaging* ; Biopsy ; Nomograms ; Retrospective Studies

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Humans ; Fibrous Dysplasia, Polyostotic/complications* ; Hemangioma

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

In this study, we investigated the anti-osteoporotic activity and mechanism of action of extract of Panax quiquefolium L. based on zebrafish model combined with metabolomics technology. A zebrafish model of prednisolone-induced osteoporosis was used to compare the anti-osteoporotic activity of Panax quiquefolium L., and the expression of osteoblast-associated genes and osteoclast-associated genes in zebrafish was detected by quantitative real-time PCR (qRT-PCR), using bone fluorescence area and fluorescence density as evaluation indexes. Metabolomics based on ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) was used to explore the change patterns of biomarkers and the metabolic pathways affected. The results showed that the 50% ethanol extracts of Panax quiquefolium L. from Jilin, Canada, Wenden and the United States can significantly improve the bone fluorescence area of zebrafish compared with model group. Furthermore, four sources 50% ethanol extracts of Panax quiquefolium L. except United States also can significantly improve the bone fluorescence density of zebrafish. In addition, PCR showed that extract of Panax quiquefolium L. can significantly up-regulated the expression of vitamin D receptor b (vdrb), collagen type I α2 (col1a2) and cysteine-rich acidic secreted protein (sparc) genes, and down-regulated the expression of matrix metalloproteinase 9 (mmp9), anti-tartrase acid phosphatase (trap) and cathepsin K (ctsk) genes. Metabolomic analysis identified 24 key differential metabolites. Furthermore, pathway analysis showed that Panax quiquefolium L. could regulate the levels of 10 key biomarkers by participating in purine metabolism, tricarboxylic acid cycle and pentose phosphate metabolism and improve the osteoporosis status of zebrafish. This study preliminically revealed the anti-osteoporosis mechanism of 50% ethanol extract from Panax quiquefolium L. through multi-component, multi-target and multi-pathway and also provides theoretical basis for clinical development and utilization of anti-osteoporosis products of Panax quiquefolium L. This experiment was approved by the Experimental Animal Welfare Ethics Committee of the Institute of Biology, Shandong Academy of Sciences (approval number: SWS20181002).