This study investigated the regulatory potential of salidroside (SAL), a primary active compound in Rhodiola rosea L., on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha (HIF-1a) pathway in osteoblasts. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to validate whether the receptor activator of nuclear factor-?B ligand (RANKL) is the downstream target gene of HIF-1a in osteoblasts. The study also utilized lipopolysaccharide (LPS)-induced mouse osteolysis to examine the impact of SAL on osteolysis in vivo. Furthermore, conditioned medium (CM) from SAL-pretreated osteoblasts was used to investigate the paracrine effects on osteoclastogenesis through the HIF-1a pathway. Hypoxic condition-induced overexpression of HIF-1a upregulated RANKL levels by binding to the RANKL promoter and enhancing transcription in osteoblastic cells. In vivo, SAL significantly alleviated bone tissue hypoxia and decreased the expression of HIF-1a by downregulating the expression of RANKL, vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and angiopoietin-like 4 (ANGPTL4). In the paracrine experiment, conditioned media from SAL-pretreated osteoblasts inhibited differentiation through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. RANKL emerges as the downstream target gene regulated by HIF-1a in osteoblasts. SAL significantly alleviates bone tissue hypoxia and bone loss in LPS-induced osteolysis through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. SAL inhibits osteoclast differentiation by regulating osteoblast paracrine secretion.
Animals ; Osteoblasts/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Glucosides/administration & dosage* ; Cell Differentiation/drug effects* ; Phenols/administration & dosage* ; Mice ; Osteoclasts/metabolism* ; RANK Ligand/genetics* ; Rhodiola/chemistry* ; Osteogenesis/drug effects* ; Signal Transduction/drug effects* ; Interleukin-6/genetics* ; Male ; RAW 264.7 Cells ; Osteolysis/genetics* ; Humans ; Mice, Inbred C57BL

BACKGROUND:Nano-zirconium dioxide has good application potential in the field of bone tissue repair.Studying the effect of nano-zirconium dioxide on osteogenic differentiation will help to promote the clinical application of nano-zirconium dioxide in the treatment of bone defects. OBJECTIVE:To explore the effect of nano-zirconium dioxide on the osteogenic differentiation of ectomesenchymal stem cells in the nasal mucosa. METHODS:Ectomesenchymal stem cells derived from rat nasal mucosa were isolated and cultured,and the biotoxicity of nano-zirconium dioxide to the cells was detected by CCK-8 assay.The biosafety concentration was selected according to the cytotoxicity,and the cells were randomly divided into a control group,a nano-zirconium dioxide group,and a nano-hydroxyapatite group.Osteogenic differentiation of cells was directionally induced in each group.On day 7 of induced differentiation,alkaline phosphatase staining was performed.qRT-PCR and western blot assay were used to detect the expression of early osteogenic markers(Runx2 and Osx).On day 21 of induced differentiation,alizarin red staining was conducted.qRT-PCR and western blot assay were utilized to determine the expression levels of late osteogenic markers(OPN and OCN). RESULTS AND CONCLUSION:(1)The median lethal concentration of nano-zirconium dioxide on ectomesenchymal stem cells in nasal mucosa was 0.6 mg/mL.In the experiment,the mass concentration of 200 μg/mL was selected for intervention.Zirconium dioxide had no significant effect on the proliferation of the cells.(2)Compared with the control group,the alkaline phosphatase staining of the cells in the nano-zirconium dioxide group was more obvious and the level of cell mineralization was higher,but there was no significant difference compared with the nano-hydroxyapatite.(3)Compared with the control group,the expression of bone-related genes and proteins increased significantly,but there was no significant difference compared with nano-hydroxyapatite.(4)The results show that nano-zirconium dioxide has good biological safety and can promote the osteogenic differentiation of ectomesenchymal stem cells in the nasal mucosa.This promoting effect is equivalent to that of nano-hydroxyapatite.

Objective To investigate the ability of combined baseline serum markers, i.e., HBV DNA, HBV RNA, HBsAg, and HBcrAg, to predict HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B (CHB) treated by nucleos(t)ide analogues. Methods A retrospective analysis was performed for 83 HBeAg-positive patients selected as subjects from the prospective CHB follow-up cohort established by Difficult & Complicated Liver Diseases and Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, from June 2007 to July 2008, and the baseline serum levels of HBV DNA, HBV RNA, HBsAg, and HBcrAg were analyzed. The t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Spearman method was used for correlation analysis. A Cox regression model was established to calculate HBeAg seroconversion prediction score, and the time-dependent receiver operating characteristic curve was used to evaluate the ability of combined markers in predicting HBeAg seroconversion. The Kaplan-Meier method was used to calculate cumulative seroconversion rate in each group, and the Log-rank test was used for comparison between groups. Results For the 83 HBeAg-positive patients, the median follow-up time was 108 months, and 44.58%(37/83) of these patients achieved HBeAg seroconversion. Compared with the non-seroconversion group, the HBeAg seroconversion group had significantly lower baseline serum levels of HBV DNA [6.23(1.99-9.28) log 10 IU/mL vs 7.69(2.05-8.96) log 10 IU/mL, Z =-2.345, P =0.019] and HBV RNA [4.81(1.40-7.53) log 10 copies/mL vs 6.22(2.00-8.49) log 10 copies/mL, Z =-1.702, P =0.010], and there were no significant differences in the levels of HBsAg and HBcrAg between the two groups ( P > 0.05). The Cox regression equation constructed based on the above serum markers showed a median score of 0.95(range 0.37-3.45) for predicting HBeAg seroconversion. In the total population, the combined score was negatively correlated with HBsAg, HBV DNA, HBV RNA, and HBcrAg ( r =-0.697, -0.787, -0.990, and -0.819, all P < 0.001). Based on the median prediction score, the patients were divided into high HBeAg seroconversion group and low HBeAg seroconversion group; as for the prediction of HBeAg seroconversion rate at 36, 60, and 84 months, the high HBeAg seroconversion group had a seroconversion rate of 43.90%, 51.20%, and 63.10%, respectively, while the low HBeAg seroconversion group had a seroconversion rate of 9.60%, 17.00%, and 19.8%, respectively, and there was a significant difference between the two groups ( χ 2 =11.6, P < 0.001). Conclusion The combined prediction score based on baseline serum HBV markers can predict HBeAg seroconversion in CHB patients treated by nucleos(t)ide analogues.

Objective To investigate the consistency between Shengxiang (S) and Xinbo (X) real-time PCR methods in the quantification of HBV RNA. Methods In the prospective follow-up cohort of 108 chronic hepatitis B (CHB) patients established from July 2007 to August 2008, 20 patients with HBeAg seroconversion were selected, and 20 patients without seroconversion were selected by propensity score matching at a ratio of 1∶ 1. The two quantification methods from S and X companies were used, and a retrospective analysis was performed for HBV RNA in serum samples at baseline and weeks 12, 24, and 48. The paired t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data. The Pearson correlation coefficient, intraclass correlation coefficient (ICC), and the Bland-Altman method were used to evaluate the consistency of the two quantification methods. Results A total of 132 serum samples were tested by S reagent, and 154 were tested by X reagent; the detection rate of HBV RNA was 100% by both reagents. A total of 131 serum samples were tested by both reagents, with 34 samples at baseline and 29, 35, and 33 samples, respectively, at weeks 12, 24, and 48 of follow-up; at these four time points, the HBV RNA quantification data detected by X reagent were significantly higher than those detected by S reagent (5.75±1.64/5.43±1.73/5.13±1.54/4.76±1.55 log 10 copies/mL vs 4.80±1.48/4.52±1.53/4.10±1.50/3.92± 1.43 log 10 copies/mL, t =8.348, t =5.341, Z =-5.086, Z =-4.762, all P < 0.001). The correlation analysis of the two methods showed a Pearson correlation coefficient of 0.915 (95% confidence interval [ CI ]: 0.836-0.957) and an ICC of 0.771(95% CI : -0.021 to 0.931) at baseline, a Pearson correlation coefficient of 0.849(95% CI : 0.701-0.927) and an ICC of 0.733(95% CI : 0.138-0.902) at week 12, a Pearson correlation coefficient of 0.951(95% CI : 0.905-0.975) and an ICC of 0.776(95% CI : -0.058 to 0.942) at week 24, and a Pearson correlation coefficient of 0.933(95% CI : 0.867-0.967) and an ICC of 0.804(95% CI : -0.014 to 0.944) at week 48 (all P < 0.05). The Bland-Altman analysis showed that the difference of 96.18%(126/131) samples tested by the two methods was within the mean difference±1.96 standard deviation. Conclusion HBV RNA quantification by X reagent is higher than that by S reagent, while the two real-time PCR quantification methods show a good consistency in CHB patients with HBeAg seroconversion and those without seroconversion.

Objective:To explore the effects of competency-based diversified training on the bedside nursing comprehensive ability aand transition shock of newly recruited nurses.Methods:A total of 62 newly recruited nurses from the Second Affiliated Hospital of Zhengzhou University in June 2018 were selected as the control group, and 70 newly recruited nurses from June 2019 were selected as the experimental group by cluster sampling. The control group received routine pre-job training, and the experimental group received diversified training based on the control group. After one year of training, the differences in the scores of bedside nursing comprehensive ability, post competency and transition shock between the two groups of nurses were analyzed.Results:After 1 year of training, the total scores and the scores of nursing problems, nursing evaluation, nursing plan, nursing theory, nursing operation and bedside nursing comprehensive ability in the experimental group were 12.20±1.76, 24.29±2.38, 13.54±1.88, 9.77±1.35, 15.14±2.30 and 79.24±6.59, which were all higher than those of the control group (10.26±1.55,22.31±1.84,10.45±1.58, 8.56±1.80, 13.27±2.38 and 69.82±4.09), the differences were statistically significant ( t value was 4.582-13.679, P<0.05). The total scores and the scores of each dimension of the Post-competency the experimental group were 31.46 ±4.32, 51.03± 4.64, 20.27± 3.78, 17.86±3.99, 58.43± 4.44, 179.37±9.97, which were all higher than those of the control group 24.76±4.12, 40.56±5.55, 16.61±2.88, 15.15± 2.96, 49.74±3.07, 146.66±17.98, the differences were statistically significant ( t value was 4.466-13.197, P<0.05). The scores of psychological knowledge, skills, social culture and development and the total scores of Transition shock in the experimental group were 30.90±3.15, 19.69±2.74, 32.17±3.06, 103.81±12.24, which were all higher than those in the control group (25.69±2.76, 15.92±3.24, 27.50±4.15, 88.32±11.54), the differences were statistically significant ( t value was 7.237-10.040, P<0.05). Conclusions:competency-based diversified training can effectively improve the bedside nursing comprehensive ability and post competency, reduce their transition shock, and has strong clinical reference significance.

Objective:To improve the determination method for the total anthraquinone of the Rhei Radix et Rhizoma in the Pharmacopoeia of the People’s Republic of China, and compare this method with the method in the pharmacopoeia to determine the feasibility of such method. Methods:By changing the determination of total anthraquinone from biphasic hydrolysis to monophase hydrolysis, the method included in the pharmacopoeia was improved to determine the total anthraquinone content in Rhei Radix et Rhizoma. Chromatographic conditions were Symmetry C18 (4.6 mm × 250 mm, 5 μm) chromatographic column; the mobile phase is methanol-0.1% phosphoric acid water (85:15); the flow rate was 1 ml/min; the column temperature is 30 ℃; the detection wavelength is 254 nm. Results:The concentrations of aloe-emodin, rhein, emodin, chrysophanol, physcion in the range of 0.003 3-0.332 0 μg, 0.006 9-0.668 0 μg, 0.002 3-0.232 0 μg, 0.010 4-1.040 0 μg, 0.008 4-0.836 0 μg have good linear relationship with the peak area; RSDs of precision, stability and repeatability were less than 2%; the recovery rates of aloe-emodin, rhein, emodin, chrysophanol and physcion were 101.50%, 99.30%, 99.62%, 101.57%, and 103.11%, and the RSDs were less than 2%. Conclusion:The improvement method is simple, accurate, reliable and reproducible, which could be used for the quality control of Rhei Radix et Rhizoma.

Chronic hepatitis B virus (HBV) infection and end-stage liver disease caused by such infection pose a serious threat to the health of Chinese citizens. The presence of HBV cccDNA is the main reason for the difficulties in the treatment of chronic hepatitis B and recurrence after drug withdrawal. HBV RNA, as a new serum marker, is produced by cccDNA transcription, and theoretically, it can reflect the level and transcriptional activity of cccDNA in hepatocytes. This article mainly introduces the formation of serum HBV RNA and analyzes its significance in evaluating the activity or status of cccDNA in liver tissue and predicting patients’ response during antiviral therapy and after drug withdrawal. Moreover, it is pointed out that further large-scale clinical studies are needed to verify and improve the clinical significance of serum HBV RNA measurement, so as to further optimize the regimens of antiviral therapy and guide the precision treatment of patients.

Objective:To investigate the mutation characteristics and clinical relevance of Gilbert syndrome (GS) and Crigler-Najjar syndrome (CNS) in relation to uridine diphosphate glucuronosyltransferase A1 (UGT1A1) gene.Methods:The characteristics of UGT1A1 gene mutation and their clinical relevance were analyzed by searching PubMed and Human Gene Mutation Databases.Results:A total of 163 mutation sites were found in the UGT1A1 gene since November 16, 2018. The following patterns existed at the above sites: (1) the numbers of gene mutations occurring between different exons of UGT1A1 was related to GS or CNS phenotypes, and were positively correlated with the length of the exon; (2) nonsense point mutations was mainly occurred in type I of CNS; (3) GS, Crigler-Najjar syndrome type II compound heterozygous mutation sites had a certain combination and distribution, among which - 3279t > G mutation was found in all four GS complex heterozygous compositions; (4) UGT1A1 gene mutation sites reported in Asia had marked aggregation in c.211-c.558.Conclusion:UGT1A1 gene mutation characteristics and clinical relevance varies with different mutation sites, reporting areas and populations. This study has reference value for basic research and clinical diagnosis and treatment of GS and CNS.

Objective? To investigate the training, operation and examination of nursing care for lymphedema in Jiangsu Province. Methods? We selected 99 nurses provided nursing care for lymphedema at 13 class Ⅲ hospitals of prefecture-level city in Jiangsu Province as subjects by purposive sampling. All of nurses were investigated with the self-designed questionnaire involving general information, application and training of nursing care for lymphedema, nursing operation and examination of lymphedema. Results? Among 99 nurses, 68 (68.69%) nurses could carry out training regularly, and 59 (59.60%) nurses participated in training on nursing care for lymphedema. The main causes failing to could carry out training regularly included the teaching staff and lack of related content. Conclusions? At present, the training of nursing care for lymphedema needs to be strengthened. There is a pressing need to formulate the unified standardized operation and examination standards so as to improve the quality of work and professional connotation of nursing care for lymphedema.

The application of direct-acting antiviral agents significantly increases the rate of sustained virologic response in patients with hepatitis C,but there are still some patients who have no response during treatment or experience recurrence after treatment.Related influencing factors are research hotspots at present.This article reviews the influencing factors for the therapeutic effect of direct-acting antiviral agents in hepatitis C from the perspectives of HCV resistance-related mutations,HCV genotypes,viral load,degree of liver lesions,and drug combination,in order to provide a reference for clinical prevention and treatment of chronic hepatitis C.