Objective To explore the biological effects and changes of metabolites of Guilu erxian glue(GLE)in vivo in the pre-vention and treatment of postmenopausal osteoporosis(PMO),based on non-targeted metabolomics.Methods Fifty SD female rats were divided into five groups using the random number table method:sham group,model group(OVX),and low-,medium-,and high-dose GLE(GLE-L,GLE-M and GLE-H)groups,with ten mice in each group.After 1 week of modeling,the drug was given by gavage,and samples were collected 8 weeks later.Bone microstructure was detected by MicroCT,bone metabolism-related indices were analyzed by immunohistochemistry(IHC),and a serum metabolite atlas was constructed using the LC-MS/MS technique to observe the distribution differences of metabolites and related pathways.Results The MicroCT results showed that GLE could increase the percentage of bone trabeculae and restore bone microstructure(P<0.05,GLE-M group vs.OVX group).IHC analysis showed that GLE could increase Runx2 expression in femur(P<0.05,GLE-M group vs.OVX group).There were four co-regulated metabolites in the sham group,GLE-H group,and OVX group,including 3-(3-methoxyphenyl)propionic acid,acetamide,Equol,and 1-oleoacyl-SN-glycerol-3-phosphocholine,which showed high expression in the sham group,low expression in the OVX group,and high expression in the GLE-M group.The KEGG pathway result showed that the main pathways involved between the sham group and OVX group were steroid hormone biosynthesis and cortisol synthesis and secretion.Tryptophan metabolism and phenylalanine metabolism were observed in the GLE group and OVX group.Conclusion GLE may prevent PMO by regulating metabolites in the body.

Objective To explore the biological effects and changes of metabolites of Guilu erxian glue(GLE)in vivo in the pre-vention and treatment of postmenopausal osteoporosis(PMO),based on non-targeted metabolomics.Methods Fifty SD female rats were divided into five groups using the random number table method:sham group,model group(OVX),and low-,medium-,and high-dose GLE(GLE-L,GLE-M and GLE-H)groups,with ten mice in each group.After 1 week of modeling,the drug was given by gavage,and samples were collected 8 weeks later.Bone microstructure was detected by MicroCT,bone metabolism-related indices were analyzed by immunohistochemistry(IHC),and a serum metabolite atlas was constructed using the LC-MS/MS technique to observe the distribution differences of metabolites and related pathways.Results The MicroCT results showed that GLE could increase the percentage of bone trabeculae and restore bone microstructure(P<0.05,GLE-M group vs.OVX group).IHC analysis showed that GLE could increase Runx2 expression in femur(P<0.05,GLE-M group vs.OVX group).There were four co-regulated metabolites in the sham group,GLE-H group,and OVX group,including 3-(3-methoxyphenyl)propionic acid,acetamide,Equol,and 1-oleoacyl-SN-glycerol-3-phosphocholine,which showed high expression in the sham group,low expression in the OVX group,and high expression in the GLE-M group.The KEGG pathway result showed that the main pathways involved between the sham group and OVX group were steroid hormone biosynthesis and cortisol synthesis and secretion.Tryptophan metabolism and phenylalanine metabolism were observed in the GLE group and OVX group.Conclusion GLE may prevent PMO by regulating metabolites in the body.

Postmenopausal osteoporosis (PMO) is a clinically refractory bone metabolic disease that often occurs in women after menopause. According to its clinical manifestations, it is classified as " bone flaccidity" and " bone withering" in traditional Chinese medicine (TCM). Based on the theory of "kidney qi heat", this paper explains the etiology and pathogenesis of PMO. It is proposed that yin deficiency, depletion of liquid, and yin not containing yang form the basis of its pathogenesis. Furthermore, the internal heat of yang hyperactivity and crippled backbones are the central links that lead to the mutual loss of yin and yang and the withering of bones. Based on the above pathogenesis, the early treatment of the disease is based on nourishing yin and promoting liquid, supplementing qi and nourishing blood production using Yiyin Zengye Decoction with modification. In the medium term, the treatment is based on nourishing yin, clearing heat, invigorating the kidney, and supplementing essence using Ziyin Qingre Decoction with modification. In the final terminal stage, the treatment is based on nourishing yin, tonifying yang, and strengthening the foundation using Yinyang Shuangbu Decoction with modification. At the same time, the correlation between "kidney qi heat" and inflammatory and immune reaction is explored to provide new concepts for clinical research and improve the clinical application value of TCM in the prevention and treatment of PMO.

Objective To investigate the effect and mechanism of salidroside on1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease(PD)in mice.Methods C57BL/6J mice were induced by MPTP to establish a PD mouse model and the movement track of mice was re-corded by open field experiment.The expression of tyrosine hydroxylase(TH),α-synuclein(α-syn),nuclear factor E2 associated factor 2(Nrf2)and quinone oxidoreductase 1(NQO1)were detected by immunohistochemistry in brain tissue of mice.SN4741 cells were stimulated by MPTP to establish a PD cell model in vitro.MPTP stimulation of SN4741 cells to establish an in vitro cell mod-el of PD.After pretreatment with salidroside,TUNEL was used to detect cell apoptosis in each group.The expressions of TH,α-syn,Nrf2 and NQO1 were detected by immunofluorescence.Nrf2 expres-sion was knocked down by being transfected with si-RNA,and apoptosis condition was detected by TUNEL assay.The expression levels of interleukin-1β(IL-1β)and interleukin-18(IL-18)protein in brain tissue extract and cell culture were detected by enzyme-linked immunosorbent assay(ELISA).Results The open field experiment results showed that salidroside could improve 3 min total distance of activity,average speed and activity track of PD mice(P＜0.05).Compared with the PD model mice,the salidroside treated mice showed significantly increased expression of TH,Nrf2 and NQO1 in the brain,and reduced expression of IL-18,α-Syn,IL-1β.Compared with the MPTP stimulated cells,the salidroside pretreatment group showed a decrease in cell apoptosis and an increase in the expressions of TH,Nrf2 and NQO1,but reduced expressions in α-Syn,IL-1β and IL-18.After si-RNA knockdown of Nrf2 expression,the protective effect of salidroside on MPTP stimulated cells weakened or even disappeared.Conclusion Salidroside may alleviate neuronal apoptosis by activating Nrf2-ARE signaling pathway,which is expected to be a new drug for PD treatment.

Objective To investigate the effect and mechanism of salidroside on1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease(PD)in mice.Methods C57BL/6J mice were induced by MPTP to establish a PD mouse model and the movement track of mice was re-corded by open field experiment.The expression of tyrosine hydroxylase(TH),α-synuclein(α-syn),nuclear factor E2 associated factor 2(Nrf2)and quinone oxidoreductase 1(NQO1)were detected by immunohistochemistry in brain tissue of mice.SN4741 cells were stimulated by MPTP to establish a PD cell model in vitro.MPTP stimulation of SN4741 cells to establish an in vitro cell mod-el of PD.After pretreatment with salidroside,TUNEL was used to detect cell apoptosis in each group.The expressions of TH,α-syn,Nrf2 and NQO1 were detected by immunofluorescence.Nrf2 expres-sion was knocked down by being transfected with si-RNA,and apoptosis condition was detected by TUNEL assay.The expression levels of interleukin-1β(IL-1β)and interleukin-18(IL-18)protein in brain tissue extract and cell culture were detected by enzyme-linked immunosorbent assay(ELISA).Results The open field experiment results showed that salidroside could improve 3 min total distance of activity,average speed and activity track of PD mice(P＜0.05).Compared with the PD model mice,the salidroside treated mice showed significantly increased expression of TH,Nrf2 and NQO1 in the brain,and reduced expression of IL-18,α-Syn,IL-1β.Compared with the MPTP stimulated cells,the salidroside pretreatment group showed a decrease in cell apoptosis and an increase in the expressions of TH,Nrf2 and NQO1,but reduced expressions in α-Syn,IL-1β and IL-18.After si-RNA knockdown of Nrf2 expression,the protective effect of salidroside on MPTP stimulated cells weakened or even disappeared.Conclusion Salidroside may alleviate neuronal apoptosis by activating Nrf2-ARE signaling pathway,which is expected to be a new drug for PD treatment.

Objective:To explore the clinical application and long-term safety of hydroxychloroquine sulfate (HCQ) in the treatment of rheumatic diseases.Methods:A multi-center cross-sectional study was conducted between August 2017 and August 2018 in a random sample of eleven medical institutions of rheumatology and immunology in China. Patients who took HCQ for more than 3 months were enrolled into this study. The cumulative dose and long-term side effects of HCQ were recorded. The changes of laboratory indexes before and after treatment with HCQ were analyzed. Categorical variables were presented with counts and proportions, and evaluated by Chi-square test. Continuous parametric data were presented as Mean±standard deviation, and evaluated by Student's t test or Mann-Whitney U test. P-values less than 0.05 were considered statistically significant. Results:A total of 886 patients with rheumatic diseases were enrolled into this study, including 505 cases with systemic lupus erythematosus (57.0%), 210 cases with rheumatoid arthritis (23.7%), 80 cases with Sj?gren's syndrome (9.0%), 57 cases with undifferentiated connective tissue disease (6.4%), 12 cases of systemic vasculitis (1.4%), 10 cases of mixed connective tissue disease (1.1%), 7 cases of myositis (0.8%) and 5 cases with systemic sclerosis (0.6%). The most common long-term side effects of HCQ was skin or mucous lesions (12.4%) and vision problems (8.0%). Other adverse reactions included problems of digestive system (3.0%), nervous system (2.1%), musculoskeletal system (1.1%) and cardiovascular system (0.9%). 140 cases (15.8%) had stopped taking HCQ during the treatment. More than half of them decided to stop taking medicine by themselves. Fifty-four patients (6.1%) stopped using HCQ due to side effects while 24 of them took it again, and another 12 patients (1.4%) stopped the drug due to remission of illness. Patients were divided into three groups according to the cumulative dose of HCQ: less than 500 g, 500-1 000 g and more than 1 000 g respectively. There was significant difference in the incidence of long-term side effects among the three groups ( χ2=6.382, P=0.041). The last group (more than 1 000 g) suffered the highest incidence of long-term adverse reactions (37.1%). No severe adverse drug reactions were observed in this study. Conclusion:Hydroxychloroquine is widely used in the treatment of rheumatic diseases. The incidence of long-term side effects is 20.4%, is 6.1% lead to drug withdrawal, which are especially related to the cumulative doses. It should be adjusted properly according to the clinical application.

OBJECTIVETo analyze the clinical feature and constituent ratio of adult hip fractures in Southwest China.

METHODSThe data of adult inpatients and outpatients with hip fractures treated between January 2010 and December 2011 in 11 hospitals of the Southwest China were collected and analyzed. The data includes gender, age, age distribution and fracture pattern according to AO classification.

RESULTSThere were a total of 2,833 adult hip fractures, including 1,340 (47.30%) males and 1,493 (52.70%) females, with a male-to-female incidence ratio of 1: 1.11 and a mean age of (66±18) years. The highest frequency of hip fractures was seen in the 71 to 85 years age group (42.18%, 1,195/2,833). There were 844 fractures (29.79%) in the young and middle-aged group (16-<60 years) and 1 898 fractures (70.21%) in the geriatric group (≥60 years). Men had a higher rate than women (men: 577 fractures, 68.4%) in the young and middle-aged group, while women had a higher rate than men (women: 1,226 fractures, 61.64%) in the geriatric group, with a significant difference in the sex distribution between the two groups (χ2=214.001, P<0.01). The proportion of intertrochanteric fracture (type 31-A), femoral neck (type 31-B) and femoral head fracture (type 31-C) was 46.59%, 49.74% and 3.67% respectively. The highest frequency of the sub-type in each fracture type was type 31-A2, type 31-B2 and type 31-C2.

CONCLUSIONSWomen have a higher rate than men in Southwest China. Geriatric patients are more than the young and middle-aged patients. The femoral neck fractures, intertrochanteric fractures and femoral head fractures are in descending orders according to the proportion of the three different hip fractures.

Aged ; Aged, 80 and over ; China ; epidemiology ; Female ; Femoral Fractures ; Femoral Neck Fractures ; Femur ; Femur Head ; Femur Neck ; Hip Fractures ; epidemiology ; Humans ; Incidence ; Male ; Middle Aged