Pinoresinol diglucoside activates Nrf2 pathway to improve osteoporosis in mice / 中华内分泌外科杂志

Objective:Rosin alcohol two glycosidase (pinores inoldiglucoside, PDG) effect on the improvement of the osteoporosis in mice and the possible mechanism of action.Methods:A mouse model of osteoporosis was established by removing bilateral ovaries. According to the random number table method, 50 mice were divided into model (MOD) group (equal volume of normal saline), positive control (PC) group (0.2 mg/kg estradiol), PDG-low dose (L) group (5 mg/kg) PDG), PDG-high dose (H) group (10 mg/kg PDG by gavage) and PDG-H+ML385 group (10 mg/kg PDG by gavage after intramuscular injection of 30 mg·kg-1 ML385), 10 mice in each group; Another 10 mice without any ovarian treatment were selected as sham group (intragastric administration of the same amount of normal saline). After 3 weeks of drug intervention, the serum alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP), interleukin-6 (IL-6) and tumor necrosis factor were detected by enzyme-linked immunosorbent assay (ELISA) -α (TNF-α). The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by dual energy X-ray. The mRNA and protein expression levels of nuclear factor related factor 2 (Nrf2), oxidase heme oxygenase 1 (HO-1), quinone oxidoreductase 1 (NQO1) were detected by real-time fluorescence quantitative PCR (qRT-PCR) and Western blot, respectively.Results:The serum ALP levels in Sham, MOD, PC, PDG-L, PDG-H and PDG-H + ML385 groups were (25.88±3.42), (47.42±5.32), (36.20±3.37), (38.95±3.24), (29.66±2.64), (39.57±2.06) U/dL, respectively; The serum trap levels were (2.18±0.40), (4.69±0.83), (3.58±0.38), (3.67± 0.48), (2.93±0.26), (3.81±0.49) U/L, respectively; BMD (153.04±12.96), (86.25±6.71), (126.53±8.99), (119.77±8.84), (139.18±15.94), (92.09±4.17) mg/cm 2; The expression levels of Nrf2 mRNA were 1.00±0.00, 0.35±0.04, 0.67±0.05, 0.54±0.03, 0.82±0.08 and 0.48±0.04, respectively; The expression levels of HO-1 mRNA were 1.00±0.00, 0.25±0.03, 0.56±0.03, 0.47± 0.03, 0.71±0.04 and 0.37±0.04, respectively; The expression levels of nqo1mrna were 1.00±0.00, 0.38± 0.02, 0.63±0.03, 0.58±0.04, 0.79±0.05 and 0.44±0.03, respectively; Nrf2 protein expression levels were 0.98±0.08, 0.26±0.04, 0.52 ±0.06, 0.46±0.03, 0.86±0.07, 0.45±0.05. HO-1 protein expression levels were 0.39±0.02, 0.09±0.01, 0.15 ±0.03, 0.17±0.03, 0.26±0.03, 0.12±0.02. NQO1 protein expression levels were 0.53±0.03, 0.21±0.02, 0.38±0.04, 0.29±0.02, 0.55±0.03, 0.24±0.04, respectively; The levels of serum IL-6 were (104.25±11.35), (515.38±74.48), (351.78± 65.12), (364.73±36.64), (246.18±17.52), (408.93±32.56) pg/ml, respectively; The levels of serum TNF-α were (33.79±3.55), (170.11±19.24), (76.09±8.99), (84.95±6.12), (66.98±3.73), (119.04±9.75) pg/mL, respectively; The serum SOD levels were (258.47±19.25), (72.15±8.12), (187.60±14.63), (152.61±12.36), (204.22±19.65), (138.01±13.62) U/mL, respectively; The serum MDA levels were (2.02±0.27), (4.75±0.73), (3.19±0.46), (3.7±0.49), (2.91±0.42), (4.10 ±0.25) μmol/L respectively. There were significant differences between MOD group and Sham group, or PC, PDG-L, PDG-H, PDG-H+ML385 group and MOD group,or PDG-H+ML385 group and PDG-H ( P<0.05) . Conclusion:PDG can reduce bone inflammation and oxidative stress by activating Nrf2 pathway and improve the state of osteoporosis.

Impact of interleukin-6 gene polymorphisms and its interaction with obesity on osteoporosis risk in Chinese postmenopausal women

AIMS@#To investigate the association of four single-nucleotide polymorphisms (SNPs) of the IL-6 gene with osteoporosis (OST) susceptibility.@*METHODS@#PCR restriction fragment length polymorphism (PCR-RFLP) was carried out for SNPs detection. Generalized multifactor dimensionality reduction (GMDR) model and logistic regression model were used to examine the interaction between SNP and obesity on OST.@*RESULTS@#Logistic regression model revealed that G allele of rs1800796 and the T allele of rs2069849 were associated with increased OST risk, compared to those with wild genotype. However, no significant correlations were found when analyzing the association of rs1800795 and rs1554606 with OST risk. GMDR analysis suggested that the interaction model composed of the rs1800796 and obesity was the best model with statistical significance (P value from sign test [P] = 0.012), indicating a potential gene-environment interaction between rs1800796 and obesity. Overall, the two-locus models had a cross-validation consistency of 10/10 and had the testing accuracy of 0.641. We also conducted stratified analysis for rs1800796 genotype and obesity, and found that obese subjects with CG or GG genotype have the highest OST risk, compared to subjects with CC genotype, and normal BMI OR (95% CI) = 2.21 (1.52-3.49), after adjustment for age, smoke, and alcohol consumption status.@*CONCLUSIONS@#Our results suggested that the C allele of rs1800796 and the C allele of rs2069849 of IL-6 gene interaction between rs1800796 and abdominal obesity were all associated with increased OST risk.

Cervical laminoplasty using titanium miniplate for multisegmental cervical spondylotic myelopathy / 中国医师杂志

Objective To evaluate the clinical outcome of cervical laminoplasty using titanium miniplate ( AO arch) for the treatment of multisegmental cervical spondylotic myelopathy (MCSM).Methods 21 patients with MCSM were operated by cervical posterior unilateral open-door laminoplasty combined with titanium miniplate internal fixation.The JOA score,sagittal diameter of the spinal canal in the midline (SD) and cervical curvature index according to the measurement of Penning method before surgery and at postoperative follow-up intervals were measured and compared by one-way analysis of variance.Results All patients were followed up for 9 ～48 months.There were no severe adverse events.CT sean showed bony fusion at hinge side since six months after operation.According to the JOA score evaluation system,al final follow-up period,9 cases were excellent,7 good,3 ordinary and 2 cases bad.Recovery rate was 62.5 ％ at final follow-up interval.Cervical SD before surgery and in posloperative one month were (9.2 ± 1.1 )mm,(13.5 ± 1.4) mm,respectively.The difference was significant between them( t =3.02,P ＜ 0.01 ),but there was no improvement since one month postoperatively ( P ＞ 0.05 ).Cervical curvature index was ( 12.6 ± 14.7 ) ° preoperatively,it was ( 17.1 ± 12.4 ) ° at final follow-up interval,indicating that cervical curvature index made obvious progress at final follow-up interval ( t =8.26,P ＜ 0.01 ),but there was no significant change within six months postoperatively ( P ＞ 0.05 ).Conclusions Cervical laminoplasty combined with titanium miniplate can enlarge and maintain cervical SD,ameliorate cervical curvature and neurological function,and it is an ideal alternative treatment for MCSM.