Biomechanical analysis of adjacent segments after correction surgery for adult idiopathic scoliosis: a finite element analysis.

The biomechanical aspects of adjacent segment degeneration after Adult Idiopathic Scoliosis (AdIS) corrective surgery involving postoperative changes in motion and stress of adjacent segments have yet to be investigated. The objective of this study was to evaluate the biomechanical effects of corrective surgery on adjacent segments in adult idiopathic scoliosis by finite element analysis. Based on computed tomography data of the consecutive spine from T1-S1 of a 28-year-old male patient with adult idiopathic scoliosis, a three-dimensional finite element model was established to simulate the biomechanics. Two posterior long-segment fixation and fusion operations were designed: Strategy A, pedicle screws implanted in all segments of both sides, and Strategy B, alternate screws instrumentation on both sides. The range of motion (ROM), Maximum von Mises stress value of intervertebral disc (IVD), and Maximum von Mises stress of the facet joint (FJ) at the fixation adjacent segment were calculated and compared with data of the preoperative AdIS model. Corrective surgery decreased the IVD on the adjacent segments, increased the FJ on the adjacent segments, and decreased the ROM of the adjacent segments. A greater decrease of Maximum von Mises stress was observed on the distal adjacent segment compared with the proximal adjacent segment. The decrease of Maximum von Mises stress and increment of Maximum von Mises stress on adjacent FJ in strategy B was greater than that in strategy A. Under the six operation modes, the change of the Maximum von Mises stress on the adjacent IVD and FJ was significant. The decrease in ROM in the proximal adjacent segment was greater than that of the distal adjacent segment, and the decrease of ROM in strategy A was greater than that in strategy B. This study clarified the biomechanical characteristics of adjacent segments after AdIS corrective surgery, and further biomechanical analysis of two different posterior pedicle screw placement schemes by finite element method. Our study provides a theoretical basis for the pathogenesis, prevention, and treatment of adjacent segment degeneration after corrective surgery for AdIS.

Influence of polymorphisms in insulin-like growth factor-1 on the risk of osteoporosis in a Chinese postmenopausal female population.

We conducted a case-control study in a Chinese postmenopausal population, and explore the potential role of the promoter region variation of the IGF-1 gene in bone mineral density and osteoporosis risk. 485 postmenopausal women with a primary diagnosis of osteoporosis and 485 age-matched controls were selected between 2012 and 2014. The Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was used for rs35767, rs2288377 and rs5742612 of IGF-1 genotyping. By conditional regression analysis, individuals carrying TT genotype and CT+TT genotype of rs35767 were found to be correlated with an elevated risk of osteoporosis, with adjusted ORs (95% CI) of 1.90 (1.23-2.93) and 1.35 (1.04-1.76), respectively. Our study found that CT+TT genotype of rs35767 was significantly associated with moderate increased risk of osteoporosis in smokers and drinkers, and the ORs (95% CI) were 2.11 (1.06-4.20) and 2.36 (1.29-4.32), respectively. We found that those carrying CT+TT genotype of rs35767 had a significant lower BMD levels at L1-L4 vertebrae, femoral neck, total hip and trochanter compared to those with CC genotype. Our study suggests that TT genotype and CT+TT genotype of IGF-I rs35767 were associated with risk of osteoporosis and BMD levels.

[Advances in genome-wide association study of tuberculosis].

Tuberculosis, caused by Mycobacterium tuberculosis (MTB), is one of the oldest and most influential diseases in the history due to its devastating effect on health and high mortality rate worldwide. Tuberculosis causes more human deaths than any other single infectious disease and the incidence of the tuberculosis is increasing dramatically in recent years. Genome-wide association study (GWAS) has been used to delineate the genetic basis of tuberculosis, and several susceptibility genes and loci were found, which provids important clues to the early intervention and treatment of tuberculosis. However, due to difference in the population structure and host-pathogen interactions, GWAS on tuberculosis faces great challenges. In this review, we introduced the achievements of GWAS on tuberculosis, and illustrated challenges and strategies in the future study.

Lack of association between polymorphisms from genome-wide association studies and tuberculosis in the Chinese population.

Genome-wide association studies (GWAS) have identified rs4331426 and rs2057178 as being associated with tuberculosis (TB) in African populations. Both are common single nucleotide polymorphisms (SNPs) in Africans, but they are much rarer in Eurasian populations. In order to corroborate these results, we carried out a case-control study in the Chinese population; these 2 SNPs were genotyped in 600 pulmonary TB patients and 618 healthy controls. The results showed that neither of the SNPs was associated with TB, even after stratification by gender, age, and smear status. Considering the limitation of poor coverage of variations in commercial available genotyping platforms in African populations, further GWAS should be conducted in other populations such as Indian and Chinese. Moreover, future genetic studies on host susceptibility to TB need to take into account all the variables, including host, environment, pathogen, and interactions.

Association of angiotensinogen gene M235T and angiotensin-converting enzyme gene I/D polymorphisms with essential hypertension in Han Chinese population: a meta-analysis.

BACKGROUND: The polymorphisms of angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) genes have been linked to increased risk of essential hypertension in multiple populations, but the results were inconsistent. OBJECTIVES AND METHODS: To evaluate the associations of these polymorphisms with essential hypertension, we carried out a meta-analysis of the association studies within Han Chinese population. In this study, we reviewed two most commonly investigated polymorphisms, AGT M235T and ACE I/D, and provided summary estimates regarding their associations with essential hypertension. PubMed and China Biological Medicine Database were searched, and a total of 71 studies (31 studies for AGT M235T and 40 studies for ACE I/D) comprising 10 547 essential hypertension patients and 9217 controls from 23 provinces and special districts in China were finally included in this study. RESULTS: Statistically significant associations with essential hypertension were identified for TT genotype of AGT M235T polymorphism (odds ratio 1.54, 95% confidence interval 1.16-2.03, P = 0.002) and DD genotype of ACE I/D polymorphism (odds ratio 1.61, 95% confidence interval 1.32-1.98, P < 0.0001). Under dominant, recessive, and additive genetic models, positive associations were also found. The heterogeneity existed among the studies (P < 0.05), whereas the publication bias did not exist in both AGT analysis (P = 0.052) and ACE analysis (P = 0.103). CONCLUSION: The present meta-analysis suggests that AGT M235T and ACE I/D modulate the risk of essential hypertension in Han Chinese population.

A novel dual PI3Kalpha/mTOR inhibitor PI-103 with high antitumor activity in non-small cell lung cancer cells.

PI-103, the first synthetic multitargeted compound which simultaneously inhibits PI3Kalpha and mammalian target of rapamycin (mTOR) shows high antitumor activity in glioma xenografts. In the present study, clear antitumor activity was observed with PI-103 treatment in two gefitinib-resistant non-small cell lung cancer (NSCLC) cell lines, A549 and H460, by simultaneously inhibiting p70s6k phosporylation and Akt phosphorylation in response to mTOR inhibition. In addition, H460 cells with activating mutations of PIK3CA were more sensitive to PI-103 than A549 cells with wild-type PIK3CA. PI-103 was found to inhibit growth by causing G0-G1 arrest in A549 and H460 cells. Western blotting showed that PI-103 induced down-regulation of cyclin D1 and E1 and simultaneously up-regulated p21 and p27, associated with arrest in the G0-G1 phase of the cell cycle. Furthermore, p53, the tumor suppressor which transcriptionally regulates p21, was also upregulated with PI-103 treatment. Collectively, our results suggest that multitargeted intervention is the most effective tumor therapy, and the cooperative blockade of PI3Kalpha and mTOR with PI-103 shows promise for treating gefitinib-resistant NSCLC.