Pharmacogenetic Correlates of Antipsychotic-Induced Weight Gain in the Chinese Population / 神经科学通报·英文版

Antipsychotic-induced weight gain (AIWG) is a common adverse effect of this treatment, particularly with second-generation antipsychotics, and it is a major health problem around the world. We aimed to review the progress of pharmacogenetic studies on AIWG in the Chinese population to compare the results for Chinese with other ethnic populations, identify the limitations and problems of current studies, and provide future research directions in China. Both English and Chinese electronic databases were searched to identify eligible studies. We determined that > 25 single-nucleotide polymorphisms in 19 genes have been investigated in association with AIWG in Chinese patients over the past few decades. HTR2C rs3813929 is the most frequently studied single-nucleotide polymorphism, and it seems to be the most strongly associated with AIWG in the Chinese population. However, many genes that have been reported to be associated with AIWG in other ethnic populations have not been included in Chinese studies. To explain the pharmacogenetic reasons for AIWG in the Chinese population, genome-wide association studies and multiple-center, standard, unified, and large samples are needed.

Glucocorticoids+cyclophosphamide+tacrolimus capsules in type Ⅲ+Ⅴ and Ⅳ+Ⅴ lupus nephritis / 中国生化药物杂志

Objective To explore the efficacy and safety of glucocorticoids+cyclophosphamide+tacrolimus capsules (GC+CTX+FK506) in the treatment of patients with type Ⅲ+V and Ⅳ+Vlupus nephritis. Methods The 31 cases with first diagnosis as systemic lupus erythematosus (SLE) with type Ⅲ+V and Ⅳ+Vlupus nephritis (LN) were selected, then divided into group A (CTX+GC) with 16 cases and group B (FK506+CTX+GC) with 15 cases. The group A received CTX+GC during treatment, group B received GC+CTX+FK506 for the first three months, and received FK506+GC for the last three months. The patients were followed up once monthly to observe the efficacy and safety,the efficacy was analysed after 6 months. Results After treatment, the total efficacy in group B was significantly higher than group A (86.7%vs.50.0%, P<0.05). The 24 h urine protein of group B was lower than group A(P<0.05). The plasma albumin of group B was higher than group A (P<0.05). After treatment, the systemic lupus erythematosus disease activity index (SLEDAI) in two groups were lower and C3 level was higher than those pre-treatment(P<0.05), but there was no significant difference in above indicators between two groups. There was one case menelipsis in group A, and one case with transient increasing of creatinine. Conclusion The FK506+CTX+GC could reduce urine protein sifnificantly compared with CTX+GC without serious adverse reaction.

Osthole ameliorates glutamate-induced toxicity in HT22 cells via activating PI3K/Akt signaling pathway / 中南大学学报(医学版)

OBJECTIVE@#To investigate the neuroprotective effects of osthole (OST) on glutamate-induced toxicity in hippocampal HT22 cells and to explore the correlation between the protection and phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling pathway.
@*METHODS@#The cell injury model of HT22 was induced by glutamate and the cell viability was detected by MTS assay. The lactate dehydrogenase (LDH) release and the caspase-3 activity were determined by commercial kits. Western blot analysis was utilized to detect the protein levels of PI3K, Akt, p-PI3K and p-Akt. 
@*RESULTS@#OST markedly improved the cell survival and decreased the LDH release in glutamate-treated HT22 cells in a dose-dependent manner. Furthermore, the levels of p-PI3K and p-Akt proteins were significantly increased in glutamate and OST-co-treated HT22 cells. The effect of OST on p-Akt phosphorylation in HT22 cells was attenuated in the presence of PI3K specific inhibitor (LY294002).
@*CONCLUSION@#OST protects HT22 cells from glutamate excitotoxicity through a mechanism involving the activation of PI3K/Akt signaling pathway.

Effects of chrysophanol on BDNF and iNOS together with oxidative stress in rats with diabetes-associated cognitive decline / 中国药理学通报

Aim To assess the protective role of chry-sophanol in rats with diabetes-associated cognitive de-cline (DACD) and explore the potential molecular mechanisms.Methods The learning and memory performance was assessed by Morris water maze test;the activities of AChE,ChAT,iNOS and oxidative stress markers including CAT,SOD and GSH-PX in the hippocampus were detected using respective com-mercial kits.The level of BDNF was also measured with commercial ELISA kit.Results Chrysophanol significantly improved learning and memory functions in the diabetic groups.Additionally,the activities of AChE,BDNF also found to be evidently increased, while decreased activities of ChAT,iNOS,CAT,SOD and GSH-PX were observed in the hippocampus of dia-betic rats.Conclusions Collectively,chrysophanol has a protective role against DACD and this neuropro-tection is associated with increasing BDNF level.Chry-sophanol can also suppress the activities of iNOS, CAT,SOD and GSH-PX in diabetic rats.It is likely to be a novel therapeutic drug for the treatment of diabetic patients with cognitive deficits in clinical practice.

Characteristics of pelvic diaphragm hiatus in pregnant women with stress urinary incontinence detected by transperineal three-dimensional ultrasound / 中华妇产科杂志

Objective To identify the morphological characteristics of pelvic diaphragm hiatus in pregnant women with stress urinary incontinence ( SUI) by transperineal three-dimensional (3-D) ultrasound.Methods From Oct.2008 to Mar.2009,145 pregnant women (third trimester group) at 37-41 weeks of gestation underwent transperineal 3-D ultrasound investigation at Department of Obstetrics and Gynecology,the Sixth People's Hospital,Shanghai Jiaotong University,including 38 pregnant women with stress urinary incontinence (SUI) and the other 107 non SUI pregnant women.In the mean time,50 normal nulliparous healthy women were chosen as control group.The morphological characteristics of pelvic diaphragm hiatus,the diameter of pelvic diaphragm hiatus,pubovisceral muscle thickness and genitohiatal and levator ani angle were measured at rest,on maximum Valsalva and maximum pelvic floor contraction by 3-D ultrasound,respectively.Results Loosen connective tissue and pubococcygeus avulsion were observed in some pregnant women at third trimester.The area of pelvic diaphragm hiatus were (15.2 ±1.9),(16.4 ± 2.0) and (13.6±1.9) cm2,pubovisceral muscle thickness were (0.72 ±0.11),(0.68 ±0.14) and(0.77 ±0.11) cm,levator ani angle were (60 ±8) °,(57±10) ° and (64 ± 14)° at rest,on maximum Valsalva and maximum pelvic floor contraction respectively.These parameters were significantly increased than those in control group[(11.2 ±2.6),(14.5 ±4.5) and (9.2 ±2.6) cm2; (0.66 ±0.10),(0.67 ± 0.14) and (0.71 ±0.14) cm; (50 ±4) °,(51 ±5) ° and (46 ±5)°]at three maneuvers,respectively ( P <0.05).And those parameters of the anteroposterior hiatal diameter,lateral hiatal diameter,perimeter of pelvic diaphragm hiatus and area of pelvic diaphragm hiatus in SUI pregnant women were increased than those in non SUI pregnant women at three maneuvers,respectively (P < 0.05 ).Pubovisceral muscle thickness in SUI pregnant women was significantly lower than that in non SUI pregnant women at maximum pelvic floor contraction (P < 0.05 ),but there were not significant difference between SUI and non SUI pregnant women at rest and on maximum Valsalva in pubovisceral muscle thickness and genitohiatal and levator ani angle (P >0.05).Conclusions Pelvic floor anatomic remodeling is identified in late pregnant women.When compared with non pregnant women,the loosen pelvic floor connective tissue and the bigger diameters of pelvic diaphragm are observed in late pregnant women.It is observed that the increased diameters of pelvic diaphragm and decreased thickness of pubovisceral muscle in later pregnant SUI women than those in non SUI pregnant women.