Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons (MNs) with large unmet medical needs. Multiple pathological mechanisms are considered to contribute to the progression of ALS, including neuronal oxidative stress and mitochondrial dysfunction. Honokiol (HNK) has been reported to exert therapeutic effects in several neurologic disease models including ischemia stroke, Alzheimer's disease and Parkinson's disease. Here we found that honokiol also exhibited protective effects in ALS disease models both in vitro and in vivo. Honokiol improved the viability of NSC-34 motor neuron-like cells that expressed the mutant G93A SOD1 proteins (SOD1-G93A cells for short). Mechanistical studies revealed that honokiol alleviated cellular oxidative stress by enhancing glutathione (GSH) synthesis and activating the nuclear factor erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) pathway. Also, honokiol improved both mitochondrial function and morphology via fine-tuning mitochondrial dynamics in SOD1-G93A cells. Importantly, honokiol extended the lifespan of the SOD1-G93A transgenic mice and improved the motor function. The improvement of antioxidant capacity and mitochondrial function was further confirmed in the spinal cord and gastrocnemius muscle in mice. Overall, honokiol showed promising preclinical potential as a multiple target drug for ALS treatment.

Objective :To explore rehabilitative effect of low—frequency (1Hz ,LF) repetitive transcranial magnetic stimulation (rTMS) combined functional electrical stimulation (FES) on lower limb spasm and motor function in pa—tients with subacute ischemic stroke (SAIS).Methods : A total of 92 SAIS patients with lower limb spasm and motor dysfunction hospitalized in our department were randomly divided into sham stimulation + FES group (sham stimu—lation group ,n＝45) and low—frequency rTMS + FES group (LF—rTMS group ,n＝47) ,both groups were continu—ously treated for three weeks .Lower limb motor function and spasm severity were assessed by Fugl—Meyer motor as—sessment (FMA) and modified Ashworth scale (MAS) respectively before and after treatment ,and motor evoked potential (MEP) was detected .Results : Compared with before treatment ,there was significant rise in FMA score , and significant reductions in MAS score and MEP in two groups after three—week treatment , P＝ 0.001 all ;com—pared with sham stimulation group ,there was significant rise in FMA score [16. 0 (13.0 ,23. 5 ) scores vs. 19. 0 (16.0 ,27.0) scores] ,and significant reductions in MAS score [1. 5 (1. 3 ,1.5) scores vs. 1. 0 (0. 5 ,1. 5) scores] and MEP [ (24.64 ± 0. 39) ms vs. (24.43 ± 0.31) ms] in LF—rTMS group after treatment , P＜0.05 or ＜ 0. 01 . Conclusion : Compared with sham stimulation + FES ,LF—rTMS + FES can more significantly improve lower limb spasm and motor function in patients with subacute ischemic stroke .

Objective To discuss the clinical effect of prophylactic abdominal aorta balloon occlusion with Fogarty catheter before cesarean section in treating delivery woman with pernicious placenta previa.Methods The clinical data of 12 delivery women with pernicious placenta previa,who received prophylactic abdominal aorta balloon occlusion with Fogarty catheter before cesarean section,were retrospectively analyzed.The curative effect was evaluated.Results The average intraoperative blood loss in the 12 patients was (1256±318) ml.The uterus was successfully retained in 9 patients.Hysterectomy had to be carried out in 3 patients because of refractory hemorrhage;one of them had to receive total hysterectomy together with bladder repair as the placenta had penetrated into the bladder wall.After delivery no complications,such as infection,delayed hemorrhage,lower limb thrombosis,etc.,occurred.All 12 neonates were born smoothly.Conclusion Prophylactic abdominal aorta balloon occlusion with Fogarty catheter before cesarean section can effectively reduce intraoperative blood loss and help save the uterus.Therefore,it is a safe and effective therapeutic means for delivery woman with pernicious placenta previa before the performance of cesarean section.

Objective: To investigate the effects and mechanism of Holothurian Glycosaminoglycan (hGAG) alone in combination with cisplatin (DDP) on apoptosis of pulmonary adenocarcinoma cell A549. Methods: A549 cells were separately treated with blank, hGAG, DDP and hGAG combined with DDP (hGAG + DDP). The cell morphology in 4 groups was observed using light microscope. CCK8 assay was used to determine the cell viability. Flow cytometry by Hoechst 33258 and AnnexinV-FITC/PI staining was applied to detect cell apoptosis. Western blot was then used to detect the protein expression of Bax, Bcl-2, survivin and caspase-3. Results: After treatment for 24 h, the inhibitory rates of A549 cells in control, hGAG, DDP and hGAG + DDP groups were 0, (19.74±5.39)%, (42.01±2.57)% and (53.89±4.58)%, respectively. Moreover, after treatment for 48 h and 72 h, the inhibitory rates in each group were 0, (23.17±4.78)% and (29.17±4.21 )%, (54.00±7.64)% and (59.35±7.31)%, as well as (77.58±4.26)% and (79.94±4.58)%, respectively. The cell viability was significantly lower in drug treatment groups compared with those in control group at the same time point (P<0.05). Hochest 33258 staining showed that no obvious apoptotic cells were detected in the control group, while apoptotic cells were visible in hGAG, cisplatin and combination groups. Flow cytometry showed that cell apoptotic rates were (2.38±0.59)%, (12.59±4.22)%, (16.36±3.63)% and (44.60±5.45)% in the control, hGAG, DDP and hGAG + DDP groups, respectively. The cell apoptosis was significantly lower in drug treatment groups compared with those in control group at the same time point (P<0.05). Furthermore, western blot results showed that the expression of Bax and caspase-3 protein was increased (P<0.05), whereas Bcl-2 and survivin was decreased (P<0.05) in the hGAG+ DDP group compared with cisplatin alone (P<0.05). Conclusions HGAG can inhibit the proliferation and promote the apoptosis of human lung adenocarcinoma A549 cells. Meanwhile, it can strengthen the chemosensitivity of A549 cells to DDP via up-regulation of Bax, caspase-3 and down-regulation of Bcl-2 and survivin.

Objective: To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m², 10 mg/m² or 12 mg/m² as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) . Methods: A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m²) as induction chemotherapy in newly diagnosed patients of adult AML. Results: Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m² group, IDA 10 mg/m² group and IDA 12 mg/m² group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m² group and IDA 12 mg/m² group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m² group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m² was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m² when compared with the IDA 8 mg/m² was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×10⁹/L in IDA 8 mg/m² group, IDA 10 mg/m² group and IDA 12 mg/m² group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×10⁹/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) . Conclusions For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m² is clinically superior to IDA 8 mg/m² and IDA 12 mg/m² in favorable intermediate AML subgroup. However, idarubicin 12 mg/m² is more suitable to adverse AML subgroup.

To analyse and compare the characteristics of the intestinal absorption of puerarin, baicalin, berberine and liquiritin in different combinations of Gegenqinlian decoction based on pharmacokinetic parameters, a sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was applied for the quantification of four components in rat's plasma. And pharmacokinetic parameters were determined from the plasma concentration-time data with the DAS software package. The influence of different combinations on pharmacokinetics of four components was studied to analyse and compare the absorption difference of four components, together with the results of the in vitro everted gut model and the rat single pass intestinal perfusion model. The results showed that compared with other combinations, the AUC values of puerarin, baicalin and berberine were increased significantly in Gegenqinlian decoction group, while the AUC value of liquiritin was reduced. Moreover, the absorption of four components was increased significantly supported by the results from the in vitro everted gut model and the rat single pass intestinal perfusion model, which indicated that the Gegenqinlian decoction may promote the absorption of four components and accelerate the metabolism of liquiritin by the cytochrome P450.

ObjectiveTo discuss the clinical diagnosis and treatment of multiple endocrine neoplasia ( MEN ) 2A, and report the mutation of the RET proto-oncogene in a pedigree of three patients with MEN 2A.MethodsBilateral adrenalectomy was performed on two of the three patients with hypertension and bilateral adrenal-conserving adrenal pheochromocytoma resection was performed on the other patient. All three patients were treated by total thyroidectomy and neck lymphadenectomy. Twelve family members were recruited to the study. Peripheral blood was collected and total genomic DNA was prepared for polymerase chain reaction (PCR). PCR products of exon 10 and exon 11 of the RET proto-oncogene were purified and a direct DNA sequence analysis was performed.ResultsThe pathological diagnosis of the specimens was bilateral adrenal pheochromocytoma and medullary thyroid carcinoma in all the three patients. There was no tumor recurrence or distant metastasis after 1.5 - 5 years of follow-up. A missense mutation of TGC (Cys)to CGC (Arg) at codon 634 in exon 11 of the RET proto-oncogene was detected in all three patients. Genetic screening identified two mutation carriers in the other members of this pedigree.ConclusionGenetic mutation screening and surgical intervention may be helpful to the members of high-risk families.

Objective To establish the reference ranges of the spatial angles among cardiac chambers and great vessels in second and third trimester fetuses measured by spatiotemporal image correlation (STIC).Methods Volume images of 352 normal fetuses from 20 to 38 weeks of gestation were recruited in the study.An off-line analysis of acquired volume datasets was carried out with multiplanar mode.Parameters measured included angles between:(1) the 4-chamber view and the left ventricular long axis view; (2) the left ventricular long axis view and main pulmonary artery; and (3) the ductal arch and aortic arch.The relationships between above-mentioned angles and gestational age were assessed by correlation and regression analysis.Results The angle between the 4-chamber view and the left ventricular long axis view (range:55.7° - 35.7°,mean:45.7° ± 5.12°) was uncorrelated with gestational age (r = 0.03,P = 0.51).In contrast,the angle between the left ventricular long axis view and main pulmonary artery,and the angle between the ductal arch and aortic arch were correlated with gestational age (P ＜ 0.001),and the correlation coefficient was - 0.53 and 0.57 respectively.The best-fit exponential curve regression equations of the angle between the left ventricular long axis view and main pulmonary artery was:Y = 154- 4.24X +0.05X2 ,and the angle between the ductal arch and aortic arch was:Y = - 20.8 + 2.65X - 0.37X2.Conclusions The angles among cardiac chambers and great arteries of fetuses from 20 to 38 weeks of gestation can be quantitatively measured by STIC.The reference ranges provide a reliable quantitative standard to estimate the spatial relationships of the cardiac large arteries of fetuses,which may be clinically useful in prenatal screening congenital heart disease.

A sensitive and reliable liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI-MS/MS) method was established to simultaneously quantitate four categories of compounds (isoflavonoids, flavonoids, alkaloids and saponins) in Gegen-Qinlian decoction (GQD). These compounds were separated by a Shiseido CAPCELL PAK C18 column with a linear gradient consisting of 0.1% (v/v) formic acid in water (A) and 0.1% (v/v) formic acid in acetonitrile (B), and delivered at a flow rate of 0.3 mL/min. All the analytes were determined by electrospray positive ionization tandem mass spectrometry in a multiple reaction monitoring (MRM) mode. Linearity, accuracy, precision, recovery and stability of the method were evaluated with the validation over the range of 4.0-538 5 ng/mL. The proposed method was applied to the analysis of a Chinese herbal preparation GQD successfully.

OBJECTIVE To find out the reasons for the failure of sterilization of low temperature plasma antiseptic,and make corresponding measures to improve and standardize the plasma sterilization methods.METHODS A total of 280 times with the plasma sterilization by Johnson & Johnson STERRAD100S from the November 2007 to 2008 were conducted.RESULTS Among the antiseptic 280 pots,255 pots were completed smoothly.Another 25 pots were finished after removing the barriers.CONCLUSIONS The STERRAD100S low temperature plasma antiseptic is used standardizedly,taking effective measure,to speed up cycling rate of surgery instruments,reducing precious instrument's purchase and enhancing the antiseptic effect.It can positively use in operating room for antiseptic disinfection.