A rapid GC-FID method was developed to simultaneously determine residual levels of triethylamine(TEA),1,1,3,3-tetramethylguanidine(TMG),and diisopropylamine(DIPA)in the synthetic route of an active pharmaceutical ingredient(API).Due to the severe absorption of amines on GC stationary phases,GC columns with various stationary phases were evaluated for optimal peak shape and reproducibility.The final conditions used the Agilent CP-Volamine column to resolve the three amines in 12 min.Various inlet liners were also screened to further improve the sensitivity of the analysis.The Restek Siltek? liner was selected to achieve the desired detectability for the method.The quantitation limits were 4,3,and 4 μg/mL for TEA,DIPA,and TMG in the presence of API,respectively.All three amines showed good linearity(r＞0.999)and recoveries(＞90％)over the concentration range of 3 to 16 μg/mL.The testing of residual amines was initially performed at the penultimate stage of the synthesis.However,this work demonstrates that TMG can act as a proton sponge to react with salicylic acid,the counter ion of the penultimate,to form a volatile component that elutes at a different retention time.Consequently,in the final method,these three amines were monitored in the final API to circumvent the matrix interference.Key parameters of the method were qualified per method validation requirements in ICH guidelines.The method was successfully applied for batch testing during development and implemented as an in-process control procedure at manufacturing sites.

Objective To investigate the effects of sufentanil on stress hormone and hemodynamic parameters in patients with sepsis in ICU. Methods A prospective randomized controlled study was carried out to select 46 patients with sepsis admitted to the ICU of Guangzhou Red Cross Hospital from October 2014 to August 2016. The patients were randomly divided into the control group(group C), fentanyl group (group F) and sufentanil group (group S). Patients in group C were given active treatment of the primary disease, and anti-infection, nutritional support, maintenance of electrolyte balance and other comprehensive treatment. Patients in group F and group S were treated in the same way as group C, while fentanyl and sufentanil were applied separately into them. The analgesic goal was behavioral pain scale (BPS) ≤3 points. The changes of stress hormone [adrenocorticotropic hormone (ACTH), glucocorticoids (GC), norepinephrine (NE) and epinephrine (E)] and hemodynamic parameters [heart rate (HR), mean arterial pressure (MAP) and central venous pressure (CVP)] before and after treatment were compared, and adverse drug reactions were recorded. The quantitative data were compared by analysis of variance or t test, and the repeated measurement data were analyzed by repeated measures analysis of variance. The enumeration data were compared by Chi-square test or Fisher exact probability method. Results There were no significant changes in the levels of NE and E before treatment and at 2 and 6 h after the treatment in the three groups (P>0.05). Compared with before treatment, there were no significant changes in ACTH and GC levels at 2 and 6 h after treatment in group C (P>0.05), and ACTH and GC levels decreased in group F and group S at 2 and 6 h after treatment (P<0.05). Compared with group C, the levels of ACTH and GC in group F and group S were lower than those in group C at 2 and 6 h after treatment (P<0.05), but there was no significant difference between group F and group S (P>0.05). Compared with before treatment, the levels of HR were decreased at 2 and 6 h after the treatment in the three groups (P<0.05). Compared with group C, the levels of HR in group F and group S was lower than that in group C at 2 and 6 h after treatment (P<0.05), but there was no significant difference between group F and group S (P>0.05). Compared with before treatment, the levels of MAP increased in different degrees at 2 and 6 h after treatment in the three groups; Except for group F, there was significant difference between group C and group S (P<0.05). The levels of MAP in group F were lower than those in group C and group S at 2 and 6 h after treatment (P<0.05), but there was no significant difference between group S and group C (P>0.05). Conclusions Sufentanil has certain advantages in alleviating stress response in patients with sepsis in ICU. Its efficacy and safety are similar to that of fentanyl. What' more, it has more stable hemodynamics.

Objective:To study the effect of curcumin on enterocyte apoptosis and its protective effect on intestinal mucosal barrier in septic rats.Methods:Eighty-seven 3-month male Sprague-Dawley (SD) rats were divided into Sham group, model group and curcumin group by random number table method, with 29 rats in each group. The septic rat model was reproduced by cecal ligation and puncture (CLP). 4 mL dimethyl sulfoxide solution were intraperitoneally injected in both Sham group and model group, 200 mg/kg curcumin dissolved by 4 mL dimethyl sulfoxide solution were intraperitoneally injected in curcumin group 10 minutes after operation. The blood samples (15 rats in each group) were collected 2, 12, 24 hours after operation, and the levels of serum procalcitonin (PCT), tumor necrosis factor-α(TNF-α), D-lactic acid and diamine oxidas (DAO) were tested by enzyme linked immunosorbent assay (ELISA). The ileum tissues were collected 12 hours, 24 hours after operation in three groups, water content was tested by weighting, pathologic structure was observed by light microscope, the enterocyte apoptosis was tested by terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling method (TUNEL). The 7-day survival rate was observed in three groups (14 rats in each group).Results:The serum levels of PCT, TNF-α, D-lactic acid and DAO were higher in model group at 2, 12, 24 hours after operation than those in Sham group, PCT, TNF-α levels were significantly higher in model group than those in Sham group 2 hours after operation [PCT (μg/L): 1.89±0.17 vs. 0.10±0.02, TNF-α (ng/L): 216.51±1.47 vs. 85.25±8.20, both P < 0.01], D-lactic acid, DAO levels were significantly higher in model group than those in Sham group 12 hours after operation [D-lactic acid (mg/L): 40.53±7.76 vs. 11.29±1.28, DAO (ng/L): 1 120.40±302.35 vs. 330.02±81.28, both P < 0.01]. Compared with model group, the levels of serum PCT, TNF-α, D-lactic acid and DAO were lower in curcumin group 2, 12, 24 hours after operation, the statistical difference appeared from 12 hours after operation [PCT (μg/L): 5.37±0.44 vs. 8.67±0.64, TNF-α(ng/L): 211.12±4.31 vs. 313.30±18.46, D-lactic acid (mg/L): 29.74±1.41 vs. 40.53±7.76, DAO (ng/L): 810.71±201.41 vs. 1 120.40±302.35, all P < 0.05], curcumin group had lower water content in ileum tissues 12 hours, 24 hours after operation [(68.34±0.68)% vs. (70.55±0.87)%, (69.41±0.59)% vs. (71.69±0.87)%, both P < 0.05]. The pathologic structures of intestinal villus were normal in Sham group, however, in model group intestinal villus were atrophic, edematous and shorten 12 hours after operation, it was further exacerbated 24 hours after operation. Compared with model group, the pathologic structures of intestinal villus in curcumin group were relived 12 hours, 24 hours after operation. The number of apoptotic enterocytes were significantly increased in model group compared with Sham group 24 hours after operation (cells: 25.48±6.10 vs. 4.00±2.04, P < 0.05), and the number of apoptotic enterocytes was lower in curcumin group than that in model group at the same time (cells: 15.48±3.75 vs. 25.48±6.10), the difference was statistically significant (both P < 0.05). Seven-day survival rate was significantly lower in curcumin than that in model group [42.9% (6/14) vs. 50.0% (7/14)], however, the difference was not statistically significant ( P > 0.05). Conclusion:Curcumin can protect the intestinal mucosal barrier by inhibiting enterocyte apoptosis in septic rats.

Objective To investigate the feasibility of manual reduction with inverse shift for pronation-extorsion trimalleolar fracture by applying the finite element method combined with clinical experience. Methods Based on CT images and anatomical features of bone, ligaments and other tissues as well as material parameters, a normal ankle model with completed muscles and bones for a Chinese young male was established. According to the related characteristics of the pronation-extorsion trimalleolar fractures, fracture was simulated in the proper position to make osteotomy model. The finite element model of pronation-extorsion trimalleolar fractures was thus established and then applied with mechanical loading to simulate manual reduction with inverse shift. Results The established finite element model of pronation-extorsion trimalleolar fractures was effectively restored by the displacement loading. Conclusions The finite element analysis on pronation-extorsion trimalleolar fractures by inverse shift maneuver could further prove the feasibility, effectiveness and scientificity of manual reduction with inverse shift based on clinical experience.