Cephalosporins are widely used antibiotics owing to their broad activity spectra and low toxicity. Many of these medically important compounds are made chemically from 7-aminodeacetoxycephalosporanic acid. At present, this intermediate is made by synthetic ring-expansion of the inexpensive penicillin G to form G-7-ADCA, followed by enzymatic removal of the side chain to obtain 7-ADCA. The chemical synthetic process is expensive, complicated and environmentally unfriendly. Environmentally compatible enzymatic process is favorable compared with chemical synthesis. In our previous research, metabolic engineered Escherichia coli strain (H7/PG15) was constructed and used as whole-cell biocatalyst for the production of G-7-ADC with penicillin G as substrate. The whole-cell biocatalysis was studied by single factor experiment, including the composition of substrates and the conversion conditions (OD600, pH, concentration of penicillin G, MOPS, glucose, time and FeSO4). After optimization, 15 mmol/L of G-7-ADCA was obtained. The process is convenient, efficient and economic. This work would facilitate the industrial manufacturing and further product research.
Anti-Bacterial Agents ; biosynthesis ; Biocatalysis ; Cephalosporins ; biosynthesis ; Escherichia coli ; metabolism ; Metabolic Engineering

Objective To evaluate the value of continuous glucose monitoring system (CGMS) in the gestational patients with impaired glucose regulation. Methods The glucose level in the subcutaneous tissue was monitored by CGMS for 3 days in 6 patients with gestational diabetes mellitus (GDM) and 6 patients with gestational impaired glucose tolerance (GIGT). The fluctuation coefficient of blood glucose, percentage of hyperglycemic time, and percentage of hypoglycemic time were calculated. Results As shown by CGMS, the fluctuation coefficient of blood glucose, mean glucose level, percentage of hyperglycemic time, percentage of hypoglycemic time, mean fasting blood glucose, and mean postprandial blood glucose (PBG) levels were not significantly different between GDM group and GIGT group (P ＞ 0. 05). The time for reaching the peak PBG level ranged 90-120minutes in both two groups (P ＞ 0. 05). No sensor-related adverse events were noted. Conclusions It is safe to apply CGMS sensor in pregnant women. The blood glucose profiles are comparable between GDM and GIGT patients by CGMS; therefore, control of blood glucose should be equally strict in patients with GIGT as those with GDM.

OBJECTIVETo assess the clinical outcomes of balloon kyphoplasty assisted with calcium phosphate cement (CPC) in treating osteoporotic vertebral fractures (OVF).

METHODSFrom January 2009 to January 2011, 26 patients with osteoporotic vertebral fractures were treated with balloon kyphoplasty assisted with CPC, including 31 vertebrae. There were 15 males and 11 females with an average age of (71.67 +/- 4.36) years old (ranged from 60 to 89 years). Course of disease was from 0.5 to 7 days with an average of 3.2 days. Clinical outcomes were assessed by the visual analogue scale (VAS) and the oswestry disability index (ODI). Vertebral height loss and kyphotic angle were measured by X-rays.

RESULTSAll patients were followed up for 10 to 24 months with an average of 18 months. Before operation, 24 hours after operation and at final follow-up, VAS scores were 7.91 +/- 1.20, 3.22 +/- 1.12, 1.92 +/- 0.83, respectively; ODI scores were 40.00 +/- 1.15, 17.00 +/- 2.12, 13.00 +/- 1.42, respectivesly; vertebral heights were (18.21 +/- 3.21), (23.82 +/- 3.10), (21.85 +/- 3.24) mm, respectivesly; vertebral kyphosis angles were (18.21 +/- 3.21) degrees, (7.42 +/- 3.13) degrees, (10.01 +/- 3.11) degrees, respectivesly. There was significant difference between preoperation and 24 hours after operation, and between final follow-up and preoperation (P < 0.05). There was no significant difference between final follow-up and 24 hours after operation (P > 0.05).

CONCLUSIONBalloon kyphoplasty assisted with calcium phosphate cement (CPC) is effective for the treatment of osteoporotic vertebral fractures (OVF), which can expeditiously relieve pain and effectively rebuild height of vertebral body and kyphotic angle, and also has advantages of minimal trauma and good security.

Aged ; Aged, 80 and over ; Bone Cements ; Calcium Phosphates ; therapeutic use ; Female ; Humans ; Kyphoplasty ; methods ; Male ; Middle Aged ; Osteoporotic Fractures ; surgery ; Spinal Fractures ; surgery ; Visual Analog Scale

Objective To study the pharmacokinetics and pharmacodynamics of the 40/60 premixed recombinant human insulin injection preparation,and to compare with 30/70 preparation,regular insulin,and neutral protamine Hagedorn (NPH).Methods In this positive control,single dose,open label,Latin square crossover study,20 male healthy volunteers were recruited from May 2006 to March 2007,and divided into four groups.On 4 test days,40/60 preparation,30/70 preparation,regular insulin,and NPH were administered to each of the 4 groups,the interval was 7-70 days before 2 test days.The pharmacokinetics and pharmacodynamics were evaluated by euglycemic glucose clamp technique.Results According to the analysis of variance,there were statistically significant differences in pharmacokinetics and pharmacodynamics of the 4 insulin formulations between the 4 groups (all P ＜ 0.05).For the 40/60 premixed recombinant human insulin,the pharmacokinetic parameter time to peak (Tmax) and mean retention time (MRT) were (105.00 ±24.33) minutes and (321.77 ± 56.29) minutes,respectively;the glucose-lowering effects reflected by the pharmacodynamic parameter Tmax and MRT were (167.75 ± 26.48) minutes and (248.33 ± 14.96) minutes,respectively.Compared with 30/70 premixed recombinant human insulin,40/60 preparation showed no significant differences in the pharmacokinetics parameters of blood insulin concentration,including peak concentration [(91.67 ± 13.03) mU/L vs.(84.96 ± 14.75) mU/L,P =0.119],Tmax [(105.00 ± 24.33) minutes vs.(122.25 ± 39.35) minutes,P =0.128],MRT [(321.77 ± 56.29) minutes vs.(332.12 ± 49.20) minutes,P =0.645] and area under the curve in 0-16 hours [AUCIns 0-16,(24 918 ± 6 610)h · mU/L vs.(26 768 ± 8 032)h· mU/L,P=0.084];however,statistically significant differences were observed in AUCIns0-4 [(16 991 ± 3 673) h · mU/L vs.(12 407 ± 3 441) h · mU/L,P =0.042] and AUCIns 0-8 [(23 283 ± 4 939) h · mU/L vs.(19 397 ±5 314)h · mU/L,P =0.046].Pharmacodynamic parameters showed no statistically significant differences (all P ＞ 0.05).Compared with 30/70 premixed insulin,the relative bioavailability of 40/60 premixed insulin was (118.9 ± 35.9) ％,and the relative biological effectiveness was (106.6 ± 35.2) ％.There was no clinically significant abnormalities in the safety indexes before and after the tests.No hypoglycemic events,allergic reactions,or local injection adverse reaction occurred in this trial.Conclusions The 40/60 premixed recombinant human insulin preparation demonstrated different properties in insulin absorption in 8 hours after injection compared with the 30/70 preparation,mainly because of the difference in proportions of short-and intermediate-acting insulin in the mixture.This new premixed insulin may provide a new option for personalized diabetes management.

Objective To study the pharmacokinetics and pharmacodynamics of recombinant human insulin preparations SciLin TM R and Humulin (R) R,and to evaluate their bioequivalence in Chinese healthy volunteers.Methods In this positive control,single dose,open label,randomized cross-over study,20 male healthy volunteers were recruited from March to October 2007,and tested on two experimental days with an interval of 7-14 days.The volunteers were divided into two groups with a random number table,one group was injected with SciLin TMR for the first time and Humulin (R) R for the second time,the other group was injected with the opposite.The pharmacokinetics and pharmacodynamic properties were evaluated by euglycemic glucose clamp study.Results Time to peak concentration [Tmax,(105.8 ± 19.1) minutes vs.(103.5 ± 18.1) minutes,P =0.389) and time to maximum glucose infusion rate [TGIRmax,(132.8 ± 16.8) minutes vs.(132.8 ± 18.6) minutes,P =0.697] for SciLin TMR and Humulin(R) R were similar.The relative bioavailability of SciLin TMR was (102.2 ± 7.6) ％,and the relative biological effectiveness was (107.4 ± 18.8) ％.The 90％ confidence interval(CI) of peak concentration(Cmax) and area under the curve of blood glucose concentration at 0-10 hours (AUCIns 0-10) of SciLin TM R were 99.32 ％-102.62 ％ (equivalent range 70％-143 ％) and 98.98 ％-104.99 ％ (equivalent range 80％-125％),respectively;90％ CI of the maximum glucose infusion rate (GIRmax) and AUCGIR0-10 were 97.36％ ～ 103.49％ (equivalent range 70％-143％) and 98.72％-113.54％ (equivalent range 80％-125％),respectively,indicating that SciLin TMR and Humulin (R) R was bioequivalent.There was no clinically significant abnormalities in the safety indexes before and after the tests.During the trial,no hypoglycemic events,allergic reactions,or local injection adverse reaction occurred.Conclusion The studied recombinant human insulin preparation SciLin TMR may be bioequivalent as Humulin (R) R.

Objective To study the difference of body weight gain in the first and second trimesters between pregnant women with abnormal gestational glucose metabolism and those with normal gestational glucose metabolism.Methods We retrospectively analyzed the data of pregnant women visited the obstetric clinic of Peking Union Medical College Hospital from January 2010 to May 2011,with or without abnormal glucose metabolism.The data of body weight gain in the first and second trimesters,body mass index (BMI) before pregnancy,BMI in the end of second trimester,age,obesity history,diabetes family history,insulin level in the oral glucose tolerance test (OGTT),and lipid profile of these women were collected.Results Altogether 216 pregnant women with abnormal glucose metabolism (case group) and 230 pregnant women with normal glucose metabolism (control group) were included in this study.In the case group,the increment of body weight in the first and second trimesters was 10.0 (8.1,12.5) kg,and the increment of BMI was (4.01 ± 1.43) kg/m2,BMI in the end of the second trimester was (25.84 ± 3.14) kg/m2;in comparison,the increments of body weight and BMI in the first and second trimesters were 9.5 (7.0,11.5) kg and (3.60 ± 1.43) kg/m2,respectively,BMI in the end of the second trimester was (25.1 ± 3.00) kg/m2 in the control group,all significantly lower than in the case group (all P ＜ 0.05).The BMI before pregnancy was higher in the case group than in the control group [(21.84 ±2.99) kg/m2 vs.(21.50 ±2.82) kg/m2],but with no statistical significance (P＞0.05).Compare with the control group,the case group had older age [(33.17 ±3.65) years vs.(31.68±3.36) years],higher fasting insulin level [11.2 (7.1,16.3) mU/Lvs.8.9 (6.5,13.7) mU/L],higher peak insulin level in OGTT [135.3 (99.7,208.0) mU/L vs.104.9 (75.6,144.4) mU/L],higher homeostasis model assessment for insulin resistance (HOMA-IR) [2.40 (1.49,3.47) vs.1.82 (1.28,2.71)],and triglyceride [2.62 (2.04,3.31) mmol/L vs.2.18 (1.81,2.81) mmol/L],all with significant differences (all P ＜ 0.05).There were no significant differences in obesity history,family history of diabetes and history of menstrual disorder between the two groups (all P ＞ 0.05).Conclusions The body weight gain is higher in the pregnant women with abnormal glucose metabolism than in those with normal glucose metabolism in the first and second trimesters.Large increment of body weight is likely to be a risk factor for abnormal gestational glucose metabolism.

Objcetive: To investigate the effect of resveratrol (RES)combined with cisplatin (DDP)on the cholangiocarcinoma cell line FRH-0201 in vitro. Methods: FRH-0201 cells were exposed to different concentrations of RES or (and)DDP. Cell morphological changes were observed by light and fluorescence microscopy. Inhibition of cell proliferation was measured by MTT and colony-forming assay. And the flow cytometry were performed to detect the cell apoptosis rate and cell cycle. Results: Resveratrol inhibited the proliferation of FRH-0201 cells in a time-and dose-dependent manner in the concentration of 5～320 ?mol/L and the IC50 values after the exposure of 24, 48, and 72 h were 55.35, 32.84, and 28.01 ?mol/L respectively. RES and DDP had synergetic effect in the inhibition of FRH-0201 cells. Conclusion: RES can inhibit the growth of FRH-0201 cells and has the synergetic effect with DDP.

Objective To assess the clinical value of HRCT in diagnosis of cholesteatomatous tympanitis.Methods HRCT findings of 26 patients with cholesteatomatous tympanitis proved by surgery and pathology were analyzed.Results HRCT findings of cholesteatomatous tympanitis included:soft tissue mass in the superior tympanium,tympanal sinus and mastoid(100%,26/26),destruction of the bone includeing ossicles chain (92%,24/26),secutum(46%,12/26),facial nerve canal (54%,14/26);enlargement of the tympaniosinus with sclerosing borders;intracranial complications including temple abscess(1 case),meningitis(1 case).Conclusion HRCT is of great value in diagnosis of cholesteatomatous tympanitis.

Objective To evaluate the efficacy and safety of methotrexate(MTX)on the hip involve ment in patients with ankylosing spondylitis(AS).Methods Among the AS patients with hip joint involvement admitted to the department from 1999—2002,50 patients were treated with sulfasalazine(SSZ)(control group, CG)and 48 MTX(observation group,OG).One kind of NSAIDs was taken by the patients in both groups as the basic therapy.The treatment was maintained in both groups after being discharged.Patients were followed-up for three years.The observation parameters included symptoms,signs,Bath AS disease activity index(BASDAI), Bath AS functional index(BASFI),hip joint function score,the CT staging of hip joint involvement,serum in- flammation markers,laboratory tests and side effects.The data were analyzed with SPSS10.0 statistics software. Results At the 1st,2nd and 3rd year,44,38 and 32 cases in the OG and 45,38 and 31 cases in the CG were followed up respectively.During the three-year follow-up period,the hip joint function score of the OG was significantly higher than that of the CG(P

Objective To explore the relationship between glycated albumin ( GA ) in 2 consecutive months and hemoglobin A1c ( HbA1c) in diabetes patients.Methods Totally 100 consecutive patients with main diagnosis of diabetes mellitus were enrolled retrospectively from April 2015 to January 2016 in outpatient clinic of endocrinology of Peking Union Medical College Hospital, who had undertaken GA tests every 4 weeks for 2 successive months and had HbA1c test in the second month.GA was measured with liquid enzymatic method. HbA1c was measured by ion-exchange high performance liquid chromatography.The relationship between HbA1c and GA for the 2 successive months was determined.Results A total of 85 patients were enrolled.The regres-sion equation between HbA1c (y) and average GA (j) for successive 2 months was y=3.187+0.218j (adjusted R2 =0.520, P=0.000), which showed a similar effect as the regression equation for HbA1c and the levels of GA tested for the 2 successive months (adjusted R2 =0.514, P=0.000), and both had more significant regressive effect than the regression equation for HbA1c and single measurement of GA (adjusted R2 =0.392, P=0.000). Conclusions The regressive effect between HbA1c and GA (or the average of GA) in successive 2 months is bet-ter than that with single measurement of GA, hence could better predict HbA1c in clinical practice.