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 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.

SUMMARY We analyzed the clinicopathological characteristics of one patient with Rhupus syndrome as-sociated nephropathy in Peking University People ’s Hospital, and reviewed the related literature .The pa-tient was a middle aged female .She developed rheumatoid arthritis first , and then manifested mild sys-temic lupus erythematosus together with positive anti-neutrophil cytoplasmic antibodies ( ANCA ) and cryoglobulinemia several years later .The renal biopsy was performed and manifested as lupus nephritis . The transmission electron microscopy revealed cryoglobulinemia associated renal damage .This report shows that the clinicopathological characteristics in patients with Rhupus syndrome associated nephropathy are complicated .The renal pathology can be used as a diagnostic tool .

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.

Objective To establish the technique of hyperinsulinemic euglycemic clamp and to study the reference value of insulin sensitivity index in healthy Chinese. Methods According to the feedback mathematical model developed by DeFronzo, the technique of hyperinsulinemic euglycemic clamp was used in 90 healthy Chi- nese [ male:female =71 = 19; age; (28. 3±6. 1) years; body mass index (20. 9±1.5) kg/m2 ] to study die glu-cose metabolized rate. Blood samples were obtained at timed intervals in the fasting state and during the clamp for the measurement of glucose, insulin and C peptide. Results During the clamp tests, the blood glucose levels were con-trolled within 10% of target value. The coefficient of variation of glucose levels was 3. 8% 0.1%. In the steady state, the insulin sensitivity index (glucose metabolized rate, M value ) was (7.78±2.30) mg· kg-1 min-1, which was distributed normally. The lowest quartile of M value was 6. 286 mg·kg -1 min-1'. The coefficient of variation of M value was 9.4%±2.8%. Conclusion The technique of hyperinsulinemic euglycemic clamp and the reference value of insulin sensitivity index in healthy Chinese are successfully established in our center.

Objective （ ） To explore the influence of perceived organizational support POS and psychological resilience on （ - ）Methods presenteeism behavior in medical staff in the prevention and control of coronavirus disease COVID 19 . Doctors - - and nurses engaged in the front line work of prevention and control in the four designated hospitals for the treatment of COVID ， 19 in Guangdong Province Hunan Province and Jiangsu Province were selected as the research subjects using a random cluster ， - - sampling method. The Survey of Perceived Organizational Support Scale the 10 item Connor Davidson Resilience Scale and - ， Results Standford Presenteeism Scale 6 were used to investigate their POS psychological resilience and presenteeism. The ， （ ），（ ） （ ）， total scores of POS psychological resilience and presenteeism were 44.9±7.6 31.2±5.7 and 18.5±3.7 respectively. （ Both POS and psychological resilience had negative effect on presenteeism standardized regression coefficient were −0.59 ， P ） ［ and −0.38 both <0.01 . Psychological resilience played a partial mediating role between POS and presenteeism 95% （ - ）， ］ Conclusion confidence interval −0.22 −0.09 the mediating effect ratio was 23.4% . Both POS and psychological - ， resilience can directly affect the presenteeism behavior of medical staff in COVID 19 prevention and control and POS can also indirectly affect their presenteeism by affecting psychological resilience.

Objective （ ） To explore the influence of perceived organizational support POS and psychological resilience on （ - ）Methods presenteeism behavior in medical staff in the prevention and control of coronavirus disease COVID 19 . Doctors - - and nurses engaged in the front line work of prevention and control in the four designated hospitals for the treatment of COVID ， 19 in Guangdong Province Hunan Province and Jiangsu Province were selected as the research subjects using a random cluster ， - - sampling method. The Survey of Perceived Organizational Support Scale the 10 item Connor Davidson Resilience Scale and - ， Results Standford Presenteeism Scale 6 were used to investigate their POS psychological resilience and presenteeism. The ， （ ），（ ） （ ）， total scores of POS psychological resilience and presenteeism were 44.9±7.6 31.2±5.7 and 18.5±3.7 respectively. （ Both POS and psychological resilience had negative effect on presenteeism standardized regression coefficient were −0.59 ， P ） ［ and −0.38 both <0.01 . Psychological resilience played a partial mediating role between POS and presenteeism 95% （ - ）， ］ Conclusion confidence interval −0.22 −0.09 the mediating effect ratio was 23.4% . Both POS and psychological - ， resilience can directly affect the presenteeism behavior of medical staff in COVID 19 prevention and control and POS can also indirectly affect their presenteeism by affecting psychological resilience.

Objective （ ） To explore the influence of perceived organizational support POS and psychological resilience on （ - ）Methods presenteeism behavior in medical staff in the prevention and control of coronavirus disease COVID 19 . Doctors - - and nurses engaged in the front line work of prevention and control in the four designated hospitals for the treatment of COVID ， 19 in Guangdong Province Hunan Province and Jiangsu Province were selected as the research subjects using a random cluster ， - - sampling method. The Survey of Perceived Organizational Support Scale the 10 item Connor Davidson Resilience Scale and - ， Results Standford Presenteeism Scale 6 were used to investigate their POS psychological resilience and presenteeism. The ， （ ），（ ） （ ）， total scores of POS psychological resilience and presenteeism were 44.9±7.6 31.2±5.7 and 18.5±3.7 respectively. （ Both POS and psychological resilience had negative effect on presenteeism standardized regression coefficient were −0.59 ， P ） ［ and −0.38 both <0.01 . Psychological resilience played a partial mediating role between POS and presenteeism 95% （ - ）， ］ Conclusion confidence interval −0.22 −0.09 the mediating effect ratio was 23.4% . Both POS and psychological - ， resilience can directly affect the presenteeism behavior of medical staff in COVID 19 prevention and control and POS can also indirectly affect their presenteeism by affecting psychological resilience.

Objective To evaluate the clinical and biochemical characteristics of pregnant women with different glucose tolerance status,and their secretion characteristics of insulin,glucagon and glucagon-like peptide-1 (GLP-1) after oral glucose challenge.Methods We analyzed 74 cases pregnant women with positive results of 50 g glucose challenge test in 24-28 gestational weeks,who received regular obstetrical follow-up in Peking Union Medical College Hospital from January 2009 to June 2012.A further 100 g oral glucose tolerance test (OGTT) was performed,based on which the included women were divided into three groups,namely gestational diabetes mellitus (GDM) group (n =25),impaired glucose tolerance (IGT) group (n =25) and normal glucose tolerance (NGT) group (n =24).The general clinical data and biochemical indexes of the three groups were compared,and the indexes about insulin resistance and the function of pancreatic islet beta cells were calculated.Glucose,insulin,glucagon and GLP-1 were measured in OGTT.The secretion characteristics of each of these hormones and their correlation with other indicators were evaluated.Results Compared with the NGT group,the GCT [(9.21 ±0.75) mmol/L vs.(8.52 ±0.50) mmol/L,P ＜0.05] and glycosylated hemoglobin A1c [(5.39±0.34)％ vs.(5.18 ±0.20)％,P＜0.05] were significantly higher in the GDM group.In OGTT,the area under curve (AUC) of glucose in the GDM group was significantly higher than that inthe IGT group and NGT group [(26.58 ±2.02) mmol/(L · h) vs.(23.20 ± 1.51) mmoL/(L · h),(26.58 ± 2.02) mmol/(L · h) vs.(19.84 ± 1.95) mmol/(L · h),both P ＜ 0.05].The peak values of insulin secretion in the GDM group and IGT group were delayed to 2 hours after OGTT.The 3-hour insulin level in the GDM group was significantly higher than that in the NGT group (P ＜ 0.05).Compared with the NGT group,the glucagon levels in each time point after OGTT and the AUC of glucagon levels were reduced in the GDM group and the IGT group,but with no significant differences.The peak glucagon levels in the 3 groups all appeared at 3 hours after OGTT.The GLP-1 levels in each time point of OGTT were gradually increased from the NGT group to the IGT group to the GDM group,but no significant differences were found.The peak value of GLP-1 level was presented at 1 hour after OGTT in the NGT group and the IGT group and at 2 hours after OGTT in the GDM group.The valley values of GLP-1 level in the 3 groups all appeared at 3 hours after OGTT.In comparison with the NGT group,the ratios of GLP-1 to blood glucose levels (GLP/BG) at 1-hour and 2-hour were significantly decreased in the GDM group (P ＜ 0.05).The AUC of glucagon levels in OGTT were negatively correlated with fasting blood glucose (r =-0.287,P =0.013) and 1-hour glucose levels (r =-0.266,P =0.022) in OGTT and positively correlated with insulin secretion sensitivity index (ISSI) (r =0.297,P =0.010) and HOMA-β (r =0.236,P =0.043).Moreover,the AUC of GLP-1 levels in OGTT was negatively correlated with the levels of C-reactive protein (r =-0.264,P =0.035).The AUC of GLP/BG in OGTT was positively correlated with ISSI (r=0.406,P＜0.001).Conclusions Pregnant women with GDM and IGT in the second trimester have insulin resistance and dysfunction of pancreatic islet β cells.Potential GLP-1 resistance and inadequate secretion may exist in GDM patients.GLP/BG may be a better parameter to evaluate the secretion function of L cells in pregnancy and an effective parameter to estimate the compensatory function of pancreatic β cells indirectly.Glucagon levels may not start to change obviously before 28 gestational weeks.