Inosine:A broad-spectrum anti-inflammatory against SARS-CoV-2 infection-induced acute lung injury via suppressing TBK1 phosphorylation / 药物分析学报

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-induced cytokine storms constitute the primary cause of coronavirus disease 19(COVID-19)progression,severity,criticality,and death.Gluco-corticoid and anti-cytokine therapies are frequently administered to treat COVID-19,but have limited clinical efficacy in severe and critical cases.Nevertheless,the weaknesses of these treatment modalities have prompted the development of anti-inflammatory therapy against this infection.We found that the broad-spectrum anti-inflammatory agent inosine downregulated proinflammatory interleukin(IL)-6,upregulated anti-inflammatory IL-10,and ameliorated acute inflammatory lung injury caused by mul-tiple infectious agents.Inosine significantly improved survival in mice infected with SARS-CoV-2.It indirectly impeded TANK-binding kinase 1(TBK1)phosphorylation by binding stimulator of interferon genes(STING)and glycogen synthase kinase-3β(GSK3β),inhibited the activation and nuclear trans-location of the downstream transcription factors interferon regulatory factor(IRF3)and nuclear factor kappa B(NF-κB),and downregulated IL-6 in the sera and lung tissues of mice infected with lipopoly-saccharide(LPS),H1N1,or SARS-CoV-2.Thus,inosine administration is feasible for clinical anti-inflammatory therapy against severe and critical COVID-19.Moreover,targeting TBK1 is a promising strategy for inhibiting cytokine storms and mitigating acute inflammatory lung injury induced by SARS-CoV-2 and other infectious agents.

Evaluation of the chemical profile from four germplasms sources of Pruni Semen using UHPLC-LTQ-Orbitrap-MS and multivariate analyses / 药物分析学报

Pruni Semen,the seed of several unique Prunus plants,is a traditional purgative herbal material.To determine the authentic sources of Pruni Semen,46 samples from four species were collected and analyzed.Ten compounds including multiflorin A(Mul A),a notable purative compound,were isolated and identified by chemical separation and nuclear magnetic resonance spectroscopy.Seventy-six communal components were identified by ultra-high performance liquid chromatography with linear ion trap-quadrupole Orbitrap mass spectrometry,and acetyl flavonoid glycosides were recognized as characteristic constituents.The flavonoids were distributed in the seed coat and cyanogenic glycosides in the kernel.Based on this,methods for identifying Pruni Semen from different sources were established using chemical fingerprinting,quantitative analysis of the eight principal compounds,hierarchical cluster analysis,principal component analysis,and orthogonal partial least squares discriminant analysis.The results showed that the samples were divided into two categories:one is the small seeds from Prunus humilis(Ph)and Prunus japonica(Pj),and the other is the big seeds from Prunus pedunculata(Pp)and Prunus triloba(Pt).The average content of Mul A was 3.02.6.93,0.40,and 0.29 mg/g,while the average content of amygdalin was 18.5,17.7,31.5,and 30.9 mg/g in Ph,Pj,Pp,and Pt,respectively.All the above information suggests that small seeds might be superior sources of Pruni Semen.This is the first comprehensive report on the identification of chemical components in Pruni Semen from different species.

Risk of gestational diabetes recurrence and the development of type 2 diabetes among women with a history of gestational diabetes and risk factors: a study among 18 clinical centers in China / 中华医学杂志(英文版)

BACKGROUND@#Gestational diabetes mellitus (GDM) brings health issues for both mothers and offspring, and GDM prevention is as important as GDM management. It was shown that a history of GDM was significantly associated with a higher maternal risk for GDM recurrence. The incidence of GDM recurrence was unclear because of the incidence of second-child was low before 2016 in China. We aim to investigate the prevalence of GDM recurrence and its associated high-risk factors which may be useful for the prediction of GDM recurrence in China.@*METHODS@#A retrospective study was conducted which enrolled participants who underwent regular prenatal examination and delivered twice in the same hospital of 18 research centers. All participants were enrolled from January 2018 to October 2018, where they delivered the second baby during this period. A total of 6204 women were enrolled in this study, and 1002 women with a history of GDM were analyzed further. All participants enrolled in the study had an oral glucose tolerance test (OGTT) result at 24 to 28 weeks and were diagnosed as GDM in the first pregnancy according to the OGTT value (when any one of the following values is met or exceeded to the 75-g OGTT: 0 h [fasting], ≥5.10 mmol/L; 1 h, ≥10.00 mmol/L; and 2 h, ≥8.50 mmol/L). The prevalence of GDM recurrence and development of type 2 diabetes mellitus were calculated, and its related risk factors were analyzed.@*RESULTS@#In 6204 participants, there are 1002 women (1002/6204,16.15%) with a history of GDM and 5202 women (5202/6204, 83.85%) without a history of GDM. There are significant differences in age (32.43 ± 4.03 years vs. 33.00 ± 3.34 years vs. 32.19 ± 3.37 years, P  < 0.001), pregnancy interval (4.06 ± 1.44 years vs. 3.52 ± 1.43 years vs. 3.38 ± 1.35 years, P  = 0.004), prepregnancy body mass index (BMI) (27.40 ± 4.62 kg/m2vs. 23.50 ± 3.52 kg/m2vs. 22.55 ± 3.47 kg/m2, P < 0.001), history of delivered macrosomia (22.7% vs. 11.0% vs. 6.2%, P < 0.001) among the development of diabetes mellitus (DM), recurrence of GDM, and normal women. Moreover, it seems so important in the degree of abnormal glucose metabolism in the first pregnancy to the recurrence of GDM and the development of DM. There are significant differences in OGTT levels of the first pregnancy such as area under the curve of OGTT value (18.31 ± 1.90 mmol/L vs. 16.27 ± 1.93 mmol/L vs. 15.55 ± 1.92 mmol/L, P < 0.001), OGTT fasting value (5.43 ± 0.48 mmol/L vs. 5.16 ± 0.49 mmol/L vs. 5.02 ± 0.47 mmol/L, P < 0.001), OGTT 1-hour value (10.93 ± 1.34 mmol/L vs. 9.69 ± 1.53 mmol/L vs. 9.15 ± 1.58 mmol/L, P < 0.001), OGTT 2-hour value (9.30 ± 1.66 mmol/L vs. 8.01 ± 1.32 mmol/L vs. 7.79 ± 1.38 mmol/L, P < 0.001), incidence of impaired fasting glucose (IFG) (fasting plasma glucose ≥5.6 mmol/L) (31.3% vs. 14.6% vs. 8.8%, P < 0.001), and incidence of two or more abnormal OGTT values (68.8% vs. 39.7% vs. 23.9%, P < 0.001) among the three groups. Using multivariate analysis, the factors, such as age (1.07 [1.02-1.12], P = 0.006), prepregnancy BMI (1.07 [1.02, 1.12], P  = 0.003), and area under the curve of OGTT in the first pregnancy (1.14 [1.02, 1.26], P  = 0.02), have an effect on maternal GDM recurrence; the factors, such as age (1.28 [1.01-1.61], P  = 0.04), pre-pregnancy BMI (1.26 [1.04, 1.53], P = 0.02), and area under the curve of OGTT in the first pregnancy (1.65 [1.04, 2.62], P = 0.03), have an effect on maternal DM developed further.@*CONCLUSIONS@#The history of GDM was significantly associated with a higher maternal risk for GDM recurrence during follow-up after the first pregnancy. The associated risk factors for GDM recurrence or development of DM include age, high pre-pregnancy BMI, history of delivered macrosomia, the OGTT level in the first pregnancy, such as the high area under the curve of OGTT, IFG, and two or more abnormal OGTT values. To prevent GDM recurrence, women with a history of GDM should do the preconception counseling before preparing next pregnancy.

Exercises down regulate Toll-like receptor 4 signaling pathway in obese and overweight pregnant women / 中华围产医学杂志

Objective:To explore the effect of exercise intervention on regulation of Toll-like receptor 4 (TLR4) signaling pathway in overweight and obese pregnant women.Methods:The cohort was based on a randomized controlled trial (RCT) carried out by the same research group in Peking University First Hospital from December 2014 to July 2016. Overweight and obese patients who delivered by elective cesarean section without pregnancy complications were recruited, among which 12 cases in the exercise group and 11 cases in the control group were selected. Real-time polymerase chain reaction, Western Blot, and Luminex experiments were used to compare the expression of TLR4-myeloid differentiation factor 8(MyD88)-nuclear factor-κB(NF-κB) pathway in peripheral blood mononuclear cell (PBMC), rectus abdominis muscle, omental adipose, and subcutaneous adipose, as well as the levels of inflammatory factors (TNF-α, IL-1β, IL-10) in plasma between the two groups. Two independent samples t-test, generalized estimating equation, Chi-square test, and Pearson correlation analysis were adopted for statistical analysis. Results:(1) The expression of inflammatory factors TNF-α and IL-1β in the exercise group showed a downward trend compared with the control in the second and third trimester, but none of the differences were statistically significant (all P>0.05). (2) The mRNA expression of TLR4, MyD88, and NF-κB and the protein expression of TLR4 and NF-κB in PBMC of the exercise group were significantly lower than those in the control group during pregnancy (TLR4 mRNA: 0.06±0.03 vs 0.10±0.04 in the second trimester, 0.05±0.02 vs 0.11±0.05 in the third trimester, χ2=8.07; MyD88 mRNA: 0.09±0.03 vs 0.11±0.03 in the second trimester, 0.10±0.04 vs 0.17±0.06 in the third trimester, χ2=5.81; NF-κB mRNA: 0.10±0.03 vs 0.17±0.08 in the second trimester, 0.08±0.03 vs 0.20±0.08 in the third trimester, χ2=14.71; TLR4 protein: 1.7±0.5 vs 1.9±0.8 in the second trimester, 1.7±0.4 vs 2.3±0.8 in the third trimester, χ2=5.83; NF-κB protein: 1.0±0.4 vs 1.5±0.4 in the second trimester, 1.2±0.3 vs 1.5±0.5 in the third trimester, χ2=4.73; all P<0.05). Moreover, the differences in the mRNA expression of TLR4, MyD88, and NF-κB and TLR4 protein expression in PBMC between the two groups gradually increased. (3) NF-κB in rectus abdominis and omental adipose tissue (0.04±0.02 vs 0.08±0.04, t=－3.72; 0.25±0.05 vs 0.63±0.21, t=－5.41; both P<0.05) and TLR4 and MyD88 in subcutaneous adipose tissue (0.12±0.03 vs 0.30±0.10, t=－5.30; 0.24±0.09 vs 0.44±0.08, t=－5.38; both P<0.05) were observed a decreased mRNA level in the exercise group compared with the control group. The protein level of MyD88 and NF-κB in omental adipose tissue and NF-κB in subcutaneous adipose tissue in the exercise group were significantly lower than those in the control group (1.1±0.5 vs 2.0±0.8, t=－3.15; 1.3±0.5 vs 2.0±0.9, t=－2.23; 1.2±0.5 vs 1.9±0.8, t=－2.80, all P<0.05). (4) The expressions of TLR4 and NF-κB mRNA ( r=0.453 and 0.485) in rectus abdominis muscle, NF-κB mRNA, TLR4 and MyD88 protein ( r=0.539, 0.437 and 0.527) in omental adipose in the two groups were positively correlated with the level of fasting blood glucose ( P<0.05). Conclusions:Regular exercise during pregnancy can down-regulate the expression and activation of the TLR4-MyD88-NFκB pathway in overweight and obese pregnant women. The expression of related factors along this pathway has a certain correlation with fasting blood glucose.

Effects of glycemic control on placental glucose transporters in women with hyperglycemia in pregnancy / 中华围产医学杂志

Objective:To investigate the expression of placental glucose transport protein (GLUT)1 and 4 in women with hyperglycemia in pregnancy.Methods:A total of 48 full-term singleton pregnant women who underwent elective cesarean section at Peking University First Hospital from January 2017 to December 2019 were included retrospectively, and were divided into pregestational diabetes mellitus (PGDM) group, gestational diabetes mellitus (GDM) group, and normal glucose tolerance (NGT) group (16 women in each). According to the blood glucose level after control during pregnancy, the PGDM and GDM groups were further divided into PGDM-, GDM-well controlled subgroups (both n=10), and PGDM-, GDM-uncontrolled subgroups (both n=6). The expression of GLUT1 and GLUT4 proteins, detected by Western blot, between different groups were compared and the correlation between GLUT1 and GLUT4 protein expression and the pre-pregnancy body mass index (BMI), pre-delivery weight,gestational weight gain (GWG), and neonatal birth weight were analyzed using two independent samples t-test, one-way analysis of variance, Kruskal-Wallis H-test, Chi-square test, and Pearson correlation analysis. Results:(1) The pre-pregnanct BMI and insulin treatment ratio in PGDM group were higher than those in GDM group and NGT group [27.0 kg/m 2 (22.1-29.9 kg/m 2) vs 22.9 kg/m 2 (20.5-25.7 kg/m 2) and 21.7 kg/m 2 (20.5-24.3 kg/m 2); 13/16 vs 1/16 and 0/16; all P<0.05]. In the PGDM group, fasting blood glucose at the second trimester and mean glycosylated hemoglobin during the second and the third trimester were higher than those in the GDM group [(6.1±1.2) vs (5.0±0.4) mmol/L; (5.9±0.5)% vs (5.2±0.3)%; both P<0.05]. (2) GLUT1 protein level was the highest in the PGDM group, followed by the GDM and NGT group (1.251±0.354 vs 1.004±0.368 vs 0.733±0.216, both P<0.05). And all the subgroups had higher protein level than NGT group [PGDM-good (1.270±0.417); PGDM-uncontrolled (1.218±0.245), GDM-well controlled (0.900±0.424); GDM-uncontrolled (1.177±0.158); LSD test,all P<0.05]. The variation of GLUT4 protein level was consistent with GLUT1. There was no significant difference in GLUT1 and GLUT4 expression between PGDM-uncontrolled and PGDM-well controlled subgroups, neither between GDM-uncontrolled and GDM-well controlled subgroups (all P>0.05). (3) GLUT1 and GLUT4 in the PGDM-well controlled subgroup, as well as GLUT1 in the GDM-uncontrolled subgroup, had a positive correlation with GWG ( r=0.635, 0.810, and 0.833, all P<0.05). Conclusions:The increased expression of placental GLUT1 and GLUT4 were associated with different types of gestational hyperglycemia and GWG. However, glucose control has little effect on placental GLUT expression.

Effects of interpregnancy interval on pregnancy outcomes of subsequent pregnancy: a multicenter retrospective study / 中华妇产科杂志

Objective:To explore the effects of interpregnancy interval (IPI) on pregnancy outcomes of subsequent pregnancy.Methods:A multicenter retrospective study was conducted in 21 hospitals in China. Information of age, height, pre-pregnancy weight, IPI, history of diseases, complications of pregnancy, gestational age of delivery, delivery mode, and pregnancy outcomes of the participants were collected by consulting medical records of pregnant women who had two consecutive deliveries in the same hospital during 2011 to 2018. The participants were divided into 4 groups according to IPI:<18 months, 18-23 months, 24-59 months and ≥60 months. According to the WHO′s recommendation, with the IPI of 24-59 months group as a reference, to the effects of IPI on pregnancy outcomes of subsequent pregnancy were analyzed. Stratified analysis was further carried out based on age, history of gestational diabetes mellitus (GDM), macrosomia, and premature delivery, to explore the differences in the effects of IPI on pregnancy outcomes among women with different characteristics.Results:A total of 8 026 women were included in this study. There were 423, 623, 5 512 and 1 468 participants in <18 months group, 18-23 months group, 24-59 months group and ≥60 months group, respectively. (1) The age, pre-pregnancy body mass index (BMI), history of cesarean section, GDM, gestational hypertension and cesarean section delivery rate of <18 months group, 18-23 months group, 24-59 months group and ≥60 months group were gradually increased, and the differences were statistically significant ( P<0.05). (2) After adjusting for potential confounding factors, compared with women in the IPI of 24-59 months group, the risk of premature delivery, premature rupture of membranes, and oligohydramnios were increased by 42% ( OR=1.42, 95% CI: 1.07-1.88, P=0.015), 46% ( OR=1.46, 95% CI: 1.13-1.88, P=0.004), and 64% ( OR=1.64, 95% CI: 1.13-2.38, P=0.009) respectively for women in the IPI≥60 months group. No effects of IPI on other pregnancy outcomes were found in this study ( P>0.05). (3) After stratified by age and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of oligohydramnios for women with advanced age ( OR=2.87, 95% CI: 1.41-5.83, P=0.004); and <18 months could increase the risk of premature rupture of membranes for women under the age of 35 ( OR=1.59, 95% CI: 1.04-2.43, P=0.032). Both the risk of premature rupture of membranes ( OR=1.58, 95% CI: 1.18-2.13, P=0.002) and premature delivery ( OR=1.52, 95% CI: 1.07-2.17, P=0.020) were significantly increased in the IPI≥60 months group. After stratified by history of GDM and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would lead to an increased risk of postpartum hemorrhage for women with a history of GDM ( OR=5.34, 95% CI: 1.45-19.70, P=0.012) and an increased risk of premature rupture of membranes for women without a history of GDM ( OR=1.44, 95% CI: 1.10-1.90, P=0.009). After stratified by history of macrosomia and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months could increase the proportion of cesarean section for women with a history of macrosomia ( OR=4.11, 95% CI: 1.18-14.27, P=0.026) and the risk of premature rupture of membranes for women without a history of macrosomia ( OR=1.46, 95% CI: 1.12-1.89, P=0.005). After stratified by history of premature delivery and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of premature rupture of membranes for women without a history of premature delivery ( OR=1.47, 95% CI: 1.13-1.92, P=0.004). Conclusions:Both IPI≥60 months and <18 months would increase the risk of adverse pregnancy outcomes in the subsequent pregnancy. Healthcare education and consultation should be conducted for women of reproductive age to maintain an appropriate IPI when they plan to pregnant again, to reduce the risk of adverse pregnancy outcomes in the subsequent pregnancy.

Study on the Quality Standards of Mongolian Medicine Cynanchum thesioides / 中国药房

OBJECTIVE：To establish the quality standards of Mongolian medicine Cynanchum thesioides. METHODS ：TLC was used for the qualitative identification of C. thesioides . According to 2015 edition of Chinese Pharmacopeia （part Ⅳ），the moisture，total ash and ethanol-soluble extract were determined. HPLC method was used to determine the content of thesioideoside in C. thesioides . RESULTS ：TLC spots were clear ，there were same yellow green fluorescent spots on the corresponding position of the sample （C. thesioides ）and control （thesioideoside）. In 22 batches of samples ，contents of moisture were 6.18％-12.97％，total ash were 4.64％-7.95％，ethanol-soluble extract were 12.46％-32.70％. The linear range of thesioideoside were 0.048-3.050 μg（R2＝ 0.999 9）. RSDs of precision ， stability， repeatability and durability tests were all less than 1％ . The recoveries were 104.03％-106.36％（RSD＝0.96％，n＝6）. The contents of thesioideoside in 22 batches of C. thesioides were 0.006 2％-0.130 5％. CONCLUSIONS：It is suggested that the moisture and total ash should not exceed 11.50％ and 7.50％，respectively；the contents of ethanol-soluble extract and the sioideoside are no less than 17.00％ and 0.05％，respectively. The established quality standards can be used for quality control of Mongolian medicine C. thesioides .

Preparation and evaluation of azithromycin-loaded microspheres for oral administration / 中国药科大学学报

@#To mask the bitterness of azithromycin（AZI） and improve patient compliance, an AZI-loaded microsphere (AZI-EC MS) for oral administration was prepared by O/W emulsion solvent evaporation with ethylcellulose (EC) as carrier. The release profiles and taste-masking effect of AZI-EC MS were preliminarily assessed. Its physical properties and morphology were then investigated by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). The results indicated that the polymer weight of EC could influence the drug release behavior. With a drug polymer ratio of 1∶1 and mixed EC (N22/T10, 7∶3) as carrier, the cumulative release of AZI-EC MS at 0.5 h was less than 40% and reached 90% at 8 h; the drug loading efficiency of microspheres was (48.95 ± 0.86)% with smooth spherical morphology. The AZI bitterness threshold is 9.93 μg/mL with a strong bitter taste, which indicated a better taste masking effect. Therefore, AZI-EC MS prepared in this study can mask AZI bitterness and improve patient compliance, setting the stage for the research of new AZI preparations.

Activation of mammaLian target of rapamycin signaLing pathway in pLacentaL tissues of gravidas with gestationaL diabetes meLLitus / 中华围产医学杂志

Objective To investigate the activation of mammalian target of rapamycin (mTOR) signaling pathway in placental tissues of gestational diabetes mellitus (GDM) women and in JEG3 cells after high glucose treatment. Methods Placental tissues were collected from 60 singleton pregnant women at term, who underwent elective cesarean section in Peking University First Hospital from December 2016 to June 2017, including 30 GDM women (GDM group) and 30 normal glucose tolerance (NGT) women (NGT group). Expressions of mTOR, Rictor, Raptor, S6 kinase (S6K) and phosphorylated-S6K (p-S6K), which were mTOR signaling pathway-related molecules in those placental tissues were detected by real-time fluorescence quantitative polymerase chain reaction, Western blotting and immunohistochemistry. At the same time, JEG3 cells were treated with glucose of different concentrations (5.5, 10.0, 15.0, 25.0 and 50.0 mmol/L) for 24 h, and the expressions of mTOR, S6K and p-S6K were detected by Western blotting. Two independent samples t-test, one-way analysis of variance test and Spearman correlation analysis were used for statistical analysis. ResuLts Compared with the NGT group, the pre-pregnancy body mass index(BMI), neonatal birth weight, fasting blood glucose(FBG), and 1 h and 2 h post-load blood glucose in oral glucose tolerance test (OGTT) of the GDM group were significantly increased [pre-pregnant BMI: (21.6±2.7) vs (23.4±3.5) kg/m2, t= － 2.192; neonatal birth weight: (3 337.5±347.7) vs (3 618.3±580.9) g, t=－2.727; FBG: (4.6±0.4) vs (5.2±0.8) mmol/L, t=－3.947; 1 h glucose level: (7.4±1.2) vs (9.6±1.9) mmol/L, t=－5.332; 2 h glucose level: (6.3±1.0) vs (8.1±1.5) mmol/L, t=－5.314; all P<0.05]. The mRNA expressions of mTOR, Rictor and Raptor were significantly higher in the GDM group than in the NGT group (0.051±0.015 vs 0.031±0.011, t=－5.635; 0.038±0.017 vs 0.026±0.010, t=－3.485; 0.036±0.012 vs 0.025±0.011, t=－3.312; all P<0.05). The expression of mTOR, Rictor, Raptor and p-S6K protein in the GDM group were enhanced as compared with those in the NGT group (0.834±0.432 vs 0.386±0.361, t= － 2.249;0.589±0.236 vs 0.262±0.075, t= － 3.726; 0.767±0.345 vs 0.323±0.109, t= － 3.472; 1.847±1.025 vs 0.834±0.432, t=－2.575; all P<0.05). The results of immunohistochemistry also showed that the p-S6K in the placental tissues of the GDM group was higher than that of the NGT group (0.29±0.09 vs 0.18±0.08, t=－3.122, P=0.004). The expressions of mTOR protein (0.190±0.085, 0.301±0.089, 0.419±0.065, 0.562±0.108, 0.412±0.058, F=18.351, P<0.05) and p-S6K protein (0.753±0.150, 1.146±0.289, 2.148±0.188, 2.248±0.115, 2.134±0.214, F=66.242, P<0.05) in JEG3 cells treated with different concentrations of glucose (5.5, 10.0, 15.0, 25.0 and 50.0 mmol/L) were significantly different and increased with increasing concentrations of glucose (r=0.314, P=0.035; r=0.457, P=0.002). ConcLusions The up-regulated expressions of mTOR signaling pathway-related molecules in GDM placenta and high glucose-treated trophoblast cells (JEG3 cells) indicate a possible correlation between mTOR signaling pathway and GDM. However, the specific mechanisms need further study.

Analysis of the maternal glucolipid metabolism in twin pregnancies complicated by gestational diabetes mellitus / 中华妇产科杂志

Objective@#To explore the characteristics of maternal glucose and lipid metabolism in twin pregnancies complicated by gestational diabetes mellitus (GDM).@*Methods@#The clinical features of twin and singleton pregnancies complicated by GDM, which delivered in Peking University First Hospital from January 1st, 2012 to December 31st, 2017 were retrospectively analyzed. A total of 286 twin pregnancies with GDM (GDM-T group) were collected, and 572 singleton pregnancies complicated by GDM (GDM-S group) which were matched by delivery time in a ratio of 1∶2 among all singleton pregnancies with GDM. The characteristics of maternal glucolipid metabolism in the second trimesters of pregnancy was compared between two groups.@*Results@#(1) Compared with GDM-S group, the maternal delivery age were lower [(32±4), (33±4) years] and prepregnancy body mass index (BMI) were higher [(24±4), (23±4) kg/m2] in GDM-T group, the differences were statistically significant (all P<0.05). The incidence of chronic hypertension was found no significant difference (P=0.581). (2) The 3 points of glucose values in 75 g oral glucose tolerance test (OGTT) and OGTT-area under curve (AUC) had no significant difference between GDM-T and GDM-S group.When compared with GDM-S group, the maternal glycosylated hemoglobin levels [(5.41±0.35)%, (5.32±0.28)%], the insulin resistance index (4.07±0.77, 2.63±1.50) and the proportion of insulin use (7.7%, 4.4%) were all significantly higher in GDM-T group (all P<0.05). The values of triglyceride [(3.4±1.4), (2.6±1.2) mmol/L], total cholesterol [(6.3±1.1), (6.0±1.0) mmol/L], low density lipoprotein cholesterol [(3.3±0.9), (3.1±0.8) mmol/L] were significantly higher and values of high density lipoprotein cholesterol [(1.7±0.4), (2.0±0.5) mmol/L] were significantly lower in GDM-T group than GDM-S group (all P<0.05). (3) There was no significant difference in the incidence of gestational hypertension between the two groups (P>0.05). When compared with GDM-S group, the incidences of preeclampsia and small for gestational age were both significantly higher (13.3% vs 2.4%; 28.7% vs 1.7%) and the incidence of large for gestational age was significantly lower in GDM-T group (4.5% vs 15.2%; all P<0.05).@*Conclusions@#The insulin resistance is aggravated in twin pregnancies and the characteristics of lipid metabolism are different between singleton and twin pregnant women complicated by GDM, and there are more complications in twin GDM pregnancies.

Hemoglobin levels in the third trimester and adverse pregnancy outcomes / 中华围产医学杂志

Objective@#To investigate the relation between hemoglobin (Hb) levels in the third trimester and associated adverse pregnancy outcomes.@*Methods@#A retrospective analysis was conducted on 38 624 singleton gravidas recruited from 21 hospitals in three major cities in China from June 2013 to May 2015. Hb levels of all subjects were determined in the third trimester (≥28 weeks). Demographic data and clinical information were collected individually. The recruited gravidas were divided into four groups as follows: anemic group: Hb <110 g/L (n=6 256), control group: 110 g/L≤ Hb <130 g/L (n=22 484), high-level group: 130 g/L ≤ Hb <150 g/L (n=9 460), and super high-level group: Hb ≥ 150 g/L (n=424). One-way ANOVA and Chi-square test were used for statistical analysis.@*Results@#(1) Compared with the control group, anemic group had significantly higher incidences of preterm labor, low birth weight, neonatal admission and neonatal complications [4.9% (1 095/22 484) vs 6.9% (431/6 256), 3.1% (708/22 484) vs 4.3% (272/6 256), 6.2% (1 392/22 484) vs 9.2% (577/6 256), and 7.7% (1 741/22 484) vs 10.2% (640/6 256); χ2=930.905, 21.360,70.506 and 39.837, all P<0.001]; high-level group showed significantly increased incidences of hypertensive disorders of pregnancy and preeclampsia [2.3% (515/22 484) vs 3.2% (305/9 460) and 1.4% (313/22 484) vs 1.7% (161/9 460); χ2=23.203 and 6.072, both P<0.017], but decreased incidences of preterm labor, neonatal admission and neonatal complications [4.9% (1 095/22 484) vs 3.7% (346/9 460), 6.2% (1 392/22 484) vs 5.5% (517/9 460) and 7.7% (1 741/22 484) vs 6.7% (631/9 460); χ2=331.947, 6.245 and 11.154, all P<0.017]; super high-level group had significantly raised incidences of hypertensive disorders of pregnancy, preeclampsia and low birth weight [2.3% (515/22 484) vs 4.7% (20/424), 1.4% (313/22 484) vs 3.5% (15/424) and 3.1% (708/22 484) vs 5.2% (20/424); χ2=10.742, 13.575 and 6.512, all P<0.017]. (2) A concentration gradient analysis was performed to further analyze Hb levels in the third trimester in relation to adverse pregnancy outcomes and the results revealed that with the increase of Hb concentration, the incidences of hypertensive disorders of pregnancy, preeclampsia and low birth weight showed U-shaped distributions, while the incidences of preterm birth, neonatal admission and neonatal complications showed decreasing trends (χ2=31.233, 16.147, 25.618, 85.383, 97.824 and 68.677, respectively; all P<0.05).@*Conclusions@#Abnormal levels of Hb in the third trimester of pregnancy, including anemia and elevated Hb concentration are related to adverse pregnancy outcomes.

Hemoglobin levels in the third trimester and adverse pregnancy outcomes / 中华围产医学杂志

Objective To investigate the relation between hemoglobin (Hb) levels in the third trimester and associated adverse pregnancy outcomes.Methods A retrospective analysis was conducted on 38 624 singleton gravidas recruited from 21 hospitals in three major cities in China from June 2013 to May 2015.Hb levels of all subjects were determined in the third trimester (≥ 28 weeks).Demographic data and clinical information were collected individually.The recruited gravidas were divided into four groups as follows:anemic group:Hb ＜110 g/L (n=6 256),control group:110 g/L ≤ Hb ＜130 g/L (n=22 484),high-level group:130 g/L ≤ Hb ＜150 g/L (n=9 460),and super high-level group:Hb ≥ 150 g/L (n=424).One way ANOVA and Chi-square test were used for statistical analysis.Results (1) Compared with the control group,anemic group had significantly higher incidences of preterm labor,low birth weight,neonatal admission and neonatal complications [4.9％ (1 095/22 484) vs 6.9％ (431/6 256),3.1％ (708/22 484) vs 4.3％ (272/6 256),6.2％(1 392/22 484) vs 9.2％ (577/6 256),and 7.7％ (1 741/22 484) vs 10.2％ (640/6 256);x2=930.905,21.360,70.506and 39.837,all P＜0.001];high-level group showed significantly increased incidences of hypertensive disorders of pregnancy and preeclampsia [2.3％ (515/22 484) vs 3.2％ (305/9 460) and 1.4％ (313/22 484) vs 1.7％ (161/9 460);x2=23.203 and 6.072,both P＜0.017],but decreased incidences of preterm labor,neonatal admission and neonatal complications [4.9％ (1 095/22 484) vs 3.7％ (346/9 460),6.2％ (1 392/22 484) vs 5.5％ (517/9 460) and 7.7％ (1 741/22 484) vs 6.7％ (631/9 460);x2=331.947,6.245 and 11.154,all P＜0.017];super high-level group had significantly raised incidences of hypertensive disorders of pregnancy,preeclampsia and low birth weight [2.3％ (515/22 484) vs 4.7％ (20/424),1.4％ (313/22 484) vs 3.5％ (15/424) and 3.1％ (708/22 484) vs 5.2％(20/424);x2=10.742,13.575 and 6.512,all P＜0.017].(2) A concentration gradient analysis was performed to further analyze Hb levels in the third trimester in relation to adverse pregnancy outcomes and the results revealed that with the increase of Hb concentration,the incidences of hypertensive disorders of pregnancy,preeclampsia and low birth weight showed U-shaped distributions,while the incidences of preterm birth,neonatal admission and neonatal complications showed decreasing trends (x2=31.233,16.147,25.618,85.383,97.824 and 68.677,respectively;all P＜0.05).Conclusions Abnormal levels of Hb in the third trimester of pregnancy,including anemia and elevated Hb concentration are related to adverse pregnancy outcomes.

Advances in taste-masking technology of oral paediatric medicine / 中国药科大学学报

As children are extremely sensitive to the bad taste of medicine,they have poor compliance with the bitter medicine.It is of great importance to develop the approaches of taste masking for the research of paediatric drug formulations.Besides,taste masking technology is one of the main barrier to develop children pharmaceutic preparation.This article provides an overview of the advance in taste masking technology of oral paediatric medicine in recent years,and introduces five types of taste masking technology in terms of drug,preparation and the bitter taste transduction,including principle and characteristics of these approaches,as well as their application in formulations,so as to provide some references for the development of paediatric medicine.

The Simple Clinic′S Operation Situation and Process Reengineering / 现代医院

Through surveying the hospital′s operation situation and management process of the simple clinic , and outpatient quantity in January to March 2016, we discussed and analyzed the problem of the simple clinic when working , then promoted service process reengineering , so as to the hospital′s simple clinic come into being scientific , reasonable , system management model .

Relationship between anesthetic factor and intestinal injury in patients undergoing cardiac surgery with cardiopulmonary bypass: a comparison of propofol-versus sevoflurane-based anesthesia / 中华麻醉学杂志

Objective To investigate the relationship between anesthetic factors and intestinal injury in the patients undergoing elective cardiac surgery with cardiopulmonary bypass (CPB).Methods Ninety American Society of Anesthesiologists physical status Ⅱ or Ⅲ patients of both sexes,aged 18-64 yr,with New York Heart Association grade Ⅱ or Ⅲ,undergoing elective cardiac surgery with CPB,were divided into 2 groups (n =45 each) using a random number table:propofol-based anesthesia group (group P) and sevoflurane-based anesthesia group (group S).CPB was established routinely after anesthesia induction.Before induction (T0),immediately after aortic unclamping (T1),at 30 min after aortic unclamping (T2) and at 2 h after discontinuation of CPB (T3),blood samples were collected from the radial artery for determination of the plasma endotoxin,D-lactic acid,diamine oxidase (DAO) and intestinal fatty acid-binding protein (Ⅰ-FABP) concentrations (by enzyme-linked immunosorbent assay) and plasma interleukin-6 (IL-6),IL-8 and tumor necrosis factor-alpha (TNF-o) concentrations (using radio-immunity method).Results Compared with the baseline at T0,the concentrations of plasma endotoxin,D-lactic acid,DAO,TNF-α,IL-6,IL-8 and I-FABP were significantly increased at T1-T3 in both groups (P＜0.05).Compared with group P,the concentrations of plasma endotoxin,D-lactic acid,DAO,TNF-α,IL-6,IL-8 and I-FABP were significantly decreased at T1-T3 in group S (P＜0.05).Conclusion Anesthetic factors are related to intestinal injury in patients undergoing cardiac surgery with CPB.Compared with propofol-based anesthesia,sevoflurane-based anesthesia is helpful in reducing the inflammatory response and in decreasing the degree of intestinal injury and is more suitable for the cardiac surgery with CPB.

Retrospective investigation of incidence of gestational diabetes mellitus and perinatal outcome in Beijing / 中华围产医学杂志

Objective To investigate the incidence of gestational diabetes mellitus (GDM) and perinatal outcome in Beijing in 2013. Methods Fifteen hospitals in Beijing were selected by systematic and cluster sampling method. Clinical data of 15 194 pregnant women who attended prenatal care and delivered in these hospitals between June 20 and November 30, 2013 were collected. And 2 987 pregnant women were diagnosed with GDM (GDM group), and 11 999 had no diabetes (non-GDM group). The incidence of GDM, perinatal outcome and complications in mother and infant were compared between the two groups. Two independent samples t-test and Chi-square test were used for statistical analysis. Results The incidence of GDM in Beijing was 19.7%(2 987/15 194). The average age was much higher in GDM group than in non-GDM group [(29.4±4.5) vs (28.0±4.2) years, t=285.705, P<0.05]. The pre-pregnancy weight was much higher in GDM group than in non-GDM group [(59.5±10.2) vs (56.1±8.6) kg, t=352.565, P<0.05]. The incidence of GDM in pre-pregnancy overweight and obese women [29.9%(664/2 230) and 38.8%(250/664)] was much higher than in normal pre-pregnancy weight and low pre-pregnancy weight women [18.0%(1 777/9 890) and 12.9%(273/2 118)] (χ2=296.843, P<0.05). The incidence of GDM in pluripara was higher than in primipara [21.2% (910/4 298) vs 19.4%(2 077/10 688),χ2=5.813, P<0.05]. The incidence of GDM in gradeⅢhospitals was higher than in grade Ⅱ hospitals [21.1% (1 654/7 849) vs 18.7% (1 333/7 173), χ2=13.440, P<0.05]; and the incidence in urban areas was higher than in rural areas [21.3%(2 028/9 521) vs 17.1%(896/5 249),χ2=39.137, P<0.05]. The rate of cesarean section was 47.1%(1 407/2 987) in GDM group, significantly higher than in non-GDM group [39.8% (4 782/11 999)] (χ2=72.204, P<0.05). The incidences of preterm labor [7.3%(217/2 987)], hypertensive disorders [6.3%(185/2 987)], large-for-gestational-age infants [9.2%(275/2 987)], macrosomia [9.5%(283/2 987)] and neonatal ward admission [8.6%(258/2 987)] were all significantly higher in GDM group than in non-GDM group [5.7%(686/11 999), 3.9%(454/11 999), 5.8%(694/11 999), 7.2%(861/11 999), and 6.5%(778/11 999), respectively] (χ2=10.117, 34.371, 79.378, 20.346 and 17.236, respectively, all P<0.05). Conclusions The incidence of GDM is still high in Beijing, and advanced maternal age and pre-pregnancy overweight or obesity are high risk factors for GDM. The rate of preterm labor, hypertensive disorders, and macrosomia in GDM group is higher than in normal fasting glucose group. Systematic obstetric care for GDM should be intensified in Beijing.

Lipid variations of first and third trimester in pregnant women with different pre-pregnancy body mass index / 中华围产医学杂志

ObjectiveTo investigate the influence of pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) on lipid variations of first and third trimester.MethodsA retrospective analysis was conducted on 2 593 singleton pregnant women without diabetes from 15 hospitals in Beijing from June 20 to November 30 in 2013. Serum lipid levels were determined in all of these women at the first trimester (<14 weeks) and the third trimester (≥28 weeks). Demographic data and medical information were collected individually through questionnaires. The recruited gravidas were divided into normal pre-pregnant BMI group (BMI<25) and pre-pregnant overweight and obese group (BMI≥25) according to recommendations of the Institute of Medicine (IOM). Based on the same recommendations on normal GWG, the pregnant women in the two groups were further assigned to two subgroups including normal GWG and over GWG group. The serum lipid levels in both first and third trimester and the increases from first to third trimester were compared between the normal and abnormal BMI groups with two independent samplet-test.Results(1) The levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C) in the third trimester were all significantly higher than those in the first trimester in the normal BMI group [(6.47±1.17) vs (4.63±0.80), (3.14±1.19) vs (1.22±0.70), (1.94±0.44) vs (1.85±0.49) and (3.56±1.00) vs (2.29±0.67) mmol/L,t=-61.250,-65.909,-6.448 and-49.952, allP<0.01]. And the same results were shown in the abnormal BMI group [(6.20±1.14) vs (4.75±0.88), (3.31±1.20) vs (1.44±0.70), (1.86±0.44) vs (1.65±0.37) and (3.30±0.89) vs (2.51±0.82) mmol/L, t=-18.756,-25.165,-6.905 and-12.191,allP<0.01]. Significant differences were identified between the normal and abnormal pre-pregnant BMI groups both in first and third trimester (allP<0.05). (2) The increases of TC from early to late pregnancy in the abnormal BMI group was lower than that in the normal BMI group [(1.45±1.01) vs (1.84±1.02) mmol/L,t=6.664,P<0.01], but the increase of HDL-C was higher [(0.21±0.39) vs (0.09±0.51) mmol/L,t=-4.301,P<0.01]. (3) In the normal BMI group, the increase of TC and HDL-C between the third and the first trimester was lower in the over GWG subgroups than in the normal GWG subgroups [(1.77±0.96) vs (1.89±1.05) mmo/L,t=-2.802,P=0.005; (0.06±0.41) vs (0.12±0.58) mmo/L,t=-2.588,P=0.010], but the increase of TG was higher [(2.00±1.07) vs (1.86± 1.18) mmo/L,t=3.015,P=0.003]. While in the abnormal BMI group, smaller increase of HDL-C was found in the over GWG subgroup than in the normal GWG subgroup [(0.17±0.35) vs (0.29±0.44) mmo/L,t=-2.664, P=0.008].ConclusionsThe lipid levels during pregnancy are significantly higher in late pregnancy than in early pregnancy. Pre-pregnancy BMI has much more effect on lipid variations during pregnancy than GWG, which primarily affect the lipid levels of women with normal pre-pregnancy BMI.

Analysis on clinical characteristics of multipara in 15 hospitals in Beijing area: a systematic cluster sampling survey / 中华围产医学杂志

Objective To investigate the clinical characteristics (social background,comorbidity,complications and outcomes of pregnancy) of multipara in Beijing area.Methods A systematic cluster sampling survey was conducted on 15 194 pregnant women who gave birth at 15 hospitals in Beijing from January to June in 2013.The age,gestational weeks at delivery,education background,geographical distribution,health insurance coverage,mode of delivery,comorbidity and complications of pregnancy,pregnant outcomes and other relevant clinical data were collected and analyzed with two-sample t test or Chi-square test.Results The proportion of multipara in Beijing area was 21.12％ (3 209/15 194),the per capita number of delivery was 1.23 (18 745/15 194).The ratio of women with higher education background,average monthly household income over 3 000 yuan,urban residence and social insurance in multipara were much lower than those in primipara (all P＜0.05).The mean maternal age of multipara was (30.02±4.88) years,pre-pregnancy body mass index was 22.24 ± 3.48,which were all higher than those of primipara [(27.82 ± 4.03) years and 21.54 ± 3.29,respectively,t=23.440 and 11.115,all P＜0.01].And the gestational weeks at delivery and mean weight gain during pregnancy of multipara was less than that of primipara [(39.15 ±1.67) vs (39.49 ± 1.67) weeks,t=-14.044,P=0.000;(14.66±6.24) vs (15.81 ± 5.86) kg,t=-9.448,P=0.000],while the levels of total cholesterol,triglyceride and low density lipoprotein-cholesterol and the incidence of macrosomia were significantly higher [(5.59± 1.14) vs (5.24± 1.15) mmol/L,(2.31± 1.38) vs (1.96± 1.34) mmol/L,(3.03±0.91) vs (2.82±0.87) mmol/L,t=12.867,15.718 and 10.275,all P＜0.01;9.29％ (298/3 209) vs 7.24％ (868/11 985),x2=14.926,P=0.000].Significantly lower incidences of abnormal amniotic fluid volume,premature rupture of membranes,fetal distress,abnormal labor and vaginal delivery (all P ＜ 0.01),but higher neonatal birth weight [(3 374.38 ±504.57) vs (3 328.39±488.70) g,t=4.839,P=0.000] and cesarean section rate [45.96％ (1 475/3 209) vs 42.49％(5 092/11 985),x2=12.477,P＜0.01] were found in multipara than in primipara.Compared with primipara,multipara had higher incidence of gestational diabetes mellitus,diabetes during pregnancy,pregnancy complicated with cardiovascular problems,hypertensive disorder complicating pregnancy [adjusted OR(95％CI):1.265 (1.135-1.411),1.799 (1.215 2.663),1.567 (1.221-2.347),1.647 (1.300-2.086),all P＜0.01].Conclusions The primipara is the major reproductive population in Beijing area.However,the multipara requires close antenatal care because of their susceptibility to pregnant complications.

Long-term effects of mild intrauterine hyperglycemia on glucose and lipid metabolism in intergenerational rat offspring / 中华围产医学杂志

Objective To observe the long-term effects of maternal mild hyperglycemia on the growing development and glucose and lipid metabolism in intergenerational rat offspring.Methods Streptozotocin (25 mg/kg) was administered to 14 pregnant Wistar rats intraperitoneally on the first day of gestation to induce an animal model of mild intrauterine hyperglycemia,which was successful in nine rats.Seven pregnant rats without streptozotocin intervention served as controls.Female first-generation offspring (F1) rats were intercrossed with normal male rats to obtain the second-generation offspring (F2) rats.F1 and F2 rats were divided into 8 groups:female group (group F1-G-♀) or male group (group F1-G-♂) exposed to intrauterine hyperglycemia;female group (group F1-C-♀) or male group (group F1-C-♂) exposed to intrauterine euglycemia;transgenerational female group (group F2-G-♀) or male group (group F2-G ♂)exposed to intrauterine hyperglycemia;and transgenerational female group (group F2-C-♀) or male group (group F2-C-♂) exposed to intrauterine euglycemia.Body weight of the offspring was recorded.At the age of 28 weeks,the weight of pancreas and visceral fat,fasting plasma glucose (FPG),fasting insulin,total triglyceride,total cholesterol,high-density lipoprotein-cholesterol,low-density lipoprotein-cholesterol were measured in all groups.Two sample t test was used for statistical analysis.Results (1) At 4,24 and 28 weeks old,the body weight of group F2-G-♀ [(177.3± 12.3),(314.5± 13.9) and (322.3± 16.2) g] was remarkably increased compared with group F2-C-♀ [(164.3±6.0),(290.2± 18.3) and (300.2± 16.2) g,t=-2.324,-2.584and-2.359,all P ＜ 0.05].(2) At 28 weeks,the pancreas weight and the ratio of pancreas weight to body weight of group F1-G-♀ [(0.53 ±0.05) g and (0.17±0.02)％] were decreased significantly compared with group F1-C-♀ [(0.65±0.04) g and (0.21±0.02)％,t=4.159 and 2.483,both P ＜ 0.05].The pancreas weight,ratio of pancreas weight to body weight,visceral fat weight and fat weight of mass ratio in groups F2-G-♂ and F2-G-♀ were not remarkably different from groups F2-C-♂ and F2-C-♀,respectively (all P ＞ 0.05).(3)The level of FPG at three weeks of age in F2-G-♀ group was higher than in F2-C-♀ group [(6.5±0.8) vs (4.9±1.2) mmol/L,t=-2.786,P ＜ 0.05],and it was also higher in F2-G-♂ group than in F2-C-♂ group [(6.3±0.8) vs (4.7± 1.0) mmol/L,t=-2.696,P ＜ 0.05].At 28 weeks,the FPG level was (6.7±0.6) and (8.4±2.2) mmol/L in F2-G-♀ and F2-G-♂ groups,being higher than in F2-C-♀ and F2-C-♂ groups,respectively [(5.8±0.5) and (6.2± 1.0) mmol/L,t=-2.695 and-2.337,both P ＜ 0.05].Compared with F1-C-♀ group [(0.61 ±0.10) mmol/L],the high-density lipoprotein-cholesterol level was lower in F1-G-♀ group [(0.47±0.05) mmol/L,t=2.433,P ＜ 0.05].(4) In groups F1-G-♀,F2-G-♀ and F2-G-♂,the structure of the islet cells was obviously atrophic and disordered,and β-cells were slightly decreased and distributed unevenly,but group F1-G-♂ had significantly increased β-cells with hypertrophic islet size compared with control group.Conclusions F 1 rat offsprings exposed to mild intrauterine hyperglycemia experience excessive weight gain after birth,impaired structure of the islet,metabolic abnormality,increased visceral fat weight and glucose and lipid metabolism disorder,which show intergenerational inheritance and gender differences.

Construction and function of forensic interest group for medical students of eight-year-program / 中华医学教育探索杂志

The aim of the eight year medical education program is to cultivate high-leveled and high qualified clinical and research personnel.Constructing forensic interest group for medical students of eight year program can not only cultivate the students' English learning,innovative thinking and practice ability,which is their Achilles heel but also combine eight year medical education with forensic science teaching reform.