Colorectal motility patterns and psychiatric traits in functional constipation and constipation-predominant irritable bowel syndrome: A study from China.

BACKGROUND: Functional constipation (FC) and constipation-predominant irritable bowel syndrome (IBS-C) represent a spectrum of constipation disorders. However, the majority of previous clinical investigations have focused on Western populations, with limited data originating from China. AIM: To determine and compare the colorectal motility and psychiatric features of FC and IBS-C in an Eastern Chinese population. METHODS: Consecutive chronic constipation patients referred to our motility clinic from December 2019 to February 2023 were enrolled. FC and IBS-C diagnoses were established using ROME IV criteria, and patients underwent high-resolution anorectal manometry (ARM) and a colonic transmit test using the Sitz marker study. Constipation-related symptoms were obtained through questionnaires. Anxiety and depression were assessed by the Hamilton anxiety rating scale and the Hamilton Depression Rating Scale-21. The clinical characteristics and colorectal motility patterns of FC and IBS-C patients were compared. RESULTS: No significant differences in sex, age or abdominal discomfort symptoms were observed between IBS-C and FC patients (all P > 0.05). The proportion of IBS-C patients with delayed colonic transit was higher than that of patients with FC (36.63% vs 15.91%, P < 0.05), while rectosigmoid accumulation of radiopaque markers was more common in the FC group than in the IBS-C group (50% vs 26.73%, P < 0.05). Diverse proportions of these dyssynergic patterns were noted within both the FC and IBS-C groups by ARM. IBS-C patients were found to have a higher prevalence of depression than FC patients (66.30% vs 42.42%, P < 0.05). The scores for feelings of guilt, suicide, psychomotor agitation, diurnal variation, obsessive/compulsive disorder, hopelessness, self-abasedment and gastrointestinal symptoms were significantly higher in IBS-C patients than that in FC patients (P < 0.05). For IBS-C (χ2 = 5.438, P < 0.05) but not FC, patients with normal colon transit time were significantly more likely to have anxiety than those with slow colon transit time. For IBS-C patients but not FC patients, the threshold of first constant sensation, desire to defecate and sustained urgency were all weakly correlated with the degree of anxiety (r = 0.414, r = 0.404, and r = 0.418, respectively, P < 0.05). The proportion of patients with a low threshold of desire to defecate among IBS-C patients with depression was lower than that in those without depression (69.6% vs 41.9%, χ2 = 4.054, P < 0.05). CONCLUSION: Our findings highlight both overlapping and distinctive patterns of colon transit, dyssynergic patterns, anorectal sensation, psychological distress, and associations of psychiatric and colorectal motility characteristics in FC and IBS-C patients in an Eastern Chinese population, providing valuable insights into the pathophysiological underpinnings of these disorders.

Progression to type 2 diabetes mellitus after gestational diabetes mellitus diagnosed by IADPSG criteria: Systematic review and meta-analysis.

Background: To estimate the progression rates to type 2 diabetes mellitus (T2DM) in women with gestational diabetes mellitus (GDM) diagnosed by the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria. Methods: Systematic review and meta-analysis were conducted by searching Medline, Embase, and Cochrane between January 1, 2010 and December 31, 2021 for observational studies investigating progression to T2DM after GDM. Inclusion criteria were IADPSG-diagnosed GDM, studies with both GDM and controls, postpartum follow-up duration at least one year. Data were pooled by random effects meta-analysis models. Heterogeneity was assessed by I2 statistic. The pooled relative risk for incidence of T2DM and pre-diabetes between GDM participants and controls were estimated. Reasons for heterogeneity among studies were investigated by prespecified subgroup and meta-regression analysis. Publication bias was assessed by the Begg's and Egger's tests. Results: This meta-analysis of six studies assessed a total of 61932 individuals (21978 women with GDM and 39954 controls). Women with IADPSG-diagnosed GDM were 6.43 times (RR=6.43, 95% CI:3.45-11.96) more likely to develop T2DM in the future compared with controls. For GDM women, the cumulative incidence of T2DM was 12.1% (95% CI: 6.9%-17.3%), while the pooled cumulative incidence of T2DM was estimated to be 8% (95% CI: 5-11%) in studies with 1 to 5 years of follow-up and increased to 19% (95% CI: 3-34%) for studies with more than 5 years of follow-up. Women with IADPSG-diagnosed GDM had 3.69 times (RR=3.69, 95% CI:2.70-5.06) higher risk of developing pre-diabetes (including impaired fasting glucose and/or impaired glucose tolerance) than controls. Meta-regression analysis showed that the study effect size was not significantly associated with study design, race, length of follow-up, and maternal age (P>0.05). Overall, the studies had a relatively low risk of bias. Conclusions: Women with IADPSG-diagnosed GDM have higher risk of developing T2DM and pre-diabetes. The risk of T2DM in GDM women are higher with longer follow-up duration. Our results highlight the importance of promoting postpartum screening and keeping health lifestyle as well as pharmacological interventions to delay/prevent the onset of T2DM/pre-diabetes in GDM women. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42022314776).

Risk Factors for Macrosomia in Multipara: A Multi-Center Retrospective Study.

The increased incidence of macrosomia has caused an enormous burden after the transition from the almost 40-year one-child policy to the universal two-child policy in 2015 and further to the three-child policy in 2021 in China. However, studies on risk factors of macrosomia in multipara under the new fertility policy in China are limited. We aim to explore the incidence and risk factors for macrosomia in multipara to provide the scientific basis for preventing macrosomia in multipara. A multi-center retrospective study was conducted among 6200 women who had two consecutive deliveries in the same hospital and their second newborn was delivered from January to October 2018 at one of 18 hospitals in 12 provinces in China. Macrosomia was defined as birth weight ≥ 4000 g. Logistic regression models were performed to analyze risk factors for macrosomia in multipara. The incidence of macrosomia in multipara was 7.6% (470/6200) and the recurrence rate of macrosomia in multipara was 27.2% (121/445). After adjusting for potential confounders, a higher prepregnancy BMI, higher gestational weight gain, history of macrosomia, a longer gestation in the subsequent pregnancy were independent risk factors of macrosomia in multipara (p < 0.05). Healthcare education and preconception consultation should be conducted for multipara patients with a history of macrosomia to promote maintaining optimal prepregnancy BMI and avoid excessive gestational weight gain to prevent macrosomia.

Thalidomide for prevention of camrelizumab-induced reactive cutaneous capillary endothelial proliferation.

OBJECTIVES: The study evaluated the efficacy of thalidomide in prevention of camrelizumab-induced reactive cutaneous capillary endothelial proliferation (RCCEP). METHODS: In this study, patients treated with camrelizumab plus thalidomide or camrelizumab alone were included. The occurrences, onset time, severity of RCCEP and the adverse effect of thalidomide were analysed. RESULTS: A total of 19 patients were enrolled. The incidence of RCCEP in thalidomide group (2/9, 22.2%) was significantly lower than that in camrelizumab group (8/10, 80%). The median onset time of RCCEP was 5 weeks and 4 weeks respectively. The adverse events of thalidomide were mild, and no treatment-associated interruption was observed. CONCLUSIONS: Thalidomide showed a promising in prevention of the RCCEP in patients receiving camrelizumab therapy with an acceptable safety profile.

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.

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 ±â€Š4.03 years vs. 33.00 ±â€Š3.34 years vs. 32.19 ±â€Š3.37 years, P  < 0.001), pregnancy interval (4.06 ±â€Š1.44 years vs. 3.52 ±â€Š1.43 years vs. 3.38 ±â€Š1.35 years, P  = 0.004), prepregnancy body mass index (BMI) (27.40 ±â€Š4.62 kg/m2vs. 23.50 ±â€Š3.52 kg/m2vs. 22.55 ±â€Š3.47 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 ±â€Š1.90 mmol/L vs. 16.27 ±â€Š1.93 mmol/L vs. 15.55 ±â€Š1.92 mmol/L, P < 0.001), OGTT fasting value (5.43 ±â€Š0.48 mmol/L vs. 5.16 ±â€Š0.49 mmol/L vs. 5.02 ±â€Š0.47 mmol/L, P < 0.001), OGTT 1-hour value (10.93 ±â€Š1.34 mmol/L vs. 9.69 ±â€Š1.53 mmol/L vs. 9.15 ±â€Š1.58 mmol/L, P < 0.001), OGTT 2-hour value (9.30 ±â€Š1.66 mmol/L vs. 8.01 ±â€Š1.32 mmol/L vs. 7.79 ±â€Š1.38 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.

An Introduction of EVIDEM Framework and Its Application in Healthcare Decision Making / 中国实验方剂学杂志

Evidence and value：impact on DEcisionMaking （EVIDEM） framework was developed by EVIDEM collaboration. Its core is the combination of multiple criteria decision analysis （MCDA） model and standardized health technology assessment （HTA） report， which aims to evaluate the overall value of medical interventions. It has been tested and implemented in the real-world evaluation environments. After more than 10 years of development， EVIDEM framework has been updated to version 10， and the relevant operation manuals have been published. More than 40 countries have joined the collaboration and more than 20 countries have carried out relevant studies. The framework is constructed with patients， population and sustainability as the overall goals， combing the evidence and value， forming a relatively complete decision-making framework system composed of 2 levels， 7 dimensions and 20 criteria. The two levels include normative universal criteria and contextual criteria. The normative universal criteria， namely EVIDEM core model， is the quantitative evaluation， consisting of 5 dimensions and 13 criteria. Contextual criteria， namely contextual tools， are qualitative evaluation， consisting of 2 dimensions and 7 criteria. The specific operation steps of EVIDEM framework include selecting and constructing criteria， assigning weights， integrating and evaluating evidence， quantitative and qualitative evaluation of value， comprehensive value estimation and ranking based on value estimation. EVIDEM framework is applicable to disease diagnosis， treatment， management and other fields. Its application scope includes medical insurance reimbursement， clinical practice decision-making， drug selection and so on， which can provide a method for more systematic， transparent and scientific healthcare decision-making. At present， the framework has been introduced into the field of traditional Chinese medicine and can provide a scientific and feasible evaluation tool and methodology system for the clinical comprehensive evaluation of Chinese patent medicine.

Relationship between metabolic syndrome and 1-year prognosis of elderly patients with acute cerebral infarction / 中国医师进修杂志

Objective:To investigate the relationship between metabolic syndrome and 1-year poor outcome in elderly patients with acute cerebral infarction (ACI).Methods:The clinical data of elderly patients with ACI admitted to Renqiu Kangjixintu Hospital from January 2014 to November 2018 were selected and divided into metabolic syndrome group (931 cases) and non-metabolic syndrome group (1 851 cases). The clinical data of the two groups of elderly patients with ACI were compared, and the effect of metabolic syndrome on poor outcome (modified Rankin scale>2 scores) of elderly patients with ACI in 1 year was analyzed by multivariate Logistic regression.Results:The proportion of female, hypertension, diabetes, hyperlipidemia, coronary heart disease, smoking, excessive alcohol consumption and antiplatelet drug use in the metabolic syndrome group were higher than those in the non-metabolic syndrome group: 52.74%(491/931) vs. 32.58%(603/1 851), 79.16%(737/931) vs. 64.29% (1 190/1 851), 42.32% (394/931) vs. 6.43% (119/1 851), 17.19% (160/931) vs. 11.62% (215/1 851), 18.90% (176/931) vs. 14.10% (261/1 851), 62.73% (584/931) vs. 50.89% (942/1 851), 3.73% (69/931) vs. 1.61% (15/1 851), 19.23% (179/931) vs. 15.51% (287/1 851), the levels of body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose (FPG), fasting plasma glucose (TG), total cholesterol (TC), platelet (PLT), fibrinogen (FIB), fall score were higher than those in non-metabolic syndrome group: 26.67 (25.31, 28.60) kg/m 2 vs. 23.30 (21.48, 24.91) kg/m 2, (167.17 ± 22.96) mmHg (1 mmHg = 0.133 kPa) vs. (164.21 ± 24.90) mmHg, (87.06 ± 13.10) mmHg vs. (85.76 ± 12.99) mmHg, (7.33 ± 2.64) mmol/L vs. (5.35 ± 1.38) mmol/L, (2.12 ± 1.51) mmol/L vs. (1.13 ± 0.78) mmol/L, (4.97 ± 1.31) mmol/L vs. (4.65 ± 0.99) mmol/L, 213.00 (179.00, 256.00) × 10 9/L vs. 203.00 (172.00, 241.00) × 10 9/L, 3.07 (2.63, 3.52) g/L vs. 2.94 (2.55, 3.37) g/L, (6.12 ± 1.70) scores vs. (5.93±1.74) scores, the levels of age, high density lipoprotein cholesterol (HDL-C), homocysteine (Hcy) and pressure ulcer score were lower than those of non-metabolic syndrome group: (69.29 ± 6.96) years vs. (71.28 ± 7.66) years, (0.98 ± 0.34) mmol/L vs. (1.31 ± 0.88) mmol/L, (18.93 ± 13.07) mmol/L vs. (21.66 ± 16.39) mmol/L, (18.55 ± 2.42) vs. (19.02 ± 2.43), with statistical significance ( P<0.05). After 1-year follow-up, the proportion of poor outcomes in the metabolic syndrome group was higher than that in the non-metabolic syndrome group: 21.70%(202/931) vs. 18.69% (346/1 851), with statistical significance ( P<0.05). Multivariate Logistic regression analysis showed that age, stroke, national institutes of health stroke scale (NIHSS) score at admission, systolic blood pressure, Hcy, pressure ulcer score, fall score, metabolic syndrome were independent risk factors for poor outcome of ACI in 1 year ( OR = 1.056, 1.309, 1.138, 1.005, 1.006, 0.882, 1.076 and 1.285; 95% CI 1.040 to 1.072, 1.037 to 1.652, 1.097 to 1.180, 1.000 to 1.010, 1.000 to 1.013, 0.834 to 0.933, 1.004 to 1.152 and 1.001 to 1.657; P<0.05). Conclusions:Multiple risk factors for stroke are closely related to poor outcome of ACI in the elderly. And metabolic syndrome is an independent risk factor for poor outcome of ACI in the elderly in 1 year.

Correlation between thyroglobulin antibody, thyroid peroxidase antibody,and arteriosclerosis in middle-aged and older adult patients with depression / 中国基层医药

Objective:To investigate the correlation between serum thyroglobulin antibody (TG-Ab) and thyroid peroxidase antibody (TPO-Ab) cconcentrations and arteriosclerosis development in middle-aged and older adult patients with depression.Methods:A total of 200 middle-aged and older adult patients with depression who received treatment in the Third People's Hospital of Huzhou from January 2018 to October 2019 were included in this study. They were divided into four groups ( n = 50/group) according to TG-Ab and TPO-Ab test results: TG-Ab-positive (group 1), TPO-Ab-positive (group 2), TG-Ab-positive and TPO-Ab-positive (group 3), TG-Ab-negative and TPO-Ab-negative (control group). Serum thyroid hormone level, ankle-brachial pressure index (ABI), brachial-ankle pulse wave velocity, and the incidences of intima-media thickening and plaque formation in the lower extremity arteries were compared between groups. Results:Total thyroxine concentration in the control group, groups 1, 2 and 3 was (89.96 ± 2.45) nmol/L, (101.29 ± 3.35) nmol/L, (90.09 ± 2.70) nmol/L, (97.55 ± 2.57) nmol/L, respectively. There was a significant difference in total thyroxine concentration between groups ( F = 3.85, P < 0.05). Brachial-ankle pulse wave velocity in the control group, groups 1, 2, and 3 was (1 327.55 ± 67.78) cm/s, (1 510.36 ± 83.05) cm/s, (1 422.71 ± 71.40) cm/s, (1 533.95 ± 87.01) cm/s, respectively. There was a significant difference in brachial-ankle pulse wave velocity between groups ( F = 65.12, P < 0.05). The incidence of intima-media thickening in the control group, groups 1, 2, and 3 was 18% (9/50), 50% (25/50), 32% (16/50), 60% (30/50), respectively. The incidence of plaque formation in the control group, groups 1, 2, and 3 was 22% (11/50), 56% (28/50), 40% (20/50), 70% (35/50), respectively. There were significant differences in intima-media thickening and plaque formation between groups ( χ2 = 21.83, 25.77, all P < 0.001). Logistic multivariate regression analysis showed that age ( OR = 0.953) and TG-Ab ( OR = 1.116) were independent risk factors for developing arteriosclerosis in middle-aged and older adult patients with depression ( P < 0.05). Conclusion:TG-Ab-positive results are an independent risk factor for developing arteriosclerosis in middle-aged and older adult patients with depression. TPO-Ab-positive results have a synergistic effect on the occurrence and development of arteriosclerosis in middle-aged and older adult patients with depression. Monitoring serum TG-Ab and TPO-Ab concentrations is of great clinical significance for the prevention and treatment of arteriosclerosis in middle-aged and older adult patients with depression.

Toward Heteronuclear Molecular Re(I)-Cu(II) Boxes: Structural, Luminescent, and Magnetic Properties.

The bifunctional ligands of isonicotinic acid (Py-4-COOH) and 4-pyrid-4-ylbenzoic acid (Pybz-4-COOH) instead of polypyridines were therefore reacted with (Re(CO)4)3(C3N3S3) (C3N3S3 = cyanurate trianion), resulting in the formation of two trinuclear [(Re(CO)3)3(C3N3S3)(Py-4-COOH)3] (1) and [(Re(CO)3)3(C3N3S3)(Pybz-4-COOH)3] (2), respectively. In the meantime, both complexes 1 and 2 are connected by three bifurcated hydrogen bonds between their carboxylic acid moieties Py-4-COOH and Pybz-4-COOH to form the supramolecular trigonal-prismatic and -antiprismatic structures, respectively. It is noted that complex 1 can further react with copper(II) nitrate upon deprotonation to give nonanuclear [(Re(CO)3)3(C3N3S3)(Py-4-COO)3]2Cu3(H2O)9 (3), where two trinuclear [(Re(CO)3)3(C3N3S3)(Py-4-COO)3] moieties are connected by three penta-coordinate copper(II) ions, each coordinating to two carboxylates and three water molecules, to form the trigonal-prismatic structure. Surprisingly, addition of pyrazine (pz) in the synthetic process of complex 3 resulted in serendipitous isolation of a rare example of octadecanuclear {[(Re(CO)3)3(C3N3S3)(Py-4-COO)3]2Cu3(H2O)6(pz)2}2 (4), which can be regarded as a dimer of complex 3, connected by two bridging pz ligands. Interestingly, both complexes 3 and 4 are heteronuclear molecular Re(I)-Cu(II) boxes, constructed by a complex-as-a-ligand strategy. Furthermore, complexes 1 and 2 can exhibit respective low-energy luminescence at ca. 561 and 534 nm at room temperature upon photoexcitation, and complex 3 is found to display antiferromagnetic coupling of -127.68 and -134.70 cm-1, possibly due to multiple hydrogen bonds inducing significant Cu(II)···Cu(II) coupling.

Evaluation of the value of fasting plasma glucose in the first trimester for the prediction of adverse pregnancy outcomes.

AIMS: To evaluate the importance and usefulness of fasting plasma glucose (FPG) in the first trimester in predicting adverse pregnancy outcomes. METHODS: A retrospective study of 22,398 singleton pregnancies was conducted. Participants were divided into subgroups according to first-trimester FPG (low FPG, FPG < 5.1 mmol/L; medium FPG, 5.1 mmol/L ≤ FPG < 5.6 mmol/L; high FPG, 5.6 ≤ FPG < 7.0 mmol/L) and oral glucose tolerance test(OGTT) results (normal and abnormal) during pregnancy. Patient characteristics and risk of adverse pregnancy outcomes were compared. Then, the whole population of women with abnormal OGTT served as a reference, and the relative risks of maternal and neonatal complications in normal OGTT women were analyzed by categorical analyses and logistic regression. Subgroup analyses were performed according to pre-pregnancy body mass index (BMI). RESULTS: The frequency of adverse pregnancy outcomes increased with increasing FPG levels during the first trimester, regardless of OGTT results. High FPG + Abnormal OGTT had the worst outcome. Compared to the whole population of women with abnormal OGTT, Normal OGTT + Medium FPG showed the same risk of PIH and macrosomia. Normal OGTT + High FPG showed the same risk of PIH, macrosomia as well as LGA and preterm birth. Additionally, Normal OGTT + Medium FPG + BMI ≥ 24 kg/m2 showed significantly higher risk of PIH (OR = 1.867, 1.245-2.800), macrosomia (OR = 1.748, 1.304-2.344) and LGA (OR = 1.274, 1.019-1.593). Furthermore, the OR value for PIH was 3.759 (1.680-8.412) in Normal OGTT + High FPG + BMI ≥ 24 kg/m2 compared to women with abnormal OGTT. CONCLUSIONS: First-trimester FPG values can help identify women at increased risk for adverse pregnancy outcomes. Increased attention and management should be given to women with early pregnancy FPG ≥ 5.10 mmol/L despite a normal OGTT, especially if their BMI ≥ 24 kg/m2.

Preconception diabetes mellitus and adverse pregnancy outcomes in over 6.4 million women: A population-based cohort study in China.

BACKGROUND: Diabetes mellitus (DM) increases the risk of adverse maternal and neonatal outcomes, and optimization of glycemic control during pregnancy can help mitigate risks associated with diabetes. However, studies seldom focus precisely on maternal blood glucose level prior to pregnancy. We aimed to evaluate the associations between preconception blood fasting plasma glucose (FPG) level and subsequent pregnancy outcomes. METHODS AND FINDINGS: We conducted a population-based retrospective cohort study among 6,447,339 women aged 20-49 years old who participated in National Free Pre-Pregnancy Checkups Project and completed pregnancy outcomes follow-up between 2010 and 2016 in China. During the preconception health examination, serum FPG concentration was measured, and self-reported history of DM was collected. Women were classified into three groups (normal FPG group: FPG < 5.6 mmol/L and no self-reported history of DM; impaired fasting glucose [IFG]: FPG 5.6-6.9 mmol/L and no self-reported history of DM; and DM: FPG ≥ 7.0 mmol/L or self-reported history of DM). The primary outcomes were adverse pregnancy outcomes, including spontaneous abortion, preterm birth (PTB), macrosomia, small for gestational age infant (SGA), birth defect, and perinatal infant death. Logistic regression model was used to calculate odds ratio (OR) and 95% confidence interval (CI) after adjusting for confounding variables. The mean age of women was 25.24 years, 91.47% were of Han nationality, and 92.85% were from rural areas. The incidence of DM and IFG was 1.18% (76,297) and 13.15% (847,737), respectively. Only 917 (1.20%) women reported a history of DM (awareness of their DM status), of whom 37.28% (337) had an elevated preconception FPG level (≥ 5.6 mmol/L), regarded as noncontrolled DM. A total of 1,005,568 (15.60%) women had adverse pregnancy outcomes. Compared with women with normal FPG, women with IFG had higher risks of spontaneous abortion (OR 1.08; 95% CI 1.06-1.09; P < 0.001), PTB (1.02; 1.01-1.03; P < 0.001), macrosomia (1.07; 1.06-1.08; P < 0.001), SGA (1.06; 1.02-1.10; P = 0.007), and perinatal infant death (1.08; 1.03-1.12; P < 0.001); the corresponding ORs for women with DM were 1.11 (95% CI 1.07-1.15; P < 0.001), 1.17 (1.14-1.20; P < 0.001), 1.13 (1.09-1.16; P < 0.001), 1.17 (1.04-1.32; P = 0.008), and 1.59 (1.44-1.76; P < 0.001). Women with DM also had a higher risk of birth defect (OR 1.42; 95% CI 1.15-1.91; P = 0.002). Among women without self-reported history of DM, there was a positive linear association between FPG levels and spontaneous abortion, PTB, macrosomia, SGA, and perinatal infant death (P for trend <0.001, <0.001, <0.001, 0.001, <0.001). Information about hypoglycemic medication before or during pregnancy was not collected, and we cannot adjust it in the analysis, which could result in underestimation of risks. Data on 2-hour plasma glucose level and HbA1c concentration were not available, and the glycemic control status was evaluated according to FPG value in women with DM. CONCLUSIONS: Women with preconception IFG or DM had higher risk of adverse pregnancy outcomes, including spontaneous abortion, PTB, macrosomia, SGA, and perinatal infant death. Preconception glycemic control through appropriate methods is one of the most important aspects of preconception care and should not be ignored by policy makers.

Long non-coding RNA Linc00483 accelerated tumorigenesis of cervical cancer by regulating miR-508-3p/RGS17 axis.

OBJECTIVES: The aim of this study was to uncover the underlying mechanisms of cervical cancer progression and provide potential therapeutic targets for its treatment in clinic. MATERIALS AND METHODS: Real-Time qPCR was used to determine the expression levels of Linc00483, miR-508-3p and RGS17 mRNA in cervical cancer tissues and cell lines. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) assay was conducted to determine cell apoptosis. Western Blot was performed to detect protein expression levels. Wound healing and Transwell assay were employed to determine cell migration and invasion respectively. Online software (TargetScan, miRDB and miR TarBase) were used to predict the regulating mechanisms of Linc00483, miR-508-3p and RGS17, which were validated by dual-luciferase reporter gene system. In vivo tumor-bearing mice models were established to validate the cellular results. RESULTS: Linc00483 aberrantly overexpressed in both cervical cancer tissues and cell lines comparing to the Control groups. Knock-down of Linc00483 inhibited cervical cancer cell proliferation, invasion as well as migration, and promoted cell apoptosis. In addition, miR-508-3p was identified as the downstream target of Linc00483, and miR-508-3p inhibitor abrogated the inhibiting effects of downregulated Linc00483 on cervical cancer cell viability. Furthermore, the expression levels of Linc00483 was positively correlated with RGS17 in the clinical samples and overexpressed Linc00483 increased RGS17 expression levels in cervical cancer cells by sponging miR-508-3p. The in vivo experiments showed that knock-down of Linc00483 inhibited cervical cancer cell tumorigenesis and lung metastasis in mice models. CONCLUSIONS: Knock-down of Linc00483 inhibited the development of cervical cancer by regulating miR-508-3p/RGS17 axis.

Discrimination and Chemical Phylogenetic Study of Four Pulsatilla Herbs Using UPLC-ESI-MS/MS Combined with Hierarchical Cluster Analysis.

A tissue-smashing based ultra-rapid extraction coupled with ultra-performance liquid chromatography tandem-mass spectrometry (UPLC-MS/MS) method was developed to determine 10 major triterpenoid saponins from Pulsatilla herbs. Compound 4 was characterized as betulinic acid glycoside 3-O-α-arabinopyranosyl-28-O-ß-glucopyranosyl-23-hydroxy with HR-ESI-MS, 1H-NMR and 13C-NMR experiment. The MS spectra result showed that the ionization of compound 4 was more efficient in the positive mode. Meanwhile, the ions at m/z 789.6 and m/z 627.5 were selected as precursor and product ion for the determination, respectively. The chromatographic separation was carried out on a Phenomenex Kinetex C18 column using a gradient mobile phase system composed of 0.1% formic acid both in methanol and water at a flow rate of 0.4 mL/min. The detection was performed by multiple reaction monitoring mode, using electrospray ionization in the positive and negative mode. The total run time was 6 min. The calibration curves possessed good linearity with all coefficients higher than 0.9987. The intra- and interday precisions were no more than 4.9%, and the average recoveries were from 97.6% to 103.4% with RSD <4.7%. Moreover, hierarchical cluster analysis was performed to compare and discriminate the Pulsatilla herbs based on the quantitative data. The hierarchical cluster analysis results demonstrated that Pulsatilla chinensis, Pulsatilla cernua, Pulsatilla dahurica, Pulsatilla turczainovii samples could be easily discriminated from each other based on the contents of triterpenoid saponins and the established method is feasible for quality control of Pulsatilla herbs.

Study on the evidence-based decision-making framework for reimbursement technologies in view of EVIDEM / 中国卫生政策研究

This study aimed to establish a new technology for health insurance reimbursement evidence-based decision-making framework on the basis of EVIDEM. Literature review,focus group discussion and qualitative inter-view were used to construct the preliminary decision-making framework,and expert consultation was adopted to deter-mine the necessity and weight of the criteria. The established evidence-based decision-making framework consists of guidelines of normative universal and contextual aspects. The normative aspect included following criteria, need for intervention (i.e. disease severity, size of affected population, benefit type of technology, unmet needs of reim-bursed technology),comparative outcomes of technology (i.e. comparative effectiveness,comparative safety/tolera-bility,comparative patient-perceived/patient-reported outcomes), and economic consequences of technology (i.e. cost,results of economic evaluation). The contextual aspect reflects the mission and mandate of medical insurance, population priorities and the accessibility,common goal and specific interests, political context, and affordability of medical insurance.

Effects of downregulation of HIF-2α gene on biological behaviors of hepatoma cells induced by hypoxia in vitro / 中国免疫学杂志

Objective:To explore the effects of hypoxia-inducible factor 2α genes on under hypoxia on proliferation,apoptosis, cell cycle distribution and migration of invasiveness of human hepatocellular carcinoma cell HepG2.Methods: Human hepatoma cell line HepG2 induced by cobalt chloride (CoCl2) was selected as the research object,construction of siRNA specific carrier HIF-2α, transfection of HepG2 cells under hypoxia.Real-time PCR,Western blot method in the detection of before and after transfection in each group of HIF-2α mRNA and protein expression;MTT method to detect the proliferation of HepG2 cells before and after transfection;apoptosis rate and distribution of cell cycle of HepG2 cells before and after transfection were detected by flow cytometry;Transwell test was used to detect the invasion and migration ability of HepG2 cells before and after transfection.Results: Under hypoxia,significant increased HIF-2α expression in hepatocellular carcinoma HepG2 cells.Specific transfection of HIF-2α siRNA in HepG2 cells after HIF-2α mRNA and protein expression levels were significantly inhibit cell proliferation decreased,apoptosis rate increased in the ratio of G0/G1 phase cells increased synthesis phase (S) and late (G2/M) synthesis cell ratio decreased,which in vitro invasion and migration of cells was inhibited.Conclusion:Expression of HIF-2α increases in hepatocellular carcinoma HepG2 cells under hypoxia. Specific siRNA can be cut by HIF-2α gene expression in HepG2 cells under hypoxia,to inhibit HepG2 cell proliferation,invasion, migration,and change the distribution of cell cycle and induce its apoptosis.

Effect of DEK targeting silence on proliferation and cell cycle of human hepatoma HepG2 cells / 新乡医学院学报

Objective To study the influence of targeted silencing of DEK on the proliferation and cell cycle of human hepatoma cell lines.Methods The human hepatoma cells line HepG2 were routinely cuhured and the cells were divided into blank control group,siRNA control group and DEK siRNA group when the cells grew to 90％ tusion.The cells in blank control group were cultured normally without any treatment;the cells in siRNA control group and DEK siRNA group were transfected with siRNA expression vector and DEK siRNA expression vector mediated by LipofectamineTM2000 liposomes,respectively.The expression of DEK mRNA in HepG2 cells was detected by real-time polymerase chain reaction;the expression of DEK and CyclinD1 protein in HepG2 cells was detected by Western blot;the proliferation of HepG2 cells was detected by methyl thiazolyl tetrazolium method,and the cell cycle was observed by flow cytometry.Results The expression of DEK mRNA in the blank control group,siRNA control group and DEK siRNA group was 0.826 ±0.052,0.776 ±0.051 and 0.420 ±0.050 respectively;the expression of DEK protein in the blank control group,siRNA control group and DEK siRNA group was 0.691 ± 0.073,0.726±0.061 and 0.311 ±0.038 respectively;the expression of CyclinDl protein in the blank control group,siRNA cuntrol group and DEK siRNA group was 0.712 ± 0.069,0.780 ± 0.074 and 0.434 ± 0.039 respectively.The expressions of DEK mRNA,DEK protein and CyclinD1 protein in DEK siRNA group were significantly lower than those in the blank control group and siRNA control group (P ＜ 0.05);there was no statistic difference in the expression of DEK mRNA,DEK protein and CyclinD1 protein between the blank control group and siRNA control group(P ＜0.05).The proliferation ability of HepG2 cells in DEK siRNA group after transfection of 24,48,72,96,120 h was significantly lower than that in the blank control group and siRNA control group(P ＜0.05);there was no statistic difference in the proliferation ability of HepG2 cells between the blank control group and siRNA control group at each time point(P ＜ 0.05).The proportion of G0 + G1 phase cells in DEK siRNA group was significantly higher than that in the blank control group and siRNA control group(P ＜ 0.05);the proportions of S phase and G2 + M phase cells in DEK siRNA group were significantly lower than those in the blank control group and siRNA control group(P ＜ 0.05);there was no statistic difference in the proportion of G0 + G1 phase,S phase and G2 + M phase cells between the blank control group and siRNA control group (P ＜ 0.05).The result of Pearson correlation analysis showed that the expression of CyclinD1 protein was positively correlated with the expression of DEK mRNA and protein(r =0.909,0.899;P ＜ 0.05).Conclusion DEK siRNA can inhibit the proliferation of HepG2 cells,and change the cell cycle distribution through down regulating the expression of DEK gene in HepG2 cells.This process may be related to the down regulation of the expression of CyclinD1.

Cesarean Section Rate in Singleton Primiparae and Related Factors in Beijing, China.

BACKGROUND: The cesarean section rate (CSR) has been a main concern worldwide. The present study aimed to investigate the CSR in Beijing, China, and to analyze the related factors of CS delivery. METHODS: An observational study was conducted in 15 medical centers in Beijing using a systemic cluster sampling method. In total, 15,194 pregnancies were enrolled in the study between June 20, 2013 and November 30, 2013. Independent t-tests and Pearson's Chi-square test were used to examine differences between two groups, and related factors of the CSR were examined by multivariable logistic regression. RESULTS: The CSR was 41.9% (4471/10,671) in singleton primiparae. Women who were more than 35 years old had a 7.4-fold increased risk of CS delivery compared with women <25 years old (odd ratio [OR] = 7.388, 95% confidence interval [CI] = 5.561-9.816, P < 0.001). Prepregnancy obese women had a 2-fold increased risk of CS delivery compared with prepregnancy normal weight women (OR = 2.058, 95% CI = 1.640-2.584, P < 0.001). The excessive weight gain group had a 1.4-fold increased risk of CS delivery compared with the adequate weight gain group (OR = 1.422, 95% CI = 1.289-1.568, P < 0.001). Gestational diabetes mellitus (GDM) women and DM women had an increased risk of CS delivery (1.2- and 1.7-fold, respectively) compared with normal blood glucose women. Women who were born in rural areas had a lower risk of CS delivery than did those who were born in urban areas (OR = 0.696, 95% CI = 0.625-0.775, P < 0.001). The risk of CS delivery gradually increased with a decreasing education level. Neonates weighing 3000-3499 g had the lowest CSR (36.2%). Neonates weighing <2500 g had a 2-fold increased risk of CS delivery compared with neonates weighing 3000-3499 g (OR = 2.020, 95% CI = 1.537-2.656, P < 0.001). Neonates weighing ≥4500 g had an 8.3-fold increased risk of CS delivery compared with neonates weighing 3000-3499 g (OR = 8.313, 95% CI = 4.436-15.579, P < 0.001). CONCLUSIONS: Maternal age, prepregnancy body mass index, gestational weight gain, blood glucose levels, residence, education level, and singleton fetal birth weight are all factors that might significantly affect the CSR.