Preterm Birth in China Between 2015 and 2016.

Objectives. To describe the incidence, risk factors, and potential causes of preterm birth (PTB) in China between 2015 and 2016.Methods. The China Labor and Delivery Survey was a population-based multicenter study conducted from 2015 to 2016. We assigned each birth a weight based on the sampling frame. We calculated the incidence of PTB and the multivariable logistic regression, and we used 2-step cluster analysis to examine the relationships between PTB and maternal, fetal, and placental conditions.Results. The weighted nationwide incidence of PTB was 7.3% of all births and 6.7% of live births at 24 or more weeks of gestation. Of the PTBs, 70.5% were born after 34 weeks and 42.7% were iatrogenic. Nearly two thirds of all preterm births were attributable to maternal, fetal, or placental conditions, and one third had unknown etiology.Conclusions. This study provided information on the incidence of PTB in China and identified several factors associated with PTB. The high frequency of iatrogenic PTB calls for a careful assessment and prudent management of such pregnancies, as PTB has short- and long-term health consequences.

CS2164, a novel multi-target inhibitor against tumor angiogenesis, mitosis and chronic inflammation with anti-tumor potency.

Although inhibitors targeting tumor angiogenic pathway have provided improvement for clinical treatment in patients with various solid tumors, the still very limited anti-cancer efficacy and acquired drug resistance demand new agents that may offer better clinical benefits. In the effort to find a small molecule potentially targeting several key pathways for tumor development, we designed, discovered and evaluated a novel multi-kinase inhibitor, CS2164. CS2164 inhibited the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRα and c-Kit), mitosis-related kinase Aurora B and chronic inflammation-related kinase CSF-1R in a high potency manner with the IC50 at a single-digit nanomolar range. Consequently, CS2164 displayed anti-angiogenic activities through suppression of VEGFR/PDGFR phosphorylation, inhibition of ligand-dependent cell proliferation and capillary tube formation, and prevention of vasculature formation in tumor tissues. CS2164 also showed induction of G2/M cell cycle arrest and suppression of cell proliferation in tumor tissues through the inhibition of Aurora B-mediated H3 phosphorylation. Furthermore, CS2164 demonstrated the inhibitory effect on CSF-1R phosphorylation that led to the suppression of ligand-stimulated monocyte-to-macrophage differentiation and reduced CSF-1R+ cells in tumor tissues. The in vivo animal efficacy studies revealed that CS2164 induced remarkable regression or complete inhibition of tumor growth at well-tolerated oral doses in several human tumor xenograft models. Collectively, these results indicate that CS2164 is a highly selective multi-kinase inhibitor with potent anti-tumor activities against tumor angiogenesis, mitosis and chronic inflammation, which may provide the rationale for further clinical assessment of CS2164 as a therapeutic agent in the treatment of cancer.

Preventive induction of labor for non-urgent indications at term and maternal and neonatal outcomes.

BACKGROUND: Induction of labor (IOL) is a common practice in many parts of the world. However, the benefits and risks of preventive IOL for the mother and baby have yet to be critically assessed. This study is to investigate the effects of preventive IOL for non-urgent indications at term on maternal and neonatal outcomes. METHODS: In this study, we applied a propensity score model to mimic a randomized clinical trial. Maternal and neonatal outcomes were compared between women with preventive IOL at 37-39 weeks of gestation and women with ongoing pregnancy (expectant management). The subjects were from the Consortium on Safe Labor, a study of over 200,000 births from 19 hospitals across the US from 2002 to 2008. RESULTS: Both nulliparous and multiparous women induced preventively for non-urgent indications at 37-38 weeks' gestation had lower rates of cesarean delivery compared to those delivered at later gestational weeks. However, preventive IOL was associated with increased risks of adverse neonatal outcomes (adjusted odds ratio [aOR] = 1.68, 95% confidence interval [CI], 0.97-2.92 for nulliparas; aOR = 2.22, 1.32-3.74 for multiparas) and admission to NICU (aOR = 1.48, 0.99-2.20 for nulliparas; aOR = 2.08, 1.47-2.96 for multiparas) at 37 weeks' gestation. A longer maternal hospital stay was found among all women with preventive IOL. CONCLUSIONS: Preventive IOL for non-urgent indications may be associated with a decreased risk of cesarean delivery at early term but increased risks of adverse neonatal outcomes at 37 weeks. It also results in a longer hospital stay than expectant management.

Characterization of two tartary buckwheat R2R3-MYB transcription factors and their regulation of proanthocyanidin biosynthesis.

Tartary buckwheat (Fagopyrum tataricum Gaertn.) contains high concentrations of flavonoids. The flavonoids are mainly represented by rutin, anthocyanins and proanthocyanins in tartary buckwheat. R2R3-type MYB transcription factors (TFs) play key roles in the transcriptional regulation of the flavonoid biosynthetic pathway. In this study, two TF genes, FtMYB1 and FtMYB2, were isolated from F. tataricum and characterized. The results of bioinformatic analysis indicated that the putative FtMYB1 and FtMYB2 proteins belonged to the R2R3-MYB family and displayed a high degree of similarity with TaMYB14 and AtMYB123/TT2. In vitro and in vivo evidence both showed the two proteins were located in the nucleus and exhibited transcriptional activation activities. During florescence, both FtMYB1 and FtMYB2 were more highly expressed in the flowers than any other organ. The overexpression of FtMYB1 and FtMYB2 significantly enhanced the accumulation of proanthocyanidins (PAs) and showed a strong effect on the target genes' expression in Nicotiana tabacum. The expression of dihydroflavonol-4-reductase (DFR) was upregulated to 5.6-fold higher than that of control, and the expression level was lower for flavonol synthase (FLS). To our knowledge, this is the first functional characterization of two MYB TFs from F. tataricum that control the PA pathway.

Five new secondary metabolites produced by a marine-associated fungus, Daldinia eschscholzii.

Five new compounds, including a benzopyran ribonic glycoside, daldiniside A (1), two isocoumarin ribonic glycosides, daldinisides B (2) and C (3), and two alkaloids, 1-(3-indolyl)-2R,3-dihydroxypropan-1-one (4) and 3-ethyl-2, 5-pyrazinedipropanoic acid (5), along with five known compounds (6-10), were isolated from the EtOAc extract of the marine-associated fungus, Daldinia eschscholzii. Their structures were elucidated by extensive physicochemical and spectroscopic properties, besides comparison with literature data. The absolute configurations of compounds 1-3 were corroborated by chemical transformation, GC analysis and X-ray crystallographic analysis. Meanwhile, the absolute configuration of compound 4 and the planar structure of compound 6 were also determined based on the X-ray diffraction analysis. The cytotoxicity of compounds 1-10, antifungal and anti-HIV activities of compounds 1-5 and the in vitro assay for glucose consumption of compounds 1-3 were done in the anti-diabetic model, whereas none showed obvious activity.

New norclerodane diterpenoids from the tubers of Dioscorea bulbifera.

Phytochemical investigations of the tubers of Dioscorea bulbifera L. resulted in the isolation of nine norclerodane diterpenoids, including two new compounds, diosbulbins N (1) and P (3), a new naturally occurring compound, diosbulbin O (2), and six known ones, diosbulbins A-D, F and G (4-9). Their structures were established by spectroscopic and chemical methods. The absolute stereochemistry of 1 was determined by a modified Mosher's method, and the absolute configuration of 2 was determined by a single-crystal X-ray diffraction analysis with CuKα irradiation. Compounds 1-3 were evaluated for in vitro cytotoxicity against five human cancer cell lines.

[Effect of Shugan Jianpi Recipe on LXRα/FAS signaling pathway mediated hepatocyte fatty deposits in NAFLD rats].

OBJECTIVE: To explore the effect of Shugan Jianpi Recipe (SJR) on LXRα/FAS signaling pathway mediated hepatocyte fatty deposits in nonalcoholic fatty liver disease (NAFLD) rats. METHODS: Totally 75 SPF grade male SD rats were randomly divided into 5 groups, i.e., the normal control group, the model group, the Shugan Recipe (SR) treatment groups, the Jianpi Recipe (JR) treatment group, and the SJR group. Except rats in the normal control group, the NAFLD rat model was duplicated using high fat diet (HFD). SR (Chaihu Shugan Powder) was administered to rats in the SR group. JR (Shenlin Baizhu Powder) was administered to rats in the JR group. SJR (Chaihu Shugan Powder plus Shenlin Baizhu Powder) was administered to rats in the SJR group. Changes of liver fat were analyzed using automatic biochemical analyzer. Liver cells were separated by low-speed centrifugation. Their activities and purities were identify using Typan blue and flow cytometry (FCM). Expression levels of LXRα and FAS mRNA in hepatocytes detected by Real-time quantitative PCR. Expression levels of LXRα and FAS protein were detected by Western blot. RESULTS: (1) Pathological results showed in the model group, hepatocytes were swollen with nucleus locating at the cell edge after oil red O staining; unequal sized small vacuoles could be seen inside cytoplasm. Some small vacuoles merged big vacuoles. All these indi- cated a NAFLD rat model was successfully established by high fat diet. Pathological structural changes could be impaired to some degree in all medicated groups, especially in the SR group. (2) Compared with the normal control group, expression levels of LXRα and FAS genes and proteins obviously increased in the model group (P < 0.01). Compared with the model group, their expression levels were obviously down-regulated in the JR group and the SR group (P < 0.01, P < 0.05). CONCLUSIONS: LXRα/FAS signaling pathway was an important signaling pathway for mediating lipid metabolism disorders of NAFLD rats. SJR could make hepatocyte fatty deposits tend to repair by adjusting the LXRα/FAS signaling pathway in NAFLD rats, which might be one of important mechanisms for SJR to prevent and cure NAFLD.

[Construction and tobacco transformation of COR and BBE genes hairpin RNA vector of Papaver somniferum].

The gene expressions of codeinone reductase (COR) and berberine bridge enzyme (BBE) in Papaver somniferum were blocked by RNA hairpin of RNA interference (RNAi). The complete sequences of COR and BBE genes were cloned by reverse transcription-polymerase chain reaction (RT-PCR), the results of homology comparison revealed that the cloned COR and BBE genes had high homology with the other gene family members reported in the GenBank. The target sequences of COR and BBE genes were screened in accordance with the design principle of RNAi, a 643 bp fusion gene was obtained by the method of overlapping PCR, then plant expression vector ihpRNA was constructed based on intermediate vector pHANNIBAL and plant expression vector pCEPSPS. With that 78 transgenic plants were obtained through Agrobacterium-mediated and 17 positive plants were screened by PCR, that could initially indicate that the target fragments of COR and BBE gene had been integrated into tobacco genome.

Availability and Affordability of Therapeutic Monoclonal Antibodies After the New Medical Reform in Hubei Province, China.

OBJECTIVE: In 2017, China launched a new round of medical reform (NMR) to address the inaccessibility of high-priced drugs for patients with serious diseases. This study explored the impact of the NMR on the accessibility and affordability of high-priced monoclonal antibodies (mAbs), and the effective promotion policies after the NMR. METHODS: We used a standard method developed by the World Health Organization to conduct two surveys on the availability of mAbs and their prices before and after the NMR in the public hospitals in Hubei province, China. By interviewing hospital pharmacy experts, we identified the potential value of the current NMR in improving the access to therapeutic mAbs. RESULTS: The average availability of 13 mAbs increased by 8.1% in the surveyed hospitals of Hubei province after the NMR. The median unit price of 10 mAbs dropped by 34.3%. The average affordability of a treatment cycle of 10 mAbs dropped from 680 days to 298 days of the disposable daily income for a middle-income resident (56.2% reduction). The drug price negotiation of medical insurance inclusion and the promotion of consistent evaluation of generic and original drugs could effectively promote the accessibility of mAbs. However, the zero markup of drug pricing and the limit on the proportion of drug revenues in public hospitals showed certain negative effects on the availability of mAbs. CONCLUSION: Not all current NMR policies play a positive role in promoting the accessibility of mAbs. To further improve the accessibility of mAbs in the future in China, it is therefore critical to increase the investment in independent research and development of high-quality mAbs, establish localized guidelines for the rational use of mAbs in clinical practice, and have a cost-sharing mechanism for high-priced drugs with multiple stakeholders.

Epidemiology and region-specific risk factors for low Apgar scores in China: a nationwide study.

BACKGROUND: Neonatal asphyxia is a serious public health issue. This study aimed to determine the epidemiology and region-specific risk factors for low Apgar scores, an important proxy for neonatal asphyxia, in China from 2015 to 2016. METHODS: The China Labor and Delivery Survey was a multicenter cross-sectional study including 96 hospitals distributed in 24 (out of 34) provinces. Logistic regression analysis was performed to examine the risk factors for a low Apgar score (< 7). Correspondence analyses were performed among neonates with low Apgar scores to explore the relationship between risk factors and geographical regions. The population attributable risk percentage (PAR%) was calculated for each region-specific risk factor. RESULTS: A total of 72,073 live births, including 320 births with low Apgar scores, were used for the analysis, giving a weighted rate of 3.9/1000 live births. There was a substantial difference in the incidence of low Apgar scores by geographic region, from 2.3/1000 live births in East China to 10.9/1000 live births in Northeast China. Maternal and obstetric factors are the major region-specific risk factors. In Southwest China, hypertensive disorders in pregnancy were more important contributors, with PAR% being 74.47%; in North and Northwest China, pre-pregnancy underweight was a more significant factor, with PAR% of 62.92%; in East China, infants born between 0:00 a.m. and 7:59 a.m. were a key factor, with PAR% of 80.44%. CONCLUSION: Strategies based on region-specific risk factors should be considered to reduce the burden of low Apgar scores in China.

Glycyrrhizin Inhibits SARS-CoV-2 Entry into Cells by Targeting ACE2.

Coronavirus Disease 2019 (COVID-19) is a highly infectious and pathogenic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early in this epidemic, the herbal formulas used in traditional Chinese medicine (TCM) were widely used for the treatment of COVID-19 in China. According to Venn diagram analysis, we found that Glycyrrhizae Radix et Rhizoma is a frequent herb in TCM formulas against COVID-19. The extract of Glycyrrhizae Radix et Rhizoma exhibits an anti-SARS-CoV-2 replication activity in vitro, but its pharmacological mechanism remains unclear. We here demonstrate that glycyrrhizin, the main active ingredient of Glycyrrhizae Radix et Rhizoma, prevents the coronavirus from entering cells by targeting angiotensin-converting enzyme 2 (ACE2). Glycyrrhizin inhibited the binding of the spike protein of the SARS-CoV-2 to ACE2 in our Western blot-based assay. The following bulk RNA-seq analysis showed that glycyrrhizin down-regulated ACE2 expression in vitro which was further confirmed by Western blot and quantitative PCR. Together, we believe that glycyrrhizin inhibits SARS-CoV-2 entry into cells by targeting ACE2.

Structural elucidation of a new flavone from Sarcopyramis nepalensis.

A novel flavone, named 4'-methoxy-3',5,7-trihydroxy-8-(1''-(3''',4''',5'''-trihydroxyphenyl)ethyl)flavone (1), was isolated from Sarcopyramis nepalensis, along with two known compounds syringaresinol (2) and aralidioside (3). Their structures were established by the spectroscopic analysis, especially by 2D NMR. All of the three compounds were isolated from the plant for the first time.

[Studies on the chemical constituents of Toricellia angulata var. intermedia].

OBJECTIVE: To study the chemical constituents of Toricellia angulata var. intermedia. METHODS: The constituents were isolated and purified by repeated column chromatography and their structures were elucidated by spectroscopic analysis. RESULTS: Twelve compounds including beta-sitoterol (1), 7-hydroxy-3-ethylphthalide (2), 3beta-methoxy-stigmast-7-ene (3), stigmast-5-ene (4), trans-p-methylcinnamaldehyde (5), stigmate-7-en-3beta-ol (6), o. p-dimethoxybenzoicacid (7), beta-daucosterol (8), ursolicacid (9), stearic acid (10), docosanoic acid (11), palmitic acid (12) were isolated and identified from this plant. CONCLUSION: All the compounds are isolated from the plant for the first time, compounds 3 -7, 10 -12 are isolated from this genus for the first time.

Smooth muscle SIRT1 reprograms endothelial cells to suppress angiogenesis after ischemia.

Objective: Vascular smooth muscle cells (VSMCs) undergo the phenotypic changes from contractile to synthetic state during vascular remodeling after ischemia. SIRT1 protects against stress-induced vascular remodeling via maintaining VSMC differentiated phenotype. However, the effect of smooth muscle SIRT1 on the functions of endothelial cells (ECs) has not been well clarified. Here, we explored the role of smooth muscle SIRT1 in endothelial angiogenesis after ischemia and the underlying mechanisms. Methods: We performed a femoral artery ligation model using VSMC specific human SIRT1 transgenic (SIRT1-Tg) and knockout (KO) mice. Angiogenesis was assessed in in vivo by quantification of the total number of capillaries, wound healing and matrigel plug assays, and in vitro ECs by tube formation, proliferation and migration assays. The interaction of HIF1α with circRNA was examined by using RNA immunoprecipitation, RNA pull-down and in situ hybridization assays. Results: The blood flow recovery was significantly attenuated in SIRT1-Tg mice, and markedly improved in SIRT1-Tg mice treated with SIRT1 inhibitor EX527 and in SIRT1-KO mice. The density of capillaries significantly decreased in the ischemic gastrocnemius of SIRT1-Tg mice compared with SIRT1-KO and WT mice, with reduced expression of VEGFA, which resulted in decreased number of arterioles. We identified that the phenotypic switching of SIRT1-Tg VSMCs was attenuated in response to hypoxia, with high levels of contractile proteins and reduced expression of the synthetic markers and NG2, compared with SIRT1-KO and WT VSMCs. Mechanistically, SIRT1-Tg VSMCs inhibited endothelial angiogenic activity induced by hypoxia via the exosome cZFP609. The cZFP609 was delivered into ECs, and detained HIF1α in the cytoplasm via its interaction with HIF1α, thereby inhibiting VEGFA expression and endothelial angiogenic functions. Meantime, the high cZFP609 expression was observed in the plasma of the patients with atherosclerotic or diabetic lower extremity peripheral artery disease, associated with reduced ankle-brachial index. Knockdown of cZFP609 improved blood flow recovery after hindlimb ischemia in SIRT1-Tg mice. Conclusions: Our findings demonstrate that SIRT1 may impair the plasticity of VSMCs. cZFP609 mediates VSMCs to reprogram endothelial functions, and serves as a valuable indicator to assess the prognosis and clinical outcomes of ischemic diseases.

[Observation on therapeutic effect of "Tiaoren Tongdu acupuncture" on premature ovarian insufficiency of kidney deficiency].

OBJECTIVE: To observe the clinical efficacy of "Tiaoren Tongdu acupuncture" and oral estradiol and dydrogesterone tablets (femoston) on premature ovarian insufficiency of kidney deficiency. METHODS: A total of 50 patients with premature ovarian insufficiency of kidney deficiency were randomized into an observation group and a control group, 25 cases in each one.In the observation group, "Tiaoren Tongdu acupuncture" was applied at Baihui (GV 20), Zhongwan (CV 12), Guanyuan (CV 4), Qihai (CV 6), Zhongji (CV 3), Yaoyangguan (GV 3), Yaoshu (GV 2), Mingmen (GV 4), etc. once every 2 days, 1 month as a course. In the control group, femoston was prescribed for oral administration, one tablet per time, once a day, 1 month as a course. Both of the two groups were given consecutive treatment for 3 courses. Before and after treatment, the clinical symptoms, menstrual improvement as well as the changes of estradiol (E2), luteotrophic hormone (LH) and follicle-stimulating hormone (FSH) in serum were observed in the two groups. RESULTS: After treatment, the clinical symptoms and menstrual conditions were improved (P<0.01), the levels of FSH and LH were significantly reduced (P<0.01), and the levels of E2 were significantly increased in the two groups (P<0.01). There were no significant difference in menstrual improvement rate and menstrual improvement time between the observation group and the control group (P<0.05), the recurrence rate of menopause and clinical symptom score improvement in the observation group were superior to the control group (P<0.05). In the observation group, the level of E2 in serum was lower and the levels of FSH and LH in serum were significantly lower than those in the control group (P<0.05, P<0.01). In the observation group, the rate of adverse reaction was 4.0% (1/25), which was lower than 36.0% (9/25) in the control group (P<0.05). CONCLUSION: "Tiaoren Tongdu acupuncture" has better therapeutic effect for premature ovarian insufficiency of kidney deficiency. It is superior to femoston in improving clinical symptoms and recurrence rate of menopause as well as reducing the levels of FSH and LH.

Pharmacokinetics, Safety and Tolerability of Chiglitazar, A Novel Peroxisome Proliferator-Activated Receptor (PPAR) Pan-Agonist, in Healthy Chinese Volunteers: A Phase I Study.

BACKGROUND AND OBJECTIVES: Chiglitazar is a novel configuration-restricted non-thiazolidinedione peroxisome proliferator-activated receptor pan-agonist currently in the Phase III clinical development stage for type 2 diabetes mellitus patients. The objective of this Phase I study was to evaluate the pharmacokinetics, safety and tolerability of single and multiple doses of chiglitazar tablets taken orally and the effect of food on its pharmacokinetics in healthy Chinese subjects. METHODS: A single-centre, open-label, randomised, two-stage Phase I study was carried out. In the first-stage study, we evaluated a single dose of 8, 16, or 32 mg, and multiple doses of 16 mg, taken once daily for 9 days. The effect of food consumption was also studied in this stage. In the second-stage study, a greater range of single doses (24, 48 or 72 mg) were further evaluated. Pharmacokinetics, safety and tolerability profiles were assessed at each study stage. RESULTS: After a single oral dose of chiglitazar, at doses ranging from 8 to 72 mg, the maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) were proportionally increased (165-1599 ng/mL for the mean Cmax and 1356-12,584 ng·h/mL for the mean AUC0-t), with low inter-subject variability. There were no significant changes in the mean terminal phase half-life (t1/2), which ranged from 9.0 to 11.9 h, and the clearance and volume of distribution were similar for all evaluated doses. The results from the examination of multiple dose of 16 mg once daily for nine consecutive days showed that a steady-state condition was achieved by Day 6. There was no apparent accumulation of chiglitazar observed at Day 9, as compared with the first administration. While food increased the AUC0-t of chiglitazar by about 13%, there were no effects on other parameters, including Cmax, Tmax and t1/2. There were no serious or severe adverse events observed in the single- or multiple-dose studies. CONCLUSIONS: Chiglitazar tablets showed a good dose-dependent linear pharmacokinetic profile in the dose range of 8-72 mg. There was no accumulation after multiple daily administration of chiglitazar at a dose of 16 mg.  High-fat/calorie food increased the absorption of the drug, but there were no significant changes in exposure and other pharmacokinetic parameters. Chiglitazar was safe and well tolerated in healthy Chinese subjects at the dose levels and administration regimens evaluated.

Study on Drug-Drug Interactions Between Chiglitazar, a Novel PPAR Pan-Agonist, and Metformin Hydrochloride in Healthy Subjects.

Chiglitazar (CHI) is a potent and selective peroxisome proliferator-activated receptor potentially for the treatment of patients with type 2 diabetes mellitus (T2DM). An open-label, randomized, 3-period crossover and self-controlled study was conducted to investigate drug-drug interaction potential between CHI and metformin hydrochloride (MET). Eligible subjects received a single oral dose of CHI (48 mg), MET (1000 mg), or a combination in each period, followed by serial blood sampling collected for up to 48 hours postdose, and safety was assessed throughout the trial. The area under the plasma concentration-time curves from time 0 to 48 hours (AUC0-48 h ) of CHI was similar following administration alone or with MET (AUC0-48h , 12 540 ng·h/mL [9811-15 269 ng·h/mL] vs 12 130 ng·h/mL [9304-14 956 ng·h/mL]; 90% confidence interval [CI] of its geometric mean ratio [GMR], 89.7%-103.8%), whereas the maximum concentration (Cmax ) of CHI was reduced during coadministration, as its 90%CI of the GMR was slightly outside the acceptance range for bioequivalence (Cmax , 1620 ng/mL [1418-1822 ng/mL] vs 1420 ng/mL [1049-1791 ng/mL], 90%CI GMR, 77.%-94.1%). However, it was not considered clinically meaningful. The MET exposures remained consistent in the absence or presence of CHI (AUC0-48 h , 12 570 ng·h/mL [10681-14 459 ng·h/mL] vs 13 190 [10973-15 407 ng·h/mL); 90%CI of GMR: 99.1%-110.5%; Cmax , 1790 ng/mL [1448-2132 ng/mL] vs 1820 ng/mL [1510-2130 ng/mL]; 90%CI of GMR, 94.2%-110.9%). No moderate to severe adverse events were reported. Our study indicated no clinically significant pharmacokinetic drug-drug interaction between CHI and MET and demonstrated good tolerance in subjects. These results support future application of CHI in combination with MET for treatment of T2DM.

[Correlation between XRCC2 and XRCC5 single nucleotide polymorphisms and drug-sensitivity of human lung cancer cells].

OBJECTIVE: To study the associations between XRCC2 and XRCC5 single nucleotide polymorphisms (SNPs) and chemosensitivity of human lung cancer cells. METHODS: Specimens of human lung cancer were collected from 150 patients, 120 males and 30 females, aged 58.1, during operation. MTT method was used to detect the sensitivity of the lung cancer cells to cisplatin (DDP) and carboplatin (CBP), and the patients were genotyped for polymorphisms in XRCC2 and XRCC5 genes. The polymorphisms of XRCC2 41657T C41657T and XRCC5 G74582A were detected by polymerase chain reaction-restriction fraction length polymorphism (PCR-RFLP), and the polymorphisms of XRCC2 G4234C and XRCC5 C74468A were detected by primer-introduced restriction analysis- polymerase chain reaction (PIRA-PCR). The correlation of these polymorphisms of these polymorphisms with the drug-sensitivity of lung cancer cells was analyzed. RESULTS: The sensitive rates of the lung cancer cells to CBP and DDP in the patients with XRCC2 41657T allele (C/T + T/T genotype) were 70.2% and 66.7% respectively, both significantly higher the those in the patients with C/C genotype [53.7% (chi(2) = 3.97, P = 0.046) and 49.5% (chi(2) = 4.25, P = 0.039) respectively]. The sensitivity levels to CBP and DDP in the patients with at least one T allele was 2.06 times (pathological type adjusted OR = 2.06, 95% CI = 1.02 - 4.18) and 2.07 times (pathological type adjusted OR = 2.07, 95% CI = 1.04 - 4.14) higher than those in the patients with C/C genotype. There was no significant difference in the distribution of genotypes of XRCC2 G4234C C allele (C/C + G/C) and G/C genotype between the sensitive group and resistant groups (chi(2) = 0.09, P = 0.766 for CBP and chi(2) = 1.63, P = 0.202 for DDP). The sensitivity rate to DDP of the patients with 41657T/4234G haplotype was 2.28 times as high as that of the patients with 41657T/4234C (OR = 2.18, 95% CI = 1.15 - 4.12). The sensitivity rates to CBP and DDP of the tumor tissues from the patients with the XRCC5 G74582A G allele (A/G + G/G), were 57.9% and 61.8% respectively, and those of the patients with the A/A genotype were 62.2% and 50.0% respectively. There was no significant differences in the genotype distribution between the sensitive and resistant groups (chi(2) = 0.28, P = 0.594 for CBP, and chi(2) = 2.13, P = 0.144 for and DDP). CONCLUSION: The XRCC2 C41657T SNP is associated with the sensitivity to CBP and DDP. The sensitive rate to the drugs of the cancer cells with the combination of C/T + T/T genotype is higher than that with C/C genotype. In the subject with 41657T/4234G the sensitivity to the drugs of the cancer cells is higher than that with 41657C/4234G haplotypes. The XRCC5 G74582A and C74468A SNPs are not associated with the sensitivity to CBP and DDP.

[Effects of Yuquan pills on pharmacokinetics of metformin hydrochloride in diabetic rats].

OBJECTIVE: To study effects of Yuquan pills on the pharmacokinetics process of metformin hydrochloride in diabetic rats. METHOD: After administration Yuquan pills 7 day to the diabetic rats, the metformin hydrochloride was orally administrated, then the blood samples were collected at different time. The concentrations of metformin hydrochloride in plasma were determined by HPLC method and the pharmacokinetic parameters were calculated. RESULT: The pharmacokinetic parameter Cmax of the controlling group and the testing group were respectively, 18.95, 21.76 mg x L(-1); t1/2 were 1,069.8, 1,767.4 min, respectively; CL/F were 0.013, 0.008 L x min(-1) x kg(-1); AUC were 10,042.1, 10,712.2 mg z L(-1) x min(-1) respectively. CONCLUSION: The pharmacokinetics process of metformin hydrochloride in diabetic rats fits one-compartment model. Yuquan pills has a significant effect on the pharmacokinetics of metformin hydrochloride in diabetic rats.

In which groups of pregnant women can the caesarean delivery rate likely be reduced safely in the USA? A multicentre cross-sectional study.

OBJECTIVES: To identify obstetrical subgroups in which (1) the caesarean delivery (CD) rate may be reduced without compromising safety and (2) CD may be associated with better perinatal outcomes. DESIGN: A multicentre cross-sectional study. SETTING: 19 hospitals in the USA that participated in the Consortium on Safe Labor. PARTICIPANTS: 228 562 pregnant women in 2002-2008. MAIN OUTCOME MEASURES: Maternal and neonatal safety was measured using the individual Weighted Adverse Outcome Score. METHODS: Women were divided into 10 subgroups according to a modified Robson classification system. Generalised estimated equation model was used to examine the relationships between mode of delivery and Weighted Adverse Outcome Score in each subgroup. RESULTS: The overall caesarean rate was 31.2%. Repeat CD contributed 29.5% of all CD, followed by nulliparas with labour induction (15.3%) and non-cephalic presentation (14.3%). The caesarean rates in induced nulliparas with a term singleton cephalic pregnancy and women with previous CD were 31.6% and 82.0%, respectively. CD had no clinically meaningful association with perinatal outcomes in most subgroups. However, in singleton preterm breech presentation and preterm twin gestation with the first twin in non-cephalic presentation, CD was associated with substantially improved maternal and perinatal outcomes. CONCLUSIONS: Women with repeat CD, term non-cephalic presentation, term twins or other multiple gestation and preterm births may be the potential targets for safely reducing prelabour CD rate, while nulliparas or multiparas with spontaneous or induced labour, women with repeat CD, term non-cephalic presentation, term twins or other multiple gestation and preterm births are potential targets for reducing intrapartum CD rate without compromising maternal and neonatal safety in the USA. On the other hand, CD may still be associated with better perinatal outcomes in women with singleton preterm breech presentation or preterm twins with the first twin in non-cephalic presentation.