Effectiveness of a breastfeeding promotion intervention model based on Society ecosystems Theory for maternal women: a study protocol of randomized controlled trial.

BACKGROUND: Breastfeeding is recognized internationally as the most scientific and effective way to feed infants and young children. According to the World Health Organization in 2022, the exclusive breastfeeding rate within 6 months is 34.1% in China, which is still far from the goal of "more than 60% exclusive breastfeeding rate of infants within 6 months" by 2030 required by China's State Council. It is necessary to promote breastfeeding and provide maternal breastfeeding guidance to increase exclusive breastfeeding. Factors influencing breastfeeding can be explained by the society ecosystems theory, distributed in macro, mezzo and micro systems. The interventions focused on breastfeeding promotion are mainly carried out in the health systems and services, home and family environment, community environment, work environment, policy environment or a combination of these facilities. But there is sparse research on integrating resources in the macro, mezzo and micro systems of maternal breastfeeding processes to promote breastfeeding behavior. A randomized controlled trial will test the effect of a breastfeeding promotion intervention model based on the society ecosystems theory versus usual prenatal and postnatal care on maternal and infant health and the exclusive breastfeeding rate at 6 months. METHODS/DESIGN: The study is a single-blind, parallel design, randomized controlled trial with an intervention group (n = 109) and a control group (n = 109) that compares the effect of a breastfeeding promotion intervention model based on the society ecosystems theory with usual prenatal and postnatal care. The intervention covers macro- (policy, culture), mezzo- (family-hospital-community) and micro- (biological, psychological and social) systems of the maternal breastfeeding process. Infant feeding patterns, neonatal morbidity and physical and mental health of antenatal and postpartum women will be collected at baseline (28 to 35 weeks of gestation), 1-, 4-, and 6-month postpartum. DISCUSSION: This is a multifaceted, multifactorial, and multi-environmental breastfeeding promotion strategy to help mothers and their families learn breastfeeding knowledge and skills. The study provides a new modality for adding breastfeeding interventions to prenatal and postnatal care for healthcare providers in the hospital and the community. TRIAL REGISTRATION: Chinese Clinical Trial Registry at www.chictr.org.cn , ChiCTR2300075795.

Maternal education and support during breastfeeding can increase maternal breastfeeding self-efficacy, promote breastfeeding behaviors, and improve maternal and infant health outcomes. The interventions focused on breastfeeding promotion are mainly carried out in the health systems and services, home and family environment, community environment, work environment, policy environment or a combination of any of these facilities. But there is sparse research on integrating in multifaceted, multifactorial, and multi-environmental resources of maternal breastfeeding processes to help pregnant women and their families learn breastfeeding knowledge and skills. The current study optimizes the existing breastfeeding promotion intervention program and construct a breastfeeding promotion intervention program to correct the public's perception of breastfeeding, increase breastfeeding self-efficacy and improve breastfeeding behavior, thus increasing the breastfeeding duration and improving maternal and infant outcomes. The program includes presenting breastfeeding-related policies and support facilities; prenatal educational sessions combined with theories and skills on breastfeeding, development of lactation, infants feeding and cares for maternal families; postnatal hands-on instruction and WeChat group peer support from hospital; home visits, group counseling and experience sharing from community and one-on-one personalized counseling throughout the intervention. The present study will be conducted to evaluate the effect of breastfeeding promotion intervention including prenatal and postnatal care on the breastfeeding duration, breastfeeding attitudes, knowledge, and self-efficacy, maternal and infant health.

Obesity as a "self-regulated epidemic": coverage of obesity in Chinese newspapers.

OBJECTIVE: The aim of this study was to investigate how obesity was covered in Chinese newspapers from 1999 to 2018, demonstrating the trends and the characteristics of obesity-related news. METHODS: Content analysis was conducted to analyze a total of 358 news articles spanning two decades (1999-2018). We explored how Chinese newspapers portrayed obesity in terms of the evidence/sources cited in articles, its impacts, drivers/causes, and solutions; and how such portrayals have evolved over time. We further compared the articles across different types of newspapers (government-sponsored vs. commercial), two subpopulations (children vs. adults), and periods of time (1999-2008 vs. 2009-2018). RESULTS: Results showed that medical experts' interviews and statistics were the two most cited types of evidence in the articles. When discussing causes and solutions of obesity, factors pertaining to personal lifestyles were mentioned most frequently. Compared to psychological and social impacts, physical health risk was stressed more often. Compared with commercial newspapers, government-funded newspapers mentioned societal drivers of obesity and suggested reforming schools more frequently. Such differences were also found between coverage of child obesity and adult obesity. Our research, furthermore, revealed significant differences of media coverage of obesity across the two decades. CONCLUSIONS: Our findings indicate that obesity was generally depicted as a "self-regulated epidemic" in Chinese newspapers. Although the revealed causes and consequences of obesity are evidently related to individual factors, more attention should be directed to the roles that the government, media, and the society can play in preventing obesity and mitigating related social/economic burden. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Chinese media coverage of eating disorders: Disorder representations and patient profiles.

OBJECTIVE: Eating disorders (EDs) are becoming more prevalent in China; however, no studies have been conducted to explore how Chinese media represented EDs, and how media representation of ED impacted public understanding of EDs. The aim of this study was to analyze articles about EDs in Chinese newspapers, and to identify any potential inaccuracies about EDs as represented in the media. METHOD: Content analysis was employed to analyze a total number of 292 news articles over the span of two decades (1998-2019). Intercoder reliability was satisfactory for all the coded categories. The analysis was conducted on two different dimensions: for individual news article and for individual patient profile. RESULTS: The bulk of news reporting on EDs was about anorexia nervosa and bulimia nervosa. A majority of individual patient profiles focused on young women. Anorexia nervosa was mentioned and discussed more frequently than bulimia nervosa. Chinese newspapers generally presented correct information concerning anorexia nervosa and bulimia nervosa, but conveyed shallow information about the etiology and treatment. There were also misconceptions of EDs as reported in Chinese media. DISCUSSION: EDs have not received sufficient attention in Chinese media, as shown by the media coverage on EDs over the last two decades. Considering the increasing prevalence of EDs in China with its large population base, effective communication strategies are needed to call public attention to this health issue, and to galvanize the medical community and the society to devote more resources to improve the prevention and treatment of EDs in China.

Influences of an NR1I2 polymorphism on heterogeneous antiplatelet reactivity responses to clopidogrel and clinical outcomes in acute ischemic stroke patients.

Pregnane X receptor (PXR) is a member of nuclear receptor subfamily 1 (NR1I2) that is a transcriptional regulator of several metabolic enzymes involved in clopidogrel metabolism. In this study we identified and evaluated the contributions of single nucleotide polymorphisms (SNPs) in NR1I2 and cytochrome P450 (CYP) 2C19 alleles to clopidogrel resistance (CR) and long-term clinical outcomes in acute ischemic stroke (IS) patients. A total of 634 patients with acute IS were recruited, who received antiplatelet medication (clopidogrel or aspirin) every day and completed a 1-year follow-up. The selected SNPs were genotyped, and platelet function was measured. Modified Rankin Scale (mRS) scores and main adverse cardiovascular and cerebrovascular events (MACCE) were noted to assess the prognosis. We showed that SNPs NR1I2 rs13059232 and CYP2C19 alleles (2*/3*) were related to CR. SNP NR1I2 (rs13059232) was identified as an independent risk factor for the long-term clinical outcomes in the clopidogrel cohorts (P < 0.001), but similar results were not observed in a matched aspirin cohort (P > 0.05). Our results suggest that NR1I2 variant (rs13059232) could serve as biomarker for clopidogrel therapy and individualized antiplatelet medications in the treatment of acute IS patients.

Characteristic and improvement on the reconstructed quality of effective perspective images' segmentation and mosaicking-based holographic stereogram.

Based on the effective perspective images' segmentation and mosaicking (EPISM) printing method, the influence of the holographic element (hogel) size on the reconstructed quality is analyzed to improve the reconstructed quality of holographic stereogram. The flipping effect and diffraction effect in the spatial domain are also discussed, and the optical transfer function of the holographic stereogram is used in the spectrum domain to evaluate the reconstructed quality. Theoretical analysis and optical experimental results show that the hogel size plays an important role on the flipping effect as well as the clarity of the reconstrued 3D perspective images of the EPISM-based holographic stereogram, and the flipping effect can be improved significantly with optimized hogel size.

Improvement of printing efficiency in holographic stereogram printing with the combination of a field lens and holographic diffuser.

In this paper, we use a field lens and a holographic diffuser together to improve the printing efficiency of a holographic stereogram printing system based on the effective perspective images' segmentation and mosaicking method. The light rays' regulation function of the field lens and the modulation function of the holographic diffuser are analyzed. Holographic diffusers with different expanding angles are optimized by numerical simulations and verified by optical experiments. We can achieve a better holographic stereogram reconstruction effect as well as a better printing efficiency when adopting a field lens and a 10° holographic diffuser together. With the proposed method, the energy efficiency can be improved, and the printing time can be reduced greatly.

Valproate induced hepatic steatosis by enhanced fatty acid uptake and triglyceride synthesis.

Steatosis is the characteristic type of VPA-induced hepatotoxicity and may result in life-threatening hepatic lesion. Approximately 61% of patients treated with VPA have been diagnosed with hepatic steatosis through ultrasound examination. However, the mechanisms underlying VPA-induced intracellular fat accumulation are not yet fully understood. Here we demonstrated the involvement of fatty acid uptake and lipogenesis in VPA-induced hepatic steatosis in vitro and in vivo by using quantitative real-time PCR (qRT-PCR) analysis, western blotting analysis, fatty acid uptake assays, Nile Red staining assays, and Oil Red O staining assays. Specifically, we found that the expression of cluster of differentiation 36 (CD36), an important fatty acid transport, and diacylglycerol acyltransferase 2 (DGAT2) were significantly up-regulated in HepG2 cells and livers of C57B/6J mice after treatment with VPA. Furthermore, VPA treatment remarkably enhanced the efficiency of fatty acid uptake mediated by CD36, while this effect was abolished by the interference with CD36-specific siRNA. Also, VPA treatment significantly increased DGAT2 expression as a result of the inhibition of mitogen-activated protein kinase kinase (MEK) - extracellular regulated kinase (ERK) pathway; however, DGAT2 knockdown significantly alleviated VPA-induced intracellular lipid accumulation. Additionally, we also found that sterol regulatory element binding protein-1c (SREBP-1c)-mediated fatty acid synthesis may be not involved in VPA-induced hepatic steatosis. Overall, VPA-triggered over-regulation of CD36 and DGAT2 could be helpful for a better understanding of the mechanisms underlying VPA-induced hepatic steatosis and may offer novel therapeutic strategies to combat VPA-induced hepatotoxicity.

One-step real-virtual combined reflection hologram: a 4f relay approach.

The production of conventional optical reflection holograms can be classified into the one-step method or the two-step method. In the one-step method, only the diverging light of an object can be recorded, and the reconstructed scene is a virtual one behind the recording medium. In the two-step method, the diverging light or the converging light can be recorded alternatively. However, the process is complicated considering double exposures. The object is first imaged by a 4f system, and then the interference patterns are recorded by single exposure. The reconstructed image can be either a virtual image behind the recording medium or a real image in front of the recording medium. The ideal imaging property of a 4f system has been demonstrated theoretically, and the proposed method has been verified experimentally.

Emerging role of NRF2 in chemoresistance by regulating drug-metabolizing enzymes and efflux transporters.

Chemoresistance is a disturbing barrier in cancer therapy, which always results in limited therapeutic options and unfavorable prognosis. Nuclear factor E2-related factor 2 (NRF2) controls the expression of genes encoding cytoprotective enzymes and transporters that protect against oxidative stress and electrophilic injury to maintain intrinsic redox homeostasis. However, recent studies have demonstrated that aberrant activation of NRF2 due to genetic and/or epigenetic mutations in tumor contributes to the high expression of phase I and phase II drug-metabolizing enzymes, phase III transporters, and other cytoprotective proteins, which leads to the decreased therapeutic efficacy of anticancer drugs through biotransformation or extrusion during chemotherapy. Therefore, a better understanding of the role of NRF2 in regulation of these enzymes and transporters in tumors is necessary to find new strategies that improve chemotherapeutic efficacy. In this review, we summarized the recent findings about the chemoresistance-promoting role of NRF2, NRF2-regulated phase I and phase II drug-metabolizing enzymes, phase III drug efflux transporters, and other cytoprotective genes. Most importantly, the potential of NRF2 was proposed to counteract drug resistance in cancer treatment.

Associations of CYP3A4, NR1I2, CYP2C19 and P2RY12 polymorphisms with clopidogrel resistance in Chinese patients with ischemic stroke.

AIM: There is a high incidence of the antiplatelet drug clopidogrel resistance (CR) in Asian populations. Because clopidogrel is a prodrug, polymorphisms of genes encoding the enzymes involved in its biotransformation may be the primary influential factors. The goal of this study was to investigate the associations of polymorphisms of CYP3A4, NR1I2, CYP2C19 and P2RY12 genes with CR in Chinese patients with ischemic stroke. METHODS: A total of 191 patients with ischemic stroke were enrolled. The patients were treated with clopidogrel for at least 5 days. Platelet function was measured by light transmission aggregometry. The SNPs NR1I2 (rs13059232), CYP3A4(*)1G (rs2242480), CYP2C19(*)2 (rs4244285) and P2RY12 (rs2046934) were genotyped. RESULTS: The CR rate in this population was 36%. The CYP2C19(*)2 variant was a risk factor for CR ((*)2/(*)2+wt/(*)2 vs wt/wt, OR: 2.366, 95% CI: 1.180-4.741, P=0.014), whereas the CYP3A4(*)1G variant had a protective effect on CR ((*)1/(*)1 vs (*)1G/(*)1G+(*)1/(*)1G, OR: 2.360, 95% CI: 1.247-4.468, P=0.008). The NR1I2 (rs13059232) polymorphism was moderately associated with CR (CC vs TT+TC, OR: 0.533, 95% CI: 0.286-0.991, P=0.046). The C allele in P2RY12 (rs2046934) was predicted to be a protective factor for CR (CC+TC vs TT, OR: 0.407, 95% CI: 0.191-0.867, P=0.018). In addition, an association was found between hypertension and CR (P=0.022). CONCLUSION: The individuals with both the CYP2C19(*)2 allele and hypertension are at high risk of CR during anti-thrombosis therapy. The CYP3A4(*)1G allele, P2RY12 (rs2046934) C allele and NR1I2 (rs13059232) CC genotype may be protective factors for CR. The associated SNPs studied may be useful to predict clopidogrel resistance in Chinese patients with ischemic stroke.

A calculus of probability or belief? Neural underpinnings of social decision-making in a card game.

For decades, the prefrontal cortex (PFC) has been the focus of social neuroscience research, specifically regarding its role in competitive social decision-making. However, the distinct contributions of PFC subregions when making strategic decisions involving multiple types of information (social, non-social, and mixed information) remain unclear. This study investigates decision-making strategies (pure probability calculation vs. mentalizing) and their neural representations using functional near-infrared spectroscopy (fNIRS) data collected during a two-person card game. We observed individual differences in information processing strategy, indicating that some participants relied more on probability than others. Overall, the use of pure probability decreased over time in favor of other types of information (e.g., mixed information), with this effect being more pronounced within-round trials than across rounds. In the brain, (1) the lateral PFC activates when decisions are driven by probability calculations; (2) the right lateral PFC responds to trial difficulty; and (3) the anterior medial PFC is engaged when decision-making involves mentalizing. Furthermore, neural synchrony, which reflects the real-time interplay between individuals' cognitive processes, did not consistently contribute to correct decisions and fluctuated throughout the experiment, suggesting a hierarchical mentalizing mechanism at work.

A reproducible and generalizable software workflow for analysis of large-scale neuroimaging data collections using BIDS Apps.

Neuroimaging research faces a crisis of reproducibility. With massive sample sizes and greater data complexity, this problem becomes more acute. Software that operates on imaging data defined using the Brain Imaging Data Structure (BIDS) - BIDS Apps - have provided a substantial advance. However, even using BIDS Apps, a full audit trail of data processing is a necessary prerequisite for fully reproducible research. Obtaining a faithful record of the audit trail is challenging - especially for large datasets. Recently, the FAIRly big framework was introduced as a way to facilitate reproducible processing of large-scale data by leveraging DataLad - a version control system for data management. However, the current implementation of this framework was more of a proof of concept, and could not be immediately reused by other investigators for different use cases. Here we introduce the BIDS App Bootstrap (BABS), a user-friendly and generalizable Python package for reproducible image processing at scale. BABS facilitates the reproducible application of BIDS Apps to large-scale datasets. Leveraging DataLad and the FAIRly big framework, BABS tracks the full audit trail of data processing in a scalable way by automatically preparing all scripts necessary for data processing and version tracking on high performance computing (HPC) systems. Currently, BABS supports jobs submissions and audits on Sun Grid Engine (SGE) and Slurm HPCs with a parsimonious set of programs. To demonstrate its scalability, we applied BABS to data from the Healthy Brain Network (HBN; n=2,565). Taken together, BABS allows reproducible and scalable image processing and is broadly extensible via an open-source development model.

Reproducing FSL's fMRI data analysis via Nipype: Relevance, challenges, and solutions.

The "replication crisis" in neuroscientific research has led to calls for improving reproducibility. In traditional neuroscience analyses, irreproducibility may occur as a result of issues across various stages of the methodological process. For example, different operating systems, different software packages, and even different versions of the same package can lead to variable results. Nipype, an open-source Python project, integrates different neuroimaging software packages uniformly to improve the reproducibility of neuroimaging analyses. Nipype has the advantage over traditional software packages (e.g., FSL, ANFI, SPM, etc.) by (1) providing comprehensive software development frameworks and usage information, (2) improving computational efficiency, (3) facilitating reproducibility through sufficient details, and (4) easing the steep learning curve. Despite the rich tutorials it has provided, the Nipype community lacks a standard three-level GLM tutorial for FSL. Using the classical Flanker task dataset, we first precisely reproduce a three-level GLM analysis with FSL via Nipype. Next, we point out some undocumented discrepancies between Nipype and FSL functions that led to substantial differences in results. Finally, we provide revised Nipype code in re-executable notebooks that assure result invariability between FSL and Nipype. Our analyses, notebooks, and operating software specifications (e.g., docker build files) are available on the Open Science Framework platform.

Cryo-EM structures of Escherichia coli Ec86 retron complexes reveal architecture and defence mechanism.

First discovered in the 1980s, retrons are bacterial genetic elements consisting of a reverse transcriptase and a non-coding RNA (ncRNA). Retrons mediate antiphage defence in bacteria but their structure and defence mechanisms are unknown. Here, we investigate the Escherichia coli Ec86 retron and use cryo-electron microscopy to determine the structures of the Ec86 (3.1 Å) and cognate effector-bound Ec86 (2.5 Å) complexes. The Ec86 reverse transcriptase exhibits a characteristic right-hand-like fold consisting of finger, palm and thumb subdomains. Ec86 reverse transcriptase reverse-transcribes part of the ncRNA into satellite, multicopy single-stranded DNA (msDNA, a DNA-RNA hybrid) that we show wraps around the reverse transcriptase electropositive surface. In msDNA, both inverted repeats are present and the 3' sides of the DNA/RNA chains are close to the reverse transcriptase active site. The Ec86 effector adopts a two-lobe fold and directly binds reverse transcriptase and msDNA. These findings offer insights into the structure-function relationship of the retron-effector unit and provide a structural basis for the optimization of retron-based genome editing systems.

Objective Facts or Misleading Hype? Associations between Features of E-Cigarette Marketing and Sales on a Chinese E-Commerce Platform.

Background: Electronic cigarettes (e-cigarettes) have been increasingly advertised and marketed in China in recent years. This study examined the practice and impact of e-cigarette online marketing on a major retail website-Tmall.com. Methods: Data were obtained by crawling 449 online pages of e-cigarette marketing. Content analysis was conducted to summarize the marketing practices for four types of e-cigarettes, and multilevel modeling (MLM) was implemented to explore factors predictive of the online sales of the products. Results: The sales volume of e-cigarettes ranged from 0 to 28,169, with the price per item varying from RMB 218.1 ($31.84) to RMB 385.5 ($56.29). Fruit (44.3%, n = 199), mint (33%, n = 148) and cream/sugar/ice (29.4%, n = 132) were the three flavors most often listed for sale online. Moreover, 63.4% (n = 285) of e-cigarette ads emphasized the role of the products as an aid to quit smoking. Nice taste (75.1%), big vapor (65.7%), high capacity batteries (67.9%), fashionable models (61.3%), discounted price (49.7%), and suitability for gifting (45.9%) were the most frequently touted product features in online ads. Type of e-cigarettes, diversity of products, number of online comments, and location of manufacturers were significantly associated with sales volume. Conclusions: Online marketing of e-cigarettes was common on one of China's leading e-commerce websites. Sellers employed advertising strategies targeting a wide range of potential consumers-from youth to the elderly. Stricter regulations of online marketing for e-cigarettes should be enforced in China.

Characteristic and optimization of the effective perspective images' segmentation and mosaicking (EPISM) based holographic stereogram: an optical transfer function approach.

Based on our proposed method for holographic stereogram printing using effective perspective images' segmentation and mosaicking (EPISM), we analyze the reconstructed wavefront errors, and establish the exit pupil function model of proposed printing system. To evaluate the imaging quality, the optical transfer function (OTF) of the holographic stereogram is modelled from the aspect of frequency response. The characteristic of the OTF with respect to the exit pupil size and the aberration are investigated in detail. We also consider the flipping effect in spatial domain. The optimization of hogel sizes, i.e., the sampling interval of original perspective images and the printing interval of synthetic effective perspective images, are given for the optimized reconstruction. Numerical simulations and optical experiments are implemented, and the results demonstrate the validity of our analysis, and the optimized parameters of hogel sizes can improve the imaging quality of full parallax holographic stereogram effectively.

Polymorphisms of peroxisome proliferator-activated receptor γ (PPARγ) and cluster of differentiation 36 (CD36) associated with valproate-induced obesity in epileptic patients.

RATIONALE: Valproate (VPA) is a choice for the treatment of primary generalized epilepsies and partial epilepsies. Unfortunately, weight gain or obesity is one of the most frequent adverse effects of VPA treatment. Genetic factors were shown to be involved in the effect. OBJECTIVE: The aim of this study was to investigate the association of selected single nucleotide polymorphisms (SNPs) of cluster of differentiation 36 (CD36) and peroxisome proliferator-activated receptor γ (PPARγ) with VPA-induced weight gain and obesity in epileptic patients. METHODS: A total of 225 Chinese Han epilepsy patients receiving VPA treatment were recruited in the study. Height and weight for the calculation of body mass index (BMI) were measured at the initiation of VPA therapy and in the follow-up examination. A BMI of 25 kg/m2 or higher was defined as obesity on the basis of the World Health Organization (WHO) criteria for Asian populations. Four SNPs in CD36 (rs1194197, rs7807607) and PPARγ (rs10865710, rs2920502) were genotyped using the Sequenom® MassArray iPlex platform. RESULTS: About 19.6% of epileptic patients receiving VPA therapy were found to become obese. After covariate analysis of age, gender, sex, height, initial BMI, and VPA dosage, the CD36 rs1194197 C allele and rs7807607 T allele (OR, 0.31; 95%CI, 0.13-0.72; P = 0.009 and OR, 0.38; 95%CI; 0.18-0.83; P = 0.02, respectively) were identified as protective factors for VPA-induced obesity. The PPARγ rs10865710 C allele carriers were found to be less likely to suffer from VPA-induced obesity compared with GG genotype carriers (OR, 0.04; 95%CI, 0.01-0.12; P < 0.001). After a Bonferroni correction for multiple comparisons, the genotypic associations of CD36 rs1194197 and PPARγ rs10865710 and the allelic association of CD36 rs7807607 with obesity remained statistically significant. CONCLUSIONS: Our data first indicated that CD36 and PPARγ polymorphisms may be associated with VPA-induced obesity and weight gain, suggesting that CD36 and PPARγ may have potential value in predicting VPA-induced obesity in Chinese Han epileptic patients.

Mechanistic understanding of the effect of Dengzhan Shengmai capsule on the pharmacokinetics of clopidogrel in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The Dengzhan Shengmai capsule (DZSM) is known in China for its remarkable curative effect as a treatment of cardiovascular diseases, such as coronary heart disease and ischemic stroke. DZSM is a Chinese herbal compound preparation that consists of four ingredients, including Erigeron breviscapus (Vaniot) Hand.-Mazz., Panax ginseng C.A. Mey, Ophiopogon japonicas (Thunb.) Ker-Gawl. and Schisandra chinensis (Turcz.) Baill., and was indexed in the Chinese Pharmacopoeia 2010. DZSM and clopidogrel are often co-prescribed in the clinic to prevent the recurrence of stroke or other cardiovascular and cerebrovascular diseases. However, the effect of DZSM on the pharmacokinetics of clopidogrel remains unclear. AIM OF THE STUDY: The purpose of the study is to explore the pharmacokinetics and potential interaction between DZSM and clopidogrel and the underlying mechanism. MATERIALS AND METHODS: Rats were used to investigate the effect of DZSM on the pharmacokinetics of clopidogrel and its active metabolite in vivo. The plasma concentrations were simultaneously determined using LC-MS/MS. The effects of DZSM on the P-gp-mediated efflux transport and CYP450-mediated metabolism of clopidogrel were investigated using MDCKII-MDR1 cells and rat liver microsomes, respectively. RESULTS: After pretreatment with DZSM, the Cmax and AUC0-∞ of clopidogrel increased from 0.4±0.1 to 1.7±0.6ng/mL and 0.9±0.4 to 2.0±0.2ng/mLh, respectively. The Cmax and AUC0-∞ of the derivatized active metabolite of clopidogrel decreased from 8.2±1.2 to 2.8±0.5ng/mL and 18.2±5.6 to 6.4±3.7ngh/mL, respectively. In MDCKII-MDR1 cells, the P-gp-mediated efflux transport of clopidogrel was significantly inhibited by the DZSM extract. In rat liver microsomes, DZSM inhibited clopidogrel metabolism with an IC50 of 0.02mg/mL. CONCLUSIONS: DZSM significantly affects the pharmacokinetics of clopidogrel and its active metabolite by inhibiting the P-gp-mediated efflux transport and CYP450-mediated metabolism of clopidogrel. Thus, caution is needed when DZSM is co-administered with clopidogrel in the clinic because the interaction of these drugs may result in altered plasma concentrations of clopidogrel and its active metabolite.

Survivin expression induced by doxorubicin in cholangiocarcinoma.

AIM: To study the role of survivin expression induced by chemotherapy agent (doxorubicin) in the development and anti-chemotherapy of cholangiocarcinoma. METHODS: Expression of survivin was detected by SP immunohistochemical technique in 33 cases of cholangiocarcinoma, 28 cases of adjacent noncancerous bile duct, and 5 cases of benign bile duct lesions. Low concentration of doxorubicin (0.05 mg/l) was added in cultured cholangiocarcinoma cell line (QBC939). The expression of survivin was detected by RT-PCR and Western blot at 24 h and 48 h after adding doxorubicin. RESULTS: Survivin was expressed in 24 of 33 cholangiocarcinoma cases (72.7%). In contrast, no expression of survivin in adjacent noncancerous and benign bile duct lesions was observed (P<0.01). No correlation was found between survivin expression and clinical features. Doxorubicin could markedly (P<0.001) up-regulate survivin mRNA and protein expression of QBC939 cells. CONCLUSION: Overexpression of survivin in cholangiocarcinomas may play an important role in the development of cholangiocarcinoma, its relationship with prognosis of cholangiocarcinoma deserves further investigation. Higher expression of survivin is induced by doxorubicin in QBC939. Survivin expression may resist apoptosis induced by chemotherapy agents.