Evaluation of appropriateness of antibiotic prescribing in primary healthcare institutions in China using proxy indicator.

Background: Our objectives were to develop a set of proxy indicators (PIs) suited for assessing antibiotic use appropriateness in China's primary healthcare institutions (PHIs), and assess performance scores of these PIs while exploring factors that influence the antibiotic appropriateness. Methods: We selected potential PIs for the PHIs through a RAND-modified Delphi procedure, and assessed clinimetric properties, focusing on measurability, applicability, and potential for improvement. PIs with favorable clinimetric properties were used to evaluate antibiotic prescription appropriateness by calculating performance scores of each PI. Institutions were categorized into three clusters representing different levels of appropriateness. We used the chi-square test and an ordinal logistic regression model at PHI level to explore factors influencing antibiotic appropriateness. Findings: Eighteen PIs were developed through two rounds of online surveys and one face-to-face meeting involving 20 stakeholders. All PIs met the clinimetric properties criteria and were used to analyze 209,662 antibiotic prescriptions across 269 PHIs. The percentage of PHIs meeting the target ranged from 3.1% to 69.3%, with 6 PIs below 10%. The appropriateness of antibiotic prescriptions was significantly associated with percentages of patients' gender of the PHIs. Interpretation: The varied and suboptimal performance of the PIs indicated the need for diverse efforts to enhance the rational antibiotic use at PHI level. It was necessary to devise distinct sets of PIs for diverse settings in future endeavors. Funding: This work was supported by the National Natural Science Foundation of China (grant numbers 72374009, 81973294).

Machine-Learning-Assisted Descriptors Identification for Indoor Formaldehyde Oxidation Catalysts.

The development of highly efficient catalysts for formaldehyde (HCHO) oxidation is of significant interest for the improvement of indoor air quality. Up to 400 works relating to the catalytic oxidation of HCHO have been published to date; however, their analysis for collective inference through conventional literature search is still a challenging task. A machine learning (ML) framework was presented to predict catalyst performance from experimental descriptors based on an HCHO oxidation catalysts database. MnOx, CeO2, Co3O4, TiO2, FeOx, ZrO2, Al2O3, SiO2, and carbon-based catalysts with different promoters were compiled from the literature. Notably, 20 descriptors including reaction catalyst composition, reaction conditions, and catalyst physical properties were collected for data mining (2263 data points). Furthermore, the eXtreme Gradient Boosting algorithm was employed, which successfully predicted the conversion efficiency of HCHO with an R-square value of 0.81. Shapley additive analysis suggested Pt/MnO2 and Ag/Ce-Co3O4 exhibited excellent catalytic performance of HCHO oxidation based on the analysis of the entire database. Validated by experimental tests and theoretical simulations, the key descriptor identified by ML, i.e., the first promoter, was further described as metal-support interactions. This study highlights ML as a useful tool for database establishment and the catalyst rational design strategy based on the importance of analysis between experimental descriptors and the performance of complex catalytic systems.

Outpatient Antibiotic Prescribing Patterns in Children among Primary Healthcare Institutions in China: A Nationwide Retrospective Study, 2017-2019.

There is scarce evidence to demonstrate the pattern of antibiotic use in children in China. We aimed to describe antibiotic prescribing practices among children in primary healthcare institutions (PHIs) in China. We described outpatient antibiotic prescriptions for children in PHIs from January 2017 to December 2019 at both the national and diagnostic levels, utilizing the antibiotic prescribing rate (APR), multi-antibiotic prescribing rate (MAPR), and broad-spectrum prescribing rate (BAPR). Generalized estimating equations were adopted to analyze the factors associated with antibiotic use. Among the total 155,262.2 weighted prescriptions for children, the APR, MAPR, and BAPR were 43.5%, 9.9%, and 84.8%. At the national level, J01DC second-generation cephalosporins were the most prescribed antibiotic category (21.0%, N = 15,313.0), followed by J01DD third-generation cephalosporins (17.4%, N = 12,695.8). Watch group antibiotics accounted for 55.0% of the total antibiotic prescriptions (N = 52,056.3). At the diagnostic level, respiratory tract infections accounted for 67.4% of antibiotic prescriptions, among which prescriptions with diagnoses classified as potentially bacterial RTIs occupied the highest APR (55.0%). For each diagnostic category, the MAPR and BAPR varied. Age, region, and diagnostic categories were associated with antibiotic use. Concerns were raised regarding the appropriateness of antibiotic use, especially for broad-spectrum antibiotics.

The changes of different restriction level adjustments on antibiotic use in China.

This quasi-experimental study aimed to investigate the changes in antibiotic use tailored by adjusting provincial antibiotic restriction lists in China using interrupted time-series analysis from 2013 to 2019. Antibiotic use was assessed as defined daily dose (DDD) per 1000 patients per day. Trends and level changes were analysed with segmented regression. The study identified 19 antibiotic formulations in four provinces with adjusted restriction levels (intervention group) and 110 formulations in the rest provinces without adjustments (comparison group). Antibiotics restriction level changed between two categories: (1) between 'highly-restricted' and 'restricted' and (2) between 'restricted' and 'non-restricted'. Analysis revealed distinct trend changes for antibiotics moving between 'highly-restricted' and 'restricted' (ß = 0.0211, P = 0.003) and 'restricted' to 'highly-restricted' (ß = -0.0039, P = 0.128) compared to the comparison group. After a 2-y adjustment period, when moving from 'restricted' to 'highly-restricted', absolute antibiotic utilisation significantly decreased (P < 0.001), with a relative decrease of 100.8% (P < 0.001) compared to the comparison group. Besides, individual antibiotics with higher consumption displayed greater responsiveness to adjustment. These findings underscore the changes in restriction level adjustments on antibiotics, highlighting antibiotic restriction list policies as crucial tools for antimicrobial stewardship.

Evaluation of prescription review and feedback policy on rational antibiotic use in primary healthcare settings in Beijing, China: a qualitative study using the Theoretical Domains Framework and the behaviour change wheel.

Objectives: To decelerate antibiotic resistance driven by inappropriate antibiotic prescribing, a prescription review and feedback (PRF) policy is implemented in primary healthcare institutions (PHIs) in Beijing, China. However, evaluation of PRF implementation in PHIs is scarce. This study aims to systematically identify the barriers and facilitators of PRF policy implementation to provide evidence for antimicrobial stewardship. Methods: We conducted key informant interviews with 40 stakeholders engaged in the implementation of PRF in Beijing, including physicians, pharmacists and administrators. Interviews were audio recorded and transcribed verbatim. We coded the interview transcripts and mapped informant views to domains of the Theoretical Domains Framework. We then used a behaviour change wheel to suggest possible behavioural interventions. Results: Procedural knowledge (Knowledge) and skills (Skill) of PRF were possessed by stakeholders. They felt responsible to promote the appropriate use of antibiotics (Social/professional role and identity) and believed that PRF could help to change inappropriate provider behaviours (Behavioural regulation) in prescribing antibiotics (Beliefs about consequences) under increased intention on antibiotic use (Stages of change). Moreover, informants called for a more unified review standard to enhance PRF implementation (Goals). Frequently identified barriers to PRF included inadequate capacity (Skill), using punishment mechanism (Behaviour regulation), reaching consistently lower antibiotic prescription rates (Goals), lack of resources (Environmental context and resources) and perceived pressure coming from patients (Social influences). Conclusions: Stakeholders believed that PRF implementation promoted the rational use of antibiotics at PHIs in Beijing. Still, PRF was hampered by inconsistencies in review process and resources needed for PRF implementation.

Exploring Facilitators and Barriers to Delayed Antibiotic Prescribing in Rural Northwest China: A Qualitative Study Using the Theoretical Domains Framework and Behavior Change Wheel.

BACKGROUND: Antimicrobial resistance, exacerbated by antibiotic misuse, poses a global threat. Though delayed antibiotic prescribing (DAP) can mitigate antibiotic overuse, its adoption in developing nations, such as China, is limited. This study probed barriers and facilitators to DAP in Xinjiang, characterized by extensive rural landscapes and primary care institutions (PCIs). METHODS: Adopting a qualitative methodology, we conducted key informant interviews with thirty participants across six county hospitals in Xinjiang using VooV Meeting. Employing a two-stage sampling method targeting economically diverse areas, our interviews spanned physicians, pharmacists, patients, and caregivers. We organized the data according to the Theoretical Domains Framework (TDF) and the Behavior Change Wheel (BCW), spotlighting behavioral and policy elements impacting DAP. RESULTS: Our research included thirty interviewees. Twelve physicians contemplated delayed prescriptions, while five adult patients and six caregivers encountered recommendations for delayed antibiotic prescriptions. Six patients sought pharmacists' advice on antibiotic necessity. Prominent TDF domains were memory, attention, and beliefs about consequences. Critical intervention functions included education and environmental restructuring, while vital policy categories encompassed communication/marketing and guidelines. CONCLUSIONS: Countering antibiotic misuse and resistance in China necessitates overcoming barriers through strategic resource distribution, comprehensive education, rigorous training, and consistent monitoring, thereby promoting DAP adoption. The adoption of DAP in rural healthcare settings in China has the potential to significantly reduce antibiotic misuse, thereby mitigating the global threat of antimicrobial resistance.

NUAK1 promotes tumor metastasis through upregulating slug transcription in esophageal squamous cell carcinoma.

BACKGROUND: Metastasis is still a major cause of poor pathological outcome and prognosis in esophageal squamous cell carcinoma (ESCC) patients. NUAK1 has been reported highly expressed in many human cancers and is associated with the poor prognosis of cancer patients. However, the role of NUAK1 and its underlying signaling mechanism in ESCC metastasis remain unclear. METHODS: Expression of NUAK1 in ESCC was detected by real-time quantitative RT-PCR (qRT-PCR), Western blotting and immunohistochemical staining. MTT, colony formation, wound-healing and transwell assays were used to determine the role NUAK1 in vitro. Metastasis was evaluated by use of an experimental pulmonary metastasis model in BALB/c-nu/nu mice. The mechanisms were assessed by using coimmunoprecipitation, immunofluorescence and dual-luciferase reporter gene experiments. RESULTS: NUAK1 was highly expressed in ESCC tissues compared with the adjacent normal esophageal epithelial tissues. Moreover, the elevated expression of NUAK1 positively correlated with tumor invasion depth, lymph node metastasis, pathological TNM stage, and poor survival in ESCC patients. Further experiments showed that NUAK1 overexpression did not change the cell viability and colony formation of ESCC cells, while remarkably promoted the migration and invasion in vitro and experimental pulmonary metastasis in vivo. Mechanistically, NUAK1 enhanced the transcription level of Slug, which enhanced the migratory and invasive capability of ESCC cells. Consistently, silencing Slug almost completely diminished the migration and invasion of NUAK1-overexpressing ESCC cells. Further studies demonstrated that NUAK1 upregulated the transcription activity of Slug through activating the JNK/c-Jun pathway. CONCLUSION: These results demonstrated that NUAK1 promoted the metastasis of ESCC cells through activating JNK/c-Jun/Slug signaling, indicating NUAK1 is a promising therapeutic target for metastatic ESCC.

Inpatient antibacterial use trends and patterns, China, 2013-2021.

Objective: To analyse trends and patterns in inpatient antibacterial use in China's tertiary and secondary hospitals between 2013 and 2021. Methods: The analysis involved quarterly data from hospitals covered by China's Center for Antibacterial Surveillance. We obtained information on hospital characteristics (e.g. province, a de-identified hospital code, hospital level and inpatient days) and antibacterial characteristics (e.g. generic name, drug classification, dosage, administration route and usage volume). We quantified antibacterial use as the number of daily defined doses per 100 patient-days. The analysis took into account the World Health Organization's (WHO's) Access, Watch, Reserve classification of antibiotics. Findings: Between 2013 and 2021, overall antibacterial use in inpatients decreased significantly from 48.8 to 38.0 daily defined doses per 100 patient-days (P < 0.001). In 2021, the variation between provinces was almost twofold: 29.1 daily defined doses per 100 patient-days in Qinghai versus 55.3 in Tibet. The most-used antibacterials in both tertiary and secondary hospitals throughout the study period were third-generation cephalosporins, which comprised around one third of total antibacterial use. Carbapenems entered the list of most-used antibacterial classifications in 2015. The most frequently used antibacterials in WHO's classification belonged to the Watch group: usage increased significantly from 61.3% (29.9/48.8) in 2013 to 64.1% (24.4/38.0) in 2021 (P < 0.001). Conclusion: Antibacterial use in inpatients decreased significantly during the study period. However, the rising proportion of last-resort antibacterials used is concerning, as is the large gap between the proportion of antibacterials used belonging to the Access group and WHO's global target of no less than 60%.

Synthesis and stability of switchable CO2-responsive foaming coupled with nanoparticles.

CO2-responsive foaming has been drawing huge attention due to its unique switching characteristics in academic research and industrial practices, whereas its stability remains questionable for further applications. In this paper, a new CO2-switchable foam was synthesized by adding the preferably selected hydrophilic nanoparticle N20 into the foaming agent C12A, through a series of analytical experiments. Overall, the synergy between cationic surfactants and nanoparticles with a contact angle of 37.83° is the best. More specifically, after adding 1.5 wt% N20, the half-life of foam is 14 times longer than that of pure C12A foam. What's more, the C12A-N20 solution is validated to own distinctive CO2-N2 switching features because very slight foaming degradations are observed in terms of the foaming volume and half-life time even after three cycles of CO2-N2 injections. This study is of paramount importance pertaining to future CO2 foam research and applications in energy and environmental practices.

Trends of Fixed-Dose Combination Antibiotic Consumption in Hospitals in China: Analysis of Data from the Center for Antibacterial Surveillance, 2013-2019.

Background: Fixed-dose combination (FDC) antibiotics can be clinically inappropriate and are concerning with regards to antimicrobial resistance, with little usage data available in low- and middle-income countries. Methods: Based on retrospective data from the Center for Antibacterial Surveillance, we investigated the consumption of FDC antibiotics in hospital inpatient settings in China from 1 January 2013 to 31 December 2019. The metric for assessing antibiotic consumption was the number of daily defined doses per 100 bed days (DDD/100BDs). FDC antibiotics were classified according to their composition and the Access, Watch, Reserve (AWaRe) classification of the World Health Organization. Results: A total of 24 FDC antibiotics were identified, the consumption of which increased sharply from 8.5 DDD/100BDs in 2013 to 10.2 DDD/100BDs in 2019 (p < 0.05) despite the reduction in the total antibiotic consumption in these hospitals. The increase was mainly driven by FDC antibiotics in the Not Recommended group of the AWaRe classification, whose consumption accounted for 63.0% (6.4 DDD/100BDs) of the overall FDC antibiotic consumption in 2019, while the consumption of FDC antibiotics in the Access group only accounted for 13.5% (1.4 DDD/100BDs). Conclusion: FDC antibiotic consumption significantly increased during the study period and accounted for a substantial proportion of all systemic antibiotic usage in hospitals in China. FDC antibiotics in the Not Recommended group were most frequently consumed, which raises concerns about the appropriateness of FDC antibiotic use.

Outpatient Antibiotic Prescribing Patterns and Appropriateness for Children in Primary Healthcare Settings in Beijing City, China, 2017-2019.

(1) Background: Few studies have focused on antibiotic use and appropriateness in children in primary health institutions (PHIs). This study aimed to identify the patterns and appropriateness of antibiotic use for children in PHIs in Beijing, China. (2) Methods: Outpatient prescriptions of 327 PHIs from 2017 to 2019 for patients <18 years old were collected. Prescriptions were described using quantity indicators. Antibiotics were categorized according to ATC classification J01 and Access, Watch, Reserve grouping. Appropriateness was reviewed by experts using three subtypes of irrational prescriptions (irregular, inappropriate, and abnormal). (3) Results: 20,618 prescriptions were collected in total. The antibiotic prescription rate (APR) was 15.1% (N = 3113). Among antibiotic prescriptions, J01FA Macrolides were the most used (N = 1068, 34.9%). The Watch group constituted 89.0% (N = 2818) of total antibiotic use. Bronchitis (N = 1059, 35.2%) was the most common diagnosis. A total of 292 instances of irrational antibiotic use were identified, with inappropriate prescriptions being the most prevalent subtype (N = 233, 79.8%). (4) Conclusion: Although APR for children in PHIs in Beijing was relatively low, the pattern of antibiotic use differed from other countries. Further studies are needed to optimize antibiotic use for children in PHIs under different levels of economic development.

Antibiotic use and irrational antibiotic prescriptions in 66 primary healthcare institutions in Beijing City, China, 2015-2018.

OBJECTIVES: To identify the patterns of antibiotic use and irrational antibiotic prescriptions in primary healthcare institutions (PHIs) in Dongcheng District of Beijing, China. MATERIALS AND METHODS: All primary healthcare institutions (7 community healthcare centres and 59 community healthcare stations in total) in Dongcheng District were included in the study. Prescription data from January 2015 to December 2018 was derived from the Beijing Prescription Reviewing System of Primary healthcare institutions and analysed retrospectively. The antibiotic prescription rate was calculated and cases of irrational antibiotic prescriptions were identified. RESULTS: We extracted 11,166,905 prescriptions from the database. Only 189,962 prescriptions were included in the study, among which 9167 (4.8%) contained antibiotics. The antibiotic prescription rate fell from 5.2% in 2015 to 4.1% in 2018 while irrational antibiotic prescription rate increased from 10.4 to 11.8%. Acute Bronchitis was the most prevalent diagnosis (17.6%) for antibiotic prescriptions, followed by Unspecified Acute Respiratory Tract Infection (14.4%), Acute Tonsillitis (9.9%), and Urinary Tract Infection (6.4%). Around 10% of the prescriptions for the top 7 diagnoses identified were rated as irrational. Cephalosporins, fluoroquinolones, and macrolides were the most prescribed antibiotics, which accounted for 89.3% of all antibiotic prescriptions. Of all the antibiotic prescriptions, 7531 were reviewed, among which 939 (12.5%) were rated as irrational because of antibiotic use. Among all the irrational prescriptions, prescriptions with inappropriate antibiotic use and dosage accounted for the majority (54.4%). CONCLUSION: Although a relatively low level of antibiotic utilization was found in PHIs in Dongcheng District of Beijing, the utilization patterns differed considerably from developed countries and irrational prescriptions remained. Considering the imbalanced allocation of medical resources between primary healthcare setting and secondary and tertiary hospitals, there need to be more efforts invested in regions with different levels of economic development.

Efficacy and Safety of Cinobufacin Combined with Chemotherapy for Advanced Breast Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Cinobufacin is a Chinese patent medicine widely used for breast cancer in China. However, no systematic review and meta-analysis have been published to validate its effects in breast cancer treatment. We, therefore, summarize the efficacy and safety of Cinobufacin combined with chemotherapy in order to provide rigid evidence for its clinical application. METHODS: By searching multiple databases incepted to December 2019, the RCTs of breast cancer patients treated with Cinobufacin were screened according to the inclusion criteria, and the meta-analysis and sensitivity analysis were conducted using RevMan5.3. RESULTS: A total of 1163 articles were retrieved, and 16 studies were included. The total sample size was 1331 cases, including 666 cases in the treatment group receiving Cinobufacin combined with chemotherapy and 665 cases in the control group receiving chemotherapy alone. Our study found that the ORR (overall response rate) (RR = 1.35, 95% CI: [1.23, 1.49], P < 0.00001), CBR (clinical benefit rate) (RR = 1.14, 95% CI: [1.08, 1.21], P < 0.00001), KPS scores (RR = 1.98, 95% CI: [1.45, 2.68], P < 0.0001), and pain relief rate (RR = 1.34, 95% CI: [1.01, 1.78] P=0.04 of the Cinobufacin combined with chemotherapy group were better than those of the chemotherapy group, and the difference was statistically significant. Our study also discovered that the tumor markers (CA125, CA153, and CEA) in the Cinobufacin combined with chemotherapy group were lower than those in the chemotherapy group, which heterogeneity was derived from the low-quality literature included in the study, but the results were robust. In addition, in terms of safety, we found that the incidences of gastrointestinal reactions (RR = 0.58, 95% CI: [0.48, 0.70], P < 0.00001), liver and kidney damage (RR = 0.57, 95% CI: [0.38, 0.84], P=0.004), and hair loss (RR = 0.61, 95% CI: [0.40, 0.92], P=0.02) in the Cinobufacin combined chemotherapy group were lower than those in the chemotherapy group, and the difference was statistically significant, but the incidences of peripheral neurotoxicity (RR = 0.69, 95% CI: [0.26, 1.85], P=0.46) and myelosuppression (RR = 0.78, 95% CI: [0.46, 1.34], P=0.37) in the combined group were similar to those of the chemotherapy group, and the difference was not statistically significant. CONCLUSIONS: Cinobufacin combined with chemotherapy can improve the clinical efficacy of breast cancer patients, enhance the quality of life of the patients, reduce the value of tumor markers such as CA125, CA153, and CEA, and lower the occurrence of adverse reactions such as gastrointestinal reactions, liver and kidney damage, and hair loss.

Evaluation of Anti-Nociceptive and Anti-Inflammatory Effect of Luteolin in Mice.

Flavonoids are polyphenolic compounds that not only impart coloration to plants and fruits, but also protect plants from pathogens, radiation, etc. They serve as a nutrient to plants and possess immense anti-oxidant properties. Research has shown that they exhibit anti-inflammatory, anti-cancer, and neuroprotective properties in both in vitro and in vivo analyses. Luteolin is one such flavonoid belongs to the group of flavones present in herbs such as thyme, chamomile, celery, and green pepper. The epidemiological data on luteolin consumption show that luteolin has anti-inflammatory activity and protects from diseases associated with inflammation. The present study assessed the anti-nociceptive properties of luteolin, a potent anti-inflammatory agent, in mice. The results demonstrated that luteolin produces a significant and dose-dependent increase in hot plate latency and tail withdrawal time. It also reduced the number of abdominal constrictions and paw licking induced by acetic acid and glutamate, respectively. Luteolin inhibited the nociceptive responses in both phases of formalin test. The anti-inflammatory property of luteolin was also confirmed with different anti-inflammatory mice models induced by carrageenan and air pouch. Behavioral changes in luteolin-treated mice were assessed with open-field test to confirm the muscle relaxant property. The results of the current study from various pain and inflammatory models confirms that luteolin possess potent anti-nociceptive and anti-inflammatory properties and can thus be used as a drug in pain management.

Dimethyl fumarate reduces the risk of mycotoxins via improving intestinal barrier and microbiota.

The effects of dimethyl fumarate (DMF) on mycotoxins and animal growth performance are well documented. However, its mechanism of anti-mildew effects is still unknown. The current study investigated how DMF detoxified the mycotoxin and improved the growth performance using BALB/c mice model, especially its effects on intestinal barrier function and gut micro-ecology. Our study also compared with the ultraviolet radiation (UR) treatment, a traditional anti-mildew control (TC). The results indicated that the DMF treatment had a lower contents of mycotoxin, better growth performance and improved mucosal morphology (P < 0.05), accompanied with the decreased intestinal permeability and the tighter gut barrier. Moreover, the efficiency of DMF was better than TC (P < 0.05). 16S rRNA gene sequence analysis revealed that the richness and diversity of bacteria was increased in DMF treatment. The most abundant OTUs belonged to Firmicutes and Bacteroidetes, and their changes in DMF were more moderate than the TC group, suggesting a more stable micro-ecology and the positive impact of DMF on the biodiversity of intestine. Specifically, the increased abundance of bacteria producing short-chain fatty acids (SCFAs), such as Gemella, Roseburia, Bacillus and Bacteroides in DMF group and prebiotics such as Lactobacillus in TC group, suggested a more healthier microbial composition and distribution. These findings supported that DMF had significant effects on animal's growth performance and intestinal barrier function by modulating the pathway of nutrient absorption and increasing the diversity and balance of gut microbes, which also illuminate that DMF is more efficient than traditional anti-mildew method.

Effects of Dietary Mycotoxins on Gut Microbiome.

The harmful effects of mycotoxins on intestinal health have received worldwide attention. Mycotoxins are toxic secondary metabolites produced by filamentous fungi, and include aflatoxins, ochratoxins, patulin, fumonisins, zearalenone, trichothecenes, and ergot alkaloids. Insuring the absence or low levels of mycotoxins is critical for food and feed safety. Currently, the studies in this field have illuminated the adverse effects of mycotoxins on gut health including intestinal integrity and the gut-associated immune system. By affecting the proteins and peptides that serve vital functions in the immune system and host metabolism, mycotoxins are able to attack intestinal epithelium, which leads to poor intestinal health and integrity. This review focuses on the effects of exposure to mycotoxins on the intestinal barrier, especially the gut microbiome, intestinal local immune system, and tight junction proteins, which in return influence digestion, absorption, metabolism and transport of the nutrients in intestinal lumen. The crucial role of mycotoxins on microbial metabolism and antimicrobial properties is also assessed, which elucidates the relationship between exposure to mycotoxins and the intestinal microbiome. We hypothesize that the key small peptides and proteins regulate the causal relationship between mycotoxins and gut microbiome.

Effects of acute administration of ethanol on experimental arrhythmia.

Many studies have shown that the relationship between alcohol consumption and most cardiovascular diseases is U-shaped, with nondrinkers and heavier drinkers having higher risks than moderate drinkers. However, the association between cardiac arrhythmias and acute alcohol consumption is not well understood. We set up several experimental arrhythmia animal models to examine the effects of acute administration of ethanol on arrhythmia. The results showed 0.4, 0.8 and 1.6 g/kg ethanol consumption obviously delayed the onset time of atrial fibrillation (AF) (P < 0.05 or P < 0.01) and increased the survival rates on acetylcholine-CaCl2-induced AF in mice. Ethanol (0.4, 0.8 and 1.6 g/kg) consumption significantly delayed the onset time of ventricular tachycardia (VT), ventricular fibrillation (VF) and cardiac arrest (CA) (P < 0.01), and 0.4 and 0.8 g/kg ethanol consumption increased the survival rates on CaCl2-induced arrhythmia in rats. Ethanol (0.4 g/kg) essentially increased the cumulative dosage of aconitine required to CA (P < 0.05), and 0.8 g/kg, 1.6 g/kg ethanol reduced the cumulative aconitine dosage to induce VT, VF and CA (P < 0.05 or P < 0.01) on aconitine-induced arrhythmia in rats. Ethanol (0.4, 0.8 and 1.6 g/kg) consumption remarkably increased the cumulative dosage of deslanoside to induce ventricualr premature contraction (P < 0.01) on deslanoside-induced arrhythmia in guinea pigs. Collectively, our results indicate that low concentrations of ethanol had anti-arrhythmic effect on experimental arrhythmia, and high concentrations of ethanol may aggravated the occurrence of experimental arrhythmia.

[Effects of alcohol on acute myocardial ischemia induced by pituitrin in rats].

OBJECTIVE: To observe the effects of alcohol intake at different levels on acute myocardial ischemia induced by pituitrin in rats. METHODS: Forty SD male rats were randomly divided into five groups, including model control group (pituitrin, 1U/kg), positive control group (verapamil, 1 mg/kg), 5% alcohol group (0.4 g/kg), 10% alcohol group (0.8 g/kg) and 20% alcohol group (1.6 g/kg). Myocardial ischemia model was made in rats by injecting pituitrin (1U/kg) through sublingual vein. The heart rate, incidence of arrhythmia, the changes of ST segment and T wave on electrocardiogram of rats were observed and compared. RESULTS: The incidence of arrhythmia, the degree of elevated ST segment and T wave amplitude induced by pituitrin were remitted obviously in the 5% alcohol group (0.4 g/kg); The heart rate was slower and the change of ST segment and T wave were not affected in the 10% alcohol group (0.8 g/kg). The heart rate was slower and the elevated ST segment and the T wave amplitude were augmented significantly in the 20% alcohol group (1.6 g/kg). CONCLUSION: A protective effect on acute myocardial ischemia induced by pituitrin in rats was shown in the 5% alcohol group (0.4 g/kg) and an aggravation of acute myocardial ischemia induced by pituitrin was observed in the 20% alcohol group (1.6 g/kg).

[Effects of heroin exposure on the expression of caspase 3 in prefrontal lobe cortex, hippocampus and nucleus accumbens].

AIM: To investigate the expression of caspase 3 in the brain regions related to addiction, learning and memory in mice prenatally exposed to heroin and to ascertain whether postnatal apoptotic mechanism participates in neurobehavioral teratogenicity induced by maternal heroin abuse. METHODS: A mouse model was established by administration of diacetylmorphine (heroin, purity 98.5%, product ID No.171206-200614) 10 mg/(kg x d) subcutaneously to pregnant BALB/c mice on embryonic day (E)E8-E18. The offspring were divided into heroin(Her) and saline(Sal) groups according to the maternal treatment. The expression of caspase 3 in prefrontal lobe cortex(PFC), hippocampus(HP) and nucleus accumbens(Acb) was detected by RT-PCR and Western blot on mouse postnatal day(P)14. RESULTS: The mRNA and protein expression of caspase 3 were significantly increased in the areas of PFC, HP and Acb in Her group compared with Sal group(P < 0.05). CONCLUSION: E8-E18 prenatal exposure to heroin can induce apoptosis through caspase 3 activation in brain regions related to addiction, learning and memory, which indicates that apoptotic mechanism may be involved in neurobehavioral teratogenicity by heroin exposure in uterus.