The comparative analysis of gastrointestinal toxicity of azithromycin and 3'-decladinosyl azithromycin on zebrafish larvae.

The most commonly reported side effect of azithromycin is gastrointestinal (GI) disorders, and the main acid degradation product is 3'-Decladinosyl azithromycin (impurity J). We aimed to compare the GI toxicity of azithromycin and impurity J on zebrafish larvae and investigate the mechanism causing the differential GI toxicity. Results of our study showed that the GI toxicity induced by impurity J was higher than that of azithromycin in zebrafish larvae, and the effects of impurity J on transcription in the digestive system of zebrafish larvae were significantly stronger than those of azithromycin. Additionally, impurity J exerts stronger cytotoxic effects on GES-1 cells than azithromycin. Simultaneously, impurity J significantly increased ghsrb levels in the zebrafish intestinal tract and ghsr levels in human GES-1 cells compared to azithromycin, and ghsr overexpression significantly reduced cell viability, indicating that GI toxicity induced by azithromycin and impurity J may be correlated with ghsr overexpression induced by the two compounds. Meanwhile, molecular docking analysis showed that the highest -CDOCKER interaction energy scores with the zebrafish GHSRb or human GHSR protein might reflect the effect of azithromycin and impurity J on the expression of zebrafish ghsrb or human ghsr. Thus, our results suggest that impurity J has higher GI toxicity than azithromycin due to its greater ability to elevate ghsrb expression in zebrafish intestinal tract.

Pathogen distribution in pulmonary infection in chinese patients with lung cancer: a systematic review and meta-analysis.

BACKGROUND: The immunity of patients with lung cancer decreases after treatment; thus, they are easily infected with pathogenic bacteria that causes pulmonary infections. Understanding the distribution characteristics of pathogenic bacteria in pulmonary infection in patients with lung cancer after treatment can provide a basis to effectively prevent infection and rationally use antibacterial drugs. However, no meta-analyses have assessed the distribution characteristics of pathogenic bacteria in mainland China. Therefore, our meta-analysis aimed to investigate the pathogen distribution in pulmonary infection in Chinese patients with lung cancer. METHODS: A literature search was conducted to study the pathogen distribution in pulmonary infection in Chinese patients with lung cancer between January 1, 2020 and December 31, 2022, using English and Chinese databases. The relevant data were extracted. The meta-analysis was performed using a random-effects model ( I2 > 50%) with 95% confidence intervals for forest plots. Data were processed using RevMan 5.3. RESULTS: Fifteen studies (2,683 strains in 2,129 patients with pulmonary infection were cultured) met the evaluation criteria. The results showed that Gram-negative bacteria had the highest detection rate (63%), followed by Gram-positive bacteria (23%), and fungi (12%). Among the Gram-negative bacteria detected, the distribution of the main pathogenic bacteria was Klebsiella pneumonia (17%), Pseudomonas aeruginosa (14%), Escherichia coli (13%), Acinetobacter baumannii (7%), Enterobacter cloacae (4%), and Hemophilus influenza (4%). Moreover, the prevalence of pulmonary infections after chemotherapy (53%) was significantly higher than that after surgery (10%), P < 0.05. CONCLUSIONS: The prevalence of pulmonary infections after treatment, especially after chemotherapy, is high in Chinese patients with lung cancer, and Gram-negative bacteria are the predominant pathogens. Further studies are needed to monitor the prevalence of pulmonary infections and pathogen distribution in lung cancer patients in mainland China.

A pair of G-type lectin receptor-like kinases modulates nlp20-mediated immune responses by coupling to the RLP23 receptor complex.

Plant cells recognize microbial patterns with the plasma-membrane-localized pattern-recognition receptors consisting mainly of receptor kinases (RKs) and receptor-like proteins (RLPs). RKs, such as bacterial flagellin receptor FLS2, and their downstream signaling components have been studied extensively. However, newly discovered regulatory components of RLP-mediated immune signaling, such as the nlp20 receptor RLP23, await identification. Unlike RKs, RLPs lack a cytoplasmic kinase domain, instead recruiting the receptor-like kinases (RLKs) BAK1 and SOBIR1. SOBIR1 specifically works as an adapter for RLP-mediated immunity. To identify new regulators of RLP-mediated signaling, we looked for SOBIR1-binding proteins (SBPs) in Arabidopsis thaliana using protein immunoprecipitation and mass spectrometry, identifying two G-type lectin RLKs, SBP1 and SBP2, that physically interacted with SOBIR1. SBP1 and SBP2 showed high sequence similarity, were tandemly repeated on chromosome 4, and also interacted with both RLP23 and BAK1. sbp1 sbp2 double mutants obtained via CRISPR-Cas9 gene editing showed severely impaired nlp20-induced reactive oxygen species burst, mitogen-activated protein kinase (MAPK) activation, and defense gene expression, but normal flg22-induced immune responses. We showed that SBP1 regulated nlp20-induced immunity in a kinase activity-independent manner. Furthermore, the nlp20-induced the RLP23-BAK1 interaction, although not the flg22-induced FLS2-BAK1 interaction, was significantly reduced in sbp1 sbp2. This study identified SBPs as new regulatory components in RLP23 receptor complex that may specifically modulate RLP23-mediated immunity by positively regulating the interaction between the RLP23 receptor and the BAK1 co-receptor.

SUMO1-modified DNA methyltransferase 1 induces DNA hypermethylation of VWC2 in the development of colorectal cancer.

Aberrant DNA methylation of genes is closely linked to many aspects of tumor development. This study focuses on the effect of DNA hypermethylation of von Willebrand factor C domain containing 2 (VWC2) on colorectal cancer (CRC) progression and the underpinning mechanism. According to data in the bioinformatic systems, VWC2 had the highest degree of DNA methylation in colonic adenocarcinoma, and it showed DNA hypermethylation in rectal adenocarcinoma as well. CRC and the para-tumorous tissues were collected from 86 patients. VWC2 was expressed at low levels in CRC samples and inversely correlated with tumor stage and tumor biomarker expression. DNA hypermethylation and reduced expression of VWC2 were also detected in CRC cell lines HCT-116 and HT29. VWC2 overexpression suppressed the malignant growth of cells in vitro and in vivo. Co-immunoprecipitation and western blot assays showed that small ubiquitin-like modifier 1 (SUMO1) mediated SUMOylation of DNA methyltransferase 1 (DNMT1) and strengthened its protein stability, which promoted DNA methylation and suppression of the VWC2 gene. In summary, this study demonstrates that SUMO1-mediated activation of DNMT1 induces DNA methylation and downregulation of VWC2 in CRC to augment cancer development.

Natural oscillation frequencies of a Rayleigh sphere levitated in standing acoustic waves.

Acoustic levitation is an important method of container-free processing, which counteracts gravity through exerting the acoustic radiation force on levitated objects. The Gorkov potential function is used to simplify the calculation of the acoustic radiation force acting on a Rayleigh sphere whose radius is much smaller than the wave length. For the case of a plane standing wave levitation system, a systematic analysis of the sphere dynamics is provided in the axial direction, assuming a small perturbation around the stable equilibrium locations. A generalized extension to an arbitrary standing wave field is provided, which gives formal expressions of the axial and transverse natural oscillation frequencies for the sphere. Particular emphasis is put on the natural oscillation frequencies with and without taking gravity into consideration. The computational results for Gauss and Bessel standing waves are provided as two special cases, which show that the transverse natural oscillation frequency will be overestimated when neglecting gravity, especially for a sphere with a relatively large density. Corresponding experiments are conducted to verify the dependence of the transverse natural oscillation frequency on the sphere density. The results obtained in this work are expected to provide a theoretical guide for enhancing the levitation stability and inversing the physical parameters from the sphere dynamics.

Prostate Cancer Risk Prediction and Online Calculation Based on Machine Learning Algorithm.

Objective To build a prostate cancer (PCa) risk prediction model based on common clinical indicators to provide a theoretical basis for the diagnosis and treatment of PCa and to evaluate the value of artificial intelligence (AI) technology under healthcare data platforms. Methods After preprocessing of the data from Population Health Data Archive, smuothly clipped absolute deviation (SCAD) was used to select features. Random forest (RF), support vector machine (SVM), back propagation neural network (BP), and convolutional neural network (CNN) were used to predict the risk of PCa, among which BP and CNN were used on the enhanced data by SMOTE. The performances of models were compared using area under the curve (AUC) of the receiving operating characteristic curve. After the optimal model was selected, we used the Shiny to develop an online calculator for PCa risk prediction based on predictive indicators. Results Inorganic phosphorus, triglycerides, and calcium were closely related to PCa in addition to the volume of fragmented tissue and free prostate-specific antigen (PSA). Among the four models, RF had the best performance in predicting PCa (accuracy: 96.80%; AUC: 0.975, 95% CI: 0.964-0.986). Followed by BP (accuracy: 85.36%; AUC: 0.892, 95% CI: 0.849-0.934) and SVM (accuracy: 82.67%; AUC: 0.824, 95% CI: 0.805-0.844). CNN performed worse (accuracy: 72.37%; AUC: 0.724, 95% CI: 0.670-0.779). An online platform for PCa risk prediction was developed based on the RF model and the predictive indicators. Conclusions This study revealed the application value of traditional machine learning and deep learning models in disease risk prediction under healthcare data platform, proposed new ideas for PCa risk prediction in patients suspected for PCa and had undergone core needle biopsy. Besides, the online calculation may enhance the practicability of AI prediction technology and facilitate medical diagnosis.

A Phytophthora capsici RXLR effector targets and inhibits the central immune kinases to suppress plant immunity.

Receptor-like cytoplasmic kinase subfamily VII (RLCK-VII) proteins are the central immune kinases in plant pattern-recognition receptor (PRR) complexes, and they orchestrate a complex array of defense responses against bacterial and fungal pathogens. However, the role of RLCK-VII in plant-oomycete pathogen interactions has not been established. Phytophthora capsici is a notorious oomycete pathogen that infects many agriculturally important vegetables. Here, we report the identification of RXLR25, an RXLR effector that is required for the virulence of P. capsici. In planta expression of RXLR25 significantly enhanced plants' susceptibility to Phytophthora pathogens. Microbial pattern-induced immune activation in Arabidopsis was severely impaired by RXLR25. We further showed that RXLR25 interacts with RLCK-VII proteins. Using nine rlck-vii high-order mutants, we observed that RLCK-VII-6 and RLCK-VII-8 members are required for resistance to P. capsici. The RLCK-VII-6 members are specifically required for Phytophthora culture filtrate (CF)-induced immune responses. RXLR25 directly targets RLCK-VII proteins such as BIK1, PBL8, and PBL17 and inhibits pattern-induced phosphorylation of RLCK-VIIs to suppress downstream immune responses. This study identified a key virulence factor for P. capsici, and the results revealed the importance of RLCK-VII proteins in plant-oomycete interactions.

Analysis of cranial type characteristics in term infants: a multi-center study.

BACKGROUND: Positional head deformity (PHD) is defined as a change in the shape of an infant's skull due to an external force. In certain cases, it can lead to cosmetic deformities or even neurological issues due to its impact on the developing nervous system. Therefore, we conducted this study to investigate the incidence and characteristics of PHD in term infants in China and preliminarily establish a localized diagnostic reference standard. METHODS: Overall, 4456 term infants from three medical institutions in Chongqing were and divided and analyzed according to their age. Cranial vault asymmetry (CVA) and cephalic index (CI) were calculated in all infants. The current international diagnostic criteria were used to understand PHD incidence and analyze the CVA and CI distribution. RESULTS: According to the current international standards, the total detection rate of PHD in Chongqing's term infants was 81.5%, with brachycephaly alone being the most frequent (39.4%), followed by brachycephaly with plagiocephaly (34.8%) and plagiocephaly alone (6.2%). The detection rates of dolichocephaly were low: alone, 0.9% and combined with plagiocephaly, 0.2%. According to age, plagiocephaly (44.5%) and brachycephaly (82.0%) were the most frequent in the 2-3-month group. The 75th/90th/97th and 3rd/10th/25th/75th/90th/97th percentiles of CVA and CIs were 0.4/0.7/1.0 and 76.4/78.8/82.3/91.1/94.6/99.2%, respectively. CONCLUSIONS: According to the current international standards, the PHD detection rate among term infants in Chongqing was high. Therefore, a new diagnostic standard for Chinese infants was proposed where CVA ≥ 0.4 cm indicates plagiocephaly, CI ≥ 91% indicates brachycephaly, and CI ≤ 82% indicates dolichocephaly.

CYP3A4 and microRNA-122 are involved in the apoptosis of HepG2 cells induced by ILs 1-decyl-3-methylimidazolium bromide.

Ionic liquids (ILs) as green alternatives for volatile organic solvents are increasingly used in commercial applications. It is necessary to explore the cytotoxic mechanism of ILs to reduce the risk to human health. For this purpose, cell viability, apoptosis, cytochrome P450 3A4 (CYP3A4), glucose transporter type 2 (GLUT2), and microRNA-122 (miR-122) gene expression in HepG2 cells was evaluated after IL exposure. The results showed that ILs reduced the viability of HepG2 cells through apoptotic cell death. Moreover, ILs markedly upregulated the transcription and protein levels of CYP3A4, but did not affect the expression of GLUT2 in either messenger RNA level or protein level. Finally, ILs increased the expression of miR-122 and inhibition of miR-122 with miR-122 inhibitor blocked ILs-induced apoptosis in HepG2 cells. This finding may contribute to an increased understanding of the in vitro molecular toxicity mechanism of ILs to further understand IL-related human health risks.

Typical BBB morphology and implantation depth of 3830 electrode predict QRS correction by left bundle branch area pacing.

AIM: Strict criteria of typical left bundle branch block (LBBB) can help with the prediction for cardiac resynchronization therapy response. The aim of this study is to determine whether the use of strict criteria for both LBBB and right bundle branch block (RBBB) predicts successful QRS correction (≤130 ms) by left bundle branch area pacing (LBBAP). METHODS: Consecutive patients with pacemaker indications according to the present guideline who also underwent LBBAP implantation were retrospectively assessed. Inclusion criteria were patients with BBB and the baseline QRSd > 130 ms. Baseline characteristics and pacing parameters were compared between typical and atypical BBB groups. Multivariate logistic regression was used to adjust for covariates that were found in univariate analyses for successful QRS correction by LBBAP. RESULTS: Seventy-three patients were enrolled. Among them, 10 (13.6%) had atypical BBB (5 LBBB and 5 RBBB) and 63 (86.4%) had typical BBB (30 LBBB and 33 RBBB). The rate of successful QRS correction was higher in typical-BBB patients (52/63; 82.5%) than that in atypical-BBB patients (3/10; 30%), P < .001. Paced QRSd was obviously narrower in patients with typical BBB than that in patients with atypical-BBB (118 ± 14 vs 133 ± 14 ms, P = .003). In multivariate logistic regression, only typical BBB morphology and the implantation depth of 3830 pacing electrode in the ventricular septum were independent predictors for successful QRS correction. CONCLUSION: This study demonstrates that patients with typical-BBB morphology benefit more from LBBAP for QRS correction. Typical BBB morphology together with deep penetration of 3830 ventricular electrode in the interventricular septum predicts the success of QRS correction by LBBAP.

Quantification of Acute Myocardial Damage Secondary to Implantation of Electrodes for the Left Bundle Branch Area Pacing.

BACKGROUND: Different from the traditional right ventricular pacing, the left bundle branch area pacing (LBBAP) is accomplished with deeper lead implantation and more attempts. However, myocardial damage is unclear in LBBAP. OBJECTIVE: The objective of the study was to observe the change of troponin T and explore possible factors associated with greater myocardial damage in LBBAP. METHODS: Patients with an indication for pacemaker implantation underwent attempts for LBBAP by transventricular septal method. Levels of troponin T were determined before operation, 12 h and 1 week after the operation. Parameters of intraoperation and follow-up were recorded and analyzed. RESULTS: In total, successful LBBAP was achieved in 126 patients. The levels of troponin T increased significantly at 12 h after the operation compared with those before operation (96.45 ± 11.07 [69.06] vs. 16.59 ± 1.84 [11.92] ng/L, p < 0.001), while there were no significant differences between pre- and post-operative levels at 1 week. Correlation and regression analysis showed that only the number of attempts was an independent factor related to the change of troponin T. During 1 year of follow-up, LBBAP was safe and feasible with few complications. CONCLUSIONS: Myocardial damage of LBBAP was clinically significant. The number of attempts was an independent factor related to the myocardial damage.

Risk of tuberculosis in patients with immune-mediated diseases on biological therapies: a population-based study in a tuberculosis endemic region.

OBJECTIVE: Real-world epidemiological data on the risk of tuberculosis (TB) in patients with immune-mediated diseases treated with biologics are scarce in TB endemic areas. We investigated the incidence of TB in a population-based setting and stratified the risk of TB among different biological therapies. METHODS: We collected medical data from a territory-wide computerized database in Hong Kong. We reported the incidence of TB in patients treated with various classes of biologics, and calculated standardized incidence ratio by comparing with the general population. Subgroup analyses were performed based on disease subtypes and biological drugs. RESULTS: Among 2485 subjects with immune-mediated diseases (82.5% rheumatology diseases; 10.6% IBD; 6.9% dermatology diseases), 54 subjects developed active TB during 6921 person-years of follow-up. The mean age (±s.d.) was 43 (14) years, and the median follow-up duration was 24.9 months (interquartile range 4.9-45.0). The overall standardized incidence ratio of TB was 10.91 (95% CI 8.00-13.82), and patients treated with infliximab had a nearly 26 times increased risk of TB compared with the general population (standardized incidence ratio 25.95; 95% CI 17.23-34.67). The risk of TB with TNF inhibitor was higher than with a non-TNF biologic (hazard ratio 4.34; 95% CI 1.31-14.39), while the risk of infliximab was higher than etanercept and adalimumab (hazard ratio: 4.10 and 2.08, respectively). CONCLUSION: The risk of TB is much higher in patients with immune-mediated diseases on biological therapy compared with the general population, and infliximab is associated with the highest risk of TB among the biologics analysed.

Legacy and Currently Used Organic Contaminants in Human Hair and Hand Wipes of Female E-Waste Dismantling Workers and Workplace Dust in South China.

Legacy organic contaminants, such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), and several currently used organic contaminants, such as novel brominated retardants (NBFRs), organophosphate flame retardants (OPFRs), and Dechlorane Plus (DPs), were measured in the segmented hair and hand wipes of e-waste dismantling workers and in the dust from their workplace in an e-waste recycling site in South China to assess the accumulation and sources of organic contaminants in the hair shaft. The median concentrations of DPs, PBDEs, NBFRs, PCBs and OPFRs in hair samples were 23.5, 154, 156, 349, and 371 ng/g, respectively. A linear increase in organic contaminant concentrations was found along the hair shaft, with significant differences among each segment, while the age-related patterns were similar among the 7 hair segments. A linear relationship was found between the accumulation rates and the log KOW, indicating that the accumulation rates of organic contaminants along the hair shaft decreased with increasing log KOW values. Enantiomer fraction (EF) values of PCB-132 in distal segments were close to those in dust and air, while EFs in proximal segments were close to those in serum. The contributions of PCBs from external sources to hair increased with the distance from the scalp of hair segments, from 67.8% in 0-3 cm segments to 95.9% in 18-21 cm segments.

Research on the relationship between cephalosporin structure, solution clarity, and rubber closure compatibility using volatile components profile of butyl rubber closures.

OBJECTIVE: Establish an effective experimental strategy to determine the compatibility of rubber closures for drugs. SIGNIFICANCE: Various types of rubber closures with different compositions are available for drug packaging. Many additives of rubber closures can be released from rubber closures and may affect the quality of drugs and pose a risk to human health. In this study, we aimed to determine the relationship between cephalosporin structure, solution clarity, and rubber closure compatibility using volatile components profile of butyl rubber closures. METHODS: Two opposite polarity gas chromatography (GC) systems and GC-mass spectrometry (MS) were used to achieve rapid qualitative determination of the main volatile components in rubber closures. Simulated adsorption experiment was performed to investigate the adsorption of main volatile components in rubber closures by cephalosporins with different side chain structures, and to determine the effects of adsorption on solution clarity. RESULTS: A volatile components screening library of rubber closures was established and the structures of some volatile component were confirmed. The specific adsorption of the structure of cephalosporins on volatile components from rubber closures was studied. CONCLUSION: Based on the results of this study, rubber closures with good compatibility for cephalosporins with different side chain structures can be selected rapidly. This experimental strategy not only facilitates the screening of suitable rubber closures more effectively, but also enables the quick determination of volatile components adsorbed by drugs.

[Infection factors associated with neurodysplasia in early and moderately preterm infants].

OBJECTIVE: To investigate the infection factors associated with neurodysplasia in early and moderately preterm infants at a corrected age of 18 months. METHODS: The preterm infants with a gestational age of 28 weeks to <34 weeks who were admitted to the neonatal intensive care unit and followed up at the outpatient service for high-risk preterm infants from June 2015 to December 2018 were enrolled as subjects. At a corrected age of 18 months, the revised Bayley Scales of Infant Development was used to evaluate neurodevelopment. Univariate and multivariate logistic regression analyses were used to investigate the infection factors affecting neurodevelopment. RESULTS: A total of 138 early or moderately preterm infants were enrolled, among whom 59 had neurodysplasia at a corrected age of 18 months. The univariate logistic regression analysis showed that neurodysplasia was associated with late-onset infection, positive blood culture, and other systemic infections (P<0.05). The multivariate logistic regression analysis showed that late-onset infection was an independent risk factor for neurodysplasia (OR=1.510, 95%CI: 1.133-3.600, P<0.05). CONCLUSIONS: Late-onset infection can increase the risk of neurodysplasia in early and moderately preterm infants.

Dietary Silymarin Supplementation Alleviates Zearalenone-Induced Hepatotoxicity and Reproductive Toxicity in Rats.

Background: Zearalenone (ZEN) can cause serious defects in development and reproduction in humans and animals. Silymarin shows antioxidant and estrogenic effects. Objective: This study was conducted to determine if silymarin can antagonize ZEN-induced hepatic and reproductive toxicities. Methods: Thirty-five 21-d-old female Sprague-Dawley rats (n = 7/diet) were fed a control diet (Ctrl) or Ctrl plus 20 mg ZEN/kg or Ctrl plus 20 mg ZEN/kg with 100, 200, or 500 mg silymarin/kg for 6 wk. Serum, livers, ovaries, and uterus were collected at week 6 for biochemistry, hormone, and redox status and selected gene and protein assays. Results: The consumption of ZEN decreased (P < 0.05) the final body weight by 17.9%, induced liver injury, increased (P < 0.05) aspartate aminotransferase and alkaline phosphatase activities, and decreased (P < 0.05) total protein and albumin concentrations in serum by 16.7-40.6%. ZEN also caused reproductive toxicity, including decreased (P < 0.05) 17ß-estradiol and increased (P < 0.05) follicle-stimulating hormone concentrations in serum by 12.7-46.3% and induced histopathologic alterations in the liver, ovaries, and uterus. Interestingly, these alterations induced by ZEN were alleviated (P < 0.05) by silymarin supplementation at 100, 200, and 500 mg/kg. Moreover, silymarin supplementation at the 3 doses mitigated (P < 0.05) ZEN-induced impairment in hepatic glutathione peroxidase activity, total antioxidant capacity, and malondialdehyde concentration by 17.6-100%. Meanwhile, silymarin supplementation at all doses upregulated (P < 0.05) phospho-ribosomal protein S6 kinase 1 (p-RPS6KB1) and 3ß-hydroxysteroid dehydrogenase (HSD3B) by 43.0-121% but downregulated (P < 0.05) AMP-activated protein kinase (AMPK) and 3α-hydroxysteroid dehydrogenase (HSD3A) in the liver relative to the ZEN group by 11.2-40.6%. In addition, silymarin supplementation at all doses elevated (P < 0.05) HSD3B by 1.8- to 2.5-fold and decreased (P < 0.05) estrogen receptor 1 (ESR1), ATP binding cassette (ABC) c1, and Abcc5 in ovaries and the uterus by 10.7-63.2%. Conclusion: Dietary silymarin supplementation at 100, 200, and 500 mg/kg protected rats from ZEN-induced hepatotoxicity and reproductive toxicity, potentially through improvement in the antioxidant capacity and regulation in the genes related to protein synthesis, ZEN metabolism, hormone synthesis, and ABC transporters in the tissues.

Rapid Analysis of the Quality of Amoxicillin and Clavulanate Potassium Tablets Using Diffuse Reflectance Near-Infrared Spectroscopy.

The cycle-closed dimer of amoxicillin influences its critical quality and is an important impurity in amoxicillin and clavulanate potassium tablets. The quality of the tablets could be rapidly evaluated using the impurity as an indicator. Here, we report a quantitative model to determine the cycle-closed dimer in samples from different manufacturers using diffuse reflectance near-infrared (NIR) spectroscopy by partial least squares regression for one y variable (PLS1) and hierarchical cluster analysis. Because the contents of the (active pharmaceutical ingredients) APIs (amoxicillin and clavulanate potassium) and water are also the important indexes of the tablet quality, three other quantitative models were used to confirm the API data and water content. All of the four models facilitate rapid and complete control of the tablet quality. In addition, quantitative models were validated in terms of specificity, linearity, accuracy, repeatability, and intermediate precision according to the International Conference on Harmonisation guidelines by evaluating the characteristics of the NIR spectra. These results confirmed that the models were satisfactory.

[Drug Discrimination Method Based on Near Infrared Reflectance Spectrum and Balance Cascading Sparse Representation Based Classification].

The combination of near infrared spectrum and pattern recognition methods has a wide application prospect in rapid and nondestructive supervision and management of drugs. The traditional identification methods regard the smallest error rate as the goal while the imbalance of classes is ignored. This makes the positive class is overwhelming covered by the negative class and reduces its effect for the classifier, so that the classification results tend to recognize the negative class correctly, which severely affects the identification accuracy. In this paper, we mainly studied the class imbalance problems of true or false drugs via infrared spectral data of its, and then propose a balance cascading and sparse representation based classification method (BC-SRC) by combining the Balance Cascading with SRC. We sampling majority samples from the majority class for several times, which has the same size as minority samples and the majority samples we sampled can contain all the majority class samples entirely (sampling times is ceiling the result of majority samples number divide minority samples number). We can get sets of results, and then obtain the final predict labels form those results. Experiments of three databases achieved on Matlab2012a shows that the method is effective. From the experimental results, it can be seen that the method is superior to the commonly used Partial Least Squares (PLS), Extreme Learning Machine (ELM) and BP. Particularly, for the imbalanced databases, when the imbalance factor is greater than 10, the proposed method has more stable performance with higher classification accuracy than the existing ones mentioned above.

Drift of charge carriers in crystalline organic semiconductors.

We investigate the direct-current response of crystalline organic semiconductors in the presence of finite external electric fields by the quantum-classical Ehrenfest dynamics complemented with instantaneous decoherence corrections (IDC). The IDC is carried out in the real-space representation with the energy-dependent reweighing factors to account for both intermolecular decoherence and energy relaxation by which conduction occurs. In this way, both the diffusion and drift motion of charge carriers are described in a unified framework. Based on an off-diagonal electron-phonon coupling model for pentacene, we find that the drift velocity initially increases with the electric field and then decreases at higher fields due to the Wannier-Stark localization, and a negative electric-field dependence of mobility is observed. The Einstein relation, which is a manifestation of the fluctuation-dissipation theorem, is found to be restored in electric fields up to ∼10(5) V/cm for a wide temperature region studied. Furthermore, we show that the incorporated decoherence and energy relaxation could explain the large discrepancy between the mobilities calculated by the Ehrenfest dynamics and the full quantum methods, which proves the effectiveness of our approach to take back these missing processes.

Efficacy and safety of the contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive in Chinese women: a 1-year randomised trial.

OBJECTIVES: The aim of the study was to assess the efficacy and tolerability of the monthly vaginal ring (NuvaRing; 15 µg ethinylestradiol [EE] and 120 µg etonogestrel per day) compared with a monophasic (21/7) combined oral contraceptive (COC) containing 30 µg EE and 3 mg drospirenone in healthy Chinese women aged 18-40 years. METHODS: This was a phase III, open-label, randomised multicentre trial conducted in China. Participants received NuvaRing or COC for 13 cycles (3 weeks of ring/pill treatment followed by a 1-week ring-free/pill-free period). Contraceptive efficacy was assessed by in-treatment pregnancies and expressed by the Pearl Index (PI; number of pregnancies/100 woman-years of use). Cycle control was assessed by unscheduled (breakthrough) and absence of scheduled (withdrawal) bleeding events. Safety and tolerability were assessed throughout the study. RESULTS: Participants were randomised either to the NuvaRing (n = 732) or to the COC (n = 214); 588 (82.4%) and 182 (78.4%) participants, respectively, completed the study. There were 10 in-treatment pregnancies in the NuvaRing group (PI 1.92; 95% confidence interval [CI] 0.92, 3.53) and five in the COC group (PI 3.12; 95% CI 1.01, 7.29). Breakthrough bleeding/spotting ranged from 18.6% (Cycle 1) to 4.2% (Cycle 11) for NuvaRing and from 21.6% (Cycle 1) to 7.9% (Cycle 11) for COC. Absence of withdrawal bleeding ranged from 8.6% (Cycle 1) to 3.0% (Cycle 11) for NuvaRing and from 14.6% (Cycle 1) to 6.4% (Cycle 5) for COC. For NuvaRing and COC, respectively, 26.6% and 25.0% of participants had treatment-related adverse events, and 7.0% and 9.1% discontinued the study as a result. CONCLUSIONS: Once-monthly NuvaRing is efficacious and safe for use in Chinese women.