Corrigendum: Pharmacokinetics and bioequivalence study of esomeprazole magnesium enteric-coated tablets 20 mg in healthy Chinese subjects under fasting and fed conditions.

[This corrects the article DOI: 10.3389/fphar.2023.1169103.].

Pharmacokinetics and bioequivalence study of esomeprazole magnesium enteric-coated tablets 20 mg in healthy Chinese subjects under fasting and fed conditions.

Objective: The main purpose of this study was to evaluate the pharmacokinetics, bioequivalence, and safety properties between a new generic and a brand reference formulation of esomeprazole enteric-coated tablets 20 mg in healthy Chinese subjects under fasting and fed conditions. Methods: The fasting study was an open-label, randomized, two-period crossover study conducted in 32 healthy Chinese volunteers, and the fed study was a four-period crossover study conducted in 40 healthy Chinese volunteers. Blood samples were collected at the specified time points and determined to obtain the plasma concentrations of esomeprazole. The primary pharmacokinetic parameters were calculated using the non-compartment method. Bioequivalence was analyzed by the geometric mean ratios (GMRs) of the two formulations and the corresponding 90% confidence intervals (CIs). The safety of the two formulations was assessed. Results: The fasting and fed study showed that the pharmacokinetics of the two formulations was similar. Under the fasting condition, the 90% CIs of GMRs of the test-to-reference formulation were 87.92%-104.36% for Cmax, 87.82%-101.45% for AUC0-t, and 87.99%-101.54% for AUC0-∞; under the fed condition, the 90% CIs of GMRs of the test-to-reference formulation were 80.53%-94.95% for Cmax, 87.46%-97.26% for AUC0-t, and 87.46%-97.16% for AUC0-∞. The 90% CIs of GMRs fall within the bioequivalence range of 80.00%-125.00%. The two formulations had good safety and were well-tolerated, and no serious adverse events occurred. Conclusion: According to relevant regulatory standards, esomeprazole enteric-coated generic and reference products exhibited bioequivalence and good safety in healthy Chinese subjects. Clinical Trials Registration: http://www.chinadrugtrials.org.cn/index.html, identifier CTR20171347 and CTR20171484.

Quality assessment of traditional Chinese medicine using quality biomarkers: Compound DanShen dripping pills as an example.

BACKGROUND: The quality control of traditional Chinese medicine (TCM) is one of the main topics in TCM modernisation research. To date, the overwhelming majority of research has focused on chemical ingredients in the quality control of TCM. However, detecting a single or multiple chemical components cannot fully demonstrate the specificity and correlation between quality and efficacy. PURPOSE: To solve the problem that the association between quality control and efficacy is lacking. The present study was designed to establish a methodology for quality control based on quality biomarkers (Q-biomarkers) and the vasodilatation efficacy of compound DanShen dripping pills (CDDP) as a case. METHODS: Guided by the basic principles of Q-biomarkers, the compounds in TCM were determined by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Predicted targets were screened through network pharmacology. The potential Q-biomarkers were further screened through proteomics and partial least squares regression analysis. The protein-protein interaction network that combines both predicted targets and potential Q-biomarkers was constructed to screen Q-biomarkers. RESULTS: There were 32 components and 79 predictive targets for CDDP. Proteomic results indicated that the expression of 23 differential proteins changed as pharmacodynamic and componential changes. CPSF6, RILP11, TMEM209, COQ7, VPS18, PPPP1CA, NF2, and ARFRP1 highly correlated with vasodilation. Protein interaction network analysis showed that NF2 and PPPP1CA were closely related to predicted proteins. Thus, NF2 and PPPP1CA could be considered as Q-biomarkers of CDDP. CONCLUSION: Our preliminary study suggested the feasibility of the Q-biomarkers theory in the quality of TCM. The concept of Q-biomarkers provided a powerful method to strengthen the link between clinical efficacy and the quality of TCM. In conclusion, a novel, more scientific, and standard quality control method was established in this study.

Effect of Flowering Stages on the Content of Active Ingredients and Antioxidant Capability of Bletilla striata Flowers.

Bletilla striata (Thunb.) Reichb.f. is a perennial herb with abundant active ingredients. Previous research mainly focused on its tubers, however, the study on flowers, especially the variation of active ingredient contents at different flowering stages, was rarely seen. This study analyzed the total phenols, flavonoids, polysaccharides, anthocyanins, and cyanidin-3-O-glucoside content of B. striata flowers which were in cultivated in Herb Garden of Zhejiang A&F University and collected in May, 2019, in order to investigate the changes in active ingredients and antioxidant capacity among different flowering stages (bud, initial, and full bloom). Changes in radical scavenging capability of DPPH (1,1-Diphenyl-2-picrylhydrazyl radical), ABTS (2,2'-azinobis(3-ethylbenzthiazoline-6-sulphonate)), and hydroxy were analyzed. Significant differences in active ingredient content of flowers were detected among different flowering stages. The total phenolic content increased continuously during the entire flowering stage. The contents of total flavonoid, total polysaccharide, and cyanidin-3-O-glucoside reached peaks at the initial blooming stage and then fell as the flowering process continued. The antioxidant activity in initial stage was the highest than in any other flowering stages. Therefore, we conclude that the initial blooming stage is the best harvesting stage of B. striata flowers. This study provides a robust basis for the harvest and utilization of B. striata flowers in food, medical, and cosmetic industries.

Biclustering analysis of functionals via penalized fusion.

In biomedical data analysis, clustering is commonly conducted. Biclustering analysis conducts clustering in both the sample and covariate dimensions and can more comprehensively describe data heterogeneity. In most of the existing biclustering analyses, scalar measurements are considered. In this study, motivated by time-course gene expression data and other examples, we take the "natural next step" and consider the biclustering analysis of functionals under which, for each covariate of each sample, a function (to be exact, its values at discrete measurement points) is present. We develop a doubly penalized fusion approach, which includes a smoothness penalty for estimating functionals and, more importantly, a fusion penalty for clustering. Statistical properties are rigorously established, providing the proposed approach a strong ground. We also develop an effective ADMM algorithm and accompanying R code. Numerical analysis, including simulations, comparisons, and the analysis of two time-course gene expression data, demonstrates the practical effectiveness of the proposed approach.

Identification of human uridine diphosphate-glucuronosyltransferase isoforms responsible for the glucuronidation of 10,11-dihydro-10-hydroxy-carbazepine.

OBJECTIVES: To determine the kinetics of the formation of 10,11-dihydro-10-hydroxy-carbazepine (MHD)-O-glucuronide in human liver microsomes (HLMs), human intestine microsomes (HIMs), human kidney microsomes (HKMs) and recombinant human UDP-glucuronosyltransferase (UGTs), and identify the primary UGT isoforms catalyzing the glucuronidation of MHD. METHODS: The kinetics of the glucuronidation of MHD was determined in HLMs, HIMs as well as HKMs. Screening assays with 13 recombinant human UGTs, inhibition studies and correlation analysis were performed to identify the main UGTs involved in the glucuronidation of MHD. KEY FINDINGS: MHD-O-glucuronide was formed in HLMs, HIMs as well as HKMs, HLMs showed the highest intrinsic clearance of MHD. Among 13 recombinant human UGTs, UGT2B7 and UGT1A9 were identified to be the principal UGT isoforms mediating the glucuronidation of MHD, while UGT1A4 played a partial role. In addition, inhibition studies and correlation analysis further confirmed that UGT2B7 and UGT1A9 participated in the formation of MHD-O-glucuronide. CONCLUSIONS: MHD could be metabolized by UGTs in the liver, intestine and kidney, and the hepatic glucuronidation was the critical metabolic pathway. UGT2B7 and UGT1A9 were the primary UGT isoforms mediating the formation of MHD-O-glucuronide in the liver.

[Clinical strategies to prevent falls].

With the aging of population structure, the age-related balance dysfunction increases gradually, and the injuries related fall are increasing, which cause a serious social and economic burden. In addition, dizziness or vertigo is very common clinically, and these patients also have a higher risk of falling. In order to reduce the incidence of falls, targeted prevention measures are urgently needed. In this paper, the risk assessment, preventive measures and rehabilitation strategies of falls are systematically expounded, it is hoped that it will be helpful for the prevention and treatment of falls.

[Clinical characteristics analysis of patients with Meniere's disease and vestibular migraine].

Objective:To analyze the clinical characteristics of patients with Meniere's disease and vestibular migraine, improve the understanding of such diseases for accurate treatment. Method:Eighteen patients with MD and VM were reviewed and the clinical characteristics of the patients were evaluated. Result:There were 4 males and 14 females whose average age was 55.2 years old. The average onset age was 36.5 years meanwhile the headache occured 7.5 years earlier than the vertigo. The average time of vertigo attacks was 30 min-24 h; The mainly kind of headache was unilateral pulsatile headache with or without vertigo attacks; All patients showed the characteristics of photophobia or phonophobia, 7 of them showed visual aura and 9 of them experienced vertigo attacks with headache but without auditory symptoms; 11 patients experienced motion sickness and 10 patients had a related family history. Electrocochleogram abnormal was 11 ears; c-VEMP abnormal was 11 cases; Caloric test abnormal was 13 cases; Velocity step test abnormal was 4 cases. Conclusion:MD and VM shows recurrent vertigo, There are evidences of hearing loss and abnormal changes of electrocochleogram、c-VEMP and lateral semicircular canal function in MD; VM experienced migraine attacks with the characteristics of photophobia、phonophobia and visual aura; The patients can be diagnosed with overlap syndrome when they fulfill the diagnostic criteria of MD and VM at the same time and the two diseases should be treated at the same time.

[Efficacy of semicircular canal occlusion in the treatment of fifteen pateints with Meniere's disease].

Objective:To investigate the long-term efficacy of semicircular canal occlusion in the treatment of refractory Meniere's disease. Method:Fifteen patients with Meniere's disease who underwent semicircular canal occlusion were reviewed. The preoperative and postoperative frequency of vertigo ,quality of life, hearing and tinnitus level were compared. All patients were followed for more than 24 months. Result:Postoperatively, vertigo was controlled effectively in all 15 cases, and the control rate was 100%, of which 11 cases were completely controlled（Grade A） and 4 cases were basically controlled（Grade B）. The improvement rate of quality of life was 100%. The hearing worse in 4 cases（26.7%） and stabilized in 11 cases（73.3%）. The tinnitus was relieved in 7 cases（46.7%）, unchanged in 7 cases（46.7%） and aggravated in 1 case（6.7%）. Conclusion:Semicircular canal occlusion can effectively control the vertigo symptoms of refractory Meniere's disease and improve the quality of life. The long-term efficacy of semicircular canal occlusion is definite, but there is a risk of hearing loss.

Foxp2 regulates anatomical features that may be relevant for vocal behaviors and bipedal locomotion.

Fundamental human traits, such as language and bipedalism, are associated with a range of anatomical adaptations in craniofacial shaping and skeletal remodeling. However, it is unclear how such morphological features arose during hominin evolution. FOXP2 is a brain-expressed transcription factor implicated in a rare disorder involving speech apraxia and language impairments. Analysis of its evolutionary history suggests that this gene may have contributed to the emergence of proficient spoken language. In the present study, through analyses of skeleton-specific knockout mice, we identified roles of Foxp2 in skull shaping and bone remodeling. Selective ablation of Foxp2 in cartilage disrupted pup vocalizations in a similar way to that of global Foxp2 mutants, which may be due to pleiotropic effects on craniofacial morphogenesis. Our findings also indicate that Foxp2 helps to regulate strength and length of hind limbs and maintenance of joint cartilage and intervertebral discs, which are all anatomical features that are susceptible to adaptations for bipedal locomotion. In light of the known roles of Foxp2 in brain circuits that are important for motor skills and spoken language, we suggest that this gene may have been well placed to contribute to coevolution of neural and anatomical adaptations related to speech and bipedal locomotion.