BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

ObjectiveIn order to establish a systematic quality evaluation system for Fritillariae Cirrhosae Bulbus adulteration， portable near-infrared （NIR） spectroscopy was used to identify Fritillariae Cirrhosae Bulbus and its adulterants and detect their adulteration quantity. MethodA total of 72 batches of Fritillariae Cirrhosae Bulbus samples were collected and 570 batches of adulterated products （dry bulbs of Fritillaria thunbergii， F. ussuriensis， F. pallidiflora and F. hupehensis， Bulbus Tulipae， flour） were prepared， NIR spectral data of samples were collected by the portable NIR spectrometer. Linear discriminant analysis （LDA） was used to establish the qualitative correction models of Fritillariae Cirrhosae Bulbus-adulterants and adulterants of different categories， partial least squares （PLS） was used to establish the quantitative correction models of adulteration quantity of different kinds of adulterants. ResultThe recognition rates of qualitative analysis model of Fritillariae Cirrhosae Bulbus and its adulterants were 99.49% （calibration set） and 100.00% （validation set）， respectively. In different adulterant models， the recognition rates of calibration set and validation set were 70.47% and 73.68%， respectively. Moreover， the correlation coefficients of validation set （R²_P） of the six quantitative models of adulteration ratio were 0.840 2 （Fritillariae Cirrhosae Bulbus adulterated with F. thunbergii dry bulbs）， 0.960 2 （Fritillariae Cirrhosae Bulbus adulterated with F. ussuriensis dry bulbs）， 0.765 7 （Fritillariae Cirrhosae Bulbus adulterated with F. pallidiflora dry bulbs）， 0.902 5 （Fritillariae Cirrhosae Bulbus adulterated with F. hupehensis dry bulbs）， 0.957 4 （Fritillariae Cirrhosae Bulbus adulterated with Bulbus Tulipae）， 0.976 1 （Fritillariae Cirrhosae Bulbus adulterated with flour）， the root mean square error of prediction （RMSEP） were 10.948 5， 5.463 9， 13.256 4， 8.549 2， 5.655 3， 4.235 6， respectively. The two qualitative models and six quantitative models showed good prediction performance. ConclusionThe portable NIR spectroscopy can be used to identify Fritillariae Cirrhosae Bulbus and its adulterants in real time， the method is rapid and accurate， which can meet the requirements of nondestructive identification of Fritillariae Cirrhosae Bulbus on site.

ObjectiveTo explore the mechanism of Naozhenning on learning and memory ability and neuron damage in hippocampal CA1 region of post-concussion syndrome model rats based on mitochondrial function. MethodMultiple cerebral concussion （MCC） was induced in SPF Wistar rats with the free-fall impact method. Then the model rats were randomly classified into model group （equivalent volume of distilled water）， piracetam （0.43 g·kg^-1， ig） group， and low-， medium-， and high-dose NZN （5.4， 10.8， 21.6 g·kg^-1， respectively， ig） groups， with 10 rats in each group， and another 10 normal rats were included in the normal control group （equivalent volume of distilled water）. The administration lasted 14 days and then relevant indexes were detected. Morris water maze test was used to observe the changes of learning and memory ability in each group， such as escape latency， residence time in primary quadrant， and times of crossing platform. The pathological changes of hippocampal CA1 region were observed based on hematoxylin-eosin （HE） staining and Nissl staining. The ultrastructure of mitochondria was observed under the transmission electron microscope （TME） and the activity of mitochondrial respiratory chain complex Ⅰ was detected by colorimetry. The content of adenosine triphosphate （ATP） was determined by fluorescence probe and mitochondrial membrane potential （MMP） by fluorescein enzyme-linked fluorescence immunoassay. ResultCompared with the normal control group， the model group showed long escape latency， short residence time in target quadrant， few times of crossing the platform， significant decrease in counts of neurons and Nissl bodies in hippocampal CA1 region， damage of neuronal morphology and mitochondrial structure， and significant reduction of MMP and the content of mitochondrial ATP and respiratory chain complex I （P<0.05， P<0.01）. The NZN groups demonstrated short escape latency， long residence time in target quadrant， increased times of crossing the platform， small number of neurons and Nissl bodies in hippocampal CA1 region， alleviated damage of neuronal morphology and mitochondrial structure， and increase in MMP and the content of mitochondrial ATP and respiratory chain complex I （P<0.05， P<0.01）. ConclusionNZN can improve the learning and memory ability of MCC rats by improving mitochondrial structure and function and alleviating hippocampal neuron injury.

Objective:To propose a new method for detecting and evaluating traditional Chinese medicine （TCM） by artificial intelligence and machine vision technology. Method:Taking Fritillariae Cirrhosae Bulbus， Crataegi Fructus and Pinelliae Rhizoma as the research objects， big data of pictures was collected by machine vision and the image database was established. Through the intelligent analysis of the external characteristics of TCM， the deep convolutional neural network model was established to realize the functions of location detection and variety identification by means of deep learning， so as to significantly improve the accuracy of rapid identification of TCM. Result:The classification accuracy of 11 kinds of Chinese herbal pieces （raw， fried， parched and charred products of Crataegi Fructus， Pinelliae Rhizoma， Pinelliae Rhizoma Praeparatum Cum Zingibere et Alumine， Pinelliae Rhizoma Praeparatum， Pinelliae Rhizoma Praeparatum Cum Alumine and three products of Fritillariae Cirrhosae Bulbus） could be more than 99%， and the average recognition accuracy of specific categories could reach more than 97%. Conclusion:The intelligent identification technology of TCM decoction pieces realized by deep learning algorithms has the advantages of simplicity， rapidity， high precision and quantifiable detection， which can provide technical support for the quality detection and evaluation of TCM， and enrich the research ideas of quality evaluation of TCM.