Pharmacokinetics study is one of main components of pharmaceuticals development. Food and Drug Administration (FDA) approved Veregen as the first botanical drug in 2006. This article introduced FDA's requirement on pharmacokinetics study of botanical drug and pharmacokinetics studies of Veregen, summarized current requirement and status quo of pharmacokinetics study on traditional Chinese medicine (TCM) and natural medicine in China, and discussed about pharmacokinetics study strategy for TCM and natural medicine.
Catechin ; analogs & derivatives ; chemistry ; pharmacokinetics ; Chemistry, Pharmaceutical ; Drug Approval ; Drugs, Chinese Herbal ; chemistry ; pharmacokinetics ; Medicine, Chinese Traditional ; United States ; United States Food and Drug Administration ; legislation & jurisprudence

Objective To explore the effect of Numb on tubular epithelial-to-mesenchymal transition (EMT) in rat proximal epithelial cells. Methods NRK52E cells were treated with different concentrations of recombinant human transforming growth factor-β1 (TGF-β1) (0, 1, 5, 10, 15, 20 μg/L) for 48 h or 10 μg/L TGF-β1 for different times (0, 24, 48, 72 h) in vitro. The expressions of E-cadherin, a-smooth muscle actin(α-SMA) and Numb in NRK 52E cells were detected by RT-PCR, Western blot and immunofluorescence staining. Meanwhile Numb siRNA oligo was transfected into NRK 52E cells with lipofectamine before TGF-β1 treatment, then Western blot was applied to detect the protein expression of E-cadherin, α-SMA and Numb in NRK52E cells. Results TGF-β1 could induce EMT in NRK52E cells in dose- and time-dependent manner. During the progress of TGF-β1-induced EMT, the protein expression of Numb in 5, 10, 15, 20 μg/L group was 1.33 folds (P=0.024), 1.39 folds (P=0.035), 1.45 folds (P=0.025), 1.51 folds (P=0.000) respectively as compared to 0 μg/L group. Likewise, the protein and mRNA expression of Numb in 24 h, 48 h, 72 h group was 1.48 folds (P=0.046) and 1.56 folds (P=0.012), 1.54 folds (P=0.011) and 1.82 folds (P=0.008), 1.79 folds (P=0.028) and 1.82 folds (P=0.002) respectively as compared to 0 h group. Moreover, large amount of Numb was accumulated in the cytoplasm. Down-regulation of Numb expression by siRNA transfection did not influence the basal expression of E-cadherin and α-SMA in NRK 52E cells, but attenuated the progression of EMT in NRK52E cells induced by TGF-β1. The up-regulation of α-SMA protein was reduced to 18.1% (P=0.004) while the down-regulation of E-cadherin protein was reversed to 2.19 folds (P=0.004). Conclusion Numb can promote EMT in rat proximal epithelial cells.

Objective To evaluate the efficacy and safety of the hyper-CVAD/MA regimen as an intensified treatment option for 28 T cell and aggressive/highly aggressive B cell NHL in Chinese patients. Methods Clinical data of 28 NHL patients treated with hyper-CVAD/MA regimen from Jan 2005 to Sep 2008 were retrospectively analyzed. Results 27 NHL patients were available for the efficacy analysis, with a response rate of 70.4 %. For the 13 B cell lymphoma cases, the response rate was 84.6 %. The main toxicity was Grade Ⅲ or Grade Ⅳ myelosuppression in all cases and 2 treatment related deaths. Conclusion Hyper-CVAD/MA regimen had a high response rate in T cell and aggressive /highly aggressive B cell NHL lymphoma, companied by significant toxicity when treating Chinese patients. Further clinical practices are needed to pick up a suitable dose which can balance efficacy and safety.

With the rapid development of nanotechnology, the research and development of nanomedicine has become one of the current development directions of drug innovation. The pharmacokinetic characteristics of nanomedicine are significantly different from general drugs because of the scale effect based on nanostructures, and pharmacokinetics studies of nanomedicine may be different from the general drugs. This article focuses on the research strategies and considerations on non-clinical pharmacokinetics of nanomedicine, including test agents, in vivo/in vitro assays, biological sample analysis, data evaluation and analysis etc., providing references for developers.

ObjectiveTaking Shengxuebao as the model traditional Chinese medicine（TCM）， this study aims to explore the methodologies and transfer patterns in the composition changes of TCM compound preparations from liquid to solid dosage forms. MethodBased on the previously established ultra-high performance liquid chromatography（UPLC） qualitative and quantitative methods for Shengxuebao， the fingerprint profiles of three preparations of Shengxuebao（homemade decoction， commercially available granules and mixtures） were established， and nineteen components were quantitatively analyzed. The similarities of fingerprint profiles among these three preparations were assessed using the Similarity Evaluation System for Chromatographic Fingerprint of TCM（2012 edition） and the total quantum statistical moment similarity method， respectively. The molecular connectivity index （MCI） and the average molar MCI of the chemical components in the three preparations were calculated. Seventy-two MCI values across 0-8 orders， including 8 subclasses， were calculated. The average molar MCI of 0-3 orders was used to study the "imprint template" structural characteristics and transfer patterns of the medicinal component groups. ResultThe similarities of the fingerprint profile of the decoction with those of the control， granules， and mixtures were 0.971， 0.888 and 0.799， respectively， indicating that the chemical composition of the granules and mixtures differed from that of the decoction， and that the 19 components were able to basically respond to the overall situation of the component group of Shengxuebao decoction. The total mass fractions of the detectable major components in Shengxuebao decoction， granules and mixtures was measured to be 5.498 6， 2.282 0， 1.416 6 mg·g^-1， respectively. The average molar MCI of 0-3 orders showed a gradual decrease across the three preparations， with the trend of decoction>granules>mixtures， indicating subtle changes in the overall structural characteristics of the chemical components in the samples of the three preparations. ConclusionAmong the three formulations of Shengxuebao， the traditional decoction contained the highest variety and quantity of components and carried the most substantial amount of component information， with a decreasing order observed in the granules and mixtures. This study further validates that traditional decoction is a reliable and fundamental dosage form， providing a reference for the modernization of TCM dosage forms and the quality consistency evaluation of compound preparations.

Objective: To describe the dermoscopic features of extramammary Paget′s disease (EMPD) and chronic eczema of the vulva, and to explore the value of dermoscopy in the diagnosis and differential diagnosis of the above diseases. Methods: Dermoscopic images were collected from 20 patients with histopathologically confirmed vulvar EMPD and 16 patients with clinically confirmed chronic eczema of the vulva in Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Pekin Union Medical College from January 2017 to April 2018, and retrospectively analyzed. Fisher′s exact test was used to compare the prevalence of dermoscopic features between the two groups. Results: As dermoscopy showed, the milky red background was observed in 19 EMPD patients and in only 1 patient with chronic eczema, and there was a significant difference in the prevalence of milky red background between the two groups (P < 0.001) . White scales were the most common desquamation, and were observed in 9 EMPD patients and 13 patients with chronic eczema (P = 0.128) . Blood vessels were uniformly distributed in EMPD patients, including dotted-globular vessels in 19 and linear vessels in 14, while blood vessels were distributed in a patchy or clustered pattern in the patients with chronic eczema, including dotted-globular vessels in 16 and linear vessels in 7. There was a significant difference in the prevalence of different distribution patterns of blood vessels between the two groups (P < 0.001) . Bright white streaks, bright white structureless area and reticular structure were observed in 19, 20 and 19 EMPD patients respectively, and in 1, 1 and 1 patient with chronic eczema respectively, and there were significant differences in the prevalence of the above 3 structures between the two diseases (all P < 0.001) . Conclusion Vulvar EMPD and chronic eczema both show characteristic dermoscopic features, and dermoscopy is of great value to the diagnosis and differential diagnosis of EMPD.

Early weaned piglets suffer from oxidative stress and enteral infection, which usually results in gut microbial dysbiosis, serve diarrhea, and even death. Rice bran oil (RBO), a polyphenol-enriched by-product of rice processing, has been shown to have antioxidant and anti-inflammatory properties both in vivo and in vitro. Here, we ascertained the proper RBO supplementation level, and subsequently determined its effects on lipopolysaccharide (LPS)-induced intestinal dysfunction in weaned piglets. A total of 168 piglets were randomly allocated into four groups of seven replicates (42 piglets each group, (21±1) d of age, body weight (7.60±0.04) kg, and half males and half females) and were given basal diet (Ctrl) or basal diet supplemented with 0.01% (mass fraction) RBO (RBO1), 0.02% RBO (RBO2), or 0.03% RBO (RBO3) for 21 d. Then, seven piglets from the Ctrl and the RBO were treated with LPS (100 μg/kg body weight (BW)) as LPS group and RBO+LPS group, respectively. Meanwhile, seven piglets from the Ctrl were treated with the saline vehicle (Ctrl group). Four hours later, all treated piglets were sacrificed for taking samples of plasma, jejunum tissues, and feces. The results showed that 0.02% was the optimal dose of dietary RBO supplementation based on diarrhea, average daily gain, and average daily feed intake indices in early weaning piglets. Furthermore, RBO protected piglets against LPS-induced jejunal epithelium damage, which was indicated by the increases in villus height, villus height/crypt depth ratio, and Claudin-1 levels, as well as a decreased level of jejunal epithelium apoptosis. RBO also improved the antioxidant ability of LPS-challenged piglets, which was indicated by the elevated concentrations of catalase and superoxide dismutase, and increased total antioxidant capacity, as well as the decreased concentrations of diamine oxidase and malondialdehyde in plasma. Meanwhile, RBO improved the immune function of LPS-challenged weaned piglets, which was indicated by elevated immunoglobulin A (IgA), IgM, β‍‍-defensin-1, and lysozyme levels in the plasma. In addition, RBO supplementation improved the LPS challenge-induced dysbiosis of gut microbiota. Particularly, the indices of antioxidant capacity, intestinal damage, and immunity were significantly associated with the RBO-regulated gut microbiota. These findings suggested that 0.02% RBO is a suitable dose to protect against LPS-induced intestinal damage, oxidative stress, and jejunal microbiota dysbiosis in early weaned piglets.
Male ; Female ; Swine ; Animals ; Lipopolysaccharides/toxicity* ; Antioxidants/pharmacology* ; Rice Bran Oil ; Dysbiosis ; Dietary Supplements ; Diarrhea/veterinary* ; Weaning ; Body Weight