The characteristics and regulations of adaptive designs from 2008 to 2020: An overview of European Medicines Agency approvals.

OBJECTIVE: The aim of this study was to identify and characterize all European Medicines Agency (EMA) approvals derived from adaptive designs in clinical trials and to provide an update of the current status of these drugs. MATERIALS AND METHODS: Relevant files were identified in the EMA database for annual reports for the period between 2008 and 2020 using a list of suitable keywords related to adaptive designs. We recorded trial characteristics from drug approvals and used Fisher exact test to compare the characteristics. RESULTS: A total of 1,054 EMA approvals were identified, and the percentage of EMA approvals planned with adaptive trial designs increased from 1.85% in the period 2008 - 2012 to 6.19% in between 2017 - 2020. A total of 41 approvals were identified among 91 original EMA files that contained adaptive designs. The types of adaptive designs used in clinical trials increased after 2017 where the most common type used was the most common (17/41). Most approvals (32/41) comprised pivotal trials, and most assessments had not been accelerated (38/41). Of 32 confirmatory trials planned with adaptive designs, the proportion of those with additional monitoring (AM) increased significantly (p < 0.0001) from 0% in the 2008 - 2012 period to 90.48% in the 2017 - 2020 period. The percentage of approved antitumor drugs in approved drugs in ongoing clinical trials was 82.35%, compared to 20.83% in trials that were completed (p = 0.0001). The proportion of drug approved but where clinical trials were still ongoing in companies requiring post-authorization safety studies (PASSs) or post-authorization efficacy studies (PAESs) or who were granted conditional marketing authorization (CMA) significantly differed from the group of drugs approved where clinical trials were completed (p = 0.0230). CONCLUSION: A trend showing an increased number of EMA approvals related to adaptive designs was observed for the period from 2008 to 2020. Different types of adaptive trial designs could be encouraged for the designation of clinical trials, especially for antitumor drugs; meanwhile, more stringent monitoring regulations seemed to be conducted for ongoing trials of antitumor drugs with adaptive design.

A novel 450-nm laser-mediated sinoporphyrin sodium-based photodynamic therapy induces autophagic cell death in gastric cancer through regulation of the ROS/PI3K/Akt/mTOR signaling pathway.

BACKGROUND: Photodynamic therapy (PDT) has become an ideal and promising therapeutic method for fighting cancer, but its common application in clinical practice is prevented by the limitations of expensive devices in light sources and phototoxicity in photosensitizers. The aim of this study was to explore the antitumor efficiency of the novel 450-nm blue laser (BL) combined with sinoporphyrin sodium (DVDMS)-mediated PDT against human gastric cancer (GC) in vitro and in vivo, focusing on autophagy pathway. METHODS: Cell viability was detected by Cell Counting Kit-8 and colony formation assays in HGC27, MGC803, AGS, and GES-1 cells. Cell apoptosis was measured by flow cytometry and western blotting. The production of reactive oxygen species (ROS) was measured by fluorescence microscopy and flow cytometry. Autophagy was determined by transmission electron microscopy and western blotting. The antitumor effect of BL-PDT in vivo was detected by a subcutaneous tumor model in nude mice. RESULTS: The novel 450-nm laser-mediated DVDMS-based PDT caused remarkable growth inhibition and apoptosis induction in GC cells in vitro by the production of excessive ROS. Autophagy flux was induced by BL-PDT in GC cells, as determined by LC3 conversion assay, LC3 turnover assay, and mRFP-GFP-LC3 puncta assay. Furthermore, autophagy induction was demonstrated to positively contribute to BL-PDT-induced apoptotic effects on GC cells. Mechanically, ROS/PI3K/Akt/mTOR pathway was identified to involve in the regulation of BL-PDT-induced autophagy as determined by transcriptomic analysis and functional studies. Consistently, xenograft studies confirmed the significant antitumor effect of BL-PDT and its favorable safety in vivo. CONCLUSIONS: The novel 450-nm laser-mediated DVDMS-based PDT may be a safe and effective approach against GC. Our results thus provide compelling evidence for the therapeutic application of BL-PDT in human GC.

Snail promotes prostate cancer migration by facilitating SPOP ubiquitination and degradation.

Prostate cancer (PCa) is the second leading cause of cancer-associated mortality in men. Speckle-type pox virus and zinc finger protein (SPOP), the most frequently mutated gene in PCa, functions as a tumor suppressor via degradation of cancer-promoting substrates. However, its upstream regulation in PCa metastasis remains poorly determined. Here, in a Snail-induced metastatic PCa model, we observed an accelerated degradation of SPOP protein in cells, which is crucial for the PCa migration and activation of the AKT signaling pathway. Mechanistically, we demonstrated that binding to Snail promoted SPOP ubiquitination and degradation. Moreover, the bric-a-brac/tramtrack/broad complex (BTB) domain of SPOP is turned out to be essential for Snail-mediated SPOP degradation. Thus, our findings reveal a post-translational level regulation of SPOP expression that facilitates the metastasis of PCa cells.

Evaluation of anti-cancer potency of silibinin on murine renal carcinoma RenCa cells in an animal model with an intact immune system.

Silibinin is a flavonoid extract isolated from milk thistle and has been proved to be a promising chemotherapeutic drug for cancer. However, most of those studies were performed on the human cancer cells, where the effects of silibinin could only be observed on an animal model with a deficient immune system. RenCa cells were isolated from a murine spontaneous renal cell carcinoma, which resembles many features of human renal cell carcinoma, and have been used to establish animal models with a sound immune response. Herein, we investigated the anti-cancer effects of silibinin on RenCa cells, revealing that it inhibited cell viability in both dose- and time-dependent manners. Silibinin slightly triggered apoptosis and significantly induced G2-M cell cycle arrest by downregulating cyclin B1 and CDK1 and increasing expression of p21. Furthermore, silibinin significantly inhibited the growth of RenCa cell xenografts in vivo. In addition, we found that silibinin reduced programmed cell death 1 ligand 1 expression of RenCa cells in vivo and in vitro. Our findings demonstrate that silibinin can inhibit the growth of mouse tumor cells in an animal model with an intact immune system, and silibinin may decrease the immunosuppression effect of tumor cells. Our results provide new evidence for evaluation of Silibinin application in cancer therapy.

Preparative isolation of arylbutanoid-type phenol [(-)-rhododendrin] with peak tailing on conventional C18 column using middle chromatogram isolated gel column coupled with reversed-phase liquid chromatography.

Reversed-phase liquid chromatography coupled with middle chromatogram isolated gel column was employed for the efficient preparative separation of the arylbutanoid-type phenol [(-)-rhododendrin] from Saxifraga tangutica. Universal C18 (XTerra C18) and XCharge C18 columns were compared for (-)-rhododendrin fraction analysis and preparation. Although tailing and overloading occurred on the XTerra C18 column, the positively charged reversed-phase C18 column (XCharge C18) overcame these drawbacks, allowing for favorable separation resolution, even when loading at a on a preparative scale (3.69 mg per injection). The general separation process was as follows. First, 365.0 mg of crude (-)-rhododendrin was enriched from 165 g Saxifraga tangutica extract via a middle chromatogram isolated gel column. Second, separation was performed on an XTerra C18 preparative column, from which 73.8 mg of the target fraction was easily obtained. Finally, the 24.0 mg tailing peak of (-)-rhododendrin on XTerra C18 column was selectively purified on the XCharge C18 analytical column. These results demonstrate that the tailing nonalkaloid peaks can be effectively used for preparative isolation on XCharge C18 columns.

An efficient strategy based on liquid-liquid extraction and pH-zone-refining counter-current chromatography for selective enrichment, separation, and purification of alkaloids and organic Acids from natural products.

This study presents an efficient strategy based on liquid-liquid extraction and pH-zone-refining counter-current chromatography for selective enrichment, separation, and purification of alkaloids and organic acids from natural products. First, an acid or base modified two-phase solvent system with maximum or minimum partition coefficient was developed for the liquid-liquid extraction of the crude extract. As a result, alkaloids or organic acids could be selectively enriched in the upper or lower phase. Then pH-zone-refining counter-current chromatography was employed to separate and purify the selectively enriched alkaloids or organic acids efficiently. The selective enrichment and separation of five bufadienolide from toad venom of Bufo marinus was used as an example to show the advantage of this strategy. As a result, 759 mg of selectively enriched bufadienolide was obtained from 2 g of crude extract and the total content of five targets was increased from 14.64 to 83%. A total of 31 mg of marinobufagin-3-adipoyl-l-arginine, 42 mg of telocinobufagin-3-pimeloyl-l-arginine, 51 mg of telocinobufagin-3-suberoyl-l-arginine, 132 mg of marinobufagin-3-suberoyl-l-arginine, and 57 mg of bufalin-3-suberoyl-l-arginine were all simultaneously separated from 500 mg of selectively enriched sample, with the purity of 92.4, 97.5, 90.3, 92.1, and 92.8%, respectively.

Accurate bracket placement using a computer-aided design and computer-aided manufacturing-guided bonding device: An in vivo study.

INTRODUCTION: A protocol was introduced to achieve accurate bracket placement in vivo, which consisted of operative procedures for precise control, and a computer-aided design and computer-aided manufacturing-guided bonding device. To evaluate the accuracy of this protocol, a 3-dimensional assessment was performed. METHODS: Ten consecutive patients were enrolled. Strictly following the protocol, from December 2017 to March 2018, brackets were placed on the teeth of each patient using the device. To evaluate the accuracy, deviations of positions and orientations for bracket placement were measured. Each patient was followed up after 3 months regarding bracket failures. RESULTS: The guided bonding device was used in all cases, and a total of 205 brackets were successfully bonded and evaluated. Except for 15.12% brackets with torque deviation over 2°, the deviations in mesiodistal, buccolingual, vertical, rotation, and angulation were below the clinical acceptable range (0.5 mm in translation or 2° in orientation) for all brackets. In the 3-month follow-up, there was no bracket failure in any patient. CONCLUSION: This protocol transferred the planned bracket position from the digital setup to patient's dentition with generally high positional accuracy.

Silicon nitride/titanium oxide hybrid waveguide design enabling broadband athermal operation.

This paper presents a special design of a new kind of silicon nitride/titanium oxide hybrid waveguide with multi-layer materials laminate structure aiming at broadband athermal operation. By incorporating three layers of titanium oxide whose thermo-optic coefficient (TOC) is negative in the waveguide core and upper cladding regions, the thermal drift of the conventional strip waveguide induced by the positive TOC of silicon nitride is fully compensated, with the effective TOC of the hybrid waveguide achieving zero at 1550 nm and only varying extremely slightly within ±6×10-7/K in the wavelength band from 1350 to 1850 nm. In addition, due to the inherent alternate growth manner of titanium dioxide and silicon nitride thin layers, this new kind of multi-layer material laminate structure waveguide holds the potential of avoiding the challenging growth of low-stress crack-free single-layer silicon nitride film thick enough for realizing an anomalous dispersion waveguide. Furthermore, we numerically demonstrate the different influences of the temperature change on optical frequency comb generation between the traditional waveguide and the hybrid waveguide, and we find that the athermal hybrid waveguide is much more temperature insensitive than the strip waveguide.

Investigation of the local dispersion change in anomalous dispersion microcavity and quantitative analysis of the phase-matching in Kerr comb generation.

We numerically simulate Kerr comb generation in an anomalous dispersion microcavity by modal expansion method and demonstrate that the initiation of comb generation is affected by the change of local dispersion possibly caused by avoided mode crossings. We also quantitatively analyze the instantaneous phase matching of different modes and reveal the characteristics of energy distribution in different modes in the dynamics of comb generation. We demonstrate that the local dispersion change can control the Kerr comb to transform between Type I and Type II combs. We also find that local dispersion is closely related to the stability of the power of Kerr comb lines, something that can change the dynamical state of the system near the Hamiltonian-Hopf bifurcation under an anomalous dispersion regime from a quasi-periodic oscillation state to a periodic state (Turing patterns).

Effects of inferior tibiofibular syndesmosis injury and screw stabilization on motion of the ankle: a finite element study.

PURPOSE: Traditional studies of syndesmosis injury and screw stabilization have been conducted in cadaveric models, which cannot yield sufficient and exact biomechanical data about the interior of the ankle. The purpose of this study was to evaluate the effects of inferior tibiofibular syndesmosis injury (ITSI) and screw stabilization on the motion of the ankle with finite element analysis. METHODS: Three-dimensional models of the ankle complex were created with CT images of a volunteer's right ankle in three states: normal, post-ITSI, and stabilization with a screw 2.5 cm above (parallel to) the ankle. Simulated loads were applied under three conditions: neutral position with single foot standing, internal rotation, and external rotation of the ankle. RESULTS: Compared with the normal state, ITSI increased the relative displacement between the lower extremes of the tibia and fibula in the anteroposterior and mediolateral directions and the angular motion of the tibia, fibula, and talus at internal and external rotations (ERs). However, when stabilized with syndesmotic screws, the range of motion (ROM) and all these parameters significantly decreased. CONCLUSION: ITSI can lead to internal and ER instability of the ankle joint. Screw stabilization is effective in controlling the instability, but may reduce markedly the ROM of the ankle joint. Through this study, it can be proposed that the screws should be removed once the healing is gained in order to restore normal function of the ankle joint as soon as possible.

Down-regulation of SLC14A1 in prostate cancer activates CDK1/CCNB1 and mTOR pathways and promotes tumor progression.

Prostate cancer (PCa) is the most common cancer among men in the United States and the leading cause of cancer-related death. The Solute Carrier Family 14 Member 1 (SLC14A1) is a member of urea transporters which are important for the regulation of urine concentration. However, the physiological significance of SLC14A1 in PCa still remains unclear. In the present study, via bioinformatics analysis and experiments, we found that expression of SLC14A1 is significantly decreased in PCa progression, which could be attributed to hypermethylation on SLC14A1 promoter region. Moreover, its low expression and hypermethylation on SLC14A1 promoter are closely related to the poor prognosis of PCa patients. On the other hand, overexpression of SLC14A1 inhibited cell proliferation and metastasis while its overexpression also suppressed CDK1/CCNB1 pathway and mTOR/MMP-9 signaling pathway. Additionally, SLC14A1 expression is enriched in prostate basal-type cells. In summary, our study indicates that its low expression level and promoter hypermethylation of SLC14A1 may represent novel indicators for PCa progression and prognosis, and SLC14A1 could inhibit the progression of PCa.

Erratum: KLF5 downregulation desensitizes castration-resistant prostate cancer cells to docetaxel by increasing BECN1 expression and inducing cell autophagy: Erratum.

[This corrects the article DOI: 10.7150/thno.33282.].

Melatonin suppresses Akt/mTOR/S6K activity, induces cell apoptosis, and synergistically inhibits cell growth with sunitinib in renal carcinoma cells via reversing Warburg effect.

BACKGROUND: Metabolic alteration drives renal cell carcinoma (RCC) development, while the impact of melatonin (MLT), a neurohormone secreted during darkness, on RCC cell growth and underlying mechanisms remains unclear. METHODS: We detected concentration of metabolites through metabolomic analyses using UPLC-MS/MS, and the oxygen consumption rate was determined using the Seahorse Extracellular Flux analyzer. RESULTS: We observed that MLT effectively inhibited RCC cell growth both in vitro and in vivo. Additionally, MLT increased ROS levels, suppressed antioxidant enzyme activity, and induced apoptosis. Furthermore, MLT treatment upregulated key TCA cycle metabolites while reducing aerobic glycolysis products, leading to higher oxygen consumption rate, ATP production, and membrane potential. Moreover, MLT treatment suppressed phosphorylation of Akt, mTOR, and p70 S6 Kinase as well as the expression of HIF-1α/VEGFA in RCC cells; these effects were reversed by NAC (ROS inhibitors). Conversely, MLT synergistically inhibited cell growth with sunitinib and counteracted the Warburg effect induced by sunitinib in RCC cells. CONCLUSIONS: In conclusion, our results indicate that MLT treatment reverses the Warburg effect and promotes intracellular ROS production, which leads to the suppression of Akt/mTOR/S6K signaling pathway, induction of cell apoptosis, and synergistically inhibition of cell growth with sunitinib in RCC cells. Overall, this study provides new insights into the mechanisms underlying anti-tumor effect of MLT in RCC cells, and suggests that MLT might be a promising therapeutic for RCC.

Associations between interleukin-6 gene -174 C/G and -572 C/G polymorphisms and the risk of gastric cancer: a meta-analysis.

BACKGROUND AND OBJECTIVES: Epidemiological studies have evaluated the associations between interleukin-6 (IL-6) gene -174 C/G (rs1800795) and -572 C/G (rs1800796) polymorphisms and gastric cancer (GC) risk, but results and conclusions remain controversial. In order to derive a more precise estimation of the associations, we performed this meta-analysis. METHODS: A meta-analysis was conducted to estimate the associations between IL-6 gene -174 C/G and -572 C/G polymorphisms and GC risk. RESULTS: Nine articles involving 13 studies were included in the final meta-analysis, covering a total of 1,581 GC cases and 2,563 controls. For IL-6 gene -174 C/G polymorphism, nine studies were combined showing no evidence for associations between IL-6 gene -174 C/G polymorphism and GC risk. For IL-6 gene -572 C/G polymorphism, four studies were combined. There was also lack of evidence for significant association between IL-6 gene -572 C/G polymorphism and GC risk. In addition, the similar results were obtained in the subgroup analyses and cumulative meta-analysis. CONCLUSIONS: The present meta-analysis suggests that IL-6 gene -174 C/G and -572 C/G polymorphisms are not associated with GC risk. However, due to the small subjects included in analysis and the selection bias in some studies, the results should be interpreted with caution.

Integrated Analysis and Identification of Critical RNA-Binding Proteins in Bladder Cancer.

RBPs in the development and progression of BC remains unclear. Here, we elucidated the role of RBPs in predicting the survival of patients with BC. Clinical information and RNA sequencing data of the training and validation cohorts were downloaded from the Cancer Genome Atlas and Gene Expression Omnibus databases, respectively. Survival-related differentially expressed RBPs were identified using Cox regression analyses. A total of 113 upregulated and 54 downregulated RBPs were observed, with six showing prognostic values (AHNAK, MAP1B, LAMA2, P4HB, FASN, and GSDMB). In both the GSE32548 and GSE31684 datasets, patients with low-risk scores in survival-related six RBPs-based prognostic model showed longer overall survival than those with high-risk scores. AHNAK, MAP1B, P4HB, and FASN expression were significantly upregulated in both BC tissues and cell lines. BC tissues from high-risk group showed higher proportions of naive CD4+ T cells, M0 and M2 macrophages, and neutrophils and lower proportions of plasma cells, CD8+ T cells, and T-cell follicular helper compared to low-risk group. AHNAK knockdown significantly inhibited the proliferation, invasion, and migration of BC cells in vitro and inhibited the growth of subcutaneous tumors in vivo. We thus developed and functionally validated a novel six RBPs-based prognostic model for BC.

Lung transcriptome analysis for the identification of genes involved in the hypoxic adaptation of plateau pika (Ochotona curzoniae).

The plateau pika, a typical hypoxia-tolerant mammal lives 3000-5000 m above sea level on the Qinghai-Tibet Plateau, has acquired many physiological and morphological characteristics and strategies in its adaptation to sustained, high-altitude hypoxia. Blunted hypoxic pulmonary vasoconstriction is one such strategy, but the genes involved in this strategy have not been elucidated. Here, we investigated the genes involved and their expression profiles in the lung transcriptome of plateau pikas subjected to different hypoxic conditions (using low-pressure oxygen cabins). A slight, right ventricular hypertrophy was observed in pikas of the control group (altitude: 3200 m) vs. those exposed to 5000 m altitude conditions for one week. Our assembly identified 67,774 genes; compared with their expression in the control animals, 866 and 8364 genes were co-upregulated and co-downregulated, respectively, in pikas subjected to 5000 m altitude conditions for 1 and 4 w. We elucidated pathways that were associated with pulmonary vascular arterial pressure, including vascular smooth muscle contraction, HIF-1 signalling, calcium signalling, cGMP-PKG signalling, and PI3K-Akt signalling based on the differentially expressed genes; the top-100 pathway enrichments were found between the control group and the group exposed to 5000 m altitude conditions for 4 w. The mRNA levels of 18 candidate gene showed that more than 83% of genes were expressed and the number of transcriptome The up-regulated genes were EPAS1, Hbα, iNOS, CX40, CD31, PPM1B, HIF-1α, MYLK, Pcdh12, Surfactant protein B, the down-regulated genes were RYR2, vWF, RASA1, CLASRP, HIF-3α. Our transcriptome data are a valuable resource for future genomic studies on plateau pika.

Preparative separation of 1,1-diphenyl-2-picrylhydrazyl inhibitors originating from Saxifraga sinomontana employing medium-pressure liquid chromatography in combination with reversed-phase liquid chromatography.

Traditional Tibetan medicines elaborately document the health benefits of Saxifraga sinomontana. However, there have been limited reports on its chemical make-up, presumably because of the complicated separation and purification process. In this work, a methanolic extract of Saxifraga sinomontana was utilized for targeted separation of 4 key 1,1-diphenyl-2-picrylhydrazyl inhibitors employing the medium-pressure liquid chromatography, reversed-phase liquid chromatography in combination with on-line reversed-phase liquid chromatography-1,1-diphenyl-2-picrylhydrazyl detection. Pre-treatment of the sample was carried out by employing medium-pressure liquid chromatography using MCI GEL® CHP20P as the stationary phase, furnishing 2.4 g of fraction Fr3 and 3.4 g of fraction Fr4 (the percentage retrieval was 32.7%). The 1,1-diphenyl-2-picrylhydrazyl inhibitors contained in fractions Fr3 and Fr4 were subjected to additional separation using a C18 (ReproSil-Pur C18 AQ) column and yielded 106.2 mg of Fr3-1, 246.9 mg of Fr3-2, 248.5 mg of Fr4-1 and 41.8 mg of Fr4-2. The degree of purity, structures and 1,1-diphenyl-2-picrylhydrazyl inhibition activity of the isolated DPPH inhibitors were determined, and four 1,1-diphenyl-2-picrylhydrazyl inhibitors including two new diarylnonanoids (3-methoxy-4-hydroxyphenol-(6'-O-galloyl)-1-O-ß-d-glucopyrano side with IC50 of 39.6 µM, 3,4,5-trimethoxyphenyl-(6'-O-galloyl)-1-O-ß-d-glucopyranoside with IC50 of 46.9 µM, saximonsin A with IC50 of 11.4 µM, and saximonsin B with IC50 of 20.6 µM) were isolated with a percentage purity above 95%. The methodology thus evolved has good efficacy for preparatively isolating high-purity 1,1-diphenyl-2-picrylhydrazyl inhibitors from extracts of Saxifraga sinomontana and could be efficiently utilized for rapidly isolating 1,1-diphenyl-2-picrylhydrazyl inhibitors from other natural products.

Cell-mediated injectable blend hydrogel-BCP ceramic scaffold for in situ condylar osteochondral repair.

The existing approaches for healing mandibular condylar osteochondral defects, which are prevalent in temporomandibular joint disorders (TMD), are sparse and not reparative. To address this, regenerative medicine in situ has transpired as a potential therapeutic solution as it can effectively regenerate composite tissues. Herein, injectable self-crosslinking thiolated hyaluronic acid (HA-SH)/type I collagen (Col I) blend hydrogel and BCP ceramics combined with rabbit bone mesenchymal stem cells (rBMSCs)/chondrocytes were used to fabricate a new bi-layer scaffold to simulate specific structure of rabbit condylar osteochondral defects. The in vitro results demonstrated that the blend hydrogel scaffold provided suitable microenvironment for simultaneously realizing proliferation and chondrogenic specific matrix secretion of both rBMSCs and chondrocytes, while BCP ceramics facilitated rBMSCs proliferation and osteogenic differentiation. The in vivo results confirmed that compared with cell-free implant, the rBMSCs/chondrocytes-loaded bi-layer scaffold could effectively promote the regeneration of both fibrocartilage and subchondral bone, suggesting that the bi-layer scaffold presented a promising option for cell-mediated mandibular condylar cartilage regeneration.

Large-scale preparative isolation of bergenin standard substance from Saxifraga atrata using polyamide coupled with MCI GEL® CHP20P as stationary phases in medium pressure chromatography.

In this study, polyamide and MCI GEL® CHP20P were employed as stationary phases in medium pressure chromatography (MPC) for the efficient preparative separation of bergenin from Saxifraga atrata. Ethanol-water, methanol-water, and acetonitrile-water mobile phases all showed good enrichment capacity for bergenin fraction when polyamide was used as a stationary phase. After 5 cycles of polyamide MPC using acetonitrile/water, 1.2 g of bergenin fraction was isolated from 180 g Saxifraga atrata herb. Further purification of this fraction was conducted using MCI GEL® CHP20P styrene-divinylbenzene beads. The bergenin fraction was separated into two fractions, and after three runs of MPC, 714.2 mg of bergenin with purity above 99% was obtained. The results demonstrate that the combination of polyamide and styrene-divinylbenzene MPC can be utilized for preparative isolation of compounds from natural products with high yield and purity.