The tanshinones from the plant of Salvia miltiorrhiza.

Six undescribed tanshinones, (+)-2-Cl-tanshindiol C (1), (-)-2-Cl-tanshindiol C (2), (+)-tanshinoic acid D (3), (-)-tanshinoic acid D (4), (-)-tanshinoic acid E (5), and (+)-tanshinoic acid E (6), were isolated from the rhizome of Salvia miltiorrhiza Bunge. Their structures were elucidated based on the spectroscopic data (UV, IR, HR-ESI-MS, and NMR). The bioactive assays of all these compounds for the antioxidant activities in cardiomyocytes upon hypoxia stimulation were evaluated. The results suggested that compounds 5 and 6 exhibited good antioxidant activities in cardiomyocytes and the cell survival rates were 46.3% and 57.9% (10-5 mol/L), respectively.

Prognosis and conditional nomogram of cervical spine fracture in patients with severe spinal cord injury: a multicenter retrospective study.

INTRODUCTION: Cervical spine fractures with severe spinal cord injury (SCI) are common following cervical spine trauma and are associated with a high mortality rate. Understanding the mortality patterns of patients with cervical spine fractures and severe SCI can offer valuable evidence to surgeons and family members who are required to make critical healthcare decisions. The authors aimed to evaluate the instantaneous death risk and conditional survival (CS) of such patients and developed conditional nomograms to account for different periods of survivors and predict the survival rates. METHODS: Their instantaneous death risks were calculated using the hazard function, and the Kaplan-Meier method was used to evaluate the survival rates. Cox regression was used to choose the variables for the construction of the nomograms. The area under the receiver operating characteristic curve and calibration plots were used to validate the performance of the nomograms. RESULTS: The authors finally included 450 patients with cervical spine fractures and severe SCI using propensity score matching. The instantaneous death risk was the highest during the first 12 months after injury. Surgical treatment can help decrease the instantaneous death risk quickly, especially in early-term surgery. The 5-year CS increased constantly from 73.3% at baseline to 88.0% after 2 years of survival. Conditional nomograms were constructed at baseline and in those who survived for 6 and 12 months. The area under the receiver operating characteristic curve and calibration curves indicated that the nomograms had a good performance. CONCLUSION: Their results improve our understanding of the instantaneous death risk of patients in different periods following injury. CS demonstrated the exact survival rate among medium-term and long-term survivors. Conditional nomograms are suitable for different survival periods in predicting the probability of survival. Conditional nomograms help in understanding the prognosis and improve the shared decision-making approaches.

Bioactive graphene oxide-functionalized self-expandable hydrophilic and osteogenic nanocomposite for orthopaedic applications.

Polymethyl methacrylate (PMMA) bone cement (PBC) is commonly used in orthopaedic surgery. However, polymerization volumetric shrinkage, exothermic injury, and low bioactivity prevent PBC from being an ideal material. The developed expandable P(MMA-AA-St) well overcomes the volumetric shrinkage of PBC. However, its biomechanical properties are unsatisfactory. Herein, graphene oxide (GO), a hydrophilic material with favourable biomechanics and osteogenic capability, was added to P(MMA-AA-St) to optimize its biomechanics and bioactivity. The GO-modified self-expandable P(MMA-AA-St)-GO nanocomposite (PGBCs) exhibited outstanding compressive strength (>70 â€‹MPa), water absorption, and volume expansion, as well as a longer handling time and a reduced setting temperature. The cytocompatibility of PGBCs was superior to that of PBC, as demonstrated by CCK-8 assay, live-dead cell staining, and flow cytometry. In addition, better osteoblast attachment was observed, which could be attributed to the effects of GO. The improved level of osteogenic gene and protein expression further illustrated the improved cell-material interactions between osteoblasts and PGBCs. The results of an in vivo study performed by filling bone defects in the femoral condyles of rabbits with PGBCs demonstrated promising intraoperative handling properties and convenient implantation. Blood testing and histological staining demonstrated satisfactory in vivo biosafety. Furthermore, bone morphological and microarchitecture analyses using bone tissue staining and micro-CT scanning revealed better bone-PGBCs contact and osteogenic capability. The results of this study indicate that GO modification improved the physiochemical properties, cytocompatibility, and osteogenic capability of P(MMA-AA-St) and overcame the drawbacks of PBC, allowing its material derivatives to serve as effective implantable biomaterials.

Study on the different responses of different winter wheat cultivars to dry hot wind.

Dry hot wind (DHW) is one of the main agro-meteorological disasters that occur during the grain filling stage of winter wheat in northern China. In this study, three major winter wheat cultivars planted at the Mazhuang experimental station, Xinji city, Hebei Province, including Henong 6119 (HN6119), Gaoyou 5218 (GY5218), and Jimai 325 (JM325), were analyzed. Through natural DHW and artificially simulated DHW experiments, we investigated how the physiological parameters of the three cultivars were affected on the day with DHW and the day before and after DHW occurred. Comparative analysis of the different responses among the physiological parameters of the three cultivars demonstrated that HN6119 experienced less leaf water loss by reducing its stomata conductance and transpiration rate under natural DHW conditions, while GY5218 and JM325 experienced more leaf water loss by increasing their stomata conductance and transpiration rates under natural DHW conditions. The net photosynthetic rate, transpiration rate, and stomata conductance of HN6119 recovered after the DHW conditions, while those of GY5218 and JM325 showed a continuously decreasing trend. The leaf photosynthetic water use efficiency decreased on DHW days because the net photosynthesis rate was reduced for HN6119, but the transpiration rate increased for GY5218 and JM325. HN6119 showed a significant positive correlation between physiological parameters, while GY5218 and JM325 showed a poor correlation after being affected by DHW conditions. The effect of artificial simulation under mild and severe DHW stress on the thousand kernel weight (TKW) of HN6119, GY5218 and JM325 was 0.01%, 3.51%, 3.57% and 0.36%, 8.12%, 8.84%, respectively. HN6119 showed better resistance to DHW, followed by GY5218, and JM325 showed the weakest resistance.

Two dimers generated by lithospermic decarboxylation coupling from Danshen.

To further reveal the active ingredients of Danshen, we systematically studied its chemical components and obtained two new lithospermic acid derivatives (compounds 1 and 2) together with five known phenylpropionic acids (compounds 3-7) from the dried rhizomes of Salvia miltiorrhiza. The structures of the two new compounds were determined by multiple spectral analyses (UV, IR, HR-ESI-MS, NMR, and ECD). In addition, the absolute configurations were established by chiral analysis and calculated and experimental circular dichroism spectra. Biological research indicated that compound 1 could significantly inhibit the proliferation of isoproterenol (ISO)-treated cardiac fibroblasts (AC16 cells), and MMP9 was found to be the most likely target of compound 1. The protein expression and mRNA levels of MMP9 were increased in ISO-induced AC16 cells, which could be reversed by treatment with compound 1. Furthermore, this treatment could alleviate the migration and activation of ISO-induced cardiac fibroblasts.

The phenolic acids from the plant of Salvia miltiorrhiza.

Seven new phenolic acids, 7, 8-epiblechnic acid (1), 8-epiblechnic acid 9-ehthyl-9'-methyl ester (2), 9'-ehyl-isolithospermate (3), 9''-methyl-isolithospermate (4), 9'-ethyl-9''-methyl-isolithospermate (5), 9', 9''-dimethyl-isolithospermate (6), sebesteniod E (7), were isolated from the roots of Salvia miltiorrhiza. Their structures were elucidated by detailed spectroscopic means including UV, IR, HRESIMS, and NMR data spectra. The bioactive assays of compounds 1-7 against neuroprotection activities were determined. The results suggested that compound 4 exhibited a moderate glutamate-induced neuroprotective activity and the cell survival rate was 24.0% (10-5 mol/L), while compound 2 showed weak activity (survival rate: 7.58%, 10-5 mol/L), using PHPB (survival rate: 7.56%, 10-5 mol/L) as positive control.

The complete chloroplast genome of Scoparia dulcis (Plantaginaceae).

Here, we report the complete chloroplast genome of Scoparia dulcis L. The genome is 153,701 bp in size. Two inverted repeats (IRs) with a total of 50,546 bp were identified. The rest of the sequence was separated into two single-copy regions, including a large single-copy (LSC) region (85,029 bp) and a small single-copy (SSC) region (18,126 bp), respectively. The genome of S. dulcis comprised of 129 genes, including 85 protein-coding genes, 8 rRNA genes, and 36 tRNA genes. Phylogenetic analysis showed that S. dulcis was strongly allied with Bacopa monnieri.

Experimental Study of Chloride Resistance of Polypropylene Fiber Reinforced Concrete with Fly Ash and Modeling.

Herein, the paper reports an experimental investigation lasting one year on the chloride resistance of polypropylene fiber (PF) reinforced concrete with fly ash (FA). Four influential factors at four levels were studied, viz. water to binder ratio (w/b) (0.53, 0.34, 0.29, and 0.25), PF dosage (0%, 0.06%, 0.08%, and 0.1% in volume basis of the total volume of concrete), FA content (0%, 15%, 25%, and 35% in mass substitution ratio of cement) and concentration of NaCl solution (0%, 3%, 5%, and 7%). Dry-wet cyclic immersion and long-term soaking were taken into consideration in addition to the aforementioned factors. A L16(44) orthogonal table was used to sequence influencing factors and to determine the optimal combination. Results showed that 7% NaCl solution caused the highest chloride content in 0-5 mm depth, whilst the w/b ratio of 0.25 curbed the chloride penetration within 10 mm even for concrete subjected to dry-wet cyclic immersion for 360 d. Subsequently, a respond surface model (RSM) basing on polynomials was constructed to visually evaluate the effect of PF dosage and FA content. Results clarified that a cubic model was more precise and PF dosage and FA content turned out to have the positive facilitation to chloride resistance. The positive effect of PF however is not consistent and commensurate for concrete with varied fly ash content. Finally, a fuzzy logic based nonlinear model accommodating all seven influencing factors was verified to be proper and adaptive in predicting chloride content.

Biomechanical comparison of four types of instrumentation constructs for revision surgery in lumbar adjacent segment disease: A finite element study.

BACKGROUND: Different constructs are applied in revision surgery (RS) for adjacent segment disease (ASD) aiming to further decompress and fixate the affected segment(s) in two ways: replacing or preserving the primary implants. This study aimed to compare the biomechanical properties of four constructs with different configurations. METHODS: An T12-L5 finite element (FE) model was constructed and validated. Primary surgery was performed at L4-L5 and instrumented from L3 to L5. Thereafter, RS was undertook by decompressing L2-L3 and fixated with implant-replacing construct A, or implant-preserving construct B, C or D. Range of motion (ROM) and intervertebral disc pressure (IDP) were compared. Maximum von Mises stress on the rods between Construct A and B was evaluated. RESULTS: An obvious reduction of ROM was observed when the FE model was instrumented with four constructs respectively. The overall changing characteristics of ROM were approximately identical among four constructs. The changing characteristic of IDP among four constructs was similar. The degree of IDP reduction of Construct B was comparable to Construct A, while that of Construct C was comparable to Construct D. Maximum von Mises stress on the rods between Construct A and B indicated that no stress concentration was recorded at the locking part of the connector rod. CONCLUSIONS: The biomechanics of implant-preserving constructs were comparable to the traditional implant-replacing construct. The location of side-by-side connector could not affect the stability of Construct C and D. Construct B might be an optimal choice in RS for less dissection, less complication and more convenience in manipulation.

Wandering rod: form lumbar spine into left pleural cavity with nerve irritated symptoms.

Spinal instrumented rod migrating from the surgical site to another remote site in the body is rare. Some cases result in organ or blood vessel injury. Most reported cases were asymptomatic until the finally injuries were generated. We report a unique case of spinal implant failure in which the rod moved from lumbar spine into chest 13 years post lumbar instrumentation. The migrated rod caused no damage to the organs in the pleural cavity but did cause an atypical pleural irritation syndrome which seemed to correlate with the mechanical irritation caused by the rod. These atypical symptoms of rod migration have not been reported previously.

Implant Preservation versus Implant Replacement in Revision Surgery for Adjacent Segment Disease After Thoracolumbar Instrumentation: A Retrospective Study of 43 Patients.

OBJECTIVE: To evaluate the mechanical properties of a new connector rod aiming to preserve implants in revision surgery (RS) for adjacent segment disease, a problematic complication of instrumented spinal fusion, and to assess its clinical applicability. METHODS: The mechanical properties of the connector-rod construct (implant preservation) and traditional rod construct (implant replacement) were evaluated and compared. Forty-three patients underwent RS for adjacent segment disease in the thoracolumbar spine with implant preservation or replacement, and radiological and clinical outcomes were assessed. RESULTS: Mechanical properties in group A were comparable to those in group B. Total mean time from prior surgery to RS was 6.86 ± 1.08 years. Surgical time and blood loss values of group A were 40.14% and 29.29% statistically significantly smaller than values of group B. In group B, 12% (3/25) of patients developed surgical site infections. In both groups, the visual analog scale leg score decreased significantly after RS. Early postoperative (at 1-month and 3-month follow-up) Oswestry Disability Index and visual analog scale back scores of group A were significantly lower than those of group B; the difference in the visual analog scale back score between groups was significant until the 6-month follow-up. No implant failures occurred, and spinal fusion was achieved in all cases. CONCLUSIONS: The connector rod is considered safe and can reduce the surgical time, blood loss, risk of complications, and medical costs. Better early postoperative clinical outcomes can be achieved with the rod owing to less surgical trauma.

Neuroprotective effects of Ginkgolide B in focal cerebral ischemia through selective activation of prostaglandin E2 receptor EP4 and the downstream transactivation of epidermal growth factor receptor.

The present study was undertaken to identify whether prostaglandin E2 receptor is the potential receptor/binding site for Ginkgolide A, Ginkgolide B, Ginkgolide K, and Bilobalide, the four main ingredients of the Ginkgo biloba L., leaves. Using functional assays, we identified EP4, coupled with Gs protein, as a target of Ginkgolide B. In human neuroblastoma SH-SY5Y cells suffered from oxygen-glucose deprivation/reperfusion, Ginkgolide B-activated PKA, Akt, and ERK1/2 as well as Src-mediated transactivation of epidermal growth factor receptor. These resulted in downstream signaling pathways, which enhanced cell survival and inhibited apoptosis. Knockdown of EP4 prevented Ginkgolide B-mediated Src, epidermal growth factor receptor (EGFR), Akt, and ERK1/2 phosphorylation and neuroprotective effects. Moreover, Src inhibitor prevented Ginkgolide B-mediated EGFR transactivation and the downstream Akt and ERK1/2 activation, while the phosphorylation of PKA induced by Ginkgolide B was not affected, indicating Ginkgolide B might transactivate EGFR in a ligand-independent manner. EP4 knockdown in a rat middle cerebral artery occlusion (MCAO) model prevented Ginkgolide B-mediated infarct size reduction and neurological assessment improvement. At the same time, the increased expressions of p-Akt, p-ERK1/2, p-PKA, p-Src, and p-EGFR and the deceased expression of cleaved capases-3 induced by Ginkgolide B in cerebral cortex were blocked due to EP4 knockdown. In conclusion, Ginkgolide B exerts neuroprotective effects in rat MCAO model through the activation of EP4 and the downstream transactivation of EGFR.

Effects of Revision Rod Position on Spinal Construct Stability in Lumbar Revision Surgery: A Finite Element Study.

Revision surgery (RS) is a necessary surgical intervention in clinical practice to treat spinal instrumentation-related symptomatic complications. Three constructs with different configurations have been applied in RS. One distinguishing characteristic of these configurations is that the revision rods connecting previous segments and revision segments are placed alongside, outside, or inside the previous rods at the level of facetectomy. Whether the position of the revision rod could generate mechanical disparities in revision constructs is unknown. The objective of this study was to assess the influence of the revision rod position on the construct after RS. A validated spinal finite element (FE) model was developed to simulate RS after previous instrumented fusion using a modified dual-rod construct (DRCm), satellite-rod construct (SRC), and cortical bone trajectory construct (CBTC). Thereafter, maximum von Mises stress (VMS) on the annulus fibrosus and cages and the ligament force of the interspinous ligament, supraspinous ligament, and ligamentum flavum under a pure moment load and a follower load in six directions were applied to assess the influence of the revision rod position on the revision construct. An approximately identical overall reducing tendency of VMS was observed among the three constructs. The changing tendency of the maximum VMS on the cages placed at L4-L5 was nearly equal among the three constructs. However, the changing tendency of the maximum VMS on the cage placed at L2-L3 was notable, especially in the CBTC under right bending and left axial rotation. The overall changing tendency of the ligament force in the DRCm, SRC, and CBTC was also approximately equal, while the ligament force of the CBTC was found to be significantly greater than that of the DRCm and SRC at L1-L2. The results indicated that the stiffness associated with the CBTC might be lower than that associated with the DRCm and SRC in RS. The results of the present study indicated that the DRCm, SRC, and CBTC could provide sufficient stabilization in RS. The CBTC was a less rigid construct. Rather than the revision rod position, the method of constructing spinal instrumentation played a role in influencing the biomechanics of revision.

Protective effect of paeoniflorin on H / 中国天然药物

This study was to investigate the protective effect of paeoniflorin (PF) on hydrogen peroxide-induced injury. Firstly, "SMILES" of PF was searched in Pubchem and further was used for reverse molecular docking in Swiss Target Prediction database to obtain potential targets. Injury-related molecules were obtained from GeenCards database, and the predicted targets of PF for injury treatment were selected by Wayne diagram. For mechanism analysis, the protein-protein interactions were constructed by String, and the KEGG analysis was conducted in Webgestalt. Then, cell viability and cytotoxicity assay were established by CCK8 assay. Also, the experimental cells were allocated to control, model (200 μmol·L

Three 11,12-seco-tanshinone derivatives from the rhizomes of Salvia miltiorrhiza.

Three new compounds named tanshinoic acid A (1), tanshinoic acid B (2), and tanshinoic acid C (3) were isolated from the rhizomes of Salvia miltiorrhiza, together with two known compounds methyl salvianolate A (4) and methyl salvianolate C (5). Their structures were determined on the basis of spectroscopic data (UV, IR, HRESIMS, 1 D and 2 D NMR). The in vitro assay indicated that 4 and 5 could improve the survived rate of cells on oxygen glucose deprivation (OGD) induced neurons damage model and glutamate-induced neurons damage model at a concentration of 10 µM. [Formula: see text].

Thermosensitive injectable decellularized nucleus pulposus hydrogel as an ideal biomaterial for nucleus pulposus regeneration.

Extracellular matrix loss is one of the early manifestations of intervertebral disc degeneration. Stem cell-based tissue engineering creates an appropriate microenvironment for long term cell survival, promising for NP regeneration. We created a decellularized nucleus pulposus hydrogel (DNPH) from fresh bovine nucleus pulposus. Decellularization removed NP cells effectively, while highly preserving their structures and major biochemical components, such as glycosaminoglycan and collagen II. DNPH could be gelled as a uniform grid structure in situ at 37°C for 30 min. Adding adipose marrow-derived mesenchymal stem cells into the hydrogel for three-dimensional culture resulted in good bioactivity and biocompatibility in vitro. Meanwhile, NP-related gene expression significantly increased without the addition of exogenous biological factors. In summary, the thermosensitive and injectable hydrogel, which has low toxicity and inducible differentiation, could serve as a bio-scaffold, bio-carrier, and three-dimensional culture system. Therefore, DNPH has an outstanding potential for intervertebral disc regeneration.

Nedaplatin-Induced Arrhythmia: Retrospective Analysis of Three Cases.

Nedaplatin (NDP) is a second-generation platinum derivative that was developed in Japan. Nowadays, it is being widely used in the management of lung cancer, esophageal cancer, head and neck cancers, especially when cisplatin and carboplatin cannot be tolerated or show drug resistance. To the best of our knowledge, there are few reported cases of NDP-induced bradycardia in the relevant medical literature. The current report presents three patients treated with NDP chemotherapy-induced serious arrhythmias. The three cases developed sinus tachycardia and atrial premature beats, complete left bundle branch block, and bigeminy ventricular premature contraction, in the second, sixth and second cycle, respectively. No one died of cardiac toxicity. These were treated with dexamethasone, 5 mg intravenous injection and diphenhydramine 20 mg, intramuscular injection. The heart rhythm returned to normal in 30 minutes, a day, and four days, respectively.

Augmented PMMA distribution: improvement of mechanical property and reduction of leakage rate of a fenestrated pedicle screw with diameter-tapered perforations.

OBJECTIVE This study investigated the optimum injection volume of polymethylmethacrylate (PMMA) to augment a novel fenestrated pedicle screw (FPS) with diameter-tapered perforations in the osteoporotic vertebral body, and how the distribution characteristics of PMMA affect the biomechanical performance of this screw. METHODS Two types of FPSs were designed (FPS-A, composed of 6 perforations with an equal diameter of 1.2 mm; and FPS-B, composed of 6 perforations each with a tapered diameter of 1.5 mm, 1.2 mm, and 0.9 mm from tip to head. Each of 28 human cadaveric osteoporotic vertebrae were randomly assigned to 1 of 7 groups: FPS-A1.0: FPS-A+1.0 ml PMMA; FPS-A1.5: FPS-A+1.5 ml PMMA; FPS-A2.0: FPS-A+2.0 ml PMMA; FPS-B1.0: FPS-B+1.0 ml PMMA; FPS-B1.5: FPS-B+1.5 ml PMMA; FPS-B2.0: FPS-B+2.0 ml PMMA; and conventional pedicle screws (CPSs) without PMMA. After the augmentation, 3D CT was performed to assess the cement distribution characteristics and the cement leakage rate. Axial pullout tests were performed to compare the maximum pullout force thereafter. RESULTS The CT construction images showed that PMMA bone cement formed a conical mass around FPS-A and a cylindrical mass around FPS-B. When the injection volume was increased from 1.0 ml to 2.0 ml, the distribution region of the PMMA cement was enlarged, the PMMA was distributed more posteriorly, and the risk of leakage was increased. When the injection volume reached 2.0 ml, the risk of cement leakage was lower for screws having diameter-tapered perforations. The pullout strengths of the augmented FPS-A groups and FPS-B groups were higher than that of the CPS group (p < 0.0001). All FPS-B groups had a higher pullout strength than the FPS-A groups. CONCLUSIONS The diameter of the perforations affects the distribution of PMMA cement. The diameter-tapered design enabled PMMA to form larger bone-PMMA interfaces and achieve a relatively higher pullout strength, although statistical significance was not reached. Study results indicated 1.5-ml of PMMA was a conservative volume for PMMA augmentation; more cement injection would significantly increase the risk of cement leakage.

[Correlation between the expression of Pim-1 and androgen-deprivation therapy for prostate cancer].

OBJECTIVE: To investigate the expression of the Pim-1 gene in the LNCaP cells of the animal model of orthotopically implanted prostate cancer by surgical castration simulating androgen-deprivation therapy. METHODS: We equally allocated 32 male BALBc-nu mice into 4 groups, androgen-dependent prostate cancer (ADPC), androgen-deprivation therapy (ADT) , castration-resistant prostate cancer (CRPC) and blank control, and established the models of orthotopically implanted tumor using human prostate cancer LNCaP cells. We detected and ,compared the expressions of Pim-1, PSA, and androgen receptor (AR) in the tumor tissues of different groups by RT-PCR. qRT-PCR, ELSIA and immunohistochemistry. RESULTS: The relative gray scales in the ADPC and CRPC groups were 0.59 ± 0.01 and 1.14 ± 0.02, with statistically significant differences from 0.62 ± 0.03 in the ADT group (P < 0.05), and the Δ Ct values of Pim-1 were 6.15 ± 0.34 and 4.56 ± 0.23 in the former two groups, also with significant differences from 5.11 ± 0.21 in the latter (P < 0.05). The results of 2-ΔΔ Ct relative quantification analysis showed that the amplification products of Pim-1 in the ADT and CRPC groups increased 2.05 and 3.01 times respectively that of the ADPC group. The concentration of PSA was significantly higher in the ADPC ([480 ± 25] pg/ml) and CRPC ([870 ± 23] pg/ml) than in the ADT ([170 ± 32] pg/ml) and blank control groups (0 µg/L) (P < 0.01). The mean optical densities of Pim-1 and AR proteins were 0.017 ± 0.002 and 0.032 ± 0.009 in the ADPC group and 0.024 ± 0.002 and 0.040 ± 0.011 in the CRPC group, both with significant differences from those in the ADT group (0.018 ± 0.001 and 0.019 ± 0.006) (P < 0.01). CONCLUSION: Pim-1 is highly expressed in nude mice with prostate cancer receiving androgen-deprivation therapy and plays an important role in the progression and metastasis of prostate cancer.

What is the next generation therapeutic strategy for castration-resistant prostate cancer.

Prostate cancer (PCa) is one of the most common cancers in the world. Since androgen receptor (AR) signal plays key roles in the PCa progression, targeting androgens via the current androgen deprivation therapy (ADT) is the main therapeutic strategy for advanced PCa. However, most patients who receive ADT, including the second generation anti-androgens enzalutamide (also known as MDV3100) may finally develop the castration (or anti-androgen) resistance after 12-24 months treatment. In the manuscript by Asangani et al., the authors demonstrated that targeting the amino-terminal bromodomains of BRD4 could preferentially suppress human castration-resistant prostate cancer (CRPC) cell lines. While further studies are required to understand the full impact of their findings, the innovative approach provides a potential novel epigenetic approach for the concerted blockade of oncogenic drivers in CRPC.